Marine Biological Laboratory Library Woods Hole, Massachusetts Gift of F. R. Lillie estate - 1977 i-O m a I A TEXT BOOK OP PHYSIOLOGY A TEXT BOOK OF PHYSIOLOGY BY M. FOSTER, M.A., M.D., LL.D., F.R.S., PROFESSOR OF PHYSIOLOGY IN THE UNIVERSITY OF CAMBRIDGE, AND FELLOW OF TRINITY COLLEGE, CAMBRIDGE. WITH ILLUSTRATIONS. FIFTH EDITION, LARGELY REVISED. PART I., COMPRISING BOOK I. Blood. The Tissues of Movement. The Vascular Mechanism. Hontfon : MACMILLAN AND CO. AND NEW YORK. 1888 [The Right of Translation is reserved.] (Cambrtogc : PBINTED BY C. J. CLAY, M.A. & SONS, AT THE UNIVERSITY PRESS. First Edition 1876. Second Edition 1877. Third Edition 1879. Fourth Edition 1883. Reprinted 1884, 1886. Fifth Edition 1888. PREFACE. IN the present edition I have made considerable changes and additions ; but in the changes I have tried to maintain the character of the book as presented in previous editions ; and the additions, with the exception of the histological paragraphs, are caused not by any attempt to add new matter or to enlarge the general scope of the work, but by an effort to explain more fully and at greater length what seem to me to be the most funda- mental and most important topics. I have been led to introduce some histological statements, not with the view of in any way relieving the student from the necessity of studying distinct histological treatises, but in order to bring him to the physio- logical problem with the histological data fresh in his mind. I have therefore dealt very briefly with the several histological points and confined myself to matters having a physiological bearing. My friends Dr Gaskell, Mr Langley and Dr Lea have given me great assistance throughout, and their names might fitly appear on the title page, were it not that the present arrange- ment makes me alone responsible for all shortcomings. I have also to thank my senior demonstrator Mr L. E. Shore, M.B. and my junior demonstrator Mr Wingfield, M.A. for much valuable aid. The second and third parts will follow this first part as soon as possible. CONTENTS OF PART I. INTRODUCTION. PAGE §§ 1 — 3. Distinctive characters of living and dead bodies .... 1 § 4. Living substance, food and waste ........ 3 § 5. Protoplasm and the physiological unit 4 § 6. Histological differentiation and physiological division of labour. Tissues and functions ......... 6 § 7. The two chief classes of tissues 6 § 8. Muscular and nervous tissues 7 § 9. Tissues of digestion and excretion ........ 7 § 10. Organs. — Muscles and nerves of the organs of nutrition ... 8 § 11. The blood and the vascular system 8 § 12. The main problem of physiology 9 BOOK I. BLOOD. THE TISSUES OF MOVEMENT. THE VASCULAR MECHANISM. CHAPTER I. BLOOD. § 13. The general work of the Blood 13 SECTION I. THE CLOTTING OF BLOOD. § 14. The phenomena of clotting 15 § 15. The characters of fibrin 17 § 16. Serum-paraglobulin ; its characters 18 viii CONTENTS. PAGE § 17. Serum-albumin ; its characters ........ 19 § 18. The circumstances whicli affect the rapidity of clotting ... 20 § 19. The preparation of plasmiue and fibrinogen 22 § 20. Fibrin-ferment ; its action. Nature of the process of clotting . . 23 § 21. Why blood clots when shed 26 § 22. The influence on clotting exerted by the living blood vessels . . '27 § 23. The nature of this influence ; the action of the white corpuscles . 2£ SECTION II. THE CORPUSCLES OF THE BLOOD. The Red Corpuscles. § 24. The structure of the red corpuscles ; laky blood ; stronia, and globin ............ 31 § 25. The number of red corpuscles in human blood; method of enumeration 34 § 26. The destruction of red corpuscles 35 § 27. The formation of red corpuscles, in the embryo and in the adult ; hsmatoblasts .......... 36 The White Corpuscles. § 28. The structure of the white corpuscles; characters of the cell-substance 38 § 29. The chemical bodies present in white corpuscles 40 § 30. The white corpuscles as a type of living matter; metabolism, katabolic and anabolic changes. The nature and relations of the ' granules ' ; living substance, food and waste . ...... 41 § 31. The origin of the white corpuscles. Leucocytes ..... 44 § 32. The disappearance of the white corpuscles. Their influence on the plasma. Different kinds of white corpuscles .... 45 Blood Platelets. § 33. The characters of blood platelets 47 SECTION III. THE CHEMICAL COMPOSITION OF BLOOD. § 34. General chemical characters 49 § 35. Chemical composition of serum ........ 49 § 36. Chemical composition of red corpuscles ...... 50 § 37. Chemical composition of white corpuscles 51 SECTION IV. THE QUANTITY OF BLOOD AND ITS DISTRIBUTION IN THE BODY. .§ 38. The determination of the quantity of blood in the body, and the main facts of its distribution . 52 CONTENTS. ix CHAPTER II. THE CONTRACTILE TISSUES. PAGE § 39. The movements of the body carried out by means of various kinds of contractile tissues .......... 54 SECTION I. THE PHENOMENA OP MUSCLE AND NERVE. Muscular and Nervous Irritability. § 40. Irritability ; contractility ; stimuli 56 §41. Independent muscular irritability ; action of urari .... 57 § 42. Simple and tetanic contractions 58 § 43. The muscle-nerve preparation 58 § 44. Various forms of stimuli. Induction Coil. Key. Magnetic Inter- rupter. Electrodes. Method of graphic record .... 59 The Phenomena of a Simple Muscular Contraction. § 45. The muscle curve. Myographs. Time measurements. Signals . 68 § 46. Analysis of a simple muscle curve 74 § 47. Variations of the muscle curve. The shortening accompanied by thickening 77 § 48. Simple muscular contractions rare in the living body .... 78 § 49. Tetanic contractions. Analysis of the curve of tetanus ... 78 § 50. Various degrees of tetanic contractions 82 § 51. Diminution and disappearance of irritability after death ... 83 SECTION II. ON THE CHANGES WHICH TAKE PLACE IN A MUSCLE DURING A CONTRACTION. The Change in Form. § 52. Gross structure of muscle, arrangement of muscular fibres, blood vessels and nerves . . . . . . . . .84 § 53. The wave of contraction ; its length, velocity and other characters . 86 § 54. Minute structure of muscular fibre ; nature of striation ... 88 § 55. The visible changes which take place in a muscular fibre during a contraction ........... 91 § 56. The appearances presented when the fibre is examined with polarized light 93 § 57. Nature of the act of contraction 94 x CONTENTS. The Chemistry of Muscle. PAGE §58. Contrast of living and dead muscle; rigor mortis .... 95 § 59. Chemical bodies present in dead muscle ; niyosin, syntonin . . 96 § 60. Chemistry of living muscle; muscle-plasma, muscle-clot and muscle- serum, myoglobulin, histo-hasmatin 98 § 61. Acid reaction of rigid muscle; development of carbonic acid in rigor mortis . 99 § 62. Other constituents of muscle 101 § 63. Chemical changes during contraction ; development of carbonic acid and acid reaction 102 § 64. Summary of the chemistry of muscle ....... 104 Thermal Changes. § 65. Heat given out during a contraction. Comparison of muscle with a stearn engine 104 Electrical Changes. §66. Non-polarisable electrodes. Muscle currents; their distribution and nature 106 § 67. Negative variation of the muscle current; currents of action. The rheoscopic frog Ill The Changes in a Nerve during the passage of a Nervous Impiilse. § 68. Structure of a nerve. Primitive sheath or neurilernma, medulla, axis cylinder, nodes of Eanvier. The axis cylinder the essential part 113 § 69. Nerve endings in striated muscular fibres. Henle's sheath. End- plates 118 § 70. Non-medullated nerve fibres 120 §71. The chemistry of a nerve; cholesteriu, lecithin, cerebrin, protagon . 121 § 72. The nervous impulse; the electrical changes accompanying it. These changes travel in both directions along the nerve . . . 123 § 73. Summary of the changes occurring in a muscle and nerve as the result of stimulation . . . 125 SECTION III. THE NATURE OF THE CHANGES THROUGH WHICH AN ELECTRIC CURRENT IS ABLE TO GENERATE A NERVOUS IMPULSE. Action of the Constant Current. §74. Action of the constant current; making and breaking contractions . 126 § 75. Electrotonus. Effect of the constant current on the irritability of the nerve. Katelectrotonus. -Anelectrotonus .... 128 § 76. Electrotouic currents .......... 130 § 77. Relation of electrotonus to nervous impulses, and to the effects of the constant current 132 § 78. Action of the constant current on muscle 134 CONTENTS. xi SECTION IV. THE MUSCLE-NERVE PREPARATION AS A MACHINE. PAGE § 79. The influence of the nature and mode of application of the stimulus on the magnitude of the contraction. Maximal and minimal stimuli. Influence of abruptness and duration of stimulus. Some parts of a nerve more irritable than others . . . 136 § 80. Frequency of repetition necessary to produce tetanus ; pale and red muscles. The muscular sound ....... 139 § 81. The influence of the load; effect of resistance. The work done . 141 § 82. The influence of the size and form of the muscle .... 142 SECTION V. THE CIRCUMSTANCES WHICH DETERMINE THE DEGREE OP IRRITABILITY OF MUSCLES AND NERVES. § 83. Diminution and disappearance of irritability after severance from the body. Effect of division of nerves ; degeneration of nerve fibres. Regeneration . . . . . . . ... . 143 § 84. The influence of temperature 145 § 85. The influence of blood-supply 146 § «6. The influence of functional activity. Exercise. Fatigue. The causes of exhaustion 148 SECTION VI. THE ENERGY OF MUSCLE AND NERVE AND THE NATURE OF MUSCULAR AND NERVOUS ACTION. § 87. Nature of the act of contraction and the act of relaxation. The relation of the energy of work to the energy of heat. The relation of nitrogenous metabolism to the energy of contraction . . 151 § 88. The nature of a nervous impulse 154 SECTION VII. ON SOME OTHER FORMS OF CONTRACTILE TISSUE. Plain, smooth or unstriated Muscular Tissue. §89. Structure of plain muscular tissue ; characters of the fibre-cell . . 157 § 90. Arrangement and termination of nerves in unstriated muscle . . 158 § 91. The chemistry of unstriated muscle 159 § 92. The characters of the contraction of unstriated muscle. Peristaltic contractions. 'Spontaneous' contractions. Tonic contractions 159 xii CONTENTS. Ciliary Movement. PAGE § 93. Structure of a ciliated epithelium cell 162 § 94. Nature of ciliary movement. Circumstances affecting ciliary move- ments 163 Amoeboid Movements. § 95. Nature of an amcfiboid movement ; its relation to a muscular con- traction 166 CHAPTER III. ON THE MORE GENERAL FEATURES OP NERVOUS TISSUES. § 96. The general arrangement of the nervous system. Cerebro -spinal and splanchnic or sympathetic system; somatic and splanchnic nerves 169 § 97. The structure of spinal ganglia. The ganglionic nerve cell. Bipolar, unipolar and apolar nerve cells ....... 173 § 98. The structure of ganglia of the splanchnic or sympathetic system. Multipolar cells. Spiral cells 176 § 99. Grey matter and white matter of the central nervous system. Structure of a nerve cell of the spinal cord ; axis cylinder process 177 § 100. Functions of nerve cells 178 § 101. Keflex actions; the machinery required. The circumstances de- termining the nature of a reflex action. Reflex actions often purposeful 179 § 102. Automatic actions 183 § 103. Inhibitory nerves 184 CHAPTER IV. THE VASCULAR MECHANISM. SECTION I. THE STRUCTURE AND MAIN FEATURES OF THE VASCULAR APPARATUS. § 104, The chief work of the blood carried on in the capillaries and other minute vessels .......... 186 The Structure of Arteries, Veins and Capillaries. § 105. On some features of connective tissue. Gelatiniferous fibrillffi. Connective-tissue corpuscles ....... 187 § 106. Elastic fibres 189 CONTENTS. xiii PAGE § 107. The structure of capillaries; epithelioid cells. The size of capillaries and variations in their calibre 190 § 108. The structure of minute arteries 193 § 109. The structure of larger arteries ....... 194 § 110. The structure of the veins 196 § 111. Some points in the structure of the heart 197 § 112. The main features of the vascular apparatus 198 SECTION II. THE MAIN FACTS OF THE CIRCULATION. § 113. Behaviour of arteries contrasted with that of veins .... 201 §114. Blood-pressure in an artery and in a vein 202 § 115. Methods of registering blood-pressure; mercurial manometer. Ky- mograph. The blood-pressure curve 204 § 116. Characters of the blood-pressure in various arteries and veins. Blood-pressure in the capillaries. Fall of blood-pressure in the minute vessels .......... 207 § 117. The circulation through the capillaries, and small vessels. Peripheral resistance 209 Hydraulic Principles of the Circulation. § 118. The three main physical facts of the circulation; the central pump, the peripheral resistance and the elastic tubing . . . 211 § 119. The conversion of the intermittent into a continuous flow by means of the elastic reaction of the arteries ...... 212 § 120. Artificial Model. Arterial and venous pressure with great and with little peripheral resistance ....... 214 § 121. Additional aids to the circulation in the living body . . . 219 Circumstances determining the Rate of the Flow. § 122. Methods of determining the rate of the flow. Hsemadromometer, Eheometer, Haernatachometer. The rate of flow in arteries, veins and capillaries 220 § 123. The rate of flow dependent on the width of the bed . . . . 223 § 124. The time of the entire circuit 225 § 125. Summary of the main physical facts of the circulation . . . 226 SECTION III. THE HEART. The Phenomena of the Normal Beat. § 126. The visible movements 228 §127. The cardiac cycle ; the series of events constituting a beat . . 229 § 128. The change of form 232 xiv CONTENTS. PAGE § 129. The cardiac impulse 234 § 130. The sounds of the heart 235 Endocardiac Pressure. § 131. Methods of determining endocardiac pressure. Minimum and maximum manometer. The negative pressure in the cardiac cavities 238 § 132. Cardiac sound and tambour 240 § 133. Discussion of cardiac curves 243 § 134. The main events occurring in the ventricle during a beat . . 246 § 135. The nature and causes of the negative pressure .... 247 § 136. The duration of the several phases of the cardiac cycle . . . 249 § 137. Summary of the events constituting a beat 251 § 138. The work done 253 SECTION IV. THE PULSE. § 139. Methods of recording the pulse. The sphygmograph. The pulse curve 255 § 140. Pulse tracing from an artificial model ; the features of the pulse wave 257 § 141. Characters of the pulse curve ; influence of pressure exerted by lever 260 § 142. The changes undergone by the pulse wave along the arterial tract . 261 § 143. The velocity of the pulse wave 262 § 144. The length of the pulse wave 263 § 145. Dicrotism. Secondary elevations. Katacrotic and anacrotic tracings 264 § 146. The causes of the dicrotic wave 266 § 147. The predicrotic wave 270 § 148. Causes of anacrotic waves 271 § 149. Venous pulse 271 SECTION V. THE REGULATION AND ADAPTATION OF THE VASCULAR MECHANISM. The Regulation of the Beat of the Heart. § 150. The two great regulators ; changes in the heart-beat and changes in the peripheral mechanism ........ 273 The Histology of the Heart. § 151. Cardiac muscular tissue. The structure of the frog's heart . . 274 § 152. The structure of the mammalian heart 276 § 153. The nerves of the heart. The ganglia of the heart .... 277 The Development of the Normal Beat. § 154. Graphic record of the heart-beat. The beat of the frog's heart. The sequence of events, and the descending scale of rhythmic power ............ 280 CONTENTS. xv PAGE § 155. The causes of the spontaneous rhythmic beat; the relations of the ganglia ; the features of the cardiac tissue 284 § 156. The cardiac tissue and not the ganglia chiefly concerned in the maintenance of the sequence of events 288 The Government of the Heart-Beat by the Nervous System. § 157. Inhibition in the frog by stimulation of vagus nerves. Features of inhibition 290 § 158. Augmentation of the heart-beat. Antagonism of augmentation and inhibition. Course of augrneutor fibres in the frog . . . 292 § 159. Eeflex inhibition. Cardio-inhibitory centre 295 §160. Inhibition in the mammal; effect on blood-pressure. Course of aug- mentor fibres in the dog 296 § 161. Nature of augmentor and inhibitory effects. Action of atropin and rnuscarm 300 Other Influences regulating or modifying the Beat of the Heart. § 162. Influences of blood, and substances contained in the blood. Influence of the distension of the cavities. Relation of heart-beat to blood- pressure 303 SECTION VI. CHANGES IN THE CALIBRE OF THE MINUTE ARTERIES. VASO-MOTOR ACTIONS. § 163. Changes of calibre in arteries as seen in the web of a frog's foot and elsewhere. Vaso-motor nerves 306 § 164. The vascular phenomena in a rabbit's ear . . . 307 § 165. The effects on the vessels of the ear of dividing and stimulating the cervical sympathetic nerve . § 166. Course of vaso-motor fibres of the ear . . 309 § 167. The effects on the vessels of the submaxillary gland of stimulating the chorda tympani nerve; vaso-constrictor and vaso-dilator fibres 310 § 168. Vaso-motor nerves of other parts of the body. Constrictor and dilator fibres in the sciatic and brachial nerves 313 The Course of Vaso-constrictor and Vaso-dilator fibres. § 169. Course of vaso-constrictor fibres . . 317 § 170. Course of vaso-dilator fibres The Effects, of Vaso-motor actions. § 171. Local and general effects of the constriction and dilation of an artery or set of arteries Vaso-motor Functions of the Central Nervous System. § 172. Vaso-dilator fibres usually employed as part of a reflex action . 321 § 173. Loss of tone resulting from the division of the spinal cord at various levels. Vaso-motor centre in the medulla oblongata xvi CONTENTS. PAGE § 174. The Depressor nerve § 175. Else of blood-pressure from stimulation of afferent nerves; pressor 323 effects 325 § 176. The limits of the medullary vaso-motor centre .... 326 § 177. The relation of the medullary vaso-motor centre to other spinal vaso-motor centres. Nature of dilation, tone, and constriction of blood vessels 327 § 178. Summary of vaso-motor actions 330 § 179. Instances of vaso-rnotor actions. Blushing. Effect of warmth on skin 331 § 180. Vaso-motor nerves of the veins 333 SECTION VII. THE CAPILLARY CIRCULATION. § 181. The normal capillary circulation. The axial core and the plasmatic layer 334 § 182. Changes in the capillary circulation induced by irritants. The phenomena of inflammation 336 § 183. The migration of the white corpuscles 337 § 184. Stagnation or stasis. The diapedesis of the red corpuscles. Nature of the inflammatory changes ....... 338 § 185. Changes in the peripheral resistance due to changes in the blood . . 339 SECTION VIII. CHANGES IN THE QUANTITY OF BLOOD. § 186. Effects of increasing and of diminishing the total quantity of blood 341 SECTION IX. A REVIEW OP SOME OF THE FEATURES OF THE CIRCULATION. § 187. The constant and variable factors 343 § 188. Variations in the circulation due to variations in the distension of the cavities 344 § 189. Influence on the heart-beat of the supply of blood, and other nutritive conditions ......... 344 § 190. Causes of an irregular heart-beat 345 § 191. Causes of the sudden cessation of the heart-beat, and sudden death 346 § 192. Blushing and the effects of warmth on the skin. Effects of alcohol on the vascular mechanism 347 § 193. The influence of exercise on the vascular mechanism . . . 349 § 194. The effects of food on the vascular mechanism .... 351 § 195. Relations and mutual actions of heart-beat and vaso-motor system . 351 LIST OF FIGURES IN PART I. FIG. PAGE 1. A muscle-nerve preparation .... ... 59 2. Diagram of du Bois-Reymond key . . 61 3. Diagram illustrating apparatus arranged for experiments with muscle and nerve 63 4. Diagram of an Induction Coil 65 5. The Magnetic Interrupter 66 6. The Magnetic Interrupter with Helmholtz's arrangement for equalizing the make and break shocks ........ 67 7. A muscle curve from the gastrocnernius of a frog 69 8. The same, with the recording surface moving slowly .... 69 9. The same, with the recording surface travelling very rapidly ... 70 10. The Pendulum Myograph 71 11. Diagram of an arrangement of a vibrating tuning fork with a Despretz signal 73 12. Curves illustrating the measurement of the velocity of a nervous impulse 75 13. Tracing of a double muscular contraction 79 14. Muscle curve. Single induction shocks repeated slowly ... 79 15. The same, repeated more rapidly 79 16. The same, repeated still more rapidly ....... 80 17. Tetanus produced with the ordinary magnetic interrupter ... 81 18. Non-polarisable electrodes ......... 107 19. Diagram illustrating the electric currents of nerve and muscle . . 108 20. Diagram illustration of the progression of electric changes . . . 112 21. Diagram of ascending and descending constant current .... 128 22. Diagram of the electrotouic changes in irritability 130 •23. Diagram illustrating electrotonic currents 131 24. Scheme of the nerves of a segment of spinal cord 170 25. Apparatus for investigating blood-pressure . . . 205 26. Tracing of arterial pressure in dog 206 27. Tracing of arterial pi-essure in rabbit 207 28. Ludwig's Kymograph . 208 29. Diagram of fall of blood-pressure in arteries, capillaries and veins . . 209 30. Arterial model 215 31. Tracing from arterial model with little peripheral resistance . . . 216 31*. The same with increased peripheral resistance 217 xviii LIST OF FIGURES KsT PART I. FIG. PAGE 32. Ludwig's Stromuhr 221 33. Chauveau and Lortet's Hsematachometer 223 34. Diagram illustrating causes determining the velocity of the flow . . 224 35. Tracing from heart of cat 233 36. Minimum and maximum Manometer 239 37. Marey's Tambour, and cardiac sound 241 38. Tracing from right auricle and ventricle 242 39. Curve of endocardiac pressure 243 40. Tracing from heart of cat 244 41. Cardiogram from man 244 42. Fick's spring Manometer ......... 255 43. Diagram of a Sphygmograph 256 44. Pulse tracing from radial artery ........ 257 45. Diagram of artificial pulse tracings ....... 258 46. Diagram of progression of pulse wave 259 47. Pulse tracing with different pressures 260 48. Pulse tracing from dorsalis pedis artery 261 49. Pulse tracing from carotid artery 264 50. Anacrotic pulse tracing 265 51. Dicrotic pulse tracing 265 52. A perfusion canuula 281 53. Diagram of apparatus for registering the beat of a frog's heart . . 281 54. Inhibition of heart-beat in the frog 291 55. Diagram of the course of cardiac augmentor fibres in the frog . . 292 56. Cardiac inhibition in the mammal 296 57. The course of cardiac inhibitory and augmentor fibres in the dog . . 298 58. Diagram of the course of vaso-constrictor fibres 310 59. Diagram of the nerves of the submaxillary gland 311 60. The depressor nerve 324 61. Rise of pressure due to stimulation of the sciatic nerve . . . 325 EERATUM. P. 215, 1. 18, for sphymographs read sphygmographs. INTRODUCTION. § 1. DISSECTION, aided by microscopical examination, teaches us that the body of man is made up of certain kinds of material, so differing from each other in optical and other physical characters and so built up together as to give the body certain structural features. Chemical examination further teaches us that these kinds of material are composed of various chemical substances, a large number of which have this characteristic that they possess a considerable amount of potential energy capable of being set free, rendered actual, by oxidation or some other chemical change. Thus the body as a whole may, from a chemical point of view, be considered as a mass of various chemical substances, representing altogether a considerable capital of potential energy. § 2. This body may exist either as a living body or (for a certain time at least) as a dead body, and the living body may at any time become a dead body. At what is generally called the moment of death (but artificially so, for as we shall see the processes of death are numerous and gradual) the dead body so far as structure and chemical composition are concerned is exceed- ingly like the living body ; indeed the differences between the two are such as can be determined only by very careful examination, and are still to a large extent estimated by drawing inferences rather than actually observed. At any rate the dead body at the moment of death resembles the living body in so far as it represents a capital of potential energy. From that moment onwards however the capital is expended ; by processes which are largely those of oxidation, the energy is gradually dissipated, leaving the body chiefly in the form of heat. While these chemical pro- cesses are going on the structural features disappear, and the body, with the loss of nearly all its energy, is at last resolved into "dust and ashes." F. 1 2 THE LIVING AND THE DEAD BODY. The characteristic of the dead body then is that, being a mass of substances of considerable potential energy, it is always more or less slowly losing energy, never gaining energy ; the capital of energy present at the moment of death is more or less slowly diminished, is never increased or replaced. § 3. When on the other hand we study a living body we are struck with the following salient facts. 1. The living body moves of itself, either moving one part of the body on another or moving the whole body from place to place. These movements are active; the body is not simply pulled or pushed by external forces, but the motive power is in the body itself, the energy of each movement is supplied by the body itself. 2. These movements are determined and influenced, indeed often seem to be started, by changes in the surroundings of the body. Sudden contact between the surface of the body and some foreign object will often call forth a movement. The body is sensitive to changes in its surroundings, and this sensitiveness is manifested not only by movements but by other changes in the body. 3. It is continually generating heat and giving out heat to surrounding things, the production and loss of heat, in the case of man and certain other animals, being so adjusted that the whole body is warm, that is of a temperature higher than that of sur- rounding things. 4. From time to time it eats, that is to say takes into itself supplies of certain substances known as food, these substances being in the main similar to those which compose the body and being like them chemical bodies of considerable potential energy, capable through oxidation or other chemical changes of setting free a considerable quantity of energy. 5. It is continually breathing, that is, taking in from the surrounding air supplies of oxygen. 6. It is continually, or from time to time, discharging from itself into its surroundings so-called waste matters^ which waste matters may be broadly described as products of oxidation of the substances taken in as food, or of the substances composing the body. Hence the living body may be said to be distinguished from the dead body by three main features. The living body like the dead is continually losing energy (and losing it more rapidly than the dead body,_ the special breathing arrangements permitting a more rapid oxidation of its substance), but unlike the dead body is by means of food continually restoring its substance and replenishing its store of energy. The energy set free in the dead body by the oxidation and other chemical changes of its substance leaves the body almost ex- clusively in the form of heat, whereas a great deal of energy leaves the living body as mechanical work, the result of various move- ments of the body, and as we shall see a great deal of the energy INTRODUCTION. 3 which ultimately leaves the body as heat, exists for a while within the living body in other forms than heat, though eventually trans- formed into heat. The changes in the surroundings affect the dead body at a slow rate and in a general way only, simply lessening or increasing the amount or rate of chemical change and the quantity of heat thereby set free, but never diverting the energy into some other form such as that of movement ; whereas changes in the surround- ings may in the case of the living body rapidly, profoundly and in special ways affect not only the amount but also the kind of energy set free. The dead body left to itself slowly falls to pieces, slowly dissipates its store of energy, and slowly gives out heat ; a higher or lower temperature, more or less moisture, a free or scanty supply of oxygen, the advent of many or few putrefactive organisms, these may quicken or slacken the rate at which energy is being dis- sipated but do not divert that energy from heat into motion; whereas in the living body so slight a change of surroundings as the mere touch by a hair of some particular surface, may so affect the setting free of energy as to lead to such a discharge of energy in the form of movement that the previously apparently quiescent body may be suddenly thrown into the most violent convulsions. The differences therefore between living substance and dead substance though recondite are very great, and the ultimate object of physiology is to ascertain how it is that living substance can do what dead substance cannot, can renew its substance, and replenish the energy which it is continually losing, and can according to the nature of its surroundings vary not only the amount but also the kind of energy which it sets free. Thus there are two great divisions of physiology : one having to do with the renewal of substance and the replenishment of energy, the other having to do with the setting free of energy. § 4. Now the body of man (or one of the higher animals) is a very complicated structure consisting of different kinds of material which we call tissues, such as muscular, nervous, connective, and the like, variously arranged in organs such as heart, lungs, muscles, skin &c., all built up to form the body according to certain morphological laws. But all this complication, though advan- tageous and indeed necessary for the fuller life of man, is not essential to the existence of life. The amoeba is a living being ; it renews its substance, replenishes its store of energy, and sets free energy now in one form, now in another; and yet the amoeba may be said to have no tissues and no organs ; at all events this is true of closely allied but not so well known simple beings. Using the more familiar amoeba as a type, and therefore leaving on one side the nucleus, and any distinction between endosarc and ectosarc, we may say that its body is homogeneous in the sense that if we divided it into small pieces, each piece would be like all 1—2 4 PROTOPLASM. the others. In another sense it is not homogeneous. For we know that the amoeba receives into its substance material as food, and that this food or part of it remains lodged in the body, until it is made use of and built up into the living substance of the body, and each piece of the living substance of the body must have in or near it some of the material which it is about to build up into itself. Further we know that the amoeba gives out waste matters such as carbonic acid and other substances, and each piece of the amoeba must contain some of these waste matters about to be, but not yet, discharged from the piece. Each piece of the amoeba will therefore contain these three things, the actual living substance, the food about to become living substance and the waste matters which have ceased to be living substance. Moreover we have reasons to think that the living substance does not break down into the waste matters which leave the body at a single bound, but that there are stages in the downward progress between the one and the other. Similarly, though our knowledge on this point is less sure, we have reason to think that the food is not incorporated into the living substance at a single step, but that there are stages in the upward progress from the dead food to the living substance. Each piece of the body of the amoeba will therefore contain substances representing various stages of becoming living, and of ceasing to be living, as well as the living substance itself. And we may safely make this statement though we are quite unable to draw the line where the dead food on its way up becomes living, or the living substance on its way down becomes dead. § 5. Nor is it necessary for our present purpose to be able to point out under the microscope, or to describe from a histological point of view, the parts which are living and the parts which are dead food or dead waste. The body of the amoeba is frequently spoken of as consisting of ' protoplasm.' The name was originally given to the matter forming the primordial utricle of the vegetable cell as distinguished from the cell wall on the one hand, and from the fluid contents of the cell or cell sap on the other, and also we may add from the nucleus. It has since been applied very generally to such parts of animal bodies as resemble, in their general features, the primordial utricle. Thus the body of a white blood corpuscle, or of a gland cell, or of a nerve cell, is said to consist of protoplasm. Such parts of animal bodies as do not in their general features resemble the matter of the primordial utricle are not called protoplasm or, if they at some earlier stage did bear such resemblance, but no longer do so, are sometimes, as in the case of the substance of a muscular fibre, called 'differentiated proto- plasm.' Protoplasm in this sense sometimes appears, as in the outer part of most amoebae, as a mass of glassy-looking material, either continuous or interrupted by more or less spherical spaces or vacu- oles filled with fluid, sometimes as in a gland cell as a more refrac- INTRODUCTION. 5 tive, cloudy-looking, or finely granular material arranged in a more or less irregular network, or spongework, the interstices of which are occupied either by fluid or by some material different from itself. We shall return however to the features of this 'protoplasm' when we come to treat of white blood corpuscles and other 'protoplasmic' structures. Meanwhile it is sufficient for our present purpose to note that lodged in the protoplasm, discontinuous with it, and forming no part of it, are in the first place collections of fluid, of watery solutions of various substances, occupying the more regular vacuoles or the more irregular spaces of the network, and in the second place discrete granules of one kind or another, also forming no part of the protoplasm itself, but lodged either in the bars or substance of the protoplasm or in the vacuoles or meshes. Now there can be little doubt that the fluids and the discrete granules are dead food or dead waste, but the present state of our knowledge will not permit us to make any very definite statement about the protoplasm itself. We may probably conclude, indeed we may be almost sure that protoplasm in the above sense is not all living substance, that it is made up partly of the real living substance, and partly of material which is becoming living or has ceased to be living ; and in the case where protoplasm is described as forming a network, it is possible that some of the material occupying the meshes of the network may be, like part of the network itself, really alive. ' Protoplasm ' in fact, as in the sense in which we are now using it, and shall continue to use it, is a morphological term ; but it must be borne in mind that the same word ' protoplasm ' is also frequently used to denote what we have just now called 'the real living substance.' The word then embodies a physiological idea ; so used it may be applied to the living substance of all living structures, whatever the micro- scopical features of those structures ; in this sense it cannot at present, and possibly never will be recognised by the microscope, and our knowledge of its nature must be based on inferences. Keeping then to the phrase ' living substance ' we may say that each piece of the body of the amoeba consists of living substance, in which are lodged, or with which are built up in some way or other, food and waste in various stages. Now an amoeba may divide itself into two, each half exhibiting all the phenomena of the whole ; and we can easily imagine the process to be repeated, until the amoeba was divided into a multitude of exceedingly minute amoebae, each having all the properties of the original. But it is obvious, as in the like division of a mass of a chemical substance, that the division could not be repeated indefinitely. Just as in division of the chemical mass we come to the chemical molecule, further division of which changes the properties of the substance, so in the continued division of the amoeba we should come to a stage in which further division interfered with the physiological actions, we should come 6 DIVISION OF LABOUR. to a physiological unit, corresponding to but greatly more complex than the chemical molecule 1. This unit to remain a physiological unit and to continue to live must contain not only a portion of the living substance but also the food for that living substance, in several at least of the stages, from the initial raw food up to the final ' living ' stages, and must similarly contain various stages of waste. § 6. Now the great characteristic of the typical amoeba (leaving out the nucleus) is that, as far as we can ascertain, all the physio- logical units are alike ; they all do the same things. Each and every part of the body receives food more or less raw and builds it up into its own living substance ; each and every part of the body may be at one time quiescent and at another in motion ; each and every part is sensitive and responds by movement or otherwise to various changes in its surroundings. The body of man, in its first stage, while it is as yet an ovum, if we leave aside the nucleus and neglect differences caused by the unequal distribution of food material or yolk, may also be said to be composed of like parts or like physiological units. By the act of segmentation however the ovum is divided into parts or cells which early shew differences from each other; and these differences rapidly increase as development proceeds. Some cells put on certain characters and others other characters ; that is to say the cells undergo histological differentiation. And this takes place in such a way that a number of cells lying together in a group become eventually converted into a tissue, and the whole body becomes a collection of such tissues arranged together according to morphological laws, each tissue having a definite structure, its cellular nature being sometimes preserved, sometimes obscured or even lost. This histological differentiation is accompanied by a physio- logical division of labour. Each tissue may be supposed to be composed of physiological units, the units of the same tissue being alike but differing from the units of other tissues ; and corre- sponding to this difference of structure, the units of different tissues behave or act differently. Instead of all the units as in the amoeba doing the same things equally well, the units of one tissue are told off as it were to do one thing especially well, or especially fully, and thus the whole labour of the body is divided among the several tissues. § 7. The several tissues may thus be classified according to the work which they have to do ; and the first great distinction is into (1) the tissues which are concerned in the setting free of energy in special ways, and (2) the tissues which are concerned in replenishing the substance and so renewing the energy of the body. Each physiological unit of the amoeba while it is engaged in 1 Such a physiological unit might be called a somacule. INTRODUCTION. 7 setting free energy so as to move itself, and by reason of its sen- sitiveness so directing that energy as to produce a movement suitable to the conditions of its surroundings, has at the same time to bear the labour of taking in raw food, of selecting that part of the raw food which is useful and rejecting that which is useless, and of working up the accepted part through a variety of stages into its own living substance ; that is to say it has at the same time that it is feeling and moving to carry on the work of digesting and assimilating. It has moreover at the same time to throw out the waste matters arising from the changes taking place in its own substance, having first brought these waste matters into a condition suitable for being thrown out. § 8. In the body of man movements as we shall see are broadly speaking carried out by means of muscular tissue, and the changes in muscular tissue which lead to the setting free of energy in the form of movement are directed, governed, and adapted to the surroundings of man, by means of nervous tissue. Rays of light fall on the nervous substance of the eye called the retina, and set up in the retina changes which induce in the optic nerve other changes, which in turn are propagated to the brain as nervous impulses, both the excitation and the propagation involving an expenditure of energy. These nervous impulses reaching the brain may induce other nervous impulses which travelling down certain nerves to certain muscles may lead to changes in those muscles by which they suddenly grow short and pull upon the bones or other structures to which they are attached, in which case we say the man starts ; or the nervous impulses reaching the brain may produce some other effects. Similarly sound falling on the ear, or contact between the skin and some foreign body, or some change in the air or other surroundings of the body, or some change within the body itself may so affect the nervous tissue of the body that nervous impulses are started and travel to this point or to that, to the brain or elsewhere and eventually may either reach some muscular tissue and so give rise to movements, or may reach other tissues and produce some other effect. The muscular tissue then may be considered as given up to the production of movement, and the nervous tissue as given up to the generation, transformation and propagation of nervous impulses. In each case 'there is an expenditure of energy, which in the case of the muscle, as we shall see, leaves the body partly as heat, and partly as work done, but in the case of nervous tissue is wholly or almost wholly transformed into heat before it leaves the body ; and this expenditure necessitates a replenishment of energy and a renewal of substance. § 9. In order that these master tissues, the nervous and mus- cular tissues, may carry on their important works to the best ad- vantage, they are relieved of much of the labour that falls upon each physiological unit of the amoeba. They are not presented TISSUES AND ORGANS. with raw food, they are not required to carry out the necessary transformations of their immediate waste matters. The whole of the rest of the body is engaged (1) in so preparing the raw food, and so bringing it to the nervous and muscular tissues that these may build it up into their own substance with the least trouble, and (2) in receiving the waste matters which arise in muscular and nervous tissues, and preparing them for rapid and easy ejection from the body. Thus to certain tissues, which we may speak of broadly as ' tissues of digestion,' is allotted the duty of acting on the food and preparing it for the use of the muscular and nervous tissues; and to other tissues, which we may speak of as "tissues of excretion," is allotted the duty of clearing the body from the waste matters generated by the muscular and nervous tissues. § 10. These tissues are for the most part arranged in machines or mechanisms called organs, and the working of these organs in- volves movement. The movements of these organs are carried out, like the other movements of the body, chiefly by means of muscular tissue governed by nervous tissue. Hence we may make a dis- tinction between the muscles which are concerned in producing an effect on the world outside man's body, the muscles by which man does his_ work in the world, and the muscles which are concerned in carrying out the movements of the internal organs. And we may similarly make a distinction between the nervous tissue con- cerned in carrying out the external work of the body and that concerned in regulating the movements and, as we shall see, the general conduct of the internal organs. But these two classes of muscular and nervous tissue though distinct in work, and as we shall see often different in structure, are not separated or isolated. On the contrary while it is the main duty of the nervous tissue as a whole, the nervous system as we may call it, to carry out, by means of nervous impulses passing hither and thither, what may be spoken of as the work of man, and in this sense is the master tissue, it also serves as a bond of union between itself and the muscles doing external work on the one hand, and the organs of digestion or excretion on the other, so that the activity and con- duct of the latter may be adequately adapted to the needs of the former. § 11. Lastly the food prepared and elaborated by the digestive organs is carried and presented to the muscular and nervous tissues in the form of a complex fluid known as blood, which, driven by means of a complicated mechanism known as the vascular system, circulates all over the body, visiting in turn all the tissues of the body, and by a special arrangement known as the respiratory mechanism, carrying in itself to the several tissues a supply of oxygen as well as of food more properly so called. The motive power of this vascular system is supplied as in the case of the digestive system by means of muscular tissue, the INTRODUCTION. 9 activity of which is similarly governed by the nervous system, and hence the flow of blood to this part or that part is regulated according to the needs of the part. § 12. The above slight sketch will perhaps suffice to shew not only how numerous but how varied are the problems with which Physiology has to deal. In the first place there are what may be called general problems, such as How the food after its preparation and elaboration into blood is built up into the living substance of the several tissues ? How the living substance breaks down into the dead waste ? How the building up and breaking down differ in the different tissues in such a way that energy is set free in different modes, the muscular tissue contracting, the nervous tissue thrilling with a nervous impulse, the secreting tissue doing chemical work, and the like ? To these general questions the answers which we can at present give can hardly be called answers at all. In the second place there are what may be called special problems, such as What are the various steps by which the blood is kept replenished with food and oxygen, and kept free from an accumulation of waste, and how is the activity of the digestive, respiratory and excretory organs, which effect this, regulated and adapted to the stress of circumstances ? What are the details of the working of the vascular mechanism by which each and every tissue is for ever bathed with fresh blood, and how is that working delicately adapted to all the varied changes of the body ? And, compared with which all other special problems are insignifi- cant and preparatory only, How do nervous impulses so flit to and fro within the nervous system as to issue in the movements which make up what we sometimes call the life of man ? It is to these special problems that we must chiefly confine our attention, and we may fitly begin with a study of the blood. BOOK I. BLOOD. THE TISSUES OF MOVEMENT. THE VASCULAR MECHANISM. CHAPTER I. BLOOD. § 13. THE several tissues are traversed by minute tubes, the capillary blood vessels, to which blood is brought by the arteries, and from which blood is carried away by the veins. These capillaries form networks the meshes of which, differing in form and size in the different tissues, are occupied by the elements of the tissue which consequently lie outside the capillaries. The blood flowing through the capillaries consists, under normal conditions, of an almost colourless fluid, the plasma, in which are carried a number of bodies, the red, and the white corpuscles. Outside the capillary walls, filling up such spaces as exist between the capillary walls and the cells or fibres of the tissue, or between the elements of the tissue themselves, is found a colourless fluid, resembling in many respects the plasma of blood and called lymph. Thus all the elements of the tissue and the outsides of all the capillaries are bathed with lymph, which, as we shall see hereafter, is continually flowing away from the tissue along special channels to pass into lymphatic vessels and thence into the blood. As the blood flows through the capillaries certain constituents of the plasma (together with, at times, white corpuscles, and under exceptional circumstances red corpuscles) pass through the capillary wall into the lymph, and certain constituents of the lymph pass through the capillary wall into the blood within the capillary. There is thus an interchange of material between the blood within the capillary and the lymph outside. A similar interchange of material is at the same time going on between the lymph and the tissue itself. Hence, by means of the lymph acting as middleman, a double interchange of material takes place between the blood within the capillary and the tissue outside the capillary. In every tissue, so long as life lasts and the blood flows through the blood vessels, a double stream, now rapid now slow, is passing from the blood to the tissue and from the tissue to the blood. The stream from the blood to the tissue carries to the tissue the material which the tissue needs for building itself up and for doing its work, including the all important oxygen. The 14 BLOOD AN INTERNAL MEDIUM. [BOOK i. stream from the tissue to the blood carries into the blood certain of the products of the chemical changes which have been taking place in the tissue, products which may be simple waste, to be cast out of the body as soon as possible, or which may be bodies capable of being made use of by some other tissue. A third stream, that from the lymph lying in the chinks and crannies of the tissue along the lymph channels to the larger lymph vessels, carries away from the tissue such parts of the material coming from the blood as are not taken up by the tissue itself and such parts of the material coming from the tissue as do not find their way into the blood vessel. In most tissues, as in muscle for instance, the capillary net- work is so close set and the muscular fibre lies so near to the blood vessel that the lymph between the two exists only as a very thin sheet ; but in some tissues as in cartilage the blood vessels lie on the outside of a large mass of tissue, the interchange between the central parts of which and the nearest capillary blood vessel is carried on through a long stretch of lymph passages. But in each case the principle is the same ; the tissue, by the help of lymph, lives on the blood; and when in succeeding pages we speak of changes between the blood and the tissues, it will be understood, whether expressly stated so or no, that the changes are effected by means of the lymph. The blood may thus be regarded as an 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. All the tissues take up oxygen from the blood and give up carbonic acid to the blood, but not always at the same rate or at the same time. Moreover the several tissues take up from the blood and give up to the blood either different things or the same things at different rates or at different times. From this it follows, on the one hand, that the composition and characters of the blood must be for ever varying in different parts of the body and at different times ; and on the other hand, that the united action of all the tissues must tend to establish and maintain an average uniform composition of the whole mass of blood. The special changes which blood is known to undergo while it passes through the several tissues will best be dealt with when the individual tissues and organs come under our considera- tion. At present it will be sufficient to study the main features which are presented by blood, brought so to speak, into a state of equilibrium by the common action of all the tissues. Of all these main features of blood, the most striking if not the most important is the property it possesses of clotting when shed. SECT. I. THE CLOTTING OF BLOOD. § 14. 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 bulk as the previously fluid blood, and if carefully shaken out will present 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 slightly concave. 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 chiefly white. The fibrils are composed of a substance called fibrin. Hence we may speak of the clot as consisting of fibrin and corpuscles ; and the act of clotting is obviously a substitution for the plasma of fibrin and serum, followed by a separation of the fibrin and corpuscles from the serum. 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 clotting is generally complete in from one 1C PHENOMENA OF CLOTTING. [BOOK i. to several hours. The times however will be found to vary accord- ing to circumstances. Among animals the rapidity of clotting varies exceedingly in different species. The blood of the horse clots with remarkable slowness; so slowly indeed that many of the red and also some of the white corpuscles (both these being speci- fically 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 por- tions 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 certain abnormal conditions of the body. If a portion of horse's blood be surrounded by a cooling mix- ture of ice and salt, and thus kept at about 0° C., clotting may be almost indefinitely postponed. Under these circumstances a more complete descent of the corpuscles takes place, and a con- siderable quantity of colourless transparent plasma free from blood- corpuscles may be obtained. A portion of this plasma removed from the freezing mixture clots in the same manner 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 this colourless plasma, or of a similar plasma which may be obtained from almost any blood by means which we will presently describe, be diluted with many times its bulk of a 0'6 p.c. solution of sodium chloride1 clotting is 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 clotting 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 clot is stirred or whipped with a bundle of rods (or anything presenting a large amount of rough surface), no jelly-like clotting 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 clotting. 1 A solution of sodium chloride of this strength will hereafter be spoken of as ' normal saline solution. ' CHAP, i.] BLOOD. 17 Putting these facts together, it is very clear that the pheno- mena of the clotting of blood are caused by the appearance in the plasma of fine fibrils of fibrin. So 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 formation they begin to shrink, and while shrinking enclose in their meshes the corpuscles but squeeze out the fluid parts of the blood. Hence the appearance of the shrunken coloured clot and the colourless serum. § 15. Fibrin, whether obtained by whipping freshly-shed blood, or by washing either a normal clot, or a clot obtained from colourless plasma, exhibits the same general characters. It belongs to that class, of complex unstable nitrogenous bodies called proteids which form a large portion of all living bodies and an essential part of all living structures. Our knowledge of proteids is at present too imperfect, and probably none of them have yet been prepared in adequate purity, to justify us in attempting to assign to them any definite formula ; but it is important to remember their general composition. 100 parts of a proteid contain rather more than 50 parts of carbon, rather more than 15 of nitrogen, about 7 of hydrogen, and rather more than 20 of oxygen ; that is to say they contain about half their weight of carbon, and only about ^th their weight of nitrogen ; and yet as we shall see they are eminently the nitro- genous substances of the body. They usually contain a small quantity (1 or 2 p.c.) of sulphur, and many also have some phosphorus attached to them in some way or other. When burnt they leave a variable quantity of ash, consisting of inorganic salts of which the bases are chiefly sodium and potassium and the acids chiefly hydrochloric, sulphuric, phosphoric and carbonic. They all give certain reactions, by which their presence may be recognised : of these the most characteristic are the following. Boiled with nitric acid they give a yellow colour, which deepens into orange upon the addition of ammonia. This is called the xanthoproteic test ; the colour is due to a product of decom- position. Boiled with the mixture of mercuric and rnercurous nitrates known as Millon's reagent they give a pink colour. Mixed with a strong solution of sodic hydrate they give on the addition of a drop or two of a very weak solution of cupric sul- phate a violet colour which deepens on heating. These are arti- ficial reactions, not throwing much if any light on the constitu- tion of proteids ; but they are useful as practical tests enabling us to detect the presence of proteids. The several members of the proteid group are at present dis- tinguished from each other chiefly by their respective solubilities, especially in various saline solutions. Fibrin is one of the least soluble ; it is insoluble in water, almost insoluble in dilute neutral saline solutions, and very sparingly soluble in more concentrated F. 2 18 PROTEIDS OF SERUM. [BOOK i. neutral saline solutions and in dilute acids and alkalis. In strong acids and alkalis it dissolves, but in the process becomes com- pletely changed into something which is no longer fibrin. In dilute acids it swells up and becomes transparent, but when the acid is i neutralized returns to its previous condition. When suspended in water and heated to 100° C. or even to 75° C., it becomes changed, and still less soluble than before ; it is said in this case to be coagulated by the heat, and as we shall see nearly all proteids have the property of being changed in nature, of undergoing coagulation and so becoming less soluble than before, by being exposed to a certain high temperature. Fibrin then is a proteid distinguished from other proteids by its smaller solubility; it is further distinguished by its peculiar filamentous structure, the other proteids when obtained in a solid form appearing either in amorphous granules or at most in viscid masses. § 16. We may now return to the serum. This is perfectly fluid, and remains fluid until it decomposes. It is of a faint straw colour, due to the presence of a special pigment substance, differing from the red matter which gives redness to the red corpuscles. Tested by the xanthoproteic and other tests it obviously contains a large quantity of proteid matter, and upon examination we find that at least two distinct proteid substances are present in it. If crystals of magnesium sulphate be added to serum and gently stirred until they dissolve, it will be seen that the serum as it approaches saturation with the salt becomes turbid instead of remaining clear, and eventually a white amorphous granular or flocculent precipitate makes its appearance. This precipitate may be separated by decantation or filtration, washed with saturated solutions of magnesium sulphate, in which it is insoluble, until it is freed from all other constituents of the serum, and thus obtained fairly pure. It is then found to be a proteid body, distinguished by the following characters among others : 1. It is (when freed from any adherent magnesium sulphate) insoluble in distilled water; it is insoluble in concentrated solutions of neutral saline bodies, such as magnesium sulphate, sodium chloride, &c., but readily soluble in dilute (e.g. 1 p.c.)' solutions of the same neutral saline bodies. Hence from its solutions in the latter it may be precipitated either by adding more neutral saline substance or by removing by dialysis the small quantity of saline substance present. When obtained in a pre- cipitated form, and suspended in distilled water, it readily dissolves into a clear solution upon the addition of a small quantity of some neutral saline body. By these various solutions and precipitations it is not really changed in nature. 2. It readily dissolves in very dilute acids (e.g. in hydro- CHAP, i.] BLOOD. 19 chloric acid even when diluted to far less than 1 p.c.), and it is similarly soluble in dilute alkalis, but in being thus dissolved it is wholly changed in nature, and the solutions of it in dilute acid and dilute alkalis give reactions quite different from those of the solu- tion of the substance in dilute neutral saline solutions. By the acid it is converted into what is called acid-albumin, by the alkali into alkali-albumin, both of which bodies we shall have to study later on. 3. When it is suspended in water and heated it becomes altered in character, coagulated, and all its reactions are changed. It is no longer soluble in dilute neutral saline solutions, not even in dilute acids and alkalis ; it has become coagulated proteid, and is now even less soluble than fresh fibrin. When a solution of it in dilute neutral saline solution is similarly heated, a similar change takes place, a precipitate falls down which on examination is found to be coagulated proteid. The temperature at which this change takes place is somewhere about 75° C., though shifting slightly according to the quantity of saline substance present in the solu- tion. The above three reactions are given by a number of proteid bodies forming a group called globulins, and the particular globulin present in blood-serum is called paraglobulin. One of the proteids present in blood-serum is then para- globulin, characterised by its solubility in dilute neutral saline solutions, its insolubility in distilled water and concentrated saline solutions, its ready solubility, and at the same time conversion into other bodies, in dilute acids and alkalis, and in its becoming converted into coagulated proteid, and so being precipitated from its solutions at 75° C. The amount of it present in blood-serum varies in various animals, and apparently in the same animal at different times. In 100 parts by weight of serum there are generally present about 8 or 9 parts of proteids altogether, and of these some 3 or 4, more or less, may be taken as paraglobulin. § 17. If the serum from which the paraglobulin has been pre- cipitated by the addition of neutral salt, and removed by filtra- tion, be subjected to dialysis, the salt added may be removed, and a clear, somewhat diluted serum free from paraglobulin may be obtained. This still gives abundant proteid reactions, so that the serum still contains a proteid, or some proteids still more soluble than the globulins, since they will remain in solution, and are not precipi- tated, even when dialysis is continued until the serum is practically freed from both the neutral salt added to it and the diffusible salts previously present in the natural serum. When this serum is heated to 75° C. a precipitate makes its appearance, the proteids still present are coagulated at this temperature. 20 PROTEIDS OF SERUM. [BOOK i. We have some reasons for thinking that more than one proteid is present, but they are all closely allied to each other, and we may for the present speak of them as if they were one, and call the proteid left in serum, after removal of the paraglobulin, by the name of albumin, or, to distinguish it from other albumins found elsewhere, serum-albumin. Serum-albumin is distinguished by being more soluble than the globulins, since it is soluble in distilled water, even in the absence of all neutral salts. Like the globulins, though with much less ease, it is converted by dilute acids and dilute alkalis into acid- or into alkali-albumin. The percentage amount of serum-albumin in serum may be put down as 4 or 5, more or less, but it varies and sometimes is less abundant than paraglobulin. In some animals (snakes) it is said to disappear during starvation. The more important characters of the three proteids which we have just studied may be stated as follows : Soluble in water and in saline solutions of all strengths serum-albumin. Insoluble in water, readily soluble in dilute saline solutions, insoluble in concentrated saline so- lutions paraglobulin. Insoluble in water, hardly soluble at all in dilute saline solutions, and very little soluble in more concentrated saline solutions fibrin. Besides paraglobulin and serum-albumin, serum contains a very large number of substances, generally in small quantity, which, since they have to be extracted by special methods, are called extractives ; of these some are nitrogenous, some non-nitrogenous. Serum contains besides important inorganic saline substances; but to these we shall return. § 18. With the knowledge which we have gained of the pro- teids of clotted blood we may go back to the question : — Clotting being due to the appearance in blood plasma of a proteid sub- stance, fibrin, which previously did not exist in it as such, what are the causes which lead to the appearance of fibrin ? We learn something by studying the most important external circumstances which affect the rapidity with which the blood of the same individual clots when shed. These are as follows : A temperature of about 40° C., which is about or slightly above the temperature of the blood of warm-blooded animals, is perhaps the most favourable to clotting. A further rise of a few degrees is apparently also beneficial, or at least not injurious ; but upon a still further rise the effect changes, and when blood is rapidly heated to 56° C. no clotting at all may take place. At this temperature certain proteids of the blood are coagulated and precipitated before clotting can take place, and with this change the power of the blood to clot is wholly lost. If however the heating be not very rapid, CHAP, i.] BLOOD. 21 the blood may clot before this change has time to come on. When the temperature instead of being raised is lowered below 40° C. the clotting becomes delayed and prolonged ; and at the temperature of 0° or 1° C. the blood will remain fluid, and yet capable of clotting when withdrawn from the adverse circumstances, for a very long, it might almost be said, for an indefinite time. A small quantity of blood shed into a small vessel clots sooner than a large quantity shed into a larger one ; and in general the greater the amount of foreign surface with which the blood comes in contact the more rapid the clotting. When shed blood is stirred or " whipped " the fibrin makes its appearance sooner than when the blood is left to clot in the ordinary way ; so that here too the accelerating influence of contact with foreign bodies makes itself felt. Similarly, movement of shed blood hastens clotting, since it increases the amount of contact with foreign bodies. So also the addition of spongy platinum or of powdered charcoal, or of other inert powders, to tardily clotting blood, will by influence of surface, hasten clotting. Conversely, blood brought into contact with pure oil does not clot so rapidly as when in contact with glass or metal ; and blood will continue to flow for a longer time without clotting through a tube smeared inside with oil than through a tube not so smeared. The influence of the oil in such cases is a physical not a chemical one ; any pure neutral inert oil will do. As far as we know these influences affect only the rapidity with which the clotting takes place, that is, the rapidity with which the fibrin makes its appearance, not the amount of clot, not the quan- tity of fibrin formed, though when clotting is very much retarded by cold changes may ensue whereby the amount of clotting which eventually takes place is indirectly affected. Mere exposure to air exerts apparently little influence on the process of clotting. Blood collected direct from a blood-vessel over mercury so as wholly to exclude the air, clots, in a general way, as readily as blood freely exposed to the air. It is only when blood is much laden with carbonic acid, the presence of which is antagonistic to clotting, that exclusion of air, by hindering the escape of the excess of carbonic acid, delays clotting. These facts teach us that fibrin does not as was once thought make its appearance in shed blood because the blood when shed ceases to share in the movement of the circulation, or because the blood is cooled on leaving the warm body, or because the blood is then more freely exposed to the air ; they further suggest the view that the fibrin is the result of some chemical change, the conversion into fibrin of something which is not fibrin, the change like other chemical changes being most active at an optimum temperature, and like so many other chemical changes being assisted by the influences exerted by the presence of inert bodies. And we have direct experimental evidence that plasma does contain an antecedent of fibrin which by chemical change is converted into fibrin. 22 PLASMA. [BOOK i. § 19. 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, clotting, 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 it contains an excess of the neutral salt. The presence of the neutral salt has acted in the same direction as cold: it has prevented the occurrence of clotting. It has not destroyed the fibrin ; for if some of the plasma be diluted with from five to ten times its bulk of water, it will clot speedily in quite a normal fashion, with the production of quite normal fibrin. The separation of the fluid plasma from the corpuscles and from other bodies heavier than the plasma is much facilitated by the use of the centrifugal machine. This consists essentially of a tireless wheel with several spokes, placed in a horizontal position and made to revolve with great velocity (1000 revolutions per minute for instance) round its axis. Tubes of metal or very strong glass are suspended at the ends of the spokes by carefully adjusted joints. As the wheel rotates with increasing velocity, each tube gradually assumes a horizontal position, bottom outwards, without spilling any of its contents. As the rapid rotation continues the corpuscles and heavier particles are driven to the bottom of the tube, and if a very rapid .movement be continued for a long time will form a compact cake at the bottom of the tube.- When the rotation, is stopped the tubes gradually return to their upright position again without anything being spilt, and the clear plasma in each tube can then be decanted off. 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 flaky, somewhat sticky precipitate will make its appearance. If this precipitate be re- moved, the fluid no longer possesses the power of clotting (or very slightly so), even though the neutral salt present be removed by dialysis, or its influence lessened by dilution. With the removal of the substance precipitated, the plasma has lost its power of clotting. 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 dissolves1, and the solution rapidly filtered gives a clear colourless filtrate, which is _at_ first perfectly fluid. Soon however the fluidity gives way to viscidity, 1 The substance itself is not soluble in distilled water, but a quantity of the neutral salts always clings to the precipitate, and thus the addition of water virtually gives rise to a dilute saline solution, in which the substance is readily soluble. CHAP, i.] BLOOD. 23 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, precipitable by saturation with neutral salts, a some- thing which, since it is soluble in very dilute saline solutions, cannot be fibrin itself, but which in solution speedily gives rise to the appearance of fibrin. To this substance its discoverer, Denis, gave the name of plasmine. The substance thus precipitated is not however a single body but a mixture of at least two bodies. If sodium chloride be carefully added to plasma to an extent of about 13 per cent, a white flaky viscid precipitate is thrown down very much like plasmine. If after the removal of the first precipitate more sodium chloride and especially if magnesium sulphate be added, a second precipitate is thrown down, less viscid and more granular than the first. The second precipitate when examined is found to be identical with the paraglobulin, coagulating at 75° C., which we have already seen to be a constituent of serum. The first precipitate is also a proteid belonging to the globulin group, but differs from paraglobulin not only in being more readily precipitated by sodium chloride, and in being when precipitated more viscid, but also in other respects, and especially in being coagulated at a far lower temperature than paraglobulin, viz. at 56° C. Now while isolated paraglobulin cannot by any means known to us be converted into fibrin, and its presence in the so-called plasmine does not seem to be essential to the formation of fibrin out of plasmine, the presence in plasmine of the body coagulating at 56° C. does seem essential to the conversion of plasmine into fibrin, and we have reason for thinking that it is itself converted, in part at least, into fibrin. Hence it has received the name of Jibrinogen. § 20. The reasons for this view are as follows. Besides blood which clots naturally when shed, there are certain fluids in the body which do not clot naturally, either in the body or when shed, but which by certain artificial means may be made to clot, and in clotting to yield quite normal fibrin. Thus the so-called serous fluid taken some hours after death1 from the pericardial, pleural or peritoneal cavities, the fluid found in the enlarged serous sac of the testis, known as hydrocele fluid, and other similar fluids, will in the majority of cases, when obtained free from blood or other admixtures, remain fluid almost indefinitely, shewing no disposition whatever to clot2. Yet in most cases at 1 If it be removed immediately after death it generally clots readily and firmly, giving a colourless clot consisting of fibrin and white corpuscles. 2 In some specimens, however, a spontaneous coagulation, generally slight, but in exceptional cases massive, may be observed. 24 FIBRIN FERMENT. [BOOK i. all events, these fluids, when a little blood, or a piece of blood clot, or a little serum is added to them, will clot rapidly and firmly1, giving rise to an unmistakeable clot of normal fibrin, differing only from the clot of blood in that, when serum is used, it is colourless, being free from red corpuscles. Now blood (or blood clot, or serum) contains many things, to any one of which the clotting power thus seen might be attributed. But it is found that in many cases clotting may be induced in the fluids of which we are speaking by the mere addition, and that even in exceedingly small quantity, of a substance which can be extracted from blood, or from serum, or from blood clot, or even from washed fibrin, or indeed from other sources, a substance whose exact nature is uncertain, it being doubtful whether it is a proteid at all, and whose action is peculiar. If serum, or whipped blood or a broken-up clot be mixed with a large quantity of alcohol and allowed to stand some days, the proteids present are in time so changed by the alcohol as to become insoluble in water. Hence if the copious precipitate caused by the alcohol, after long standing, be separated by filtration from the alcohol, dried at a low temperature, not exceeding 40° C., and extracted with distilled water, the aqueous extract contains very little proteid matter, indeed very little organic matter at all. Nevertheless even a small quantity of this aqueous extract added alone to certain specimens of hydrocele fluid or other of the fluids spoken of above, will bring about a speedy clotting. The same aqueous extract has also a remarkable effect in hastening the clotting of fluids which, though they will eventually clot, do so very slowly. Thus plasma may, by the careful addition of a certain quantity of neutral salt and water, be reduced to such a condition that it clots very slowly indeed, taking perhaps days to complete the process. The addition of a small quantity of the aqueous extract we are describing will however bring about a clotting which is at once rapid and complete. The active substance, whatever it be, in this aqueous extract exists in small quantity only, and its clotting virtues are at once and for ever lost when the solution is boiled. Further, there is no reason to think that the active substance actually enters into the formation of the fibrin to which it gives rise. It appears to belong to a class of bodies playing an important part in physiological processes and called ferments, of which we shall have more to say hereafter. We may therefore speak of it as the fibrin ferment, the name given to it by its discoverer Alexander Schmidt. This fibrin ferment is present in and may be extracted from clotted or whipped blood, and from both the clot 2 and the serum of clotted blood ; and since in most if not all cases where blood or 1 In a few cases no coagulation can thus be induced. - A powerful solution of fibrin ferment may be readily prepared by simply extracting a washed blood clot with a 10 p.c. solution of sodium chloride. CHAP, i.] BLOOD. 