mill IMIllHI i|M|ll|l|lllll||!lllllll| HX64089487 QP34 .St4 A manual of physiolo RECAP (^I>3i StY tntljeCitpoflrmgork COLLEGE OF PHYSICIANS AND SURGEONS LIBRARY Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/manualofphysioloOOstew A MANUAL OF PHYSIOLOGY. Frofi {onthejt-at) (aide titej") BiM Plate I . Fi8h Mammal Camel Blood of mammal u ' w '®^<- \ i /' y Frog's vorpufcle after addition of water Mamvialiaii after addition ofgyrup Mammalian after addition of tail '«^^®^3." » • Q 1, Red blood-corpuscles. s 5 ^' h fi-y x;-^:::.->... ,# -• 2. The colourless corpuscleg of human blood, x 1000. a, coarsely granular oxyphile cells; b, finely granular oxyphile cells; c, hyaline cells, d, lymphocyte ; e, finely granular basophile cells (Kanthack and Hardy). The magnification is much greater than in 1. Blood in capillary Nucleus Muscle fibre - Conrmctivc tiisue -m Transverse section at level of nueUus ^tite^ cell more highly magnified Transverse seetioi ' '"- of branch of muscle cell \ VV 3. Hffimin crystals. 4. Section of heart, x 300- (Stained with hsematoxylin.) A MANUAL OF PHYSIOLOGY, WITH PRACTICAL EXERCISES. G. N. STEWART, M.A., D.Sc, M.D. Edin., D.P.H.Camb., OF DOWNING COLLEGE, CAMBRIDGE; PROFESSOR OF PHYSIOLOGY IN THE WESTEKN RESERVE UNIVERSITY, CLEVELAND; FORMERLY GEORGE HENRY LEWES STUDENT ; EXAMINER IN PHYSIOLOGY IN THE UNIVERSITY OF AP.ERDEEN ; SENIOR DEMONSTRATOR O*' PHYSIOLOGY IN THE OWENS COLLEGE, VICTORIA UNIVERSITY, ETC. WITH NUMEROUS ILLUSTRATIONS, INCLUDING FIVE COLOURED PLATES. UNIVERSITY \5\ fm PI SERIES LONDON : BAILLIERE, TINDALL AND COX, 21 & 22, KING WILLIAM STREET, STRAND. [PARIS. MADRID.] 1895. [Ail rights resefi'eii.] PREFACE At the present day, to teach Physiology by means of formal lectures and systematic text-books alone is no more satis- factory than it would be to till the farms of America with the wooden plough of Bengal. Some benefit can certainly be gained from the mere reading of a good text-book or listening to a good lecturer ; but the result will be meagre in comparison with the capabilities of the subject, and the knowledge thus acquired will be more likely to sink to the level of " cram " than to rise to the level of education. In this book an attempt has been made to interweave formal exposition with practical work, in the way my experience at the Harvard Medical School and the Western Reserve University has shown to be best suited to the needs and the opportunities of the American student. An arrangement of the Practical Exercises with reference to the systematic course has this great advantage — that by a little care it is possible to secure that the student shall be actually working at a given subject at the time it is being lectured on. Cross-reference from lecture-room to laboratory, and from laboratory to lecture-room, from the detailed discussion of the relations of a phenomenon to the living fact itself, is thus rendered easy, natural, and fruitful. As some teachers may wish to know how a course such as that described in the Practical Exercises may be conducted for a fairly large class, a few words on the method we have followed may not be out of place. It is obvious that many of the exercises require more than one person for their per- formance ; and it may be said that, except in the case of the simpler experiments and the chemical work as a whole, which each student does for himself, it has been found convenient to divide the class into groups of four, each group remaining together throughout the session. It is A. I 2 PREFACE, i possible that some may find a group of four too large a unit, and it is certain that three, or perhaps even two, would be better ; but in a large school so minute a subdivision is hardly possible, without entailing excessive labour on the teachers. The systematic portion of the book is so arranged that it can equally well be used independently of the practical work, and aims at being in itself a complete exposition of the subject, adapted to the requirements of the student of medicine. I have to acknowledge my obligations to Professor Michael Foster, of Cambridge, for the use of his laboratory and its library ; to Professor Burdon Sanderson, of Oxford, for permission to reproduce several of his figures illustrating the electrical changes in active muscle ; to Dr. Arthur Clarkson for the drawings represented in Plate L, i-io and 15, Plate II., Plate III., i, Plate V., i and 2, and Fig. go ; to Mr. Sollmann, my demonstrator, for most of the figures in the section on Vision ; and to my pupil, Mr. Kelley, for Plate III., 4, Plate IV., 4, and twelve of the figures in the text. Figs. 2, 75-79> 84, 93, 96-99, 108, 131, 153, 210, 237j 255, and 265, have been borrowed from Beaunis' ** Physiologic." The figures of leucocytes in Plate 1 , 11-13, are taken, by permission, from a paper by Dr. Kanthack and Mr. Hardy. Messrs. Jung, Petzold, Reichert, and Zeiss have supplied me with several electrotypes of instruments. Fig. 83 is borrowed from Hermann's " Handbuch der Physiologic." My best thanks are due to my friends, Mr. Stanley Kent and Dr. Lorrain Smith, for reading the proof-sheets of several of the chapters (the former. Chapters I. to III.; the latter, Chapters HI., VII., and VIII.). As to the matter of the text, it is hardly necessary to say that this book does not aspire to the dubious distinction of originality ; and it is literally impossible to acknowledge all the sources from which information has been derived. In many cases names have been quoted, but names no less worthy of mention have often been of necessity omitted. G. N. STEWART. Cambridge, September., 1895. CONTENTS. I'AGE Introduction - - - . . - u CHAPTER I. The Circulating Lkjuids of the Body - - - 17 Blood-corpuscles - - - - - 18 Blood-plates - - - - - - 21 Life-history of the corpuscles - - - - 22 Coagulation of blood - - - - - 26 Chemical composition of blood - - '33 Haemoglobin and its derivatives - - - 34 Quantity of blood - - - - - 39 Lymph and chyle - - - - - 40 Functions of blood and lymph - - - - 42 CHAPTER IL The Circulation of the Blood and Lymph - - 53 The beat of the heart - - - - 60 The sounds of the heart - - - - 62 The cardiac impulse - - - - - 64 The pulse - - - - - - 69 Blood-pressure - - - - - 79 Velocity of the blood - - - - - 87 The volume-pulse - - - - - 96 The circulation in the capillaries - - - 97 The circulation in the veins - - - - 100 The circulation-time ----- 102 The relation of the nervous system to the circulation - 107 Nerves of the heart - - - - - loS Vaso-motor nerves - - - - - 123 The lymphatic circulation - - - - 140 CONTENTS. CHAPTER III. PAGE Respiration - - - - - - i6o Mechanical phenomena of respiration - - - 164 Types of respiration - - - - - 170 Respiratory pressure - - - - - I74 Intra-thoracic pressure - - - - I74 Relation of respiration to the nervous system - - 175 Chemistry of respiration - - - - 183 The gases of the blood . . . . iqq Influence of respiration on blood-pressure - - 208 Voice and speech ..... 218 CHAPTER IV. Digestion ...... 233 Mechanical phenomena of digestion - - - 237 Chemistry of the digestive juices - - - 247 Saliva ..... 248 Gastric juice .... - 253 Pancreatic juice .... 258 Bile -----. 262 Succus entericus .... 269 Secretion of the digestive juices - - - 270 Changes in pancreas and parotid during secretion - 273 Changes in gastric glands during secretion - - 274 Changes in mucous glands during secretion - 276 Influence of the nervous system on the salivary glands - 286 Influence of the nervous system on the gastric glands - 295 Influence of the nervous system on the pancreas - - 297 Influence of the nervous system on the secretion of bile - 298 Influence of the nervous system on the secretion of intestinal juice ...... 300 Digestion as a vi^hole ..... 302 CHAPTER V. Absorption - - - - - - 312 Formation of lymph - - - . . 317 Absorption of fat - - - - - 318 Absorption of water, salts, and sugar - - - 320 Absorption of proteids .... 320 CONTENTS. CHAPTER VI. PAGE Excretion ...--. 330 Excretion by the kidneys - - - - 33i Chemistry of urine - - - - - 33i Secretion of urine . . - - - 340 Influence of the circulation on the secretion ot urine - 350 Micturition - - - - "355 Excretion by the skin ... - 357 CHAPTER VII. Metabolism, Nutrition, and Dietetics - - - 372 Metabolism of proteids ... - 372 Formation of urea .... - 374 Metabolism of carbo-hydrates — glycogen - - 381 Metabolism of fat - - - - - 3^7 Income and expenditure of the body - - - 39^ Nitrogenous equilibrium . . - - 393 Carbon equilibrium ----- 4^3 Dietetics ------ 4°? Internal secretion - - - - -414 CHAPTER VIII. Animal Heat - - - - - - 4i''^ Heat-loss ------ 4-3 Heat-production ----- 4-5 Thermotaxis ... - - 434 Fever ----■■ 443 Distribution of heat - - - - - 447 CHAPTER IX. Muscle - - - - - - 462 Physical introduction - - - - 462 Physical properties of muscle - - - - 478 The muscular contraction - - - - 484 Optical phenomena of - - - ■ 485 Mechanical phenomena of - - - 486 Thermal phenomena of - - ■ S^S Chemical phenomena of - - - 509 Source of the energy of muscular contraction - -511 Rigor mortis - - - " "5^3 CONTENTS. CHAPTER X. PAGE Nerve - - - - - - - 518 The nerve-impulse ; its initiation and conduction - - 519 Electrotonus ..... 523 Velocity of the nerve-impulse - . . . 530 Nutrition of nerve . - . . . 5^3 Classification of nerves - - . . 538 CHAPTER XI. Electro-Physiology - - - - - 555 Currents of rest and action - - - - 556 Polarization of muscle and nerve - - - 565 Electrotonic currents . - . . ^7 Glandular currents - - - - - 573 Eye-currents ..... 574 Electric fishes ..... 575 CHAPTER XII. The Central Nervous System - - - - 586 Structure of ..... 587 Arrangement of grey and white matter in the spinal cord - 594 Arrangement of grey and white matter in the upper part of the cerebro-spinal axis .... ^gg functions of the central nervous system - - - 610 Functions of the spinal cord .... 612 Reflex action ..... 622 Automatism of the spinal cord - - - . 628 The cranial nerves ----- 633 The functions of the brain . . - . g^g Functions of the cerebellum - - . . 642 Co-ordination of movements - - . . 650 Functions of the cerebral cortex - - - 654 Motor areas ..... 657 Sensory areas ..... 661 CHAPTER XIII. The Senses - - - - - - 682 Vision ...... 684 Hearing --.... 750 Smell and taste - - - - - 760 Tactile senses - - . . . 762 Muscular sense ..... 766 CONTENTS. CHAPTER XIV. PAGE Reproduction ------ 774 Regeneration of tissues . . - . 774 jNIenstruation ----- 775 Development of the ovum - - - . 775 Physiology of the embryo . - . . 77^ PRACTICAL EXERCISES. INTRODUCTION. 1. General reactions of proteids - - - - 14 2. Special reactions of groups of proteids - - -14 3. Carbo-hydrates - - - - - - '5 4. Emulsification of fats - - - - - 16 CHAPTER I. 1. Blood, reaction of - - - - - 44 2. Blood, specific gravity of - - - - 44 3. Blood, opacity of — to make blood 'laky ' - - - 45 4. Blood, coagulation of - - - - - 45 5. Fibrin-ferment, preparation of - - - - 47 6. Intravascular coagulation - - - - 47 7. Serum - - - - - - 47 8. Cell-free plasma - - - - - - 48 g. Enumeration of the corpuscles - - - 48 10. Blood-pigment - - - - - -49-52 CHAPTER II. 1. IMicroscopic examination of the circulating blood - - 142 2. Anatomy of frog's heart - . - - 143 3. The beat of the heart ----- 143 4 ' Apex ' preparation of heart . - - - 143 5. Heart-tracings ..... 143 6. Dissection of vagus and cardiac sympathetic in frog - - 147 7. Stimulation of vagus in frog . . - - 148 8. Stimulation of the junction of sinus and auricles - - 148 g. Effect of muscarine and atropia - - - - i4g 10. Stannius' experiment ... - - 149 11. Stimulation of cardiac sympathetic in frog - - - 149 8 CONTENTS. PAGE 12. The action of the mammalian heart - - - 150 13. Action of the valves of the heart - - - - 152 14 Cardiogram - - - - - - 154 15. Blood-pressure tracing - - - - - I54 16. Section and stimulation of cervical sympathetic in rabbit - 155 17. Stimulation of the depressor in rabbit - - - 156 18. Determination of the circulation-time - - - 156 ig. Sphygmographic tracings - - - - I59 20. Plethysmographic tracings - - - - I59 CHAPTER in. 1. Tracing of respiratory movements (dog) - - - 230 2. Measurement of COo and HoO given off in respiration - 232 3. Section of both vagi . . . - - 232 CHAPTERS IV. AND V. 1. Saliva ...... 322 2. Gastric juice ------ 324 3. Pancreatic juice . . . _ . 326 4. Bile - - - - - - - 327 5. Fasces ..... 6. Absorption of fat - 7. Time required for digestion and absorption of various food sub- stances ...... 329 8. Time required for food to pass through alimentary canal - 329 CHAPTER VI. 1. Specific gravity of urine _ . . . 361 2. Reaction of urine ..... 361 3. Chlorides in urine .... - 361 4. Phosphates in urine . - . . . 362 5. Sulphates in urine ..... 362 6. Indoxyl in urine ..... 363 7. Urea ...... 363 8. Total nitrogen in urine . - - - - 365 9. Uric acid ...... 366 10. Kreatinin ..._.. 367 11. Hippuric acid - ..... 367 12. Proteids in urine ..... 368 13. Sugar in urine . . . . . 370 14. Catheterism - - - - - -371 CONTENTS. CHAPTERS VII. AND VIII. PAGE 1. Glycogen - - - - - - 453 2. Glycosuria -.---. 454 3. Estimation of CO3 and HoO given off - - - 455 4. Measurement of heat given off in respiration - - 458 5. Variations in urea with proteids in food - - - 460 6. Nitrogenous metabolism .... 460 7. Thyroidectomy ..... 450 8. Thyroidectomy with thyroid feeding - - - 461 CHAPTERS IX. AND X. 1. Difference of make and break shocks - - - 539 2. Stimulation of nerve and muscle by voltaic current - - 541 3. Mechanical stimulation - - - . . 542 4. Thermal stimulation ..... ^42 5. Chemical stimulation . - . . . 542 6. Ciliary motion ..... 542 7. Direct excitability of muscle . . . . C43 8. Graphic record of twitch .... 54-1 9. Influence of temperature on the muscle-curve - - 543 10. Influence of load on the muscle-curve - - - 545 11. Influence of fatigue on the muscle-curve - - - 545 12. Seat of exhaustion in fatigue of the muscle-nerve preparation - 545 13. Seat of exhaustion in fatigue for voluntary muscular contraction 546 14. Influence of veratria on muscular contraction - . 547 15. Latent period ------ 547 16. Summation of stimuli - - - . . 548 17. Superposition of contractions . - . . 548 18. Composition of tetanus - ... - 549 19. Velocity of the nerve-impulse .... 549 20. Chemistry of muscle . - . . . 551 21. Reaction of muscle ..... 552 22. Specific gravity of muscle - - - ■ 553 23. Action of suprarenal extract on muscle - - - 554 CHAPTER XI. 1. Galvani's experiment ..... 