25 blood clot or serum produces clotting in hydrocele or pericardial fluid, an exactly similar clotting may be induced by the mere addition of fibrin ferment, we seem justified in concluding that the clotting virtues of the former are due to the ferment which they contain. Now when fibrinogen is precipitated from plasma as above described by sodium chloride, redissolved, and reprecipitated, more than once, it may be obtained in solution, by help of a dilute neutral saline solution, in an approximately pure condition, at all events free from other proteids. Such a solution will not clot spontaneously ; it may remain fluid indefinitely ; and yet on the addition of a little fibrin ferment it will clot readily and firmly, yielding quite normal fibrin. This body fibrinogen is also present and may be separated out from the specimens of hydrocele, pericardial, and other fluids which clot on the addition of fibrin ferment, and when the fibrinogen has been wholly removed from these fluids they refuse to clot on the addition of fibrin ferment. Paraglobulin, on the other hand, whether prepared from plasmine by separation of the fibrinogen, or from serum, or from other fluids in which it is found, cannot be converted by fibrin ferment or indeed by any other means into fibrin. And fibrinogen isolated as de- scribed above, or serous fluids which contain fibrinogen, can be made, by means of fibrin ferment, to yield quite normal fibrin in the com- plete absence of paraglobulin. A solution of paraglobulin obtained from serum or blood clot will it is true clot pericardial or hydrocele fluids containing fibrinogen, or indeed a solution of fibrinogen, but this is apparently due to the fact that the paraglobulin has in these cases some fibrin ferment mixed with it ; it is also possible that under certain conditions the presence of paraglobulin may be favourable to the action of the ferment. When the so-called plasmine is precipitated as directed in § 19 fibrin ferment is carried down with the fibrinogen and para- globulin, and when the plasmine is re-dissolved the ferment is present in the solution and ready to act on the fibrinogen. Hence the re-dissolved plasmine clots spontaneously. When fibrinogen is isolated from plasma by repeated precipitation and solution, the ferment is washed away from it, and the pure ferment-free fibrin- ogen, ultimately obtained, does not clot spontaneously. So far it seems clear that there does exist a proteid body, fibrin- ogen, which may by the action of fibrin ferment be directly, without the intervention of other proteids, converted into the less soluble fibrin. Our knowledge of the constitution of proteid bodies is too imperfect to enable us to make any very definite statement as to the exact nature of the change thus effected ; but we may say this much. Fibrinogen and fibrin have about the same elementary com- position, fibrin containing a trifle more nitrogen. When fibrinogen is converted into fibrin by means of fibrin ferment, the weight of 26 FIBRINOGEN AND FIBRIN. [BOOK i. the fibrin produced is always less than that of the fibrinogen which is consumed, and there is always produced at the same time a certain quantity of another proteid, belonging to the globulin family. There are reasons however why we cannot speak of the ferment as splitting up fibrinogen into fibrin and a globulin ; it seems more probable that the ferment converts the fibrinogen first into a body which we might call soluble fibrin, and then turns this body into veritable fibrin ; but further inquiries on the subject are needed. It may be added that among the conditions necessary for the due action of fibrin ferment on fibrinogen, the presence of a certain quantity of some neutral salt seems to be one. In the total absence of all neutral salts the ferment cannot convert the fibrinogen into fibrin. There are some reasons also for thinking that the presence of a lime salt such as calcium sulphate, though it may be in minute quantity only, is essential. § 21. We may conclude then that the plasma of blood when shed, or at all events soon after it has been shed, contains fibrino- gen ; and it also seems probable that the clotting comes about because the fibrinogen is converted into fibrin by the action of fibrin ferment ; but we are still far from a definite answer to the question, why blood remains fluid in the body and yet clots when shed ? We have already said that blood, or blood plasma, brought up to a temperature of 56°C. as soon as possible after its removal from the living blood vessels, gives a proteid precipitate and loses its power of clotting. This may be taken to shew that blood, as it circulates in the living blood vessels, contains fibrinogen as such, and that when the blood is heated to 56" C., which is the coagu- lating point of fibrinogen, the fibrinogen present is coagulated and precipitated, and consequently no fibrin can be formed. Further, while clotted blood undoubtedly contains an abundance of fibrin ferment, no ferment, or a minimal quantity only, is present in blood as it leaves the blood vessels. If blood be received directty from the blood vessels into alcohol, the aqueous extract prepared as directed above contains no ferment or merely a trace. Appa- rently the ferment makes its appearance in the blood as the result of changes taking place in the blood after it has been shed. We might from this be inclined to conclude that blood clots when shed but not before, because, fibrinogen being always present, the shedding brings about changes which produce fibrin ferment, not previously existing, and this acting on the fibrinogen gives rise to fibrin. But we meet with the following difficulty. A very considerable quantity of very active ferment may be injected into the blood current of a living animal without necessarily producing any clotting at all. Obviously either blood within the blood vessels does not contain fibrinogen as such, and the fibrinogen detected by heating the blood to 56° C. is the result of changes CHAP, i.] BLOOD. 27 which have already ensued before that temperature is reached ; or in the living circulation there are agencies at work which prevent any ferment which may be introduced into the circula- tion from producing its usual effects on fibrinogen ; or there are agencies at work which destroy or do away with the fibrin, little by little, as it is formed. § 22. And indeed when we reflect how complex blood is, and of what many and great changes it is susceptible, we shall not wonder that the question we are putting cannot be answered off hand. The corpuscles with which blood is crowded are living structures and consequently are continually acting upon and being acted upon by the plasma. The red corpuscles it is true are, as we shall see, peculiar bodies, with a restricted life and a very specialized work, and possibly their influence on the plasma is not very great ; but we have reason to think that the relations between the white cor- puscles and the plasma are close and important. Then again the blood is not only acting upon and being acted upon by the several tissues as it flows through the various capillaries, but along the whole of its course, through the heart, arteries, capil- laries and veins, is acting upon and being acted upon by the vascular walls, which like the rest of the body are alive, and being alive are continually undergoing and promoting change. That relations of some kind, having a direct influence on the clotting of blood, do exist between the blood and the vascular walls is shewn by the following facts. 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 clotting begins. Thus some hours after death the blood in the great veins may be found still perfectly fluid. Yet such blood has not lost its power of clotting ; it still clots when removed from the body, and clots too when received over mercury without exposure to air, shewing that, though the blood, being highly venous, is rich in carbonic acid and contains little or no oxygen, its fluidity is not due to any excess of carbonic acid or absence of oxy- gen. Eventually it does clot even within the vessels, but perhaps never so firmly and completely as when shed. It clots first in the larger vessels, but remains fluid in the smaller vessels for a very long time, for many hours in fact, since in these the same bulk of blood is exposed to the influence of, and reciprocally exerts an influence on, a larger surface of the vascular walls than in the larger vessels. And if it be urged that the result is here due to influences exerted by the body at large, by the tissues as well as by the vascular walls, this objection will not hold good against the following experiment. If the jugular vein of a large animal, such as an ox or horse, be carefully ligatured when full of blood, and the ligatured portion 28 INFLUENCE OF BLOOD VESSELS. [BOOK i. 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 a glass or other 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 clotting taking place. A similar relation of the fluid to its containing living wall is seen in the case of those serous fluids which clot 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 pericardial fluid (which, as we have already seen, during life, and some little time after death, possesses the power of clotting) 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 pipette clots at once. This relation between the blood and the vascular wall may be disturbed or overridden : clotting may take place or may be induced within the living blood vessel. When the lining membrane is injured, as when an artery or vein is sharply ligatured, or when it is diseased, as for instance in aneurism, a clot is apt to be formed at the injured or diseased spot ; and in certain morbid conditions of the body clots are formed in various vascular tracts. Absence of motion, which in shed blood, as we have seen, is unfavourable to clotting, is apt within the body to lead to clotting. Thus when an artery is ligatured, the blood in the tract of artery on the cardiac side of the ligature, between the ligature and the branch last given off by the artery, ceasing to share in the circulation, remains motionless or nearly so, and along this tract a clot forms, firmest next to the ligature and ending near where the branch is given off; this perhaps may be explained by the fact that the walls of the tract suffer in their nutrition by the stagnation of the blood, and that consequently the normal relation between them and the contained blood is disturbed. That the blood within the living blood vessels, though not actu- ally clotting under normal circumstances, may easily be made to clot, that the blood is in fact so to speak always on the point of clot- ting, is shewn by the fact that a foreign body, such as a needle thrust into the interior of a blood vessel or a thread drawn through and left in a blood vessel, is apt to become covered with fibrin. Some influence exerted by the needle or thread, whatever may be the character of that influence, is sufficient to determine a clotting, which otherwise would not have taken place. The same instability of the blood as regards clotting is strikingly shewn, in the case of the rabbit at least, by the result of injecting into the blood vessels a small quantity of a solution of a peculiar proteid prepared from certain structures such as the thymus body. CHAP. i.J BLOOD. 29 Massive clotting of the blood in almost all the blood vessels, small and large, takes place with great rapidity, leading to the sudden death of the animal. In contrast to this effect may be mentioned the result of injecting into the blood vessels of a dog a quantity of a solution of a body called albumose, of which we shall hereafter have to treat as a product of the digestion of proteid substances, to the extent of "3 grm. per kilo of body weight. So far from producing clotting, the injected albumose has such an effect on the blood that for several hours after the injection shed blood will refuse to clot of itself and remain quite fluid, though it can be made to clot by special treatment. § 23. All the foregoing facts tend to shew that the blood as it is flowing through the healthy blood vessels is, as far as clotting is concerned, in a state of unstable equilibrium, which may at any moment be upset, even within the blood vessels, and which is upset directly the blood is shed, with clotting as a result. Our present knowledge does not permit us to make an authoritative statement as to the exact nature of this equilibrium. There are reasons how- ever for thinking that the white corpuscles play an important part in the matter. Wherever clotting occurs naturally, white corpuscles are present ; and this is true not only of blood but also of such specimens of pericardial or other serous fluids as clot naturally. When horse's blood is kept fluid by being retained within the jugular vein, as mentioned a little while back, and the vein is hung upright, the corpuscles both red and white sink, leaving an upper layer of plasma almost free from corpuscles. This upper layer will be found to have lost largely its power of clotting spon- taneously, though the power is at once regained if the white corpuscles from the layers beneath be returned to it. And many other arguments, which we cannot enter upon here, may be adduced all pointing to the same conclusion, that the white corpuscles play an important part in the process of clotting. But it would lead us too far into controversial matters to attempt to define what that part is, or to explain the exact nature of the equilibrium of which we have spoken, or to discuss such questions as — Whether the ordinary white corpuscles, or corpuscles of a special kind are con- cerned in the matter ? Whether the corpuscles, when clotting takes place, give out something, e.g. fibrinogen or ferment or both or something else, or whether the corpuscles simply in some way or other assist in the transformation of some previously existing con- stituents of the plasma ? Whether the influence exerted by the condition of the vascular wall is exerted directly on the plasma or indirectly on the corpuscles ? Whether, as some have thought, the peculiar bodies of which we shall presently speak under the name of blood platelets have any share in the matter, and if so what ? These questions are too involved and the discussion of them too long to be entered upon here. What we do know is that in blood soon after it has been shed, 30 CLOTTING OF BLOOD. [Bpoic i. the body which we have called fibrinogen is present as also the body which we have called fibrin ferment, that the latter acting on the former will produce fibrin, and that the appearance of fibrin is undoubtedly the cause of what is called clotting. We seem justi- fied in concluding that the clotting of shed blood is due to the conversion by ferment of fibrinogen into fibrin. The further infer- ence that clotting within the body is the same thing as clotting outside the body and similarly due to the transformation of fibrino- gen by ferment into fibrin, though probable, is not proved. We do not yet know the exact nature and condition of the blood within the living blood vessels, and until we know that we cannot satis- factorily explain why blood in the living blood vessels is usually fluid but can at times clot. SEC. 2. THE CORPUSCLES OF THE BLOOD. The Red Corpuscles. § 24. The redness of blood is due exclusively to the red cor- puscles. The plasma as seen in thin layers within the living blood vessels appears colourless, as does also a thin layer of serum ; but a thick layer of serum (and probably of plasma) has a faint yellowish tinge due as we have said to the presence of a small quantity of a special pigment. The corpuscles appear under the microscope as fairly homo- geneous, imperfectly translucent biconcave discs with a diameter of 7 to 8 /A and a thickness of 1 to 2 //,. Being discs they are circular in outline when seen on the flat, but rod-shaped when seen in profile as they are turning over. Being biconcave, with a thicker rounded rim surrounding a thinner centre, the rays of light in passing through them, when they are examined by transmitted light, are more refracted at the rim than in the centre. The effect of this is that, when viewed at what may be considered the proper focus, the centre of a corpuscle appears clear, while a slight opacity marks out indistinctly the inner margin of the thicker rim, whereas, when the focus is shifted either up or down, the centre becomes dark and the rest of the corpuscle clear. Any body of the same shape, and com- posed of substance of the same refractive power, would produce the same optical effects. Otherwise the corpuscle appears homogeneous without distinction of parts and without a nucleus. A single cor- puscle seen by itself has a very faint colour, looking yellow rather than red, but when several corpuscles lie one upon the top of the other the mass is distinctly red. The red corpuscle is elastic, in the sense that it may be deformed by pressure or traction, but when the pressure or traction is re- moved regains its previous form. Its shape is also much influenced by the physical conditions of the plasma, serum, or fluid in which for the time being it is. If the plasma or serum be diluted with water, the disc, absorbing water, swells up into a sphere, becoming 32 STRUCTURE OF RED CORPUSCLE. [BOOK i. a disc again on the removal of the dilution. If the serum be con- centrated, the disc, giving out water, shrinks irregularly and assumes various forms ; one of these forms is that of a number of blunted protuberances projecting all over the surface of the corpuscle, which is then said to be crenate ; in a drop of blood examined under the microscope, crenate corpuscles are often seen at the edge of the cover slip where evaporation is leading to concentration of the plasma, or, as it should then perhaps rather be called, serum. In blood just shed the red corpuscles are apt to adhere to each other by their flat surfaces, much more than to the glass or other surface with which the blood is in contact, and hence arrange themselves in rolls. This tendency however to form rolls very soon diminishes after the blood is shed. Though a single corpuscle is somewhat translucent, a compara- tively thin layer of blood is opaque ; type for instance cannot be read through even a thin layer of blood. When a quantity of whipped blood (or blood otherwise de- prived of fibrin) is frozen and thawed several times it changes colour, becoming of a darker hue, and is then found to be much more transparent, so that type can now be easily read through a moderately thin layer. It is then spoken of as laky blood. The same change may be effected by shaking the blood with ether, or by adding a small quantity of bile salts, and in other ways. Upon examination of laky blood it is found that the red corpuscles are "broken up" or at least altered, and that the redness which pre- viously was confined to them is now diffused through the serum. Normal blood is opaque because each corpuscle while permitting some rays of light (chiefly red) to pass through, reflects many others, and the brightness of the hue of normal blood is due to this reflec- tion of light from the surfaces of the several corpuscles. Laky blood is transparent because there are no longer intact corpuscles to present surfaces for the reflection of light, and the darker hue of laky blood is similarly due to the absence of reflection from the several corpuscles. When laky blood is allowed to stand a sediment is formed (and may be separated by the centrifugal machine) which on examination is found to consist of discs, or fragments of discs, of a colourless substance exhibiting under high powers an obscurely spongy or reticular structure. These colourless thin discs seen flat-wise often appear as mere rings. The substance composing them stains with various reagents and may thus be made more evident. The red corpuscle then consists obviously of a colourless frame- work, with which in normal conditions a red colouring matter is associated; but by various means the colouring matter may be driven from the framework and dissolved in the serum. The framework is spoken of as stroma ; it is a modified or differentiated protoplasm, and upon chemical analysis yields pro- teid substances, some of them at least belonging to the globulin CHAP, i.] BLOOD. 33 group, and other matters, among which is the peculiar complex fat called lecithin of which we shall have to speak in treating of nervous tissue. In the nucleated red corpuscles of the lower vertebrata this differentiated stroma, though forming the chief part of the cell body around the nucleus, is accompanied by a variable amount of undifferentiated protoplasm, but the latter in the mammalian red corpuscle is either absent altogether or reduced to a minimum. Whether any part of this stroma is living, in the sense of being capable of carrying on a continual double chemical change, of continually building itself up as it breaks down, is a question too difficult to be discussed here. The red colouring matter which in normal conditions is associa- ted with this stroma may by appropriate means be isolated, and, in the case of the blood of many animals, obtained in a crystalline form. It is called Hcemoglobin, and may by proper methods be split up into a proteid belonging to the globulin group, and into a / coloured pigment, containing iron, called Hcematin. Haemoglobin is therefore a very complex body. It is found to have remarkable relations to oxygen, and indeed as we shall see the red corpuscles by virtue of their haemoglobin have a special work in respiration ; they carry oxygen from the lungs to the several tissues. We shall therefore defer the further study of haemoglobin until we have to deal with respiration. The red corpuscle then consists of a disc of colourless stroma with which is associated in a peculiar way the complex coloured body haemoglobin. Though the haemoglobin, as is seen in laky blood, is readily soluble in serum (and it is also soluble in plasma), in the intact normal blood it remains confined to the corpuscle ; obviously there is some special connection between the stroma and the haemo- globin ; it is not until the stroma is altered, we may perhaps say killed (as by repeated freezing and thawing), that it loses its hold on the haemoglobin, which thus set free passes into solution in the serum. The disc of stroma when separated from the haemoglobin has as we have just said an obscurely spongy texture ; but we do not know accurately the exact condition of the stroma in the intact corpuscle or how it holds the haemoglobin. There is certainly no definite membrane or envelope to the corpuscle, for by exposing blood to a high temperature, 60° C., the corpuscle will break up into more or less spherical pieces, each still consisting of stroma and haemoglobin. The quantity of stroma necessary to hold a quantity of haemo- globin is exceedingly small. Of the total solid matter of a cor- puscle more than 90 p.c. is haemoglobin. A red corpuscle in fact is a quantity of haemoglobin held together in the form of a disc by a minimal amount of stroma. Hence whatever effect the stroma per se may have upon the plasma, this, in the case of mammals at all events, must be insignificant : the red corpuscle is practically simply a carrier of haemoglobin. P. 3 34 NUMBER OF RED CORPUSCLES. [BOOK i. § 25. The average number of red corpuscles in human blood may be probably put down at about 5 millions in a cubic milli- metre (the range in different mammals is said to be from 3 to 18 millions), but the relation of corpuscle to plasma varies a good deal even in health, and very much in disease. Obviously the relation may be affected (1) by an increase or decrease of the plasma, (2) by an actual decrease or increase of red corpuscles. Now the former must frequently take place. The blood as we have already urged is always being acted upon by changes in the tissues and indeed is an index of those changes ; hence the plasma must be con- tinually changing, though always striving to return to the normal condition. Thus when a large quantity of water is discharged by the kidney, the skin or the bowels, that water comes really from the blood, and the drain of water must tend to diminish the bulk of the plasma, and so to increase the relative number of red cor- puscles, though the effect is probably soon remedied by the passage of water from the tissues into the blood. So again when a large quantity of water is drunk, this passes into the blood and tends temporarily to dilute the plasma (and so to diminish the relative number of red corpuscles) though this condition is in turn soon remedied by the passage of the superfluous fluid to the tissues and excretory organs. The greater or less number of red corpuscles then in a given bulk of blood may be simply due to less or more plasma, but we have reason to think that the actual number of the corpuscles in the blood does vary from time to time. This is especially seen in certain forms of disease, which may be spoken of under the general term of anaemia (there being several kinds of angemia) in which the number of red corpuscles is distinctly diminished. The redness of blood may however be influenced not only by the number of red corpuscles in each cubic millimetre of blood but also by the amount of haemoglobin in each corpuscle, and to a less degree by the size of the corpuscles. If we compare, with a common standard, the redness of two specimens of blood unequally red, and then determine the relative number of corpuscles in each, we may find that the less red specimen has as many corpuscles as the redder one, or at least the deficiency in redness is greater than can be accounted for by the paucity of red corpuscles. Obviously in such a case the red corpuscles have too little haemoglobin. In some cases of anaemia the deficiency of haemoglobin in each cor- puscle is more striking than the scantiness of red corpuscles. The number of corpuscles in a specimen of blood is determined by mixing a small but carefully measured quantity of the blood with a large quantity of some indifferent fluid, e.g. a 5 p.c. solution of sodium sulphate, and then actually counting the corpuscles in a known minimal bulk of the mixture. This perhaps may be most conveniently done by the method generally known as that of Gowers (Hsemacytometer) improved by Malassez. A CHAP, i.] BLOOD. 35 glass slide, in a metal frame, is ruled into minute rectangles, e.g. ^ mm. by i mm., so as to give a convenient area of o^-th of a square mm. Three small screws in the frame permit a coverslip to be brought to a fixed distance, e.g. i mm., from the surface of the slide. The blood having been diluted, e.g. to 100 times its volume, a small quantity of the diluted (and thoroughly mixed) blood, sufficient to occupy fully the space between the coverslip and the glass slide when the former is brought to its proper position, is placed on the slide, and the coverslip brought down. The volume of diluted blood now lying over each of the rectangles will be y^jth (— x i) of a cubic mm. ; and if, when the cor- puscles have subsided, the number of corpuscles lying within a rectangle be counted, the result will give the number of corpuscles previously dis- tributed through y^^th of a cubic mm. of the diluted blood. This multiplied by 1 00 will give the number of corpuscles in 1 cubic mm. of the diluted blood, and again multiplied by 100 the number in 1 cubic mm. of the entire blood. It is advisable to count the number of cor- puscles in several of the rectangles, and to take the avei'age. For the convenience of counting, each rectangle is subdivided into a number of very small squares, e.g. into 20, each with a side of Tr^th mm., and so an area of ^g^th of a square mm. Since the actual number of red corpuscles in a specimen of blood (which may be taken as a sample of the whole blood) is sometimes more, sometimes less, it is obvious that either red cor- puscles may be temporarily withdrawn from and returned to the general blood current, or that certain red corpuscles are after a while made away with, and that new ones take their place. We have no satisfactory evidence of the former being the case in normal conditions, whereas we have evidence that old corpuscles do die and that new ones are born. § 26. The red corpuscles, we have already said, are continually engaged in carrying oxygen, by means of their haemoglobin, from the lungs to the tissues ; they load themselves with oxygen at the lungs and unload at the tissues. It is extremely unlikely that this act should be repeated indefinitely without leading to changes which may be familiarly described as wear and tear, and which would ultimately lead to the death of the corpuscles. We shall have to state later on that the liver discharges into the alimentary canal, as a constituent of bile, a considerable quan- tity of a pigment known as bilirubin, and that this substance has remarkable relations with, and indeed may be regarded as a deriva- tive of hcematin, which as we have seen (§ 24) is a product of the decomposition of haemoglobin. It appears probable in fact that the bilirubin of bile (and this as we shall see is the chief biliary pigment and the source of the other biliary pigments) is not formed wholly anew in the body but is manufactured in some way or other out of haematin derived from haemoglobin. This must entail a daily con- sumption of a considerable quantity of haemoglobin, and, since we know no other source of haemoglobin besides the red corpuscles, and have no evidence of red corpuscles continuing to exist after 3—2 36 FORMATION OF RED CORPUSCLES. [BOOK i. having lost their haemoglobin, must therefore entail a daily destruc- tion of many red corpuscles. Even in health then a number of red corpuscles must be con- tinually disappearing ; and in disease the rapid and great diminu- tion which may take place in the number of red corpuscles shews that large destruction may occur. We cannot at present accurately trace out the steps of this disappearance of red corpuscles. In the spleen pulp, red corpuscles have been seen in various stages of disorganisation, some of them lying within the substance of large colourless corpuscles, and as it were being eaten by them. There is also evidence that destruction takes place in the liver itself, and indeed elsewhere. But the subject has not yet been adequately worked out. § 27. This destruction of red corpuscles necessitates the birth of new corpuscles, to keep up the normal supply of haemoglobin ; and indeed the cases in which after even great loss of blood by haemorrhage a healthy ruddiness returns, and that often rapidly, shewing that the lost corpuscles have been replaced, as well as the cases of recovery from the disease anaemia, prove that red cor- puscles are, even in adult life, born somewhere in the bod)7. In the developing embryo of the mammal the red corpuscles of the blood are not haemoglobin-holding non-nucleated discs of stroma, but coloured nucleated cells which have arisen in the following way. In certain regions of the embryo there are formed nests of nuclei imbedded in that kind of material of which we have already (§ 5) spoken, and of which we shall have again to speak as im- differentiated protoplasm. The special features of this uhdifferen- tiated protoplasm are due to the manner in which its living basis (§ 5), in carrying on its continued building up and breaking down, disposes of itself, its food, and its products. These are for a while so arranged as to form a colourless mass with minute colourless solid particles or colourless vacuoles imbedded in it, the whole having a granular appearance. After a while this granular looking protoplasm is in large measure gradually replaced by material of different optical and chemical characters, being for instance more homogeneous and less "granular" in appearance; this new material is stroma, and as it is formed, there is formed with it and in some way or other held by it a colouring matter, haemoglobin. We cannot at present say anything definite as to the way in which and the steps by which the original protoplasm is thus to a large extent differentiated into stroma and haemoglobin. All we know is that the existence of what we have called living substance is necessary to the formation of stroma and haemoglobin. We there- fore seem justified in speaking of this living substance as manu- facturing these substances, but we do not know whether the living substance turns itself so to speak into stroma or haemoglobin or both, or whether by some agency, the nature of which is at present unknown to us, it converts some of the material which is present in CHAP, i.] BLOOD. 37 the protoplasm and which we may regard as food for itself, into one or other or both of these bodies. When this differentiation has taken place or while it is still going on, the material in which the nuclei are imbedded divides into separate cell-bodies for the several nuclei ; and thus the nest of nuclei is transformed into a group of nucleated red corpuscles, each corpuscle consisting of a nucleus imbedded in a hsemoglobin- holding stroma to which is still attached more or less of the original undifferentiated protoplasm. Still later on in the life of the embryo the nucleated red cor- puscles are replaced by ordinary red corpuscles, by non-nucleated discs composed almost exclusively of haemoglobin-holding stroma. How the transformation takes place, and especially how the nucleus comes to be absent is at present a matter of considerable dispute ; there is much however to be said for the view that the normal red corpuscle is a portion only of a cell, that it is a fragment of cell substance which has been budded off and so has left the nucleus behind. In the adult as in the embryo the red corpuscles appear to be formed out of preceding coloured nucleated cells. In the interior of bones is a peculiar tissue called marrow, which in most parts, being very full of blood-vessels, is called red marrow. In this red marrow the capillaries and minute veins form an intricate labyrinth of relatively wide passages with very thin walls, and through this labyrinth the flow of blood is compara- tively slow. In the passages of this labyrinth are found coloured nucleated cells, that is to say, cells the cell substance of which has undergone more or less differentiation into haemoglobin and stroma. And there seems to be going on in red marrow a multiplication of such coloured nucleated cells, some of which transformed, in some way or other, into red non-nucleated discs, that is into ordinary red corpuscles, pass away into the general blood current. In other words, a formation of red corpuscles, not wholly unlike that which takes place in the embryo, is in the adult continually going on in the red marrow of the bones. According to some observers the coloured nucleated cells arise by division, in the marrow, from colourless cells, not unlike but probably distinct in kind from ordinary white corpuscles, the formation of hsemoglobin taking place subsequent to cell-division. Other observers, apparently with reason, urge that, whatever their primal origin, these coloured nucleated cells arise, during post-em- bryonic life, by the division of previous similar coloured cells, which thus form, in the marrow, a distinct class of cells continually under- going division and thus giving rise to cells, some of which become red corpuscles and pass into the blood stream, while others remain in the marrow to undergo further division and so to keep up the supply. Such repeatedly dividing cells may fitly be called hcvmatoblasts. A similar formation of red corpuscles has also been described, 38 WHITE CORPUSCLES. [BOOK i. though with less evidence, as taking place in the spleen, especially under particular circumstances, such as after great loss of bluod. The formation of red corpuscles is therefore a special process taking place in special regions ; we have no satisfactory evidence that the ordinary white corpuscles of the blood are, as they travel in the current of the circulation, transformed into red corpuscles. The red corpuscles then, to sum up, are useful to the body on account of the hemoglobin which constitutes so nearly the whole of their solid matter. What functions the stroma may have besides the mere so to speak mechanical one of holding the haemoglobin in the form of a corpuscle, we do not know. The primary use of the haemoglobin is to carry oxygen from the lungs to the tissues, and it would appear that it is advantageous to the economy that the hemoglobin should be as it were bottled up in corpuscles rather than simply diffused through the plasma. How long a corpuscle may live, fetching and carrying oxygen, we do not exactly know ; the red corpuscles of one animal, e.g. a bird, injected into the vessels of another, e.g. a mammal, disappear within a few days; but this affords no measure of the life of a corpuscle in its own home. Eventually however the red corpuscle dies, its place being supplied by a new one. The haemoglobin set free from the dead corpuscles appears to have a secondary use in forming the pigment of the bile and possibly other pigments. The White or Colourless Corpuscles. § 28. The white corpuscles are far less numerous than the red ; a specimen of ordinary healthy blood will contain several hundred red corpuscles to each white corpuscle, though the proportion, even in health, varies considerably under different circumstances, ranging 4 from 1 in 300 to 1 in 700. But though less numerous, the white corpuscles are probably of greater importance to the blood itself than are the red corpuscles ; the latter are chiefly limited to the special work of carrying oxygen from the lungs to the tissues, while the former probably exert a considerable influence on the blood plasma itself, and help to maintain it in a proper condition. When seen in a normal condition, and ' at rest ' the white cor- puscle is a small spherical colourless mass, varying in size, but with an average diameter of about 10/u, and presenting generally a finely but sometimes a coarsely granular appearance. The surface even when the corpuscle is perfectly at rest, is not absolutely smooth and even but somewhat irregular, thereby contributing to the granular appeai^ance ; and at times these irregularities are exagger- ated into protuberances or ' pseudopodia ' of varying size or form, the corpuscle in this way assuming various forms without changing its bulk, and by the assumption of a series of forms shifting its place. Of these ' amoeboid movements ' as they are called we shall have to speak later on. CHAP, i.] BLOOD. 39 In carrying on these amoeboid movements the corpuscle may transform itself from a spherical mass into a thin flat irregular plate ; and when this occurs there may be seen at times in the midst of the extended finely granular mass or cell body, a smaller body of different aspect and refractive power, the nucleus. The normal presence of a nucleus in the white corpuscle may also be shewn by treating the corpuscle with dilute acetic acid which swells up and renders more transparent the cell body but makes the nucleus more refractive and more sharply defined, and so more conspicuous, or by the use of staining reagents, the majority of which stain the nucleus more readily and more deeply than the cell body. In what perhaps may be considered a typical white corpuscle, the nucleus is a spherical mass about 2—3 /u, in diameter, but it varies in size in different corpuscles, and not unfrequently is irregular in form, at least after the action of reagents. It occasionally appears as if about to divide into fragments, and sometimes a corpuscle may contain two or even more (then generally small) nuclei. Though staining readily with staining reagents, the nucleus of an ordinary white corpuscle does not shew the nuclear network which is so characteristic, as we shall see, of the nuclei of many cells, and which in these is the part of the nucleus which especially stains ; in the closely allied lymph corpuscles, to which we shall have immediately to refer, a nuclear network is present. The cell body of the white corpuscle may be taken as a good example of what we have called undifferentiated protoplasm. Opti- cally it consists of a uniformly transparent but somewhat refractive material or basis, in which are imbedded minute particles, generally spherical in form, and in which sometimes occur minute vacuoles filled with fluid ; it is rarely if ever that any distinct network, like that which is sometimes observed in other cells, can be seen in the cell body of a white corpuscle whether stained or no. The im- bedded particles are generally very small, and for the most part distributed uniformly over the cell body giving it the finely granular aspect spoken of above ; sometimes however the particles are rela- tively large, making the corpuscle coarsely granular, the coarse granules being frequently confined to one or another part of the cell body. These particles or granules whether coarse or fine vary in nature ; some of them, as shewn by their greater refractive power, their staining with osmic acid, and their solution by solvents of fat, are fatty in nature ; others may similarly be shewn by their reactions to be proteid in nature. The material in which these granules are imbedded, and which forms the greater part of the cell body, has no special optical features ; so far as can be ascertained it appears under the micro- scope to be homogeneous, no definite structure can be detected in it. It must be borne in mind that the whole corpuscle consists largely of water, the total solid matter amounting to not much more than 10 per cent. The transparent material of the cell body 40 COMPOSITION OF WHITE CORPUSCLES. [BOOK i. must therefore be in a condition which we may call semi-fluid, or semi-solid, without being called upon to define what we exactly mean by these terms. This approach to fluidity appears to be connected with the great mobility of the cell body as shewn in its amoeboid movements. § 29. When we submit to chemical examination a sufficient mass of white corpuscles separated out from the blood by special means and obtained tolerably free from red corpuscles and plasma (or apply to the white blood corpuscles the chemical results obtained from the more easily procured lymph corpuscles which as we shall see are very similar to and indeed in many ways closely related to the white corpuscles of the blood), we find that this small solid matter of the corpuscle consists largely of certain proteids. One of these proteids is a body either identical with or closely allied to the proteid called myosin, which we shall have to study more fully in connection with muscular tissue. At present we may simply say that myosin is a body intermediate between fibrin and globulin, being less soluble than the latter and more soluble than the former; thus while it is hardly at all soluble in a 1 p.c. solution of sodium chloride or other neutral salt it is, unlike fibrin, speedily and wholly dissolved by a 10 p.c. solution. Myosin is further interesting because, as we shall see, just as fibrin is formed in the clotting of blood from fibrinogen, so myosin is formed out of a preceding myosinogen, during a kind of clotting, which takes place in muscular fibre and which is spoken of as rigor mortis. And we have reasons for thinking that in the living white blood corpuscle there does exist a body identical with or allied to myosinogen, a body which we may speak of as being in a fluid condition ; and that on the death of the corpuscle this body is converted, by a kind of clotting, into myosin, or into an allied body, which being solid, gives the body of the corpuscle a stiffness and rigidity which it did not possess during life. Besides this myosin or myosin-like proteid, the white corpuscles also contain either paraglobulin itself or some other member of the globulin group, as well as a body or bodies like to or identical with serum-albumin. In addition there is present, in somewhat considerable quantity, a substance of a peculiar nature, which since it is confined to the nuclei of the corpuscles and further seems to be present in all nuclei, has been called nuclein. This nuclein, which though a complex nitrogenous body is very different in composition and nature from proteids, is remarkable on the one hand for being a very stable inert body, and on the other for containing a large quantity (according to some observers nearly 10 p.c.) of phosphorus, which appears to enter more closely into the structure of the molecule than it does in the case of proteids. Next in importance to the proteids, as constant constituents of CHAP, i.] BLOOD. 41 the white corpuscles, come certain fats. Among these the most conspicuous is the complex fatty body lecithin. In the case of many corpuscles at all events we have evidence of the presence of a member of the large group of carbohydrates, comprising starches and sugar, viz. the starch-like body glycogen, which we shall have to study more fully hereafter. This glycogen may exist in the living corpuscle as glycogen, but it is very apt after the death of the corpuscle to become changed by hydration into some form of sugar, such as maltose or dextrose. Lastly the ash of the white corpuscles is characterised by containing a relatively large quantity of potassium and of phos- phates and by being relatively poor in chlorides and in sodium. But in this respect the corpuscle is merely an example of what seems to be a general rule (to which however there may be exceptions) that while the elements of the tissues themselves are rich in potassium and phosphates, the blood plasma or lymph on which they live abounds in chlorides and sodium salts. § 30. In the broad features above mentioned, the white blood corpuscle may be taken as a picture and example of all living tissues. If we examine the histological elements of any tissue, whether we take an epithelium cell, or a nerve cell, or a cartilage cell, or a muscular fibre, we meet with very similar features. Studying the element morphologically, we find a nucleus1 and a cell body, the nucleus having the general characters described above with frequently other characters introduced, and the cell body consisting of at least more than one kind of material, the materials being sometimes so disposed as to produce the optical effect simply of a transparent mass in which granules are imbedded, in which case we speak of the cell body as protoplasmic, but at other times so arranged that the cell body possesses differentiated structure. Studying the element from a chemical point of view we find proteids always present, and among these bodies identical with or more or less closely allied to myosin, we generally have evidence of the presence also of fat of some kind and of some member or members of the carbohydrate group, and the ash always contains potassium and phosphates, with sulphates, chlorides, sodium and calcium, to which may be added magnesium and iron. We stated in the Introduction that living matter is always undergoing chemical change ; this continued chemical change we may denote by the term metabolism. We further urged that so long as living matter is alive, the chemical change or metabolism is of a double kind. On the one hand, the living substance is continually breaking down into simpler bodies, with a setting free of energy ; this part of the metabolism we may speak of as made up_of katabolic changes. On the other hand the living substance is continually building itself up, embodying energy into itself and so replenishing its store of energy; this part of the metabolism 1 The existence of rnultiuuclear structures does uot affect the present argument. 42 METABOLISM. [Boon i. we may speak of as made up of anabolic changes. We also urged that in every piece of living tissue there might be (1) the actual living substance itself, (2) material which is present for the purpose of becoming, and is on the way to become, living substance, that is to say, food undergoing or about to undergo anabolic changes, and (3) material which has resulted from, or is resulting from, the breaking down of the living substance, that is to say, material which has undergone or is undergoing katabolic changes, and which we speak of as waste. In using the word "living substance," however, though we may for convenience sake speak of it as a substance, we must remember that in reality it is not a substance in the chemical sense of the word, but material under- going a series of changes. If, now, we ask the question, which part of the body of the white corpuscle (or of a similar element of another tissue) is the real living substance, and which part is food or waste, we ask a question which we cannot as yet definitely answer. We have at present no adequate morphological criteria to enable us to judge, by optical characters, what is really living and what is not. One thing we may perhaps say ; the material which appears in the cell body in the form of distinct granules, merely lodged in the more transparent material, cannot be part of the real living substance; it must be either food or waste. Many of these granules are fat, and we have at times an opportunity of observing that they have been introduced into the corpuscle from the surrounding plasma. The white corpuscle as we have said has the power of executing amoeboid movements ; it can creep round objects, envelope them with its own substance, and so put them inside itself. The granules of fat thus introduced may be subsequently extruded or may disappear within the corpuscle ; in the latter case they are obviously changed, and apparently made use of by the corpuscle. In other words, these fatty granules are apparently food material, on their way to be worked up into the living substance of the corpuscle. But we have also evidence that similar granules of fat may make their appearance wholly within the corpuscle ; they are pro- ducts of the activity of the corpuscle. We have further reason to think that in some cases, at all events, they arise from the breaking down of the living substance of the corpuscle, that they are what we have called waste products. But all the granules visible in a corpuscle are not necessarily fatty in nature ; some of them may undoubtedly be proteid granules, and it is possible that some of them may at times be of carbo- hydrate or other nature. In all cases however they are either food material or waste products. And what is true of the easily distinguished granules is also true of other substances, in solution or in a solid form, but so disposed as not to be optically re- cognised. CHAP, i.] BLOOD. 43 Hence a part, and it may be no inconsiderable part, of the body of a white corpuscle may be not living substance at all, but either food or waste. Further it does not necessarily follow that the whole of any quantity of material, fatty or otherwise, intro- duced into the corpuscle from without, should actually be built up into and so become part of the living substance ; the changes from raw food to living substance are as we have already said probably many, and it may be that after a certain number of changes, few or many, part only of the material is accepted as worthy of being made alive, and the rest, being rejected, becomes at once waste matter ; or the material may, even after it has undergone this or that change, never actually enter into the living substance but all become waste matter. We say waste matter, but this does not mean useless matter. The matter so formed may without entering into the living substance be of some subsidiary use to the corpuscle, or as probably more often happens, being discharged from the cor- puscle, may be of use to some other part of the body. We do not know how the living substance builds itself up, but we seem com- pelled to admit that, in certain cases at all events, it is able in some way or other to produce changes on material while that material is still outside the living substance as it were, before it enters into and indeed without its ever actually entering into the composition of the living substance. On the other hand we must equally admit that some of the waste substances are the direct products of the katabolic changes of the living substance itself, were actually once part of the living substance. Hence we ought perhaps to distinguish the products of the activity of living matter into waste products proper, the direct results of katabolic changes, and into bye products which are the results of changes effected by the living matter outside itself and which cannot therefore be con- sidered as necessarily either anabolic or katabolic. Concerning the chemical characters of the living matter itself we cannot at present make any very definite statement. We may say that the proteid myosin, or rather the proteid antecedent or antecedents of myosin, enter in some way into its structure, but we are not justified in saying that the living substance consists only of proteid matter in a peculiar condition. And indeed the per- sistency with which some representative of fatty bodies, and some representative of carbohydrates always appear in living tissue would perhaps rather lead us to suppose that these equally with proteid material were essential to its structure. Again though the behaviour of the nucleus as contrasted with that of the cell body leads us to suppose that the living substance of the former is a different kind of living substance from that of the latter, we do not know exactly in what the difference consists. The nucleus as we have seen contains nuclein which perhaps we may regard as a largely modified proteid ; but a body which is remarkable for its stability, for the difficulty with which it is changed by chemical 44 ORIGIN OF WHITE CORPUSCLES. |BOOK i. reagents, cannot be regarded as an integral part of the essentially mobile living substance of the nucleus. In this connection it may be worth while to call again attention to the fact that the corpuscle contains a very large quantity indeed of water, viz. about 90 p.c. Part of this, we do not know how much, probably exists in a more or less definite combination with the protoplasm, somewhat after the manner of, to use what is a mere illustration, the water of crystallization of salts. If we imagine a whole group of different complex salts continually occupied in turn in being crystallized and being decrystallized, the water thus en- gaged by the salts will give us a rough image of the water which passes in and out of the substance of the corpuscle as the result of its metabolic activity. We might call this "water of metabolism." Another part of the water, carrying in this case substances in solu- tion, probably exists in spaces or interstices too small to be seen with even the highest powers of the microscope. Still another part of the water similarly holding substances in solution exists at times in definite spaces visible under the microscope, more or less regularly spherical, and called vacuoles. We have dwelt thus at length on the white corpuscle in the first place because as we have already said what takes place in it is in a sense a picture of what takes place in all living structures, and in the second place because the facts which we have mentioned help us to understand how the white corpuscle may carry on in the blood a work of no unimportant kind ; for from what has been said it is obvious that the white corpuscle is continually acting upon and being acted upon^by the plasma. § 31. To understand however the work of these white cor- puscles we must learn what is known of their history. In successive drops of blood taken at different times from the same individual, the number of colourless corpuscles will be found to vary very much, not only relatively to the red corpuscles, but also absolutely. They must therefore ' come and go.' In treating of the lymphatic system we shall have to point out that a very large quantity of fluid called lymph, containing a very considerable number of bodies very similar in their general charac- ters to the white corpuscles of the blood, is being continually poured into the vascular system at the point where the thoracic duct joins the great veins on the left side of the neck, and to a less extent where the other large lymphatics join the venous system on the right side of the neck. These corpuscles of lymph, which, as we have just said, closely resemble, and indeed are with difficulty distinguished from the white corpuscles of the blood, but of which, when they exist outside the vascular system, it will be convenient to speak of as leucocytes, are found along the whole length of the lymphatic system, but are more numerous in the lymphatic vessels after these have passed through the lymphatic glands. These lymphatic glands are partly composed of CHAP, i.] BLOOD. 45 what is known as adenoid tissue, a special kind of connective tissue arranged as a delicate network. The meshes of this are crowded with colourless nucleated cells, which though varying in size, are for the most part small, the nucleus being surrounded by a relatively small quantity of cell substance. Many of these cells shew signs that they are undergoing cell-division, and we have reason to think that cells so formed, acquiring a larger amount of cell substance, become veritable leucocytes. In other words, leu- cocytes multiply in the lymphatic glands, and leaving the glands by the lymphatic vessels, make their way to the blood. Patches and tracts of similar adenoid tissue, not arranged however as dis- tinct glands but similarly occupied by developing leucocytes and similarly connected with lymphatic vessels, are found in various parts of the body, especially in the mucous membranes. Hence we may conclude that from various parts of the body, the lymphatics are continually bringing to the blood an abundant supply of leucocytes, and that these in the blood become ordinary white corpuscles. This is probably the chief source of the white cor- puscles, for though the white corpuscles have been seen dividing in the blood itself, no large increase takes place in that way. § 32. It follows that since white corpuscles are thus continu- ally being added to the blood, white corpuscles must as continually either be destroyed, or be transformed, or escape from the interior of the blood vessels ; otherwise the blood would soon be blocked with white corpuscles. Some do leave the blood vessels. In treating of the circulation we shall have to point out that white corpuscles are able to pierce the walls of the capillaries and minute veins and thus to make their way from the interior of the blood vessels into spaces filled with lymph, the "lymph spaces," as they are called, of the tissue lying outside the blood vessels. This is spoken of as the " migra- tion of the white corpuscles." In an " inflamed area " large numbers of white corpuscles are thus drained away from the blood into the lymph spaces of the tissue ; and it is probable that a similar loss takes place, more or less, under normal conditions. These migrating corpuscles may, by following the devious tracts of the lymph, find their way back into the blood ; some of them how- ever may remain, and undergo various changes. Thus, in inflamed areas, when suppuration follows inflammation, the white corpuscles which have migrated may become 'pus corpuscles,' or, where thickening and growth follow upon inflammation, may, according to many authorities, become transformed into temporary or perma- nent tissue, especially connective tissue ; but this transformation into tissue is disputed. When an inflammation subsides without leaving any effect a few corpuscles only will be found in the tissue ; those which had previously migrated must therefore have been disposed of in some way or another. In speaking of the formation of red corpuscles (§ 27) we saw 46 WORK OF WHITE CORPUSCLES. [BOOK i. that not only it is not proved that the nucleated corpuscles which give rise to red corpuscles are ordinary white corpuscles, but that in all probability the real hsematoblasts, the parents of red cor- puscles, are special corpuscles developed in the situations where the manufacture of red corpuscles takes place. So far therefore from assuming, as is sometimes done, that the white corpuscles of the blood are all of them on their way to become red corpuscles, it may be doubted whether any of them are. In any case however, even making allowance for those which migrate, a very consider- able number of the white corpuscles must 'disappear' in some way or other from the blood stream, and we may perhaps speak of their disappearance as being a 'destruction' or 'dissolution.' We have as yet no exact knowledge to guide us in this matter, but we can readily imagine that, upon the death of the corpuscle, the substances composing it, after undergoing changes, are dissolved by and become part of the plasma. If so, the corpuscles as they die must repeatedly influence the composition and nature of the plasma. But if they thus affect the plasma in their death, it is even more probable that they influence it during their life. Being alive they must be continually taking in and giving out. As we have already said they are known to ingest, after the fashion of an amoeba, solid particles of various kinds such as fat or carmine, present in the plasma, and probably digest such of these particles as are nutritious. But if they ingest these solid matters they pro- bably also carry out the easier task of ingesting dissolved matters. If however they thus take in, they must also give out ; and thus by the removal on the one hand of various substances from the plasma, and by the addition on the other hand of other substances to the plasma, they must be continually influencing the plasma. We have already said that the white corpuscles in shed blood as they die are supposed to play an important part in the clotting of blood ; similarly they may during their whole life be engaged in carrying out changes in the proteids of the plasma which do not lead to clotting, but which prepare the proteids for their various uses in the body. Pathological facts afford support to this view. The disease called leucocythgemia (or leukaemia) is characterised by an increase of the white corpuscles, both absolute and relative to the red corpuscles, the increase, due to an augmented production or possibly to a retarded destruction, being at times so great as to give the blood a pinkish grey appearance, like that of blood mixed with pus. We accordingly find that in this disease the plasma is in many ways profoundly affected and fails to nourish the tissues. As a further illustration of the possible action of the white cor- puscles we may state that, according to some observers in certain diseases in which minute organisms, such as bacteria, make their appearance in the blood, the white corpuscles ' take up ' these CHAP, i.] BLOOD. 47 bacteria into their substance, and thus probably, by exerting an influence on them, modify the course of the disease of which these bacteria are the essential cause. If the white corpuscles are thus engaged during their life in carrying on important labours, we may expect them to differ in appearance according to their condition. Some of the corpuscles are spoken of as 'faintly' or 'finely ' granular. Other corpuscles are spoken of as ' coarsely ' granular, their cell substance being loaded with conspicuously discrete granules. It may be of course that there are two distinct kinds of corpuscles, having different functions and possibly different origins and histories ; but since intermediate forms are met with containing a few coarse granules only, it is more probable that the one form is a phase of the other, that a faintly granular corpuscle by taking in granules from without or by pro- ducing granules within itself as products of its metabolism, may become a coarsely granular corpuscle. Whether however the white corpuscles are really all of one kind, or whether they are different kinds performing different functions, must at present be left an open question. Blood Platelets. § 33. In a drop of blood examined with care immediately after removal, may be seen a number of exceedingly small bodies (2 ^ to 3 /A in diameter) frequently disc-shaped but sometimes of a rounded or irregular form, homogeneous in appearance when quite fresh but apt to assume a faintly granular aspect. They are called blood platelets. They have been supposed by some to become developed into and indeed to be early stages of the red corpuscles, and hence have been called hsematoblasts ; but this view has not been confirmed, indeed, as we have seen (§ 27), the real haemato- blasts or developing red corpuscles are of quite a different nature. They speedily undergo change after removal from the body, apparently dissolving in the plasma ; they break up, part of their substance disappearing, while the rest becomes granular. Their granular remains are apt to run together forming in the plasma the shapeless masses which have long been known and described as "lumps of protoplasm." By appropriate reagents, however, these platelets may be fixed and stained in the condition in which they appear after leaving the body. The substance composing them is peculiar, and though we may perhaps speak of them as consisting of living material, their nature is at present obscure. They may be seen within the living blood vessels, and therefore must be regarded as real parts of the blood and not as products of the changes taking place in blood after it has been shed. 48 BLOOD PLATELETS. [Booic i. When a needle or thread or other foreign body is introduced into the interior of a blood vessel, they are apt to collect upon, and indeed are the precursors of the clot which in most cases forms around the needle or thread. They are also found in the thrombi or plugs which sometimes form in the blood vessels as the result of disease or injury. Indeed it has been maintained that what are called white thrombi (to distinguish them from red thrombi which are plugs of corpuscles and fibrin) are in reality aggregations of blood platelets ; and for various reasons blood platelets have been supposed to play an important part in the clotting of blood, carrying out the work which in this respect is by others attributed to the white corpuscles. But no very definite statement can at present be made about this ; and indeed the origin and whole nature of these blood platelets is at present obscure. SEC. 3. THE CHEMICAL COMPOSITION OF BLOOD. § 34. We may now pass briefly in review the chief chemical characters of blood, remembering always that, as we have already urged, the chief chemical interests of blood are attached to the changes which it undergoes in the several tissues ; these will be considered in connection with each tissue at the appropriate place. The average specific gravity of human blood is 1055, varying from 1045 to 1075 within the limits of health. The reaction of blood as it flows from the blood vessels is found to be distinctly though feebly alkaline. If a drop be placed on a piece of faintly red highly glazed litmus paper, and then wiped off, a blue stain will be left. The whole blood contains a certain quantity of gases, viz. oxygen, carbonic acid and nitrogen, which are held in the blood in a pecu- liar way, which vary in different kinds of blood, and so serve especially to distinguish arterial from venous blood, and which may be given off from blood when exposed to an atmosphere, according to the composition of that atmosphere. These gases of blood we shall study in connection with respiration. The normal blood consists of corpuscles and plasma. If the corpuscles be supposed to retain the amount of water proper to them, blood may, in general terms, be considered as consisting by weight of from about one-third to somewhat less than one-half of corpuscles, the rest being plasma. As we have already seen, the number of corpuscles in a specimen of blood is found to vary considerably, not only in different animals and in different individuals, but in the same individual at different times. The plasma, is resolved by the clotting of the blood into serum and fibrin. § 35. The serum contains in 100 parts Proteid substances about 8 or 9 parts. Fats, various extractives, and saline matters „ 2 or 1 „ Water „ 90 F. 4 50 COMPOSITION OF BLOOD. [Boon i. The proteids are paraglobulin and serum-albumin (there being probably more than one kind of serum-albumin) in varying propor- tion. We may perhaps, roughly speaking, say that they occur in about equal quantities. Conspicuous and striking as are the results of clotting, mas- sive as appears to be the clot which is formed, it must be remem- bered that by far the greater part of the clot consists of corpuscles. The amount by weight of fibrin required to bind together a number of corpuscles in order to form even a large firm clot is exceedingly small. Thus the average quantity by weight of fibrin in human blood is said to be '2 p.c. ; the amount however which can be ob- tained from a given quantity of plasma varies extremely, the varia- tion being due not only to circumstances affecting the blood, but also to the method employed. The fats, which are scanty, except after a meal or in certain pathological conditions, consist of the neutral fats, stearin, palmitin, and olein, with a certain quantity of their respective alkaline soaps. The peculiar complex fat lecithin occurs in very small quantities only; the amount present of the peculiar alcohol cholesterin which has so fatty an appearance is also small. Among the extractives present in serum may be put down nearly all the nitrogenous and other substances which form the extractives of the body and of food, 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 or of 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 important chemical feature of the saline constitution of the serum is the preponderance, at least in man and most animals, of sodium salts over those of potassium. In this respect the serum offers a marked contrast to the corpuscles. 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 some amount of sodium carbonate, or more correctly sodium bicarbonate, and potassium chloride, with small quantities of sodium sulphate, sodium phosphate, calcium phosphate, and magnesium phosphate. And of even the small quantity of phosphates found in the ash, part of the phosphorus exists in the serum itself not as a phosphate but as phosphorus in some organic body. § 36. The red corpuscles contain less water than the serum, the amount of solid matter being variously estimated at from 30 to 40 or more p.c. The solids are almost entirely organic matter, the inorganic salts amounting to less than 1 p.c. Of the organic matter again by far the larger part consists of haemoglobin. In 100 parts of the dried organic matter of the corpuscles of human blood, about CHAP, i.] BLOOD. 51 90 parts are haemoglobin, about 8 parts are proteid substances, and about 2 parts are other substances. Of these other substances one of the most important, forming about a quarter of them and apparently being always present, is lecithin. Cholesterin appears also to be normally present. The proteid substances which form the stroma of the red corpuscles appear to belong chiefly to the globulin family. As regards the inorganic constituents, the cor- puscles are distinguished by the relative abundance of the salts of potassium and of phosphates. This at least is the case in man ; the relative quantities of sodium and potassium in the corpuscles and serum respectively appear however to vary in different animals ; in some the sodium salts are in excess even in the corpuscles. § 37. The proteid matrix of the white corpuscles, we have stated to be composed of myosin (or an allied body) paraglobulin, and possibly other proteids. The nuclei contain nuclein. The white corpuscles are found to contain in addition to proteid ma- terial, lecithin and other fats, glycogen, extractives and inorganic salts, there being in the ash as in that of the red corpuscles a pre- ponderance of potassium salts and of phosphates. The main facts of interest then in the chemical composition of the blood are as follows. The red corpuscles consist chiefly of haemoglobin. The organic solids of serum consist partly of serum- albumin, and partly of paraglobulin. The serum or plasma contrasts in man at least, 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. 4—2 SEC. 4. THE QUANTITY OF BLOOD, AND ITS DISTRIBUTION IN THE BODY. § 38. The quantity of blood contained in the whole vascular system is a balance struck between the tissues which give to, and those which take away from the blood. Thus the tissues of the alimentary canal largely add to the blood water and the material derived from food, while the excretory organs largely take away water and the other substances constituting the excretions. Other tissues both give and take ; and the considerable drain from the blood to the lymph spaces which takes place in the capillaries is met by the flow of lymph into the great veins. From the result of a few observations on executed criminals it has been concluded that the total quantity of blood in the human body is about y^th of the body weight. But in various animals, the proportion of the weight of the blood to that of the body has been found to vary very considerably in different individuals ; and probably this holds good for man also, at all events within certain limits. In the same individual the quantity probably does not vary largely. A sudden drain upon the water of the blood by great activity of the excretory organs, as by profuse sweating, or a sudden addition to the water of the blood, as by drinking large quantities of water or by injecting fluid into the blood vessels, is rapidly compensated by the passage of water from the tissues to the blood or from the blood to the tissues. As we have already said the tissues are continually striving to keep up an average composition of the blood, and in so doing keep up an average quantity. In starvation the quantity (and quality) of the blood is maintained for a long time at the expense of the tissues, so that after some days deprivation of food and drink, while the fat, the muscles, and other tissues have been largely diminished, the quantity of blood remains nearly the same. CHAP, i.] BLOOD. 53 The total quantity of blood present in an animal body is estimated 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, and the amount of blood in them is estimated as before by comparison with a specimen of diluted blood. The quantity of blood, as calculated from the two washings, together with the escaped and directly measured blood, gives the total quantity of blood in the body. The method is not free from objections, but other methods are open to still graver objections. The blood is in round numbers distributed as follows : About one-fourth in the heart, lungs, large arteries and veins, li vpy ,, ., ,, ,, 1J.VC1, „ ,, „ „ 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 the blood passing through the liver and skeletal muscles far exceed those which take place in the rest of the body. CHAPTER II. THE CONTRACTILE TISSUES. § 39. IN order that the blood may nourish the several tissues it is carried to and from them by the vascular mechanism ; and this carriage entails active movements. In order that the blood may adequately nourish the tissues, it must be replenished by food from the alimentary canal, and purified from waste by the excretory organs ; and both these processes entail movements. Hence before we proceed further we must study some of the general characters of the movements of the body. Most of the movements of the body are carried out by means of the muscles of the trunk and limbs, which being connected with the skeleton are frequently called skeletal muscles. A skeletal muscle when subjected to certain influences suddenly shortens, bringing its two ends nearer together; and it is the shortening, acting upon various bony levers or by help of other mechanical arrangements, which produces the movement. Such a temporary shortening, called forth by certain influences and due as we shall see to changes taking place in the muscular tissue forming the chief part of the muscle, is technically called a contraction of the muscle; and the muscular tissue is spoken of as a contractile tissue. The heart is chiefly composed of muscular tissue, differing in certain minor features from the muscular tissue of the skeletal muscles, and the beat of the heart is essentially a contraction of the muscular tissue composing it, a shortening of the peculiar muscular fibres of which the heart is chiefly made up. The movements of the alimentary canal and of many other organs are similarly the results of the contraction of the muscular tissue entering into the composition of those organs, of the shortening of certain muscular fibres built up into those organs. In fact almost all the move- ments of the body are the results of the contraction of muscular fibres, of various nature and variously disposed. CHAP, ii.] THE CONTRACTILE TISSUES. 55 Some few movements however are carried out by structures which cannot be called muscular. Thus in the pulmonary passages and elsewhere movement is effected by means of cilia attached to epithelium cells ; and elsewhere, as in the case of the migrating white corpuscles of the blood, transference from place to place in the body is brought about by amoeboid movements. But, as we shall see, the changes in the epithelium cell or white corpuscle which are at the bottom of ciliary or amoeboid movements are in all probability fundamentally the same as those which take place in a muscular fibre when it contracts : they are of the nature of a contraction, and hence we may speak of all these as different forms of contractile tissue. Of all these various forms of contractile tissue the skeletal muscles, on account of the more complete development of their functions, will be better studied first; the others, on account of their very simplicity, are in many respects less satisfactorily understood. All the ordinary skeletal muscles are connected with nerves. We have no reason for thinking that they are thrown into con- traction, under normal conditions, otherwise than by the agency of nerves. Muscles .and nerves being thus so closely allied, and having besides so many properties in common, it will conduce to clearness and brevity if we treat them together. SEC. 1. THE PHENOMENA OF MUSCLE AND NERVE. Muscular and Nervous Irritability. § 40. The skeletal muscles of a frog, the brain and spinal cord of which have been destroyed, do not exhibit any spontaneous movements or contractions, even though the nerves be otherwise quite intact. Left undisturbed the whole body may decompose without any contraction of any of the skeletal muscles having been witnessed. Neither the skeletal muscles nor the nerves distributed to them possess any power of automatic action. If however a muscle be laid bare and be more or less violently disturbed, if for instance it be pinched, or touched with a hot wire, or brought into contact with certain chemical substances, or sub- jected to the action of galvanic currents, it will move, that is con- tract, whenever it is thus disturbed. Though not exhibiting any spontaneous activity, the muscle is (and continues for some time after the general death of the animal to be) irritable. Though it remains quite quiescent when left untouched, its powers are then dormant only, not absent. These require to be roused or ' stimulated ' by some change or disturbance in order that they may manifest themselves. The substances or agents which are thus able to evoke the activity of an irritable muscle are spoken of as stimuli. But to produce a contraction in a muscle the stimulus need not be applied directly to the muscle ; it may be applied indirectly by means of the nerve. Thus, 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, contrac- tions are seen in the muscles to which branches of the nerve are distributed. The nerve like the muscle is irritable, it is thrown into a state of activity by a stimulus ; but unlike the muscle it does not itself contract. The stimulus does not give rise in the nerve to any visible change of form ; but that changes of some kind or other CHAP, ii.] THE CONTRACTILE TISSUES. 57 are set up and propagated along the nerve down to the muscle is shewn by the fact that the muscle contracts when a part of the nerve at some distance from itself is stimulated. Both nerve and muscle are irritable, but only the muscle is contractile, i.e. manifests its irritability by a contraction. The nerve manifests its irrita- bility by transmitting along itself, without any visible alteration of form, certain molecular changes set up by the stimulus. We shall call these changes thus propagated along a nerve, ' nervous impulses.' § 41. We have stated above that the muscle may be thrown into contractions by stimuli applied directly to itself. But it might fairly be urged that the contractions so produced are in reality due to the fact that the stimulus, although apparently applied directly to the muscle, is, after all, brought to bear on some or other of the many fine nerve-branches, which as we shall see are abundant in the muscle, passing among and between the muscular fibres in which they finally end. 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 subjected 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, -f- a ligature be passed underneath 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 rest of the body, including 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 58 MUSCULAR IRRITABILITY. [BOOK i. 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 divided high up and the part connected with the muscle gently lifted up before the urari is introduced into the system, so that no blood flows to it and so that it is protected from the influence of the poison, stimulation of the nerve will be found to produce 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, or peculiar structures in which the nerve fibres end in the muscular fibres, for urari poisoning, at least when profound, causes a slight but yet distinctly recognisable effect in the microscopic appearance of these structures) which are affected. The phenomena of urari poisoning therefore go far to prove that muscles are capable of being made to contract by stimuli applied directly to the muscular fibres themselves ; and there are other facts which support this view. § 42. When in a recently killed frog we stimulate by various means and in various ways the muscles and nerves, it will be observed that the movements thus produced, though very various, may be distinguished to be of two kinds. On the one hand the result may be a mere twitch, as it were, of this or that muscle ; on the other hand, one or more muscles may remain shortened or contracted for a considerable time, a limb for instance being raised up or stretched out, and kept raised up or stretched out for many seconds. And we find upon examination that a stimulus may be applied either in such a way as to produce a mere twitch, a passing rapid contraction which is over and gone in a fraction of a second, or in such a way as to keep the muscle shortened or contracted for as long time as, up to certain limits, we may choose. The mere twitch is called a single or simple muscular contraction ; 'the sustained contraction, which as we shall see is really the result of rapidly repeated simple contractions, is called a tetanic con- traction. § 43. In order to study these contractions adequately, we must have recourse to the ' graphic method ' as it is called, and obtain a tracing or other record of the change of form of the muscle. To do this conveniently, it is best to operate with a muscle isolated from the rest of the body of a recently killed animal, and carefully prepared in such a way as to remain irritable for some time. The muscles of cold blooded animals remain irritable after removal from the body far longer than those of warm blooded animals, and hence those of the frog are generally made use of. We shall study presently the conditions which determine this maintenance of the irritability of muscles and nerves after removal from the body. A muscle thus isolated, with its nerve left attached to it, is CHAP, ii.] THE CONTRACTILE TISSUES. 59 called a muscle-nerve preparation. The most convenient muscle for this purpose in the frog is perhaps the gastrocnemius, which should be dissected out so as to leave carefully preserved the attachment to the femur above, some portion of the tendon (tendo achillis) below, and a considerable length of the sciatic nerve with its branches going to the muscle. Fig. 1. FlG. 1. A MUSCLE-NERVE PREPARATION. in, the muscle, gastrocnemius of frog ; «, the sciatic nerve, all the branches being cut away except that supplying the muscle; /, femur; cl. clamp; t. a. tendo achillis ; sp. c. end of spinal canal. § 44. We may apply to such a muscle-nerve preparation the various kinds of stimuli spoken of above, mechanical, such as prick- ing or pinching, thermal, such as sudden heating, chemical, such as acids or other active chemical substances, or electrical ; and these we may apply either to the muscle directly, or to the nerve, thus affecting the muscle indirectly. Of all these stimuli by far the most convenient for general purposes are electrical stimuli of various kinds ; and these, except for special purposes, are best applied to the nerve, and not directly to the muscle. Of electrical stimuli again, the currents, as they are called, generated by a voltaic cell are most convenient, though the electricity generated by a rotating magnet, or that produced by friction may be employed. Making use of a cell or battery of cells, Daniell's, Grove's, Leclanche or any other, we must distinguish between the current produced by the cell itself, the constant 60 ELECTRICAL STIMULI. [BOOK i. current as we shall call it, and the induced current obtained from the constant current by means of an induction coil, as it is called ; for the physiological effects of the two kinds of current are in many ways different. It may perhaps be worth while to remind the reader of the following- facts. In a galvanic battery, the substance (plate of zinc for instance) which is acted upon and used up by the liquid is called the positive element, and the substance which is not so acted upon and used up (plate &c. of copper, platinum, or carbon, &c.) is called the negative element. A galvanic action is set up when the positive (zinc) and the negative (copper) elements are connected outside the battery by some conducting material, such as a wire, and the current is said to flow in a circuit or circle from the zinc or positive element to the copper or negative element inside the batter//, and then from the copper or negative element back to the zinc or positive element through the wire outside the battery. If the conducting wire be cut through, the current ceases to flow ; but if the cut ends be brought into contact, the current is re- established and continues to flow so long as the contact is good. The ends of the wires are called ' poles,' or when used for physiological purposes, in which case they may be fashioned in various ways, are spoken of as electrodes. When the poles are brought into contact or are connected by some conducting material, galvanic action is set up, and the current flows through the battery and wires ; this is spoken of as "making the current" or "completing or closing the circuit." When the poles are drawn apart from each other, or when some non-conducting material is interposed between them, the galvanic action is arrested; this is spoken of as "breaking the current" or " opening the circuit.' The current passes from the wire connected with the negative (copper) element in the battery to the wire connected with the positive (zinc) element in the battery ; hence the pole connected with the copper (negative) element is called the positive pole, and that connected with the zinc (positive) element is called the negative pole. When used for physiological purposes the positive pole becomes the positive electrode, and the negative pole the negative electrode. The positive electrode is often spoken of as the anode (ana, up), and the negative electrode as the kathode (kata, down). A piece of nerve of ordinary length, though not a good conductor, is still a conductor, and when placed on the electrodes, completes the circuit, permitting the current to pass through it ; in order to remove the nerve from the influence of the current it must be lifted off from the electrodes. This is obviously inconvenient ; and hence it is usual to arrange a means of opening or closing the circuit at some point along one of the two wires. This may be done in various ways : by fastening- one part of the wire into a cup of mercury and so by dipping the other part of the wire into the cup to close the circuit and make the current, and by lifting it out of the mercury to open the circuit and break the current ; or by arranging, between the two parts of the wires, a moveable bridge of good conducting material such as brass, which can be put down to close the circuit or raised up to open the circuit ; or in CHAP, ii.] THE CONTRACTILE TISSUES. 61 other ways. Such a means of closing and opening a circuit and so of making or breaking a current is called a key. A key which is frequently used by physiologists goes by the name of du Bois-Reymond's key; though undesirable in many respects it has the advantage that it can be used in two different ways. When arranged as in A. Fig. 2, the brass bridge of K, the key, being down, and forming a means of good conduction between the brass plates to which the wires are screwed, the circuit is closed and the current passes from the positive pole (end of the negative (copper) element) to the positive electrode or anode, An. through the nerve, to the negative electrode or kathode Kat. and thence back to the negative pole (end of the positive (zinc) element) in the battery; on raising the B FIG. 2. DIAGRAM OF Du BOIS-REYMOXD KEY USED, A, FOR MAKING AND BREAKING, B, FOR SHORT CIRCUITING. brass bridge the circuit is opened, the current broken, and no current passes through the electrodes. When arranged as in B, if the brass bridge be 'down,' the resistance offered by it is so small compared with the resistance offered by the nerve between the electrodes, that the whole current from the battery passes through the bridge, back to the battery, and none, or only an infinitesimal portion, passes into the nerve. When on the other hand the bridge is raised, and so the conduction between the two sides suspended, the current is not able to pass directly from one side to the other, but can and does pass along the wire through the nerve back to the battery. Hence in arrangement A, 'putting down the key' as it is called makes a current in the nerve, and 'raising' or 'opening the key' breaks the current. In arrangement B, however, putting down the key diverts the current from the nerve by sending it through the bridge, and so back to the battery ; the current instead of making the longer circuit through the electrodes makes the shorter circuit through the key ; hence this is called ' short circuiting.' When the bridge is raised the current passes through the nerve on the electrodes. Thus 'putting down' and 'raising' or 'opening' 62 INDUCTION COIL. [BOOK i. the key have contrary effects in A and B. In B, it will be observed, the battery is always at work, the current is always flowing either through the electrodes (key up) or through the key (key down) ; in A, the battery is not at work until the circuit is made by putting down the key. And in many cases it is desirable to take so to speak a sample of the current while the battery is in full swing rather than just as it begins to work. Moreover in B the electrodes are, when the key is down, wholly shut off from the current, whereas in A, when the key is up, one electrode is still in direct connection with the battery and this connection, leading to what is known as unipolar action, may give rise to stimulation of the nerve. Hence the use of the key in the form B. Other forms of key may be used. Thus in the Morse key (F. Fig. 3) contact is made by pressing down a lever handle (ha); when the pressure is removed, the handle, driven up by a spring, breaks contact. In the arrangement shewn in the figure one wire from the battery being brought to the binding screw b, while the binding screw a is connected with the other wire, putting down the handle makes con- nection between a and 6, and thus makes a current. By arranging the wires in the several binding screws in a different way, the making contact by depressing the handle may be used to short circuit. In an "induction coil" Figs. 3 and 4, the wire connecting the two elements of a battery is twisted at some part of its course into a close spiral, called the primary coil. Thus in Fig. 3 the wire x" connected with the copper or negative plate c.p. of the battery, E, joins the primary coil pr. c., and then passes on as y'", through the "key" F, to the positive (zinc) plate z.p. of the battery. Over this primary coil, but quite unconnected with it, slides another coil, the secondary coil, s.c. ; the ends of the wire forming this coil, y" and x", are continued on in the arrangement illustrated in the figure as y' and y, and as x' and x and terminate in electrodes. If these electrodes are in contact or connected with conducting material, the circuit of the secondary coil is said to be closed ; otherwise it is open. In such an arrangement it is found that at the moment when the primary circuit is closed, i.e. when the primary current is "made " a secondary "induced" current is, for an exceedingly brief period of time, set up in the secondary coil. Thus in Fig. 3 when by moving the " key " F, y" and x" previously not in connection with each other, are put into connection and the primary current thus made, at that instant a current appears in the wires y" x" &c., but almost immediately disappears. A similar almost instantaneous current is also developed when the primary current is "broken," but not till then. So long as the primary current flows with uniform intensity, no current is induced in the secondary coil. It is only when the primary current is either made or broken, or suddenly varies in intensity, that a current appears in the secondary coil. In each case the current is of very brief duration, gone in an instant almost, and may therefore be spoken of as "a shock," an induction shock; being called a "making shock" when it is caused by the making, and a " breaking shock " when it is caused by the breaking, of the primary circuit. The direction of the current in the making shock is opposed to that of the primary current; thus in CHAP, ii.] THE CONTRACTILE TISSUES. 63 64 INDUCTION COIL. [BOOK i. FIG. 3. DIAGRAM ILLUSTRATING APPARATUS ARRANGED FOR EXPERIMENTS WITH MUSCLE AND NERVE. A. The moist chamber containing the muscle-nerve preparation. The muscle m, supported by the clamp cl. , which firmly grasps the end of the femur /, is connected 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. C. du Bois-Beymond's key arranged for short-circuiting. The wires .T 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 coils s. c. of the induction-coil D. This secondary coil can be made to slide up and down over the primary coil pr. c., with which are con- nected the two wires x'" and y'". x'" is connected directly with one pole, for instance the copper pole c. p. of the battery E. y'" is carried to a binding screw a of the Morse key F, and is continued as j/lv from another binding screw l> 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 ha, 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 yiv to z. p. On removing the finger from the handle of F, a spring thrusts up the handle, and the primary circuit is in consequence immediately broken. At the instant that the primary current is either made or broken, an induced current is for the instant developed in the secondary coil s. c. If the cross bar h in the du Bois-Eeymond'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-Keyrnorid key be shut down, as in the dotted line 7t' 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 practically none passes into the nerve. The nerve being thus "short-circuited," is not affected by any changes in the current. The figure is intended merely to illustrate the general method of studying muscular contraction ; it is not to be supposed that the details here given are universally adopted or indeed the best for all purposes. the figure while the primary current flows from x" to y'", the induced making shock flows from y to x. The current of the breaking shock on the other hand flows in the same direction as the primary current from x to y, and is therefore in direction the reverse of the making shock. Compare Fig. 4, where arrangment is shewn in a diagrammatic manner. The current from the battery, upon its first entrance into the primary coil, as it passes along each twist of that coil, gives rise in the neighbouring twists of the same coil to a momentary induced current having a direction opposite to its own, and therefore tending to weaken itself. It is not until this ' self-induction ' has passed off" that the current in the primary coil is established in its full strength. Owing CHAP, ii.] THE CONTRACTILE TISSUES. G5 to this delay in the full establishment of the current in the primary coil, the induced current in the secondary coil is developed more slowly FIG. <4. DIAGRAM OF AN INDUCTION COIL. + positive pole, eud of negative element, - negative pole, end of positive element of battery, K, du Bois-Keymond's key, pr. c. primary coil, current shewn by feathered arrow, sc. c. secondary coil, current shewn by unfeathered arrow. than it would be were no such ' self-induction ' present. On the other hand when the current from the battery is 'broken,' or 'shut off' from the primary coil, no such delay is offered to its disappearance, and consequently the induced current in the secondary coil is developed with unimpeded rapidity. We shall see later on that a rapidly de- veloped current is more effective as a stimulus than is a more slowly developed current. Hence the making shock, where rapidity of pro- duction is interfered with by the self-induction of the primary coil, is less effective as a stimulus than the breaking shock whose development is not thus interfered with. The strength of the induced current depends, on the one hand, on the strength of the current passing through the primary coil, that is, on the strength of the battery. It also depends on the relative position of the two coils. Thus a secondary coil is brought nearer and nearer to the primary coil and made to overlap it more and more; the induced current becomes stronger and stronger, though the current from the battery remains the same. With an ordinary battery, the secondary coil may be pushed to some distance away from the primary coil, and yet shocks sufficient to stimulate a muscle will be obtained. For this purpose however the two coils should be in the same line ; when the secondary coil is placed cross-wise, at right angles to the primary, no induced current is developed, and at intermediate angles the induced current has intermediate strengths. When the primary current is repeatedly and rapidly made and broken, the sec.ondary current being developed with each make and with each break, a rapidly recurring series of alternating currents is developed in the secondary coil and passes through its electrodes. We shall frequently speak of this as the interrupted induction current, or more briefly the interrupted current ; it is sometimes spoken of as the F. 5 J 66 INDUCTION COIL. [BOOK i. faradaic current, and the application of it to any tissue is spoken of as faradization. Such a repeated breaking and making of the primary current may be effected in many various ways. In the instrument commonly used for the purpose, the primary current is made and broken by means of a vibrating steel slip working against a magnet ; hence the instrument is called a magnetic interrupter. See Fig. 5. FIG. 5. THE MAGNETIC INTERRUPTOR. 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 b, as far as the screw c, the point of which, armed with platinum, is in contact with a small platinum plate on b. The current passes from b through c and a connecting 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 continue 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 b, 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 thus the current is "broken " at b. (Sometimes the screwy is so arranged that when e is drawn down a platinum plate on the under surface of b is brought into contact with the platinum-armed point of the screw f. CHAP, ii.] THE CONTRACTILE TISSUES. 67 The current then passes from b not to c but 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, and is thus cut off from the primary coil. But this arrangement is unnecessary.) At the instant that the current is thus broken and so cut off from the primary coil, an induced (breaking) current is for the moment developed in the secondary coil. 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 magnetised, the bar e ceases to be attracted by them, and the spring b, 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 clown, 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 with c is alternately being made and broken, and the current is constantly passing into and being shut off from p, 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) current is developed in a secondary coil. As thus used, each 'making shock,' as explained above, is less powerful than the corresponding 'breaking shock;' and indeed it sometimes happens that instead of each make as well as each break acting as a stimulus, giving rise to a contraction, the 'breaks' only are effective, the several 'nlakes' giving rise to no contractions. By what is known as Helmholtz's arrangement, Fig. 6, however FIG. 6. THE MAGNETIC INTERRUPTOR WITH HELMHOLTZ ARRANGEMENT FOR EQUALIZING THE MAKE AND BREAK SHOCKS. the making and breaking shocks may be equalized. For this purpose the screw c is raised out of reach of the excursions of the spring b, and 5—2 68 A SIMPLE MUSCULAR CONTRACTION. [BOOK i. a moderately thick wire w, offering a certain amount only of resistance, is interposed between the upper binding screw a on the pillar «, and the binding screw c' leading to the primary coil. Under these arrange- ments the current from the battery passes through «', along the inter- posed wire to c', through the primary coil and thus as before to m. As before, by the magnetisation of m, e is drawn down and b brought in contact with/. As the result of this contact, the current from the battery can now pass by a,f, and d (shewn by the thin interrupted line) back to the battery ; but not the whole of the current, some of it can still pass along the wire w to the primary coil, the relative amount being determined by the relative resistances offered by the two courses. Hence at each successive magnetisation of m, the current in the primary coil does not entirely disappear when b is brought in contact with /; it is only so far diminished that m ceases to attract e, and hence by the release of b from f the whole current once more passes along w. Since, at what corresponds to the ' break ' the current in the primary coil is diminished only, not absolutely done away with, self-induction makes its appearance at the 'break' as well as at the 'make'; thus the 'breaking' and 'making' induced currents or shocks in the secondary coil are equalized. They are both reduced to the lower efficiency of the 'making' shock in the old arrangement; hence to produce the same strength of stimulus with this arrange- ment a stronger current must be applied or the secondary coil pushed over the primary coil to a greater extent than with the other arrange- ment. The Phenomena of a simple Muscular Contraction. § 45. If the far end of the nerve of a muscle-nerve preparation, Figs. 1 and 3, be laid on electrodes connected with the secondary coil of an induction-machine, the passage of a single induction- shock, which may be taken as a convenient form of an almost momen- tary stimulus, will produce no visible change in the nerve, but the muscle will give a twitch, a short sharp contraction, i.e. will for an instant shorten itself, becoming thicker the while, and then return to its previous condition. If one end of the muscle be attached to a lever, while the other is fixed, the lever will by its movements 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 finely pointed piece of platinum foil if the surface be smoked glass or paper), so long as the muscle remains at rest the lever will describe an even line, which we may call the base line. If how- ever the muscle shortens the lever will rise above the base line and thus describe some sort of curve above the base line. Now CHAP, ii.] THE CONTRACTILE TISSUES. 69 it is found that when a single induction-shock is sent through the nerve the twitch which the muscle gives causes the lever to de- scribe some such curve as that shewn in Fig. 7 ; the lever (after a brief interval immediately succeeding the opening or shutting the key, of which we shall speak presently,) rises at first rapidly but afterwards more slowly, shewing that the muscle is correspondingly shortening, then ceases to rise, shewing that the muscle is ceasing FIG. 7. A MUSCLE-CURVE FROM THE GASTROCNEMIUS OF THE FEOG. This curve, like all succeeding ones, unless otherwise indicated, is to be read from left to right, that is to say, while the lever and tuning-fork were stationary the recording surface was travelling from right to left. a indicates the moment at which the induction-shock is sent into the nerve, b the commencement, c the maximum, and d the close of the contraction. Below the muscle-curve is the curve drawn by a tuning-fork making 100 double vibrations a second, each complete curve representing therefore one hundredth of a second. to grow shorter, then descends, shewing that the muscle is length- ening again, and finally, sooner or later, reaches and joins the base line, shewing that the muscle after the shortening has regained its previous natural length. Such a curve described by a muscle during a twitch or simple muscular contraction, caused by a single induction-shock or by any other stimulus producing the same effect, is called a curve of a simple muscular contraction or, more shortly, a "muscle-curve." It is obvious that the exact form of the curve described by identical contractions of a muscle will depend on the rapidity with which the recording surface is travelling. Thus if the surface be travelling slowly the up-stroke corresponding to the shortening will be very abrupt and the down-stroke also very steep, as in Fig. 8, which is a curve from a gastrocnemius muscle of a frog, taken with a slowly moving drum, the tuning-fork being the same as that used in Fig. 7 ; indeed with a very slow movement, the two may be hardly separable from each other. On the other hand if the surface travel very rapidly the curve may be immensely long drawn out, as 'mmm^mmmtmtm in Fig. 9, which is a curve from a gastro- -pio. 8. cnemius muscle of a frog, taken with a very rapidly moving pendulum myograph, the tuning-fork marking about 500 vibrations a second. On examination, however, it will be 70 FIG. 9. A SIMPLE MUSCULAR CONTRACTION. [BOOK i. found that both these extreme curves are funda- mentally the same as the medium one, when account is taken of the different rapidities of the travelling surface in the several cases. 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. In the pendulum myograph the rate of move- ment can be calculated from the length of the • pendulum ; but even in this it is convenient, and in the case of the spring myograph and revolving cylinder is necessary, to measure the rate of move- ment directly by means of a vibrating tuning-fork or of some body vibrating regularly. Indeed it is best to make such a direct measurement with each curve that is taken. A tuning-fork, as is known, vibrates so many times a second according to its pitch. If a tuning- fork, armed with a light marker on one of its prongs and vibrating say 100 a second, i.e. executing a double vibration, moving forwards and backwards, 100 times a second, be brought while vibrating to make a tracing on the recording surface immedi- ately below the lever belonging to the muscle, we can use the curve or rather curves described by the tuning-fork to measure the duration of any part or of the whole of the muscle-curve. It is essential that at starting the point of the marker of the tuning-fork should be exactly underneath the marker of the lever, or rather, since the point of the lever as it moves up and down describes not a straight line but an arc of a circle of which its fulcrum is the centre and itself (from the fulcrum to the tip of the marker) the radius, that the point of the marker of the tuning-fork should be exactly 011 the arc described by the marker of the lever, either above or below it, as may prove most convenient. If then at starting the tuning-fork marker be thus on the arc of the lever marker, and we note on the curve of the tuning-fork the place where the arc of the lever cuts it at the beginning and at the end of the muscle-curve as at Fig. 7, we can count the number of vibrations of the tuning-fork which have taken place between the two marks, and so ascer- tain the whole time of the muscle curve ; if for instance there have been 10 double vibrations, each CHAP, ii.] THE CONTRACTILE TISSUES. 71 FIG. 10. THE PENDULUM MYOGEAPH. The figure is diagrammatic, the essentials only of the instrument being shewn. The smoked glass plate A swings with the pendulum B on carefully adjusted 72 A SIMPLE MUSCULAR CONTRACTION. [BOOK i. bearings at C. The contrivances by wbicb 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 swing 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 b. On depressing the catch b the glass plate is set free, swings into the new position indicated by the dotted lines, and is held in that position by the tooth a' catching on the catch b'. In the course of its swing the tooth «' coming into contact with the projecting steel rod c, knocks it on one side into the position indicated 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 similarly in 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 mark the time. occupying -^ sec., the whole curve has taken -Jjj sec. to make. In the same way we can measure the duration of the rise of the curve or of the fall or of any part of it. Though the tuning-fork may, by simply striking it, be set going long enough for the purposes of an observation, it is convenient to keep it going by means of an electric current and a magnet, very much as the spring in the magnetic interrupter (Fig. 5) is kept going. It is not necessary to use an actual tuning-fork; any rod, armed with a marker, which can be made to vibrate regularly, and whose time of vibration is known, may be used for the purpose ; thus a reed, made to vibrate by a blast of air, is sometimes em- ployed. The exact moment at which the induction-shock is thrown into the nerve may be recorded on the muscle-curve by means of a ' signal,' which may be applied in various ways. A light steel lever aruied with a marker is arranged over a small coil by means of a light spring in such a way that when the coil by the passage of a current through it becomes a magnet it pulls the lever down to itself; on the current being broken, and the magneti- sation of the coil ceasing, the lever by help of the spring flies up. The marker of such a lever is placed immediately under (i.e. at some point on the arc described by) the marker of the muscle (or other) lever. Hence by making a current in the coil and putting the signal lever down, or by breaking an already existing current, and letting the signal lever fly up, we can make at pleasure a mark corresponding to any part we please of the muscle (or other) curve. If in order to magnetise the coil of the signal, we use, as we may do, the primary current which generates the induction-shock, the break- ing or making of the primary current, whichever we use to produce the CHAP, ii.] THE CONTRACTILE TISSUES. 73 induction-shock, will make the signal lever fly up or come clown. Hence we shall have on the recording surface, under the muscle, a mark indicating the exact moment at which the primary current was broken or made. Now the time taken up by the generation of the induced current and its passage into the nerve between the electrodes is so infinitesinially small, that we may, without appreciable error, take the moment of the breaking or making of the primary current as the moment of the entrance of the induction-shock into the nerve. Thus we can mark below the muscle-curve, or, by describing the arc of the muscle lever, on the muscle-curve itself, the exact moment at which the induction-shock falls into the nerve between the electrodes, as is done at a in Figs. 7, 8, 9. In the pendulum myograph a separate signal is not needed. If, having placed the muscle lever in the position in which we intend to make it record, we allow the glass plate to descend until the tooth a just touches the rod c (so that the rod is just about to be knocked down, and so break the primary circuit) and make on the base line, which is meanwhile being described by the lever marker, a mark to indicate where the point of the marker is under these circumstances, and then bring back the plate to its proper position, the mark which we have made will mark the moment of the breaking of the primary circuit and so of the entrance of the induction-shock into the nerve. For it is just when, as the glass plate swings down, the marker of the lever comes to the mark which we have made that the rod c is knocked back and the primary current is bi'oken. FIG. 11. DIAGRAM OF AN ARRANGEMENT OF A VIBRATING TUNING-FORK WITH A DESPRETZ SIGNAL. The current flows along the wire / connected with the positive ( + ) pole or end of the negative plate (N) of the battery, through the tuning-fork, down the pin connected with the end of the lower prong, to the mercury in the cup Ho, and so by a wire (shewn in figure) to the binding screw e. From this binding screw part of the current flows through the coil d between the prongs of the tuning-fork, and thence by the wire c to the binding screw a, while another part flows through the wire g, through the coil of the Despretz signal back by the wire b, to the binding screw a. From the binding screw a the current passes back to the negative ( — ) pole or end of the positive element (P) of the battery. As the current flows through the coil of the Despretz signal from g to b, the core of coil becoming magnetized draws down the marker of the signal. As the current flows through the coil d, the core of that coil, also becoming magnetized, draws up the lower prong of the fork. But the piu is so adjusted that the drawing up of the prong lifts the point of the pin out of the mercury. In consequence the current being thus broken at Hg, flows neither through d nor through the Despretz signal. In consequence, the core of the Despretz thus ceasing to be magnetized, the marker flies back, being usually assisted by a spring (not shown in the figure). But in consequence of the current ceasing to flow through d, the core of d ceases to lift up the prong, and the pin, in the descent of 74 MUSCLE-CURVE. [BOOK i. the proug, makes contact once more with the mercury. The re-establishment of the current however once more acting on the two coils, again pulls down the marker of the signal, and again by magnetizing the core of d pulls up the prong and once more breaks the current. Thus the current is continually made and broken, the rapidity of the interruptions being determined by the vibration periods of the tuning-fork, and the lever of the signal rising and falling synchronously with the movements of the tuning-fork. A 'signal' like the above, in an improved form known as Despretz's, may be used also to record time, and thus the awkwardness of bringing a large tuning-fork up to the recording surface obviated. For this pur- pose the signal is introduced into a circuit the current of which is continually being made and broken by a tuning-fork (Fig. 11). The tuning-fork once set vibrating continues to make and break the current at each of its vibrations, and as stated above is kept vibrating by the current. But each make or break caused by the tuning-fork affects also the small coil of the signal, causing the lever of the signal to fall down or fly up. Thus the signal describes vibration curves synchronous with those of the tuning-fork driving it. The signal may similarly be worked by means of vibrating agents other than a tuning-fork. Various recording surfaces may be used. The form most generally useful is a cylinder covered with smoked paper and made to revolve by clockwork or otherwise ; such a cylinder driven by clockwork is shewn in Fig. 3. B. By using a cylinder of large radius with adequate gear, a high speed, for instance in a second, can be obtained. In the spring iiiyograjjh a smoked glass plate is thrust rapidly forward along a groove by means of a spring suddenly thrown into action. In the pendulum myograpli, Fig. 10, a smoked glass plate attached to the lower end of a long frame swinging like a pendulum, is suddenly let go at a certain height, and so swings rapidly through an arc of a circle. The dis- advantage of the last two methods is that the surface travels at a continually changing rate, whereas, in the revolving cylinder, careful construction and adjustment will secure a very uniform rate. § 46. Having thus obtained a time record, and an indication of the exact moment at which the induction-shock falls into the nerve, we may for present purposes consider the muscle-curve com- plete. The study of such a curve, as for instance that shewn in Fig. 7, taken from the gastrocnemius of a frog, teaches us the following facts : 1. That although 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 an appreciable time. In the figure, the whole curve from a to d takes up about the same time as eleven double vibrations of the tuning-fork. Since each double vibration here represents 100th of a second, the duration of the whole curve is rather more than -^ sec. 2. In the first portion of this period, from a to b, there is no visible change, no raising of the lever, no shortening of the muscle. 3. It is not until b, that is to say after the lapse of about 100th sec., that the shortening begins. The shortening as shewn CHAP, ii.] TEffi CONTRACTILE TISSUES. 75 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 shortening occupying rather more than y^ sec. 4. Arrived at the maximum of shortening, the muscle at once begins to relax, the lever descending at first slowly, then more rapidly, and at last more slowly again, until at d the muscle has regained its natural length ; the whole return from the maximum of contraction to the natural length occupying rather more than T{^ sec. Thus a simple muscular contraction, a simple spasm or twitch, produced by a momentary stimulus, such as a single 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 called the 'latent period.' 2. A phase of shortening or, in the more strict meaning of the word, 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 actions 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 along 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 FIG. 12. CURVES ILLUSTRATING THE MEASUREMENT OF THE VELOCITY OF A NERVOUS IMPULSE. 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 in exactly the same way. In (1) the stimulus enters the nerve at the time indicated by the line a, the con- traction begins at b' ; 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 «.; the contraction begins at b; the latent period therefore is indicated by the distance between a and b. 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 tuniug-fork curve below ; each double vibration of the tuning- fork corresponds to T^ or -0083 sec. 76 VELOCITY OF NERVOUS IMPULSE. [BOOK i. spot, at the moment when the point of the lever had reached exactly the same point of the travelling surface as before, two curves would be gained having the relations shewn in Fig. 12. The two curves resemble each other in almost all points, except that in the curve taken with the shorter piece of nerve, the latent period, the distance a to b as compared with the distance a to b' is shortened : the contraction begins rather earlier. A study of the two curves teaches us the following two facts : 1. Shifting the electrodes from a point of the nerve at some distance from the muscle to a point of the nerve close to the muscle has only shortened the latent period a very little. Even when a very long piece of nerve is taken the difference in the two curves is very small, and indeed in order that it may be clearly recognized or measured, the travelling surface must be made to travel very rapidly. It is obvious therefore that by far the greater part of the latent period is taken up by changes in the muscle itself, changes preparatory to the actual visible shortening. Of course, even when the electrodes are placed close to the muscle, the latent period includes the changes going on in the short piece of nerve still lying between the electrodes and the muscular fibres. To eliminate this with a view of determining the latent period in the muscle itself, the electrodes might be placed directly on the muscle poisoned with urari. If this were done, it would be found that the latent period remained about the same, that is to say, that in all cases the latent period is chiefly taken up by changes in the muscular as distinguished from the nervous elements. 2. Such difference as does exist between the two curves in the figure, 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 have already spoken of as constituting a nervous impulse ; and the above experiment shews that it takes a small but yet distinctly appreciable time for a nervous impulse to travel along a nerve. In the figure the difference between the two latent periods, the distance between b and b', 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 thus be easily calculated. This has been found to be in the frog about 28, and in man about 33 metres per second, but varies considerably es- pecially in warm-blooded animals. Thus when a momentary stimulus, such as a single induction- shock, is sent into a nerve connected with a muscle, the following CHAP, ii.] THE CONTRACTILE TISSUES. 77 events take place : a nervous impulse is started in the nerve and this travelling down to the muscle produces in the muscle first the invisible changes which constitute the latent period, secondly the changes which bring about the shortening or contraction proper, and thirdly the changes which bring about the relaxation and return to the original length. The changes taking place in each of these three phases are changes of living matter ; they vary with the condition of the living substance of the muscle, and only take place so long as the muscle is alive. Though the relaxation which brings back the muscle to its original length is assisted by the muscle being loaded with a weight or otherwise stretched, this is not essential to the actual relaxation, and with the same load the return will vary according to the condition of the muscle ; the relaxation must be considered as an essential part of the whole contraction no less than the shortening itself. § 47. Not only, as we shall see later on, does the whole con- traction vary in extent and character according to the condition of the muscle, the strength of the induction-shock, the load which the muscle is bearing, and various attendant circumstances, but the three phases may vary independently. The latent period may be longer or shorter, the shortening may take a longer or shorter time to reach the same height, and especially the relaxation may be slow or rapid, complete or imperfect. Even when the same strength of induction-shock is used the contraction may be short and sharp or very long drawn out, so that the curves described on a recording surface travelling at the same rate in the two cases appear very different ; and under certain circumstances, as when a muscle is fatigued, the relaxation, more particularly the last part of it, may be so slow, that it may be several seconds before the muscle really regains its original length. Hence, if we say that the duration of a simple muscular con- traction of the gastrocnemius of a frog, under ordinary circumstances is about -Jg- sec., of which y^ is taken up by the latent period, y§^ '' by the contraction, and T|^ by the relaxation, these must be taken as 'round numbers' stated so as to be easily remembered. The duration of each phase as well as of the whole contraction varies in different animals, in different muscles of the same animal, and in the same muscle under different conditions. The muscle curve which we have been discussing is a curve of changes in the length only of the muscle ; but if the muscle, instead of being suspended, were laid flat on a glass plate and a lever laid over its belly, we should find, upon sending an induction-shock into the nerve, that the lever was raised, shewing that the muscle during the contraction became thicker. And if we took a graphic record of the movements of the lever we should obtain a curve very similar to the one just discussed ; after a latent period the lever would rise, shewing that the muscle was getting thicker, and after- wards would fall, shewing that the muscle was becoming thin again. 78 TETANUS. [BOOK i. In other words, in contraction the lessening of the muscle length- wise is accompanied by an increase crosswise ; indeed, as we shall see later on, the muscle in contracting is not diminished in bulk at all (or only to an exceedingly small extent, about JOGJOG" °f ^ts total bulk), but makes up for its diminution in length by increasing in its other diameters. § 48. A single induction-shock is, as we have said, the most convenient form of stimulus for producing a simple muscular con- traction, but this may also be obtained by other stimuli provided that these are sufficiently sudden and short in their action, as for instance by a prick of, or sharp blow on, the nerve or muscle. For the production of a single simple muscular contraction the changes in the nerve leading to the muscle must be of such a kind as to constitute what may be called a single nervous impulse, and any stimulus which will evoke a single nervous impulse only may be used to produce a simple muscular contraction. As a rule however most stimuli other than single induction shocks tend to produce in a nerve several nervous impulses, and as we shall see the nervous impulses which issue from the central nervous system and so pass along nerves to muscles, are as a rule not single and simple but complex. Hence, as a matter of fact, a simple muscular contraction is within the living body a compara- tively rare event (at least as far as the skeletal muscles are concerned), and cannot easily be produced outside the body other- wise than by a single induction-shock. The ordinary form of muscular contraction is not a simple muscular contraction but the more complex form known as a tetanic contraction, to the study of which we must now turn. Tetanic Contractions. § 49. If a single induction-shock be followed at a certain interval by a second shock of the same strength, the first simple contraction will be followed by a second simple contraction, both contractions being separate and distinct ; and if the shocks be repeated a series of rhythmically recurring separate simple con- tractions may be obtained. If however the interval between two shocks made short, if for instance it be made only just long enough to allow the first contraction to have passed its maximum before the latent period of the second is over, the curves of the two contractions will bear some such relation to each other as that shewn in Fig. 13. 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 is raised CHAP. IL] THE CONTRACTILE TISSUES. 79 nearly double the height it would have been by either alone. If in the same way a third shock follows the second at a sufficiently FIG. 13. TRACING OF A DOUBLE MUSCLE-CURVE. While the muscle (gastrocnemius of frog) 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. short interval, a third curve is piled on the top of the second ; the same with a fourth, and so on. A more or less similar result would occur if the second contraction began at another 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. Hence the result of a repetition of shocks will depend largely on the rate of repetition. If, as in Fig. 14, the shocks follow each other so slowly that one contraction is over, or almost over, before the next begins, each contraction will be distinct, or nearly distinct, and there will be little or no combined effect. FIG. 14. MUSCLE-CURVE. SINGLE INDUCTION SHOCKS REPEATED SLOWLY. If however the shocks be repeated more rapidly, as in Fig. 15, each succeeding contraction will start from some part of the preceding one, and the lever will be raised to a greater height at each contraction. FIG. 15. MUSCLE-CURVE. SINGLE INDUCTION SHOCK REPEATED MOKE RAPIDLY. 80 TETANUS. [Boon i. If the frequency of the shocks be still further increased, as in Fig. 16, the rise due to the combination of contraction will be still more rapid, and a smaller part of each contraction will be visible on the curve. FIG. 16. MUSCLE-CUEVE. SINGLE INDUCTION SHOCK REPEATED STILL MORE RAPIDLY. In each of these three curves it will be noticed that the character of the curve changes somewhat during its development. The change is the result of commencing fatigue, caused by the repetition of the contractions, the fatigue manifesting itself by an increasing prolongation of each contraction, shewn especially in a delay of relaxation, and by an increasing diminution in the height of the contraction. Thus in Fig. 14 the contractions quite distinct at first, become fused later; the fifth contraction for instance is prolonged so that the sixth begins before the lever has reached the base line ; yet the summit of the sixth is hardly higher than the summit of the fifth, since the sixth though starting at a higher level is a somewhat weaker contraction. So also in Fig. 15, the lever rises rapidly at first but more slowly afterwards, owing to an increasing diminution in the height of the single contractions. In Fig. 16 the increment of rise of the curve due to each contraction diminishes very rapidly, and though the lever does continue to rise during the whole series, the ascent after about the sixth contraction is very gradual indeed, and the indications of the individual contractions are much less marked than at first. Hence when shocks are repeated with sufficient rapidity, it results that after a certain number of shocks, the succeeding im- pulses do 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 main- tains, subject to the depressing effects of exhaustion, so long as the shocks are repeated. When these cease to be given, the muscle returns to its natural length. When the shocks succeed each other still more rapidly than in Fig. 16 the individual contractions, visible at first, may become fused together and wholly lost to view in the latter part of the curve. When the shocks succeed each other still more rapidly CHAP, ii.] THE CONTRACTILE TISSUES. 81 (the second contraction beginning in the ascending portion of the first), it becomes difficult or impossible to trace out any of the single contractions 1. The curve then described by the lever is of the kind shewn in Fig. 17, where the primary current of an FIG. 17. TETANUS PKODUCED WITH THE ORDINARY MAGNETIC INTERRUPTOR OF AN INDUCTION-MACHINE. (Eecording surface travelling slowly.) The interrupted current is thrown in at a. induction-machine was rapidly made and broken by the magnetic interruptor, Fig. 5. The lever, it will be observed, rises at a (the recording surface is travelling too slowly to allow the latent period to be distinguished), at first very rapidly, in fact in an unbroken and almost a vertical line, and so very speedily reaches the maximum, which is maintained so long as the shocks continue to be given ; when these cease to be given, the curve descends at first very rapidly and then more and more gradually towards the base line, which it reaches just at the end of the figure. This condition of muscle, brought about by rapidly repeated shocks, this fusion of a number of simple twitches 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, what- ever be the form of stimulus employed. Thus in the case of mechanical stimuli, while a single quick blow may cause a single twitch, a pronounced tetanus may be obtained by rapidly striking successively fresh portions of a nerve. With chemical stimulation, as when a nerve is dipped in acid, it is impossible to secure a momentary application ; hence tetanus, generally irregular in character, is the normal result of this mode of stimulation. In the living body, the contractions of the skeletal muscles, brought about either by the will or otherwise, are generally tetanic in character. Even very short sharp movements, such as a sudden jerk of a limb or a wink of the eyelid, are in reality examples of tetanus of short duration. 1 The ease with which the individual contractions can be made out depends in part, it need hardly be said, on the rapidity with which the recording surface travels. F. 6 - 82 TETANUS. [BOOK i. If the lever, instead of being fastened to the tendon of a muscle hung vertically, be laid across the belly of a muscle placed in a horizontal position and the muscle be thrown into tetanus by a repetition of induction-shocks, it- will be seen that each shortening of the muscle is accompanied by a corresponding thickening, and that the total shortening of the tetanus is accompanied by a cor- responding total thickening. And indeed in tetanus we can observe more easily than in a single contraction that the muscle in contract- ing changes in form only, not in bulk. If a living muscle or group of muscles be placed in a glass jar or chamber, the closed top of which is prolonged into a narrow glass tube, and the chamber be filled with water (or preferably with a solution of sodium chloride, '6 p. c. in strength, usually called "normal saline solution," which is less injurious to the tissue than simple water) until the water rises into the narrow tube, it is obvious that any change in the bulk of the muscle will be easily shewn by a rising or falling of the column of fluid in the narrow tube. It is found that when the muscle is made to contract, even in the most forcible manner, the change of level in the height of the column which can be observed is practically insignificant : there appears to be a fall in- dicating a diminution of bulk to the extent of about one ten-thou- sandth of the total bulk of the muscle. So that we may fairly say that in a tetanus, and hence in a simple contraction, the lessening of the length of the muscle causes a corresponding increase in the other directions : the substance of the muscle is displaced not diminished. § 50. So far we have spoken simply of an induction-shock or of induction-shocks without any reference to their strength, and of a living or irritable muscle without any reference to the degree or extent of its irritability. But induction-shocks may vary in strength, and the irritability of the muscle may vary. If we slide the secondary coil a long way from the primary coil, and thus make use of extremely feeble induction-shocks, we shall probably find that these shocks, applied even to a quite fresh muscle- nerve preparation, produce no contraction. If we then gradually slide the secondary coil nearer and nearer the primary coil, and keep on trying the effects of the shocks, we shall find that after a while, in a certain position of the coils, a very feeble contraction makes its appearance. As the secondary coil comes still nearer to the primary coil the contractions grow greater and greater. After a while however, and that indeed in ordinary circumstances very speedily, increasing the strength of the shock no longer increases the height of the contraction; the maximum contraction of which the muscle is capable with such shocks however strong has been reached. If we use a tetanizing or interrupted current we shall obtain the same general results ; we may, according to the strength of the current, get no contraction at all, or contractions of various extent up to a maximum, which cannot be exceeded. Under favourable CHAP, ii.] THE CONTRACTILE TISSUES. S3- conditions the maximum contraction may be very considerable: the shortening in tetanus may amount to three-fifths of the total length of the muscle. The amount of contraction then depends on the strength of the stimulus, whatever be the stimulus ; but this holds good within certain limits only ; to this point however we shall return later on. § 51. If, having ascertained in a perfectly fresh muscle-nerve preparation the amount of contraction produced by this and that strength of stimulus, we leave the preparation by itself for some time, say for a few hours, and then repeat the observations, we shall find that stronger stimuli, stronger shocks for instance, are required to produce the same amount of contraction as before; that is to say, the irritability of the preparation, the power to respond to stimuli, has in the meanwhile diminished. After a further interval we should find the irritability still further dimin- ished : even very strong shocks would be unable to evoke con- tractions as large as those previously caused by weak shocks. At last we should find that no shocks, no stimuli, however strong, were able to produce any visible contraction whatever. The amount of contraction in fact evoked by a stimulus depends not only on the strength of the stimulus but also on the degree of irritability of the muscle-nerve preparation. Immediately upon removal from the body, the preparation pos- sesses a certain amount of irritability, not differing very materially from that which the muscle and nerve possess while within and forming an integral part of the body ; but after removal from the body the preparation loses irritability, the rate of loss being dependent on a variety of circumstances; and this goes on until, since no stimulus which we can apply will give rise to a contraction, we say the irritability has wholly disappeared. We might take this disappearance of irritability as marking the death of the preparation, but it is followed sooner or later by a curious change in the muscle, which is called rigor mortis, and which we shall study presently ; and it is convenient to regard this rigor mortis as marking the death of the muscle. The irritable muscle then, when stimulated either directly, the stimulus being applied to itself, or indirectly, the stimulus being applied to its nerve, responds to the stimulus by a change of form which is essentially a shortening and thickening. By the short- ening (and thickening) the muscle in contracting is able to do work, to move the parts to which it is attached; it thus sets free energy. We have now to study more in detail how this energy is set free and the laws which regulate its expenditure. 6—2 SEC. 2. ON THE CHANGES WHICH TAKE PLACE IN A MUSCLE DURING A CONTRACTION. The Change in Form. § 52. Gross structure of muscle. An ordinary skeletal muscle consists of elementary 'muscle fibres, bound together in variously arranged bundles by connective tissue which carries blood vessels, nerves and lymphatics. The same connective tissue besides sup- plying a more or less distinct wrapping for the whole muscle forms the two ends of the muscle, being here sometimes scanty, as where the muscle appears to be directly attached to a bone, and a small amount only of connective tissue joins the muscular fibres to the periosteum, sometimes abundant, as when the con- nective tissue in which the muscular fibres immediately end is prolonged into a tendon. Each elementary fibre, which varies even in the mammal in length and breadth (in the frog the dimensions vary very widely) but may be said on an average to be 30 or 40 mm. in length and 20/u, to 30yu- in breadth, consists of an elastic homogeneous or faintly fibrillated sheath of peculiar nature, the sarcolemma, which embraces and forms an envelope for the striated muscular substance within. Each fibre, cylindrical in form, giving a more or less circular outline in transverse section, generally tapers off at each end in a conical form. At each end of the fibre the sarcolemma, to which in life the muscular substance is adherent, becomes continuous with fibrillge of connective tissue. When the end of the fibre lies at the end of the muscle, these connective tissue fibrillae pass directly into the tendon (or into the periosteum, &c.), and in some cases of small muscles which are no longer than their constituent fibres, each fibre may thus join at each end of itself, by means of its sarcolemma, the tendon or other ending of the muscle. In a very large number of muscles however the muscle is far longer than any of its fibres, and there may even be whole bundles of fibres in CHAP, ii.] THE CONTRACTILE TISSUES. 85 the middle of the muscle which do not reach to either end. In such case the connective tissue in which the sarcolemma ends is continuous with the connective tissue which, running between the fibres and between the bundles, binds the fibres into small bundles, and the smaller bundles into larger bundles. The contraction of a muscle is the contraction of all or some of its elementary fibres, the connective tissue being passive ; hence while those fibres of the muscle which end directly in the tendon, in contracting pull directly on the tendon, those which do not so end pull indirectly on the tendon by means of the connective tissue between the bundles, which connective tissue is continuous with the tendon. The blood vessels run in the connective tissue between the bundles and between the fibres, and the capillaries form more or less rectangular networks immediately outside the sarcolemma. Lymphatic vessels also run in the connective tissue, in the lymph spaces of which they begin. Each muscular fibre is thus surrounded by lymph spaces and capillary blood vessels, but the active muscular substance of the fibre is separated from these by the sarcolemma ; hence the interchange between the blood and the muscular sub- stance is carried on backwards and forwards through the capillary wall, through some of the lymph spaces, and through the sarco- lemma. Each muscle is supplied by one or more branches of nerves composed of medullated fibres, with a certain proportion of non- medullated fibres. These branches running in the connective tissue divide into smaller branches and twigs between the bundles and fibres. Some of the nerve fibres are distributed to the blood vessels, and others end in a manner of which we shall speak later on in treating of muscular sensations ; but by far the greater part of the medullated fibres end in the muscular fibres, the arrange- ment being such that every muscular fibre is supplied with at least one medullated nerve fibre, which joins the muscular fibre somewhere about the middle between its two ends or sometimes nearer one end, in a special nerve ending, of which we shall presently have to speak, called an end plate. The nerve fibres thus destined to end in the muscular fibres divide as they enter the muscle, so that what, as it enters the muscle is a single nerve fibre, may, by dividing, end as several nerve fibres in several muscular fibres. Sometimes two nerve fibres join one muscular fibre, but in this case the end plate of each nerve fibre is still at some distance from the end of the muscular fibre. It follows that when a muscular fibre is stimulated by means of a nerve fibre, the nervous impulse travelling down the nerve fibre falls into the muscular fibre not at one end but at about its middle ; it is the middle of the fibre which is affected first by the nervous impulse, and the changes in the muscular substance started in the middle of the muscular fibre travel thence to the two ends of the fibre. 86 THE WAVE OF CONTRACTION. [BOOK i. In an ordinary skeletal muscle however, as we have said, the fibres and bundles of fibres begin and end at different distances from the ends of the muscle, and the nerve or nerves going to the muscle divide and spread out in the muscle in such a way that the end plates, in which the individual fibres of the nerve end, are distributed widely over the muscle at very different distances from the ends of the muscle. Hence, if we suppose a single nervous impulse, such as that generated by a single induction shock, or a series of such impulses to be started at the same time at some part of the trunk of the nerve in each of the fibres of the nerve going to the muscle, these impulses will reach very different parts of the muscle at about the same time and the contractions which they set going will begin, so to speak, nearly all over the whole muscle at the same time, and will not all start in any particular zone or area of the muscle. § 53. The wave of contraction. We have seen, however, that under the influence of urari the nerve fibre, is unable to excite contractions in a muscular fibre, although the irritability of the muscular fibre itself is retained. Hence, in a muscle poisoned by urari the contraction begins at that part of the muscular substance which is first affected by the stimulus, and we may start a con- traction in what part of the muscle we please by properly placing the electrodes. Some muscles, such for instance as the sartorius of the frog, though of some length are composed of fibres which run parallel to each other from one end of the muscle to the other. If such a muscle be poisoned with urari so as to eliminate the action of the nerves and stimulated at one end (an induction-shock sent through a pair of electrodes placed at some little distance apart from each other at the end of the muscle may be employed, but better results are obtained if a mode of stimulation, of which we shall have to speak presently, viz. the application of the " constant cur- rent," be adopted), the contraction which ensues starts from the end stimulated, and travels thence along the muscle. If two levers be made to rest on, or be suspended from, two parts of such a muscle placed horizontally, the parts being at a known distance from each other and from the part stimulated, the progress of the contraction . may be studied. The movements of the levers indicate in this case the thicken- ing of the fibres which is taking place at the parts 011 which the levers rest or to which they are attached ; and if we take a graphic record of these movements, bringing the two levers to mark, one immediately below the other, we shall find that the lever nearer the part stimulated begins to move earlier, reaches its maximum earlier, and returns to rest earlier than does the farther lever. The contraction, started by the stimulus, in travelling along the muscle from the part stimulated reaches the nearer lever some little time before it reaches the farther lever, and has passed by CHAP. ii. ] THE CONTRACTILE TISSUES. 87 the nearer lever some little time before it has passed by the farther lever ; and the farther apart the two levers are the greater will be the difference in time between their movements. In other words the contraction travels along the muscle in the form of a wave, each part of the muscle in succession from the end stimulated swelling out and shortening as the contraction reaches it, and then returning to its original state. And what is true of the collection of parallel fibres which we call the muscle is also true of each fibre, for the swelling at any part of the muscle is only the sum of the swelling of the individual fibres ; and if we were able to take a single long fibre and stimulate it at one end, we should be able under the microscope to see a swelling or bulging accompanied by a corresponding shortening, i.e. to see a contraction, sweep along the fibre from end to end. If in the graphic record of the two levers just mentioned we count the number of vibrations of the tuning-fork which intervene between the mark on the record which indicates the beginning of the rise of the near lever (that is the arrival of the contraction wave at this lever) and the mark which indicates the beginning of the rise of the far lever, this will give us the time which it has taken the contraction wave to travel from the near to the far lever. Let us suppose this to be -00o sec. Let us suppose the distance between the two levers to be 15 mm. The con- traction wave then has taken '005 sec. to travel 15 mm., that is to say it has travelled at the rate of 3 meters per sec. And indeed we find by this, or by other methods, that in the frog's muscles the contraction wave does travel at a rate which may be put down as from 3 to 4 meters a second, though it varies under different con- ditions. In the warm-blooded mammal the rate is somewhat greater, and may probably be put down at 5 meters a second in the excised muscle, rising possibly to 10 meters in a muscle within the living body. If again in the graphic record of the two levers we count, in the case of either lever, the number of vibrations of the tuning- fork which intervene between the mark where the lever begins to( rise and the mark where it has finished its fall and returned to the\ base line, we can measure the time intervening between the contraction wave reaching the lever, and leaving the lever on its way onward, that is to say we can measure the time which it has taken the contraction wave to pass over the part of the muscle on which the lever is resting. Let us suppose this time to be say •1 sec. But a wave which is travelling at the rate of 3 m. a second and takes '1 sec. to pass over any point must be 300 mm. long. And indeed we find that in the frog the length of the contraction wave may be put down as varying from 200 to 400 mm., and in the mammal it is not very different. Now, as we have said, the very longest muscular fibre is stated to be at most only about 40 mm. in length ; hence, in an ordinary 88 THE WAVE OF CONTRACTION. [BOOK i. contraction, during the greater part of the duration of the contrac- tion the whole length of the fibre will be occupied by the contrac- tion wave. Just at the beginning of the contraction there will be a time when the front of the contraction wave has reached for instance only half way down the fibre (supposing the stimulus to be applied, as in the case we have been discussing, at one end only), and just at the end of the contraction there will be a time for instance when the contraction has left the half of the fibre next to the stimulus, but has not yet cleared away from the other half. But nearly all the rest of the time every part of the fibre will be in some phase or other of contraction, though the parts nearer the stimulus will be in more advanced phases than the parts farther from the stimulus. This is true when a muscle of parallel fibres is stimulated artificially at one end of the muscles, and when therefore each fibre is stimulated at one end. It is of course all the more true when a muscle of ordinary construction is stimulated by means of its nerve. The stimulus of the nervous impulse impinges, in this case, on the muscle fibre at the end plate which, as we have said, is placed towards the middle of the fibre, and the contraction wave travels from the end plate in opposite directions toward each end, and has accordingly only about half the length of the fibre to run in. All the more therefore must the whole fibre be in a state of contraction at the same time. It will be observed that in what has just been said the contraction wave has been taken to include not only the con- traction proper, the thickening and shortening, but also the relaxation and return to the natural form ; the first part of the wave up to the summit of the crest corresponds to the shortening and thickening, the decline from the summit onwards corresponds to the relaxation. But we have already insisted that the relax- ation is an essential part of the whole act, indeed in a certain sense as essential as the shortening itself. § 54. Minute structure of muscular fibre. So far we have been dealing with the muscle as a whole and as observed with the naked eye, though we have incidentally spoken of fibres. We have now, confining our attention exclusively to skeletal muscles, to consider what microscopic changes take place during a contraction, what are the relations of the histological features of the muscle fibre to the act of contraction. The long cylindrical sheath of sarcolemma is occupied by muscle substance. After death the muscle substance may separate from the sarcolemma, leaving the latter as a distinct sheath, but during life the muscle substance is adherent to the sarcolemma, so that no line of separation between the two can be made out ; the movements of the one follow exactly all the movements of the other. Scattered in the muscle substance but, in the mammal, lying CHAP. ii. J THE CONTRACTILE TISSUES. 89 for the most part close under the sarcolemma are a number of nuclei, oval in shape with their long axes parallel to the length of the fibre. Around each nucleus is a thin layer of granular looking substance, very similar in appearance to that forming the body of a white blood corpuscle, and like that often spoken of as un- differentiated protoplasm. A small quantity of the same granular substance is prolonged for some distance, as a narrow conical streak from each end of the nucleus, along the length of the fibre. With the exception of these nuclei with their granular looking bed and the end plate or end plates, to be presently described, all the rest of the space enclosed by the sarcolemma from one end of the fibre to the other appears to be occupied by a peculiar material, striated muscle-substance. It is called striated because it is marked out, and that along the whole length of the fibre, by transverse bands, stretching right across the fibre, of substance which is very transparent, bright sub- stance, alternating with similar bands of substance which has a dim cloudy appearance, dim substance; that is to say the fibre is marked out along its whole length by alternate bright bands and dim bands. The bright bands are on an average about 1 //, or 1*5 /* m. and the dim bands about 2 '5 fj, or 3 p m. thick. By careful focussing, both bright bands and dim bands may be traced through the whole thickness of the fibre, so that the whole fibre appears to be com- posed of bright discs and dim discs placed alternately one upon the other along the whole length of the fibre, the arrangement being broken by the end plate and here and there by the nuclei. When a muscular fibre is treated with dilute mineral acids it is very apt to break up transversely into discs, the sarcolemma being dissolved, or so altered as easily to divide into fragments corresponding to the discs ; and a disc may thus be obtained so thin as to comprise only a single dim or bright band, or a dim band with a thin layer of bright substance above and below it, the cleavage having taken place along the middle of the bright bands. When treated with certain reagents, alcohol, chromic acid, &c., the fibre is very apt to split up (and the splitting up may be assisted by " teasing ") longitudinally into columns of variable thickness, some of which however may be exceedingly thin, and are then sometimes spoken of as ' fibrilk*.' Both these discs and fibrillas are artificial products, the results of a transverse or longitudinal cleavage of the dead, hardened or otherwise prepared muscle substance. They may moreover be obtained in almost any thickness or thinness, and these discs and fibrilte do not by themselves prove much beyond the fact that the fibre tends to cleave in the two directions. The living fibre however, though at times quite glassy looking, the bright bands appearing like transparent glass and the dim bands like ground glass, is at other times marked with longitudinal 90 MINUTE STRUCTURE OF MUSCLE. [BOOK i. lines giving rise to a longitudinal striation, sometimes conspicuous - ;'and occasionally obscuring the transverse striation. In the muscles 'of some insects each dim band has a distinct palisade appearance ' as if made up of a number of ' fibrillse ' or ' rods ' placed side by side and imbedded in some material of a different nature ; more- over these fibrillae or rods may, with greater difficulty, be traced through the bright bands, and that at times along the whole length of the fibre. And there is a great deal of evidence, into which we cannot enter here, which goes to prove that in all striated muscle, mammalian muscle included, the muscle substance is really composed of longitudinally placed natural fibrillce of a certain nature, imbedded in an interfibrillar substance of a different nature. In mammalian muscle and vertebrate muscle generally these fibrilloe are exceedingly thin and in most cases are not % sharply defined by optical characters from their interfibrillar bed ; in insect muscles and some other muscles, they are relatively large, well defined and conspicuous. The artificial fibrillae obtained by teasing may perhaps in some cases where they are exceedingly •thin correspond to these natural fibrilla?, but in the majority of cases they certainly do not. In certain insect muscles each bright band has in it two (or sometimes more) dark lines which are granular in appearance and may be resolved by adequate magnifying power into rows of granules. Since they may by focussing be traced through the whole thickness of the fibre the lines are the expression of discs. Frequently the lines in the bright bands are so conspicuous as to contribute a greater share to the transverse striation of the fibre than do the dim bands. Similar granular lines (rows or rather discs of granules), may also be seen though less distinctly, in vertebrate, including mammalian, muscle. Besides these granular lines whose position in the bright ba.nd is near to the dim bands, often appearing to form, as it were, the upper edge of the dim band below and the lower edge of the dim band above, there may be also sometimes traced another transverse thin line in the very middle of the bright band. This line, like the other lines (or bands) is the expression of a disc and has been held by some observers to represent a membrane stretched across the whole thickness of the fibre and adherent at the circumference with the sarcolemma ; in this sense it is spoken of as Krauses membrane. The reasons for believing that the line really represents a definite membrane do not however appear to be adequate. It may be spoken of as the " intermediate line." When a thin transverse section of frozen muscle is examined quite fresh under a high power, the muscle substance within the sarcolemma is seen to be marked out into a number of small more or less polygonal areas, and a similar arrangement into areas may also be seen in transverse sections of prepared muscle, though the features of the areas are somewhat different from those seen in the CHAP, ii.] THE CONTRACTILE TISSUES. 