577 2. Contraction without metals .... 578 3. Stimulation of nerve by its own demarcation current - - 578 4. Secondary contraction ... - - 578 5. Demarcation current and current of action with capillary electro- meter ...... 578 lo CONTENTS. PAGE 6. Action-current of heart ----- 580 7. Electrotonus ------ 580 8. Paradoxical contraction- ... - 581 9. Electrotonic alteration of excitability and conductivity - 581 10. Pflijger's formula of contraction - - - - 583 11. Ritter's tetanus .... - 583 12. ' Positive polarization ' ----- 584 13. Galvanotropism ... - - 584 CHAPTER XII. 1. Hemisection of spinal cord ... - 678 2. Section and stimulation of nerve-roots in frog - - 679 3. Section and stimulation of nerve-roots in rabbit - - 679 4. Reflex action ------ 680 5. Action of strychnia ----- 680 6. Excision of cerebral hemispheres in frog - - - 680 7. Excision of cerebral hemispheres in pigeon - - - 680 8. Stimulation of motor areas in dog - - - 681 9. Removal of motor areas in dog - - - - 681 CHAPTER XIII. 1. Formation of inverted image on retina - - - 768 2. Phakoscope ------ 769 3. Scheiner's experiment ----- 769 4. Kiihne's artificial eye ----- 770 5. Mapping the blind spot . - - . 771 6. Pupillo-dilator and constrictor fibres - - - 772 7. Colour-mixing ..... 772 8. Talbot's Law - - - - - - 773 9. Purkinje's Figures . . . . . 773 10. Relation of pitch and vibration frequency - - - 77;^ 11. Beats - - - - - -773 12. Acuity of touch . - . . - 773 Appendix ...... 787 Index - - - - - - - 788 INTRODUCTION. ' Life is a power superadded to matter ; organizntion arises from, and depends on, life, and is the condition of vital action ; but life never can arise out of, or depend on, organization.' — John Hunter. Living matter, whether it is studied in plants or in animals, has certain peculiarities of chemical composition and struc- ture, but especially certain peculiarities of action or function which mark it off from the unorganized material of the dead world around it. Chemical Composition of Living Matter. — Although we cannot analyze the living substance as such, we can to a certain, but limited, extent reconstruct it, so to speak, from its ruins. When subjected to analytical processes, which necessarily kill it, living matter invariably yields bodies of the class of proteids, which have approximately the following composition: Carbon, 51*5 to 54'5 per cent. ; oxygen, 20 to 23*5 per cent. ; nitrogen, 15 to 17 per cent. ; hydrogen, 6'g to 7-3 per cent., with small quantities of sulphur and generally of phosphorus. Certain carbo-hydrates, composed of carbon, hydrogen, and oxygen (the last two in the proportions necessary to form water), of which glycogen (CcHioO^) may be taken as a type, appear also to be always present. Fats, which consist of carbon, hydrogen, and oxygen, and of which tristearin, a compound of stearic acid with glycerine, of the formula C3H5, 3(Ci8H,50o), may be given as an example, are often, but perhaps not always, found. Finally, water and certain inorganic salts, such as sodium chloride, are constantly present. 12 INTRODUCTION. Structure of Living Matter — The Cell. — The investigations of the last few years have shown that protoplasm, the primitive Hving substance, when examined with sufficiently high powers, is by no means the ' homogeneous, structureless material ' it was at one time believed to be. It is rather a substance of porous or reticulated structure, a spongework or network, holding a fluid in its meshes. And in all probability the network is the true living machinery, the liquid in its interstices being perhaps pabulum, from which the waste of the living framework is made good, or material upon which it works, and which it is its business to transform. So that in building up our typical cell we start with a piece of protoplasm of reticular structure, the network in which is called the intracellular network. Somewhere in the midst of this cell-substance we find a body which, if not absolutely different in kind from the protoplasm of the cell, is yet marked off from it by very definite morphological and chemical characters. This is the nucleus, generally of round or oval shape, and bounded by an envelope. Within the envelope lies a second network, which, when the nucleus is about to divide in the manner known as indirect division, or karyokinesis, becomes converted into one or more coiled filaments or skeins. Both the network and the filaments are made up of rows of highly refractive particles, embedded in a homo- geneous matrix. These particles possess the property of staining readily and deeply with dyes, and have, therefore, been described as consisting of chromalhi ; and there is a certain amount of evidence that this chromatin is either identical with nuclein (a body con- taining the same elements as proteids, but a much larger proportion of phosphorus), or yields nuclein by its decomposition (Zacharias). The meshes of the nuclear reticulum contain a semi-fluid material, which does not readily stain. When we carry back the analysis of an organized body as far as we can, we find that every organ of it is made up of cells, which upon the whole conform to the type we have been describing, although there are many differences in details. Some organisms there are, low down in the scale, whose whole activity is confined within the narrow limits of a single cell. The Amoeba sets up in life as a cell split off from its parent. It divides in its turn, and each half is a complete Amoeba. When we come a little higher than the Amoeba, we find organisms which consist of several cells, and ' specialization of function ' begins to appear. Thus the Hydra, the ' common fresh-water Polyp ' of our ponds and marshes, has an outer set of cells, the ectoderm, and an inner set, the endoderm. Through the superficial portions of the former it learns what is going on in the world ; by the contraction of their deeply-placed processes it shapes its INTRODUCTION. 13 life to its environment. As we mount in the animal scale, specialization of structure and of function are found con- tinually advancing, and the various kinds of cells are grouped together into colonies or organs. The Functions of Living Matter. — The peculiar functions of living matter as exhibited in the animal body will form the subject of the main portion of this book; and we need only say here (i) that in all living organisms cJieniical changes go on. These may be divided into (a) integrative or anabolic changes, by which complex substances (including the living matter itself) are built up from simpler materials ; and (b) disintegrative or katabolic changes, in which complex substances (including the living substance) are broken down nto comparatively simple products. In the course of these changes, oxygen is absorbed and carbonic acid given out. (2) The living substance is excitable — that is, responds to certain external impressions, or stimuli, by actions peculiar to each kind of cell. (3) The living substance reproduces itself. All the manifold activities included under these three heads have but one source, the transformation of the energy of the food. It is not, however, upon the whole, peculiarities in food, but in molecular structure, that underlie the peculi- arities of function of different living cells. A locomotive is fed with coal ; a steam-pump is fed with coal. The one carries the mail, and the other keeps a mine from being flooded. Wherein lies the difference of action ? Clearly in the build, the structure of the mechanism, which determines the manner in which energy shall be transformed within it, not in any difference in the source of the energy. So one animal cell, when it is stimulated, shortens or contracts ; another, fed perhaps with the same food, selects certain constituents from the blood or lymph and passes them through its substance, changing them, it may be, on the way; and a third sets up impulses which, when transmitted to the other two, initiate the contraction or secretion. In the living body the cell is the machine ; the transformation of the energy of the food is the process which ' runs ' it. The structure of cells and the steps by which energy is trans- formed within them sum up the whole of biology. 14 PRACTICAL EXERCISES. PRACTICAL EXERCISES. Reactions of Proteids. 1. General Reactions of Proteids. — Egg-albumin may be taken as a type. Prepare a solution of it. In breaking the egg, take care that none of the yolk gets mixed with the white. Snip the white up with scissors in a large capsule, then add ten or fifteen times its volume of distilled water. The solution becomes turbid from the precipitation of traces of globulin, since globulins are insoluble in distilled water. Stir thoroughly, strain through several layers of muslin, and then filter through paper. (i) Add to a little of the solution in a test-tube a few drops of strong nitric acid. A precipitate is thrown down, which becomes yellow on heating. Cool, and add a drop or two of ammonia ; the colour changes to orange [^xaiitJw-proteic reaction). (2) Acidify another portion strongly with acetic acid, and add a few drops of a solution of potassium ferrocyanide. A white precipitate is obtained. Peptones do not give this reaction. (3) To a third portion add a drop or two of very dilute cupric sulphate and excess of sodium hydrate ; a violet colour appears. Peptones and proteoses (albumoses) give a pink {biuret reaction). See p. 325. (4) To another portion add Millon's reagent ; a precipitate comes down which is turned reddish on boiling. If only traces of proteid are present, no precipitate is caused, but the liquid takes on a red tinge. (5) Heat a portion to 30° C. on a water-bath. Saturate with crystals of ammonium sulphate ; the albumin is precipitated. Filter, and test the filtrate for proteids by (3). None, or only slight traces, will be found. The sodium hydrate must be added in more than sufficient quantity to drive off all the ammonia, since for reaction (3) free alkali must be present. It will be best to add a small piece of the solid hydrate. Peptones are not precipitated by ammonium sulphate, but all other proteids are. 2. Special Reactions of Groups of Proteids — (i) Coagulable Pro- teids : (a) Native Albumins.^ — (a) Heat a little of the solution of egg-albumin in a test-tube ; it coagulates. With another sample determine the temperature of coagulation as on p. 551, first slightly acidulating with dilute acetic acid. ((S) A similar experiment may be performed with serum-albumin, obtained as on p. 47. (/;) Globulins. — Use serum-globulin (p. 47), or myosin (p. 551). Fibrinogen is also a globulin, but cannot easily be obtained in quantity. Verify the following properties of globulins : (a) They coagulate on heating. (/3) They are insoluble in distilled water (p. 552). (7) They are precipitated by saturation with magnesium sulphate or sodium chloride (p. 552). PRACTICAL EXERCISES. 15 (2) Derived Albumins — {a) Acid-albwnin. — To a solution of egg- albumin add a little '2 per cent, hydrochloric acid, and heat to body temperature for a few minutes. Acid-albumin is formed. It can be produced from all albumins and globulins by the action of dilute acid. Make the following tests : (a) Add to a portion of the solution in a test-tube a few drops of a solution of litmus ; the colour becomes red. Now add drop by drop sodium carbonate or dilute sodium hydrate solution till the tint just begins to change to blue. A precipitate of acid-albumin is thrown down. Add a little more of the alkali, and the precipitate is redissolved. It can be again brought down by neutralizing with acid. (/3) Heat a portion of the solution to boiling; no precipitate is formed. (7) Add strong nitric acid ; a precipitate appears, which dissolves on heating, and the liquid becomes yellow. {U) Alkali-albumin. — To a solution of egg-albumin add a little sodium hydrate, and heat gently for a few minutes. Alkali-albumin is produced. It can also be derived by similar treatment from any albumin or globulin. (a) Neutralize as in ia), by the addition of dilute hydrochloric or acetic acid. Alkali-albumin is precipitated when neutralization has been reached. It is redissolved is excess of the acid. (/3) On heating the solution of alkali-albumin there is no coagulation. (3) Albumoses. — For preparation and reactions see p. 325. They differ from group (i) in not being coagulated by heat, and from group (2) in not being precipitated by neutralization. They are soluble, with the exception of hetero-albumose, in distilled water, and are not precipitated by saturation of their solutions with magnesium sulphate or sodium chloride. Saturation with ammonium sulphate precipitates them (p. 325). (4) Peptones.— For preparation and tests see p. 325. They differ from groups (i) and (2) in the same way as albumoses, and they differ from albumoses in not being precipitated by ammonium sulphate. (5) Fibrin. — For preparation see p. 46. It gives the general proteid reactions, is insoluble in water, and only slightly soluble in dilute solutions of neutral salts. Carbo-hydrates. I. Starch. — (i) Cut a slice from a well-washed potato; take a scraping from it with a knife, and examine with the microscope. Note the starch granules with their concentric markings, using a small diaphragm. Run a drop of dilute iodine solution under the cover-slip, and observe that the granules become bluish. Examine also with a polarization microscope. (2) Rub up a little starch in a mortar with cold water, then add boiling water and stir thoroughly. Decant into a capsule or beaker, and boil for a few minutes. After the liquid has cooled, perform the following experiments : i6 PRACTICAL EXERCISES. (a) Add a few drops of iodine solution to a little of the thin starch mucilage in a test-tube. A blue colour is produced, which disappears on heating, returns on cooling, is bleached by the addition of a little sodium hydrate, and restored by dilute acid. (/^) Test the starch solution for reducing sugar by Trommer's test (p. 323). If none is found, boil some of the mucilage with a little dilute sulphuric acid in a flask for a few minutes, and again perform Trommer's test. Abundance of reducing sugar will now be present. 2. Dextrin. — Dissolve some dextrin in boiling water. Cool. Add iodine solution to a portion ; a reddish-brown (port-wine) colour results. This is bleached by alkali, restored by acid. 3. Glycogen.— See p. 453. 4. Glucose or Dextrose. — See p. 370. 