91 fresh living fibre. These areas are spoken of as " Cohnheim's areas"; they are very much larger than the diameter of a fibrilla as indicated by the longitudinal striation, and indeed correspond to a whole bundle of such fibrillse. Their existence seems to indicate that the fibrillse are arranged in longitudinal prisms separated from each other by a larger amount of interfibrillar substance than that uniting together the individual fibrillse form- ing each prism. Lastly it may be mentioned that not only are the various granular lines at times visible with difficulty or quite invisible, but that even the distinction between dim and bright bands is on occasion very faint or obscure, the whole muscle substance, apart from the nuclei, appearing almost homogeneous. Without attempting to discuss the many and various interpre- tations of the above and other details concerning the minute structure of striated muscular fibre, we may here content ourselves with the following general conclusions. (1) That the muscle substance is composed of longitudinally disposed Jibrillcc (probably cylindrical in general form and probably arranged in longitudinal prisms) imbedded in an interfibrillar substance, which appears to be less differentiated than the fibrillse themselves and which is probably continuous with the undifferen- tiated protoplasm round the nuclei. The interfibrillar substance stains more readily with gold chloride than do the fibrillse, and hence in gold chloride specimens appears as a sort of meshwork, with longitudinal spaces corresponding to the fibrillse. (2) That the interfibrillar substance is, relatively to the fibrillse, more abundant in the muscles of some animals than in those of others, being for instance very conspicuous in the muscles of insects, in which animals we should naturally expect the less differentiated material to be more plentiful than in the muscles of the more highly developed mammal. (3) That, the fibrillse and interfibrillar substance having different refractive powers, some of the optical features of muscle may be due, on the one hand to the relative proportion of fibrillse to inter- fibrillar substance, and on the other hand to the fibrillas not being cylindrical throughout the length of the fibre but constricted at intervals, and thus becoming beaded or moniliform ; for instance the rows of granules spoken of above are by some regarded as corresponding to aggregations of interfibrillar material filling up the spaces where the fibrillse are most constricted. But it does not seem possible at the present time to make any statement which will satisfactorily explain all the various appearances met with. § 55. We may now return to the question, What happens when a contraction wave sweeps over the fibre ? Muscular fibres may be examined even under high powers of the microscope while they are yet living and contractile ; the contraction itself may be seen, but the rate at which the wave travels is too 92 MICROSCOPIC CHANGES. [BOOK i. rapid to permit satisfactory observations being made as to the minute changes which accompany the contraction. It frequently happens however that when living muscle has been treated with certain reagents, as for instance with osmic acid vapour, and sub- sequently prepared for examination, fibres are found in which a bulging, a thickening and shortening, over a greater or less part of the length of the fibre, has been fixed by the osmic acid or other reagent. Such a bulging obviously differs from a normal contraction in being confined to a part of the length of the fibre, whereas, as we have said, a normal wave of contraction, being very much longer than any fibre, occupies the whole length of the fibre at once. We may however regard this bulging as a very short, a very abbre- viated wave of contraction, and assume that the changes visible in such a short bulging also take place in a normal contraction. Admitting this assumption, we learn from such preparations that in the contracting region of the fibre, while both dim and bright bands become broader across the fibre, and correspondingly thinner along the length of the fibre, a remarkable change takes place between the dim bands, bright bands, and granular lines. We have seen that in the fibre at rest the intermediate line in the bright band is in most cases inconspicuous ; in the contracting fibre, on the contrary, a dark line in the middle of the bright band in the position of the intermediate line becomes very distinct. As we pass along the fibre from the beginning of the contraction wave, to the summit of the wave, where the thickening is greatest, this line becomes more and more striking, until at the height of the contraction, it becomes a very marked dark line or thin dark band. Pari passn with this change, the distinction between the dim and bright bands becomes less and less marked ; these appear to become confused together, until at the height of the contraction, the whole space between each two now conspicuous dark lines is occupied by a substance which can be called neither dim nor bright, but which in contrast to the dark line appears more or less bright and transparent. So that in the contracting part there is, at the height of the contraction, a reversal of the state of things proper to the part at rest. The place occupied by the bright band, in the state of rest, is now largely filled by a conspicuous dark line which previously was represented by the inconspicuous intermediate line, and the place occupied by the conspicuous dim band of the fibre at rest now seems by comparison with the dark line the brighter part of the fibre. The contracting fibre is like the fibre at rest striated, but its striation is different in its nature from the natural striation of the resting fibre ; and it is held by some that in the earlier phases of the contraction, while the old natural striation is being replaced by the new striation, there is a stage in which all striation is lost. We may add that the outline of the sarcolemma, which in the fibre at rest is quite even, becomes during the contraction indented CHAP. IL] THE CONTRACTILE TISSUES. 93 opposite the intermediate line, and bulges out in the interval between each two intermediate lines, the bulging and indentation becoming more marked the greater the contraction. § 56. We can learn something further about this remarkable change by examining the fibre under polarized light. When ordinary light is sent through a Nicol prism (which is a rhomb of Iceland spar divided into two in a certain direction, the halves being subsequently cemented together in a special way) it undergoes a change in passing through the prism and is said to be polarized. One effect of this polarization is that a ray of light which has passed through one Nicol prism will or will not pass through a second Nicol according to the relative position of the two prisms. Thus if the second Nicol be so placed that what is called its " optic- axis " be in a line with or parallel to the optic axis of the first Nicol the light passing through the first Nicol will also pass through the second. But if the second Nicol be rotated until its optic axis is at right angles with the optic axis of the first Nicol none of the light passing through the former will pass through the latter; the prisms in this position are said to be 'crossed.' In intermediate positions more or less light passes through the second Nicol according to the angle between the two optic axes. Hence when one Nicol is placed beneath the stage of a microscope so that the light from the mirror is sent through it, and another Nicol is placed in the eye-piece, the field of the microscope will appear dark when the eye-piece Nicol is rotated so that its optic axis is at right angles to the optic axis of the lower Nicol, and consequently the light passing through the lower Nicol is stopped by it. If however the optic axis of the eye-piece Nicol be parallel to that of the lower Nicol, the light from the latter will pass through the former and the field will be bright ; and as the eye-piece is gradually rotated from one position to the other the brightness of the field will diminish or increase. Both the Nicols are composed of doubly refractive material. If now a third doubly refractive material be placed on the stage and therefore between the two Nicols, the light passing through the lower Nicol will (in a certain position of the doubly refractive material on the stage, that is to say when its optic axes have a certain position) pass through it and also through the crossed Nicol in the eye-piece. Hence the doubly refractive material on the stage (or such parts of it as are in the proper position in respect to their optic axes) will, when the eye-piece Nicol is crossed, appear illuminated and bright on a dark field. In this way the existence of doubly refractive material in a preparation may be detected. When muscle prepared and mounted in Canada balsam is examined in the microscope between Nicol prisms, one on the stage below the object, and the other in the eye-piece, the fibres stand out as bright objects on the dark ground of the field when the axes of the prisms are crossed. On closer examination it is seen that the parts which are bright are chiefly the dim bands. 94 MUSCLE UNDER POLARIZED LIGHT. [BOOK i. This indicates that it is the dim bands which are doubly refractive, anisotropic, or are chiefly made up of anisotropic substance ; there seems however to be some slight amount of anisotropic substance in the bright K ^nds though these as a whole appear single refrac- tive or isotropic. The fibre accordingly appears banded or striated with alternate bands of anisotropic and isotropic material. Accord- ing to most authors such an alternation of anisotropic and (chiefly) isotropic bands which is obvious in a dead and prepared fibre exists also in the living fibre ; but some maintain that the living fibre is uniformly anisotropic. Now when a fibre contracts, in spite of the confusion previously mentioned between dim and bright bands, there is 110 confusion between the anisotropic and isotropic material. The anisotropic, doubly refractive bands, bright under crossed Nicols, occupying the position of the dim band in the resting fibre, remain doubly refrac- tive, bright under crossed Nicols, even at the very height of the con- traction. The isotropic, singly refractive, bands, dark under crossed Nicols, occupying the position of the bright bands in the fibre at rest, remain isotropic and dark under crossed Nicols at the very height of the contraction. All that can be seen is that the singly refractive isotropic bands become very thin indeed during the contraction, while the anisotropic bands, though of course becoming thinner and broader in the contraction, do not become so thin as do the isotropic bands ; in other words, while both bands become thinner and broader, the doubly refractive anisotropic band seems to increase at the expense of the singly refractive isotropic band. § 57. We call attention to these facts because they shew how complex is the act of contraction. The mere broadening and shortening of each section of the fibre is at bottom, a transloca- tion of the molecules of the muscle substance. If we imagine a company of 100 soldiers ten ranks deep, with ten men in each rank, rapidly, but by a series of gradations, to extend out into a double line with 50 men in each line, we shall have a rough image of the movement of the molecules during a muscular contraction. But from what has been said it is obvious that the movement, in striated muscle at least, is a very complicated one ; in other forms of contractile tissue it may be, as we shall see, more simple. Why the movement is so complicated in striated muscle, what purposes it serves, why the skeletal muscles are striated we do not at present know. Apparently where swift and rapid contraction is required the contractile tissue is striated muscle ; but how the striation helps so to speak the contraction we do not know. We cannot say what share in the act of contraction is to be allotted to the several parts. Since during a contraction, the fibre bulges out more opposite to each dim disc and is indented opposite to each bright disc, since the dim disc is more largely composed of anisotropic material than the rest of the fibre, and since the anisotropic material in the position of the dim disc increases during a contraction, we might CHAP, ir.] THE CONTRACTILE TISSUES. 95 perhaps infer that the dim disc rather than the bright disc is the essentially active part. Assuming that the fibrillar substance is more abundant in the dim discs, while the interfibrillar substance is more abundant in the bright discs, and that the fibrillar sub- stance is anisotropic (and hence the dim discs largely anisotropic) while the interfibrillar substance is isotropic, we might also be inclined to infer it is the fibrillar and not the interfibrillar sub- stance which really carries out the contraction; but even this much is not yet definitely proved. One thing must be remembered. The muscle substance though it possesses the complicated structure, and goes through the re- markable changes which we have described, is while it is living and intact in a condition which we are driven to speak of as semi-fluid. The whole of it is essentially mobile. The very act of contraction indeed shews this; but it is mobile in the sense that no part of it, except of course the nuclei and sarcolemma, neither dim nor bright substance, neither fibrillar nor interfibrillar substance can be regarded as a hard and fast structure. A minute iiema- toid worm has been seen wandering in the midst of the substance of a living contractile fibre ; as it moved along, the muscle sub- stance gave way before it, and closed up again behind it, dim bands and bright bands all falling back into their proper places. We may suppose that in this case the worm threaded its way in a fluid interfibrillar substance between and among highly extensible and elastic fibrillse. But even on such a view, and still more on the view that the fibrillar substance also was broken and closed up again, the maintenance of such definite histological features as those which we have described in material so mobile can only be effected, even in the fibre at rest, at some considerable expenditure of energy ; which energy it may be expected has a chemical source. During the contraction there is a still further expenditure of energy, some of which, as we have seen, may leave the muscle as 'work done ; ' this energy likewise may be expected to have a chemical source. We must therefore now turn to the chemistry of muscle. The Chemistry of Muscle. § 58. We said, in the Introduction, that it was difficult to make out with certainty the exact chemical differences between dead and living substance. Muscle however in dying undergoes a remarkable chemical change, which may be studied with com- parative ease. We have already said that all muscles, within a certain time after removal from the body, or, if still remaining part of the body, within a certain time after ' general ' death of the body, lose their irritability, and that the loss of irritability, which even when rapid, is gradual, is succeeded by an event which is somewhat more sudden, viz. the entrance into the condition known 96 CHEMISTRY OF MUSCLE. [BOOK i. as rigor mortis. The occurrence of rigor mortis, or cadaveric rigidity, as it is sometimes called, which may be considered as the token of the death of the muscle, is marked by the following features. The living muscle possesses a certain translucency, the rigid muscle is distinctly more opaque. The living muscle is very extensible and elastic, it stretches readily and to a considerable extent when a weight is hung upon it or when any traction is applied to it, but speedily and, under normal circumstances, completely returns to its original length when the weight or traction is removed ; as we shall see however the rapidity and completeness of the return depends on the condition of the muscle, a well nourished active muscle regaining its normal length much more rapidly and com- pletely than a tired and exhausted muscle. A dead rigid muscle is much less extensible and at the same time much less elastic ; the muscle now requires considerable force to stretch it, and when the force is removed, does not, as before, return to its former length. To the touch the rigid muscle has lost much of its former softness, and has become firmer and more resistent. The entrance into rigor mortis is moreover accompanied by a shortening or contraction, which may, under certain circumstances, be con- siderable. The energy of this contraction is not great, so that any actual shortening is easily prevented by the presence of even a slight opposing force. Now the chemical features of the dead rigid muscle are also strikingly different from those of the living muscle. § 59. If a dead muscle, from which all fat, tendon, fascia, and connective tissue have been as much as possible removed, and which has been freed from blood by the injection of 'normal ' 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 a neutral salt, ammonium chloride being the best, a large portion of it will become dissolved ; the solution however is more or less imperfect and filters with difficulty. If the 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. Myosin is a proteid, giving the ordinary proteid reactions, and having the same general elementary composition as other proteids. It is soluble in dilute saline solutions, especially those of ammonium chloride, and may be classed in the globulin family, though it is not so soluble as paraglobulin, requiring a stronger solution of a neutral salt to dissolve it; thus while soluble in a 5 or 10 p. c. solution of such a salt, it is far less soluble in a 1 p. c. solution, which as we have seen readily dissolves paraglobulin. From its solutions in neutral saline solution it is precipitated by saturation with a neutral CHAP. IL] THE CONTRACTILE TISSUES. 97 salt, preferably sodium chloride, and may be purified by being washed with a saturated solution, dissolved again in a weaker solution, and reprecipitated by saturation. Dissolved in saline solutions it readily coagulates when heated, i.e. is converted into coagulated proteid, and it is worthy of notice that it coagulates at a comparatively low temperature, viz. about 56° C. ; this it will be remembered is the temperature at which fibrinogen is co- agulated, whereas paraglobulin, serum-albumin, and many other proteids do not coagulate until a higher temperature, 75° C. is reached. Solutions of myosin are precipitated by alcohol, and the precipitate, as in the case of other proteids, becomes by continued action of the alcohol, altered into coagulated insoluble proteid. We have seen that paraglobulin, and indeed any member of the globulin group, is very readily changed by the action of dilute acids into a body called acid- albumin, characterised by not being soluble either in water or in dilute saline solutions but readily soluble in dilute acids and alkalis, from its solutions in either of which it is precipitated by neutralisation, and by the fact that the solutions in dilute acids and alkalis are not coagulated by heat. When therefore a globulin is dissolved in dilute acid, what takes place is not a mere solution but a chemical change; the globulin cannot be got back from the solution, it has been changed into acid-albumin. Similarly when globulin is dissolved in dilute alkalis it is changed into alkali-albumin; and broadly speaking alkali- albumin precipitated by neutralisation can be changed by solution with dilute acids into acid-albumin, and acid-albumin by dilute alkalis into alkali-albumin. Now myosin is similarly, and even more readily than is globulin, converted into acid-albumin, and by treating a muscle either washed or not, directly with dilute hydrochloric acid, the myosin may be converted into acid-albumin and dissolved out. Acid-albumin obtained by dissolving muscle in dilute acid used to be called syntonin, and it used to be said that a muscle contained syntonin ; the muscle however contains myosin, not syntonin, but it may be useful to retain the word syntonin to denote acid-albumin obtained by the action of dilute acid on myosin. By the action of dilute alkalis, myosin may similarly be converted into alkali- albumin. From what has been above stated it is obvious that myosin has many analogies with fibrin, and we have yet to mention some striking analogies; it is however much more soluble than fibrin, and speaking generally it may be said to be intermediate in its character between fibrin and globulin. On keeping, and especially on drying, its solubility is much diminished. Of the substances which are left in washed muscle, from which all the myosin has been extracted by ammonium chloride solution, little is known. If washed muscle be treated directly with dilute hydrochloric acid, a large part of the material of the muscle passes, F. 7 98 MUSCLE PLASMA. [BOOK i. as we have said, at once into syntonin. The quantity of syntonin thus obtained may be taken as roughly representing the quantity of myosin previously existing in the muscle. A more prolonged action of the acid may dissolve out other proteids, besides myosin, left after the washing. The portion insoluble in dilute hydro- chloric acid consists in part of the gelatine yielding and other substances of the sarcolemma and of the connective and other tissues between the bundles, of the nuclei of these tissues and of the fibres themselves, and in part, possibly, of some portions of the muscle substance itself. We are not however at present in a position to make any very definite statement as to the relation of the myosin to the structural features of muscle. Since the dim bands are rendered very indistinct by the action of 10 p.c. sodium chloride solution, we may perhaps infer that myosin enters largely into the composition of the dim bands, and therefore of the fibrillee ; but it would be hazardous to say much more than this. § 60. Living muscle may be frozen, and yet, after certain precautions will, on being thawed, regain its irritability, or at all events will for a time be found to be still living in the sense that it has not yet passed into rigor mortis. We may therefore take living muscle which has been frozen as still living. If living contractile muscle, freed 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 just below 0°C. is sufficiently fluid to be filtered, though with difficulty. The slightly opalescent filtrate, or muscle-plasma 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. 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 an albumin very similar to, if not identical with, serum-albumin, a globulin differing somewhat from, and coagulating at a lower temperature than paraglobulin, and which to distinguish it from the globulin of blood has been called myo- globulin, some other proteids which need not be described here, and various ' extractives ' of which we shall speak directly. Such muscles as are red also contain a small quantity of haemoglobin, and of another allied pigment called histohcematin, to which pigments indeed their redness is due. Thus while dead muscle contains myosin, albumin, and other proteids, extractives, and certain insoluble matters, together with gelatinous and other substances not referable to the muscle CHAP, ii.] THE CONTRACTILE TISSUES. 9& substance itself, living muscle contains no myosin, but some substance or substances which bear somewhat the same relation to myosin that the antecedents of fibrin do to fibrin, and which give rise to myosin upon the death of the muscle. There are indeed reasons for thinking that the myosin arises from the conversion of a previously existing body which may be called myosinogen, and that the conversion takes place, or may take place, by the action of a special ferment, the conversion of myosinogen into myosin being very analogous to the conversion of fibrinogen into fibrin. We may in fact speak of rigor mortis as characterised by a coagulation of the muscle-plasma, comparable to the coagulation of blood-plasma, but differing from it inasmuch as the product is not fibrin but myosin. The rigidity, the loss of suppleness, and the diminished translucency appear to be at all events largely, though probably not wholly, due to the change from the fluid plasma to the solid myosin. We might compare a living muscle to a number of fine transparent membranous tubes containing blood-plasma. When this blood-plasma entered into the 'jelly' stage of coagulation, the system of tubes would present many of the phenomena of rigor mortis. They would lose much of their suppleness and translucency, and acquire a certain amount of rigidity. § 61. There is however one very marked and important difference between the rigor mortis of muscle and the coagulation of blood. Blood during its coagulation undergoes a slight change only in its reaction; but muscle during the onset of rigor mortis becomes distinctly acid. A living muscle at rest is in reaction neutral, or, possibly from some remains of lymph adhering to it, faintly alkaline. If on the other hand the reaction of a thoroughly rigid muscle be tested, it will be found to be most distinctly acid. This development of an acid reaction is witnessed not only in the solid untouched fibre but also in expressed muscle-plasma ; it seems to be associated in some way with the appearance of the myosin. The exact causation of this acid reaction has not at present been clearly worked out. Since the coloration of the litmus pro- duced is permanent, carbonic acid, which as we shall immediately state, is set free at the same time, cannot be regarded as the active acid, for the reddening of litmus produced by carbonic acid speedily disappears on exposure. On the other hand it is possible to ex- tract from rigid muscle a certain quantity of lactic acid, or rather of a variety -of lactic acid known as sarcolactic acid1; and it has been thought that the appearance of the acid reaction of rigid muscle is due to a new formation or to an increased formation of this sarcolactic acid. There is much to be said in favour of this 1 There are many varieties of lactic acid, which are isomeric, having the same composition C3H6O;!, but differ in their reactions and especially in the solubility of their zinc salts. The variety present in muscle is distinguished as sarcolactic acid. 7—2 100 RIGOR MORTIS. [BOOK i. view, but it cannot at present be regarded as established beyond dispute. Coincident with the appearance of this acid reaction, though as we have said, not the direct cause of it, a large development of carbonic acid takes place when muscle becomes rigid. Irritable living muscular substance like all living substance is continually respiring, that is to say, is continually consuming oxygen and giving out carbonic acid. In the body, the arterial blood going to the muscle gives up some of its oxygen, and gains a quantity of carbonic acid, thus becoming venous as it passes through the muscle capillaries. Even after removal from the body, the living muscle continues to take up from the surrounding atmosphere a certain quantity of oxygen and to give out a certain quantity of carbonic acid. At the onset of rigor mortis there is a very large and sudden increase in this production of carbonic acid, in fact an outburst as it were of that gas. This is a phenomenon deserving special attention. Knowing that the carbonic acid which is the outcome of the res- piration of the whole body is the result of the oxidation of carbon- holding substances, we might very naturally suppose that the in- creased production of carbonic acid attendant on the development of rigor mortis is due to the fact that during that event a certain quantity of the carbon-holding constituents of the muscle are suddenly oxidized. But such a view is negatived by the following facts. In the first place, the increased production of carbonic acid during rigor mortis is not accompanied by a corresponding in- crease in the consumption of oxygen. In the second place, a muscle (of a frog for instance) contains in itself no free or loosely attached oxygen ; when subjected to the action of a mercurial air- pump it gives off no oxygen to a vacuum, offering in this respect a marked contrast to blood; and yet, when placed in an atmosphere free from oxygen, it will not only continue to give off carbonic acid while it remains alive, but will also exhibit at the onset of rigor mortis, the same increased production of carbonic acid that is shewn by a muscle placed in an atmosphere containing oxygen. It is obvious that in such a case the carbonic acid does not arise from the direct oxidation of the muscle substance, for there is no oxygen present at the time to carry on that oxidation. We are driven to suppose that during rigor mortis, some complex body, containing in itself ready formed carbonic acid so to speak, is split up, and thus carbonic acid is set free, the process of oxidation by which that carbonic acid was formed out of the carbon-holding constituents of the muscle having taken place at some anterior date. Living resting muscle, then, is alkaline or neutral in reaction, and the substance of its fibres contains a coagulable plasma. Dead rigid muscle on the other hand is acid in reaction, and no longer contains a coagulable plasma, but is laden with the solid myosin. CHAP, ii.] THE CONTRACTILE TISSUES. 101 Further, the change from the living irritable condition to that of rigor mortis is accompanied by a large and sudden development of carbonic acid. It is found moreover that there is a certain amount of parallel- ism between the intensity of the rigor mortis, the degree of acid reaction and the quantity of carbonic acid given out. If we suppose, as we fairly may do, that the intensity of the rigidity is dependent on the quantity of myosin deposited in the fibres, and the acid reaction to the development if not of lactic acid, at least ( of some other substance, the parallelism between the three products, \ myosin, acid-producing substance, and carbonic acid, would suggest / the idea that all three are the results of the splitting-up of the same highly complex substance. No one has at present however succeeded in isolating or in otherwise definitely proving the exist- ence of such a body, and though the idea seems tempting, it may in the end prove totally erroneous. § 62. As to the other proteids of muscle, such as the albumin and the globulin, we know as yet nothing concerning the parts which they play and the changes which they undergo in the living muscle or in rigor mortis. Besides the fat which is found, and that not unfrequently in abundance, in the connective tissue between the fibres, there is also present in the muscular substance within the sarcolemma, always some, and at times a great deal, of fat, chiefly ordinary fat, viz. stearin, palmitin, and olein in variable proportion, but also the more complex fat lecithin. As to the function of these several fats in the life of the muscle we know little or nothing. Carbohydrates, the third of the three great classes in which we may group the energy holding substances of which the animal body and its food are alike composed, viz. proteids, fat and carbo- hydrates, are represented in muscle by a peculiar body, glycogen, which we shall have to study in detail later on. We must here merely say that glycogen is a body closely allied to starch, having a formula, which may be included under the general formula for starches x (C6H]0O5), and may like it be converted by the action of acids, or by the action of particular ferments known as amylolytic ferments, into some form of sugar, dextrose (C6H1206) or some allied sugar. Many, if not all, living muscles contain a certain amount, and some, under certain circumstances, a considerable amount of glycogen. During or after rigor mortis this glycogen is very apt to be converted into dextrose, or an allied sugar. The muscles of the embryo at an early stage contain a relatively enormous quantity of glycogen, a fact which suggests that the glycogen of muscle is carbohydrate food of the muscle about to be wrought up into the living muscular substance. The bodies which we have called extractives are numerous and varied. They are especially interesting since it seems probable that they are waste products of the metabolism of the muscular 102 CHEMICAL CHANGES. [BOOK i. substance, and the study of them may be expected to throw light on the chemical change which muscular substance undergoes during life. Since, as we shall see, muscular substance forms by far the greater part of the nitrogenous, that is proteid portion of the body, the nitrogenous extractives of muscle demand peculiar attention. Now the body urea, which we shall have to study in detail later on, far exceeds in importance all the other nitrogenous extractives of the body as a whole, since it is practically the one form in which nitrogenous waste leaves the body ; if we include with urea, the closely allied uric acid (which for present purposes may simply be regarded as a variety of urea), we may say that all the nitrogen taken in as food sooner or later leaves the body as urea; compared with this all other nitrogenous waste thrown out from the body is insignificant. Of the urea which thus leaves the body, a con- siderable portion must at some time or other have existed, or to speak more exactly its nitrogen must have existed as the nitrogen of the proteids of muscular substance. Nevertheless no urea at all is, in normal conditions, present in muscular substance either living and irritable, or dead and rigid ; urea does not arise in muscular substance itself as one of the immediate waste products of muscular substance. There is however always present, in relatively considerable amount, on an average about '25 p. c. of wet muscle, a remarkable body, kreatin. This is in one sense a compound of urea : it may be split up into urea and sarcosin. This latter body is a methyl glycin, that is to say, a glycin in which methyl has been sub- stituted for hydrogen, and glycin itself is amido-acetic acid, a compound of amidogen, that is a representative of ammonia, and acetic acid. Hence kreatin contains urea, which has close relations with ammonia, together with another representative of ammonia, and a surplus of carbon and hydrogen arranged as a body belonging to the fatty acid series. We shall have to return to this kreatin and to consider its relations to urea and to muscle when we come to deal with urine. The other nitrogenous extractives, such as karnin, hypoxanthin (or sarkin), xanthin, taurin, &c., occur in small quantity, and need not be dwelt on here. Among non-nitrogenous extractives the most important is the sarcolactic acid, of which we have already spoken ; to this may be added sugar in some form or other either coming from glycogen or from some other source. The ash of muscle, like the ash of the blood corpuscles and indeed the ash of the tissues in general as distinguished from the blood or plasma or lymph on which the tissues live, is character- ised by the preponderance of potassium salts and of phosphates ; these form in fact nearly 80 p.c. of the whole ash. § 63. We may now pass on to the question, What are the chemical changes which take place when a living resting muscle CHAP, ii.] THE CONTRACTILE TISSUES. 103 enters into a contraction ? These changes are most evident after the muscle has been subjected to a prolonged tetanus; but there can be no doubt that the chemical events of a tetanus are, like the physical events, simply the sum of the results of the con- stituent single contractions. In the first place, the muscle becomes acid, not so acid as in ; rigor mortis, but still sufficiently so, after a vigorous tetanus, to turn blue litmus distinctly red. The cause of the acid reaction like that of rigor mortis is doubtful, but is in all probability the same in both cases. In the second place, a considerable quantity of carbonic acid is set free ; and the production of carbonic acid in muscular contrac- tion is altogether similar to the production of carbonic acid during rigor mortis : it is not accompanied by any corresponding increase in the consumption of oxygen. This is evident even in a muscle through which the circulation of blood is still going on ; for though the blood passing through a contracting muscle gives up more oxygen than the blood passing through a resting muscle, the increase in the amount of oxygen taken up falls below the increase in the carbonic acid given out. But it is still more markedly shewn in a muscle removed from the body ; for in such a muscle both the contraction and the increase in the production of carbonic acid will go on in the absence of oxygen. A frog's muscle suspended in an atmosphere of nitrogen will remain irritable for some considerable time, and at each vigorous tetanus an increase in the production of carbonic acid may be readily ascertained. Moreover there seems to be a correspondence between theNl energy of the contraction and the amount of carbonic acid and the degree of acid reaction produced, so that, though we are now treading on somewhat uncertain ground, we are naturally led to the view that the essential chemical process lying at the bottom of a muscular contraction as of rigor mortis is the splitting up of some highly complex substance. But here the resemblance between rigor mortis and contraction ends. We have no satisfactory evidence of the formation during a contraction of any body like myosin. And this difference in chemical results tallies with an important difference between rigid muscle and contracting muscle. The rigid muscle as we have seen becomes less extensible, less elastic, less translucent; the contracting muscle remains no less trans- lucent, elastic, and extensible than the resting muscle, indeed there are reasons for thinking that the muscle in contracting Becomes actually more extensible for the time being. But if during a contraction myosin is not formed, what changes of proteid or nitrogenous matter do take place ? We do not know. We have no evidence that kreatin, or any other nitrogenous extractive is increased by the contraction of muscle, we have no evidence of any nitrogen waste at all as the result of a contraction; and indeed, as we shall see later on, the study of the waste 104 THERMAL CHANGES. [BOOK i. products of the body as a whole lead us to believe that the energy of the work done by the muscles of the body comes from the potential energy of carbon compounds, and not of nitrogen com- pounds at all. But to this point we shall have to return. § 64. We may sum up the chemistry of muscle somewhat as follows. During life the muscular substance is continually taking up from the blood, that is from the lymph, proteid, fatty and carbo- hydrate material, saline matters and oxygen ; these it builds up into itself, how we do not know, and so forms the peculiar complex living muscular substance. The exact nature of this living sub- stance is unknown to us. What we do know is that it is largely composed of proteid material, and that such bodies as myosinogen, myoglobulin, and albumin have something to do with the building of it up. During rest this muscular substance, while taking in and build- ing itself up out of or by means of the above mentioned materials is continually giving off carbonic acid and continually forming- nitrogenous waste such as kreatin. It also probably gives off some amount of sarcolactic acid, and possibly other non-nitrogenous waste matters. During a contraction there is a great increase of carbonic acid given off, of either lactic acid, or some other substance giving rise to an acid reaction, a greater consumption of oxygen, though the increase is not equal to the increase of carbonic acid, but, as far as we can learn, no increase of nitrogenous waste. During rigor mortis, there is a similar increased production of carbonic acid and of some other acid producing substance, ac- companied by a remarkable conversion of myosinogen into myosin, by which the rigidity of the dead fibre is brought about. Thermal Changes. § 65. The chemical changes during a contraction set free a quantity of energy, but only a portion of this energy appears in the 'work done,' a considerable portion takes on the form of heat. Though we shall have hereafter to treat this subject more fully, the leading facts may be given here. Whenever a muscle contracts, its temperature rises, indicating that heat is given out. When a mercury thermometer is plunged into a mass of muscles, such as those of the thigh of the dog, a rise of the mercury is observed upon the muscles being thrown into a prolonged contraction. More exact results however are obtained by means of a thermopile, by the help of which the rise of tempera- ture caused by a few repeated single contractions, or indeed by a single contraction, may be observed, and the amount of heat given out approximatively measured. CHAP, ii.] THE CONTRACTILE TISSUES. 105 The thermopile may consist either of a single junction in the form of a needle plunged into the substance of the muscle; or of several junctions either in the shape of a flat surface carefully opposed to the surface of muscle (the pile being balanced so as to move with the contracting muscle, and thus to keep the contact exact), or in the shape of a thin wedge, the edge of which comprising the actual junctions is thrust into a mass of muscles and held in position by them. In all cases the fellow junction or junctions must be kept at a constant temperature. Another delicate method of determining the changes of temperature of a tissue is based upon the measurement of alterations in electric resistance which a fine wire, in contact with or plunged into the tissue, undergoes as the temperature of the tissue changes. It has been calculated that the heat given out by the muscles of the thigh of a frog in a single contraction amounts to 3'1 micro-units of heat1 for each gramme of muscle, the result being obtained by dividing by five the total amount of heat given out in five succes- sive single contractions. It will however be safer to regard these figures as illustrative of the fact that the heat given out is consider- able rather than as data for elaborate calculations. Moreover we have no satisfactory quantitative determinations of the heat given out by the muscles of warm-blooded animals, though there can be no doubt that it is much greater than that given out by the muscles of the frog. There can hardly be any doubt that the heat thus set free is the product of chemical changes within the muscle, changes, which though they cannot for the reasons given above (§ 63) be regarded as simple and direct oxidations, yet, since they are processes dependent on the antecedent entrance of oxygen into the muscle, may be spoken of in general terms as a combustion. So that the muscle may be likened to a steam-engine, in which the combus- tion of a certain amount of material gives rise to the development of energy in two forms, as heat and as movement, there being certain quantitative relations between the amount of energy set free as heat and that giving rise to movement. We must however carefully guard ourselves against pressing this analogy too closely. In the steam-engine, we can distinguish clearly between the fuel which through its combustion is the sole source of energy, and the machinery, which is not consumed to provide energy and only suffers wear and tear. In the muscle we cannot with certainty at present make such a distinction. It may be that the chemical changes at the bottom of a contraction do not involve the real living material of the fibre but only some substance, manufactured by the living material and lodged in some way, we do not know how, in the living material ; it may be that when a fibre contracts it is this substance within the fibre which explodes and not the fibre itself. If we further suppose that this substance is some complex 1 The micro-unit being a milligramme of water raised one degree centigrade. 106 ELECTRICAL CHANGES. [BOOK i. compound of carbon and hydrogen into which no nitrogen enters, we shall have an explanation of the difficulty referred to above (§ 63), namely, that nitrogenous waste is not increased by a contraction. The special contractile, carbon-hydrogen substance may then be compared to the charge of a gun, the products of its explosion being carbonic and sarcolactic acids, while the real living material of the fibre may be compared to the gun itself, but to a gun which itself is continually undergoing change, far beyond mere wear and tear, among the products of which change nitrogenous bodies like kreatin are conspicuous. This view will certainly explain why kreatin is not increased during the contraction while the carbonic and lactic acids are. But it must be remembered that such a view is not yet proved; it may be the living material of the fibre as a whole which is continually breaking down in an explosive decom- position and as continually building itself up again out of the material supplied by the blood. In a steam-engine only a certain amount of the total potential energy of the fuel issues as work, the rest being lost as heat, the proportion varying, but the work rarely, if ever, exceeding one- tenth of the total energy and generally being less. In the case of the muscle we are not at present in a position to draw up an exact equation between the latent energy on the one hand and the two forms of actual energy on the other. We have reason to think that the proportion between heat and work varies considerably under different circumstances, the work sometimes rising as high as one-fifth, sometimes possibly sinking as low as one twenty- fourth of the total energy ; and observations seem to shew that the greater the resistance which the muscle has to overcome, the larger the proportion of the total energy expended which goes out as work done. The muscle in fact seems to be so far self- regulating, that the more work it has to do, the greater, within certain limits, is the economy with which it works. Lastly it must be remembered that the giving out of heat by the muscle is not confined to the occasions, when it is actually con- tracting. When, at a later period, we treat of the heat of the body generally, evidence will be brought forward that the muscles even when at rest are giving rise to heat, so that the heat given out at a contraction is not some wholly new phenomenon, but a temporary exaggeration of what is continually going on at a more feeble rate. Electrical Changes. § 66. Besides chemical and thermal changes a remarkable electric change takes place whenever a muscle contracts. .}fuscle-cur rents. If a muscle be removed in an ordinary CHAP, ii.] THE CONTRACTILE TISSUES. 107 manner from the body, and two non-polarisable electrodes1, con- nected with a delicate galvanometer of many convolutions and FlG. 18. NON-POLAKISABLE ELECTRODES. 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. high resistance, be placed on two points of the surface of the muscle, a deflection of the galvanometer will take place indicating the existence of a current passing through the galvanometer from the one point of the muscle to the other, the direction and amount of the deflection varying according to the position of the points. The 'muscle-currents' thus • revealed are seen to the best advantage when the muscle chosen is a cylindrical or prismatic one with parallel fibres, and when the two tendinous ends are cut off by clean incisions at right angles to the long axis of the muscle. The muscle then presents a transverse section (artificial) at each end and a longitudinal surface. We may speak of the latter as being divided into two equal parts by an imaginary transverse line on its surface called the 'equator,' containing all the points of the surface midway between the two ends. Fig. 19 is a diagrammatic representation of such a muscle, the line ab being the equator. In such a muscle the development of the muscle-currents is found to be as follows. The greatest deflection is observed when one electrode is placed 1 These (Fig. 18) consist essentially of a slip of thoroughly amalgamated zinc dipping into a saturated solution of zinc sulphate, which in turn is brought into connection with the nerve or muscle by means of a plug or bridge of china-clay moistened with normal 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 be- tween 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 platinum is in itself sufficient to develope a current. 108 MUSCLE CURRENTS. [BOOK i. at the mid-point or equator of the muscle, and the other at either cut end ; and the deflection is of such a kind as to shew that posi- tive currents are continually passing from the equator through the galvanometer to the cut end; that is to say, the cut end is negative relatively to the equator. The currents outside the muscle may be considered as completed by currents in the muscle from the cut end to the equator. In the diagram Fig. 19, the arrows indicate the FIG. 19. DIAGRAM ILLUSTRATING THE ELECTRIC CURRENTS OF NERVE 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 lines, as from a, at equator, to x or to y 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 from x to y there is no current, as indicated by the dotted lines. direction of the currents. If the one electrode be placed at the equator ab, the effect is the same at whichever of the two cut ends x or y the other is placed. If, one electrode remaining 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 to each other. 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. If one electrode be placed at the circumference of the transverse section and the other at the centre of the transverse section, there CHAP, ii.] THE CONTRACTILE TISSUES. 109 will be a current through the galvanometer from the former to the latter; there will be a current of similar direction but of less inten- sity when one electrode is at the circumference g of the transverse section and the other at some point h nearer the centre of the trans- verse section. In fact, the points which are relatively most positive and most negative to each other are points on the equator and the two centres of the transverse sections ; and the intensity of the cur- rent between any two points will depend 011 the respective distances of those points from the equator and from the centre of the trans- verse section. Similar currents may be observed when the longitudinal surface is not the natural but an artificial one ; indeed they may be witnessed in even a piece of muscle provided it be of cylindrical shape and composed of parallel fibres. These ' muscle-currents ' are not mere transitory currents dis- >C appearing as soon as the circuit is closed ; on the contrary they last a very considerable time. They must therefore be maintained by some changes going on in the muscle, by continued chemical action in fact. They disappear as the irritability of the muscle vanishes, and are connected with those nutritive, so-called vital changes which maintain the irritability of the muscle. Muscle-currents such as have just been described, may, we repeat, be observed in any cylindrical muscle suitably prepared, and similar currents, with variations which need not be discussed here, may be seen in muscles of irregular shape with obliquely or otherwise ar- ranged fibres. And du Bois-Reymond, to whom chiefly we are indebted for our knowledge of these currents, has been led to re- gard them as essential and important properties of living muscle. He has moreover advanced the theory that muscle may be con- sidered as composed of electro- motive particles or molecules, each of which like the muscle at large has a positive equator and negative ends, the whole muscle being made up of these molecules in somewhat the same way, (to use an illustration which must not however be strained or considered as an exact one) as a magnet may be supposed to be made up of magnetic particles each with its north and south pole. There are reasons however for thinking that these muscle- currents have no such fundamental origin, that they are in fact of surface and indeed of artificial origin. Without entering into the controversy on this question, the following important facts may be mentioned. 1. When a muscle is examined while it still retains uninjured its natural tendinous terminations, the currents are much weaker than when artificial transverse sections have been made ; the natural tendinous end is less negative than the cut surface. But the tendinous end becomes at once negative when it is dipped in water or acid, indeed when it is in any way injured. ""The less roughly in fact a muscle is treated the less evident are the muscle- 110 MUSCLE CURRENTS. [BOOK i. currents; and it is maintained that if adequate care be taken to maintain a muscle in an absolutely natural condition no such cur- rents as those we have been describing exist at all, that natural living muscle is isoelectric as it is called. 2. The surface of the uninjured inactive1 ventricle of the frog's heart, which is practically a mass of muscle, is isoelectric, no current is obtained when the electrodes are placed on any two points of the surface. If however any part of the surface be injured, or if the ventricle be cut across so as to expose a cut surface, the injured spot or the cut surface becomes at once most powerfully negative towards the uninjured surface, a strong current being developed which passes through the galvanometer from the uninjured surface to the cut surface or to the injured spot. The negativity thus developed in a cut surface passes off in the course of some hours, but may be restored by making a fresh cut and exposing a fresh surface. The temporary duration of the negativity after injury, and its renewal upon fresh injury, in the case of the ventricle, in contrast to the more permanent negativity of injured skeletal muscle, is explained by the different structure of the two kinds of muscle. The cardiac muscle as we shall hereafter see is composed of short fibre-cells ; when a cut is made a certain number of these fibre- cells are injured, giving rise to negativity, but the injury done to them stops with them and is not propagated to the cells with which they are in contact ; hence upon their death the negativity and the current disappear. A fresh cut involving new cells, pro- duces fresh negativity and a new current. In the long fibres of the skeletal muscle, on the other hand, the effects of the injury are slowly propagated along the fibre from the spot injured. Now, when a muscle is cut or injured the substance of the fibres dies at the cut or injured surface. And many physiologists, among whom the most prominent is Hermann, have been led by the above and other facts to the conclusion that muscle-currents do not exist naturally in untouched, uninjured muscles, that the muscular substance is naturally, when living, isoelectric, but that whenever a portion of the muscular substance dies, it becomes while dying negative to the living substance, and thus gives rise to currents. They explain the typical currents (as they might be called) mani- fested by a muscle with a natural longitudinal surface and artificial transverse sections, by the fact that the dying cut ends are negative relatively to the rest of the muscle. Du Bois-Reymond and those with him offer special explanations of the above facts and of other objections which have been urged against the theory of naturally existing electro-motive molecules. Into these we cannot enter here. We must rest content with the statement that in an ordinary muscle currents such as have been described may be witnessed, but that strong arguments may be 1 The necessity of its being inactive will be seen subsequently. CHAP, ii.] THE CONTRACTILE TISSUES. Ill adduced in favour of the view that these currents are not 'natural' phenomena but essentially of artificial origin. It will therefore be best to speak of them as currents of rest. § 67. Currents of action. Negative variation of the Muscle- current. The controversy whether the "currents of rest" observable in a muscle be of natural origin or not, does not affect the truth or the importance of the fact that an electrical change takes place and a current is developed in a muscle whenever it enters into a contraction. When currents of rest are observable in a muscle these are found to undergo a diminution upon the occurrence of a contraction, and this diminution is spoken of as 'the negative variation' of the currents of rest. The negative variation may be seen when a muscle is thrown into a single contraction, but is most readily shewn when the muscle is tetanized. Thus if a pair of electrodes be placed on a muscle, one at the equator, and the other at or near the transverse section, so that a considerable deflection of the galvanometer needle, indicating a considerable current of rest, be gained, 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 of any 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. Not only may this negative variation be shewn by the galvano- meter, but it, as well as the current of rest, 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 the muscles and nerves need to be very irritable and in thoroughly good condition. Two muscle-nerve preparations A and B having been made, and each placed on a glass plate for the sake of insula- tion, the nerve of the one B is allowed to fall on the muscle of the other A 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, viz. the 'current of rest' of the muscle A, passes through the nerve ; this acts as a stimulus to the nerve, and so causes a contraction in the muscle connected with a nerve. Thus the muscle A acts as a battery, the completion of the circuit of which by means of the nerve of B serves as a stimulus, causing the muscle 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 A is made up, there is a negative variation of the muscle-current of A. Each negative variation of the muscle- current of A serves as a stimulus to the nerve of B, and is hence 112 MUSCLE CURRENTS. [BOOK i. the cause of a spasm in the muscle of B ; and the stimuli following each other rapidly, as being produced by the tetanus of A they must do, 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 swing 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. But an electrical change may be manifested even in cases when no currents of rest exist. We have stated (§ 66) that the surface of the uninjured inactive ventricle of the frog's heart is isoelectric, no currents being observed when the electrodes of a galvanometer are placed on two points of the surface. Nevertheless a most distinct current is developed whenever the ventricle contracts. This may be shewn either by the galvanometer or by the rheo- scopic frog. If the nerve of an irritable muscle-nerve preparation be laid over a pulsating ventricle, each beat is responded to by a twitch of the muscle of the preparation. In the case of ordinary muscles too instances occur in which it seems impossible to regard the electrical change manifested during the contraction as the mere diminution of a preexisting current. Accordingly those who deny the existence of 'natural' muscle- currents speak of a muscle as developing during a contraction a ' current of action,' occasioned as they believe by the muscular sub- stance as it is entering into the state of contraction becoming negative towards the muscular substance which is still at rest, or has returned to a state of rest."' In fact, they regard the negativity of muscular substance as characteristic alike of beginning death and of a beginning contraction. So that in a muscular contraction a wave of negativity, starting from the end-plate when indirect, or from the point stimulated when direct stimulation is used, passes along the muscular substance to the ends or end of the fibre. If for instance we suppose two electrodes placed on two points (Fig. 20) A and B of a fibre about to be stimulated by a single induc- tion-shock at one end. Before the stimulation the fibre is isoelectric, and the needle of the galvanometer stands at zero. At a certain time after the shock has been sent through the stimulating electrodes (x), as the wave of contraction is travelling down the fibre, the sec- tion of the fibre beneath A will become negative towards the rest of the fibre and so negative towards the portion of the fibre under B, FIG. 20. CHAP, ii.] THE CONTRACTILE TISSUES. 113 i.e. A will be negative relatively to B, and this will be shewn by a deflection of the needle. A little later B will be entering into contraction, and will be becoming negative towards the rest of the fibre including the part under A, whose negativity by this time is passing off, that is to say B will now be negative towards A, and this will be shewn by a deflection of the needle in a direction opposite to that of the deflection which has just previously taken place. Hence between two electrodes placed along a fibre a single wave of contraction will give rise to two currents of different phases, to a diphasic change ; and this indeed is found to be the case. This being so it is obvious that the electrical result of tetauizing a muscle when wave after wave follows along each fibre is a com- plex matter ; but it is maintained that the apparent negative variation of tetanus can be explained as the net result of a series of currents of action due to the individual contractions, the second phase of the current in each contraction being less marked than the first phase. We cannot however enter more fully here into a discussion of this difficult subject. Whichever view be taken of the nature of these muscle-currents, and of the electric change during contraction, whether we regard that change as a 'negative variation' or as a 'current of action/ •'it is important to remember that it takes place entirely during the latent period. It is not in any way the result of the change of form, it is the forerunner of that change of form. Just as a nervous impulse passes down the nerve to the muscle without any visible changes, so a molecular change of some kind, attended by no visible events known to us at present, but only by an electrical change, runs along the muscular fibre from the end-plate to the ends of the fibre, preparing the way for the visible change of form which is to follow. This molecular invisible change is the work of the latent period, and careful observations have shewn that it, like the visible contraction which follows at its heels, travels along the fibre from a spot stimulated towards the ends of the fibres, in the form of a wave having about the same velocity as the contrac- tion, viz. about 3 metres a second1. The Changes in a Nerve during the passage of a Nervous Impulse. § 68. The change in the form of a muscle during its contrac- tion is a thing which can be seen and felt ; but the changes in a nerve during its activity are invisible and impalpable. We stimu- late one end of a nerve going to a muscle, and we see this followed 1 In the muscles of the frog; but as we have seen having probably a higher velocity in the intact mammalian muscles, within the living body, and varying according to circumstances. F. 8 114 STRUCTURE OF A NERVE. [BOOK i. by a contraction of the muscle attached to the other end ; or we stimulate a nerve still connected with the central nervous system, and we see this followed by certain movements, or by other tokens which shew that disturbances have been set up in the central nervous system. We know therefore that some changes or other, constituting what we have called a nervous impulse, have been propagated along the nerve : but the changes are such as we cannot see. It is possible however to learn something about them. Structure of a Nerve. An ordinary nerve going to a muscle is composed of elementary nerve fibres, analogous to the elementary muscle fibres, running lengthwise along the nerve and bound up together by connective tissues carrying blood vessels and lym- phatics. Each fibre is a long rod or cylinder, varying in diameter from less than 2/i to 20/u, or even more, and the several fibres are arranged by the connective tissue into bundles or cords running along the length of the nerve. A large nerve such as the sciatic contains many cords of various sizes; in such a case the connective tissue between the fibres in each cord is more delicate than that which binds the cords together ; each cord has a more or less distinct sheath of connective tissue, and a similar but stouter sheath protects the whole nerve. In smaller nerves the cords are less in number, and a very small nerve may consist, so to speak, of one cord only, that is to say it has one sheath for the whole nerve and fine connective tissue binding together all the fibres within the sheath. When a large nerve divides or sends off branches, one or more cords leave the trunk to form the branch ; when nerves are joined to form a plexus, one or more cords leaving one nerve join another nerve ; it is, as a rule, only when a very small nerve is dividing near its end into delicate twigs that division or branching of the nerve is effected or assisted by division of the nerve fibres themselves. Nearly all the nerve fibres composing an ordinary nerve, such as that going to a muscle, though varying very much in thickness, have the same features, which are as follows. Seen under the microscope in a perfectly fresh condition, without the use of any reagents, each fibre appears as a transparent but somewhat refractive, and therefore bright-looking, rod, with a sharply defined outline, which is characteristically double, that is to say, the sharp line which marks the outside of the fibre is on each side of the fibre accompanied by a second line parallel to itself and following such gentle curves as it shews, but rather nearer the axis of the fibre. This is spoken of as the double contour, and is naturally more conspicuous and more easily seen in the thicker than in the thinner fibres. The substance of the fibre between the two inner contour lines appears, in the perfectly fresh fibre, homogeneous. If the fibre be traced along its course for some little distance there will be seen at intervals an appearance as if the fibre had been CHAP. ii. J THE CONTRACTILE TISSUES. 115 strangled by a ligature tied tightly round it ; its transverse diameter is suddenly narrowed, and the double contour lost, the fibre above and below being united by a narrow short isthmus only. This is called a node, a node of Ranvier, and upon examina- tion it will be found that each fibre is marked regularly along its length by nodes at intervals of about a millimeter. If the fibre be examined with further care there will be seen or may be seen, about midway between every two nodes, an oval nucleus lying embedded as it were in the outline of the fibre, with its long axis parallel or nearly so to the axis of the fibre. If some of the fibres be torn across it may sometimes be seen that at the torn end of a fibre, though the double contour ceases, the outline of the fibre is continued as a delicate transparent membranous tubular sheath ; this is the primitive sheath or neurilemma1. Lying in the axis of this sheath and sometimes projecting for some distance from the torn end of a fibre, whether the sheath be displayed or no, may, in some cases, be seen a dim or very faintly granular band or thread, about one-third or half the diameter of the fibre; this is the axis cylinder ; it becomes lost to view as we trace it back to where the fibre assumes a double contour. This axis cylinder stains readily with ordinary staining reagents, and being in this and in other respects allied in nature to the cell-substance of a leucocyte or to the muscle-substance of a muscular fibre, has often been spoken of as protoplasmic. Lying about the torn ends of the fibres may be seen drops or minute irregular masses, remarkable for exhibiting a double contour like that of the nerve fibre itself; and indeed drops of this double contoured substance may be seen issuing from the torn ends of the fibres. Treated with osmic acid these drops and masses are stained black ; they act as powerful reducing reagents, and the reduced osmium gives the black colour. Treated with ether or other solvents of fat they moreover more or less readily dissolve. Obviously they are largely composed of fat and we shall see that the fat composing them is of a very complex nature. Now a nerve fibre shewing a double contour stains black with osmic acid ; but the staining is absent or very slight where the double contour ceases as at a torn end or at the nodes of Ranvier ; the axis cylinder stains very slightly indeed with osmic acid and the sheath hardly at all. So also when a transverse section is made through a nerve or a nerve cord, each fibre appears in section as a dark black ring surrounding a much more faintly stained central area. Further, when a double contoured nerve fibre is treated with ether, or other solvents of fat, the double contour vanishes, and the 1 This word was formerly used to denote the connective tissue sheath wrapping round the whole nerve. It seemed undesirable however to use two such analogous terms as sarcolemma and neurilemma for two things obviously without analogy, and hence neurilemma is now used for that part of the nerve which is obviously analogous to the sarcolemma in muscle, viz. the sheath of the fibre. 8—2 116 STRUCTURE OF A NERVE FIBRE. [BOOK i. whole fibre becomes more transparent ; and if such a fibre, either before or after the treatment with ether, be stained with carmine or other dye, the axis cylinder will be seen as a stained band or thread lying in the axis of a tubular space defined by the neurilemma which stains only slightly except at and around the nuclei which, as we have seen, are embedded in it at intervals. In the entire fibre the tubular space between the axis cylinder and the sheath is filled with a fatty material, the medulla, which from its fatty nature has such a refractive power as to exhibit a double contour when seen with transmitted light, on which account the fibre itself has a double contour. It is this refractive power of the medulla which gives to a nerve fibre and still more so to a bundle of nerve fibres or to a whole nerve a characteristic opaque white colour when viewed by reflected light. As we shall see, all nerve fibres do not possess a medulla, and hence such a fibre as we are describing is called a medullated Jibre. A typical medullated fibre consists then of the following parts. 1. The axis cylinder, a central cylindrical core of so called 'protoplasmic' material, delicate in nature and readily undergoing change, sometimes swelling out, sometimes shrinking, and hence in various specimens appearing now as a thick band, now as a thin streak in the axis of the tubular sheath, and giving in cross section sometimes a circular, sometimes an oval, and not unfrequently a quite irregular outline. Probably in a perfectly natural condition it occupies about one half the diameter of the nerve, but even its natural size varies in different nerve fibres. When seen quite fresh it has simply a dim cloudy or at most a faintly granular appearance ; under the influence of reagents it is apt to become fibrillated longitudinally, and has been supposed to be in reality composed of a number of delicate longitudinal fibrill^ united by an interfibrillar substance, but this is not certain. It is further said to be protected on its outside by a transparent sheath, the axis cylinder sheath, but this also is disputed. The axis cylinder passes unbroken through successive nodes of Ranvier, the constriction of the node not affecting it otherwise than perhaps to narrow it. Now the fibres of a spinal nerve (omitting for the present the fibres coming from the sympathetic nerves) may be traced back either to the spinal ganglion on the posterior root, or along the anterior root to the anterior cornua of the spinal cord ; and as we shall see the axis cylinders of the fibres are, in both cases, prolongations of processes of nerve cells, in the former case of cells of the ganglion, in the latter case of cells of the anterior cornua. In each case a process of a cell becoming the axis cylinder of a nerve fibre runs an unbroken course, passes as a continuous band of peculiar living matter, through node after node right down to the termination of the fibre in the tissue in which the fibre ends ; the only obvious change which CHAP, ii.] THE CONTRACTILE TISSUES. 117 it undergoes is that, in many if not all cases, it divides near its termination in the tissue, and in some cases the divisions are numerous and join or anastomose freely. Obviously the axis cylinder is the essential part of the nerve fibre. 2. The primitive sheath or neurilemma, a tubular sheath of transparent apparently homogeneous material, not unlike that of a sarcolemma in nature. At each node the neurilemma is con- stricted so as to embrace the axis cylinder closely, but is at the same time thickened by some kind of cement material. Staining reagents, especially silver nitrate, appear to enter the nerve fibre from without more readily at a node than elsewhere, staining the fibre most at the node, and creeping upwards and downwards from the node along the axis cylinder ; hence it has been supposed that the nutritive fluid, the lymph, enters into the fibre and so gets access to the axis cylinder more readily at the nodes than else- where. About midway between every two nodes is placed a long oval nucleus, on the inside of the neurilemma, pushing the medulla, as it were, inwards, and so lying in a shallow bay of that substance. Immediately surrounding the nucleus is a thin layer of granular substance of the kind which we have spoken of as undifferentiated protoplasm ; in young newly formed fibres at all events and possibly in all fibres a very thin layer of this same substance is continued all over the segment between the nodes, on the inner surface of the neurilemma between it and the medulla. 3. The medulla. This is a hollow cylinder of fatty material of a peculiar nature filling all the space between the neurilemma on the outside and the axis cylinder within, and suddenly ceasing at each node. It thus forms a close fitting hollow jacket for the axis cylinder between every two nodes. The fatty material is fluid, at least at the temperature of the body, but appears to be held in its place as it were by a network of a substance called neurokeratin, allied to the substance keratin, which is the basis of the horny scales of the epidermis and of other horny structures ; this network is most marked towards the outside of the medulla. So long as the nerve is in a fresh living, perfectly normal condition, the medulla appears smooth and continuous, shewing 110 marks beyond the double contour; but in nerves removed from the body for examination (and according to some observers, at times in nerves still within the body) clefts make their appearance in the medulla running obliquely inwards from the neurilemma to the axis cylinder, and frequently splitting up the metlulla in such a way that it appears to be composed of a number of hollow cones partially slid one over the other along the axis cylinder. These clefts are spoken of as indentations. At a later stage of alteration the medulla may divide into a number of small irregular masses separated by fluid; and since each small piece thus separated has a double contour, like a drop of medulla exuded from the end of a fibre, the whole fibre has an irregular ' curdy ' appearance. 118 STRUCTURE OF A NERVE FIBRE. [BOOK i. The essential part then of a medullated nerve fibre (of a spinal nerve) is the axis cylinder, which is really a prolongation of a process from a nerve cell in a spinal ganglion or in the spinal cord, running an unbroken course through node after node, never in its course, as far as we know, joining another axis cylinder and very rarely dividing until it approaches its end, where it may divide freely, the divisions in some cases anastomosing freely. We may conclude, and all we know supports the conclusion, that the changes, making up what we have called a nervous impulse, take place, primarily and chiefly at all events, in this essential part of the nerve fibre, the axis cylinder. The neurilemma and medulla together form a wrapping for the nourishment and protec- tion of the axis cylinder, the fatty medulla probably serving partly as prepared food for the axis cylinder, partly as a mechanical support ; possibly it may also play a part as an insulator in the electric phenomena. It is easy moreover to see that while the axis cylinder along its whole length is practically (whatever be the exact manner of its formation in the embryo) a part of the cell of which it is an elongated process, each segment between every two nodes repre- sents a cell wrapping round the axis cylinder process, of which cell the nucleus between the nodes is the nucleus, the neurilemma the envelope or cell wall, and (though this is perhaps not quite so clear) the medulla the cell substance largely converted into fatty material, a cell in fact which is really outside the axis cylinder or nerve fibre proper. It is along the axis cylinder that the nervous impulses sweep, and each wrapping cell only serves to nourish and protect the segment of the axis cylinder between its two nodes. And we accordingly find that both at the beginning of the nerve fibre in the ganglion cell or spinal cord and at its end in the tissue, both neurilemma and medulla disappear, the axis cylinder only being left. A nerve going to a muscle is chiefly composed of medullated fibres as just described, the majority of which, ending in end- plates in the muscular fibres, are the fibres which conduct the nervous impulses to the muscle, causing it to contract, and may hence be spoken of as motor nerve fibres. Some of the fibres however end in other parts, such as the tendon, or the connective tissue between the bundles, and some in the blood vessels. There are reasons for thinking that some of these convey impulses from the muscle to the central nervous system and are consequently spoken of as sensory or afferent fibres ; concerning those connected with the blood vessels we shall speak in dealing with the vascular system. § 69. Nerve-endings in striated muscular fibres. A nerve on entering a muscle divides into a number of branches which, running in the connective tissue of the muscle, form a plexus round the bundles of muscle fibres, the smaller branches forming a plexus CHAP. IL] THE CONTRACTILE TISSUES. 119 round the muscle fibres themselves. From this plexus are given off a number of nerve fibres, running singly, each of which joining a muscle fibre ends in an end-plate. In forming these plexuses the individual nerve fibres divide repeatedly, the division always taking place at a node of Ranvier, so that what is a single nerve fibre as the nerve enters the muscle may give rise to several nerve fibres ending in several muscle fibres. The nerve fibre joins the muscle fibre at about its middle or somewhat nearer one end, and occasionally two nerve fibres may join one muscle fibre and form two end-plates. The general distribution of the bundles of nerve fibres and single nerve fibres is such that some portion of the muscle is left free from nerve fibres ; thus at the lower and at the upper end of the sartorius of the frog there is a portion of muscle quite free from nerve fibres. A single nerve fibre, running by itself, has, outside the neuri- lemma an additional delicate sheath of fine connective tissue known as Henles sheath, which appears to be a continuation of the connective tissue forming the sheath of the nerve branch from which the fibre sprang, or uniting the fibres together in the branch. The actual ending of the nerve fibre in the muscle fibre differs in different classes of animals. In mammals and some other animals the single nerve fibre joins the muscle fibre in a swelling or projection having a more or less oval base, and appearing when seen sideways as a low conical or rounded eminence. At the summit of this eminence the nerve fibre loses both its sheath of Henle and its neurilemma, one or other or both (for on this point observers do not agree) becoming continuous with the sarcolemma of the muscle fibre. At the summit of the eminence, where the sheaths fuse, the fibre, now consisting only of axis cylinder and medulla, loses its medulla abruptly, (in the muscles of the tongue the nerve fibre in many cases loses its medulla at some considerable distance before it joins the muscle fibre to form the end-plate) while the axis cylinder branches out in all directions, ^he somewhat varicose branches, which sometimes anastomose, forming a low conical mass, which when viewed from above has an arborescent or labyrinthine appearance. On the branches of this arboresceiice may lie one or more somewhat granular oval nuclei. The arborescence itself has, like the axis cylinder of which it is a development, a very faintly granular or cloudy appearance, but lying between it and the actual muscle substance is a disc or bed of somewhat coarsely granular material, called the sole of the end-plate, on which the ramified arborescent axis cylinder rests, more or less overlapping it at the edge, but with which it appears not to be actually continuous. Lying in the midst of this ' sole ' are a number of clear oval transparent nuclei. The end-plate then beneath the sarcolemma consists of two 120 END-PLATES. [BOOK i. parts, the ramified axis cylinder, and the granular nucleated sole, the two apparently, though in juxtaposition, not being continuous. According to some observers the sole is continuous with and indeed is a specialized part of that substance pervading the whole muscu- lar fibre which we spoke of as interh'brillar substance. We cannot enter here into a discussion of the probable meaning and use of these structures or how they effect what seems obviously their function, the transformation of the changes constituting a nervous impulse into the changes, .which running along the muscle fibre in the latent period as forerunners of the changes entailing actual contraction, may be spoken of as con- stituting a muscle impulse. It is of interest to observe that certain analogies may be drawn between an end plate and the histological elements of the so-called electrical organs of certain animals. The element of the electric organ of the torpedo, for instance, may be regarded as a muscle fibre in which the nerve ending has become highly developed, while the muscle substance has been arrested in its development and has not become striated. In amphibia (e.g. in frogs) the ending of a nerve fibre in a muscle fibre is somewhat different. A nerve fibre about to end in a muscle fibre divides into a brush of several nerve fibres, each of which, losing its sheath of Henle and sarcolemma, enters the same muscle fibre, and then losing its medulla runs longitudinally along the fibre for some distance, it and its branches dividing several times in a characteristically forked manner, and bearing at intervals oval nuclei. In other animals forms of nerve ending are met with more or less intermediate between that seen in the mammal and that seen in the frog. § 70. Besides the medullated nerve fibres described in § 68, there are in most nerves going to muscles a few and in some nerves, going to other parts, a large number of nerve fibres which do not possess a medulla, and hence are called non-medullated fibres ; these are especially abundant in the so-called sympathetic nerves. A non-medullated fibre which, like a medullated fibre, may have any diameter from 2/j, or less to 20/i or more, is practically a naked axis cylinder, not covered with medulla, but bearing on its outside at intervals oval nuclei disposed longitudinally. These nuclei appear wholly analogous to the nuclei of the neurilemma of a medullated fibre, and probably belong to a sheath enclosing each fibre, though it is not easy to demonstrate the independent exist- ence of such a sheath in the case of most non-medullated fibres. In the similar fibres constituting the olfactory nerve a sheath is quite conspicuous. Unlike the medullated fibres these non-medul- lated divide and also join freely ; like them each may be regarded as a process of a nerve cell. Of such non-medullated fibres a scanty number are found in nerves going to muscles scattered among the medullated fibres CHAP. ii.J THE CONTRACTILE TISSUES. 121 and bound up with them by connective tissue. They appear to have no connection with the muscular fibres, but to be distributed chiefly to the blood vessels ; and the function of non-medullated fibres had better be considered in connection with nerves of which they form a large part, such as certain nerves going to blood vessels and to secreting organs. But it may be stated that though they possess no medulla they are capable of propagating nervous impulses in the same way as medu Hated nerves ; and this fact may be taken as indicating that the medulla cannot serve any very important function as an electric insulator. § 71. The chemistry of a nerve. We have spoken of the medulla as fatty, and yet it is in reality very largely composed of a substance which is not (in the strict sense of the word) a fat. When we examine chemically a quantity of nerve (or what is practically the same thing a quantity of that part of the central nervous system which is called white matter, and which as we shall see is chiefly composed, like a nerve, of medullated nerves, and is to be preferred for chemical examination because it contains a relatively small quantity of connective tissue), we find that a very large proportion, according to some observers about half, of the dried matter consists of the peculiar body cholesterin. Now cholesterin is not a fat but an alcohol ; like glycerin however, which is also an alcohol, it forms compounds with fatty acids ; and though we do not know definitely the chemical condition in which cholesterin exists during life in the medulla, it is more than probable that it exists in some combination with some of the really fatty bodies also present in the medulla, and not in a free isolated state. It is singular that besides being present in such large quantities in nervous tissue, and to a small extent in other tissues and in blood, cholesterin is a normal constituent of bile, and forms the greater part of gall stones when these are present ; in gall stones it is undoubtedly present in a free state Besides cholesterin ' white ' nervous matter contains a less but still considerable quantity of a complex fat, whose nature is disputed. According to some authorities rather less than half this complex fat consists of the peculiar body lecithin, which we have already seen to be present also in blood corpuscles and in muscle. Lecithin contains the radicle of stearic acid (or of oleic, or of palmitic acid) associated not, as in ordinary fats, with simple glycerin, but with the more complex glycerin-phosphoric acid, and further combined with a nitrogenous body, neurin. an am- monia compound of some considerable complexity ; it is therefore of remarkable nature since, though a fat, it contains both nitrogen and phosphorus. According to the same authorities the remainder of the complex fat consists of another fatty body, also apparently containing nitrogen but no phosphorus, called cerebrin. Other authorities regard both these bodies, lecithin and cerebrin, as products of decomposition of a still more complex fat, called 122 THE CHEMISTRY OF NERVES. [BOOK i. protagon. Obviously the fat of the white matter of the central nervous system and of spinal nerves (of which fat by far the greater part must exist in the medulla, and form nearly the whole of the medulla) is a very complex body indeed, especially so if the cholesterin exists in combination with the lecithin, or cerebrin (or protagon). Being so complex it is naturally very unstable, and in- deed, in its instability resembles proteid matter. Hence probably the reason why the medulla changes so rapidly and so profoundly after the death of the nerve. It seems moreover that a certain though small quantity of proteid matter forms part of the medulla, and it is possible that this exists in some kind of combination with the complex fat ; but our knowledge on this point is imperfect. The presence in such large quantity of this complex fatty medulla renders the chemical examination of the other consti- tuents of a nerve very difficult, and our knowledge of the chemical nature of, and of the chemical changes going on in the axis cylinder, is very limited. Examined under the microscope the axis cylinder gives the xanthoproteic reaction and other indications that it is proteid in nature ; beyond this we are largely confined to inferences. We infer that its chemical nature is in a general way similar to that of the cell substance of the nerve cell of which it is a process. We infer that the chemical nature of the cell substance of a nerve cell, being of the kind which is frequently called ' protoplasmic,' is, in a general way, similar to that of other ' protoplasmic ' cells, for instance of a leucocyte. Now where we can examine con- veniently such cells we find, as we have said § 30, the proteids present in them to be some form of albumin, some form of globulin, and either myosin itself, or antecedents of myosin, or some allied body. In other words, the proteid basis of the kind of cell sub- stance which is frequently spoken of as " undifferentiated proto- plasm," does not, in its broad features, differ materially from the proteid basis of that " differentiated protoplasm," which we have called muscle substance. Hence we infer that in their broad chemical features the axis cylinder of a nerve fibre and the cell body of a nerve cell resemble the substance of a muscle fibre ; and this view is supported by the fact that both kreatin and lactic acid are present as ' extractives,' certainly in the central nervous system, and probably in nerves. The resemblance is of course only a general one ; there must be differences in chemical nature between the axis cylinder which propagates a nervous impulse without change of outward form and the muscle fibre which contracts ; but we cannot at present state exactly what these differences really are. After the fats of the medulla (and the much smaller quantity of fat present in the axis cylinder), the proteids of the axis cylinder, and the other soluble substances present in one or the other, or gathered round the nuclei of the neurilemma, have by various means been dissolved out of a nerve fibre, certain substances still CHAP, ii.] THE CONTRACTILE TISSUES. 123 remain. One of these in small quantity is the nuclein of the nuclei ; another in larger quantity is the substance neurokeratin which forms as we have seen a supporting framework for the medulla, and whose most marked characteristic is perhaps its resistance to solution. In the ash of nerves there is a preponderance of potassium salts and phosphates but not so marked as in the case of muscle. § 72. The nervous impulse. The chemical analogy between the substance of the muscle and that of the axis cylinder would naturally lead us to suppose that the progress of a nervous impulse along a nerve fibre was accompanied by chemical changes similar to those taking place in a muscle fibre. Whatever changes how- ever do or may take place are too slight to be recognized by the means at our disposal. We have no satisfactory evidence that in a nerve even repeated nervous impulses can give rise to an acid reaction or that the death of a nerve fibre leads to such a reaction. The grey matter of the central nervous system it is true is said to be slightly acid during life and to become more acid after death ; but in this grey matter nerve cells are relatively abundant ; the white matter, composed chiefly of nerve fibres, is and remains, during action as well as rest, and even after death, neutral or slightly alkaline. Nor have we satisfactory evidence that the progress of a nervous impulse is accompanied by any setting free of energy in the form of heat. In fact, beyond the terminal results, such as a muscular con- traction in the case of a nerve going to a muscle, or some affection of the central nervous system in the case of a nerve still in connec- tion with its nervous centre, there is one event and one event only which we are able to recognize as the objective token of a nervous impulse, and that is an electric change. For a piece of nerve removed from the body exhibits nearly the same electric pheno- mena as a piece of muscle. It has an equator which is electrically positive relatively to the two cut ends. In fact the diagram Fig. 19, and the description which was given in § 66 of the electric changes in muscle may be applied almost as well to a nerve, except that the currents are in all cases much more feeble in the case of nerves than of muscles, and the special currents from the circumference to the centre of the transverse sections cannot well be shewn in a slender nerve ; indeed it is doubtful if they exist at all. During the passage of a nervous impulse the 'natural nerve- current ' undergoes a negative variation, just as the ' natural muscle current ' undergoes a negative variation during a con- traction. There are moreover reasons in the case of the nerve, as in the case of the muscle, which lead us to doubt the pre-existence of any such ' natural ' currents. A nerve in an absolutely natural condition appears to be, like a muscle, isoelectric ; hence we may 124 ELECTRIC CURRENTS IN NERVES. [BOOK i. say that in a nerve during the passage of a nervous impulse, as in a muscle during a muscular contraction, a ' current of action ' is developed. This ' current of action ' or ' negative variation ' may be shewn either by the galvanometer or by the rheoscopic frog. If the nerve of the 'muscle nerve preparation' B (see § 67) be placed in an appropriate manner on a thoroughly irritable nerve A (to which of course no muscle need be attached), touching for instance the equator and one end of the nerve, then single induction-shocks sent into the far end of A will cause single spasms in the muscle of B, while tetanization of A, i. e. rapidly repeated shocks sent into A, will cause tetanus of the muscle of B. That this current, whether it be regarded as an independent ' current of action ' or as a negative variation of a ' pre-existing ' current, is an essential feature of a nervous impulse is shewn by the fact that the degree or intensity of the one varies with that of the other. They both travel too at the same rate. In describing the muscle-curve, and the method of measuring the muscular latent period, we have incidentally shewn (§ 46) how at the same time the velocity of the nervous impulse may be measured, and stated that the rate in the nerves of a frog is about 28 metres a second. By means of a special and somewhat complicated apparatus it is ascertained that the current of action travels along an isolated piece of nerve at the same rate. It also, like the molecular change in a muscle preceding the contraction, and indeed like the contraction itself, travels in the form of a wave, rising rapidly to a maximum at each point of the nerve and then more gradually declining again. The length of the wave may by special means be measured, and is found to be about 18 mm. When an isolated piece of nerve is stimulated in the middle, the current of action is propagated equally well in both directions, and that whether the nerve be a chiefly sensory or a chiefly motor nerve, or indeed if it be a nerve-root composed exclusively of motor or of sensory fibres. Taking the current of action as the token of a nervous impulse, we infer from this that when a nerve fibre is stimulated artificially at any part of its course, the nervous impulse set going travels in both directions. We used just now the phrase 'tetanization of a nerve,' meaning the application to a nerve of rapidly repeated shocks such as would produce tetanus in the muscle to which the nerve was attached, and we shall have frequent occasion to employ the phrase. It must however be understood that there is in the nerve, in an ordinary way, no summation of nervous impulses comparable to the summation of muscular contractions. Putting aside certain cases which we cannot discuss here we may say that the series of shocks sent in at the far end of the nerve start a series of impulses ; these travel down the nerve and reach the muscle as a series of distinct impulses ; and the first changes in the muscle, the molecular CHAP, ii.] THE CONTRACTILE TISSUES. 125 latent-period changes, also form a series the members of which are distinct. It is not until these molecular changes become trans- formed into visible changes of form that any fusion or summation takes place. § 73. Putting together the facts contained in this and the pre- ceding sections, 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 that the induced current passes into the nerve, changes occur, of whose nature we know nothing certain except that they cause a ' current of action ' or ' negative variation ' of the ' natural ' nerve-current. These changes propagate themselves along the nerve in both directions 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 what we may call a muscle impulse, with a shorter steeper wave, and a greatly diminished velocity (about 3 m. per sec.). This muscle impulse, of which we know hardly more than that it is marked by a current of action, travels from each end- plate in both directions to the end of the fibre, where it appears to be lost, at all events we do not know what becomes of it. As this impulse wave, whose development takes place entirely within the latent period, leaves the end-plate it is followed by an explosive decomposition of material, leading to a discharge of carbonic acid, to the appearance of some substance or substances with an acid reaction, and probably of other unknown things, with a consider- able development of heat. This explosive decomposition gives rise to the visible contraction wave, which travels behind the invisible muscle impulse at about the same rate, but with a vastly increased wave-length. The fibre, as the wave passes over it, swells and shortens and thus brings its two ends nearer together. When repeated shocks are given, wave follows wave of nervous impulse, muscle impulse, and visible contraction ; but the last do not keep distinct, they are fused into the continued shortening which we call tetanus. SEC. 3. THE NATURE OF THE CHANGES THROUGH WHICH AN ELECTRIC CURRENT IS ABLE TO GENE- RATE A NERVOUS IMPULSE. Action of the Constant Current. § 74. In the preceding account, the stimulus applied in order to give rise to a nervous impulse has always been supposed to be an induction-shock, single or repeated. This choice of stimulus has been made on account of the almost momentary duration of the induced current. Had we used a current lasting for some consider- able time the problems before us would have become more com- plex, in consequence of our having to distinguish between the events taking place while the current was passing through the nerve from those which occurred at the moment when the current was thrown into the nerve or at the moment when it was shut off from the nerve. These complications do arise when instead of employing the induced current as a stimulus, we use a constant current, i.e. when we pass through the nerve (or muscle) a current direct from the battery without the intervention of any induction- coil. Before making the actual experiment, we might perhaps naturally suppose that the constant current would act as a stimu- lus throughout the whole time during which it was applied, that, so long as the current passed along the nerve, nervous impulses would be generated, and that these would throw the muscle into some- thing at all events like tetanus. And under certain conditions this does take place ; occasionally it does happen that at the moment the current is thrown into the nerve the muscle of the muscle- nerve preparation falls into a tetanus which is continued until the current is shut off; but such a result is exceptional. In the vast majority of cases what happens is as follows. At the moment that the circuit is made, the moment that the current is thrown into the nerve, a single twitch, a simple contraction, the so-called making contraction, is witnessed ; but after this has passed away CHAP. IL] THE CONTRACTILE TISSUES. 127 the muscle remains absolutely quiescent in spite of the current continuing to pass through the nerve, and this quiescence is maintained until the circuit is broken, until the current is shut off from the nerve, when another simple contraction, the so- called breaking contraction., is observed. The mere passage of a constant current of uniform intensity through a nerve does not under ordinary circumstances act as a stimulus generating a nervous impulse ; such an impulse is only set up when the current either falls into or is shut off from the nerve. It is the entrance or the exit of the current, and not the continuance of the current, which is the stimulus. The quiescence of the nerve and muscle during the passage of the current is however dependent on the current remaining uniform in intensity or at least not being suddenly increased or diminished. Any sufficiently sudden and large increase or diminution of the intensity of the current will act like the entrance or exit of a current, and by generating a nervous impulse give rise to a contraction. If the intensity of the current however be very slowly and gradually increased or di- minished, a very wide range of intensity may be passed through without any contraction being seen. , It is the sudden change from one condition to another, and not the condition itself, which causes the nervous impulse. In many cases, both a ' making ' and a ' breaking ' contraction, each a simple twitch, are observed, and this is perhaps the commonest event ; but when the current is very weak, and again when the current is very strong, either the breaking or the making contraction may be absent, i. e. there may be a contraction only when the current is thrown into the nerve or only when it is shut off from the nerve. Under ordinary circumstances the contractions witnessed with the constant current either at the make or at the break, are of the nature of a ' simple ' contraction, but, as has already been said, the application of the current may give rise to a very pronounced tetanus. Such a tetanus is seen sometimes when the current is made, lasting during the application of the current, sometimes when the current is broken, lasting some time after the current has been wholly removed from the nerve. " The former is spoken of as a ' making,' the latter as a ' breaking ' tetanus. But these excep- tional results of the application of the constant current need not detain us now. The great interest attached to the action of the constant current lies in the fact, that during the passage of the current, in spite of the absence of all nervous impulses and therefore of all muscular contractions, the nerve is for the time both between and on each side of the electrodes profoundly modified in a most peculiar manner. This modification, important both for the light it throws on the generation of nervous impulses and for its practical applications, is known under the name of electroton as. 128 ELECTROTONUS. [BOOK i. § 75. Electrotonus. The marked feature 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-polarizable) electrodes (Fig. 21, 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-coil. 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. A. TT -* x B. FIG. 21. MUSCLE-NERVE PREPARATIONS, with the nerve exposed in A to a descending and in B to an ascending constant current. In each a is the anode, k the kathode of the constant current, x represents the spot where the induction-shocks used to test the irritability of the nerve are sent in. That contraction may be taken as a measure of the irritability of the nerve at the point x. Now let the polarizing current be thrown in, and let the kathode or negative pole be nearest the muscle, as in Fig. 21 A, so that the current passes along the nerve in a direction from the central nervous system towards the muscle; such a current is spoken of as a descending one. The entrance of the polarizing current into the nerve will produce CHAP, ii.] THE CONTRACTILE TISSUES. 129 a ' making ' contraction ; this we may neglect. 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 polarizing current be now shut off, a ' breaking ' contraction will probably be produced ; this also we may neglect. If now the point x after a short interval be again tested with the same induction-shock as before, the contraction will be no longer greater, but of the same amount, or perhaps not so great, as at first. During the passage of the polarizing current, therefore, the irritability of the nerve at the point x has been temporarily increased, since the same shock applied to it causes a greater contraction during the presence than in the absence of the current. But this is only true so long as the polarizing 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. 21 B, the irritability of the nerve at x would have been found to be diminished instead of increased by the polarizing current ; the contraction obtained during the passage of the constant current would be less than before the passage of the current or might be absent altogether, and the contraction after the current had been shut off would be as great or perhaps greater than before. That is to say, when a constant current is applied to a nerve, the irritability of the nerve between the polar- izing electrodes and the muscle is, during the passage of the current, 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). The same result, mutatis mutandis, and with some qualifications which we need not discuss, 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 ) 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 katelectrotonus, and the nerve is said to be in a katelectrotonic condition. 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 determining the irritability. The result holds good not only with a single induction-shock, but also with a tetanizing inter- rupted current, with chemical and with mechanical stimuli. It further appears to hold good not only in a dissected nerve-muscle preparation but also in the intact nerves of the living body. The F. 130 ELECTROTONUS. [BOOK i. increase and decrease of irritability are most marked in the immediate neighbourhood of the electrodes, but spread for a considerable distance in each direction 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 a neutral or 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. 22). 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. In the experiments just described the increase or decrease of irritability is taken to mean that the same stimulus starts in the one case a larger or more powerful and in the other case a smaller or less energetic impulse; but we have reason to think that the mere propagation or conduction of impulses started elsewhere is also affected by the electrotonic condition. At all events anelectrotonus appears to offer an obstacle to the passage of a nervous impulse. FIG. 22. DIAGRAM ILLUSTRATING THE VARIATIONS OF IRRITABILITY DURING ELECTRO- TONUS, WITH POLARIZING CURRENTS OF INCREASING INTENSITY (from Pfliiger). The anode is supposed to be placed at A, the 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 irritability. yl represents the effect of a weak current; the indifferent point xl is near the anode A. In ?/._,, a stronger current, the indifferent point .r2 is nearer the kathode B, the diminution of irritability in anelectrotonus and the increase in katelectro- tonus being greater than in yl ; the effect also spreads for a greater distance along the extrapolar regions in both directions. In y3 the same events are seen to be still more marked. § 76. Electrotonic Currents. During the passage of a constant current through a nerve, variations in the electric currents belonging to the nerve itself may be observed ; and these variations have certain relations to the variations of the irritability of the nerve. Thus if a constant current supplied by the battery P (Fig. 23) be applied CHAP. IL] THE CONTRACTILE TISSUES. 131 to a piece of nerve by means of two non-polarizable electrodes p, p', the "currents of rest" obtainable from various points of the nerve will be different during the passage of the polarizing current from those which were manifest before or after the current was applied; and, moreover, the changes in the nerve-currents produced by the polarizing current will not be the same in the neighbourhood of the anode (p) as those in the neighbourhood of the kathode (p'). Thus let G and H be two galvanometers so connected with the two ends of the nerve as to afford good and clear evidence of the " currents of rest." Before the polarizing current is thrown into the nerve, the needle of H 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 h FIG. 23. DIAGRAM ILLUSTRATING ELECTROTONIC CURRENTS. P the polarizing battery, with k a key, p the anode, and p' the kathode. At the left end of the piece of nerve the natural current flows through the galvanometer G from g to {/', in the direction of the arrows ; its direction therefore is the same as that of the polarizing current; consequently it appears increased, as indicated by the sign + . The current at the other end of the piece of nerve, from /< to /;', through the galvanometer H, flows in a contrary direction to the polarizing current ; it consequently appears to be diminished, as indicated by the sign — . N.B. For simplicity's sake, the polarizing current is here supposed to be thrown in at the middle of a piece of nerve, and the galvanometer placed at the two ends. Of course it will be understood that the former may be thrown in anywhere, and the latter connected with any two pairs of points which will give currents. 9—2 132 ELECTROTONUS. [BOOK i. will flow in the direction of the arrow. Similarly the needle of G will by its deflection indicate the existence of a cuiTent 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 pft'i the currents Sbtgg', hh' will undergo a "negative variation," that is, the nerve at each point will exhibit a "current of action" correspond- ing to the nervous impulse, which, at the making of the polarizing current, passes in both directions along the nerve, and may cause a contraction in the attached muscle. The current of action is, as we have seen, of extremely short duration, it is over and gone in a small fraction of a second. It therefore must not be confounded with a permanent effect which, in the case we are dealing with, is observed in both galvanometers. This effect, which is dependent on the direction of the polarizing current, is as follows : Supposing that the polarizing current is flowing in the direction of the arrow in the figure, that is, passes in the nerve from the positive electrode or anode p to the negative electrode or kathode p', it is found that the current through the galvanometer G is increased, while that through H is diminished. The polarizing current has caused the appearance in the nerve outside the electrodes of a current, having the same direction as itself, called the ' electrotonic ' current ; and this electrotonic current adds to, or takes away from, the natural nerve-current or "current of rest" according as it is flowing in the same direction as that or in. an opposite direction. The strength of the electrotonic current is dependent on the strength of the polarizing current, and on the length of the intrapolar region which is exposed to the polarizing current. When a strong polarizing current is used, the electromotive force of the electrotonic current may be much greater than that of the natural nerve-current. The strength of the electrotonic current varies with the irritability, or vital condition of the nerve, being greater with the more irritable nerve ; and a dead nerve will not manifest electrotonic currents. More- over, the propagation of the current is stopped by a ligature, or by crushing the nerve. We may speak of the conditions which give rise to this electrotonic current as a physical electrotonus analogous to that physiological electro- tonus which is made known by variations in irritability. The physical electrotonic current is probably due to the escape of the polarizing current along the nerve under the peculiar conditions of the living nerve; but we must not attempt to enter here into this difficult subject or into the allied question as to the exact connection between the physical and the physiological electrotonus, though there can be little •doubt that the latter is dependent on the former. § 77. These variations of irritability at the kathode and anode respectively thus brought about by the action of the constant current are interesting theoretically, because we may trace a con- nection between them and the nervous impulse which is the result of the making or breaking of a constant current. For we have evidence that a nervous impulse is generated when a portion of the nerve passes suddenly from a normal CHAP, ii.] THE CONTRACTILE TISSUES. 133 condition to a state of katelectrotonus or from a state of anelec- trotonus back to a normal condition, but that the passage from a normal condition to anelectrotonus or from katelectrotonus back to a normal condition is unable to generate an impulse. Hence when a constant current is 'made' the impulse is generated only at the kathode where the nerve passes suddenly into katelectrotonus ; when the current on the other hand is ' broken ' the impulse is generated only at the anode where the nerve passes suddenly back from anelectrotonus into a normal condition. We have an indirect proof of this in the facts to which we drew attention a little while back, viz. that a contraction sometimes occurs at the ' breaking ' only, sometimes at the ' making ' only of the constant current, sometimes at both. For it is found that this depends partly on the strength of the current in relation to the irritability of the nerve, partly on the direction of the current, whether ascending or descending ; and the results obtained with strong, medium and weak descending and ascending currents have been stated in the form of a ' law of contraction.' We need not enter into the details of this ' law ' but will merely say that the results which it formulates are best explained by the hypothesis just stated. We may add that when the constant current is applied to certain structures composed of plain muscular fibres, whose rate of contraction we have seen to be slow, the making contraction may be actually seen to begin at the kathode and travel towards the anode, and the breaking contraction to begin at the anode and travel thence towards the kathode. . Since in katelectrotonus the irritability is increased, and in anelectrotonus decreased, both the entrance from the normal condition into katelectrotonus and the return from anelectrotonus to the normal condition are instances of a passage from a lower stage of irritability to a higher stage of irritability. Hence the phenomena of electrotonus would lead us to the conception that a stimulus in provoking a nervous impulse produces its effect by, in some way or other, suddenly raising the irritability to a higher pitch. But what we are exactly to understand by raising the irritability, what molecular change is the cause of the rise, and how either electric or other stimuli can produce this change are matters which we cannot discuss here. Besides their theoretical importance the phenomena of electro- ' tonus have also a practical interest. When an ascending current is passed along a nerve going to a muscle or group of muscles the region between the electrodes and the muscle is thrown into anelectrotonus and its irritability is diminished. If the current be of adequate strength the irritability may be so much lessened that nervous impulses cannot be generated in that part of the nerve or cannot pass along it. Hence by this means the irregular contractions of muscles known as ' cramp ' may be abolished. Similarly, by bringing into a condition of anelectrotonus a portion 134 EFFECTS OF CONSTANT CURRENT. [BOOK i. of a sensory nerve in which violent impulses are being generated, giving rise in the central nervous system to sensations of pain, the impulses are toned down or wholly abolished, and the pain ceases. So on the other hand we may at pleasure heighten the irritability of a part by throwing it into katelectrotonus. In this way the constant current, properly applied, becomes a powerful remedial means. We said just now that probably every stimulus produces its effect on a nerve by doing what the constant current does when it acts as a stimulus, viz. suddenly raising the irritability of the nerve to a higher pitch. At any rate the stimulus so often employed in experiments, the induction-shock, acts exactly in the same way as the constant current. The induction-shock is a current of short duration, developed very suddenly but disappear- ing more gradually, and this is true both of a making induction- shock, a shock due to the making of the primary current, and of a breaking shock, a shock due to the breaking of the primary current. The two differ in direction (hence if the making shock be ascending, the breaking shock will be descending and vice versa) and in the fact that the breaking shock is more suddenly developed and hence more potent than the making shock ; but otherwise they act in the same way. In each case, since the induced current is developed rapidly but disappears more slowly, there is a sudden development of electrotonus, of katelectrotonus at the kathode and of anelectrotonus at the anode, and a more gradual return to the normal condition. Now there are many reasons for thinking that in all cases the passing from the normal condition to katelectrotonus at the kathode is a more potent stimulus than the return from anelectrotonus to the normal condition at the anode, and this will be still more so if the return to the normal condition be much slower than the entrance into electrotonus, as is the case in an induction-shock. And it would appear that in an induction-shock, which as we have said disappears much more slowly than it is developed, we have to deal not with two stimuli, one at the shock passing into a nerve and one at the shock leaving the nerve, but with one only, that produced at the shock passing into the nerve. Hence when an induction-shock is sent into a nerve, one stimulus only is developed and that at the kathode only, the establishment of katelectrotonus. This is true whether the shock be a making or a breaking shock, i.e. due to the making or breaking of the primary current, though of course owing to the change of direction in the induced current what was the kathode at the making shock becomes the anode at the breaking shock. Lastly, though we are dealing now with nerves going to muscles, that is to say with motor nerves only, we may add that what we have said about electrotonus and the development of nervous impulses by it appears to apply equally well to sensory nerves. § 78. In a general way muscular fibres behave towards an CHAP. IL] THE CONTRACTILE TISSUES. 135 electric current very much as do nerve fibres ; but there are certain important differences. In the first place muscular fibres, devoid of nerve fibres, are much more readily thrown into contractions by the breaking and making of a constant current than by the more transient induction-shock ; the muscular substance seems to be more sluggish than the nervous substance and requires to be acted upon for a longer time. This fact may be made use of, and indeed is in medical practice made use of, to determine the condition of the nerves supplying a muscle. If the intramuscular nerves be still in good condition, the muscle as a whole responds readily to single induction-shocks because these can act upon the intramuscular nerves. If these nerves on the other hand have lost their irrita- bility, the muscle does not respond readily to single induction- shocks, or to the interrupted current, but can still easily be thrown into contractions by the constant current. In the second place while in a nerve no impulses are as a rule generated during the passage of a constant current, between the break and the make, provided that it is not too strong, and that it remains uniform in strength, in_an urarized muscle on the other hand, even with moderate and perfectly uniform currents, a kind of tetanus or apparently a series of rhythmically repeated contractions is very frequently witnessed during the passage of the current. The exact nature and cause of these phenomena in muscle, we must not however discuss here. SEC. 4. THE MUSCLE-NERVE PREPARATION AS A MACHINE. § 79. The facts described in the foregoing sections shew that a muscle with its nerve may be justly regarded as a machine which, when stimulated, will do a certain amount of work. But the actual amount of work which a muscle-nerve preparation will do is found to depend on a large number of circumstances, and conse- quently to vary within very wide limits. These variations will be largely determined by the condition of the muscle and nerve in respect to their nutrition ; in other words, by the degree of irrita- bility manifested by the muscle or by the nerve or by both. But quite apart from the general influences affecting its nutrition and thus its irritability, a muscle-nerve preparation is affected as regards the amount of its work by a variety of other circumstances, which we may briefly consider here, reserving to a succeeding section the study of variations in irritability. The influence of the nature and mode of application of the stimulus. When we apply a weak stimulus, a weak induction- shock, to a nerve we get a small contraction, a slight shortening of the muscle ; when we apply a stronger stimulus, a stronger induction- shock, we get a larger contraction, a greater shortening of the muscle. We take, other things being equal, the amount of contraction of the muscle as a measure of the nervous impulse, and say that in the former case a weak or slight, in the latter case a stronger or larger nervous impulse has been generated. Now the muscle of the muscle-nerve preparation consists of many muscular fibres and the nerve of many nerve fibres ; and we may fairly suppose that in two experiments we may in the one experiment bring the induction-shock or other stimulus to bear on a few nerve fibres only, and in the other experiment on many or even all the fibres of the nerve. In the former case only those muscular fibres in which the few nerve fibres stimulated end will be thrown into contraction, the others remaining quiet, and the shortening of the muscle as a whole, since only a few fibres take part in it, will necessarily be less than when all the fibres of the nerve CHAP, ii.] THE CONTRACTILE TISSUES. 137 are stimulated and all the fibres of the muscle contract. That is to say, the amount of contraction will depend on the number of fibres stimulated. For simplicity's sake however we will in what follows, except when otherwise indicated, suppose that when a nerve is stimulated, all the fibres are stimulated and all the muscular fibres contract. In such a case the stronger or larger nervous impulse leading to the greater contraction will mean the greater disturbance in each of the nerve fibres. What we exactly mean by the greater disturbance we must not discuss here ; we must be content with regarding the greater or more powerful or more intense nervous impulse as that in which, by some mode or other, more energy is set free. So far as we know at present this difference in amount or intensity, of the energy set free, is the chief difference between various nervous impulses. Nervous impulses may differ in the velocity which they travel, in the length and possibly in the form of the impulse wave, but the chief difference is in strength, in, so to speak the height, of the wave. And our present knowledge will not permit us to point out any other differences, any differences in fundamental nature for instance, between nervous impulses generated by different stimuli, between for example the nervous impulses generated by electric currents and those generated by chemical or mechanical stimuli, or by those changes in the central nervous system which give rise to what may be called natural motor nervous impulses as distinguished from those produced by artificial stimulation of motor nerves 1. This being premised, we may say that, other things being equal, the magnitude of a nervous impulse, and so the magnitude of the ensuing contraction, is directly dependent on what we may call the strength of the stimulus. Thus taking a single induction- shock as the most manageable stimulus, we find that if, before we begin, we place the secondary coil (Fig. 4, sc.) a long way off the primary coil pr. c., no visible effect at all follows upon the discharge of the induction-shock. The passage of the momentary weak current is either unable to produce any nervous impulse at all, or the weak nervous impulse to which it gives rise is unable to stir the sluggish muscular substance to a visible contraction. As we slide the secondary coil towards the primary, sending in an induction-shock at each new position, we find that at a certain distance between the secondary and primary coils, the muscle responds to each induction-shock2 with a contraction which makes 1 It will be observed that we are speaking now exclusively of the nerve of a muscle-nerve preparation, i.e. of what we shall hereafter term a motor nerve. Whether sensory impulses differ essentially from motor impulses will be considered later on. 2 In these experiments either the breaking or making shock must be used, not sometimes one and sometimes the other, for, as we have stated, the two kinds of shock differ in efficiency, the breaking being the most potent. 138 CHARACTERS OF STIMULI. [BOOK i. itself visible by the slightest possible rise of the attached lever. This position of the coils, the battery remaining the same and other things being equal, marks the minimal stimulus giving rise to the minimal contraction. As the secondary coil is brought nearer to the primary, the contractions increase in height corre- sponding to the increase in the intensity of the stimulus. Very soon however an increase in the stimulus caused by further sliding the secondary coil over the primary fails to cause any increase in the contraction. This indicates that the maximal stimulus giving rise to the maximal contraction has been reached ; though the shocks increase in intensity as the secondary coil is pushed further and further over the primary, the contractions remain of the same height, until fatigue lowers them. With single induction-shocks then the muscular contraction, and by inference the nervous impulse, increases with an increase in the intensity of the stimulus, between the limits of the minimal and maximal stimuli; and this dependence of the nervous impulse, and so of the contraction, on the strength of the stimulus may be observed not only in electric but in all kinds of stimuli. It may here be remarked that in order for a stimulus to be effective, a certain abruptness in its action is necessary. Thus as we have seen the constant current when it is passing through a nerve with uniform intensity does not give rise to a nervous impulse, and indeed it may be increased or diminished to almost any extent without generating nervous impulses, provided that the change be made gradually enough ; it is only when there is a sudden change that the current becomes effective as a stimulus. And the reason why the breaking induction-shock is more potent as a stimulus than the making shock is because as we have seen (§ 44) the current which is induced in the secondary coil of an induction-machine at the breaking of the primary circuit, is more rapidly developed, and has a sharper rise than the current which appears when the primary circuit is made. Similarly a sharp tap on a nerve will produce a contraction, when a gradually increasing pressure will fail to do so 5s- and in general the efficiency of a stimulus of any kind will depend in part on the suddenness or abruptness of its action. A stimulus, in order that it may be effective, must have an action of a certain duration, the time necessary to produce an effect varying according to the strength of the stimulus and being different in the case of a nerve from what it is in the case of a muscle. It would appear that an electric current applied to a nerve must have a duration of at least about '0015 sec. to cause any contraction at all, and needs a longer time than this to produce its full effect. A muscle fibre apart from its nerve fibre requires a still longer duration of the stimulus, and hence, as we have already stated, a muscle poisoned by urari, or which has otherwise lost the action of its nerves, will not respond as readily to induction-shocks as to CHAP. IL] THE CONTRACTILE TISSUES. 139 the more slowly acting, breaking and making of a constant current. In the case of electric stimuli, the same current will produce a stronger contraction when it is sent along the nerve than when it is sent across the nerve ; indeed it is maintained that a current which passes through a nerve in an absolutely transverse direction is powerless to generate impulses. It would also appear, at all events up to certain limits, that the longer the piece of nerve through which the current passes, the greater is the effect of the stimulus. When two pairs of electrodes are placed on the nerve of a long and perfectly fresh and successful nerve-preparation, one near to the cut end, and the other nearer the muscle, it is found that the same stimulus produces a greater contraction when applied through the former pair of electrodes than through the latter. This has been interpreted as meaning that the impulse started at the farther electrodes gathers strength, like an avalanche, in its progress to the muscle. It is more probable, however, that the larger contraction produced by stimulation of the part of the nerve near the cut end is due to the stimulus setting free a larger impulse, i.e. to this part of the nerve being more irritable. The mere section, possibly by developing nerve currents, increases for a time the irritability at the cut end. A similar greater irritability may however also be observed in the part of the nerve nearer the spinal cord while it is still in connection with the spinal cord; and it is possible that the irritability of a nerve may vary considerably at different points of its course. § 80. We have seen that when single stimuli are repeated with sufficient frequency, the individual contractions are fused into tetanus ; as the frequency of the repetition is increased, the individual contractions are less obvious on the curve, until at last we get a curve on which they seem to be entirely lost and which we may speak of as a complete tetanus. By such a tetanus a much greater contraction, a much greater shortening of the muscle is of course obtained than by single contractions. The exact frequency of repetition required to produce complete tetanus will depend chiefly on the length of the individual contractions, and this varies in different animals, in different muscles of the same animal, and in the same muscle under different conditions. In a cold-blooded animal a single contraction is as a rule more prolonged than in a warm-blooded animal, and tetanus is consequently produced in the former by a less frequent repe- tition of the stimulus. A tired muscle has a longer contraction than a fresh muscle, and hence in many tetanus curves the individual contractions, easily recognised at first, disappear later on, owing to the individual contractions being lengthened out by the exhaustion caused by the tetanus itself. In many animals, 140 REPETITION OF CONTRACTIONS IN TETANUS. [BOOK i. e.g. the rabbit, some muscles (such as the adductor magnus femoris) are pale, while others (such as the semitendinosus) are red. The red muscles are not only more richly supplied with blood vessels, but the muscle substance of the fibres contains more haemoglobin than the pale, and there are other structural differ- ences. Now the single contraction of one of these red muscles is more prolonged than a single contraction of one of the pale muscles produced by the same stimulus. Hence the red muscles are thrown into complete tetanus with a repetition of much less frequency than that required for the pale muscles. Thus, ten stimuli in a second are quite sufficient to throw the red muscles of the rabbit into complete tetanus, while the pale muscles require at least twenty stimuli in a second. So long as signs of the individual contractions are visible on the curve of tetanus it is easy to recognise that each stimulation produces one of the constituent single contractions, and that the number so to speak of the vibrations of the muscle making up the tetanus corresponds to the number of stimulations; but the question whether, when we increase the number of stimulations beyond that necessary to produce a complete tetanus, we still increase the number of constituent single contractions is one not so easy to answer. And connected with this question is another difficult one. What is the rate of repetition of single contractions making up those tetanic contractions which as we have said are the kind of contractions by which the voluntary, and indeed other natural, movements of the body are carried out ? What is the evidence that these are really tetanic in character ? When a muscle is thrown into tetanus, a more or less musical sound is produced. This may be heard by applying a stethoscope directly over a contracting muscle, and a similar sound but of a more mixed origin and less trustworthy may be heard when the masseter muscles are forcibly contracted or when a finger is placed in the ear, and the muscles of the same arm are contracted. When the stethoscope is placed over a muscle, the nerve of which is stimulated by induction-shocks repeated with varying frequency, the note heard will vary -with the frequency of the shocks, being of higher pitch with the more frequent shocks. Now it has been thought that the vibrations of the muscle giving rise to the " muscle sound " are identical with the single contractions making up the tetanus of the muscle. And since, in the human body, when a muscle is thrown into contraction in a voluntary effort, or indeed in any of the ordinary natural movements of the body, the fundamental tone of the sound corresponds to about 19 or 20 vibrations a second, it has been concluded that the con- traction taking place in such cases is a tetanus of which the individual contractions follow each other about 19 or 20 times a second. But investigations seem to shew that the vibrations CHAP, ii.] THE CONTRACTILE TISSUES. 141 giving rise to the muscle sound do not really correspond to the shortenings and relaxations of the individual contractions, and that the pitch of the note cannot therefore be taken as an indication of the number of single contractions making up the tetanus ; indeed, as we shall see in speaking of the sounds of the heart, a single muscular contraction may produce a sound which though differing from the sound given out during tetanus has to a certain extent musical characters. Nevertheless the special characters of the muscle sound given out by muscles in the natural movements of the body may be taken as shewing at least that the contractions of the muscle in these movements are tetanic in nature, and the similarity of the note in all the voluntary efforts of the body and indeed in all movements carried out by the central nervous system is at least consonant with the view that the repetition of single contractions is of about the same frequency in all these movements. What that frequency is, and whether it is exactly identical in all these movements, is not at present perhaps absolutely determined ; but certain markings on the myographic tracings of these movements and other facts seem to indicate that it is about 12 a second. § 81. The Influence of the Load. It might be imagined that a muscle, which, when loaded with a given weight, and stimulated by a current of a given intensity, had contracted to a certain extent, would only contract to half that extent when loaded with twice the weight and stimulated with the same stimulus. Such however is not necessarily the case ; the height to which the weight is raised may be in the second instance as great, or even greater, than in the first. That is to say, the resistance offered to the contraction actually augments the contraction, the tension of the muscular fibre increases the facility with which the explosive changes resulting in a contraction take place. And we have other evidence that anything which tends to stretch the muscular fibres, that any tension of the muscular fibres, whether during rest or during contraction, increases the metabolism of the muscle. There is, of course, a limit to this favourable action of the resistance. As the load continues to be increased, the height of the contraction is diminished, and at last a point is reached at which the muscle is unable (even when the stimulus chosen is the strongest possible) to lift the load at all. In a muscle viewed as a machine we have to deal not merely with the height of the contraction, that is with the amount of shortening, but with the work done. And this is measured by multiplying the number of units of height to which the load is raised into the number of units of weight of the load. Hence it is obvious from the foregoing observations that the work done must be largely dependent on the weight itself. Thus there is a certain weight of load with which in any given muscle, stimu- 142 THE WORK DONE. [BOOK i. lated by a given stimulus, the most work will be done ; as may be seen from the following example : Load, in grammes 0 50 100 150 200 250 Height of contractions in millimeters 14 9 7 5 2 0 Work done, in gram-millimeters ... 0 450 700 750 400 0 § 82. The Influence of the Size and Form of the Muscle. Since all known muscular fibres are much shorter than the wave-length of a contraction, it is obvious that the longer the fibre, the greater will be the shortening caused by the same contraction wave, the greater will be the height of the contraction with the same stimulus. Hence in a muscle of parallel fibres, the height to which the load is raised as the result of a given stimulus applied to its nerve, will depend on the length of the fibres, while the maximum weight of load capable of being lifted will depend on the number of the fibres, since the load is distributed among them. Of two muscles therefore of equal length (and of the same quality) the most work will be done by that which has the larger number of fibres, that is to say, the fibres being of equal width, which has the greater sectional area; and of two muscles with equal sectional areas, the most work will be done by that which is the longer. If the two muscles are unequal both in length and sectional area, the work done will be the greater in the one which has the larger bulk, which contains the greater number of cubic units. In speaking therefore of the work which can be done by a muscle, we may use as a standard a cubic unit of bulk, or, the specific gravity of the muscle being the same, a unit of weight. We learn then from the foregoing paragraphs that the work done, by a muscle-nerve preparation, will depend, not only on the activity of the nerve and muscle as determined by their own irritability, but also on the character and mode of application of the stimulus, on the kind of contraction (whether a single spasm, or a slowly repeated tetanus or a rapidly repeated tetanus) on the load itself, and on the size and form of the muscle. Taking the most favourable circumstances, viz. a well nourished, lively preparation, a maximum stimulus causing a rapid tetanus and an appropriate load, we may determine the maximum work done by a given weight of muscle, say one gramme. This in the case of the muscles of the frog has been estimated at about four gram-metres for one gramme of muscle. SEC. 5. THE CIRCUMSTANCES WHICH DETERMINE THE DEGREE OF IRRITABILITY OF MUSCLES AND NERVES. § 83. A muscle-nerve preparation, at the time that it is re- moved from the body, possesses a certain degree of irritability, it responds by a contraction of a certain amount to a stimulus of a certain strength, applied to the nerve or to the muscle. After a while, the exact period depending on a variety of circumstances, the same stimulus produces a smaller contraction, i.e. the irritability of the preparation has diminished. In other words, the muscle or nerve or both have become partially ' exhausted ' ; and the exhaustion subsequently increases, the same stimulus producing smaller contractions, until at last all irritability is lost, no stimulus however strong producing any contraction whether applied to the nerve or directly to the muscle ; and eventually the muscle, as we have seen, becomes rigid. V The progress of this exhaustion is more rapid in the nerves than in the muscles ; for some time after the nerve-trunk has ceased to respond to even the strongest stimulus, contractions may be obtained by applying the stimulus directly to the muscle. It is much more rapid in the warm-blooded than in the cold-blooded animals. The muscles and nerves of the former lose their irritability, when removed from the body, after a period varying according to circumstances from a few minutes to two or three hours ; those of cold-blooded animals (or at least of an amphibian or a reptile) may under favourable conditions remain irritable for two, three, or even more days. The duration of irritability in warm-blooded animals may however be considerably prolonged by reducing the temperature of the body before death. If with some thin body a sharp blow be struck across a muscle which has entered into the later stages of exhaustion, a wheal lasting for several seconds is developed. This wlieal appears to be a contraction wave limited to the part struck, and disappearing very slowly, without extending to the neighbouring muscular substance. It has been called 144 DEGENERATION OF NERVES. [BOOK i. an 'iclio-musciilar' contraction, because it may be brought out even when ordinary stimuli have ceased to produce any effect. It may however be accompanied at its beginning by an ordinary contraction. It is readily produced in the living body on the pectoral and other muscles of persons suffering from phthisis and other exhausting diseases. This natural exhaustion and diminution of irritability in muscles and nerves removed from the body may be modified both in the case of the muscle and of the nerve, by a variety of circum- stances. Similarly, while the nerve and muscle still remain in the body, the irritability of the one or of the other may be modified either in the way of increase or of decrease by certain general influences, of which the most important are, severance from the central nervous system, and variations in temperature, in blood- supply, and in functional activity. The Effects of Severance from tJte Central Nervous System. When a nerve, such for instance as the sciatic, is divided in situ, in the living body, there is first of all observed a slight increase of irritability, noticeable especially near the cut end ; but after a while the irritability diminishes, and gradually disappears. Both the slight initial increase and the subsequent decrease begin at the cut end and advance centrifugally towards the peripheral terminations. This centrifugal feature of the loss of irritability is often spoken of as the Bitter- Valli law. In a mammal it may be two or three days, in a frog, as many, or even more weeks, before irritability has disappeared from the nerve- trunk. It is maintained in the small (and especially in the intramuscular) branches for still longer periods. This centrifugal loss of irritability is the forerunner in the peripheral portion of the divided nerve of structural changes which proceed in a similar centrifugal manner. The medulla suffers changes similar to those seen in nerve fibres after removal from the body ; its double contour and its characteristic indentations be- come more marked, it breaks up into small irregular fragments, or drops. Mingled with the fat particles of the medulla are seen small masses of proteid material which appear to be derived from the protoplasm around the nuclei. Meanwhile the axis cylinder also breaks up into fragments, and the nuclei of the neurilemma divide and multiply. The fatty constituents sub- sequently decrease in amount, the proteid material increasing or not diminishing, and thus the contents of the neurilemma between each two nodes is reduced to a mass of proteid material, in which the fragments of the axis cylinder can no longer be recognised. This mass which still retains some fat globules, is studded with nuclei. If no regeneration takes place these nuclei with their proteid bed eventually disappear. In the central portion of the divided nerve similar changes may be traced as far only as the next node of Ranvier. Beyond this the nerve usually remains in a normal condition. CHAP, ii.] THE CONTRACTILE TISSUES. 145 Regeneration, when it occurs, is apparently carried out by the peripheral growth of the axis-cylinders of the intact central portion. When the cut ends of the nerve are close together the axis-cylinders growing out from the central portion run into and between the shrunken neurilemmas of the peripheral portion ; but much uncertainty still exists as to the exact parts which the proliferated nuclei and the proteid material referred to above, and the old axis-cylinders of the peripheral portion respectively play in giving rise to the new structures of the regenerated fibre. Such a degeneration may be observed to extend down to the very endings of the nerve in the muscle, including the end-plates, but does not at first affect the muscular substance itself. The muscle, though it has lost all its nervous elements, still remains irritable towards stimuli applied directly to itself: an additional proof of the existence of an independent muscular irritability. For some time the irritability of the muscle, as well towards stimuli applied directly to itself as towards those applied through the impaired nerve, seems to be diminished ; but after a while a peculiar condition (to which we have already alluded § 78) sets in, in which the muscle is found to be not easily stimulated by single induction-shocks but to respond readily to the make or break of a constant current. In fact it is said to become even more sensitive to the latter mode of stimulation than it was when its nerve was intact and functionally active. At the same time it also becomes more irritable towards direct mechanical stimuli, and very frequently fibrillar contractions, more or less rhythmic and apparently of spontaneous origin, though their causation is ob- scure, make their appearance. This phase of heightened sensitiveness of a muscle, especially to the constant current, appears to reach its maximum, in man at about the seventh week after nervous impulses have ceased, owing to injury to the nerves or nervous centre, to reach the muscle. If the muscle thus deprived of its nervous elements be left to itself its irritability, however tested, sooner or later diminishes; but if the muscle be periodically thrown into contractions by artificial stimulation with the constant current, the decline of irritability and attendant loss of nutritive power may be postponed for some considerable time. But as far as our experience goes at present the artificial stimulation cannot fully replace the natural one, and sooner or later the muscle like the nerve suffers degeneration, loses all irritability and ultimately its place is taken by connective tissue. § 84. The influence of temperature. We have already seen that sudden heat, (and the same might be said of cold when sufficiently intense), applied to a limited part of a nerve or muscle, as when the nerve or muscle is touched with a hot wire, will act as a stimulus. It is however much more difficult to gene- rate nervous or muscular impulses by exposing a whole nerve or muscle to a gradual rise of temperature. Thus according to most P. 10 146 INFLUENCE OF TEMPERATURE. [BOOK i. observers a nerve belonging to a muscle1 may be either cooled to 0° C. or below, or heated to 50° or even 100° C., without dis- charging any nervous impulses, as shewn by the absence of con- traction in the attached muscle. The contractions moreover may be absent even when the heating has not been very gradual. A muscle may be gradually cooled to 0° C. or below without any contraction being caused ; but when it is heated to a limit, which in the case of frog's muscles is about 45°, of mammalian muscles about 50°, a sudden change takes place : the muscle falls, at the limiting temperature, into a rigor mortis, which is initiated by a forcible contraction or at least shortening. Moderate warmth, e. g. in the frog an increase of temperature up to somewhat below 45° C., favours both muscular and nervous irritability. All the molecular processes are hastened and facili- tated : the contraction is for a given stimulus greater and more rapid, i.e. of shorter duration, and nervous impulses are generated more readily by slight stimuli. Owing to the quickening of the chemical changes, the supply of new material may prove insuffi- cient ; hence muscles and nerves removed from the body lose their irritability more rapidly at a high than at a low temperature. The gradual application of cold to a nerve, especially when the temperature is thus brought near to 0°, slackens all the molecular processes, so that the wave of nervous impulse is lessened and pro- longed, the velocity of its passage being much diminished, e.g. from 28 metres to 1 metre per sec. At about 0° the irritability of the nerve disappears altogether. When a muscle is exposed to similar cold, e. g. to a tempera- ture very little above zero, the contractions are remarkably pro- longed ; they are diminished in height at the same time, but not in proportion to the increase of their duration. Exposed to a temperature of zero or below, muscles soon lose their irritability, without however undergoing rigor mortis. After an exposure of not more than a few seconds to a temperature not much below zero, they may be restored, by gradual warmth, to an irritable con- dition, even though they may appear to have been frozen. When kept frozen however for some few minutes, or when exposed for a less time to temperatures of several degrees below zero, their irritability is permanently destroyed. When after this they are thawed, they are at first supple and as we have seen may be made to yield muscle plasma ; but they very speedily enter into rigor mortis of a most pronounced character. § 85. The influence of blood-supply. When a muscle still within the body is deprived by any means of its proper blood- supply, as when the blood vessels going to it are ligatured, the same gradual loss of irritability and final appearance of rigor mortis are observed as in muscles removed from the body. Thus 1 The action of cold and heat on sensory nerves will be considered in the later portion of the work. CHAP, ii.] THE CONTRACTILE TISSUES. 