5. Cane-sugar. — Perform Trommer's test with a sample of a solution. No reaction is obtained. Now put the rest of the solution in a flask. Add TT^^th of its bulk of strong hydrochloric acid, and boil for a short time.' Again perform Trommer's test. It shows that much reducing sugar is now present. The cane-sugar has been 'inverted,' i.e., changed into a mixture of dextrose and levulose. Fats — Emulsification. — Put in one watch-glass a few drops of neutral (fresh) olive-oil, and in another a few drops of a rancid oil containing fatty acids. Add a dilute solution of sodium carbonate to each. An emulsion will be formed in the second watch-glass, but not in the first. Examine it under the microscope, and note the globules of oil of various sizes. A MANUAL OF PHYSIOLOGY. CHAPTER I. THE CIRCULATING LIQUIDS OF THE BODY. In the living cells of the animal body chemical changes are constantly going on ; energy, on the whole, is running down ; complex substances are being broken up into simpler combinations. So long as life lasts, food must be brought to the tissues, and waste products carried away from them. In lowly forms like the amoeba, these functions are per- formed by interchange at the surface of the animal without any special mechanism ; but in all complex organisms they are the business of special liquids, which circulate in finely branching channels, and are brought into close relation at various parts of their course with absorbing organs, with eliminating organs, and with the tissue elements in general. In the higher animals three circulating liquids have been distinguished : blood, lymph, and chyle. But it is to be remarked that chyle is only lymph derived from the walls of the alimentary canal, and therefore, during digestion, containing certain freshl}— absorbed constituents of the food ; while both ordinary lymph and chyle ultimately find their way into the blood, and are in their turn recruited from it. The blood contains at one time or another every- thing which is about to become part of the tissues, and everything which has ceased to belong to them. It is at once the scavenger and the food-provider of the cell. But no bloodvessel enters any cell ; and if we could unravel the l8 A MANUAL OF PHYSIOLOGY. complex mass of tissue elements which essentially constitute what we call an organ, we should see a sheet of cells, with capillaries in very close relation to them, but everywhere separated from them by a thin layer of lymph. And to describe in a word the circulation of the food substances, we may say that the blood feeds the lymph, and the lymph feeds the cell. Morphology of the Blood. The blood consists essentially of a liquid part, the plasma, in which are suspended cellular elements, the corpuscles. When the circulation in a frog's web or lung or in the tail of a tadpole is examined under the microscope, the blood- vessels are seen to be crowded with oval bodies — of a yellowish tinge in a thin layer, but in thick layers crimson — which move with varying velocity, now in single file, now jostling each other two or three abreast, as they are borne along in the axis of an apparently scanty stream of trans- parent liquid. Nearer the walls of the vessels, sometimes clinging to them for a little and then being washed away again, may be seen, especially as the blood-flow slackens, a few comparatively small, round, colourless cells. The oval bodies are the red or coloured corpuscles ; the colourless elements are the white blood-corpuscles or leucocytes ; the liquid in which they float is the plasma (' Practical Exercises,' p. 142). The Red Blood-corpuscles differ in shape and size and in other respects in different animal groups. In amphibians, such as the frog and the newt, they are flattened ellipsoids containing a nucleus, and the same is true of nearly all the other vertebrates, except mammals. In mammals they are discs, hollowed out on both the flat surfaces, or biconcave, and possess no nucleus. But the red corpuscles of the llama and the camel, although non-nucleated, are ellipsoidal in shape like those of the lower vertebrates. As to size, the average diameter in man is between 7 and 8 /x.* In the frog the long diameter is about 22 /x, while in Proteus it is as much as 60 /tt, and in Amphiuma, the corpuscles of which can be seen with the naked eye, nearly 80 yu, (Plate I., i). * A micro-millimetre, represented by symbol /<, is jo\j(T millimetre. THE CIRCULATING LIQUIDS OF THE BODY. 19 The corpuscles consist of a spongy framework or stroma (Rollett), or an envelope of fatty nature (Schafer), to which they owe their great elasticity — that is, the power of re- covering their original shape after being distorted in any way — and within which is contained a solution of haemo- globin, a highly complex pigment. When blood with disc-shaped corpuscles is shed, there is a great tendency for the corpuscles to run together into groups resembling rouleaux, or piles of coin. No satisfactory explanation of this curious fact has yet been given. Crenation of the corpuscles, a condition in which they become studded with line projections, is caused by the addition of moderately strong salt solution, by the passage of shocks of electricity at high potential, as from a Le)'den jar, by simple exposure to the air, and in poisoning with Calabar bean. Concentrated saline solutions, which abstract Bipha-nir :^\r Ma n \_\. Cat XVN ^she^J, \-\ Goat , 77- i Mu sh: -deer Fio. I. — Diagram showing kelative Size of Reu Corpuscles of various Animals. water from the corpuscles and cause them to shrink, make the colour of blood a brighter red, because more light is now reflected from the crumpled surfaces. On the other hand, the addition of water renders the corpuscles spheri- cal ; more of the light passes through them, less is reflected, and the colour becomes dark crimson (Plate I.). The White Blood-corpuscles, or Leucocytes. — The red cor- puscles are peculiar to blood. The white corpuscles may be looked upon as peripatetic portions of the mesoblast (see Chap. XIV.), and some of them ought not in strictness to be called blood-corpuscles. They are more truly body cor- puscles. Similar cells are found in many situations, and wander everywhere in the spaces of the connective tissue. 20 A MANUAL OF PHYSIOLOGY. They pass into the bloodvessels with the lymph, and may pass out of them again in virtue of their amoeboid power. They consist of undifferentiated living substance or ' protoplasm/ and under the microscope appear as granular, colourless, transparent bodies, spherical in form when at rest, and containing a nucleus, often tri- or multi-lobed. Many of the leucocytes of frog's blood at the ordinary temperature, and of mammalian blood when artificially heated on the warm stage, may be seen to undergo slow changes of form. Processes called pseudopodia are pushed out at one portion of the surface, retracted at another, and thus the corpuscle gradually moves or ' flows ' from place to place, and envelops or eats up substances, such as grains of carmine, which come in its way. This kind of motion was first P'iG. 2. — AMa:BoiD Movement. A, B, C, D, successive changes in the form of an amoeba. observed in the amceba, and is therefore called amoeboid. The leucocytes of human blood are not all of the same size, and differ also in other respects. They may be classified (i) according to the presence or absence of granules in their protoplasm, and the fineness or coarseness of the granules ; (2) according to the chemical nature of the dyes with which the granules stain. The most recent work on this subject is a striking paper by Kanthack and Hardy. They find that Ehrlich's ' neutrophile ' cells are in reality oxyphile — that is, their granules do not stain with neutral dyes, such as fuchsin or methyl green, but do stain with acid dyes like eosin (Plate I., 2). They classify the wandering cells of the blood into five varieties, as follows : THE CIRCULATING LKJUIDS OF THE BODY. 21 r(i) Coarsely granular (horse- Oxyphile (granules stain- J shoe-shaped nucleus) - lo-ii /t in diam. ing with eosin). j (2) Finelygranular (irregular ( branching nucleus) - - 8-9 /t „ Basophile (granules stain- ( (3) Finely granular (tri-lobed ingwith methylene blue). I nucleus) - - - -7^' » (4) Hyaline cells, free from granules (one nucleus, generally spherical) - - 8'5-io^ „ (5) Lymphocytes, possessing a single large nucleus with comparatively little proto- plasm around it - - 6 ^ „ In the blood of a guinea-pig 2 to 3 per cent, of the colour- less cells consisted of (i), 62 per cent, of (2), 07 per cent, of (3), II per cent, of (4) and 24 per cent, of (5). Blood-plates. — When blood is examined immediately after being shed, small colourless bodies of various shapes — some- times flat and of nearly circular outline, sometimes irregular • Fig. 3.— Curve showing the Number of Red Corpuscles at Different Ages (after Sorensen's Estim.\tions). The figures along the horizontal axis are years of age, those along the vertical axis millions of corpuscles per cub. mm. of blood. — may be seen. These are the blood-plates or platelets. They can be best studied when the blood is run directly into some fixing solution such as Hayem's (NaCl, i grm. ; NaoS04, 5 grm.; HgCL, 0*5 grm.; HoO, 200 grm.). Their significance is unknown ; but they are not produced by the breaking up of other elements of the shed blood, for they have been observed within the living vessels — in the mesentery of the guinea-pig and rat (Osier). Enumeratioii of the Blood-corpuscles. — This is done by taking a measured quantity of blood, diluting it to a known extent with a liquid which does not destroy the corpuscles, and counting the number in a given volume of the diluted blood (p. 48). 22 A MANUAL OF PHYSIOLOGY. The average number of red corpuscles in a cubic milli- metre of blood is about 5,000,000. In anaemia it may sink to as low as a third of this. When much water passes out from the blood, as in profuse sweating, the number of corpuscles per cubic millimetre may be greater than normal. The number of white blood-corpuscles in shed blood, as usually examined, is not as great as the number in the circulating blood, for some are almost immediately de- stroyed. The number remaining is on the average about 10,000 per cub. mm., or one leucocyte for every 500 red blood-corpuscles. In leucocythaemia the number is enormously increased ; an increase has also been observed in certain infective diseases as part of the inflammatory reaction. There are also physiological variations, even within short periods of time ; for example, the number of lympho- cytes is increased when digestion is going on. The number of blood-plates is about 300,000 to the cub. mm. of blood. Life-history of the Corpuscles. — The corpuscles of the blood, Hke the body itself, fulfil the allotted round of life, and then die. They arise, perform their functions for a time, and disappear. But although the place and mode of their origin, the seat of their destruction or decay, and the average length of their life, have been the subjects of active research and still more active discussion for many years, much yet remains unsettled. In the embryo the red corpuscles, even of those forms (mammals) which have non-nucleated corpuscles in adult life, are at first possessed of nuclei. In the human foetus, at the fourth week all the red corpuscles are nucleated, Later on the nucleated corpuscles gradually diminish in number, and at birth they have almost or altogether dis- appeared, some of them, at least, having been converted by a shrivelling of the nucleus into the ordinary non-nucleated form. In the newly-born rat, which comes into the world in a comparatively immature state, many of the red corpuscles may be seen to be still nucleated. The first corpuscles formed in embryonic life are developed outside of the embryo altogether (in the guinea-pig). Even before the heart has as yet begun to beat certain cells of the mesoblast THE CIRCULATING LIQUIDS OF THE BODY. 23 (see Chap. XIV.) in a zone (' vascular area ') around the growing embryo, begin to sprout into long, anastomosing processes, which afterwards become hollowed out to form capillary blood-vessels. At the same time clumps of nuclei, formed by division of the original nuclei of the cells, gather at the nodes of the network. Around each nucleus clings a little lump of protoplasm, which soon develops haemoglobin in its substance ; and the new-made corpuscles float away within the new-made vessels. In later embryonic life the nucleated corpuscles seem in part to be developed in the liver, spleen, red bone-marrow, and the blood itself by division of previously existing nucleated corpuscles, in part to be formed endogenously within special cells in the liver, spleen, and perhaps the lymphatic glands. Fig. 4. — Curve showing Pkoportion ok White Corpuscles to Red at Different Times of the Day (after the Results of Hirt). At I the morning meal was taken ; at II the mid-day meal ; at III the evening meal. During active digestion the number of lymphocytes in the blood is greatly increased, both absolutely and relatively to the number of the other leucocytes. In the mammal in extra-uterine life the chief seat of formation of the red blood-corpuscles seems to be the red marrow of the bones of the skull and trunk, and of the ends of the long bones of the limbs. For a short time, how- ever, after birth the formation of non-nucleated corpuscles may still go on in other situations, as in certain cells in the omentum of the rabbit (Ranvier), and in the subcutaneous connective-tissue corpuscles (Schafer) ; while at any time the spleen (Bizzozero and Salvioli) in dogs and guinea-pigs, and probably other organs, may in emergency — for instance, when the number of blood-corpuscles has been seriously diminished by haemorrhage — take on a blood-forming func- 24 A MANUAL OF PHYSIOLOGY. tion. In the red marrow special nucleated, feebly amoeboid cells, originally colourless or nearly so, multiply by mitosis or indirect division, and are transformed by various stages into the ordinary non-nucleated red corpuscles, which are washed away in the blood-stream. These blood-forming cells have received the name of erythroblasts or haematoblasts. A constant destruction of red blood-corpuscles must go on, for the bile-pigment and the pigments of the urine are derived from blood-pigment. The bile-pigment is formed in the liver. It contains no iron ; but the liver-cells are rich in iron, and on