147 if the abdominal aorta be ligatured, the muscles of the lower limbs lose their irritability and finally become rigid. So also in systemic death, when the blood-supply to the muscles is cut off by the cessation of the circulation, loss of irritability ensues, and rigor mortis eventually follows. In a human corpse the muscles of the body enter into rigor mortis in a fixed order : first those of the jaw and neck, then those of the trunk, next those of the arms, and lastly those of the legs. The rapidity with which rigor mortis conies on after death varies considerably, being determined both by external circumstances and by the internal conditions of the body. Thus external warmth hastens and cold retards the onset. After great muscular exertion, as in hunted animals, and when death closes wasting diseases, rigor mortis in most cases comes on rapidly. As a general rule it may be said that the later it is in making its appearance, the more pronounced it is, and the longer it lasts ; but there are many exceptions, and when the state is recognized as being fundamentally due to a clotting of myosin, it is easy to under- stand that the amount of rigidity, i.e. the amount of the clot, and the rapidity of the onset, i.e. the quickness with which coagulation takes place, may vary independently. The rapidity of onset after muscular exercise and wasting disease may perhaps be, in part, dependent on an increase of acid reaction, which is produced under those circumstances in the muscle, for this seems to be favourable to the coagulation of the muscle plasma. When rigor mortis has once become thoroughly established in a muscle through deprivation of blood, it cannot be removed by any subsequent supply of blood. Thus where the abdominal aorta has remained ligatured until the lower limbs have become completely rigid, untying the ligature will not restore the muscles to an irritable condition ; it simply hastens the decomposition of the dead tissues by supplying them with oxygen and: in the case of the mammal, with warmth also. A muscle however may acquire as a whole a certain amount of rigidity on account of some of the fibres becoming rigid, while the remainder, though they have lost their irritability, have not yet advanced into rigor mortis. At such a juncture a renewal of the blood-stream may restore the irritability of those fibres which were not yet rigid, aud thus appear to do away with rigor mortis ; yet it appears that in such cases the fibres which have actually become rigid never regain their irrita- bility, but undergo degeneration. Mere loss of irritability, even though complete, if stopping short of the actual coagulation of the muscle substance, may be with care removed. Thus if a stream of blood be sent artificially through the vessels of a separated (mammalian) muscle, the irrita- bility may be maintained for a very considerable time. On stopping the artificial circulation, the irritability diminishes and in time entirely disappears ; if however the stream be at once resumed, the irritability will be recovered. By regulating the flow, the 10—2 148 INFLUENCE OF ACTIVITY. [BOOK i. irritability may be lowered and (up to a certain limit) raised at pleasure. From the epoch however of interference with the nor- mal blood- stream there is a gradual diminution in the responses to stimuli, and ultimately the muscle loses all its irritability and becomes rigid, however well the artificial circulation be kept up. This failure is probably in great part due to the blood sent through the tissues not being in a perfectly normal condition ; but we have at present very little information on this point. Indeed with respect to the quality of blood thus essential to the maintenance or restoration of irritability, our knowledge is definite with regard to one factor only, viz. the oxygen. If blood deprived of its oxygen be sent through a muscle removed from the body, irritability, so far from being maintained, seems rather to have its disappearance hastened. '-In fact, if venous blood continues to be driven through a muscle, the irritability of the muscle is lost even more rapidly than in the entire absence of blood. It would seem that venous blood is more injurious than none at all. If exhaustion be not carried too far, the muscle may however be revived by a proper supply of oxygenated blood. The influence of blood-supply cannot be so satisfactorily studied in the case of nerves as in the case of muscles ; there can however be little doubt that the effects are analogous. § 86. The influence of functional activity. This too is more easily studied in the case of muscles than of nerves. When a muscle within the body is unused, it wastes ; when used, it (within certain limits) grows. Both these facts shew that the nutrition of a muscle is favourably affected by its functional activity. Part of this may be an indirect effect of the increased blood-supply which occurs when a muscle contracts. When a nerve going to a muscle is stimulated, the blood vessels of the muscle dilate. Hence at the time of the contraction more blood flows through the muscle, and this increased flow continues for some little while after the contraction of the muscle has ceased. But, apart from the blood-supply, it is probable that the ex- haustion caused by a contraction is immediately followed by a reaction favourable to the nutrition of the muscle ; and this is a reason, possibly the chief reason, why a muscle is increased by use, that is to say, the loss of substance and energy caused by the contraction is subsequently more than made up for by increased metabolism during the following period of rest. Whether there be a third factor, whether muscles for in- stance are governed by so-called trophic nerves which affect their nutrition directly in some other way than by influencing either their blood-supply or their activity, must at present be left undecided. A muscle, even within the body, after prolonged action is fatigued, i.e. a stronger stimulus is required to produce the same contraction ; in other words, its irritability may be lessened by CHAP, ii.] THE CONTRACTILE TISSUES. 149 functional activity. Whether functional activity therefore is in- jurious or beneficial depends on its amount in relation to th'e condition of the muscle. It may be here remarked that as a muscle becomes more and more fatigued, stimuli of short duration, such as induction-shocks, sooner lose their efficacy than do stimuli of longer duration, such as the break and make of the constant current. The sense of fatigue of which, after prolonged or unusual exer- tion, we are conscious in our own bodies, is probably of complex origin, and its nature, like that of the normal muscular sense of which we shall have to speak hereafter, is at present not thoroughly understood. It seems to be in the first place the result of changes in the muscles themselves, but is possibly also caused by changes in the nervous apparatus concerned in muscular action,"and especially in those parts of the central nervous system which are concerned in the production of voluntary impulses. In any case it cannot be taken as an adequate measure of the actual fatigue of the muscles ; for a man who says he is absolutely exhausted may under excite- ment perform a very large amount of work with his already weary muscles. The will in fact rarely if ever calls forth the greatest contractions of which the muscles are capable. Absolute (temporary) exhaustion of the muscles, so that the strongest stimuli produce no contraction, may be produced even within the body by artificial stimulation : recovery takes place on rest. Out of the body absolute exhaustion takes place readily. Here also recovery may take place. Whether in any given case it does occur or not, is determined by the amount of contraction causing the exhaustion, and by the previous condition of the muscle. In all cases recovery is hastened by renewal (natural or artificial) of the blood-stream. The more rapidly the contractions follow each other, the less the interval between any two contractions, the more rapid the exhaustion. A certain number of single induction-shocks repeated rapidly, say every second or oftener, bring about exhaustive loss of irritability more rapidly than the same number of shocks repeated less rapidly, for instance every 5 or 10 seconds. Hence tetanus is a ready means of producing exhaustion. In exhausted muscles the elasticity is much diminished ; the tired muscle returns less readily to its natural length than does the fresh one. The exhaustion due to contraction may be the result : — Either of the consumption of the store of really contractile material present in the muscle. Or of the accumulation in the tissue of the products of the act of contraction. Or of both of these causes. The restorative influence of rest, in the case of a muscle removed from the circulation, may be explained by supposing that during the repose, either the internal changes of the tissue 150 CAUSES OF EXHAUSTION. [BOOK i. manufacture new explosive material out of the comparatively raw material already present in the fibres, or the directly hurtful pro- ducts of the act of contraction undergo changes by which they are converted into comparatively inert bodies. A stream of fresh blood may exert its restorative influence not only by quickening the above two events, but also by carrying off the immediate waste products while at the same time it brings new raw material. It is not known to what extent each of these parts is played. ^That the products of contraction are exhausting in their effects, is shewn by the facts that the injection of a solution of the muscle-extractives into the vessels of a muscle produces exhaustion, and that exhausted muscles are recovered by the simple injection of inert saline solutions into their blood vessels. But the matter has not yet been fully worked out. One important element brought by fresh blood is oxygen. This, as we have seen, is not necessary for the carrying out of the actual contraction, and yet is essential to the maintenance of irritability. The oxygen absorbed by the muscle apparently enters in some peculiar way into the formation of that complex explosive material the decomposition of which in the act of contraction, though it gives rise to carbonic acid and other products of oxidation, is not in itself a process of direct oxidation. SEC. 6. THE ENERGY OF MUSCLE AND NERVE, AND THE NATURE OF MUSCULAR AND NERVOUS ACTION. § 87. We may briefly recapitulate some of the chief results arrived at in the preceding pages as follows. A muscular contraction itself is essentially a trauslocation of molecules, a change of form not of bulk. We cannot say however anything definite as to the nature of this translocation or as to the way in which it is brought about. For instance we cannot satisfactorily explain the connection between the striation of a mus- cular fibre and a muscular contraction. Nearly all rapidly contract- ing muscles are striated, and we must suppose that the striation is of some use ; but it is not essential to the carrying out of a contraction, for as we shall see the contraction of a non-striated muscle is fundamentally the same as that of a striated muscle. But whatever be the exact way in which the translocation is effected, it is in some way or other the result of a chemical change, of an explosive decomposition of certain parts of the muscle substance. The energy which is expended in the mechanical work done by the muscle has its source in the energy latent in the muscle substance and set free by that explosion. Concerning the nature of that ex- plosion we only know at present that it results in the production of carbonic acid and in an increase of the acid reaction, and that heat is set free as well as the specific muscular energy. .There is a general parallelism between the extent of metabolism taking place and the amount of energy set free ; the greater the de- velopment of carbonic acid, the larger is the contraction and the higher the temperature. It is important to remember that, as we have already urged, relaxation, the return to the original length, is an essential part of the whole contraction no less than the shortening itself. It is true that the return to the original length is assisted by the stretching exerted by the load, and in the case of muscles within the living body is secured by the action of antagonistic muscles or 152 THE ENERGY OF MUSCLE. [BOOK i. by various anatomical relations ; but the fact that the completeness and rapidity of the return are dependent on the condition of the muscle, that is on the complex changes within the muscle making up what we call its nutrition, the tired muscle relaxing much more slowly than the untired muscle, shews that the relaxation is due in the main to intrinsic processes going on in the muscle itself, processes which we might characterize as the reverse of those of contraction. In fact, to put the matter forcibly, adopting the illustration used in § 57, and regarding relaxation as a change of molecules from a 'formation' of one hundred in two lines of fifty each to a formation of ten columns each ten deep, it would be possible to support the thesis that the really active forces in muscle are those striving to maintain the latter formation in columns and that the falling into double lines, that is to say the contraction, is the result of these forces ceasing to act ; in other words that the contracted state of the muscular fibre is what may be called the natural state, that the relaxed condition is only brought about at the expense of changes counteracting the natural tendencies of the fibre. Without going so far as this however we may still recognize that both contraction and relaxation are the result of changes which, since they seem to be of a chemical nature in the one case, are probably so in the other also. And though in the absence of exact knowledge it is dangerous to specu- late, we may imagine that these chemical events leading to relaxation or elongation are of an opposite or antagonistic character to those whose issue is contraction. It has not been possible hitherto to draw up a complete equa- tion between the latent energy of the material and the two forms of actual energy set free, heat and movement. The proportion of energy given out as heat to that taking on the form of work varies under different circumstances ; and it would appear that on the whole a muscle would not be much more efficient than a steam-engine in respect to the conversion of chemical action into mechanical work, were it not that in warm-blooded animals the heat given out is not, as in the steam-engine, mere loss, but by keep- ing up the animal temperature serves many subsidiary purposes. It might be supposed that in a contraction by which work is actually done, as compared with the same contraction when no work is done, there is a diminution of the increase of temperature corre- sponding to the amount of work done, that is to say, that the mechanical work is done at the expense of energy which other- wise would go out as heat. Probable as this may seem it has not yet been experimentally verified. Of the exact nature of the chemical changes which underlie a muscular contraction we know very little, the most important fact being, that the contraction is not the outcome of a direct oxidation, but the splitting up or explosive decomposition of some complex substance or substances. The muscle does consume oxygen, and CHAP, ii.] THE CONTRACTILE TISSUES. 153 the products of muscular metabolism are in the end products of oxidation, but the oxygen appears to be introduced not at the moment of explosion but at some earlier date. As to the real nature of this explosive material we are as yet in the dark ; we do not know for certain whether we ought to regard it as a single substance (in the chemical sense) or as a mixture of more substances than one. We may however perhaps be allowed provisionally to speak of it at all events as a single substance and to call it 'contrac- tile material' or we may adopt a term which has been suggested and call it inogen. We shall have occasion to point out later on, that the living- substance of certain cells is able to manufacture and to lodge in the substance of the cell relatively considerable quantities of fat where- by the cell becomes a fat cell, the fat so formed and lodged being subsequently by some means or other discharged from the cell. We shall also have occasion to point out that in a somewhat similar way the living material of certain gland cells manufactures and lodges in itself certain substances which when the cell 'secretes' undergo more or less change and are ejected from the cell. These substances appear to be products of the activity of the living sub- stance of the cell, and to be so related to that living substance that, though discontinuous with it and merely lodged in it they are still capable of being so influenced by it as to undergo change more or less sudden, more or less profound. And we may, resting on the analogy of these fat cells and gland cells, suppose that the living substance of the muscle manufactures and lodges in itself this contractile material or inogen which is capable of being so in- fluenced by the living substance as to undergo an explosive decomposition. But we here meet with a difficulty. The muscular fibre as a whole is eminently a nitrogenous proteid body ; the muscular fibres of the body form the greater part of the whole proteid mass of the body. Moreover the ordinary continued metabolism of the muscular fibre as a whole is essentially a nitro- genous metabolism ; as we shall have to point out later on the muscles undoubtedly supply a great part of that large nitrogenous waste which appears in the urine as urea; the nitrogenous meta- bolism of the muscle during the twenty-four hours must therefore be considerable, and under certain circumstances, as for instance during fever, this nitrogenous metabolism may be still further largely increased. On the other hand, as we have already shewn, there can be no doubt that the act of contraction, the explosive decomposition of the inogen, does not increase the nitrogenous metabolism of the muscle. Shall we conclude then that the inogen is essentially a non-nitro- genous body lodged in the nitrogenous muscle substance ? Not only have we no positive evidence of this, but the analogy between contraction and rigor mortis is directly opposed to such a view ; for it is almost impossible to resist the conclusion that the stuff which 154 THE ENERGY OF MUSCLE AND NERVE. [BOOK i. gives rise to the myosin clot, the carbonic acid, and lactic acid or other acid-producing substances of rigor mortis, is the same stuff which gives rise to the carbonic acid and lactic acid or other acid- producing substances of a contraction. The difference between the two seems to be that in the contraction the nitrogenous product of the decomposition of the inogen does not appear as solid myosin but assumes the form of some soluble proteid. The important fact concerning the two acts, rigor mortis and contraction, is that, while the great non-nitrogenous product of the decomposition of the inogen, viz. carbonic acid, is simple waste matter containing no energy, fit only to be cast out of the body at once (and the same is nearly true of the other non-nitrogenous product, lactic acid), the nitrogenous product being a proteid is still a body containing much energy, which in the case of the living muscle may after the contraction be utilized by the muscle itself or, being carried away into the blood-stream, by some other parts of the body. But if this view be correct the ordinary metabolism going on while the muscle is at rest must differ in kind as well as, and per- haps more than, in degree from the metabolism of contraction ; for the former as we have just said is essentially a nitrogenous meta- bolism largely contributing to the nitrogenous waste of the body at large. Whether in the muscle at rest this nitrogenous metabolism is confined to that part of the muscle in which the inogen is lodged and does not involve the inogen itself, or whether the inogen as well as the rest of the fibre undergoes metabolism when the muscle is at rest, going off in puffs, so to speak, instead of in a large explosion, its nitrogenous factors being at the same time involved in the change, are questions which we cannot at present settle. § 88. While in muscle the chemical events are so prominent that we cannot help considering a muscular contraction to be essentially a chemical process, with electrical changes as attendant phenomena only, the case is different with nerves. Here the electrical pheno- mena completely overshadow the chemical. Our knowledge of the chemistry of nerves is at present of the scantiest, and the little we know as to the chemical changes of nervous substance is gained by the study of the central nervous organs rather than of the nerves. We find that the irritability of the former is closely dependent on an adequate supply of oxygen, and we may infer from this that in nervous as in muscular substance a metabolism, of in the main an oxidative character, is the real cause of the development of energy; and the axis-cylinder, which as we have seen is most probably the active element of a nerve-fibre, undoubtedly resembles in many of its chemical features the substance of a muscular fibre. But we have as yet no satisfactory experimental evidence that the passage of a nervous impulse along a nerve is the result, like the contraction of a muscular fibre, of chemical changes, and like it accompanied by an evolution of heat. On the other hand, the electric phenomena are so CHAP, ii.] THE CONTRACTILE TISSUES. 155 prominent that some have been tempted to regard a nervous impulse as essentially an electrical change. But it must be remembered that the actual energy set free in a nervous impulse is, so to speak, in- significant, so that chemical changes too slight to be recognized by the means at present at our disposal would amply suffice to provide all the energy set free. On the other hand, the rate of transmission of a nervous impulse, putting aside other features, is alone sufficient to prove that it is something quite different from an ordinary electric current. The curious disposition of the end-plates, and their remarkable analogy with the electric organs which are found in certain animals, has suggested the view that the passage of a nervous impulse from the nerve fibre into the muscular substance is of the nature of an electric discharge. But these matters are too difficult and too abstruse to be discussed here. It may however be worth while to remind the reader that in every contraction of a muscular fibre, the actual change of form is preceded by invisible changes propagated all over the fibre and occupying the latent period, and that these changes resemble in their features the nervous impulse of which they are, so to speak, the continuation rather than the contraction of which they are the forerunners and to which they give rise. So that a muscle, even putting aside the visible terminations of the nerve, is fundamentally^ a muscle and a nerve besides. SEC. 7. ON SOME OTHER FORMS OF CONTRACTILE TISSUE. Plain, Smooth or Unstriated Muscular Tissue. § 89. This, in vertebrates at all events, rarely occurs in isolated masses or muscles, as does striated muscular tissue, but is usually found taking part in the structure of complex organs, such for instance as the intestines ; hence the investigation of its properties is beset with many difficulties. It is usually arranged in sheets, composed of flattened bundles or bands bound together by connective tissue carrying blood vessels, lymphatics and nerves. Some of these bundles or bands may be split up into smaller bands similarly united to each other by con- nective tissue, but in many cases the whole sheet being thin is made up directly of small bands. Each small band is composed of a number of elementary fibres or fibre cells, which in a certain sense are analogous to the striated elementary fibres, but in many respects differ widely from them. Each unstriated elementary fibre is a minute object, from 50 ^ to 200 /ji in length and from 5 /A to 10 /j, in breadth ; it is therefore, in size, of a wholly different order from a striated fibre. It is fusi- form or spindle-shaped, somewhat flattened in the middle and tapering to a point at the ends, which in some cases are branched ; but the exact form of the fibre will differ according as the muscle is in a state of contraction or relaxation. Midway between the two ends and in the centre of the fusiform body lies a nucleus, which in a normal condition is elliptical in out- line, with its long axis lying lengthwise, but which under the influence of reagents is very apt to become rod-shaped ; hence in prepared specimens the presence of these rod-shaped nuclei is very characteristic of plain muscular tissue. The nucleus has the ordinary characters of a nucleus, and very frequently two nucleoli are conspicuous. Around the nucleus is CHAP. IL] THE CONTRACTILE TISSUES. 157 gathered a small quantity of granular protoplasm, like that around the nuclei of a striated fibre, and this is continued along the axis of the fibre for some distance from each pole of the nucleus, gradually tapering away, and so forming a slender granular core in the median portion of the fibre. The rest of the fibre, forming its chief part, is composed of a transparent but somewhat refractive substance, which is either homogeneous oXexhibits a delicate longitudinal fibrillation ; this is the muscle substance of the fibre and corresponds to the muscle substance of the striated fibre, but is not striated. Sometimes the whole fibre is thrown into a series of transverse wrinkles, which give it a striated appearance, but this is a very different striation from that produced by an alternation of dim and bright bands. No such alternation of bands is to be seen in the plain muscular fibre ; the whole of the substance of the fibre around the nucleus and core is homogeneous, or at least exhibits no differentiation be- yond that into fibrillaa and inter fibrillar substance, and even this distinction is doubtful. The fibre has a sharp clear outline but is not limited by any distinct sheath corresponding to the sarcolemma, at least according to most observers. It is obvious that the plain muscular fibre is a nucleated cell, the cell substance of which has become differentiated into con- tractile substance, the cell otherwise being but slightly changed ; whereas the much larger striated fibre is either a number of cells fused together or a cell which has undergone multiplication in so far that its nucleus has given rise to several nuclei, but in which no division of cell substance has taken place. A number of such fusiform nucleated cells or fibres or fibre cells are united together, not by connective tissue' but by a peculiar proteid cement substance into a flat band or bundle, the tapering- end of one fibre dovetailing in between the bodies of other fibres. So long as this cement substance is intact it is very difficult to isolate an individual fibre, but various reagents will dissolve or lessen this cement, and then the fibres separate. Small flat bands thus formed of fibres cemented together are variously arranged by means of connective tissue, sometimes into -a plexus, sometimes into thicker larger bands, which in turn may be bound up as we have said into sheets of varying thickness. In the plexus of course the bands run in various directions, but in the sheets or membranes they follow for the most part the same direction, and a thin transverse section of a somewhat thick sheet presents a number of smaller or larger areas, corresponding to the smaller or larger bands which are cut across. The limits of each area are more or less clearly defined by the connective tissue in which blood vessels may be seen, the area itself being composed of a number of oval outlines, the sections of the flattened individual fibres ; in hardened specimens the outlines may from 158 STRUCTURE OF PLAIN MUSCLE. [BOOK i. mutual pressure appear polygonal. In the centre of some of these sections of fibres the nucleus may be seen, but it will of course be absent from those fibres in the which plane of section has passed either above or below the nucleus. When a thin sheet of plain muscle is spread out or teased out under the microscope, the bands may also be recognized, and at the torn ends of some of the bands the individual fibres may be seen projecting after the fashion of a palisade. Blood vessels and lymphatics are carried by the connective tissue, and form capillary networks and lymphatic plexuses round the smaller bands. § 90. The arrangement of the nerves in unstriated muscle differs from that in striated muscle. Whereas in striated muscle me- dullated fibres coming direct from the anterior roots of spinal nerves predominate, in plain muscle^non-medullated fibres are most abundant ; in fact the nerves going to plain muscles are not only small but are almost exclusively composed of non-medullated fibres and come to the muscles from the so-called sympathetic system. Passing into the connective tissue between the bundles the nerves divide and, joining again, form a plexus around the bundles ; that is to say, a small twig consisting of a few, or perhaps only one axis-cylinder, coming from one branch will run alongside of or join a similar small twig coming from another branch; the indivi- dual axis-cylinders however do not themselves coalesce. From such primary plexuses, in which a few medullated fibres are present among the non-medullated fibres, are given off still finer, " inter- mediate " plexuses consisting exclusively of non-medullated fibres ; these embrace the smaller bundles of muscular fibres. The branches of these plexuses may consist of a single axis-cylinder, or may even be filaments corresponding to several or to a few only of the fibrillse of which an axis-cylinder is supposed to be composed. From these intermediate plexuses are given off single fibrillae or very small bundles of fibrillse, which running in the cement substance between the individual fibres form a fine net- work around the individual fibres, which network differs from the plexuses just spoken of inasmuch as some of the filaments com- posing it appear to coalesce. The ultimate ending of this network has not yet been conclusively traced ; but it seems probable that fibrils from the network terminate in small knobs or swellings lying on the substance of the muscular fibres, somewhat after the fashion of minute end-plates. A similar termination of nerves in a plexus or network is met with in other tissues, and is not confined to non-medullated fibres. A medullated fibre may end in a plexus, and when it does so loses first its medulla and subsequently its neurilemma, the plexus becoming ultimately like that formed by a non-medullated fibre and consisting of attenuated axis-cylinders with thickenings, and some- times with nuclei, at the nodal points. CHAP. IL] THE CONTRACTILE TISSUES. 159 § 91. As far as we know plain muscular tissue in its chemical features resembles striated muscular tissue. It contains albumin, some forms of globulin, and antecedents of myosin which upon the death of the fibres become myosin ; for plain muscular tissue after death becomes rigid, losing its extensibility and probably becoming acid, though the acidity is not so marked as in striated muscle. Kreatin has also been found, as well as glycogen, and indeed it seems probable that the whole metabolism of plain muscular tissue is fundamentally the same as that of the striated muscles. § 92. In their general physical features plain muscular fibres also resemble striated fibres, and like them they are irritable and contractile ; when stimulated they contract. The fibres vary in natural length in different situations, those of the blood vessels for instance being shorter and stouter than those of the intestine ; but in the same situation the fibres may also be found in one of two different conditions. In the one case the fibres are long and thin, in the other case they are reduced in length, it may be to one half or even to one third, and are correspondingly thicker, broader and less pointed at the ends, their total bulk remaining unaltered. In the former case they are relaxed or elongated, in the latter case they are contracted. The facts of the contraction of plain muscular tissue may be studied in the intestine, the muscular coat of which consists of an outer thin sheet composed of fibres and bundles of fibres disposed longitudinally and of an inner much thicker sheet of fibres disposed circularly ; in the ureter a similar arrangement of two coats obtains. If a mechanical or electrical (or indeed any other) stimulus be brought to bear on a part of a fresh living still warm intestine (the small intestine is the best to work with) a circular contraction is seen to take place at the spot stimulated ; the intestine seems nipped in ringwise, as if tied round with an invisible cord ; and the part so constricted, previously vascular and red, becomes pale and bloodless. The individual fibres of the circular coat in the region stimulated have each become shorter, and the total effect of the shortening of the multitude of fibres all having the same circular disposition is to constrict or narrow the lumen or tube of the in- testine. The longitudinally disposed fibres of the outer longitudinal coat will at the same time similarly contract or shorten in a longitudinal direction, but this coat being relatively much thinner than the circular coat, the longitudinal contraction is altogether overshadowed by the circular contraction. A similar mode of con- traction is also seen when the ureter is similarly stimulated. The contraction thus induced is preceded by a very long latent period and lasts a very considerable time, in fact several seconds, after which relaxation slowly takes place. We may say then that over the circularly dispersed fibres of the intestine (or ureter) at the spot in question there has passed a contraction- wave remarkable for its long latent period and for the slowness of its development, 160 CONTRACTION OF PLAIN MUSCLES. [BOOK i. the wave being propagated from fibre to fibre. From the spot so directly stimulated, the contraction may pass also as a wave (with a length of 1 cm. and a velocity of from 20 to 30 millimetres a second in the ureter), along the circular coat both upwards and downwards. The longitudinal fibres at the spot stimulated are as we have said also thrown into contractions of altogether similar character, and a wave of contraction may thus also travel longitudi- nally along the longitudinal coat both upwards and downwards. It is evident however that the wave of contraction of which we are now speaking is in one respect different from the wave of contrac- tion treated of in dealing with striated muscle. In the latter case the contraction-wave is a simple wave propagated along the in- dividual fibre and starting from the end-plate or, in the case of direct stimulation, from the part of the fibre first affected by the stimulus ; we have no evidence that the contraction of one fibre can communicate contraction to neighbouring fibres or indeed in any way influence neighbouring fibres. In the case of the intestine or ureter, the wave is complex, being the sum of the contraction- waves of several fibres engaged in different phases and is propagated from fibre to fibre, both in the -direction of the fibres, as when the whole circumference of the intestine is engaged in the contraction, or when the wave travels longitudinally along the longitudinal coat, and also in a direction at right angles to the axes of the fibres, as when the contraction-wave travels lengthways along the circular coat of the intestine, or when it passes across a breadth of the longitudinal coat ; that is to say, the changes leading to contraction are communicated not only in a direct manner across the cement substance uniting the fibres of a bundle but also in an indirect manner, probably by means of nerve fibres, from bundle to bundle across the connective tissue between them. Moreover, it is obvious that even the contraction-wave which passes along a single un- striated fibre differs from that passing along a striated fibre, in the very great length both of its latent period and of the duration of its contraction. Hence, much more even than in the case of a striated muscle, the whole of each fibre must be occupied by the contraction-wave, and indeed be in nearly the same phase of the contraction at the same time. Waves of contraction thus passing along the circular and longi- tudinal coats of the intestine constitute what is called peristaltic action. Like the contractions of striated muscle the contractions of plain muscles may be started by stimulation of nerves going to the part, the nerves supplying plain muscular tissue, running for the most part as we have said in the so-called sympathetic system, but being as we shall see ultimately connected with the spinal cord or brain. Here however we come upon an im- portant distinction between the striated skeletal muscles, and the plain muscles of the viscera. As a general rule the skeletal CHAP, ii.] THE CONTRACTILE TISSUES. 161 muscles are thrown into contraction only by nervous impulses reaching1 them along their nerves ; spontaneous movements of the skeletal muscles, that is contractions arising out of changes in the muscles themselves are extremely rare, and when they occur are abnormal; so-called 'cramps' for instance, which are prolonged tetanic contractions of skeletal muscles independent of the will, though their occurrence is largely due to the condition of the muscle itself, generally the result of overwork, are probably actually started by nervous impulses reaching them from without. On the other hand the plain muscles of the viscera, of the intestine, uterus and ureter, for instance, and of the blood vessels very fre- quently fall into contractions and so carry out movements of the organs to which they belong quite independently of the central nervous system. These organs exhibit 'spontaneous' movements quite apart from the will, quite apart from the central nervous system, and under favourable circumstances continue to do this for some time after they have been entirely isolated and removed from the body. So slight indeed is the connection between the move- ments of organs and parts supplied with plain muscular fibres, and the will, that these muscular fibres have sometimes been called in- voluntary muscles; but this name is undesirable since some muscles consisting entirely of plain muscular fibres (e.g. the ciliary muscles by which the eye is accommodated for viewing objects at different distances) are directly under the influence of the will, and, some muscles composed of striated fibres, (e.g. those of the heart) are wholly removed from the influence of the will. We shall best study however the facts relating to the move- ments of parts provided with plain muscular fibres when we come to consider the parts themselves. Like the skeletal muscles, whose nervous elements have been rendered functionally incapable (§ 78), plain muscles are much more sensitive to the making and breaking of a constant current than to induction-shocks ; a current, when very brief, like that of an induction-shock, produces little or no effect. The plain muscles seem to be remarkably susceptible to the influences of temperature. When exposed to low temperatures they readily lose the power of contracting ; thus the movements of the intestine are said to cease at a temperature below 19° C. Variations in temperature have also very marked effect on the duration and extent of the contractions. Associated probably with this susceptibility is the rapidity with which plain muscular fibres, even in cold-blooded vertebrates, lose their irritability after removal from the body and severance from their blood- supply. Thus while, as we have seen, the skeletal muscles of a frog can be experimented upon for many hours, (or even for two or three days) after removal from the body, and the skeletal muscles of a mammal for a much less but still considerable time, it is matter of very great difficulty to secure the continuance of movements of the F. 11 162 CILIARY MOVEMENT. [BOOK i. intestine or of other organs supplied with plain muscular fibres, even in the case of the frog, for any long period after removal from the body. The contraction of plain muscular fibres is as we said very slow in its development and very long in its duration, even when started by a momentary stimulus, such as a single induction-shock. The contraction after a stimulation often lasts so long as to raise the question, whether what has been produced is not a single contrac- tion but a tetanus. Tetanus, however, that is the fusion of a series of contractions seems to be of rare occurrence, though probably it may be induced, in plain muscular tissue ; but the ends of tetanus are gained by a kind of contraction which, rare or at least not prominent in skeletal muscle, becomes of great importance in plain muscular tissue, by a kind of contraction called a tonic contraction. The subject is one not without difficulties, but it would appear that a plain muscular fibre may remain for a very considerable time in a state of contraction, the amount of shortening thus maintained being either small or great : it is then said to be in a state of tonic contraction. This is especially seen in the case of the plain muscular tissue of the arteries, and we shall have to return to this matter in dealing with the circulation. The muscular tissue which enters into the construction of the heart is of a peculiar nature, being on the one hand striated, and on the other in some respects similar to plain muscular tissue, but this we shall consider in dealing with the heart itself. Ciliary Movement. § 93. Nearly all the movements of the body which are not due to physical causes, such as gravity, the diffusion of liquids &c., are carried out by muscles, either striated or plain ; but some small and yet important effects in the way of movement are produced by the action of cilia, and by those changes of protoplasm which are called amoeboid. Cilia are generally appendages %of epithelial cells. An epithelium consists of a number of cells, arranged in a layer, one, two or more cells deep, the cell bodies of the constituent cells being in contact with each other or united merely by a minimal amount of cement substance, not separated by an appreciable quantity of intercellular material. As a rule no connective tissue or blood vessel passes between the cells, but the layer of cells rests on a basis of vascular connective tissue, from which it is usually separated by a more or less definite basement membrane, and from the blood vessels of which its cells draw their nourishment. The cells vary in form, and the cell body round the nucleus may be protoplasmic in appearance or may be differentiated in various ways. An epithe- lium bearing cilia is called a ciliated epithelium. Various passages of the body, such as, in the mammal, parts of the nasal chambers CHAP, ii.] THE CONTRACTILE TISSUES. 163 and of the respiratory and generative passages, are lined with ciliated epithelium, and by the action of cilia, fluid containing various particles and generally more or less viscid is driven outwards along the passages towards the exterior of the body. A typical epithelium cell, such as may be found in the trachea, is generally somewhat wedge-shaped with its broad end circular or, rather, polygonal in outline, forming part of the free surface of the epithelium, and with its narrow end, which may be a blunt point or may be somewhat branched and irregular, plunged among smaller subjacent cells of the epithelium, or reaching to the con- nective tissue below. The cell body is, over the greater part of its extent, composed of protoplasm with the usual granular appearance. At about the lower third of the cell is placed, with its long axis vertical, an oval nucleus, having the ordinary characters of a nucleus. So far the ciliated cell resembles an ordinary epithelium cell ; but the free surface of the cell is formed by a layer of hyaline transparent somewhat refractive substance which when the cell is seen, as usual, in profile appears as a hyaline refractive band or border. From this border there project outward a variable number, 10 to 30, delicate tapering hair-like filaments, varying in length, but generally about a quarter or a third as long as the cell itself; these are the cilia. Immediately below this hyaline border the cell substance often exhibits more or less distinctly a longitudinal striation, fine lines passing down from the hyaline border towards the lower part of the cell substance round the nucleus. The hyaline border itself usually exhibits a striation as if it were split up into blocks, each block correspond- ing to one of the cilia, and careful examination leads to the conclusion that the hyaline border is really composed of the fused thicker basal parts of the cilia. The cell body has no distinct external membrane or envelope and its substance is in close contact with that of its neighbours, being united to them either by a thin layer of some cement substance, or by the simple cohesion of their respective surfaces. At all events the cells do cohere largely together, and it is difficult to obtain an isolated living cell, though the cells may be easily separated from each other when dead by the help of dis- sociating fluids. When a cell is obtained isolated in a living state, it is very frequently found to have lost its wedge shape and to have become more or less hemispherical or even spherical ; under the unusual conditions, and freed from the support of its neigh- bours, the cell body changes its form. The general characters just described are common to all ciliated epithelium cells, but the cells in different situations vary in certain particulars, such as the exact form of the cell body, the number and length of the cilia &c. § 94. Ciliary action, in the form in which it is most common 11—2 164 CILIARY MOVEMENT. [BOOK i. in mammals and indeed vertebrates, consists in the cilium (i.e. the tapering filament spoken of above) being at one moment straight or vertical, at the next moment being bent down suddenly into a hook or sickle form, and then more slowly returning to the straight erect position. When the cilia are vigorous, this double move- ment is repeated with very great rapidity, so rapidly that the individual movements cannot be seen ; it is only when, by reason of fatigue, the action becomes slow that the movement itself can be seen ; what is seen otherwise is simply the effect of the movement. The movements when slow have been counted at about eight (double movements) in a second ; probably when vigorous they are repeated from twelve to twenty times a second. The flexion takes place in one direction only, and all the cilia of each cell, and indeed of all the cells of the same epithelium move in the same direction. Moreover the same direction is maintained during the whole life of the epithelium ; thus the cilia of the epithelium of the trachea and bronchial passages move during the whole of life in such a way as to drive the fluid lying upon them upwards towards the mouth ; as far as we know in vertebrates, or at least in mammals, the direction is not and cannot by any means be reversed. The flexion is very rapid but the return to the erect position is much slower ; hence the total effect of the blow, supposing the cilium and the cell to be fixed, is to drive the thin, layer of fluid in which the cilium is working, and which always exists over the epithelium, and any particles which may be floating in that fluid in the same direction as that in which the blow is given. If the cell be not attached but floating free the effect of the blow may be to drive the cell itself backward; and when perfectly fresh ciliated epithelium is teased out and examined in an inert fluid such as normal saline solution, isolated cells or small groups of cells may be seen rowing themselves about as it were by the action of their cilia. All the cilia of a cell move, as we have just said, in the same direction, but not quite at the same time. If we call the side of the cell towards which the cilia bend the front of the cell and the opposite side the back, the cilia at the back move a trifle before those at the front so that the movement runs over the cell in the direction of the movement itself. Similarly, taking any one cell, the cilia of the cells behind it move slightly before, and the cilia of the cells in front of it slightly after, its own cilia move. Hence in this way along a whole stretch of epithelium the movement or bending of the cilia sweeps over the surface in ripples or waves, very much as, when the wind blows, similar waves of bending sweep over a field of corn or tall grass. By this arrangement the efficacy of the movement is secured, and a steady stream of fluid carrying particles is driven over the surface in a uniform continued direction ; if the cilia of separate cells, and still more if the CHAP, ii.] THE CONTRACTILE TISSUES. 165 separate cilia of each cell, moved independently of the others, all that would be produced would be a series of minute ' wobbles,' of as little use for driving the fluid definitely onwards as the efforts of a boat's crew all rowing out of time are for propelling the boat. Swift bending and slower straightening is the form of ciliary movement generally met with in the ciliated epithelium of mam- mals and indeed of vertebrates ; but among the invertebrates we find other kinds of movement, such as a to and fro movement, equally rapid in both directions, a cork-screw movement, a simple undulatory movement, and many others. In each case the kind of movement seems adapted to secure a special end. Thus even in the mammal while the one-sided blow of the cilia of the epithelial cells secures a flow of fluid over the epithelium, the tail of the spermatozoon, which is practically a single cilium, by moving to and fro in an undulatory fashion drives the head of the sperma- tozoon onwards in a straight line, like a boat driven by a single oar worked at the stern. Why and exactly how the cilium of the epithelial cells bends swiftly and straightens slowly, always acting in the same direction, is a problem difficult at present to answer fully. Some have thought that the body of the cell is contractile, or contains contractile mechanisms pulling upon the cilia, which are thus simple passive puppets in the hands of the cells. But there is no satisfactory evidence for such a view. On the whole the evidence is in favour of the view that the action is carried out by the cilium itself, that the bending is a contraction of the cilium, and that the straight- ening corresponds to the relaxation of a muscular fibre. But even then the exact manner in which the contraction bends and the relaxation straightens the filament is not fully explained. We have no positive evidence that a longitudinal half, the inside we might say, of the filament is contractile, and the other half, the outside, elastic, a supposition which has been made to explain the bending and straightening. In fact no adequate explanation of the matter has as yet been given, and it is really only on general grounds we conclude that the action is an effect of contractility. In the vertebrate animal, cilia are, as far as we know, wholly independent of the nervous system, and their movement is pro- bably ceaseless. In such animals however as Infusoria, Hydrozoa, &c. the movements in a ciliary tract may often be seen to stop and to go on again, to be now fast now slow, according to the needs of the economy, and, as it almost seems, according to the will of the creature ; indeed in some of these animals the ciliary move- ments are clearly under the influence of the nervous system. Observations with galvanic currents, constant and interrupted, have not led to any satisfactory results, and, as far as we know at present, ciliary action is most affected by changes of temperature and chemical media. Moderate heat quickens the movements, but a rise of temperature beyond a certain limit (about 40"C. in the case 166 AMCEBOID MOVEMENTS. [BOOK i. of the pharyngeal membrane of the frog) becomes injurious ; cold retards. Very dilute alkalis are favourable, acids are injurious. An excess of carbonic acid or an absence of oxygen diminishes or arrests the movements, either temporarily or permanently, according to the length of the exposure. Chloroform or ether in slight doses diminishes or suspends the action temporarily, in excess kills and disorganises the cells. Amoeboid Movements. § 95. The white blood corpuscles, as we have said (§ 28), are able of themselves to change their form and by repeated changes of form to move from place to place. Such movements of the substance of the corpuscles are called amoeboid, since they closely resemble and appear to be identical in nature with the movements executed by the amoeba and similar organisms. The movement of the endoplasm of the vegetable cell seems also to be of the same kind. The amoeba changes its form (and shifts its place) by throwing out projections of its substance, called pseudopodia, which may be blunt and short, broad bulgings as it were, or may be so long and thin as to be mere filaments, or may be of an intermediate character. As we watch the outline of the hyaline ectosarc we may see a pseudopodium beginning by a slight bulging of the outline ; the bulging increases by the neighbouring portions of the ectosarc moving into it, the movement under the microscope reminding one of the flowing of melted glass. As the pseudo- podium grows larger and engages the whole thickness of the ectosarc at the spot, the granules of the endosarc may be seen streaming into it forming a core of endosarc in the middle of the bulging of ectosarc. The pseudopodium may continue to grow larger and larger at the expense of the rest of the body, and eventually the whole of the amoeba including the nucleus may as it were have passed into the pseudopodium ; the body of the amoeba will now occupy the place of the pseudopodium instead of its old place ; in other words it will in changing its form have also changed its place. During all these movements, and during all similar amoeboid movements, the bulk of the organism will, as far as can be ascertained, have remained unchanged ; the throwing out a pseu- dopodium in one direction is accompanied by a corresponding retraction of the body in other directions. If as sometimes happens the organism throws out pseudopodia in various directions at the same time, the main body from which the pseudopodia project is reduced in thickness ; from being a spherical lump for instance it becomes a branched film. The movement is brought about not by increase or decrease of substance but by mere translocation of particles; a particle which at one moment was in one position CHAP, ii.] THE CONTRACTILE TISSUES. 167 moves into a new position, several particles thus moving towards the same point cause a bulging at that point, and several particles moving away from the same point cause a retraction at that point ; but no two particles get nearer to each other so as to occupy together less space and thus lead to condensation of sub- stance, or get farther from each other so as to occupy more space and thus lead to increase of bulk. In this respect, in that there is no change of bulk, but only a shifting of particles in their relative position to each other, the amoeboid movement resembles a muscular contraction ; but in other respects the two kinds of movement seem different, and the question arises, have we the right to speak of the substance which can only execute amoeboid movements as being contractile ? We may, if we admit that contractility is at bottom simply the power of shifting the relative position of particles, and that muscular contraction is a specialized form of contraction. In a plain muscular fibre (which we may take as simpler than the striated muscle) the shifting of particles is specialized in the sense that it has always a definite relation to the long axis of the fibre ; when the fibre contracts a certain number of particles assume a new position by moving at right angles to the long axis of the fibre, and the fibre in consequence becomes shorter and broader. In a white blood corpuscle, amoeba, or other organism executing amoeboid movements, the shifting of the particles is not limited to any axis of the body of the organism ; at the same moment one particle or one set of particles may be moving in one direction, and another particle or another set of particles in another direction. A pseudopodium, short and broad, or long thin and filamentous, may be thrust out from any part of the surface of the body and in any direction ; and a previously existing pseudopodium may be shortened, or be wholly drawn back into the substance of the body. In the plain muscle fibre the fact that the shifting is specialized in relation to the long axis of the fibre, necessitates that in a contraction the shortening, due to the particles moving at right angles to the long axis of the fibre, should be followed by what we have called relaxation due to the particles moving back to take up a position in the long axis ; and we have several times insisted on relaxation being an essential part of the total act of contraction. If no such movement in the direction of relaxation took place, the fibre would by repeated contractions be flattened out into a broad thin film at right angles to its original long axis, and would thus become useless. A spherical white blood corpuscle may, by repeated contractions, i. e. amoeboid movements, transform itself into such a broad thin film ; but in such a condition it is not useless. It may remain in that condition for some time, and by further contractions, i.e. amoeboid movements, may assume other shapes or revert to the spherical form. 168 AMCEBOID MOVEMENTS. [BOOK i. So long as we narrow our idea of contractility to what we see in a muscular fibre, and understand by contraction a movement of particles in relation to a definite axis, necessarily followed by a reversal of the movement in the form of relaxation, we shall find a difficulty in speaking of the substance of the amoeba or of the white blood corpuscle as being contractile. If however we conceive of contractility as being essentially the power of shifting the position of particles in any direction, without change of bulk (the shifting being due to intrinsic molecular changes about which we know little save that chemical decompositions are concerned in the matter), we may speak of the substance of the amoeba and white blood corpuscle as being contractile, and of muscular con- traction as being a specialized kind of contraction. The protoplasm of the amoeba or of a white corpuscle is, as we have said, of a consistency which we for want of better terms call semi-solid or semi-fluid. Consequently when no internal changes are prompting its particles to move in this or that direction, the influences of the surroundings will tend to give the body, as they will other fluid or semi-fluid drops, a spherical form. Hence the natural form of the white corpuscle is more or less spherical. If under the influence of some stimulus internal or external, some of the particles are stirred to shift their place, amoeboid move- ments follow, and the spherical form is lost. If however all the particles were stirred to move with equal energy, they would neutralize each other's action, no protrusion or retraction would take place at any point of the surface and the body would remain a sphere. Hence in extreme stimulation, in what in the muscle corresponds to complete tetanus, the form of the body is the same as in rest ; and the tetanized sphere would not be appreciably smaller than the sphere at rest, for that would imply change of bulk, but this as we have seen does not take place. This result shews strikingly the difference between the general contractility of the amoeba, and the special contractility of the muscle. CHAPTER III. ON THE MORE GENERAL FEATURES OF NERVOUS TISSUES. § 96. IN the preceding chapter we have dealt with the proper- ties of nerves going to muscles, the nerves which we called motor, and have incidentally spoken of other nerves which we called sensory. Both these kinds of nerves are connected with the brain and spinal cord and form part of the General Nervous System. We shall have to study hereafter in detail the brain and spinal cord ; but the nervous system intervenes so repeatedly in the processes carried out by other tissues that it will be desirable, before pro- ceeding further, to discuss some of its more general features. The Nervous System consists (1) of the Brain and Spinal Cord forming together the cerebrospinal axis or central nervous system, (2) of the nerves passing from that axis to nearly all parts of the body, those which are connected with the spinal cord being called spinal and those which are connected with the brain, within the cranium, being called cranial, and (3) of ganglia distributed along the nerves in various parts of the body. The spinal cord obviously consists of a number of segments or metameres, following in succession along its axis, each metamere giving off on each side a pair of spinal nerves ; and a similar division into metameres may be traced in the brain, though less distinctly, since the cranial nerves are arranged in manner some- what different from that of the spinal nerves. We may take a single spinal metamere, represented diagrammatically in Fig. 24, as illustrating the general features of the nervous system ; and since the half on one side of the median line resembles the half on the other side we may deal with one lateral half only. 170 A NEURAL METAMERE. [BOOK i. FIG. 24. SCHEME OF THE NERVES OF A SEGMENT OF THE SPINAL COED. Gr grey, W white matter of spinal cord. A anterior, P posterior root. G ganglion on the posterior root. N whole nerve, N' spinal nerve proper, ending in M skeletal or somatic muscle, S somatic sensory cell or surface, A' in other ways. V visceral nerve (white ramus communicans) passing to a ganglion of the sympathetic chain S, and passing on as V to supply the more distant ganglion f plain muscular tissue, promote the flow along the veins coming from that canal, and when we come to deal with the spleen we shall see that the plain muscular fibres which are so abundant in that organ in some animals, serve by rhythmical contractions to pump the blood regularly away from the spleen along the splenic veins. When we come to deal with respiration we shall see that each enlargement of the chest constituting an inspiration tends to draw the blood towards the chest, and each return or retraction of the chest walls in expiration tends to drive the blood away from the chest. The arrangement of the valves of the heart causes this action of the respiratory pump to promote the flow of blood in the direction of the normal circulation ; and indeed were the heart perfectly motionless the working of this respiratory pump alone would tend to drive the blood from the venae cava3 through the heart into the aorta, and so to keep up the circulation ; the force so exerted however would, without the aid of the heart, be able to overcome a very small part only of the resistance in the capillaries and small vessels of the lungs and so would prove actually ineffectual. There are then several helps to the flow along the veins, but it must be remembered that however useful, they are helps only and not the real cause of the circulation. The real cause of the flow is the ventricular stroke, and this is sufficient to drive the blood from the left ventricle to the right auricle, even when every muscle of the body is at rest and breathing is for a while stopped, when therefore all the helps we are speaking of are wanting. 220 THE RATE OF FLOW. [BOOK i. Circumstances determining the Rate of the Flow. § 122. We may now pass on to consider briefly the rate at which the blood flows through the vessels, and first the rate of flow in the arteries. When even a small artery is severed a considerable quantity of blood escapes from the proximal cut end in a very short space of time. That is to say, the blood moves in the arteries from the heart to the capillaries with a very considerable velocity. By various methods, this velocity of the blood-current has been measured at different parts of the arterial system ; the results, owing to imper- fections in the methods employed, cannot be regarded as satis- factorily exact, but may be accepted as approximately true. They shew that the velocity of the arterial stream is greatest in the largest arteries near the heart, and diminishes from the heart towards the capillaries. Thus in a large artery of a large animal, such as the carotid of a dog or horse, and probably in the carotid of a man, the blood flows at the rate of^OO or 500 mm. a second. In the very small arteries the rate is probably only a few mm. a second. Methods. The Hpemadromometer of Volkmann. An artery, e.g. a carotid, is clamped in two places, and divided between the clamps. Two cannulse, of a bore as nearly equal as possible to that of the artery, or of a known bore, are inserted in the two ends. The two cannulse are con- nected by means of two stopcocks, which work together, with the two ends of a long glass tube, bent in the shape of a U, and filled with normal saline solution, or with a coloured innocuous fluid. The clamps on the artery being released, a turn of the stopcocks permits the blood to enter the proximal end of the long U tube, along which it courses, driving the fluid out into the artery through the distal end. Attached to the tube is a graduated scale, by means of which the velocity with which the blood flows along the tube may be read off. Even supposing the cannulse to be of the same bore as the artery, it is evident that the conditions of the flow through the tube are such as will only admit of the result thus gained being considered as an approximative estimation of the real velocity in the artery itself. The Rheometer (Stromuhr) of Ludwig. This consists of two glass bulbs, A and £, Fig. 32, communicating above with each other and with the common tube C by which they can be filled. Their lower ends are fixed in the metal disc D, which can be made to rotate, through two right angles, round the lower disc E. In the upper disc are two holes, a and b, continuous with A and B respectively, and in the lower disc are two similar holes, a and b', similarly continuous with the tubes G and H. Hence, in the position of the discs shewn in the figure, the tube G is continuous through the two discs with the bulb A and the tube // with the bulb B. On turning the disc D through two right angles the tube G becomes continuous with B instead of A, and the tube H with A instead of B. There is a further arrangement, omitted from the figure for the CHAP, iv.] THE VASCULAR MECHANISM. •2-21 sake of simplicity, by which when the disc D is turned through one instead of two right angles from either of the above positions, G becomes directly continuous with H, both being completely shut off from the bulbs. FIG. 32. LUDWIG'S STROMUHK AND A DIAGRAMMATIC REPRESENTATION OF THE SAME. The ends of the tubes // and G are made to tit exactly into two cannulse inserted into the two cut ends of the artery about to be experi- mented upon, and having a bore as nearly equal as possible to that of the artery. The method of experimenting is as follows. The disc D, being placed in the intermediate position, so that a and b are both cut off from a' and b', the bulb A is filled with pure olive oil up to the mark x, and the bulb B, the rest of A, and the junction 0, with defibrinated blood; and (7 is then clamped. The tubes H and G are also filled with de- fibrinated blood, and G is inserted into the cannula of the central, H into that of the peripheral, end of the artery. On removing the clamps from the artery the blood flows through G to H, and so back into the artery. The observation now begins by turning the disc D into the position shewn in the figure ; the blood then flows into A, driving the oil there contained out before it into the bulb B, in the direction of the arrow, the detibrinated blood previously present in B passing by // into the artery, and so into the system. At the moment that the blood is seen to rise to the mark x, the disc D is with all possible rapidity turned through two right angles; and thus the bulb B, now largely filled with oil, placed in communication with G. The blood-stream now drives the oil back into A, and the new blood in A through H into the artery. As soon as the oil has wholly returned to its original position, the disc is again turned round, and A once more placed in communication with £, MEASUREMENT OF RATE OF FLOW. [BOOK i. and the oil once more driven from A to B. And this is repeated several times, indeed generally until the clotting of the blood or the admixture of the oil with the blood puts an end to the experiment. Thus the flow of blood is used to till alternately with blood or oil the space of the bulb A, whose cavity as far as the mark x has been exactly measured ; hence if the number of times in any given time the disc D has to be turned round be known, the number of times A has been filled is also known, and thus the quantity of blood which has passed in that time through the cannula connected with the tube G is directly measured. For instance, supposing that the quantity held by the bulb A when filled up to the mark x is 5 c.c., and supposing that from the moment of allowing the first 5 c.c. of blood to begin to enter the tube to the moment when the escape of the last 5 c.c. from the artery into the tube was complete, 100 seconds had elapsed, during which time 5 c.c. had been received 10 times into the tube from the artery (all but the last 5 c.c. being returned into the distal portion of the artery), obviously -5 c.c. of blood had flowed from the proximal section of the artery in one second. Hence supposing that the diameter of the cannula (and of the artery, they being the same) were 2 mm., with a sectional area therefore of 3-14 square mm., an outflow through the section of '5 c.c. or 500 c.mm. in a second would give (|-JT), a velocity of about 159 mm. in a second. The Hfematachometer of Vierordt is constructed on the principle of measuring the velocity of the current by observing the amount of devia- tion undergone by a pendulum, the free end of which hangs loosely in the stream. A square or rectangular chamber, one side of which is of glass and marked with a graduated scale in the form of an arc of a circle, is connected by means of two short tubes with the two cut ends of an artery ; the blood consequently flows from the proximal (central) portion of the artery through the chamber into the distal portion of the artery. Within the chamber and suspended from its roof is a short pendulum, which when the blood-stream is cut off from the chamber hangs motionless in a vertical position, but when the blood is allowed to flow through the chamber, is driven by the force of the current out of its position of rest. The pendulum is so placed that a marker attached to its free end travels close to the inner surface of the glass side along the arc of the graduated side. Hence the amount of deviation from a vertical position may easily be read off on the scale from the outside. The graduation of the scale having been carried out by experimenting with streams of known velocity, the velocity can at once be calculated from the amount of deviation. An instrument based on the same principle has been invented by Chauveau and improved by Lortet, Fig. 33. In this the part which cor- responds to the pendulum in Vierordt's instrument is prolonged outside the chamber, and thus the portion within the chamber is made to form the short arm of a lever, the fulcrum of which is at the point where the wall of the chamber is traversed and the long arm of which projects out- side. A somewhat wide tube, the wall of which is at one point composed of an indiarubber membrane, is introduced between the two cut ends of an artery. A long light lever pierces the indiarubber membrane. The short expanded arm of this lever projecting within the tube is moved on its fulcrum in the indiarubber ring by the current of blood passing through the tube, the greater the velocity of the current, the larger being CHAP, iv.] THE VASCULAR MECHANISM. 223 the excursion of the lever. The movements of the short arm give rise to corresponding movements in the opposite direction of the long arm outside the tube, and these, by means of a marker attached to the end FlG. 33. H^EMATACHOMETER OF ClIAUVEAU AND LoETET. of the long arm, may be directly inscribed on a recording surface. This instrument is very well adapted for observing changes in the velocity of the flow. In determining actual velocities, for which purpose it has to be experimentally graduated, it is not so useful. In the capillaries, the rate is slowest of all. In the web of the frog the flow as judged by the movement of the red corpuscles may be directly measured under the microscope by means of a micro- meter, and is found to be about half a millimetre in a second ; but this is probably a low estimate, since it is only when the circulation is somewhat slow, slower perhaps than what ought to be considered the normal rate, that the red corpuscles can be distinctly seen. In the mammal the rate has been estimated at about '75 millimetres a second but is probably quicker even than this. As regards the veins, the flow is very slow in the small veins emerging from the capillaries but increases as these join into larger trunks, until in a large vein, such as the jugular of the dog, the rate is about 200 mm. a second. § 123. It will be seen then that the velocity of the flow is in inverse proportion to the width of the bed, to the united sectional areas of the vessels. It is greatest at the aorta, it diminishes along the arterial system to the capillaries, to the united bases of the cones spoken of in § 112, where it is least, and from thence increases again along the venous system. And indeed it is this width of the bed and this alone which 224 THE RATE OF FLOW. [BOOK i. determines the general velocity of the flow at various parts of the system. The slowness of the flow in the capillaries is not due to there being so much more friction in their narrow channels than in the wider canals of the larger arteries. For the peripheral resist- ance caused by the friction in the capillaries and small arteries is an obstacle not only to the flow of blood through these small vessels where the resistance is actually generated, but also to the escape of the blood from the large into the small arteries, and indeed from the heart into the large arteries. It exerts its influence along the whole arterial tract. ^And it is obvious that if it were this peripheral resistance which checked the flow in the capillaries, there could be no recovery of velocity along the venous tract. The blood is flowing through a closed system of tubes, the blood vessels, under the influence of one propelling force, the systole of the ventricle, for this is the force which drives the blood from ventricle to auricle, though as we have seen its action is modified in the several parts of the system. In such a system the same quantity of fluid must pass each section of the system at the same time, otherwise there would be a block at one place, and a deficiency at another. If, for instance, a fluid is made to flow by some one force, pressure or gravity, through a tube A (Fig. 34) with an enlargement B, it is obvious that the same quantity of fluid must pass through the section b as passes through the section a in the same time, for instance a second. Otherwise, if less passes through b than a, the fluid would accumu- late in B, or if more, B would be emptied. In the same way just as much must pass in the same time through the section c as passes through a or b. But if just as many particles of water have to get through the narrow section a in the same time as they have to get through the broader section c, they must move quicker through a than through c, or more slowly through c than through a. For the same reason water flowing along a river impelled by one force, viz. that of gravity, rushes rapidly through a ' narrow ' and flows sluggishly when the river widens out into a ' broad.' The flow through B will be similarly slackened if B instead of being simply a single enlargement of the tube A consists of a number of small tubes branching out from A, with a united sectional area greater than the sectional area of A. In each of such small tubes, at the line c for instance, the flow will be slower than at a, where the small tubes branch out from A, or at b, where they join again to form a single tube. Hence it is that the blood rushes swiftly through the arteries, tarries slowly through the capillaries, but quickens its pace again in the veins. An apparent contradiction to this principle that the rate of a FIG. 34. CHAP, iv.] THE VASCULAR MECHANISM. 225 flow is dependent on the width of the bed is seen in the case where, the fluid having alternative routes, one of the routes is temporarily widened. Suppose a tube A dividing into two branches of equal length x and y which unite again to form the tube V. Suppose, to start with, that x and y are of equal diameter; then the resistance offered by each being equal, the flow will be equally rapid through the two, being just so rapid that as much fluid passes in a given time through x and y together as passes through A or through V. But now suppose y to be widened ; the widening will diminish the resistance offered by y, and in consequence, supposing that no material change takes place in the pressure or force which is driving the fluid along, more fluid will now pass along y in a given time than did before, that is to say the rapidity of the flow in y will be increased. It will be increased at the expense of the flow through x, since it will still hold good that the flow through x and y together is equal to the flow through A and through V. We shall have occasion later on to point out that a small artery, or a set of small arteries, may be more or less suddenly widened, without materially affecting the general blood-pressure which is driving the blood through the artery or set of arteries. In such cases the flow of blood through the widened artery or arteries is for the time being increased in rapidity, not only in spite of but actually in consequence of the artery being widened. It must be understood in fact that this dependence of the rapidity of the flow on the width of the bed applies to the general rate of flow of the whole circulation, and that, besides the above instance, other special and temporary variations occur due to par- ticular circumstances. Thus changes of pressure may alter the rapidity of flow. The cause of the flow through the whole system is the pressure of the ventricular systole manifested as what we have called blood-pressure. At each point along the system nearer the left ventricle, and therefore further from the right auricle, the pressure is greater than at a point further from the left ventricle and so nearer the right auricle ; it is this difference of pressure which is the real cause of the flow from the one point to the other; and other things being equal the rapidity of the flow will depend on the amount of the difference of pressure. Hence temporary or local variations in rapidity of flow may be caused by the establishment of temporary or local differences of pressure. For example at any point along the arterial system the flow is in- creased in rapidity during the temporary increase of pressure due to the ventricular systole, i.e. the pulse, and diminished during the subsequent temporary decrease, the increase and decrease being the more marked the nearer the point to the heart. And we shall probably meet later on with other instances. § 124. Time of the entire circuit. It is obvious from the fore- going that a red corpuscle in performing the whole circuit, in F. 15 226 TIME OF THE ENTIRE CIRCUIT. [BOOK i. travelling from the left ventricle back to the left ventricle, would spend a large portion of its time in the capillaries, minute arteries and veins. The entire time taken up in the whole circuit has been approximately estimated by measuring the time it takes for an easily recognized chemical substance after injection into the jugular vein of one side to appear in the blood of the jugular vein of the other side. While small quantities of blood are being drawn at frequently repeated intervals from the jugular vein of one side, or while the blood from the vein is being allowed to fall in a minute stream on an absor- bent paper covering some travelling surface, an iron salt such as potas- sium ferrocyanide (or preferably sodium ferrocyanide as being more innocuous) is injected into the jugular vein of the other side. If the time of the injection be noted, and the time after the injection into one side at which evidence of the presence of the iron salt can be detected in the sample of blood from the vein of the other side be noted, this gives the time it has taken the salt to perform the circuit ; and on the supposition that mere diffusion does not materially affect the result, the time which it takes the blood to perform the same circuit is thereby given. In the horse this time has been experimentally determined at about 30 sees, and in the dog at about 15 sees. In man it is probably from 20 to 25 sees. Taking the rate of flow through the capillaries at about 1 mm. a sec. it would take a corpuscle as long a time to get through about 20 mm. of capillaries as to perform the whole circuit. Hence, if any corpuscle had in its circuit to pass through 10 mm. of capillaries, half the whole time of its journey would be spent in the narrow channels of the capillaries. Inasmuch as the purposes served by the blood are chiefly carried out in the capillaries, it is obviously of advantage that its stay in them should be prolonged. Since, however, the average length of a capillary is about '5 mm., about half a second is spent in the capillaries of the tissues and another half second in the capillaries of the lungs. § 125. We may now briefly summarise the broad features of the circulation, which we have seen may be explained on purely physical principles, it being assumed that the ventricle delivers a certain quantity of blood with a certain force into the aorta at regular intervals, and that the physical properties of the blood vessels remain the same. We have seen that owing to the peripheral resistance offered by the capillaries and small vessels the direct effect of the ventricular stroke is to establish in the arteries a mean arterial pressure which is greatest at the root of the aorta and diminishes towards the small arteries, some of it being used up to drive the blood from the aorta to the small arteries, but which retains at the region of the small arteries sufficient power to drive through the CHAP, iv.] THE VASCULAR MECHANISM. 