treatment with hydrochloric acid and potassium ferrocyanide, a section of liver is coloured by Prussian blue. Iron must, therefore, be removed by the liver from the blood-pigment or from one of its derivatives ; and there is other evidence that the liver is one of the places in which red corpuscles are actually destroyed. Destruction of the corpuscles also seems to take place in the spleen and bone-marrow. Although the statement that free blood- pigment exists in the plasma of the splenic vein is incor- rect, red corpuscles have been seen in various stages of decomposition within cells in the splenic pulp ; and de- posits containing iron have been found there and in the red bone-marrow in certain pathological conditions. The lymphocytes are undoubtedly, the coarsely granular oxyphile cells probably, and the hyaline cells possibly, derived from the lymph. The lymphocytes are probably identical with the small lymph-corpuscles, and have little, if any, power of amoeboid movement. They are formed largely in the lymphatic glands, for the lymph coming to the glands is much poorer in corpuscles than that which leaves them. The lymphatic glands, however, are not the only seat of formation of leucocytes, for lymph contains some corpuscles before it has passed through an}' gland ; and although a certain number of these may have found their way by diapedesis from the blood, others are formed in the diffuse adenoid tissue, or in special collections of it, such as the tonsils, the Peyer's patches and solitary follicles of the intestine, and the splenic corpuscles. To a very small extent white blood- corpuscles may multiply by division in the blood. THE CIRCULATING LIQUIDS OF THE BODY. 25 The fate of the leucocytes is even less known than that of the red corpuscles, for they contain no characteristic substance like the blood-pigment by which their destruction may be traced. That they are constantly breaking down is certain, for they are constantly being produced. But we do not know whether, under normal conditions, this process takes place exclusively in the blood-plasma or in particular organs or tissues. Physical and Chemical Properties of the Blood. Fresh blood varies in colour, from scarlet in the arteries to purple-red in the veins. It is a somewhat viscid liquid, with a saline taste and a peculiar odour. Its reaction is alkaline to litmus-paper, chiefly owing to the presence of di-sodium phosphate (Na.jHPOJ and sodium carbonate. The alkalinity is not constant ; it is increased during diges- tion, when the acid of the gastric juice is being secreted from the blood, and particularly when the food contains much alkali. It is diminished by muscular exertion, owing to the formation of lactic acid ; and since acid substances seem to be produced in all active tissues, the alkalinity of venous is less than that of arterial blood. The average alkalinit}' of human blood is that of a '4 per cent, solution of sodium hydrate (Loewy). The average specific gravity of blood is about 1066 at birth. It falls during infancy to about 1050 in the third year, then rises till puberty is reached to about 1058 in males (at the seventeenth year), and 1055 in females (at the fourteenth year). It remains at this level during middle life in males, but falls somewhat in females. In chlorotic anaemia of young women it may be as low as 1030 or 1035. It rises in starvation. Sleep and regular exercise increase it (Lloyd Jones). Even in thin layers blood is opaque, owing to reflection of the light by the red corpuscles. It becomes transparent or ' laky ' when by any means the pigment is brought out of the corpuscles and goes into true solution. Repeated freezing and thawing of the blood, the addition of water. 26 A MANUAL OF PHYSIOLOGY. the passage of electrical currents, constant and induced, and many chemical agents, cause this change. Since changes begin in the blood as soon as it is shed, having for their outcome clotting or coagulation, we have to gather from the composition of the stable factors of clotted blood, or of blood which has been artificially prevented from clotting, some notion of the composition of the un- altered fluid as it circulates within the vessels. The first step, therefore, in the study of the chemistry of blood is the study of coagulation. Coagulation of the Blood. — When blood is shed its viscidity soon begins to increase, and after an interval, varying with the kind of blood, the temperature of the air and other conditions, it sets into a firm jelly. This jelly gradually shrinks and squeezes out a straw-coloured liquid, the serum. Under the microscope the serum is seen to contain few or no red corpuscles ; these are nearly all in the clot, entangled in the meshes of a kind of network of fine fibrils composed of fibrin. In uncoagulated blood no such fibrils are present, they have accordingly been formed by a change in some constituent or constituents of the normal blood. Now, it has been shown that there exists in the plasma — the liquid portion of un- clotted blood — a substance from which fibrin can be derived, while no such substance is present in the corpuscles. In various ways coagulation can be prevented or delayed, and the plasma separated from the corpuscles. For example, the blood of the horse clots very slowly, and a low tempera- ture lessens the rapidity of coagulation of every kind of blood. If horse's blood is run into a vessel surrounded by ice and allowed to stand, the corpuscles, being of greater specific gravity than the plasma, gradually sink to the bottom, and the clear straw-yellow plasma can be pipetted ofL Or, again, the addition of neutral salts to blood may be used to delay coagulation, the blood being run direct from the animal into, say, a third of its volume of saturated magnesium sulphate solution. The plasma may then be conveniently separated from the corpuscles by means of a centrifugal machine. Again, two ligatures may be placed on a large bloodvessel, so that a portion of it can be excised THE CIRCULATING LIQUIDS OF THE BODY. 27 full of blood and suspended vertically ; coagulation is long delayed, and the corpuscles sink to the lower end. In these and many other ways plasma free from corpuscles can be got ; and it is found that when the conditions which restrained coagulation are removed — when, for example, the temperature of the horse's plasma is allowed to rise, or the magnesium sulphate plasma is diluted with several times its bulk of water — clotting takes place, with formation of fibrin in all respects similar to that of ordinary blood-clot. The corpuscles themselves cannot form a clot. From this we conclude that the essential process in coagulation of the blood is the formation of fibrin from some constituent of the plasma, and that the presence of corpuscles in ordinary blood-clot is accidental. In accordance with this conclu- sion, we find that other animal liquids entirely free from red corpuscles, such as lymph and fresh pericardial fluid, clot spontaneously, with formation of fibrin ; and when fibrin is removed from newly-shed blood by whipping it with a bundle of twigs or a piece of wood, it will no longer coagu- late, although all the corpuscles are still there. In haemo- philia, a hereditary disease, the blood does not clot properly, and a mere prick may give rise to great haemorrhage. The condition is said to be associated with a deficiency of fibrin, or fibrin-forming material. What, now, is the substance in the plasma which is changed into fibrin when blood coagulates ? If plasma, obtained in any of the ways described above, be saturated with sodium chloride, a precipitate is thrown down. The filtrate separated from this precipitate does not coagulate on dilution with water; but the precipitate itself — the so- called plasmine of Denis — on being dissolved in a little water does form a clot. Fibrin is therefore derived from some- thing in this precipitate. Now, ' plasmine ' contains two proteid bodies — fibrinogen, which coagulates by heat at about 56° C, and serum-globulin, which coagulates at about 75° C, and it was at one time believed that both of these entered into the formation of fibrin (Schmidt). Hammer- sten, however, has shown that fibrinogen alone is a precursor of fibrin ; pure serum-globulin neither helps nor hinders 28 A MANUAL OF PHYSIOLOGY. its formation. This observer isolated fibrinogen from blood- plasma by adding sodium chloride till about 13 per cent, was present. With this amount the fibrinogen is precipi- tated, while serum-globulin is not precipitated till 20 per cent, of salt is reached. After precipitation of the fibrinogen the plasma no longer coagulates ; and a solution of pure fibrinogen can be made to clot and to form fibrin, while a solution of serum-globulin cannot. Blood-serum, too, which contains abundance of serum-globulin, but no fibrinogen, will not coagulate. So far, then, we have reached the conclusion that fibrin is formed by a change in a substance, fibrinogen, which can be obtained by certain methods from blood-plasma. It may be added that there is evidence that fibrinogen exists as such in the circulating blood ; for if unclotted blood be suddenly heated to about 56°, the temperature of heat- coagulation of fibrinogen, the blood loses its power of clotting. Since fibrinogen is readily soluble in dilute saline solutions and fibrin only soluble with great difficulty, we may say that in coagulation of the blood a substance soluble in the plasma passes into an insoluble form. How is this change determined when blood is shed ? We have said that a solution of pure fibrinogen can be made to coagulate, but it does not coagulate of itself. The addition of another substance in extremely minute quantity is neces- sary. This other substance is fibrin-ferment, which can be obtained by precipitating blood-serum, or defibrinated blood, with fifteen to twenty times its bulk of spirit, letting the whole stand for a month or more, and then extracting the pre- cipitate with water (Schmidt). All the ordinary proteids of the blood have been rendered insoluble by the alcohol, but the fibrin-ferment passes into solution in the water, for the addition of a trace of the extract to a pure solution of fibrinogen, which of itself would not clot, causes coagulation. The active substance itself does not seem to be used up in the process, nor to enter bodily into the fibrin formed ; a small quantity of it can cause an indefinitely large amount of fibrinogen to clot ; its power is abolished by boiling. For these reasons it is considered to be a ferment. THE CIRCULATING LIQUIDS OF THE BODY. 29 This action of the fibrin-ferment on fibrinogen helps to explain many experiments in coagulation. Thus, transuda- tions like hydrocele fluid do not clot spontaneously, although they contain fibrinogen, which can be precipitated from them by a stream of carbonic acid or by sodium chloride. But the addition of a little fibrin-ferment causes hydrocele fluid to coagulate. So does the addition of serum, not because of the serum-globulin which it contains, as was once believed, but because of the fibrin-ferment in it. The addition of blood-clot, either before or after the corpuscles have been washed away, or of serum-globulin obtained from serum, also causes coagulation of hydrocele fluid, and for a similar reason, the fibrin-ferment having a tendency to cling to everything derived from a liquid containing it. On Fig. 5. — Diagram of Clot with Buffy Coat. t/, Lower portion of clot with red corpuscles ; w, white corpuscles in upper layer of clot ; c, cupped upper surf.ice of clot ; s, serum. the other hand, serum, which does not of itself clot, although fibrin-ferment is present in it, because the fibrinogen has all been changed into fibrin during coagulation of the blood, can be made to coagulate by the addition of hydrocele fluid, which contains fibrinogen. We have thus arrived a step farther in our attempt to explain the coagulation of the blood : it is essentially due to the formation of fibrin from the fibrinogen of the plasma under the influence of fibrin -ferment. What is the source of the fibrin-ferment ? It exists only in small amount in the circulating blood ; for when blood is received into alcohol direct from an artery, only a little ferment is found in it. In all probability the white blood- corpuscles and other cells contain a substance which is not actual fibrin-ferment, but from which fibrin-ferment is readily 30 A MANUAL OF PHYSIOLOGY. derived ; in other words, a zymogen, or mother-substance of fibrin-ferment. When blood is shed, the active ferment is speedily formed, and coagulation of the fibrinogen ensues. This surmise is strengthened by the fact, already men- tioned, that in freshly-shed blood destruction of leucocytes takes place ; and Hardy has shown that the blood of the crayfish, which coagulates with extreme rapidity, contains certain colourless corpuscles which, immediately it is shed, break up with explosive suddenness, and that substances which hinder the breaking up of these corpuscles restrain coagulation. Further, the white layer or ' buffy coat ' which tops the tardily-formed clot of horse's blood (Fig. 5), and consists of the lighter, and therefore more slowly sinking, white corpuscles, causes clotting in otherwise incoagulable liquids like hydrocele fluid, much more readily than the red portion of the clot, and yields far more fibrin-ferment on treatment with alcohol. But when we have traced the fibrin-ferment to the leuco- cytes, and the fibrinogen to the plasma, and have seen that interaction of the two causes the formation of fibrin, we have not yet got to the bottom of coagulation. The researches of late years have shown that a third factor is involved : calcium is present in some form or other wherever coagulation occurs. Active fibrin-ferment is rich in calcium. The follow- ing facts illustrate the role of the calcium : The addition of a soluble oxalate to blood ('i or *2 per cent, potassium oxalate) prevents coagulation by precipitating the calcium as insoluble calcium oxalate. From plasma prepared in this way a nucleo-albumin* maybe obtained which contains little or no calcium and does not cause coagulation, but which on treatment with a calcium salt acquires the properties of fibrin ferment, and yields an ash rich in calcium. Injection of peptone into the veins of a dog deprives the blood for a time of its power of coagulation, apparently by reason of the .affinity of peptone for calcium, salts, for its action can be prevented by injection of calcium chloride (Pekelharing), and imitated by injection of potassium oxalate. Soaps hinder * Nucleo-albumins are bodies which yield, on digestion with pepsin and hydrochloric acid, proteoses, peptones, and an indigestible residue of nuclein, a substance rich in phosphorus. THE CIRCULATING LIQUIDS OF THE BODY. 31 coagulation in the same way. A watery extract of the leech also prevents coagulation, and a substance can be obtained from the plasma chemically identical with fibrin-ferment, but with no power of causing coagulation (Dickinson). Wooldridge's 'tissue fibrinogen' — a mixture of protagon and nucleo-albumin extracted by water from the thymus, testis, kidney, lymphatic glands and other organs, and pre- cipitated with dilute acetic acid — causes extensive intra- vascular clotting when injected into the blood of an animal, but does not cause coagulation of a solution of pure fibrinogen, nor hasten the coagulation of blood-plasma outside of the body. It therefore contains no actual fibrin- ferment, but it does contain a substance, which, according to Pekelharing, can be changed into the ferment, for after treatment with a calcium salt it causes fibrinogen to coagu- late. When the so-called 'tissue fibrinogen,' which must be carefully distinguished from true fibrinogen, is injected into the blood, the nucleo-albumin in it perhaps combines with the calcium of the plasma, and is developed into active fibrin-ferment. Pekelharing's theory may be thus summed up: Active fibrin-ferment only differs from its inert precursor, a nncleo- albiunin, in its richness in calcium, and by the action of a calcium salt the former may be produced from the latter. Fibrin contains much calcium; and it is a very plausible suggestion that fibrin is a calcium compound of fibrinogen, and that in coagulation the calcium is handed over or transferred to it by the fibrin-ferment. Recently, however, Halliburton and Brodie, who have prepared nucleo-albumin from many organs by extraction with sodium chloride and precipitation with excess of water, as well as by the acetic acid method, have brought forward evidence that the nucleo-albumin is neither identical with fibrin-ferment nor with its zymogen. For (i) fibrin- ferment cannot be obtained from nucleo - albumin by Schmidt's method (p. 28), the nucleo-albumin being easily rendered insoluble by alcohol, fibrin-ferment only with difficulty ;* (2) fibrin-ferment favours the coagulation of blood-plasma only after it has been shed, it does not cause * Halliburton now admits that fibrin-ferment contains a nucleo-albumin. 32 A MANUAL OF PHYSIOLOGY. intra- vascular clotting; nucleo-albumin only favours the coagulation of intra-vascular plasma. And it may be asked why it is that fibrin -ferment formed, on Pekelharing's hypothesis, in the circulating blood from injected nucleo- albumin, should be able to cause coagulation, while ready- made fibrin-ferment does not possess this power ? The mere asking of this question is not, however, necessarily fatal to that hypothesis. For it is conceivable that fibrin- ferment freshly formed from nucleo-albumin within the vessels, ' nascent ' fibrin-ferment, so to speak, may be able to overcome the influences that restrain intra-vascular coagulation, while fibrin-ferment introduced from without may fail to do so. Whether, as a matter of fact, the amount of fibrin-ferment obtainable from the blood of an animal into which nucleo-albumin has been injected is greater than the amount yielded by the blood of the same animal before injection, has not been determined. That some ready-made fibrin-ferment, or its zymogen, exists in living plasma is shown by the experiments of Alexander Schmidt. He finds that the blood-plasma of the horse, entirely freed from formed elements by filtration through several folds of filter paper at a temperature of 0° to 0*5° C, remains fluid at the ordinary temperature of the air for hours, but eventually coagulates. On this and other evidence he bases the view that substances formed by the breaking down of white blood-corpuscles in shed blood are not the only cause of coagulation, although they undoubtedly greatly accelerate it. According to Schmidt, zymoplastin, or mother-substance of fibrin-ferment, is produced in the body from all, or most, protoplasmic cells, from white blood- corpuscles among the rest, but not exclusively, nor even pre-eminently, from them. The zymoplastic substance passes continually into the blood, and fibrin-ferment is con- tinually formed from it, but is always being neutralized by other chemical processes. So that living blood within the living vessels may be said to be acted upon by two sets of influences, one tending to coagulation, the other opposing it. Under normal conditions the processes which make for coagulation never obtain the upper hand ; but anything THE CIRCULATING LIQUIDS OF THE BODY. 33 which interrupts the circulation, and consequently the free interchange between blood and tissues, interferes with the entrance of the substances that render the fibrin-ferment inactive. In the clotting of extravascular plasma, free from corpuscles, Schmidt sees the continuation, under modified conditions, of a normal process always going on within the bloodvessels. In the lungs it would seem that the forces which favour coagulation are feeble, or the forces that resist it strong, for blood, after passing many times through the pulmonary circulation without being allowed to enter the systemic vessels, loses its power of clotting (Ludwig and Pawlow). The Chemical Composition of Blood. The serum of coagulated blood represents the plasma mimes fibrinogen ; the clot represents the corpuscles plits fibrin. Thus : Plasma — Fibrin(ogen) = Serum. Corpuscles -\- Fibrin = Clot. Plasma + Corpuscles = Serum + Clot = Blood. Bulky as the clot is, the quantity of fibrin is trifling ("2 to '4 per cent, in human blood). The plasma (or serum) is about two-thirds by weight of the entire blood, the corpuscles Fig. 6.— Diagram showing Relative Quantity of Solids and Water in Red Corpuscles and Plasma. about one-third. The plasma contains about 10 per cent, of solids, the red corpuscles about 40 per cent., the entire blood about 20 per cent. Serum contains 8 to g per cent, of proteids, about "S per cent, of inorganic salts, and small quantities of neutral fats, urea, kreatin, grape-sugar, lactic acid, and other substances. The proteids are seruin-albuinin and scriim-globnlin. In the rabbit the former, in the horse the latter, is the more abundant ; in man they exist in not far from equal amount. 3 34 A MANUAL OF PHYSIOLOGY. Senim-alhumin belongs to the class of native albumins. It is soluble in distilled water, and is not precipitated by saturating its solutions with certain neutral salts. Heated in neutral or slightly acid solution, it coagulates first at 73°, then at ']']'', then at 84° C. But this is not sufficient proof that it consists of a mixture of three proteids coagulating respectively at these temperatures, as has been held. Serum-glohulin belongs to the globulin group of proteids. It is insoluble in distilled water, and is precipitated in saturated solutions of neutral salts. When heated, it coagulates at 75° C. (p. 47). The chief inorganic salt of serum is sodium chloride. Potassium salts are very sparingly represented. The Red Corpuscles. — The pigment haemoglobin makes up about go per cent, of the solids, the proteids of the stroma Fig. 7. — DiAGKAiM of Spectroscope. A, source of light ; B, layer of blood ; C, collimator for rendering rays parallel ; D, prism ; E, telescope. about 8 per cent., lecithin and cholesterin less than i per cent., inorganic salts (chiefly phosphates and chloride of potassium) i'5 per cent. Hcsmoglobin. — The most remarkable property of this body is its power of combining loosely with oxygen when exposed to an atmosphere containing it, and of again giving it up in the presence of oxidizable substances or in an atmosphere in which the partial pressure of oxygen (Chap. III.) has been reduced below a certain limit. It is this property which enables haemoglobin to perform the part of an oxygen- carrier to the tissues, a function which will be more minutely considered when we come to deal with respira- tion. THE CIRCULATING LIQUIDS OF THE BODY. IS The bright-red colour of blood drawn from an artery or of venous blood after free exposure to air is due to the fact that the haemoglobin is in the oxidized state — in the state of oxyhsemoglobin, as it is called. If the oxygen is removed by means of reducing agents, such as ammonium sulphide, or by exposure to the vacuum of an air-pump, the colour darkens, the blood-pigment being now in the form of reduced In ordinary venous blood a large proportion haemoglobin Oxyhasmoglobin Reduced heemoglobin Methaemoglobin (in acid solution) H,-Emochromogen Haematoporphyrin (in acid solution) HamatoporphyriM (in alkaline solu- tion)^ SSwi CD E ^ F Fig. 8. — Table of Spectra of H.t.moglobin and its Derivatives. B, oxygen line ; D, sodium line ; C and F, hydrogen lines ; b, magnesium line. of the pigment is in this condition, but there is always oxyhsemoglobin present as well. In asphyxia, however, the whole of the oxyhasmoglobin may disappear. Crystallization of Hcsmoglohin. — In the circulating blood the haemoglobin is related in such a way to the stroma or to the envelope of the corpuscles that, although the latter are suspended in a liquid readily capable of dissolving the 36 A MANUAL OF PHYSIOLOGY. pigment, it yet remains in normal circumstances strictly within them. In a few invertebrates, however, it is normally in solution in the plasma. When in any way it is brought into solution outside the body it shows in many animals, but not in all, a tendency to crystallize. The crystals differ in shape in different animals. Thus, in the goose they are rhombic tables, in the guinea-pig tetrahedra or octahedra, in the dog four-sided prisms. As a rule, the haemoglobin cr3'stallizes in the form of oxyhsemoglobin, but in man in the reduced form (Copeman). When a solution of oxyhaemoglobin of moderate strength is examined with the spectroscope, two well-marked absorp- tion bands are seen, one a little to the right of Fraunhofer's line D, and the other a little to the left of E, The addition Fig. 9. — Ckystals of H.kmoglobin. a, human ; b, squirrel ; r, guinea pig. of a reducing agent, such as ammonium sulphide, causes these bands to disappear, and they are replaced by a less sharply-defined band, of which the centre is about equidistant from D and E. This is the characteristic band of reduced haemoglobin. The spectrum of ordinary venous blood shows the bands of oxyhaemoglobin. By the action of acids or alkalies oxyhaemoglobin is split into haematin and proteid bodies, of which the exact nature is little known. When the haemoglobin is acted on by acids in the absence of oxygen, heemochromogen is first formed, which is then changed into haematoporphyrin, or iron-free haematin. If oxygen be present, haematin is the final product. By the action of alkalies reduced hasmo- THE CIRCULATING LIQUIDS OF THE BODY 37 globin yields haemochromogen, which is stable in alkaline solution, and gives a beautiful spectrum with two bands, bearing some resemblance to those of oxyhaemoglobin, but placed nearer the violet end. The band next the red end of the spectrum is much sharper than the other. Hamatin, the most frequent result of the splitting up of haemoglobin, is generally obtained as an amorphous substance of bluish-black colour and a metallic lustre, in- soluble in water, but soluble in dilute alkalies and acids, or in alcohol containing them. In addition to the iron of the haemoglobin, hsematin contains the four chief elements of proteid bodies, C, H, N and O (see Practical Exercises). HcEmatoporphyrin, or iron-free haematin, may be obtained OxijHb- Canonic oxidtHb. \ Two Haenicch rbmotit ti bana ffaematofiorfthi/rin('ucidj Methaetnoijflobiiv "i ftcidHaematin \ '^.* Alkaline Haemattn rr% Reduced Hb. V"""^ Fig. io. — Diagram to show the Chief Characteristics by which H.-i;mo- GLUBIN and some OF ITS DERIVATIVES MAY BE RECOGNISED SPECTKO- scopicALLY. The Position of the middle of each Band is indicated ROUGHLY BY A VERTICAL LiNE. from blood or haemoglobin by the action of strong sulphuric acid. Haemochromogen in acid solution readily loses its iron, and is changed into haematoporphyrin. The spectrum of the latter in acid solution shows two bands, one just to the left of D, the other about midway between D and E. Methcemoglohin differs from the other derivatives of haemo- globin described in still possessing the proteid element, and therefore the capacity of being again changed into haemo- globin. It has by some been regarded as a more highly oxidized haemoglobin than oxyha^moglobin. Rebutting evidence has, however, been offered to the effect that the same quantity of oxygen is required to saturate both pig- ments. Methaemoglobin is formed when blood is oxidized 38 A MA NUA L OF PH YSIOL O G Y. in various ways — e.g., by the addition of crystals of ferri- cyanide of potassium, or of nitrite of amyl, or by electrolysis, in the neighbourhood of the anode. It very often appears in blood or in an oxyhaemoglobin solution which is allowed to stand. It has been found in the urine in haemoglobinuria, in the fluid of ovarian cysts, and in haematoceles. The strongest band in its spectrum is in the red, between C and D, but nearer C, nearly in the same position as the band of acid-haematin. Reducing agents change methaemo- globin into reduced haemoglobin; but it maybe seen that the methasmoglobin passes rapidly, on the addition of ammonium sulphide, through the stage of oxyhaemoglobin to reduced haemoglobin, the oxyhaemoglobin bands springing out for a moment and then disappearing. Carbonic oxide hcBmoglobin is a representative of a class of haemoglobin compounds analogous to oxyhaemoglobin, in which the loosely-combined oxygen has been replaced by other gases (CO, NO) in firmer union. Its spectrum shows two bands very like those of oxyhaemoglobin, but a little nearer the violet end. COHb is formed in poisoning with coal gas. Owing to the great stability of the compound, the Hb can no longer be oxidized in the lungs, and death may take place from asphyxia. It is, however, gradually broken up, and this is an indication that artificial respira- tion may sometimes be of use in such cases. Reducing agents, such as amm.onium sulphide, do not break up COHb, and therefore do not alter the spectrum. HcBmin is a compound of haematin and hydrochloric acid, which crystallizes in the form of small rhombic plates, of a brownish or brownish-black colour. They are insoluble in water, but readily soluble in dilute alkalies (see p. 52). Chemistry of the White Blood Corpuscles. — The composition of pus-cells and the leucocytes of lymphatic glands has been investigated. The chief constituents of the latter are a globulin coagulating by heat at 48° to 50° C. ; a nucleo- albumin coagulating in 5 per cent. MgSO^ solution at 75° C, and causing coagulation of the blood on injection into the veins of rabbits; an albumin coagulating at y^° C; and a THE CIRCULATING LIQUIDS OF THE BODY. 39 ferment with powers like the pepsin of the gastric juice. In pus-cells glycogen has been found. The duantity of Blood. — The quantity of blood in an animal is best determined by the method of Welcker. The animal is bled from the carotid into a weighed flask. When blood has ceased to flow, the vessels are washed out with water or normal saline solution, and the last traces of blood are removed by chopping up the body, after the intestinal contents have been cleared away, and extracting it with water. The extract and washings are mixed and weighed ; a given quantity of the mixture is placed in a haematino- meter (a glass trough with parallel sides, e.g.), and a weighed quantity of the unmixed blood diluted in a similar vessel till the tint is the same in both. From the amount of dilution required, the quantity of blood in the watery Liver 29-5 Muscles 2 9-2 Great Ws^ehHe artklungs 2 21 'Bones 8-2 Jntt stint Slig/enital organs 63 Skin Zl Kidneys IG Nerve Centres LZ Spleen. 