227 small arteries, capillaries and veins just as much blood as is being thrown into the aorta by the ventricular stroke. We have seen further that in the large arteries at each stroke the pressure rises and falls a little above and below the mean, thus constituting the pulse, but that this extra distension with its subsequent recoil diminishes along the arterial tract and finally vanishes ; it dimin- ishes and vanishes because it too, like the whole force of the ventricular stroke, of a fraction of which it is the expression, is used up in establishing the mean pressure ; we shall however consider again later on the special features of this pulse. We have seen further that the task of driving the blood through the peripheral resistance of the small arteries and capillaries consumes much of this mean pressure, which consequently is much less in the small veins than in the corresponding small arteries, but that sufficient remains to drive the blood, even without the help of the auxiliary agents which are generally in action, from the small veins right back to the auricle. Lastly we have seen that while the above is the cause of the flow from ventricle to auricle, the changing rate of the flow, the diminishing swiftness in the arteries, the sluggish crawl through the capillaries, the increasing quickness through the veins are determined by the changing width of the vascular 'bed.' Before we proceed to consider any further details as to the phenomena of the flow through the vessels, we must turn aside to study the heart. 15—2 SEC. 3. THE HEART. § 126. The heart is a valvular pump which works on me- chanical principles, but the motive power of which is supplied by the contraction of its muscular fibres. Its action consequently presents problems which are partly mechanical, and partly vital. Regarded as a pump, its effects are determined by the frequency of the beats, by the force of each beat, by the character of each beat — whether, for instance, slow and lingering, or sudden and sharp — and by the quantity of fluid ejected at each beat. Hence, with a given frequency, force, and character of beat, and a given quantity ejected at each beat, the problems which have to be dealt with are for the most part mechanical. The vital problems are chiefly con- nected with the causes which determine the frequency, force, and character of the beat. The quantity ejected at each beat is governed more by the state of the rest of the body, than by that of the heart itself. The Phenomena of the Normal Beat. The visible movements. When the chest of a mammal is opened and artificial respiration kept up the heart may be watched beating. Owing to the removal of the chest-wall, what is seen is not absolutely identical with what takes place within the intact chest, but the main events are the same in both cases. A complete beat of the whole heart, or cardiac cycle, may be observed to take place as follows. The great veins, inferior and superior venae cavas and pulmonary veins, are seen, while full of blood, to contract in the neighbourhood of the heart : the contraction runs in a peristaltic wave towards the auricles, increasing in intensity as it goes. Arrived at the auricles, which are then full of blood, the wave suddenly spreads, at a rate too rapid to be fairly judged by the eye, over the whole of those CHAP, iv.] THE VASCULAR MECHANISM. 229 organs, which accordingly contract with a sudden sharp systole. In the systole, the walls of the auricles press towards the auriculo- ventricular orifices, and the auricular appendages are drawn inwards, becoming smaller and paler. During the auricular systole, the ven- tricles may be seen to become turgid. Then follows, as it were immediately, the ventricular systole, during which the ventricles become more conical. Held between the fingers they are felt to become tense and hard. As the systole progresses, the aorta and pulmonary arteries expand and elongate, the apex is tilted slightly upwards, and the heart twists somewhat on its long axis, moving from the left and behind towards the front and right so that more of the left ventricle becomes displayed. As the systole gives way to the succeeding diastole, the ventricles resume their previous form and position, the aorta and pulmonary artery shrink and shorten, the heart turns back towards the left, and thus the cycle is completed. In the normal beat, the two ventricles are perfectly synchronous in action, they contract at the same time and relax at the same time, and the two auricles are similarly synchronous in action. It has been maintained however that the synchronism may at times not be perfect. Before we attempt to study in detail the several parts of this complicated series of events, it will be convenient to take a rapid survey of what is taking place within the heart during such a cycle. § 127. The cardiac cycle. We may take as the end of the cycle the moment at which the ventricles having emptied their contents have relaxed and returned to the diastolic or resting posi- tion and form. At this moment the blood is flowing freely with a fair rapidity but as we have seen at a very low pressure through the venae cavce into the right auricle (we may confine ourselves at first to the right side), and since there is now nothing to keep the tricuspid valve shut, some of this blood probably finds its way into the ventricle also. This goes on for some little time, and then comes the sharp short systole of the auricle, which, since it begins as we have seen as a wave of contraction running for- wards along the ends of the venaa cavse, drives the blood not back- wards into the veins but forwards into the ventricle ; this end is further secured by the fact that the systole has behind it on the venous side the pressure of the blood in the veins, increasing as we have seen backwards towards the capillaries, and before it the. relatively empty cavity of the ventricle in which the pressure is at first very low. By the complete contraction of the auricular walls the complete or nearly complete emptying of the cavity is ensured. No valves are present in the mouth of the superior vena cava, for they are not needed ; and the imperfect Eustachian valve at the mouth of the inferior vena cava cannot be of any great use in the adult, though in its more developed state in 230 THE CARDIAC CYCLE. [BOOK i. the foetus it had an important function in directing the blood of the inferior vena cava through the foramen ovale into the left auricle. The valves in the coronary vein are however probably of some use in preventing a reflux into that vessel. As the blood is being driven by the auricular systole into the ventricle, a reflux current is probably set up, by which the blood, passing along the sides of the ventricle, gets between them and the flaps of the tricuspid valve and so tends to float these up. It is further probable that the same reflux current, continuing somewhat later than the flow into the ventricle, is sufficient to bring the flaps into apposition, without any regurgitation into the auricle, at the close of the auricular systole, before the ventri- cular systole has begun. According to some authors however the closure of the valve is effected, at the very beginning of the ven- tricular systole, by the contraction of the papillary muscles ; the chordte tendinege of a papillary muscle are attached to the adjacent edges of two flaps, so that the shortening of the muscle tends to bring these edges into apposition. The auricular systole is as we have said immediately followed by that of the ventricle. Whether the contraction of the ven- tricular walls (which as we shall see is a simple though prolonged contraction and not a tetanus) begins at one point and swiftly travels over the rest of the fibres, or begins all over the ventricle at once, is a question not at present definitely settled ; but in any case the walls exert on the contents a pressure which is soon brought to bear on the whole contents and very rapidly rises to a maximum. The only effect of this increasing intra- ventricular pressure upon the valve is to render the valve more and more tense, and in consequence more secure, the chordae tendineae (the slackening of which through the change of form of the ventricle is probably obviated by a regulative contraction of the papillary muscles) at the same time preventing the valve from being inverted or even bulging largely into the auricle, and indeed, according to some observers, keeping the valvular sheet actually convex to the ventricular cavity, by which means the complete emptying of the ventricle is more fully effected. The connection, to which we have just referred, of the chordae of the same papillary muscle with the adjacent edges of two flaps, also assists in keeping the flaps in more complete apposition. Moreover the extreme borders of the valves, outside the attachments of the chorda?, are exces- sively thin, so that when the valve is closed, these thin portions are pressed flat together back to back ; hence while the tougher central parts of the valves bear the force of the ventricular systole, the opposed thin membranous edges, pressed together by the blood, ti lore completely secure the closure of the orifice. At the commencement of the ventricular systole the semilunar valves of the pulmonary artery are closed, and are kept closed by the high pressure of the blood in the arterv. As however the CHAP, iv.] THE VASCULAR MECHANISM. 231 ventricle continues to press with greater and greater force on its contents, making the ventricle hard and tense to the touch, the pressure within the ventricle becomes greater than that in the pulmonary artery and this greater pressure forces open the semi- lunar valves and allows the escape of the contents into the artery. The ventricular systole may be seen and felt in the exposed heart to be of some duration, it is strong enough and long enough to empty the ventricle completely ; indeed, as we shall see, it probably lasts longer than the discharge of blood, so that there is a brief period during which the ventricle is empty but yet contracted. During the ventricular systole the semilunar valves are pressed outwards towards but not close to the arterial walls, reflux currents probably keeping them in an intermediate position, so that their orifice forms an equilateral triangle with curved sides ; they thus offer little obstacle to the escape of blood from the cavity of the ventricle. The ventricle as we have seen propels the blood with great force and rapidity into the pulmonary artery and the whole contents are speedily ejected. Now, when a force which is driving a fluid with great rapidity along a closed channel suddenly ceases to act, the fluid, by its momentum, continues to move onward after the force has ceased ; in consequence of this a negative pressure makes its appearance in the rear of the fluid, and, sucking the fluid back again, sets up a reflux current. So when the last portions of blood leave the ventricle a negative pressure makes its appearance behind them, and leads to a reflux current from the artery towards the ventricle. This alone would be sufficient to bring the valves together; and, in the opinion of some, is the real cause of the closure of the valves ; others however, as we shall see later on, maintain that subsequent to this reflux due to mere negative pressure a somewhat later reflux, in which the elastic reaction of the arterial walls is concerned, more completely fills and renders tense the pockets, causing their free margins to come into close and firm contact, and thus entirely blocks the way. The corpora Arantii meet in the centre, and the thin membranous festoons or lunulce are brought into exact apposition. As in the tricuspid valves, so here, while the pressure of the blood is borne by the tougher bodies of the several valves, each two thin adjacent lunulse, pressed together by the blood acting on both sides of them, are kept in complete contact, without any strain being put upon them ; in this way the orifice is closed in a most efficient manner. There is no adequate foundation for the view put forward by Briicke that during the ventricular systole the flaps are pressed back flat against the arterial walls, and in the case of the aorta completely cover up the orifices of the coronary arteries, so that the flow of blood from the aorta into the coronary arteries can take place only during the ventricular diastole or at the very beginning of the systole, and not at all during the systole itself. 232 THE CHANGE OF FORM OF THE HEART. [BOOK i. The ventricular systole now passes off, the muscular walls relax, the ventricle returns to its previous form and position, and the cycle is once more ended. What thus takes place in the right side takes place in the left side also. There is the same sudden sharp auricular systole beginning at the roots of the pulmonary veins, the same systole of the ventricle but, as we shall see, one much more powerful and exerting much more force ; the mitral valve with its two flaps acts exactly like the tricuspid valve, and the action of the semi- lunar valves of the aorta simply repeats that of the valves of the pulmonary artery. We may now proceed to study some of the cardiac events in detail. § 128. The change of form. The exact determination of the changes in form and position of the heart, especially of the ven- tricles, during a cardiac cycle is attended with difficulties. The ventricles for instance are continually changing their form ; they change while their cavities are being filled from the auricles, they change while the contraction of their walls is getting up the pressure on their contents, they change while under the influence of that pressure their contents are being discharged into the arteries, and they change when, their cavities having been emptied, their muscular walls relax. We may take it for granted that the internal cavities are obliterated by the systole, for it is probable that practically the whole contents are driven out at each stroke, and probably also each cavity is emptied from its apex towards the mouth of the artery. With regard to changes in external form, there seems no doubt that-khe side-to-side diameter is much lessened. It seems also clear that the front-to-back diameter is greater during the whole time of the systole than during the diastole, the increase taking- place during the first part of the systole. If a light lever be placed on the surface of the heart of a mammal, the chest having been opened and artificial respiration being kept up, some such curve as that represented in Fig. 35 is obtained. The rise of the lever in describing such a curve is due to the elevation of the part of the front surface of the heart on which the lever is resting. Such an elevation might be caused, especially if the lever were placed near the apex, by the heart being " tilted " upwards during the systole, but only a small portion at most of the rise can be attributed to this cause ; the rise is perhaps best seen when the lever is placed in the middle portion of the ven- tricle, and must be chiefly due to an increase in the front-to-back diameter of the ventricle during the beat. We shall discuss this curve later on in connection with other curves and may here simply say that the part of the curve from b' to d probably corre- sponds to the actual systole of the ventricle, that is to the time CHAP, iv.] THE VASCULAR MECHANISM. 233 during which the fibres of the ventricle are undergoing contrac- tion, the sudden fall from d onwards representing the relaxation a\ b\b\ c\ c\ d\ WVWWlMWWMWWWWwtf^^ FIG. 35 J. TRACING FROM HEART OF CAT, OBTAINED BY PLACING A LIGHT LEVER ON THE VENTRICLE, THE CHEST HAVING BEEN OPENED. THE TUNING-FORK CURVE MARKS 50 VIBRATIONS PER SEC. which forms the first part of the diastole. If this interpretation of the curve be correct, it is obvious that the front-to-back diameter is greater during the whole of the systole than it is during diastole, since the lever is raised up all this time. This increase of the front-to-back diameter combined with a decrease of the side-to-side diameter has for a result a change in the form of the section of the base of the ventricles. During the diastole this has somewhat the form of an ellipse with the 1 The vertical or rather curved lines (segments of circles) introduced into this and many other curves are of use for the purpose of measuring parts of the curve. A complete curve should exhibit an ' abscissa ' line. This may be drawn by allowing the lever, arranged for the experiment but remaining at rest, to mark with its point on the recording surface set in motion ; a straight line, the abscissa line, is thus described, and may be drawn before or after the curve itself is made, and may be placed above or preferably below the curve. When a tuning-fork or other time marker is used, the line of the time marker or a line drawn through the curves of the tuning-fork will serve as an abscissa line. After a tracing has been made, the recording surface should be brought back to such a position that the point of the lever coincides with some point of the curve which it is desired to mark ; if the lever be then gently moved up and down, the point of the lever will describe a segment of a circle (the centre of which lies at the axis of the lever), which segment should be made long enough to cut both the curve and the abscissa line (the tuning-fork curves or other time marking line) where this is drawn. By moving the recording surface backwards and forwards similar segments of circles may be drawn through other points of the curve. The lines a, b, c in Fig. 35 were thus drawn. The distance between any two of these points may thus be measured on the tuning-fork curve or other time curve, or on the abscissa line. Similar lines may be drawn on the tracing after its removal from the recording instrument in the following way. Take a pair of compasses, the two points of which are fixed just as far apart as the length of the lever used in the experiment, measured from its axis to its writing point. By means of the compasses find the position on the tracing of the centre of the circle of which any one of the previously drawn curved lines forms a segment. Through this centre draw a line parallel to the abscissa. By keeping one point of the compass on this line but moving it along the line backwards or forwards a segment of a circle may be drawn so as to cut any point of the curve that may be desired, and also the abscissa line or the time line. Such a segment of a circle may be used for the same purposes as the original one and any number of such segments may be drawn. 234 THE CARDIAC IMPULSE. [BOOK i. long axis from side to side, but with the front part of the ellipse much more convex than the back, since the back surface of the ventricles is somewhat flattened. During the systole this ellipse is by the shortening of the side- to-side diameter and the increase of the front-to-back diameter converted into a figure much more nearly resembling a circle. It is urged moreover that the whole of the base is constricted and that the greater efficiency of the auriculo-ventricular valves is thereby secured. As to the behaviour of the long diameter from base to apex observers are not agreed. Some maintain that it is shortened, and others that it is practically unchanged. If any shortening does take place it must be largely compensated by the elon- gation of the great vessels, which, as stated above, may be seen in an inspection of the beating heart. For there is evidence that the apex, though as we have seen it is during the systole somewhat twisted round, and at the same time brought closer to the chest-wall, does not change its position up or down, i.e. in the long axis of the body. If in a rabbit or dog a needle be thrust through the chest-wall so that its point plunges into the apex of the heart, though the needle quivers, its head moves neither up nor down as it would do if its point in the apex moved down or up. Broadly speaking then during systole the ventricles undergo a diminution of total volume, equal to the volume of contents discharged into the great vessels (for the walls themselves like all muscular structures retain their volume during contraction save for changes which may take place in the quantity of blood contained in their blood vessels, or of lymph in the intermuscular spaces), while they undergo a change of form which may be described as that from a roughly hemispherical figure with an irregularly elliptical section to a more regular cone with a circular base. § 129. Cardiac Impulse. If the hand be placed on the chest, a shock or impulse will be felt at each beat, and on examination this impulse, 'cardiac impulse,' will be found to be synchronous with the systole of the ventricle. In man, the cardiac impulse may be most distinctly felt in the fifth costal interspace, about an inch below and a little to the median side of the left nipple. In an animal the same impulse may also be felt in another way, viz. by making an incision through the diaphragm from the abdo- men, and placing the finger between the chest-wall and the apex. It then can be distinctly recognized as the result of the hardening of the ventricle during the systole. And the impulse which is felt on the outside of the chest is chiefly the effect of the same hardening of the stationary portion of the ventricle in contact with the chest-wall, transmitted through the chest- wall to the finger. In its flaccid state, during diastole, the apex is (in a standing position at least) at this point in contact CHAP, iv.] THE VASCULAR MECHANISM. 235 with the chest-wall, lying between it and the tolerably resistant diaphragm. During the systole, while being brought even closer to the chest- wall, by the tilting of the ventricle and by the move- ment to the front and to the right of which we have already spoken, it suddenly grows tense and hard. The ventricles, in executing their systole, have to contract against resistance. They have to produce within their cavities, pressures greater than those in the aorta and pulmonary arteries, respectively. This is, in fact, the object of the systole. Hence, during the swift systole, the ventricular portion of the heart becomes suddenly tense, somewhat in the same way as a bladder full of fluid would become tense and hard when forcibly squeezed. The sudden pres- sure exerted by the ventricle thus become suddenly tense and hard, aided by the closer contact of the apex with the chest-wall (which however by itself without the hardening of contraction would be insufficient to produce the effect), gives an impulse or shock both to the chest-wall and to the diaphragm, which may be felt readily both on the chest-wall, and also through the diaphragm when the abdomen is opened and the finger inserted. If the modification of the sphygmograph (of which we shall speak in dealing, later on, with the pulse), called the cardiograph, be placed on the spot where the impulse is felt most strongly, the lever is seen to be raised during the systole of the ventricles, and to fall again as the systole passes away, very much as if it were placed on the heart directly. A tracing may thus be ob- tained, see Fig. 41, of which we shall have to speak more fully immediately, see § 133. If the button of the lever be placed, not on the exact spot of the impulse, but at a little distance from it, the lever will be depressed during the systole. While at the spot of impulse itself the contact of the ventricle is increased during systole, away from the spot the ventricle retires from the chest-wall (by the diminution of its right-to-left dia- meter), and hence, by the rnediastinal attachments of the peri- cardium, draws the chest- wall after it. § 130. The Sounds of the Heart. When the ear is applied to the chest, either directly or by means of a stethoscope, two sounds are heard, the first a comparatively long dull booming sound, the second a short sharp sudden one. Between the first and second sounds, the interval of time is very short, too short to be measurable, but between the second and the succeeding first sound there is a distinct pause. The sounds have been likened to the pronunciation of the syllables lubb diip, so that the cardiac cycle, as far as the sounds are concerned, might be represented by : — lubb^ dup, jgause. The second sound which is short and sharp presents no difficul- ties.-^Itis coincident in point of time with the closure of the semilunar valves, and is heard to the best advantage over the second right costal cartilage close to its junction with the sternum, 236 THE SOUNDS OF THE HEART. [BOOK i i.e. at the point where the aortic arch comes nearest to the surface, and to which sounds generated at the aortic orifice would be best conducted. Its characters are such as would belong to a sound generated by membranes like the semilunar valves being sud- denly made tense and so thrown into vibrations. It is obscured and altered, or replaced by ' a murmur,' when the semilunar valves are affected by disease, and may be artificially obliterated, a murmur taking its place, by passing a wire down the arteries and hooking up the aortic valves. There can be no doubt in fact that the second sound is due to the semilunar valves being thrown into vibrations at their sudden closure. The sound heard at the second right costal cartilage is chiefly that generated by the aortic valves, and murmurs or other alterations in the sound caused by changes in the aortic valves are heard most clearly at this spot. But even here the sound is not exclusively of aortic origin, for in certain cases in which the semilunar valves on the two sides of the heart are not wholly synchronous in action, the sound heard here is double (" reduplicated second sound "), one being due to the aorta, and one to the pulmonary artery. When the sound is listened to on the left side of the sternum at the same level, the pulmonary artery is supposed to have the chief share in producing what is heard, and changes in the sound heard more clearly here than on the right side are taken as indications of mischief in the pulmonary valves. The first sound, longer, duller, and of a more 'booming' character than the second, heard with greatest distinctness at the spot where the cardiac impulse is felt, presents many difficulties in the way of a complete explanation. ' It is heard distinctly when the chest-walls are removed. The cardiac impulse therefore can have little or nothing to do with it. In point of time it is coincident with the systole of the ventricles, and may be heard to the greatest advantage at the spot of the cardiac impulse, that is to say, at the place where the ventricles come nearest to the surface, and to which sounds generated in the ventricle would be best conducted. It is more closely coincident with the closure and consequent vibrations of the auriculo- ventricular valves than with the entire systole ; for on the one hand it dies away before the second sound begins, whereas, as we shall see, the actual systole lasts up to if not beyond the closure of the semilunar valves, and on the other hand the auriculo-ventricular valves cease to be tense and to vibrate as soon as the contents of the ventricle are driven out. This suggests that the sound is caused by the sudden tension of the auriculo-ventricular valves, and this view is sup- ported by the facts that the sound is obscured, altered or replaced by murmurs when the tricuspid or mitral valves are diseased, and that the sound is also altered or, according to some observers, wholly done away with when blood is prevented CHAP. iv.J THE VASCULAR MECHANISM. 237 from entering the ventricles by ligature of the venae cavse. On the other hand the sound has not that sharp character which one would expect in a sound generated by the vibration of membranes such as the valves in question, but in its booming qualities rather suggests a muscular sound. Further, accord- ing to some observers, the sound, though somewhat modified, may still be heard when the large veins are clamped so that no blood enters the ventricle, and indeed may be recognized in the few beats given by a mammalian ventricle rapidly cut out of the living body by an incision carried below the auriculo-ventricular ring. Hence the view has been adopted that this first sound is s muscular sound. In discussing the muscular sound of skeletal muscle (see § 80), we saw reasons to distrust the view that this sound was generated by the repeated individual simple contractions which made up the tetanus and hence corresponded in tone to the number of those simple con tractions repeated in a second, and to adopt the view that the sound was really due to a repetition of unequal tensions occurring in a muscle during the contraction. Now the ventricular systole is undoubtedly a simple contraction, a prolonged simple contraction, not a tetanus, and therefore under the old view of the nature of a muscular sound, could not produce such a sound ; but accepting the other view and reflecting how complex must be the course of the systolic wave of contraction over the twisted fibres of the ventricle we shall not find great difficulty in supposing that that wave is capable in its progress of producing such repetitions of unequal tensions as might give rise to a ' muscular sound,' and consequently in regarding the first sound as mainly so caused. Accepting such a view of the origin of the sound we should expect to find the tension of the muscular fibres and so the nature of sound dependent on the quantity of fluid present in the ventricular cavities and hence modified by ligature of the great veins, and still more by the total removal of the auricles with the auriculo-ventricular valves. We may add that we should expect to find it modified by the escape of blood from the ven- tricles into the arteries during the systole itself, and might regard this as explaining why it dies away before the ventricle has ceased to contract. Moreover seeing that the auriculo-ventricular valves must be thrown into sudden tension at the onset of the ventricular systole, which as we have seen is developed with considerable rapidity, not far removed at all events from the rapidity with which the semilunar valves are closed, a rapidity therefore capable of giving rise to vibrations of the valves adequate to produce a sound, it is difficult to escape the conclusion that the closure of these valves must also generate a sound, which in a normally beating heart is mingled in some way with the sound of muscular origin, although the ear cannot detect the mixture. If we accept this view that the sound is of double origin, 238 ENDOOARDIAC PRESSURE. [BOOK i. partly ' muscular,' partly ' valvular,' both causes being dependent on the tension of the ventricular cavities, AVC can perhaps more easily understand how it is that the normal first sound is at times so largely, indeed we may say so completely, altered and obscured in diseases of the aiiriculo-ventricular valves. Since the left ventricle forms the entire left apex of the heart, the murmurs or other changes of the first sound heard most distinctly at the spot of cardiac impulse belong to the mitral valve of the left ventricle. Murmurs generated in the tricuspid valve of the right ventricle are heard more distinctly in the median line below the end of the sternum. Endocardiac Pressure. § 131. Since the heart exists for the purpose of exerting pres- sure on the blood within its cavities, by which pressure the circu- lation of the blood is effected, the study of the characters of this endocardiac pressure possesses great interest. Unfortunately the observation of this pressure is attended with great difficulties. The ordinary mercury manometer which is so useful in studying the pressure in the arteries fails us when applied to the heart. It is true that a long cannula, or tube open at the end, filled with sodium carbonate solution, may be introduced into the jugular vein and so slipped down into either the right auricle or the right ventricle, or may be similarly introduced into the carotid artery and with care slipped down through the aorta, past the semilunar valves, into the left ventricle, and having been thus introduced may, like the ordinary cannula used in studying arterial pressure (§ 115), be brought into connection with a mercury manometer. In this way, as in the case of an artery, a graphic record may be obtained of the changes of pressure taking place in either of the above three cavities. But the changes in the ventricular cavities are so great and rapid, that the inertia of the mercury, an evil even in the case of an artery, comes so largely into play that the curve described by the float on the mercury is far from being an accurate record of the changes of pressure in the cavity. The mercury manometer may however be made to yield valuable results by adopting the ingenious contrivance of con- verting the ordinary manometer into a maximum or a minimum instrument. The principle of the maximum manometer, Fig. 36, consists in the introduction into the tube leading from the heart to the mercury column, of a (modified cup-ancl-ball) valve, opening, like the aortic semilunar valves, easily from the heart, but closing firmly when fluid attempts to return to the heart. The highest pressure is that which drives the longest column of fluid past the valve, raising the mercury CHAP, iv.] THE VASCULAR MECHANISM. 239 column to a corresponding height. Since this column, once past the valve, cannot return, the mercury remains at the height to which it was raised by it and thus records the maximum pressure. By reversing the direction of the valve, the manometer is converted from a maximum into a minimum instrument. FIG. 36. THE MAXIMUM MANOMETER OF GOLTZ AND GAULE. At e a connection is made with the tube leading to the heart. When the screw clanip k is closed, the valve v conies into action, and the instrument, in the position of the valve shewn in the figure, is a maximum manometer. By reversing the direction of v it is converted into a minimum manometer. When k is opened, the variations of pressure are conveyed along a, and the instrument then acts like an ordinary manometer. The maximum manometer applied to the cavity of either ventricle or of the right auricle, gives a record of the highest pressure reached within that cavity, and the minimum manometer similarly applied shews the lowest pressure reached, during the time that the instrument is applied. The maximum manometer thus employed shews that the maximum pressure in the left ventricle is distinctly greater than the mean pressure in the aorta (the ordinary mercury manometer having previously given the paradoxical result, due to the inertia of the mercury, that the mean pressure in the left ventricle might be less than in the aorta), that the maximum pressure in the right ventricle is less than in the left, and in the right auricle is still less. In the dog for example the pressure in the left ventricle reaches a maximum of about 140 mm. (mercury), in the right ventricle of about 60 ram. and in the right auricle of about 20 mm. But the chief interest attaches to the minimum pressure observed ; for the minimum manometer records a negative pressure 240 ENDOCARDIAC PRESSURE. [BOOK i. in the cavities of the heart, i.e. shews that the pressure in them may fall below that of the atmosphere. Thus in the left ventricle (of the dog) a minimum pressure varying from — 52 to — 20 mm. may be reached, the minimum of the right ventricle being from — 17 to — 16 mm., and of the right auricle from — 12 to — 7 mm.1 Part of this diminution of pressure in the cardiac cavities may be due, as will be explained in a later part of this work, to the aspiration of the thorax in the respiratory movements. But even when the thorax is opened, and artificial respiration kept up, under which circumstances no such aspiration takes place, a negative pressure is still observed, the pressure in the left ventricle still sinking as low as — 24 mm. Now, what the instrument actually shews is that at some time or other during the number of beats which took place while the instrument was applied (and these may have been very few) the pressure in the ventricle sank so many mm. below that of the atmosphere. Since the negative pressure is observed when the heart is beating quite regularly, each beat being exactly like the others, we may infer that a negative pressure occurs at some period or other of each cardiac cycle. But the instrument obviously gives us no information as to the exact phase of the beat in which the negative pressure occurs ; to this point as well as to the import- ance of this negative pressure we shall return presently. § 132. The difficulties due to the inertia of the mercury may be obviated by adopting the method of Chauveau and Marey which consists in introducing, in a large animal such as a horse, through a blood vessel into a cavity of the heart, a tube ending in an elastic bag, Fig. 37 A, fashioned something like a sound, both tube and bag being filled with air, and the tube being connected with a recording ' tambour.' A tube of appropriate curvature, A. b. Fig. 37, is furnished at its end with an elastic bag or ' ampulla ' a. When it is desired to explore simultaneously both auricle and ventricle, the sound is furnished with two ampulhe with two small elastic bags, one at the extreme end and the other at such a distance that when the former is within the cavity of the ventricle the latter is in the cavity of the auricle. Such an instrument is spoken of as a ' cardiac sound.' Each ' ampulla ' com- municates by a separate air-tight tube with an air-tight tambour (Fig. 37 B) on which a lever rests, so that any pressure on the ampulla is communicated to the cavity of its respective tambour, the lever of which is raised in proportion. When two ampulla? are used the writing points of both levers are brought to bear on the same re- cording surface exactly underneath each other. The tube is carefully introduced through the right jugular vein into the right side of the heart until the lower (ventricular) ampulla is fairly in the cavity of the right ventricle, and consequently the upper (auricular) ampulla in the cavity of the right auricle. Changes of pressure on either 1 These numbers are to be considered merely as instances which have been observed, and not as averages drawn from a large number of cases. CHAP, iv.] THE VASCULAR MECHANISM. 241 ampulla then cause movements of the corresponding lever. When the pressure, for instance, on the ampulla in the auricle is increased, the auricular lever is raised and describes on the recording surface an A FIG. 37. MAEET'S TAMBOUR, WITH CAEDIAC SOUND. A. A simple cardiac sound such as may be used for exploration of the left ventricle. The portion a of the ampulla at the end is of thin indiarubber, stretched over an open framework with metallic supports above and below. The long tube /* serves to introduce it into the cavity which it is desired to explore. B. The Tambour. The metal chamber 7/1 is covered in an air-tight manner with the indiarubber c, bearing a thin metal plate m' to which is attached the lever I moving on the hinge h. The whole tambour can be placed by means of the clamp cl at any height on the upright s'. The indiarubber tube t serves to connect the interior of the tambour either with the cavity of the ampulla of A or with any other cavity. Supposing that the tube t were connected with b, any pressure exerted on a would cause the roof of the tambour to rise and the point of the lever would be pro- portionately raised. ascending curve ; when the pressure is taken off the curve descends ; and so also with the ventricle. The 'sound' may in a similar manner be readily introduced through the carotid artery into the left ventricle and the changes taking place in that chamber also explored. When this instrument is applied to the right auricle and ventricle some such record is obtained as that shewn in Fig. 38 where the upper curve is a tracing taken from the right auricle, and the lower curve from the right ventricle of the horse, both curves being taken simultaneously on the same recording surface. In these curves the rise of the lever indicates pressure exerted F. 16 242 ENDOCARDIAC PRESSURE. [BOOK i. upon the corresponding ampulla, and the upper curve, from the right auricle, shews the sudden brief pressure b exerted by the sudden and brief auricular systole. The lower curve, from the right ventricle, shews that the pressure exerted by the ventricular systole begins almost immediately after the auricular systole, increases very rapidly indeed, so that the lever rises in almost a straight line up to c', is continued for some considerable time, and then falls very rapidly to reach the base line. But it may be doubted whether the instru- ment can be trusted to tell much more than this. The pressure recorded by each lever is the pressure exerted on the ampulla and this may continue to be exerted after all blood has been dis- charged from the cavity, the walls of the emptied cavity closing round and press- ing on the ampulla. But as we shall presently see, it is of great interest to determine, not only the force and dura- tion of the exerted , , VENTRICLE, OF THE HORSE, ventricular systole, but also whether ( AFTER CHAUVEAU AND MARET.) or no the fibres continue contracted and exerting pressure for an appreciable time after the blood has been forced out of the cavity. The figure moreover, it need hardly be said, does not, by itself, give any in- formation as to the relative amounts of pressure exerted by the auricle and ventricle respectively. In the curve the auricular lever rises about half as high as the ventricular lever ; but we must not infer from this that the auricular stroke is half as strong as the ventricular stroke ; the former is arranged so as to move much more readily, to be much more sensitive than the latter. The instrument it is true may be experimentally graduated, and may then be used to determine the actual amount of pressure ; but for this purpose is not wholly satisfactory. We may add that the irregularities seen on the ventricular curve during the ven- tricular systole and on the auricular curve at the same time have given rise to much debate and need not be discussed here. On the whole the method, though useful for giving a graphic view of the series of events within the cardiac cavities during a cardiac cycle, the short auricular pressure, the long continued ventricular pressure, lasting nearly half the whole period, and the subsequent pause when both parts are at rest or in diastole, cannot with safety be used for drawing more detailed conclusions. Perhaps the least untrustworthy method of recording the changes of endo-cardiac pressure is that recently introduced by Roy and Rolleston, though difficulties present themselves in the interpretation of the curves obtained by it. CHAP, iv.] THE VASCULAR MECHANISM. 243 By means of a short cannula introduced through a large vessel, or directly, as a trocar, through the walls of the ventricle (or auricle), the blood in the cavity is brought to bear on an easily moving piston. The movements of the piston are recorded by a lever, and the evils of inertia are met by making the piston and lever work against the torsion of a steel ribbon, the length of which, and consequently the resistance offered by which, and hence the excursions of the piston can be varied at pleasure. The curves obtained by this method vary according to circum- stances. We may take as fair examples two curves from the left ventricle, one (Fig. 39 A) of a rapidly beating, and the other (Fig. 39 B) of a slowly beating heart. a. t> b' a.' FIG. 39. CORVES OF ENDOCABDIAC PRESSURE. FROM LEFT VENTRICLE OF DOG. A. a quickly beating, B. a more slowly beating heart. The letters in this, and the succeeding Figs. 40, 41 are explained in the text. § 133. In attempting to interpret these curves with the view of learning the changes of pressure taking place in the heart, it is desirable to study them in connection with the tracing of which we have already spoken, Fig. 40, taken by means of a light lever placed on the exposed ventricle and which as we have seen is a curve of the changes taking place in the front-to-back diameter 16—2 244 EKDOCARDIAC PRESSURE. [BOOK i. of the ventricle ; or we may use what is very nearly the same thing, viz. a cardiographic tracing (Fig. 41), that is to say a tracing of the cardiac impulse, which is a curve of changes in the pressure exerted by the apex of the heart on the chest- wall. et\ b\b\ c\ c'\ WWWmWMMMMfi/W^ FIG. 40. (See Fig. 35.) Various forms of cardiograph have been used to record the cardiac impulse. In some the pressure of the impulse, as in the sphygmograph, is transmitted directly to a lever which writes upon a travelling surface. In others the impulse is, by means of an ivory button, brought to bear on an air-chamber, connected by a tube with a tambour as in Fig. 37 ; the pressure of the cardiac impulse compresses the air in the air- chamber, and through this the air in the chamber of the tambour by which the lever is raised. In such delicate and complicated movements, as those of the heart however, the use of long tubes filled with air is liable to introduce various errors. We may begin our study of these curves at any point in the cycle ; let it be the point b' in Fig. 39. From this point the curve rises very abruptly, almost in the vertical line, to a maximum at c ; and the same sudden large rise to a maximum occurs in the front-to- back diameter of the ventricles (Fig. 40) and in the pressure of the apex against the chest- wall (Fig. 41). There can be no doubt that FIG. 41. CARDIOGRAM FROJI MAN. this corresponds to the first part of the systole of the ventricles. By the sudden onset of the contraction of the ventricular fibres pressure is brought to bear on the contents of the ventricle, and there being as yet no escape for the blood, by the increasing contraction of the CHAP, iv.] THE VASCULAR MECHANISM. 245 fibres, the pressure becomes greater and greater. At the point c a change takes place in all three curves, the rise is converted into a fall, which however is very gradual as far as d. In the case of the front-to-back diameter curve (Fig. 40) we may interpret this as meaning that while the continued contraction of the muscular fibres still maintains that change in the form of the ventricle by> which the front-to-back diameter is increased, that same diameter is somewhat lessened by a diminution of the volume of the ventricles due to the escape of blood into the great arteries, and the cardio- graphic tracing admits of a similar interpretation, the apex relaxes its pressure on the chest-wall. We may extend the same inter- pretation to the pressure curve (Fig. 39). Somewhere about c the pressure in the (left) ventricle has become higher than the pressure in the aorta, and in consequence blood escapes from the former into the latter. Whether the exact moment of the opening of the valves is absolutely identical with the turn of the curve at c, the curve beginning to fall at the moment when the area of high pressure in the ventricle is made con- tinuous with the area of lower pressure in the aorta, or whether it occurs a little before c, the still increasing contraction of the ventricular fibres still increasing the pressure on the column of blood as it begins to move from the cavity of the ventricle into the aorta, may be left for the present undecided. The sudden fall from d to a admits of only one interpretation and that in all the curves ; this can only be due to the sudden relaxation of the muscular fibres of the ventricle, whereby the front-to-back diameter suddenly diminishes, the apex suddenly ceases to press on the chest-wall, and the pressure which the ventricular walls were previously exerting on the fluid in the cannula introduced into its cavity also suddenly ceases. From b' to d then the ventricular walls are still contracting ; during the whole of this time the real systole is being continued, but gives place at c? to a rapid relaxation which ushers in or forms the first part of the sequent diastole. Some little time after the beginning of this systole, somewhere about c, as we have seen, blood begins to escape from the ventricle into the aorta ; this escape is certainly completed by the time d is reached and we have reason to think that it is really completed some little time before. The entrance into the aorta of the column of blood ejected by the ventricle distends that vessel, and the distension passes on, as we have seen, along the arterial track as the pulse. If now we measure the time during which the aorta, even near the heart, is being distended by the injection of the ventricular contents, we find this to be appreciably less than the time from c to d, during which the systole of the ventricle is still going on, though the contents have already begun to escape at about c. This means that the ventricle, though empty, remains contracted for some little time after its contents have left the cavity. It is possible 246 ENDOCARDIAC PRESSURE. [Boon i. that the point c in the three figures under discussion, where the descent of the lever changes in rate, becoming less rapid, corre- sponds to the end of the outflow from the ventricle ; but this is not certain, and indeed the exact interpretation of this part of the curve is especially difficult. The escape from the ventricle is rapid and forcible ; the flow ceases suddenly. Hence, as we have already stated § 12% owing to the column of blood tending to move on by virtue of its inertia after the propelling force has ceased to act, a negative pressure makes its appearance behind the column of blood dis- charged from the ventricle, and as soon as the column is lodged in the aorta leads to a reflux towards the ventricle. This reflux would of itself have the effect of closing the valves even were the aorta a rigid tube. But the aorta is extensible and elastic and the effects of the movement of the column of fluid are combined with the effects of the movement of the arterial walls : the elastic action of the arterial walls, in a manner which we shall discuss later on in dealing with the pulse, also leads to a reflux. It has been urged that the reflux due to the negative pressure of the mere movement of the column of blood being more rapid, occurs independently of and earlier than the reflux due to the elastic recoil, the former closing the valves, the latter securing their com- plete closure. Be this so or no the valves are probably closed almost immediately after the escape of the ventricular contents, though observers are not agreed on this point, some urging that the valves are not closed until so late a period as the point d, just as relaxation is about to begin. In the curves we are now con- sidering, a notch, followed by a rise, or at least a more or less abrupt change in the course of the curve at c', is some- times observed in that part of the curve which intervenes between the first large rise and the final sudden fall ; and this secondary rise has been taken to indicate the closure of the semilunar valves. Sometimes two such notches and peaks are seen, and the occurrence of the two has been attributed to a want of synchronism in the closure of the pulmonary and aortic semilunar valves, the latter closing some little time before the former. But it is by no means clear that these notches and peaks are thus due to the closure of the valves ; they may possibly have another origin, they are not always present, and indeed it does not seem certain that the closing of the valves should neces- sarily make an impress on the ventricular curve. § 134. In the performance of the ventricle then (and what has been said of the left ventricle applies also to the right ventricle) there appear to be four stages : 1. A rapid "getting up" of pressure within the ventricle, all the valves being as yet closed ; this continues until the pressure within the ventricle, becoming greater than that in the aorta, throws open the aortic valves. CHAP, iv.] THE VASCULAR MECHANISM. 247 2. The escape of the contents of the ventricle into the aorta, the contractions of the ventricular walls still continuing. 3. Further maintenance of the contraction for some little time after the main body, at all events, of the contents have passed the aortic valves ; by this the complete emptying of the ventricle seems assured. 4. Sudden and rapid relaxation of the ventricular walls. These four events together make up a large portion, and in a quickly beating heart the greater portion, of the whole cardiac cycle. Meanwhile, that is during the time from b' to a, blood has been flowing from the great veins into the auricle ; during the interval from b' to d none of this can pass into the ventricle since this is still contracted, but with the commencement of relaxation from d onwards there is no longer any obstacle, on the contrary, as we shall see an inducement for the blood to pass from the auricle into the ventricle. For a brief time, as we have seen, there is probably an unbroken flow from the great veins (pulmonary or vense cavae) through the auricle into the ventricle, leading to a steady but slight increase of the front-to-back diameter, to a slight pressure of the apex on the chest- wall, and to a slight increase of intraventricular pressure, especially shewn in the curve of the slowly beating heart of the horse (Fig. 38). In Fig. 40, the sudden rise due to the ventricular systole is preceded by a rise b followed by a fall, forming thus, as it were, a shoulder on the curve. This has been interpreted as indicating the sharp transient auricular systole ; the sudden in- jection of the auricular contents into the ventricle increases the front-to-back diameter of the ventricle, and the momentum of the rapid stroke being considerable, the lever is in each case carried too far forward, so that the rise is followed by a fall, producing a notch. A similar though somewhat different shoulder is also seen in the cardiogram Fig. 41. In the curve of ventri- cular pressure taken by means of the cardiac sound (Fig. 38) there is a similar temporary increase 6' in the ventricular pressure coin- cident with the auricular stroke b, and in the "piston" pressure curve of the rapidly beating heart (Fig. 39 A) there is a similar shoulder b just preceding the rise of the ventricular systole. The meaning of the last curve is however doubtful, for in the similar curve of the more slowly beating heart (Fig. 39 B) it occurs immediately after the relaxation of the ventricle, some time before the occurrence of the auricular systole, and in many curves taken by the same method is absent altogether. The exact mean- ing therefore of the shoulder b in the other curves must be left at present undecided. § 135. We have still to consider the negative pressure shewn by the minimum manometer. This instrument, as we have said, 248 NEGATIVE PRESSURE IN VENTRICLES. [BOOK i. merely shews that the pressure in the ventricle (or auricle) becomes negative at some phase or other of the cardiac cycle, but does not tell us in which phase it occurs. Now there are two ways in which such a negative pressure might originate. In the first place, as we have just seen, a negative pressure makes its appearance in the rear of the column of blood driven from the ventricle into the aorta with great suddenness and rapidity. But this negative pressure, as we have also seen, follows the column into the aorta past the semilunar valves, and in part at all events determines the closure of the semilunar valves. Hence if this is the negative pressure which the minimum manometer records, it ought to be shewn not only when the end of the tube connected with the manometer is in the cavity of the ventricle, but also when the tube is slipped out of the ventricle just past the semilunar valves. When the tube however is in the latter situation the manometer does not shew the same marked negative pressure that it does when the tube is in the ventricle ; the negative pressure which occurs in the aorta at each beat is insufficient to produce such an effect on the minimum manometer as is produced when the instrument is in the ventricle. Hence we infer that the negative pressure shewn by the minimum manometer is not produced in this way. We may moreover conclude that the semilunar valves are closed before this negative pressure makes its appearance in the ven- tricle ; otherwise, however produced, it would be transmitted from the interior of the ventricle through the open valves to the root of the aorta beyond. But there is another event which might give rise to a negative pressure. The relaxation of the ventricular walls is, as the curves (Figs. 39, 40, 41) shew, a rapid process, something quite distinct from the mere filling of the ventricular cavities with blood from the auricles ; and, though some have objected to the view, it may be urged that this return of the ventricle from its contracted (and emptied) condition to its normal form would develope a nega- tive pressure. This return is probably simply the total result of the return of each fibre or fibre cell to its natural conditional! ough some have urged that the extra quantity of blood thrown into the coronary arteries at the systole helps to unfold the ventricles some- what in the way that fluid driven between the two walls of a double-walled collapsed ball or cup will unfold it. Accepting the return of the ventricles to their normal form as the cause of the negative pressure (and it may be remarked that the return of the thick-walled left ventricle naturally exerts a greater negative pressure than the thin- walled right ventricle), it is obvious that the negative pressure will assist the circulation by sucking the blood which has meanwhile been accumulated in the auricle from that cavity into the ventricle, the auriculo-ven- CHAP, iv.] THE VASCULAR MECHANISM. 249 tricular valves easily giving way. At the same time this very flow from the auricle will at once put an end to the negative pressure, which obviously can be of brief duration only. It may further be urged, in support of this view, that even when the thorax is opened, so that the respiratory movements can no longer act towards producing a negative pressure in the auricle and great veins (§ 131), a minimum manometer placed in the right auricle shews frequently no pressure at all (that is a pressure equal to that of the atmosphere) and sometimes a decidedly negative pressure. Seeing that the blood under these circum- stances is being driven along the great veins by a pressure which though low is always above that of the atmosphere, we may conclude that the negative pressure produced in the ventricle is the cause of this lowering of the pressure in the auricle, though it is unable to make itself felt along the great veins. § 136. The duration of the several phases. We may first of all distinguish certain main phases: (1) The systole of the auricles. (2) The systole, proper, of the ventricles, during which their fibres are in a state of contraction, lasting to d in Figs. 39, 40, 41. (3) The diastole of the ventricles, that is to say the time intervening between their fibres ceasing to contract, and commencing to contract again. To these we may perhaps add (4) The pause or rest of the whole heart, comprising the period from the end of the relaxation of the ventricles to the beginning of the systole of the auricles ; during this time the walls are undergoing no active changes, neither contracting nor relaxing, their cavities being simply passively filled by the influx of blood. The mere inspection of almost any series of cardiac curves however taken, those for instance which we have just discussed, will shew, apart from any accurate measurements, that the systole of_the auricles is always very brief, that the systole of the ven- tricles is always very prolonged, always occupying a considerable portion of the whole cycle, and that the diastole of the whole heart, reckoned from the end either of the systole, or of the relaxation of the ventricle, is very various, being in quickly beating hearts very short and in slowly beating hearts decidedly longer. When we desire to arrive at more complete measurements, we are obliged to make use of calculations based on various data ; and these give only approximate results. Naturally the most interest is attached to the duration of events in the human heart. The datum which perhaps has been most largely used is the"/-] interval between the beginning of the first and the occurrence of the second sound. This may be determined with approximative correctness, and is found to vary from '301 to '327 sec., occupying from 40 to 46 p. c. of the whole period^and being fairly constant for different rates of heart-beat. That is to say in a rapidly beating heart it is the pauses which are shortened and not the duration of the actual beats. 250 DURATION OF CARDIAC PHASES. [BOOK i. The observer, listening to the sounds of the heart, makes a signal at each event on a recording surface, the difference in time between the marks being measured by means of the vibrations of a tuning-fork recorded on the same surface. By practice it is found possible to reduce the errors of observation within very small limits. Now whatever be the exact causation of the first sound, it is undoubtedly coincident with the systole of the ventricles, though possibly the actual commencement of its becoming audible may be slightly behind the actual beginning of the muscular contractions. Similarly the occurrence of the second sound, which, as we have seen, is certainly due to the closure of the semilunar valves, has been taken to mark the close of the ventricular systole. And on this supposition the interval between the beginning of the first and the occurrence of the second sound has been regarded as indicating approximative^ the duration of the ventricular systole, i.e. the period during which the ventricular fibres are con- tracting. We have however urged above that the ventricles still remain contracted for a brief period after the valves are shut ; if this view be correct then the second sound does not mark the end of the systole, and the duration of the systole is rather longer than the time given above. The determination of the separate duration of each of the three periods of the ventricular systole, viz. the getting up the pressure, the discharge of the contents, and the remaining emptied but contracted, is subject to so much uncertainty that it need not be insisted on here ; it may however be said that, roughly speaking, each phase occupies probably about '1 sec. In a heart beating 72 times a minute, which may be taken as the normal rate, each entire cardiac cycle would last about 0'8 sec., and taking Oj3 sec. as the duration of the ventricular systole, the deduction of this would leave O'o sec. for the whole diastole of the ventricle including its relaxation, the latter occupying about or somewhat less than '1 sec. In the latter part of this period there occurs the systole of the auricles, the exact duration of which it is difficult to determine, it being hard to say when it really begins, but which, if the contraction of the great veins be included, may perhaps be taken as lasting on an average 01 sec. The ' passive interval ' therefore, during which neither auricle nor ventricle are undergoing contractions, lasts about -4 sec. and the absolute pause or rest during which neither auricle nor ventricle are contracting or relaxing about '3 sec. ; if however a longer period be allotted to the ventricular sj^stole, these periods must be proportionately shortened. The systole of the ventricle follows so immediately upon that of the auricles, that practically no interval exists between the two events. The duration of the several phases may for convenience sake be arranged in a tabular form as follows ; but in reading the table CHAP, iv.] THE VASCULAR MECHANISM. 251 the foregoing remarks as to the approximate or even uncertain character of some of the data must be borne in mind. sees. sees. Systole of ventricle before the open- ing of the semilunar valves, while pressure is still getting up (probably rather less than) '1 Escape of blood into aorta (about) '1 Continued contraction of the emptied ventricle (possibly rather more than) '1 „ Total systole of the ventricle (probably rather more than) Diastole of both auricle and ventricle, neither contracting, or " passive in- terval " (probably rather less than) '4 i Systole of auricle (about or less than) '1 J Diastole of ventricle, including relaxa- tion and filling, up to the beginning of the ventricular systole (probably rather less than) Total Cardiac Cycle •3 Summary. § 137. We may now briefly recapitulate the main facts con- nected with the passage of blood through the heart. The right auricle during its diastole, by the relaxation of its muscular fibres, and by the fact that all backward pressure from the ventricle is removed by the closing of the tricuspid valves, offers but little re- sistance to the ingress of blood from the veins. On the other hand, the blood in the trunks of both the superior and inferior vena cava is under a pressure, which though diminishing towards the heart remains higher than the pressure obtaining in the interior of the auricle ; the blood in consequence flows into the empty auricle, its progress in the case of the superior vena cava being assisted by gra- vity. At each inspiration this flow (as we shall see in speaking of respiration) is favoured by the diminution of pressure in the heart and great vessels caused by the respiratory movements. Before this flow has gone on very long, the diastole of the ventricle begins, its cavity dilates, the flaps of the tricuspid valve fall back, and blood for some little time flows in an unbroken stream from the vena3 cavse into the ventricle. In a short time, however, probably before very much blood has had time to enter the ventricle, the auricle is full ; and forthwith its sharp sudden systole takes place. Partly by reason of the backward pressure in the veins, which increases 252 SUMMARY OF CARDIAC EVENTS. [BOOK i. rapidly from the heart towards the capillaries, and which, at some distance from the heart is assisted by the presence of valves in the venous trunks, but still more from the fact that the systole begins at the great veins themselves and spreads thence over the auricle, the force of the auricular contraction is spent in driving the blood, not back into the veins, but into the ventricle, where the pressure is still exceedingly low. Whether there is any backward flow at all into the great veins or whether by the progressive character of the systole the flow of blood continues, so to speak, to follow up the systole without break so that the stream from the veins into the auricle is really continuous, is at present doubtful ; "though a slight positive wave of pressure synchronous with the auricular systole, travelling backward along the great veins, has been observed at least in cases where the heart is beating vigorously. The ventricle thus being filled by the auricular systole, the play of the tricuspid valves described above comes into action, the auricular systole is followed by that of the ventricle, and the pressure within the ventricle, cut off from the auricle by the tricuspid valves, is brought to bear on the pulmonary semilunar valves and the column of blood on the other side of those valves. As soon as by the rapidly increasing shortening of the ventricular fibres the pressure within the ventricle becomes greater than that in the pulmonary artery, the semilunar valves open and the still continuing systole discharges the contents of the ventricle into that vessel. As the ventricle thus rapidly and forcibly empties itself, either the transient negative pressure which makes its appear- ance in the rear of the ejected column of blood or the elastic action of the aortic walls leads to a reflux of blood towards the ventricle, the effect of which however is to close the semi- lunar valves, and thus to shut off the blood in the distended arteries from the emptied ventricle. Either immediately at or more probably some little time after this closing of the valves, the ventricular systole ends and relaxation begins ; then once more the cavity of the ventricle becomes unfolded and finally distended by the influx of blood, a negative pressure developed by the relaxation probably aiding the flow from the auricle and great veins. During the whole of this time the left side has with still greater energy been executing the same manoeuvre. At the same time that the venae cavse are filling the right auricle, the pulmonary veins are filling the left auricle. At the same time that the right auricle is contracting, the left auricle is contracting too. The systole of the left ventricle is synchronous with that of the right ventricle, but executed with greater force ; and the flow of blood is guided on the left side by the mitral and aortic valves in the same way that it is on the right by the tricuspid valves and the valves of the pulmonary artery. CHAP, iv.] THE VASCULAR MECHANISM. 253 The Work done. § 138. We can measure with approximative exactness the in- traventricular pressure, the length of each systole, and the number of times the systole is repeated in a given period, but perhaps the most important factor of all in the determination of the work of the vascular mechanism, the quantity ejected from the ventricle into the aorta at each systole, cannot as yet be said to have been accurately determined ; we are largely obliged to fall back on calculations having many sources of error. The general result of some of these calculations gives about 18CLgrmsi..(6.oz.^as the quantity of blood which is driven from each ventricle at each systole in a full-grown man of average size and weight, but this estimate is probably too high. In the dog the quantity has been experimentally determined, by allowing the heart to deliver its contents through one branch of the aorta, all others being ligatured or blocked, into a receiver, the con- tents of which are at intervals, by an ingenious contrivance, returned to the right auricle. The time taken to till the receiver and the number of beats executed during that time being noted, the average quantity ejected at a beat is thus given. It is found to vary very widely. Various methods have been adopted for calculating the average amount of blood ejected at each ventricular systole. The simplest method is to measure the capacity of the recently removed and as yet not rigid ventricle, filled with blood under a pressure equal to the calculated average pressure in the ventricle. On the supposition that the whole contents of the ventricle are ejected at each systole this would give the quantity driven into the aorta at each stroke. The other methods are very indirect. It is evident that exactly the same quantity must issue at a beat from each ventricle ; for if the right ventricle at each beat gave out rather less than the left, after a certain number of beats the whole of the blood would be gathered in the systemic circulation. Similarly, if the left ventricle gave out less than the right, all the blood would soon be crowded into the lungs. The fact that the pressure in the right ventricle is so much less than that in the left (probably 30 or 40 mm. as compared with 200 mm. of mercury), is due, not to differences in the quantity of blood in the cavities, but to the fact that the peripheral resistance which has to be overcome in the lungs is so much less than that in the rest of the body. It must be remembered that though it is of advantage to speak of an average quantity ejected at each stroke, it is more than probable that that quantity may vary within very wide limits. Taking, however, 180 grms. as the quantity, in man, ejected at 254 THE WORK DONE. [BOOK i. each stroke at a pressure of 250 mm.1 of mercury, which is equiva- lent to 3'21 metres of blood, this means that the left ventricle is capable at its systole of lifting 180 grms. 3 "21 m. high, i.e. it does 578 gram-meters of work at each beat. Supposing the heart to beat 72 times a minute, this would give for the day's work of the left ventricle nearly 60,000 kilogram-meters. Calculating the work of the right ventricle at one-fourth that of the left, the work of the whole heart would amount to 75,000 kilogram-meters, which is just about the amount of work done in the ascent of Snowdon by a tolerably heavy man. A calculation of more practical value is the following. Taking the quantity of blood as ^ of the body weight, the blood of a man weighing 75 kilos would be about 5,760 grms. If 180 grms. left the ventricle at each beat, a quantity equivalent to the whole blood would pass through the heart in 32 beats, i.e. in less than half a minute. 1 A high estimate is purposely taken here. SEC. 4. THE PULSE. § 139. We have seen that the arteries, though always dis- tended, undergo at each systole of the ventricle a temporary additional distension, a temporary additional expansion so that when the finger is placed on an artery, such as the radial, an intermittent pressure on the finger, coming and going with the FIG. 42. FICK'S SPRING MANOMETER. The flattened tube in the form of a hoop is firmly fixed at one end, while the other free end is attached to a lever. The interior of the tube, filled with spirit, is brought, by means of a tube containing sodium carbonate solution, into connection with an artery, in much the same way as in the case of the mercury manometer. The increase of pressure in the artery being transmitted to the hollow hoop, tends to straighten it, and correspondingly moves the attached lever. 256 SPHYGMOGRAPH. [BOOK i. beat of the heart, is felt, and when a light lever is placed on the artery, the lever is raised at each beat, falling between. This intermittent expansion which we call the pulse, cor- responding to the jerking outflow of blood from a severed artery, is present in the arteries only, being, except under particular circumstances, absent from the veins and capillaries. The expansion is frequently visible to the eye, and in some cases, as where an artery has a bend, may cause a certain amount of locomotion of the vessel. The temporary increase of pressure which is the cause of the temporary increase of expansion makes itself felt, as we have seen, in the curve of arterial pressure taken by the mercury manometer; but the inertia of the mercury prevents the special characters of each increase becoming visible. In Fick's spring manometer (Fig. 42), in which the increase of pressure unfolds a curved spring and so moves a lever, the inertia is much less, and satisfactory tracings may be taken by this instrument. Other instruments have also been devised for recording the special characters of each increase of pressure or of the expansion of the artery which is the result of that increase. The easiest and most common method a FIG. 43. DIAGEAM OF A SPHYGMOGRAPH (Dudgeon's). Certain supporting parts are omitted so that the multiplying levers may be displayed. a is a small metal plate which is kept pressed on the artery by the spring b. The vertical movements of a cause to and fro movements of the lever c about the fixed point d. These are communicated to and magnified by the lever e which moves round the fixed point /. The free end of this lever carries a light steel marker which rests on a strip of smoked paper g. The paper is placed beneath two small wheels and rests on a roller which can be rotated by means of clock-work contained in the box h. The paper is thus caused to travel at a uniform rate. The screw graduated in ounces Troy is brought to bear on the spring b by means of a camm and by this the pressure put on the artery can be regulated. The levers magnify the pulse movements fifty times. CHAP, iv.] THE VASCULAR MECHANISM. 