02\ Fig. II.— Diagram to illustrate the Uistkibutkj^j of the Blood in the Various Organs of a Rabbit (after Kanke's Measurements). The number.s are percentages of the total blood. solution can be calculated. This is added to the amount of unmixed blood directly determined. Many other methods have been devised on the principle of injecting a known quantity of some substance into the circulating blood, and then, after an interval has been allowed for mixture, determining the change produced in a sample. Thus, the specific gravity of a drop of blood having been measured, a certain quantity of normal saline (a "5 to •7 per cent, solution of sodium chloride) may be injected into a vein, and the specific gravity again determined. Or the electrical resistance of a small sample of blood may be measured before and after injection of a given quantity of a substance, such as sodium chloride, which reduces it. Or the total solids may be determined in a specimen before 40 A MANUAL OF PHYSIOLOGY. and after injection of a known weight of distilled water. Or an animal may be caused to inspire carbonic oxide for a given time ; from the quantity taken in, and the quantity fixed by a known weight of blood withdrawn from the animal, the weight of the whole blood may be calculated. The quantity of blood in the body was greatly over- estimated by the ancient physicians. Avicenna put it at 25 lb., and many loose statements are on record of as much as 20 lb. being lost by a patient without causing death. The proportion of blood to body-weight has been found by accurate experiments to be in man and the dog I : 13, new-born child i : 19, cat i : 14, horse i : 15, frog I : 17, rabbit i : ig. Fig. 11 illustrates the distribution of the blood in the various organs of a rabbit. The liver and skeletal muscles each contain rather more than one-fourth, the heart, lungs, and great vessels rather less than one- fourth, and the rest of the body about one-fifth, of the total blood. The kidney and spleen of the rabbit each contain one-eighth of their own weight of blood, the liver between one-third and one-fourth of its weight, the muscles only one-twentieth of their weight. Lympli and Chyle. Lymph has been defined as blood without its red cor- puscles (Johannes Miiller); it is, in fact, a dilute blood- plasma, containing leucocytes, some of which (lymphocytes) are common to lymph and blood, others (coarsely granular basophile cells) are absent from the blood. The reason of this similarity appears when it is recognised that the plasma of lymph is derived from the plasma of blood by a process of physiological filtration (or secretion) through the walls of the capillaries into the lymph-spaces that everywhere occupy the interstices of areolar tissue. Lymph, as obtained from one of the large lymphatic vessels of the limbs, or from the thoracic duct of a fasting anmial, is a colourless or some- times slightly yellowish liquid of alkaline reaction. Its specific gravity is much less than that of the blood (1015 to THE CIRCULATING LIQUIDS OF THE BODY. 41 1030). It coagulates spontaneously, but the clot is always less firm and less bulky than that of blood. The plasma contains fibrinogen, from which the fibrin of the clot is derived. Serum-albumin and serum-globulin are present in much the same relative proportion as in blood, although in smaller absolute amount. Neutral fats, urea, and sugr are also found in small quantities. The inorganic salts are the same as those of the blood-serum, and exist in about the same amount, sodium preponderating among the bases, as it does in serum. The following table shows the results of analyses of lymph from man and the horse (Munk) : Man. Horse. Water /Fibrin - 1 Other proteids Solids^ Fat 1 Extractives I Salts 95-0 p. c. 01 \ 4-1 i trace -5'o 0-3 1 05 ) 95-8 p. c. O-I ^ 2-9 trace ■ 4*2 01 1 I 'I .' Chyle is merely the name given to the lymph coming from the alimentary canal. The fat of the food is absorbed by the lymphatics, and during digestion the chyle is crowded with fine fatty globules, which give it a milky appearance. There may also be in chyle a few red blood-corpuscles, carried into the thoracic duct by a back-flow from the veins into which it opens. Chyle clots like ordinary lymph. The following is the composition of a sample analyzed by Paton, and obtained from a fistula of the thoracic duct in a man : Water Solids Inorganic Organic - Proteids Fats Cholesterin Lecithin 953'4 46-6 6-5 40" I 137 2 4 '05 0-6 0-36 The quantity of chyle flowing from the fistula was esti- mated at as much as 3 to 4 kilos per twenty-four hours, or nearly as much as the whole of the blood. The flow has 42 A MANUAL OF PHYSIOLOGY. been calculated in various animals at one-eighteenth to one- seventh of the body-weight in the twenty-four hours. The quantity of lymph in the body is unknown, but it must be very great— perhaps two or three times that of the blood. The gases of the blood and lymph will be treated of in Chapter III. The Functions of Blood and Lymph. We have already said that these liquids provide the tissues with the materials they require, and carry away from them materials which have served their turn and are done with. These materials are gaseous, liquid, and solid. Oxygen is brought to the tissues in the red corpuscles; carbonic acid is carried away from them chiefly in the plasma of the blood and lymph. The water and solids which the cells of the body take in and give out are also, at one time or another, constituents of the plasma. The heat produced in the tissues, too, is, to a large extent, conducted into the blood and distributed by it throughout the body. It is not known whether the leucocytes play any part in the normal nutrition of other cells, although it is probable that they exercise an influence on the plasma in which they live ; but they have most important functions of another kind, to which it is necessary to refer briefly here. Phagocytosis. — Certain of the amoeboid cells of blood and lymph, and the cells of the splenic pulp, are able to include or 'eat up' foreign bodies, such as bacteria, in the same way as the amoeba takes in its food. Such cells are called phago- cytes ; and it is to be remarked that this term neither com- prises all leucocytes nor excludes all other cells, for some fixed cells, such as those of the endothelial lining of bloodvessels, are phagocytes in virtue of their power of sending out pro- toplasmic processes, while the small, immobile, uninuclear leucocyte, or lymphocyte, is not a phagocyte. The functions of phagocytes are not necessarily confined to conditions of disease. During the metamorphosis of some larvae, groups of cilia and muscle - fibres may be absorbed and eaten up by leucocytes. In the metamor- THE CIRCULATING LIQUIDS OF THE BODY. 43 phosis of maggots, for example, the muscular fibres of the abdominal wall, which are absent from the adult form, are removed in this way. At the time when the tail of the tadpole disappears multitudes of leucocytes swarm into it, and some of them may be seen with fragments of muscle or nerve inside them. But the behaviour of phagocytes towards pathogenic micro-organisms is of extreme interest and importance. Metschnikoff laid the foundation of our knowledge of this subject by his researches on Daphnia, a small crustacean with transparent tissues, which can be observed under the microscope. When this creature is fed with a fungus, Monospora, the spores of the latter find their way into the body-cavity. Here they are at once attacked by the leuco- cytes, ingested, and destroyed. But after a time so many spores get through that the leucocytes are unable to deal with them all ; some of them develop into the first or ' conidium ' stage of the fungus ; the conidia poison the leucocytes, instead of being destroyed by them, and the animal generally dies. Occasionally, however, the leuco- cytes are able to destroy all the spores, and the life of the Daphnia is preserved. This battle, ending sometimes in victory, sometimes in defeat, is typical of the struggle which the phagocytes of higher animals and of man seem to engage in when the germs of disease are introduced into the organism. Metschnikoff believes that the immunity to certain diseases possessed naturally by some animals, and which may be conferred on others by vaccination with various protective substances, is, to a large extent, due to the early and complete success of the phagocytes in the fight with the bacteria ; and that in rapidly-fatal diseases — such as chicken-cholera in birds and rabbits, and anthrax in mice — the absence of any effective phagocytosis is the factor which determines the result. Others have laid stress on the action of protective substances supposed to exist in the living plasma itself, although only as yet demonstrated, if at all, in the serum. It is possible that such substances are manufactured by the leucocytes, and that they are the weapons by which leucocytes destroy the bacteria they 44 A MANUAL OF PHYSIOLOGY. ingest. In this connection it is of interest that bodies of proteid nature (albumoses), produced in the growth of bacteria (anthrax baciUi, c.g^ in artiiicial culture media, may, when injected into the blood, confer immunity against the bacteria by which they were formed. Diapedcsis. — The fact that leucocytes can pass out of the bloodvessels into the tissues (Waller, Cohnheim) has a very important bearing on the subject of phagocytosis. The phenomenon is called diapedesis, and is best seen when a transparent part, such as the web of the frog, is irritated. The first effect of irritation is an increase in the flow of blood through the affected region. If the irritation continues, or if it was originally severe, the current soon begins to slacken, the corpuscles stagnate in the vessels, and inflammatory stasis is produced. The leucocytes adhere in large numbers to the capillary walls, and then begin to pass slowly through them by amoeboid movements, the passage generally taking place at the junctions between the endothelial cells. Plasma is also poured out into the tissues, the whole forming an inflammatory exudation. Even red blood-corpuscles may pass out*of the vessels in small numbers. The exudation may be gradually reabsorbed, or destruction of tissue may ensue, and a collection of pus be formed. The cells of pus are largely, if not entirely, emigrated leucocytes. PRACTICAL EXERCISES ON CHAPTER I. N.B. — /// /he follo7vi?ii^ exercises all experiments on animals ^vhicJi •would cause pain are to he done under complete antestliesia. 1. Blood -reaction. — With a clean suture-needle prick one of the fingers behind the nail. Put a drop of blood on a piece of glazed neutral htmus paper; wash off in lo to 30 seconds with water. A blue stain will be left, showing that fresh blood is alkaline. Or soak a piece of ordinary litmus paper in salt solution. Put a drop of blood on it. The substances on which the alkaline reaction depends will diffuse out in a ring around the drop, while the Hb remains in its original position. 2. Specific Gravity — (j) Roys Method. — ^Take 25 small bottles con- taining mixtures of glycerine and water of specific gravity ro27, I '029 . . . 1-070. Begin with bottle i'osq. Pour a little of the PRACTICAL EXERCISES. 45 liquid into a small vessel. Then prick the finger with a sharp, clean suture-needle, and suck up a small drop of blood into the horizontal limb of a capillary tube with a rectangular elbow. Immerse the horizontal part of the tube in the glycerine mixture and gently blow the drop of blood into it. If it neither rises nor sinks, the specific gravity of the blood is 1059. If it sinks, the experiment must be repeated with a mixture of higher specific gravity, say i-o6i ; if it rises, with a mixture of lower specific gravity, say i'o57, etc. If the drop of blood rises in mixture i-o6i and sinks in mixture i'o59, the specific gravity is between those two figures, and may be taken as I "060. (2) Put a mixture of chloroform and benzol of specific gravity i "060 into a small glass vessel. Obtain a drop of blood as in (i). Tut it in the mixture. If it sinks, add chloroform, if it rises, add benzol, till it just remains suspended. Then with a small hydrometer measure the specific gravity of the mixture, which is now equal to that of the blood. 