257 of registering the expansion of an artery is that of simply bringing a light lever to bear on the outside of the artery. A lever specially adapted to record a pulse tracing is called a sphygmograph, the instrument generally comprising a small travelling recording surface on which the lever writes. There are many different forms of sphygmograph but the general plan of structure is the same. Fig. 43 represents in a diagrammatic form the essential parts of the sphygmograph, known as Dudgeon's. The instrument is generally applied to the radial artery because the arm affords a convenient support to the fulcrum of the lever, and because the position of the artery, near to the surface and with the support of the radius below so that adequate pressure can be brought to bear by the lever on the artery, is favourable for making observations. It can of course be applied to other arteries. When applied to the radial artery some such tracing as that shewn in Fig. 44 is obtained. At each heart-beat the lever FIG. 4-1. PULSE TRACING FKOM THE BADIAL ARTERY OF MAN. The vertical curved line, L, gives the tracing which the recording lever made when the blackened paper was motionless. The curved interrupted lines shew the distance from one another in time of the chief phases of the pulse-wave, viz. x = commencement and A end of expansion of artery, p, predicrotic notch, d, di- crotic notch. C, dicrotic crest. D, post-dicrotic crest. /, the post-dicrotic notch. These are explained in the text later on. rises rapidly and then falls more gradually in a line which is more or less uneven. § 140. We have now to study the nature and characters of the pulse in greater detail. We may say at once, and indeed have already incidentally seen, that the pulse is essentially due to the action of physical causes; it is the physical result of the sudden injection of the contents of the ventricle into the elastic tubes called arteries ; its more important features may be explained on physical principles and may be illustrated by means of an artificial model. If two levers be placed on the arterial tubes of an artificial model Fig. 30 S. a., S'. a., one near to the pump, and the other F. 17 258 ARTIFICIAL PULSE. [BOOK i. near to the peripheral resistance, with a considerable length of tubing between them, and both levers be made to write on a recording surface, one immediately below the other, so that their curves can be more easily compared, the following facts may be observed, when the pump is set to work regularly. They are perhaps still better seen if a number of levers be similarly arranged at different distances from the pump as in Fig. 45. 50V. FIG. 45. Pulse-curves described by a series of sphygmographic levers placed at intervals of 20 cm. from each other along an elastic tube into which fluid is forced by the sudden stroke of a pump. The pulse-wave is travelling from left to right, as indicated by the arrows over the primary (a) and secondary (b, c) pulse-waves. The dotted vertical lines drawn from the summit of the several primary waves to the tuning-fork curve below, each complete vibration of which occupies -^ sec., allow the time to be measured which is taken up by the wave in passing along 20 cm. of the tubing. The waves a' are waves reflected from the closed distal end of the tubing; this is indicated by the direction of the arrows. It will be observed that in the more distant lever VI. the reflected wave, having but a slight distance to travel, becomes fused with the primary wave. (From Marey.) CHAP, iv.] THE VASCULAR MECHANISM. 259 At each stroke of the pump, each lever rises until it reaches a maximum (Fig. 45 la, 2a, &c.) and then falls again, thus describing a curve. The rise is due to the expansion of the part of the tube under the lever, and the fall is due to that part of the tube returning after the expansion to its previous calibre. The curve is therefore the curve of the expansion (and return) of the tube at the point on which the lever rests. We may call it the pulse-curve. It is obvious that the expansion passes by the lever in the form of a wave. At one moment the lever is at rest : the tube beneath it is simply distended to the normal amount indicative of the mean pressure which at the time obtains in the arterial tubes of the model ; at the next moment the pulse expansion reaches the lever, and the lever begins to rise ; it continues to rise until the top of the wave reaches it, after which it falls again until finally it comes to rest, the wave having completely passed by. It may perhaps be as well at once to warn the reader that the figure which we call the pulse-curve is not a representation of the pulse-wave itself; it is simply a representation of the movements, up and down, of the piece of the wall of the tubing at the spot on which the lever rests during the time that the wave is passing over that spot. We may roughly represent the wave in the diagram Fig. 46 in which the wave shewn by the dotted line is y .--1- i i Y X FlG. 46. A ROUGH DIAGRAMMATIC EEPRESENTATION OF A PULSE WAVE PASSING OVER AN ARTERY. passing over the tube (shewn in a condition of rest by the thick double line) in the direction from H to C. It must however be remembered that the wave thus figured is a much shorter wave than is the pulse-wave in reality (that being, as we shall see, about 6 meters long), i.e. occupies a smaller length of the arterial system from the heart H towards the capillaries C. 17—2 260 ARTIFICIAL PULSE. [BOOK i. The curves below X, Y, Z represent, in a similarly diagram- matic fashion, the curves described, during the passage of the wave, by levers placed on the points x, y, z. At Z the greater part of the wave has already passed under the lever, which during its passage has already described the greater part of its curve, shewn by the thick line, and has only now to describe the small part, shewn by the dotted line, corresponding to the remainder of the wave from Z to H. At T the lever is at the summit of the wave. At X the lever has only described a small part of the beginning of the wave, viz. from C to x, the rest of the curve, as shewn by the dotted line, having yet to be described. But to return to the consideration of Fig. 45. § 141. The rise of each lever is somewhat sudden, but the fall is more gradual, and is generally marked with some irregularities which we shall study presently. The rise is sudden because the sharp stroke of the pump suddenly drives a quantity of fluid into the tubing and so suddenly expands the tube ; the fall is more gradual because the elastic reaction of the walls of the tube, which brings about the return of the tube to its former calibre after the expanding power of the pump has ceased, is more gradual in its action. These features, the suddenness of the rise or up-stroke, and the more gradual slope of the fall or down-stroke, are seen also in natural pulse-curves taken from living arteries (Figs. 44, 47, &c.). Indeed the difference between the up-stroke and the down-stroke is even more marked in the latter than in the former, the delivery of blood from the ventricle being more rapid than the issue of water from a pump as ordinarily worked. It may here be noted that the actual size of the curve, that is the amount of excursion of the lever, depends in part (as does also to a great extent the form of the curve) on the amount of pressure exerted by the lever on the tube. If the lever only just touches the tube in its expanded state, the rise will be insignificant. If on the other hand the lever be pressed down too firmly, the tube beneath will not be able to expand as it otherwise would, and the rise of the lever will be proportionately diminished. There is a certain pressure which must be exerted by the lever on the tube, the exact amount depending on the expansive power of the tubing and on the FIG. 47. PULSE TRACINGS FKOM THE SAME RADIAL ARTERY UNDER DIF- FERENT PRESSURES OF THE LEVER. The letters are explained in a later part of the text. CHAP, iv.] THE VASCULAR MECHANISM. 261 pressure exerted by the fluid in the tube, in order that the tracing may be best marked. This is shewn in Fig. 47 in which are given three tracings taken from the same radial artery with the same instrument ; in the lower curve the pressure of the lever is too great, in the upper curve too small, to bring out the characters seen most distinctly in the middle curve with a medium pressure. § 142. It will be observed that in Fig. 45 curve I., which is nearer the pump, rises higher, and rises more rapidly than curve II., which is farther away from the pump ; that is to say, at the lever farther away from the pump, the expansion is less and takes place more slowly than at the lever nearer the pump. Similarly in curve IV. the rise is still less, and takes place still less rapidly than in II., and the same change is seen still more marked in V. as compared with IV. In fact if a number of levers were placed at equal distances along the arterial tubing of the model and the model were working properly, with an adequate peripheral resis- tance, we might trace out step by step how the expansion, as it travelled along the tube, got less and less in amount and at the same time became more gradual in its development, the curve becoming lower and more flattened out, until in the neighbourhood of the artificial capillaries there was hardly any trace of it left. In other words we might trace out step by step the gradual disappearance of the pulse. The same changes, the same gradual lowering and flattening of the curve may be seen in natural pulse tracings, as for instance in Fig. 48 which is a tracing from the dorsalis pedis artery, compared A 9 with the tracing from the radial artery Fig. 47, taken from the same individual with the same — . • • • • . . instrument on the same occasion. FlG 48< PDLSE TRACING FEOM DoR. This feature is of course not ob- SALIS PEDIS TAKEN FBOM THE SAME vious in all pulse-curves taken INDIVIDUAL AS FIG. 47. from different individuals with different instruments and under varied circumstances ; but if a series of curves from different arteries were carefully taken under the same conditions it would be found that the aortic tracing is higher and more sudden than the carotid tracing which again is higher and more sudden than the radial tracing, the tibial tracing being in turn still lower and more flattened. The pulse-curve dies out by becoming lower and lower and more arid more flattened out. And a little consideration will shew us that this must be so. The systole of 'the ventricle drives a quantity of blood into the already full aorta. The sudden injection of this quantity of blood expands the portion of the aorta next to the heart, the part immediately adjacent to the semilunar valves beginning to expand 262 DISAPPEARANCE OF PULSE. [BOOK i. first, and the expansion travelling thence on to the end of this portion. In the same way the expansion travels on from this portion through all the succeeding portions of the arterial system. For the total expansion required to make room for the new quantity of blood is not provided by that portion alone of the aorta into which the blood is actually received ; it is supplied by the whole arterial system: the old quantity of blood which is replaced by the new in this first portion has to find room for itself in the rest of the arterial space. As the expansion travels onward, however, the increase of pressure which each portion transmits to the succeeding portion will be less than that which it received from the preceding portion. For the whole increase of pressure due to the systole of the ventricle has to be distributed over the whole of the arterial system ; the general mean arterial pressure is, as we have seen, maintained by repeated systoles, and any one systole has to make its contribution to that mean pressure ; the increase of pressure which starts from the ventricle must there- fore leave behind at each stage of its progress a fraction of itself; that is to say, the expansion is continually growing less, as the pulse travels from the heart to the capillaries. Moreover, while the expansion of the aorta next to the heart is so to speak the direct effect of the systole of the ventricle, the expansion of the more distant artery is the effect of the systole transmitted by the help of the elastic reaction of the arterial tract between the heart and the distant artery ; and since this elastic reaction is slower in development than the actual systole, the expansion of the more distant artery is slower than that of the aorta, the up-stroke of the pulse-curve is less sudden, and the whole pulse-curve is more flattened. The object of the systole is to supply a contribution to the mean pressure, and the pulse is an oscillation above and below that mean pressure, an oscillation which diminishes from the heart onwards, being damped by the elastic walls of the arteries, and so, little by little, converted into mean pressure until in the capillaries the mean pressure alone remains, the oscillations having dis- appeared. § 143. If in the model the points of the two levers at different distances from the pump be placed exactly one under the other on the recording surface, it is obvious that, the levers being alike except for their position on the tube, any difference in time between the movements of the two levers will be shewn by an interval between the beginnings of the curves they describe, the recording surface being made to travel sufficiently rapidly. If the movements of the two levers be thus compared, it will be seen that the far lever (Fig. 45, II.) commences later than the near one (Fig. 45, 1.); the farther apart the two levers are, the greater is the interval in time between their curves. Compare the series I. to VI. (Fig. 45). This means that the wave of expansion, the CHAP, iv.] THE VASCULAR MECHANISM. 263 pulse-wave, takes some time to travel along the tube. In the same way it would be found that the rise of the near lever began some fraction of a second after the stroke of the pump. The velocity with which the pulse-wave travels depends chiefly on the amount of rigidity possessed by the tubing. The more extensible (with corresponding elastic reaction) the tube, the slower is the wave ; the more rigid the tube becomes, the faster the wave travels ; in a perfectly rigid tube, what in the elastic tube would be the pulse, becomes a mere shock travelling with very great rapidity. The width of the tube is of much less influence, though according to some observers the wave travels more slowly in the wider tubes. The rate at which the normal pulse-wave travels in the human body has been variously estimated at from 10 to 5 meters per second. In all probability the lower estimate is the more correct one ; but it must be remembered that the rate may vary very considerably under different conditions. According to all observers the velocity of the wave in passing from the groin to the foot is greater than that in passing from the axilla to the wrist (6 m. against 5 m.). This is probably due to the fact that the femoral artery with its branches is more rigid than the axillary and its branches. So also in the arteries of children, the wave travels more slowly than in the more rigid arteries of the adult. The velocity is also increased by circumstances which heighten and decreased by those which lessen the mean arterial pressure, since with increasing pressure the arterial walls become more and with diminishing pressure less rigid. Probably also the velocity of the pulse-wave depends on conditions of the arterial walls, which we cannot adequately describe as mere differences in rigidity. In experimenting with artificial tubes it is found that different qualities of indiarubber give rise to very different results. Care must be taken not to confound the progress of the pulse- wave, i.e. of the expansion of the arterial walls, with the actual onward movement of the blood itself. The pulse-wave travels over the moving blood somewhat as a rapidly moving natural wave travels along a sluggishly flowing river. Thus while the velocity of the pulse- wave is 6 or possibly even 10 meters per sec., that of the current of blood is not more than half a meter per sec. even in the large arteries, and is still less in the smaller ones. § 144. Referring again to the caution given above not to regard the pulse-curve as a picture of the pulse-wave, we may now add that the pulse-wave is of very considerable length. If we know how long it takes for the pulse- wave to pass over any point in the arteries and how fast it is travelling, we can easily calculate the length of the wave. In an ordinary pulse-curve the artery, owing to the slow return, is seen not to regain the calibre which it had before the expansion, until just as the next expansion begins, that is to say, the pulse-wave takes the whole time of a cardiac cycle, viz. T8^ths 264 VELOCITY OF PULSE WAVE. [BOOK i. sec. to pass by the lever. Taking the velocity of the pulse-wave as 6 meters per sec. the length of the wave will be T^ths of 6 m., that is nearly 5 meters. And even if we took a smaller estimate, by supposing that the real expansion and return of the artery at any point took much less time, say ^ths sec., the length of the pulse-wave would still be more than 2 meters. But even in the tallest man the capillaries farthest from the heart, those in the tips of the toes, are not 2 m. distant from the heart. In other words, the length of the pulse-wave is much greater than the whole length of the arterial system, so that the beginning of each wave has become lost in the small arteries and capillaries some time before the end of it has finally passed away from the beginning of the aorta. We must now return to the consideration of certain special features in the pulse, which from the indications they give or suggest of the condition of the vascular system are often of great interest. § 145. Dicrotism. In nearly all pulse tracings, the curve of the expansion and recoil of the artery is broken by two, three, or several smaller elevations and depressions : secondary waves are imposed upon the fundamental or primary wave. In the sphygmographic tracing from the carotid Fig. 49 and in many of the other tracings iG. 49. PULSE-TKACING FROM CAEOTID ARTERY OF HEALTHY MAN (from Moens). x, commencement of expansion of the artery. A, summit of the first rise. C, dicrotic secondary wave. B, predicrotic secondary wave; p, notch preceding this. D, succeeding secondary wave. The curve above is that of a tuning-fork with ten double vibrations in a second. given, these secondary elevations are marked as B, C, D. When one such secondary elevation only is conspicuous, so that the pulse- curve presents two notable crests only, the primary crest and a secondary one, the pulse is said to be "dicrotic"; when two secondary crests are prominent, the pulse is often called "tri- crotic " ; where several " polycrotic." As a general rule, the secondary elevations appear only on the descending limb of the primary wave as in most of the curves given, and the curve is then spoken of as " katacrotic." Sometimes, however, the first elevation or crest is not the highest but appears on the ascending CHAP, iv.] THE VASCULAR MECHANISM. 265 portion of the main curve: such a curve is spoken of as "anacrotic" Fig. 50. Of these secondary elevations, the most frequent, conspicuous and important is the one which appears some way down on the descending limb and is marked C on Fig. 49 and on most of the curves here given. It is more or less distinctly visible on all sphygmograms, and may be seen in those of the aorta as well as of other arteries. Sometimes it is so slight as to be hardly discernible ; at other times it may be so marked as to give rise to a really double pulse (Fig. 51), i.e. a pulse which can be felt as double by the finger ; hence it has been called the dicrotic elevation or the dicrotic wave, the notch preceding the elevation being spoken of as the " dicrotic notch." \J iO. ANACROTIC MOGRAPH TRACING FROM THE ASCENDING AORTA (Aneurism). FlG. 51. TWO GRADES OF MARKED DICROTISM IN RADIAL PULSE OF MAN. (Typhoid Fever.) Neither it nor any other secondary elevations can be recognised in the tracings of blood-pressure taken with a manometer. This may be explained, as we have said § 139, by the fact that the movements of the mercury column are too sluggish to reproduce these finer variations ; but dicrotism is also conspicuous by its absence in the tracings given by more delicately responsive in- struments. Moreover, when the normal pulse is felt by the finger, most persons find themselves unable to detect any dicrotism. But that it does really exist in the normal pulse is shewn by the fact that it appears in a most unmistakeable manner in the tracing obtained by allowing the blood to spirt directly from an opened small artery, such as the dorsalis pedis, upon a recording surface. Less constant and conspicuous than the dicrotic wave but yet appearing in most sphygmograms is an elevation which appears higher up on the descending limb of the main wave; it is marked B in Fig. 49, and on several of the other curves, and is frequently called the predicrotic wave ; it may become very prominent. Some- times other secondary waves, often called ' post-dicrotic ', are seen following the dicrotic wave, as at D in Fig. 49, and some other curves ; but these are not often present and usually even when present inconspicuous. When tracings are taken from several arteries or from the same 266 DICROTISM. [Boon i. artery under different conditions of the body, these secondary waves are found to vary very considerably, giving rise to many - characteristic forms of pulse-curve. Were we able with certainty to trace back the several features of the curves to their respective causes, an adequate examination of sphygmographic tracings would undoubtedly disclose much valuable information concerning the condition of the body presenting them. Unfortunately the problem of the origin of these secondary waves is a most difficult and complex one ; so much so that the detailed interpretation of a sphygmographic tracing is still in most cases extremely un- certain. § 146. The chief interest attaches to the nature and meaning of the dicrotic wave. In general the main conditions favouring dicrotism are (1) a highly extensible and elastic arterial Avail, (2) a comparatively low mean pressure, leaving the extensible and elastic reaction of the arterial wall free scope to act, and (3) a sufficiently vigorous and sufficiently rapid stroke of the ventricle. The development of the dicrotic wave may probably be explained as follows. At each beat the time during which the contents of the left ventricle are injected into the aorta is as we have seen (§ 136) very brief. The expansion of the aorta is very sudden, and the cessation of that expansion is also very sudden. Now when fluid is being driven with even a steady pressure through an elastic tube or a system of elastic tubes, levers placed on the tube will describe curves indicating variations in the diameter of the tube, if the inflow into the tube be suddenly stopped, as by sharply turning a stop-cock ; and a comparison of levers placed at different distances from the stop-cock will shew that these variations of diameter travel down the tube from the stop-cock in the form of waves. The lever near the stop-cock will first of all fall, but speedily begin to rise again, and this subsequent rise will be followed by another fall, after which there may be one or more succeeding rises and falls, that is oscillations, with decreasing amplitudes, until the fluid comes to rest. The levers farther from the stop-cock will describe curves, similar to the above in form but of less amplitude, and it will be found that these occur somewhat later in time, the more so the farther the lever is from the stop- cock. Obviously these waves are generated at or near the stop-cock and travel thence along the tubing. We may infer that at each beat of the heart similar waves would be generated at the root of the aorta, upon the sudden cessation of the flow from the ventricle, and would travel thence along the elastic arteries. The facts that each beat is rapidly succeeded by another, and that the flow which suddenly ceases is also, by the nature of the ventricular stroke, suddenly generated, may render the waves more complicated, but will not change their essential nature. CHAP, iv.] THE VASCULAR MECHANISM. 267 The exact interpretation of the generation of these waves is perhaps not without difficulty, but two factors seem of especial importance. In the first place, as we have already more than once said, when a rapid flow is suddenly stopped a negative pressure makes its appearance behind the column of fluid. In a rigid tube this simply leads to a reflux of fluid. In an elastic tube its effects are complicated by the second factor, the elastic action and inertia of the walls of the tube. Upon the sudden cessation of the flow, the expansion of the tube, or as we may at once say, of the aorta, ceases, the vessel begins to shrink, and the lever placed on it falls, as from A onward in the pulse-curve. This shrinking is in part due to the elastic reaction of the walls of the aorta, but is increased by the "suction" action of the negative pressure spoken of above. In thus shrinking however under these combined causes, the aorta, through the inertia of its walls, overshoots the mark, it is carried beyond its natural calibre, i.e. the diameter it would possess if left to itself with the pressure inside and outside equal ; it shrinks too much, and consequently begins again to expand. This secondary expansion (taking for simplicity sake a pulse-curve in which the so-called predicrotic wave, B, is absent or inconspicuous) causes the secondary rise of the lever up to C, that is the dicrotic rise. In thus expanding again the aorta tends to draw back towards the heart the column of blood which by loss of momentum had come to rest, or indeed under the influence of the negative pressure spoken of above was already undergoing a reflux. In this secondary expansion more- over the aorta is by the inertia of its walls, aided by that of the blood, again carried, so to speak, beyond its mark, so that no sooner has it become expanded and filled with fluid to a certain extent than it again begins to shrink as from C onward. And this shrinking may in a similar manner to the first be followed by a further expansion and shrinking, giving rise to a post-dicrotic wave, or it may be to post-dicrotic Avaves. And the successive changes thus inaugurated at the root of the aorta travel as so many waves along the arterial system, diminishing as they go. It will be observed that for the development of these waves, a certain quality in the walls of the tubing is necessary. The tube must be such as possesses when at rest an open lumen ; the walls must be of such a kind that the tube remains open when empty, i. e. when the atmospheric pressure is equal inside and outside, so that when it shrinks too much, it expands again in striving to regain its natural calibre. This we have seen to be a character- istic of the arteries. A collapsible tube of thin membrane will not shew the phenomena ; such a tube when the stop-cock is turned collapses and empties itself, continuing to be collapsed without any effort to expand again. In the above explanation no mention has been made of the closing of the semilunar valves ; we shall have to speak of these 268 DICROTISM. [BOOK i. a little later on in referring to the predicrotic wave and shall see that, under the view we have just given, the closing of the semi- lunar valves is to be regarded rather as the effect than the cause of the dicrotic wave. Many authors however give an interpre- tation of the dicrotic wave different from that detailed above. Thus it is held that the primary shrinking, from A onwards, being brought to bear on the column of blood already come to rest, in face of the great pressure in front, drives the blood back against the semilunar valves, thus closing them, and that the impact of the column of blood against the valves starts a new wave of ex- pansion, which reinforcing the natural tendency of the elastic walls to expand again after their primary shrinking produces the dicrotic wave C. On this view it is the blood driven back from the valves which expands the artery; on the view given above it is the expanding artery which draws the blood back towards the valves. Moreover, quite other views have been or are held concerning this dicrotic wave. According to many authors it is what is called a ' reflected ' wave. Thus, when the tube of the artificial model bearing two levers is blocked just beyond the far lever, the primary wave is seen to be accompanied by a second wave, which at the far lever is seen close to, and often fused into, the primary wave (Fig. 45, VI. a), but at the near lever is at some distance from it (Fig. 45, I. a'), being the farther from it the longer the interval between the lever and the block in the tube. The second wave is evidently the primary wave reflected at the block and travelling backwards towards the pump. It thus of course passes the far lever before the near one. And it has been argued that the dicrotic wave of the pulse is really such a reflected wave, started either at the minute arteries and capillaries, or at the points of bifurcation of the larger arteries, and travelling backwards to the aorta. But if this were the case the distance between the primary crest and the dicrotic crest ought to be less in arteries more distant from than in those nearer to the heart, Justus in the artificial scheme the reflected wave is fused with a primary wave near the block (Fig. 45, VI. 6 a. a), but becomes more and more separated from it the farther back towards the pump we trace it (Fig. 45, I. 1 a. a). Now this is not the case with the dicrotic wave. Careful measurements shew that the distance between the primary and dicrotic crests is either greater or_ certainly not less in the smaller or more distant arteries than in the larger or nearer ones. This feature indeed proves that the dicrotic wave cannot be due to reflection at the periphery or indeed in any way a retrograde wave. Besides the multitudinous peripheral division would render one large peripherically reflected wave im- possible. Again, the more rapidly the primary wave is obliterated or at least diminished on its way to the periphery the less con- spicuous should be the dicrotic wave. Hence increased extensi- CHAP, iv.] THE VASCULAR MECHANISM. 269 bility and increased elastic reaction of the arterial walls which tend to use up rapidly the primary wave, should also lessen the dicrotic wave. But as a matter of fact these conditions, as we have said, are favourable to the prominence of the dicrotic wave. On the other hand these, and the other conditions which favour dicrotism in the pulse, are exactly those which would favour such a development of secondary waves as has been described above, and their absence would be unfavourable to the occurrence of such waves. Thus dicrotism is less marked in rigid arteries (such as those of old people) than in healthy elastic ones; the rigid wall neither expands so readily nor shrinks so readily, and hence does not so readily give rise to such secondary waves. Again dicrotism is more marked when the mean arterial pressure is low than when it is high ; indeed dicrotism may be induced when absent, or increased when slightly marked, by diminishing, in one way or another, the mean pressure. Now when the pres- sure is high, the arteries are kept continually much expanded, and are therefore the less capable of further expansion, that is to say, are, so far, more rigid. Hence the additional expansion due to the systole is not very great ; there is a less tendency for the arterial walls to swing backwards and forwards, so to speak, and hence a less tendency to the development of secondary waves. When the mean pressure is low, the opposite state of things exists ; supposing of course that the ventricular stroke is adequately vigorous (the low pressure being due, not to diminished cardiac force but to diminished peripheral resistance) the relatively empty but highly distensible artery is rapidly expanded, and falling rapidly back enters upon a secondary (dicrotic) expansion and even a third. Moreover the same principles may be applied to explain why sometimes dicrotism will appear marked in a particular artery while it remains little marked in the rest of the system. In experimenting with an artificial tubing such as the arte- rial model, the physical characters of which remain the same throughout, both the primary and the secondary waves retain the same characters as they travel along the tubing save only that both gradually diminish towards the periphery ; and in the natural circulation, when the vascular conditions are fairly uniform throughout, the pulse curve, as a rule, possesses the same general characters throughout, save that it is gradually ' damped off.' But suppose we were to substitute for the first section of the tubing a piece of perfectly rigid tubing ; this at the stroke of the pump on account of its being rigid would shew neither primary nor secondary expansion, but the expanding force of the pump's stroke would be transmitted through it to the second, elastic section, and here the primary and secondary waves would at once become evident. This is an extreme case, but the same thing would be seen to a less degree in passing from a more rigid, 270 DICROTISM. [BOOK i. that is less extensible and elastic section, to a less rigid, more extensible and elastic section ; the primary and secondary expan- sions, in spite of the general damping effect, would suddenly -increase. Similarly in the living body a pulse-curve which so long as it is travelling along arteries in which the mean pressure is high, and which are therefore practically somewhat rigid, is not markedly dicrotic, may become very markedly dicrotic when it comes to a particular artery, in which the mean pressure is low (and we shall see presently that such a case may occur), and the walls of which are therefore for the time being relatively more distensible than the rest. Lastly we may recall the observation made above § 141 that the curve of expansion of an elastic tube is modified by the pres- sure exerted by the lever employed to record it, and that hence, in the same artery, and with the same instrument, the size, form, and even the special features of the curve vary according to the amount of pressure with which the lever is pressed upon the artery. Accordingly the amount of dicrotism apparent in a pulse may be modified by the pressure exerted by the lever. In Fig. 47 for instance the dicrotic wave is more evident in the middle than in the upper tracing. § 147. The predicrotic wave, (marked B on Fig. 49, and on several other of the pulse curves), which precedes the dicrotic wave and is still more variable than that wave, being some- times slight or even invisible and sometimes conspicuous, has given rise to much controversy. In the interpretation of the dicrotic wave given in the preceding paragraph it was stated that the negative pressure developed on the cessation of the flow in the rear of the column of blood, led by itself to a reflux towards the ventricle £^and it has been suggested that this reflux meeting and closing the semilunar valves starts a small wave of expansion before the larger dicrotic wave has had time to develope itself. On this view the semilunar valves would be actually closed before the occurrence of the secondary dicrotic expansion of the arterial walls, though the larger more powerful reflux of this later event must render the closure more complete and in doing so possibly gives rise to the second sound. According however to the second view given in the same paragraph, which regards the reflux due to the shrinking of the artery in face of the great pressure in front as firmly closing the semilunar valves, and as thus starting the secondary dicrotic wave of expansion, the firm closing of the semilunar valves must take place before the begin- ning, not during the development of the dicrotic wave ; it is still possible however, even on this view as on the other, to suppose that an antecedent reflux due to the negative pressure succeeding the cessation of flow from the ventricle closes the valves and starts the predicrotic wave. But the matter is one not yet beyond the stage of controversy. CHAP, iv.] THE VASCULAR MECHANISM. 271 § 148. In an anacrotic pulse the first rise is not the highest, but a second rise B, Fig. 50, which follows and is separated from it by a notch is higher than or at least as high as itself. Such an anacrotic wave, though it may sometimes be produced temporarily in healthy persons, is generally associated with diseased conditions, usually such in which the arteries are abnormally rigid. In de-X scribing the ventricular systole we spoke of the pressure within the ventricle as reaching its maximum just before the opening of the semilunar valves ; and this is apparently the normal event ; but ,x there are curves which seem to shew that after the first sudden rise of pressure which opens the valves, followed by a brief lessening of pressure, which appears on the curve as a notch, the pressure may again rise and that to a point higher than before. And a similar curve is sometimes described by the front- to-back diameter of the ventricle. The systole opens the valves as it were with a burst ; this is followed by a slight relapse, and then the systole, strengthening again, discharges the whole of the ventricular contents into the aorta and so brings about a tardy maximum expansion. And what is thus started in the aorta travels onward over the arterial system. It is difficult to see how these anacrotic events can be produced except by a certain irregularity in the ventricular systole, and indeed the anacrotic pulse is frequently associated with some disease or defect of the ventricle. § 149. Venous Pulse. Under certain circumstances the pulse may be carried on from the arteries through the capillaries into the veins. Thus, as we shall see later on, when the salivary gland is actively secreting, the blood may issue from the gland through the veins in a rapid pulsating stream. The nervous events which give rise to the secretion of saliva, lead at the same time, by the agency of vaso-motor nerves, of which we shall presently speak, to a dilata- tion of the small arteries of the gland. When the gland is at rest, the minute arteries are, as we shall see, somewhat constricted and narrowed, and thus contribute largely to the peripheral resistance in the part ; this peripheral resistance throws into action the elastic properties of the small arteries leading to the gland, and the remnant of the pulse reaching these arteries is, as we before explained, finally destroyed. When the minute arteries are dilated, their widened channels allow the blood to flow more easily through them and with less friction ; the peripheral resistance which they normally offer is thus lessened. In consequence of this the elasti- city of the walls of the small arteries is brought into play to a less extent than before, and these small arteries cease to do their share in destroying the pulse which comes down to them from the larger arteries. As in the case of the artificial model, where the ' peripheral ' tubing is kept open, not enough elasticity is brought into play to convert the intermittent arterial flow into a con- tinuous one, and the pulse which reaches the arteries of the gland 272 VENOUS PULSE. [BOOK i. passes on through them and through the capillaries, and is con- tinued on into the veins. A similar venous pulse is also some- times seen in other organs. Careful tracings of the great veins in the neighbourhood of the heart shew elevations and depressions, which appear due to the variations of intracardiac (auricular) pressure, and which may perhaps be spoken of as constituting a "venous pulse", though they have a quite different origin from the venous pulse just described in the salivary gland ; but at present they need further elucidation. XIn cases however of insufficiency of the tricuspid valves, the systole of the ventricle makes itself distinctly felt in the great veins ; and a distension travelling backwards from the heart becomes very visible in the veins of the neck. This is sometimes spoken of as a venous pulse. Variations of pressure in the great veins due to the respiratory movements are also sometimes spoken of as a venous pulse ; the nature of these variations will be explained in treating of respi- ration. SEC. 5. THE REGULATION AND ADAPTATION OF THE VASCULAR MECHANISM. The Regulation of tlie Seat of the Heart. § 150. So far the facts with which we have had to deal, with the exception of the heart's beat itself, have been simply physical facts. All the essential phenomena which we have studied may be reproduced on a dead model. Such an unvarying mechanical vascular system would however be useless to a living body whose actions were at all complicated. The prominent feature of a living mechanism is the power of adapting itself to changes in its in- ternal and external circumstances. In such a system as we have sketched above there would be but scanty power of adaptation. The well-constructed machine might work with beautiful regu- larity ; but its regularity would be its destruction. The same quantity of blood would always flow in the same steady stream through each and every tissue and organ, irrespective of local and general wants. The brain and the stomach, whether at work and needing much, or at rest and needing little, would receive their ration of blood, allotted with a pernicious monotony. Just the same amount of blood would pass through the skin on the hottest as on the coldest day. The canon of the life of every part for the whole period of its existence would be furnished by the inborn diameter of its blood vessels, and by the unvarying motive power of the heart. Such a rigid system however does not exist in actual living beings. The vascular mechanism in all animals in which it is present is capable of local and general modifications, adapting it to local and general changes of circumstance. These modifications fall into two great classes : 1. Changes in the heart's beat. These, being central, have of course a general effect ; they influence or may influence the whole body. F. 18 274 HISTOLOGY OF THE HEART. [BOOK i. 2. Changes in the peripheral resistance, due to variations in the calibre of the minute arteries, brought about by the agency of their contractile muscular coats. These changes may be either local, affecting a particular vascular area only, or general, affecting all or nearly all the blood vessels of the body. These two classes of events are chiefly governed by the nervous system. It is by means of the nervous system that the heart's beat and the calibre of the minute arteries are brought into relation with each other, and with almost every part of the body. It is by means of the nervous system acting either on the heart, or on the small arteries, or on both, that a change of circumstances affecting either the whole or a part of the body is met by compensating or regulative changes in the flow of blood. It is by means of the nervous system that an organ has a more full supply of blood when at work than when at rest, that the tide of blood through the skin rises and ebbs with the rise and fall of the temperature of the air, that the work of the heart is tempered to meet the strain of overfull arteries, and that the arterial gates open and shut as the force of the central pump waxes and wanes. The study of these changes becomes therefore to a large extent a study of nervous actions. The circulation may also be modified by events not belonging to either of the above two classes. Thus, in this or that peripheral area, changes in the capillary walls and the walls of the minute arteries and veins may lead to an increase of the tendency of the blood corpuscles to adhere to the vascular walls, and so, quite apart from any change in the calibre of the blood vessels, may lead to increase of the peripheral resistance. This is seen in an extreme case in inflammation, but may possibly intervene to a less extent in the ordinary condition of the circulation, and may also be under the influence of the nervous system. Further, any decided change in the quantity of blood actually in circulation must also influence the working of the vascular mechanism. But both these changes are unimportant compared with the other two kinds of changes. Hence, the two most important problems for us to study are, 1, how the nervous system regulates the beat of the heart, and 2, how the nervous system regulates the calibre of the blood vessels. We will first consider the former problem. The Histology of the Heart. § 151. It will be necessary now to take up certain points concerning the minute structure of the heart, which we had previously postponed ; and since much of our knowledge of the nervous mechanism of the beat of the heart is derived from ex- periments on the hearts of cold-blooded animals, more particularly of the frog, it will be desirable to consider these as well as the mammalian heart. CHAP, iv.] THE VASCULAR MECHANISM. 275 Cardiac Muscular Tissue. The ventricle of the frog's heart is composed of minute spindle-shaped fibres or fibre cells, each containing a nucleus in its middle, and tapering to a point at each end ; sometimes however the end is forked or even branched. These fibres or fibre cells, in fact, resemble plain muscular fibres save that they are somewhat larger and that their substance is striated. The striation is due, like the striation of a striated muscle fibre, to alternate dim and bright bands, but is rarely so distinct as in a skeletal fibre ; it is very apt to be obscured by the presence of dispersed distinct granules, which, in many cases at all events, are of a fatty nature. '.Like the plain muscular fibre, the cardiac muscular fibre has no distinct sarcolemma. A number of these fibres are joined by cement substance into small bundles, and these bundles are, by help of connective tissue which carries no blood vessels, woven into an intricate network or sponge work, which forms the greater part of the wall of the ventricle. Immediately under the pericardial coating, consisting of a layer of epithelioid plates resting on a connective tissue basis, the muscular tissue forms a thin continuous sheet, but within this it spreads out into a sponge work, the meshes of which present a labyrinth of passages continuous with the cavity of the ventricle. The bars of this sponge work, varying in thickness and, though apparently irregular, arranged on a definite system, consist of bundles of muscular fibres united by connective tissue, and are coated with the same endocardial membrane (flat epithelioid plates resting on a connective tissue basis) that lines the cavity of the ventricle and indeed the whole interior of the heart. The cavity of the ventricle, in other words, opens out into a labyrinth of passages reaching nearly to the surface of the ventricle. When the ventricle is dilated or relaxed, blood flows freely into and fills this labyrinth, bathing the bars of the sponge work, which, in the absence of capillaries, depend on this blood for their nourish- ment. When the ventricle contracts, the blood is driven out of this labyrinth as well as out of the central cavity. Hence the ventricle when dilated and full of blood is of a deep red colour, when contracted and empty is extremely pale, having little more than the colour of the muscular fibres themselves, which, like striated fibres, possess in their own substance a certain amount of haemoglobin or of myohasmatin. The much thinner walls of the auricle consist of a much thinner network of similar fibres united by a relatively larger quantity of connective tissue into a thin sheet, with the pericardial mem- brane on the outside and the endocardial membrane on the inside. The fibres have in the auricle a much greater tendency to be>J branched, and many, ceasing to be spindle-shaped, become almost stellate. Among the obscurely striated, but still striated fibres are found ordinary plain muscular fibres which increase in relative number along the roots of the veins, venae cavse and pulmonales, 18—2 276 CARDIAC MUSCULAR TISSUE. [BOOK i. until at some little distance from the heart plain muscular fibres only are found. Blood vessels are absent from the walls of the auricles also. In the bulbus arteriosus, mixed up with much connective and elastic tissue, are found fusiform fibres which close to the ventricle are striated and form a thick layer, but at a certain distance from the ventricle lose their striation, or rather become mixed with plain muscular fibres, and form a thinner layer. § 152. In the mammal, both the ventricles and the auricles are formed of bundles of muscular tissue, bound together by con- nective tissue, and arranged more especially in the ventricles in a very complex system of sheets or bands disposed as spirals, and in other ways, the details of which need not detain us. In the auricular appendices and elsewhere, the bundles form irregular networks projecting into the cavities. The connective tissue binding the muscular fibres together, unlike the corresponding connective tissue in the frog's heart, is well supplied with blood vessels belonging to the coronary system. This connective tissue forms on the inner surface of the cavities a continuous sheet, the connective tissue basis of the flat epithelioid cells of the endocardium, and on the outside of the heart the visceral layer of the pericardium. The histological unit of these muscular bundles is neither a fibre nor a fusiform fibre cell, butt a more or less columnar or prismatic nucleated cell generally provided with one or more short broad processes. The nucleus, which is oval and in general resembles one of the nuclei of a striated fibre, is placed in about the middle of the cell with its long axis in the line of the long diameter of the cell. The cell body, which is not bounded by any definite sarcolemma, is striated, though obscurely so, across, the long diameter of the cell, the striations as in a skeletal muscle fibre being due to the alternation of dim and bright bands. As in the frog's heart granules are frequently abundant, obscuring the striation, which indeed even in the absence of granules is never so distinct as in the fibres of skeletal muscles. Such a cell is at each end joined by cement substance to similar cells, and a row of such cells constitutes a cardiac elementary fibre. Hence a cardiac fibre is a fibre striated, but without sarcolemma, and divided by parti- tions of cement substance into somewhat elongated divisions or cells, each containing a nucleus. Many of the cells in a fibre have a short broad lateral process. Such a process is united by cement substance to a similar process of a cell belonging to an adjoining fibre ; and by the union of a number of these processes, a number of parallel fibres are formed into a somewhat close network. Each bundle of the cardiac muscular tissue is thus itself a network. These bundles are further woven into networks by connective tissue in which run capillaries and larger blood vessels; and sheets or bundles composed of such networks are arranged as we have CHAP, iv.] THE VASCULAR MECHANISM. 277 said in a complex manner both in the auricle and ventricle. Hence the muscular substance of the mammalian heart is, at bottom, an exceedingly complex network, the element of which is a somewhat branched nucleated striated cell. It may be remarked that the ' musculi pectinati ' of the auricle and the ' columnse carnese ' of the ventricle suggest the origin of the mammalian heart from a muscular labyrinth like that of the frog's ventricle. At the commencement of the great arteries this peculiar cardiac muscular tissue ceases abruptly, being replaced by the ordi- nary structures of an artery, but the striated muscular fibres of the auricle may be traced for some distance along both the venaB cavse and vense pulmonales. Under the endocardium are frequently present ordinary plain muscular fibres, and in some cases peculiar cells are found in this situation, the cells of Purkmje, which are interesting morphologi- cally because the body of the cell round the nucleus is ordinary clear protoplasm while the outside is striated substance. Plain muscular fibres are said also to spread from the endocardium for a certain distance into the auriculo-ventricular valves. §153. The Nerves of tli e Heart. The distribution of nerves in the heart varies a good deal in different vertebrate animals, but nevertheless a general plan is more or less evident. The verte- brate heart may be regarded as a muscular tube (a single tube, if for the moment we disregard the complexity of a double circulation occurring in the higher animals) divided into a series of chambers, sinus venosus (or junction of great veins), auricle, ventricle and bulbus (or conus) arteriosus. The nerves (with the exception of a small nerve which in some animals reaches the heart by the aorta) enter the heart at the venous end of this tube, at the sinus venosus, ' and pass on towards the arterial end, diminishing in amount as they proceed, and disappearing at the aorta. Con- nected with the nerve fibres thus passing to the heart are groups, smaller or greater, of nerve cells. These like the nerve fibres are most abundant at the venous end (appearing on the nerve branches before these actually reach the heart), as a rule become fewer towards the arterial end, and finally disappear, so that (ac- cording to most observers) at the bulbus (conus) arteriosus they are entirely absent. These collections of nerve cells or ganglia may be arranged in groups according to their position. In many lower vertebrates there is a distinct ring or collar of ganglia at the junction of the sinus venosus with the auricle, where the primitive circular disposition of muscular fibres is maintained ; and there is a similar ganglionic collar at the junction of the auricle with the ventricle, where also there is similarly retained a circular dis- position of the muscular fibres forming the so-called canalis auri- cularis. And indeed in all vertebrates two similar collections of \ ganglia are more or less distinctly present. There are ganglia 278 THE NERVES OF THE HEART. [BOOK i. at the junction of the sinus with the auricle and along the entering nerve branches; these may be called the sinus ganglia. There are other ganglia at the junction of the auricle and ven- tricle ; these may be called the auriculo-ventricular ganglia. Besides these two groups there are also ganglia over the auricle in connection with nerves passing from the sinus to the ventricle. Lastly, as a general rule the main nerve branches and the ganglia are not plunged deep in the substance of the heart, but are placed superficially, immediately under the pericardial layer. From the cells and nerves so situated finer branches and fibres pass to the substance of the heart. In the frog (and other amphibia) the arrangement differs somewhat from the above plan and therefore needs a special description. The only nerves going to the heart of the frog are the two •vagi, right and left, which may be seen running along the two superior venae cava3, and becoming lost to view at the sinus where they pass from the surface to deeper parts. Each vagus is not however simply a vagus nerve, but as we shall see contains fibres derived from the splanchnic or sympathetic system. As the nerves approach the sinus, groups of nerve cells become abundant in connection with the fibres, and as the fibres spread out at the sinus many ganglia are scattered among them, forming what is called as a whole the sinus ganglion or the ganglion of Remak. From the sinus the two vagi, leaving their position under the ' pericardium plunge into the heart and run along the septum between the auricles, on the left side of the septum, one, the , anterior nerve, passing nearer the front of the heart than the other, the posterior. Several groups of cells, or small ganglia, } are connected with the two ' septal ' nerves thus passing along the septum. The nerves reaching the auriculo-ventricular ring on the an- terior side of the heart end in two ganglia lying at the base of the two large auriculo-ventricular valves. From these two ganglia, Bidders ganglia or the auriculo- ventricular ganglia, nerve fibres pass into the substance of the ventricle. Nerve cells may be traced on the fibres going to the ventricle for some little distance, but for a little distance only; over the greater part of the ventricle, the lower two-thirds for instance, the nerve fibres are free from nerve cells. Thus in the frog there are two main ganglia, sinus or Remak's ganglion, auriculo-ventricular or Bidder's ganglia. From the former there pass on the one hand scattered fibres, in connection with which are small groups of cells, to the auricular walls, and to the sinus walls, and on the other hand the two main nerves running along the septum, in connection with which are small ganglia which may be called ' septal ' ganglia. From the latter, Bidder's ganglia, fibres unaccompanied except for a short distance by nerve CHAP, iv.] THE VASCULAR MECHANISM. 279 cells pass to the substance of the ventricle, and possibly to the bul bus arteriosus. In the mammal, the arrangement appears to conform more closely to the general plan described above. The several cardiac nerves from the sympathetic chain together with branches from, the vagus, including fibres from the recurrent faryngeal, form the superficial and deep cardiac plexuses below and beneath the arch of the aorta. From these plexuses fibres are distributed to the superior vena cava and to the pulmonary veins and thence to the various parts of the heart. Ganglia are abundant on the superior vena cava and are also found on the pulmonary veins, in the walls of the auricles, in the auriculo-ventricular groove and in the basal portion of the ventricles ; further, according to some observers, in contrast to the frog's heart, a number of small ganglia may be observed over a large part of the ventricle far down towards the apex. The auricular septum, at least in its central parts, is free from ganglia. The nerves and ganglia lie for the most part superficially immediately under the pericardium. In the frog, the fibres forming the vagus nerves as they run along the superior vense cava3 are composed of medullated and non-medu Hated fibres, the latter being chiefiy if not wholly derived from the splanchnic or sympathetic system. Medullated fibres, with a larger proportion of non-medullated fibres are found in the septal nerves, running to Bidder's ganglia, but the fine fibres which pass from Bidder's ganglia to the substance of the ven- tricle are exclusively non-medullated fibres. The nerve cells in the sinus ganglia and along the ends of the vagus nerves, as well as some of the cells of the ganglia scattered over the septum, are of the kind previously (§ 98) described as spiral cells. The cells composing Bidder's ganglia, as well as many of the cells in the septum, are said to be bipolar and fusiform. In the mammal, the fibres passing to the heart are also medullated and non-medullated. Some of the medullated fibres are of fine calibre, may be traced back to the vagus, and appear to be fibres of which we shall speak presently asdnhibitory. Others of the medullated fibres are of larger calibre, and some of these at all events appear to_be sensory or at least afferent in function. Of the non-medullated fibres, some may be traced back along the cardiac nerves to the inferior cervical ganglion and are of the kind we shall speak of as augmenting. In contrast to the frog many of the fibres in the ventricle (where they lie close under the peri- cardium), are medullated, and it is probable that these are afferent fibres. The cells forming the various ganglia scattered over the mammalian heart may perhaps be classed as unipolar, and multipolar, the former being especially connected with medullated fibres, the one class being prominent in one situation, the other in another. •280 GRAPHIC RECORD OF HEART-BEAT. [BOOK i. The Development of the Normal Beat. § 154. The heart of a mammal or of a warm-blooded animal generally ceases to beat within a few minutes after being removed from the body in the ordinary way, the hearts of newly born animals continuing however to beat for a longer time than those of adults. Hence, though by special precautions and by means of an artificial circulation of blood, an isolated mammalian heart may be preserved in a pulsating condition for a much longer time, our knowledge of the exact nature and of the causes of the cardiac beat is as yet very largely based on the study of the hearts of cold-blooded animals, which will continue to beat for hours, or under favourable circumstances even for days, after they have been removed from the body with only ordinary care. We have reason to think that the mechanism by which the beat is carried on varies in some of its secondary features in different kinds of animals : that the hearts, for instance, of the eel, the snake, the tortoise and the frog, differ in some minor details of behaviour, both from each other and from the bird and the mammal ; but we may, at first at all events, take the heart of the frog as illustrating the main and important truths concerning the causes and mechanism of the beat. In studying closely the phenomena of the beat of the heart it becomes necessary to obtain a graphic record of various movements. 1. In the frog or other cold-blooded animal, a light lever may be placed directly on the ventricle (or on an auricle, V.r IX Vg S.V.C2 FlG. 55. DIAGRAMMATIC KEPRESENTATION OF THE COUKSE OF CARDIAC AuGMENTOR FIBRES IN THE FROG. T>. roots of vagus (and rxth) nerve. GV. ganglion of same. Cr. line of cranial wall. Vg. vagus trunk, ix. ninth, glosso-pharyngeal nerve. S.V.C. superior vena cava. Sy. sympathetic nerve in neck. G.C. junction of sympathetic ganglion with vagus ganglion sending i.e. intracranial fibres passing to Gasserian ganglion. The rest of the fibres pass along the vagus trunk. G' splanchnic ganglion connected with the first spinal nerve. G" splanchnic ganglion of the second spinal nerve. An.V. annulus of Vieussens. A.sb. subclavian artery. G1" splanchnic ganglion of the third spinal nerve. III. third spinal nerve, r.c. ramus communicans. The course of the augmentor fibres is shewn by the thick black line. They may- be traced from the spinal cord by the anterior root of the 3rd spinal nerve, through the ramus communicans to the corresponding splanchnic ganglion G1" and thence by the second ganglion G", the annulus of Vieussens, and the first ganglion G1 to the cervical sympathetic Sy and so by the vagus trunk to the superior vena cava S.V.C. €HAP. iv.] THE VASCULAR MECHANISM. 293 the brain, we find that just as the nerve has pierced the cranium, just where it passes through the ganglion (GV, Fig. 55), certain fibres pass into it from the sympathetic nerve of the neck, Sy, of the further connections of which we shall speak presently. This being the case we may expect that we should get different results according as we stimulated (1) the vagus in the cranium, before it was joined by the sympathetic, (2) the sympathetic fibres before they join the vagus and (3) the vagus trunk, containing the real vagus and the sympathetic fibres added. What we have pre- viously described are the ordinary results of stimulating the mixed trunk, and these as we have said are not wholly constant, though, usually and in the main, most distinct inhibitory results follow. If we stimulate the sympathetic in the neck as at Sy, Fig. 54, cutting the nerve below so as to block all impulses from passing ; downwards, and only allow impulses to pass up to the vagus and thence down the mixed vagus trunk to the heart, we get very re- markable results. -^The beat of the heart instead of being inhibited is augmented, the beats are increased either in frequency or in force, or most generally both in frequency and in force. The effect is perhaps best seen when the heart before stimulation is beating slowly and feebly ; upon stimulation of the cervical sympathetic the beats at once improve in vigour and frequency ; indeed a heart which for one reason or another has almost ceased to beat may, by proper stimulation of the sympathetic, be called back into vigorous activity. If on the other hand we stimulate the vagus before it has been joined by the sympathetic fibres (and to ensure the result not being marred by any escape of the stimulating current on to the sympathetic fibres it is necessary to stimulate the vagus within the cranium) we get pure and constant inhibitory results, the beats are for a time wholly abolished, or are slowed, or are weakened, or are both slowed and weakened. Obviously then the heart of the frog is supplied through the vagus by two sets of fibres coming from the central nervous system, the one by the vagus proper and the other by the cervical sym- pathetic nerve, and these two sets have opposite and antagonistic effects upon the heart. We find upon examination that we can make the following statements concerning them. The one set, those belonging to the vagus proper, are inhibitory; they weaken the systole and prolong the diastole, the effect with a strong stimulation being complete, so that the heart is for a time brought to a standstill. Sometimes the slowing, sometimes the weakening is the more prominent. When the nerve and the heart are in good condition, it needs only a slight stimulus, a weak cur- rent, to produce a marked effect, and it may be mentioned that the more vigorous the heart, the more rapidly it is beating, the easier is it to bring about inhibition. Although as we have said the effect is at its maximum soon after the beginning of stimulation, a very 294 AUGMENTOR FIBRES. [BOOK i. prolonged inhibition may be produced by prolonged stimulation ; indeed by rythmical stimulation of the vagus the heart may be kept perfectly quiescent for a very long time and yet beat vigor- ously upon the cessation of the stimulus. In other words, the mechanism of inhibition, that is the fibres of the vagus and the part or substance of the heart upon which these act to produce inhibition, whatever that part or substance may be, are not readily exhausted. Further the inhibition when it ceases is, frequently at all events, followed by a period of reaction, during which the heart for a while beats more vigorously and rapidly than before. Indeed the total effect of stimulating the vagus fibres is not to exhaust the heart but rather to strengthen it ; and by repeated inhibitions carefully administered, a feebly beating- heart may be nursed into vigorous activity. The other set, those joining the vagus from the sympathetic, are ' augmentor ' or ' accelerating ' fibres ; the latter name is the more common but the former is more accurate since the effect of stimulating these fibres is to increase not only the rapidity but the force of the beat ; not only is the diastole shortened but the systole is strengthened, sometimes the one result and sometimes the other being the more prominent. "f^Iu contrast with the case of the vagus fibres, a somewhat strong stimulation is required to produce an effect ; the time required for the maximum effect to be produced is also remarkably long. Moreover, at all events in the case of a heart in which the circulation is not maintained and which is therefore cut off from its normal nutritive supply ,^ -d he augmentor fibres are far less easily exhausted than are the inhibi- tory fibres. Hence when, in such a heart, both sets of fibres are stimulated together, as when the vagus trunk in the neck is stimulated, the first effects produced are those of inhibition, but these on continued stimulation may become mixed with those of augmentation and finally the latter alone remain. Lastly the contrast is completed by the fact that the augmentation resulting from the stimulation of the sympathetic is followed by a period of reaction in which the beats are feebler ; in other words augmen- tation is followed by exhaustion ; and indeed by repeated stimula- tion of these sympathetic fibres a fairly vigorous bloodless heart may be reduced to a very feeble condition. By watching the effects of stimulating the sympathetic nerve at various points of its course we may trace these augmentor fibres from their junction with the vagus down the short sympa- thetic of the neck through the first splanchnic or sympathetic ganglion connected with the first spinal nerve, G1, Fig. 55, through one or both the loops of the annulus of Vieussens, An. V, through the second ganglion, connected with the second spinal nerve, G", to the third ganglion connected with the third spinal nerve, GIH, and thence through the ramus communicans or visceral branch of that ganglion, r. c., to the third spinal CHAP, iv.] THE VASCULAR MECHANISM. 295 nerve, ///, by the anterior root of which they reach the spinal cord. § 159. Both sets of fibres then may be traced to the central nervous system ; and we find accordingly that the heart may be inhibited or augmented by nervous impulses which are started in the nervous system either by afferent impulses as part of a reflex act or otherwise, and which pass to the heart by the inhibitory or by the augmenting tract. Thus if the medulla oblongata or a particular part of the medulla oblongata which is specially connected with the vagus nerve be stimulated, the heart is inhibited ; if for instance a needle be thrust into this part the heart stands still. This region in question may be stirred to action, in a ' reflex ' manner, by afferent impulses reaching it from various parts of the body. Thus if the abdomen of a frog be laid bare, and the intestine be struck sharply with the handle of a scalpel, the heart will stand still in diastole with all the phenomena of vagus inhibition. If the nervi mesenterici or the connections of these nerves with the spinal cord be stimulated with the interrupted current, cardiac inhibition is similarly produced. If in these two experiments both vagi are divided, or the medulla oblongata is destroyed, inhi- bition is not produced, however much either the intestine or the mesenteric nerves be stimulated. This shews that the phenomena are caused by impulses ascending along the mesenteric nerves to the medulla, and so affecting a portion of that organ as to give rise by reflex action to impulses which descend the vagi as inhibitory impulses. The portion of the medulla thus mediating / between the afferent and efferent impulses may be spoken of as ) the cardio-inhibitory centre. Reflex inhibition through one vagus may be brought about by stimulation of the central end of the other. In general the alimentary tract seems in closer connection with the cardio-inhi- bitory centre than other parts of the body ; and if the peritoneal surface of the intestine be inflamed, very gentle stimulation of the inflamed surface will produce marked inhibition. But apparently stimuli if sufficiently powerful will through reflex action produce inhibition whatever be the part of the body to which they are applied. Thus crushing a frog's foot will stop the heart, and adequate stimulation of most afferent nerves will produce some amount of inhibition. The details of the reflex chain and the portion of the centre concerned in the development of augmenting impulses have not been worked out so fully as in the case of inhibitory impulses, but there can be little doubt that the former like the latter are governed by the central nervous system. § 160. So far we have been dealing with the heart of the frog, but the main facts which we have stated regarding inhi- bition and augmentation of the heart-beat apply also to other 296 INHIBITION IN THE MAMMAL. [BOOK i. vertebrate animals including mammals, and indeed we meet similar phenomena in the hearts of invertebrate animals. If in a mammal the heart be exposed to view by opening the thorax, and the vagus nerve be stimulated in the neck, the heart may be seen to stand still in diastole, with all the parts flaccid and at rest. If the current employed be too weak, the result as in the frog is not an actual arrest but a slowing or weakening of the beats. If a light lever be placed on the heart a graphic record of the ^standstill, or of the slowing, of the complete or incomplete inhibition may be obtained. The result of stimulating the vagus is also well shewn on the blood-pressure curve, the effect of complete cardiac inhibition on blood-pressure being most striking. If, while a tracing of arterial pressure is being taken, the beat of the heart be suddenly arrested, some such curve as that represented in Fig. 56 will be obtained. It will be observed that two beats follow FIG. 56. TRACING, SHEWING THE INFLUENCE OF CARDIAC INHIBITION ON BLOOD- PRESSURE. FROM A BABBIT. x the marks on the signal line when the current is thrown into, and y shut off from the_vagus. The time marker below marks seconds, the heart, as is frequently the case in the rabbit, beating very rapidly. the application of the current marked by the point a, which corresponds to the signal x on the line below. Then for a space of time no beats at all are seen, the next beat b taking place almost immediately after the shutting off the current at y. Immediately after the last beat following a, there is a sudden fall of the blood-pressure. At the pulse due to the last systole, the arterial system is at its maximum of distention ; forthwith the elastic reaction of the arterial walls propels the blood forward into the veins, and, there being no fresh fluid injected from the heart, the fall of the mercury is unbroken, being rapid at first, but slower afterwards, as the elastic force of the arterial walls is more and more used up. With the returning beats the pressure corre- CHAP, iv.] THE VASCULAR MECHANISM. 297 spondingly rises in successive leaps until the normal mean pressure is regained. The size of these returning leaps of the mercury may seem disproportionately large, but it must be remembered that by far the greater part of the force of the first few strokes of the heart is expended in distending the arterial system, a small portion only of the blood which is ejected into the arteries passing on into the veins. As the arterial pressure rises, more and more blood passes at each beat through the capillaries, and the rise of the pressure at each beat becomes less and less, until at last the whole contents of the ventricle pass at each stroke into the veins, and the mean arterial pressure is established. To this it may be added, that, as we have seen, the force of the individual beats may be somewhat greater after than before inhibi- tion. Besides, when the mercury manometer is used, the inertia of the mercury tends to magnify the effects of the initial beats. In the mammal inhibition may be brought about by impulses passing along fibres which, starting in the medulla oblongata, run down over the vagus nerve and reach the heart by the cardiac nerves. It would appear however that the inhibitory fibres do not belong to the vagus proper^Jbut leave the central nervous system by the spinal accessory nerve. Thus if the roots of the spinal accessory be divided, those of the vagus proper being left intact, the spinal accessory fibres in the vagus trunk degenerate, and when this takes place stimulation of the vagus trunk fails to produce the ordinary inhibitory effects. In the mammal as in the frog inhibition may be brought about not only by artificial stimulation of the vagus trunk, but by stimulation in a reflex manner or otherwise of the cardio-inhibitory centre. Thus the fainting which often follows upon a blow on the stomach is a repetition of the result just mentioned as obtained on the frog by striking the stomach or stimulating the nervi mesenterici. So also the fainting, complete or partial, which accompanies severe pain or mental emotion is an illustration of cardiac inhibition by the vagus. In fact cardiac inhibition so far from being a mere laboratory experiment enters repeatedly into the every day work- ing of our own organism as well as that of other living beings. Indeed there is some reason for thinking that the central nervous system by means of the cardiac inhibitory fibres keeps as it were a continual rein on the heart, for, in the dog at least, section of both vagi causes a quickening of the heart's beat. In the dog the augmentor fibres (Fig. 57) leave the spinal cord - by the anterior roots of the second and third dorsal nerves, possibly also to some extent by the fourth and fifth, pass along the rami communicantes of those nerves to the ganglion stellatum, first thoracic ganglion, or respectively to one or other of the ganglia forming part of the thoracic splanchnic or sympathetic chain immediately below, and thence upwards through the annulus of Vieussens, passing along one or other or both loops, to the inferior 298 AUGMENTOR FIBRES IN MAMMAL. [BOOK i. G.Tr.Vg,- Vg G.Th4 FIG. 57. DIAGRAMMATIC KEPRESENTATION OF THE CARDIAL INHIBITORY AND AUGMENTOR FIBRES IN THE DOG. The upper portion of the figure represents the inhibitory, the lower the augmentor fibres. CHAP, iv.] THE VASCULAR MECHANISM. 299 r. Vfj. roots of the vagus ; r. Sp. Ac. roots of the spinal accessory : both drawn very cliagrammatically. G. J. ganglion jugulare. G. Tr. Vg. ganglion truiici vagi. Sp. Ac. spinal accessory trunk. Ext. Sp. Ac. external spinal accessory. i.Sp.Ac. internal spinal accessory. V