3. Opacity of Blood — To make Blood ' Laky.' — Smear a little blood on a glass slide, and lay the slide on some printed matter. It will not be possible to read it, because the light is reflected from the corpuscles in all directions, and little of it passes through. Now add a little water to the blood and mix. The Hb is dissolved out of the corpuscles. The blood becomes transparent, or ' laky,' and the print is distinctly seen through a thin layer of it. 4. Coagulation of Blood. — ( i ) Insert a cannula into the central end of the carotid artery of a large dog anesthetized with morphia and ether (10 cc. of a 2 per cent, solution of morphia injected subcutaneously). To put a Canmi/a into an Artery. — Feel for the artery, make an incision in its course through the skin, then isolate about an inch of it with forceps or a blunt needle, clearing away the fascia carefully. Next pass a small pair of forceps under the artery, and draw two ligatures through below it. If the cannula is now to be inserted into the central end of the artery, tie the ligature which is farthest from the heart. Then between the heart and the other ligature compress the artery with a pair of bulldog forceps. Now lift the artery by the distal ligature, make a slit in it with a pair of fine scissors, and insert the cannula, previously filled with normal saline solution, which is prevented from escaping by bulldog forceps that compress the indiarubber tube on the end of it. Tie the ligature over the neck of the cannula. If the cannula is to be put into the distal end of the artery, the bulldog must be put on before the first ligature is tied, so that the piece of bloodvessel between it and the ligature may be full of blood, as this facilitates the opening of the artery. (2) Run some of the blood from the animal into a wide-mouthed jar. Notice that it begins to clot in a minute or two, and very soon the vessel can be inverted without spilling the blood. After a time the clot contracts and squeezes out the clear yellow serum. (3) Take a small thin copper or brass vessel, and place it in a freezing: mixture of ice and salt. Run into it some of the blood from 46 A MANUAL OF PHYSIOLOGY the artery. It soon freezes to a hard mass. Now take the vessel out of the freezing mixture and allow the blood to thaw. It will be seen that it remains liquid for a short time, and then clots. (4) Run some of the blood into a porcelain capsule, stirring it vigorously with a glass rod. The fibrin collects on the rod ; the blood is defibrinated and will no longer clot. (5) Take two glass cylinders, a and ft. In a put 50 cc. of a saturated solution of magnesium sulphate. In ft put 25 cc. of o'2 per cent, solution of potassium oxalate in normal saline. Run into Fig. 12. — Centkikuge (Jung). The four cylinders shown at the top of the figure are so swung that they become horizontal as soon as speed is got up. each cylinder 150 cc. of blood, mix, and let stand in a cool place for twenty-four hours. The corpuscles settle to the bottom, and the plasma (' salted plasma' from a, 'decalcified plasma' from /^) may be pipetted or siphoned off; or the plasma may be separated by means of a centrifuge (Fig. 12). (The blood may also be obtained directly from an animal at the slaughterhouse.) Now let the dog bleed to death. Observe that the flow of blood PRACTICAL EXERCISES. 47 is temporarily increased by making pressure on the abdominal walls so as to squeeze it towards the heart, by making passive pumping movements with the hind-legs, and also during the convulsions of asphyxia, which soon appear. (6) Next day perform the following experiments with the salted and decalcified plasma from (5). (a) Dilute some of the salted plasma in six test-tubes. A, B, C, D, E, F, with ten or twelve times its volume of water. Add to C and D a few drops of the solution of fibrin-ferment provided, and to E and F a little blood-serum. Put A, C, and E in a bath at 40° C. Leave B, U, and F at the temperature of the room. In a short time C and E will coagulate, D and F in a longer time ; A and B may or may not coagulate. If they do, A will coagulate before B. (/;) Put some of the decalcified plasma in two test-tubes. A' and B'. To both add a few drops of a 2 per cent, solution of calcium chloride. Place A' in a bath at 40° C, leave B' at air temperature. Both coagulate, but A' more quickly than B'. 5. Fibrin-Ferment, Preparation of. — Precii)itate blood-serum with ten times its volume of alcohol. Let it stand for several weeks, then extract the precipitate with water. The water dissolves out the fibrin-ferment, but not the other coagulated proteids. 6. Intravascular Coagulation. — Put a cannula into the external jugular vein of a rabbit under ether. Close the india-rubber tube on the cannula by a small piece of glass rod. Push the needle of a large hypodermic syringe through the indiarubber, and inject 10 to 30 cc. of the solution of tissue fibrinogen (nucleo-albumin) provided into the vein. In a short time extensive coagulation may ensue in the bloodvessels, and death may follow from failure of respiration. Rapidly open the thoracic and abdominal cavities and observe the distribution of the clot in the heart and vessels. With some rabbits, especially albinos, the experiment does not succeed. 7. Serum. — Test the reaction and take the specific gravity. Serum Proteids. — (i) Saturate serum with magnesium sulphate crystals at 30° C. The serum-globulin is precipitated. Filter off. Wash the precipitate on the filter with a saturated solution of mag- nesium sulphate. Dissolve the precipitate by the addition of a little distilled water, and perform the following tests for globulins : (a) Saturate with magnesium sulphate. A precipitate is obtained. ip) Drop into a large quantity of water, and a flocculent precipitate falls down, (r) Heat. Coagulation occurs. Determine the tempera- ture of coagulation. (2) To a portion of the filtrate from (i) add sodium sulphate to saturation. The serum-albumin is precipitated. (Neither magnesium sulphate nor sodium sulphate precipitate serum-albumin alone, but the double salt sodio-magnesium sulphate precipitates it, and this is formed when sodium sulphate is added to magnesium sulphate.) (3) Dilute another portion of the filtrate from (i) with its own bulk of water. Acidulate with dilute acetic acid, and determine the temperature of heat coagulation. (4) Precipitate the serum-globulin from another portion of serum 48 .1 MANUAL OF PHYSIOLOGY. by adding to it an equal volume of saturated solution of ammonium sul|jhate (Kauder's method). Filter. Precipitate the serum-albumin from the filtrate by saturating with ammonium sulphate crystals. (5) Acidulate some serum with dilute acetic acid and boil. Filter off the coagulum, and to the filtrate add silver nitrate. A non-proteid precipitate insoluble in nitric acid but soluble in ammonia indicates the presence of chlorides. 8. Cell-free Plasma. — This can be obtained by running horse's blood into a tall cylindrical vessel surrounded by a freezing mixture. As soon as the blood is cooled to o" C. and the red corpuscles have mostly settled to the bottom, the plasma is filtered through three folds of paper, laid on a double-walled funnel kept cool by a freezing mixture. Not only the red and white blood-corpuscles, but also the blood-plates, are retained on the filter. The filtered plasma, freed from all formed elements in this way, remains fluid for a considerable time at air temperature, but ultimately coagulates. Fig. 13. — Thoma-Zeiss H^mocytometek. M, mouth-piece of tube G, by which blood is sucked into S ; E, bead for mixing ; (C, view of slide from above ; b, in section ; c, squares in middle of B, as seen under microscope. 9. Enumeration of the Blood-corpuscles. — (Jse the Thoma-Zeiss apparatus (Fig. 13). Prick the finger to obtain a drop of blood. Suck the blood up into the capillary tube S to the mark i. Wipe off any blood which may adhere to the end of the tube. Then fill it with Hayem's solution (p. 21) or 3 per cent, sodium chloride to the mark loi. 'I'his represents a dilution of 100 times. Mix the blood and solution thoroughly, then blow out a drop or two of the liquid to remove all the solution which remains in the capillary tube. Now fill the shallow cell B with the blood mixture. Slide the cover-glass on, taking care that it does not float on the liquid, but that the cell is exactly filled. Put the slide under the microscope (say Leitz's oc. III., obj. 3), and count the number of red corpuscles in not less than ten to twenty squares. The greater the number of squares counted, the nearer will be the ap|jroximation to the truth. Now .take the average number in a square. The depth of the cell is PRACTICAL EXERCISES. 49 j^ mm., the area of each square ^\-^ sq. mm. The volume of the column of liquid standing upon a square is joVo cub. mm. One cub. mm. of the diluted blood would therefore contain 4,000 times as many corpuscles as one square. But the blood has been diluted 100 times, therefore i cub. mm. of the undiluted blood would contain 400,000 times the number of corpuscles in one square. Suppose the average for a square is found to be 13, This would corre- spond to 5,200,000 corpuscles in i cub. mm. of blood. 10. Blood pigment. — (i) Preparation of Haemoglobin Crystals. Put a small drop {a) of rat's and (/') of guinea-pig's blood on two slides. Add a drop of Canada balsam and cover. Rhombic crystals of oxy-Hb will soon form in the rat's blood, and tetrahedral Fig. 14.— Spectroscopic Examination ok Blood-pigment. crystals in the guinea-pig's (Fig. 9). These preparations can be ]:)ermanently preserved. Make another pair of preparations by adding water on the slide to rat's and guinea-pig's blood. Put on the cover-slip. The Hb is dissolved out and crystallizes first, as the water evaporates, around the edges. (2) Spectroscopic Examination of Hb and its Derivatives. — {a) With a small, direct-vision spectroscope look first at a bright part of the sky. Focus by pulling out or pushing in the eyepiece until the numerous fine dark lines (Fraunhofer's lines), running vertically across the spectrum, are seen. Narrow the slit by moving the milled edge till the lines are as sharp as they can be made. Note especially 4 50 A MANUAL OF PHYSIOLOGY. the line D in the orange, the hnes E and fi in the green and F in the blue. Always hold the spectroscope so that the red is at the left of the field. Now dip a wire into water and then into some salt or sodium carbonate, and fasten it in the flame of a fishtail burner. On examining the flame with the spectroscope, a bright yellow line will be seen occupying the position of the dark line D in the solar spectrum. This is a convenient line of reference in the spectrum, and in examining the spectra of haemoglobin and its derivatives, the position of the absorption bands with regard to the D line should always be noted. The dark lines in the solar spectrum are due to the absorption of light of a definite range of wave-lengths by metals in a state of vapour in the sun's atmosphere, and of course no dark lines are seen in the spectrum of a gas-flame. Now arrange the spectroscope, test-tube and gas-flame on a stand as in Fig. 14. Half nil the test-tube with defibrinated blood. Nothing can be seen with the spectroscope till the blood is diluted. Go on diluting till, on focussing, two bands of oxy-Hh are seen in the position indicated in Fig. 8. Draw the spectrum ; then dilute still more, and observe that the narrower left-hand band persists longer than the broader but less-defined band farther to the right. {p) Add a drop or two of ammonium sulphide solution to reduce the oxy-Hb. A single, ill-defined band now appears, occupying a position midway between the oxy-Hb bands, and the latter disappear. This is the band of reduced Hb (Fig. 8). (r) Carbonic Oxide Hb.—V'A.'~,%Q.02\-^'3L% through blood for a consider- able time. Examine some of the blood (after dilution) with the spectro- scope. Two bands, almost in the position of the oxy-Hb bands, are seen ; but no change is caused by the addition of ammonium sulphide, since carbonic oxide Hb is a more stable compound than oxy-Hb. {d) Met/icetnoglobin. — Put some blood into a test-tube, add a few drops of a dilute solution of ferricyanide of potassium, and heat gently. On diluting, a well-marked band will be seen in the red. On addition of ammonium sulphide this band disappears, the oxy-Hb bands are seen for a moment, and then give place to the band of reduced Hb (Fig. 8). {e) Acid-Hcematin. — To a little diluted blood add acetic acid and heat gently. The colour becomes brownish. The spectrum shows a band in the red between C and 1), not far from the position of the band of methcemoglobin. The addition of a dro[) or two of ammonium sulphide causes no change in the spectrum, and this is a means of distinguishing acid-hsematin from methsemoglobin. If much am- monium sulphide be added, alkali-haematin may be formed. This in its turn may be reduced by an excess of ammonium sulphide, and the spectrum of hcemochromogen may be obtained (Fig. 8). (/) Alkali-Hcematin. — To diluted blood add acetic acid and warm. Then, when the spectroscopic examination shows that acid-hamatin has been formed, neutralize with sodium hydrate. A brownish pre- cipitate of hsematin is thrown down, which dissolves in an excess of sodium hydrate, giving a solution of alkali-ha^matin. Or the sodium hydrate may be added to blood directly. The spectrum of PRACTICAL EXERCISES. 51 alkali-haematin is a broad but ill-defined band just overlapping the D line, and situated chiefly to the red side of it (Fig. 8). {g) Hcemochromogen. — To a solution of alkali-haematin add a drop or two of ammonium sulphide. The band near D disappears, and two bands make their appearance in the green (Fig. 8). {fi) Hcematoporphyrin. — To blood add strong sulphuric acid. Filter through asbestos and examine the purple liquid. Its spectrum shows two well-marked bands, one just to the left of D, and the other midway between \) and E (Fig. 8). (3) Guaiacum Test for Blood-pigment. — A test for blood pigment — much used in hospitals, and indeed a delicate one, but not always trustworthy unless certain precautions be taken — is the guaiacum test. A drop of freshly-prepared tincture of guaiacum is Fig. 15.— Fleischl's H.kmu.metek. added to the liquid to be tested, and then ozonic ether (peroxide of hydrogen). If blood-pigment be present the guaiacum strikes a blue colour ; but other ' oxygen-carriers ' — e.g.^ fresh vegetable pro- toplasm— will cause the same colour. (4) Quantitative Estimation of Haemoglobin — {a) By FleischPs Hccmometer (Fig. 15). — Fill that compartment a of the small cylinder (above the stage) which is over the tinted wedge with dis- tilled water. Put a little distilled water into the other compartment a. Now prick the finger and fill one of the small capillary tubes with blood. See that none of the blood is smeared on the outside of the tube. Then wash all the blood into the water in compartment a, and fill it to the brim with distilled water. Then by means of the milled head T move the tinted wedge K till the depth of colour is the same in the two compartments. The percentage of the normal quantity of Hb is given by the graduated scale P. For example, if 52 A MANUAL OF PHYSIOLOGY. the reading is 90, the blood contains 90 per cent, of the normal amount; if 100, it contains the normal quantity. The observations should be made in a dark room, the white surface, S, arranged below the compartments a and a , being illuminated by a lamp. It is best that each result should be the mean of two readings, one just too large and the other just too small. \b) Hoppe-Seyler^ s Method. — Two parallel-sided glass troughs are used. In one is put a standard solution of oxy-Hb of known strength ; in the other a measured quantity of the blood to be tested. The latter is diluted with water until its tint appears the same as that of the standard solution, when the troughs are placed side by side on white paper. From the quantity of water added it is easy to calculate the proportion of hemoglobin in the undiluted blood. Greater accuracy is said to be obtained, if the standard solution and the Hb of the blood are both converted into carbonic oxide Hb by passing a stream of coal-gas through them. (5) Microscopic Test for Blood-pigment. — Put a drop of blood on a slide. Heat gently over a flame, so as to evaporate the water. Then add a small crystal of common salt and a drop of glacial acetic acid ; put on a cover-glass, and again heat slowly till the liquid just begins to boil. Take the slide away from the flame for a few seconds, then heat it again for a moment ; and repeat this process two or three times. Now let the slide cool, and examine with the micro- scope (high power). The small black, or brownish-black, crystals of hemin will be seen (Plate I., 3). This is an important test where only a minute trace of blood is to be examined, as in some medico- legal cases. A blood-stain on a piece of cloth may first of all be soaked in a small quantity of distilled water, and the liquid examined with the spectroscope or the micro-spectroscope (a microscope in which a small spectroscope is substituted for the eye-piece). Then evapo- rate the liquid to dryness on a water-bath, and apply the haemin test. Or perform the hosmin test directly on the piece of cloth. In a fresh stain the blood-corpuscles might be recognised under the microscope, after the cloth had been soaked and kneaded in a little glycerine. I CHAPTER 11. THE CIRCULATION OF THE BLOOD AND LYMPH. The blood can only fulfil its functions by continual movement. This movement implies a constant transforma- tion of energy ; and in the animal body the transformation of energy into mechanical work is almost entirely allotted to a special form of tissue, muscle. In most animals there exist one or more rhythmically contractile muscular organs, or hearts, upon which the chief share of the work of keeping up the circulation falls. Comparative. — In Echinus a contractile tube connects the two vascular rings that surround the beginning and end of the aUmentary canal, and plays the part of a heart. In the lower Crustacea and in insects the heart is simply the contractile and generally sacculated dorsal bloodvessel ; in the higher Crustacea, such as the lobster, it is a well-defined muscular sac situated dorsally. A closed vascular system is the exception among invertebrates. In most of them the blood passes from the arteries into irregular spaces or lacunoe in the tissues, and thence finds its way back to the heart. Amphioxus, the lowest vertebrate, has a primitive lacunar vascular system ; a contractile dorsal bloodvessel serves as arterial or systemic heart, a contractile ventral vessel as venous or respiratory heart. From the latter, vessels go to the gills. Fishes possess only a respiratory heart, consisting of a venous sinus, auricle, and ventricle. This drives the blood to the gills, from which it is gathered into the aorta ; it has thence to find its way without further propulsion through the systemic vessels. Amphibians have two auricles and a single ventricle ; reptiles, two auricles and two incompletely-separated ventricles. In birds and mammals the respiratory and systemic hearts are com- pletely separated. The former, consisting of the right auricle and ventricle, propels the blood through the lungs ; the latter, consisting of the left auricle and ventricle, receives it from the pulmonary veins, and sends it through the systemic vessels. General View of the Circulation in Man. — The whole circuit 54 A MANUAL OF PHYSIOLOGY, •of the blood is divided into two portions, very distinct from each other, both anatomically and functionally — the respiratory or lesser circulation, and the systemic or greater circulation. Starting from the left ventricle, the blood passes along the systemic vessels — arteries, capillaries, veins — and, on returning to the heart, is poured into the right auricle, and thence into the right ventricle. From the latter it is driven through the pulmonary artery to the lungs, passes through the capillaries of these organs, and returns through the pulmonary veins to the left auricle and ventricle. The Fig. i6. — Diagram uf iiik Gln>;kai, Couk.se oi" the Cikculation. RA, LA, right and left auiic'es ; RV, LV, right and left ventricles. portal system, which gathers up the blood from the in- testines, forms a kind of loop on the systemic circulation. The lymph-current is also in a sense a slow and stagnant side-stream of the blood circulation; for substances are con- stantly passing from the bloodvessels into the lymph-spaces, and returning, although after a comparatively long interval, into the blood by the great lymphatic trunks. Physiological Anatomy of the Vascular System. — The heart is to be looked upon as a portion of a bloodvessel which has THE CIRCULATION OF THE BLOOD AND LYMPH. 55 been modified to act as a pump for driving the blood in a definite direction. Morphologically it is a bloodvessel ; and the physiological property of rhythmical contraction which belongs to the muscle of the heart in so eminent a degree is, as has been mentioned on page 53, an endowment of bloodvessels in many animals that possess no localized heart. Even in some mammals contractile bloodvessels occur; the veins of the bat's wing, for example, beat with a regular rhythm, and perform the function of accessory hearts. The whole vascular system is lined with a single layer of endothelial cells. In the capillaries nothing else is present ; the endothelial layer forms the whole thickness of the wall. In young animals, at any rate, the endothelial cells of the capillaries are capable of contracting when stimulated ; and changes in the calibre of these vessels can be brought about in this way. The walls of the arteries and veins are chiefly made up of two kinds of tissue, which render them distensible and elastic, non-striped muscular fibres and yellow elastic fibres. The muscular fibres are mainly arranged as a circular middle coat, which, especially in the smaller arteries, is relatively thick. One conspicuous layer of elastic fibres marks the boundary between the middle and inner coats. In the larger arteries elastic laminae are also scattered freely among the muscular fibres of the middle coat. The outer coat is made up chiefly of ordinary con- nective tissue. The veins differ from the arteries in having thinner walls, with the layers less distinctly marked, and containing a smaller proportion of non-striped muscle and elastic tissue ; although in some veins, those of the pregnant uterus, for instance, and the cardiac ends of the large thoracic veins, there is a great development of muscular tissue. Further, and this is of prime physiological im- portance, valves are present in many veins. These are semilunar folds of the internal coat projecting into the lumen in such a direction as to favour the flow of blood towards the heart, but to check its return. In some veins there are no valves ; for example, in those of the bones, internal organs, and central nervous system. The valves are especially well marked in the lower limbs, where the venous 56 A MANUAL OF PHYSIOLOGY. circulation is uphill. When a valve ceases to perform its function of supporting the column of blood between it and the valve next above, the foundation of varicose veins is laid ; the valve immediately below the incompetent one, having to bear up too great a weight of blood, tends to yield in its turn, and so the condition spreads. The smallest veins, or venules, are very like the smallest arteries, or arterioles, but somewhat wider and less muscular. The transition from the capillaries to the arterioles and venules is not abrupt, but may be considered as marked by the appear- ance of the non-striped muscular fibres, at first scattered singly, but gradually becoming closer and more numerous as we pass away from the capillaries, until at length they form a complete layer. In the heart the muscular element is greatly developed and differentiated. Both histologically and physiologically the fibres seem to stand between the striated skeletal muscle and the smooth muscle. In the mammal the cardiac muscular fibres are made up of short oblong cells, devoid of a sarcolemma, often branched, and arranged in anastomosing rows. Each cell has a single nucleus in the middle of it. The fibres are transversely striated, but the striae are not so distinct as in skeletal muscle. Many fibres pass from one auricle to the other, and from one ventricle to the other. The auricles and ventricles are also, in some mammals at least, connected in early life by muscular tissue ; and even in the adult traces of this connection may persist (Plate I., 4). In the frog's heart the muscular fibres are spindle-shaped, Hke those of smooth muscle, but transversely striated, like those of skeletal muscle. From the sinus to the apex of the ventricle there is a continuous sheet of muscular tissue. The problems of the circulation are partly physical, partly vital. Some of the phenomena observed in the blood-stream of a living animal can be reproduced on an artificial model ; and they may justly be called the physical phenomena of the circulation. Others are essentially bound up with the pro- perties of living tissues ; and these may be classified as the vital or physiological phenomena of the circulation. The distinction, although by no means sharp and absolute, is a THE CIRCULATION OF THE BLOOD AND LYMPH. 57 convenient one — at least, for purposes of description ; and as such we shall use it. But it must not be forgotten that the physiological factors play into the sphere of the physical, and the physical factors modify the physiological. Con- sidered in its physical relations, the circulation of the blood is the flow of a liquid along a system of elastic tubes, the bloodvessels, under the influence of an intermittent pressure produced by the action of a central pump, the heart. But the branch of dynamics which treats of the movement of liquids, or hydrodynamics, is one of the most difficult parts of physics, and, in spite of the labours of many eminent men, is as yet so little advanced that even in the physical portion of our subject we are forced to rely chiefly on empirical methods. It would, therefore, not be profitable to enter here into mathematical theory, but it may be well to recall to the mind of the reader one or two of the simplest data connected with the flow of liquids through tubes : Torricelli's Theorem. — Suppose a vessel filled with water, the level of which is kept constant ; the velocity with which the water will escape from a hole in the side of the vessel at a vertical depth h below the surface will be v= ^/-^gh, where ^ is the acceleration pro- duced by gravity.* In other words, the velocity is that which the water would have acquired in falling in vacuo through the distance h. This formula was deduced experimentally by Torricelli, and holds only when the resistance to the outflow is so small as to be negligahle. The reason of this restriction will be easily seen, if we consider that when a mass /// of water has flowed out of the opening, and an equal mass w has flowed in at the top to maintain the old level, everything is the same as before, except that energy of position equal to that possessed by a mass w at a height // has disappeared. If this has all been changed into kineiic energy E, in the form of visible motion of the escaping water, then E = -|;«z/- = »igh, i.e., v = y/2g/i. If, however, there has been any sensible resistance to the outflow, any sensible friction, some of the potential energy (energy of position), will have been spent in overcoming this, and will have ultimately been transformed into the kinetic energy of molecular motion, or heat. Next let a horizontal tube of uniform cross-section be fitted on to the orifice. The velocity of outflow will be diminished, for resist- ances now come into play. When the liquid flowing through a lube wets it, the layer next the wall of the tube is prevented by adhesion from moving on. The particles next thi<^ stationary layer rub on it, so to speak, and are retarded, although not stopped altogether. The '■■ I.e., the amount added per second to the velocity of a falling body (^=32 feet). 58 A MANUAL OF PHYSIOLOGY. next layer rubs on the comparatively slowly moving particles outside it, and is also delayed, although not so much as that in contact with the immovable layer on the walls of the tube. In this way it comes about that every particle of the liquid is hindered by its friction against others — those in the axis of the tube least, those near the periphery most — and part of the energy of position of the water in the reservoir is used up in overcoming this resistance, only the remainder being transformed into the visible kinetic energy of the liquid escaping from the open end of the tube. If vertical tubes be inserted at different points of the horizontal tube, it will be found that the water stands at continually decreasing heights as we pass away from the reservoir towards the open end of the tube. The height of the liquid in any of the vertical tubes indicates the lateral pressure at the point at which it is inserted ; in other words, the excess of potential energy, or energy of position, which at that point the liquid possesses as compared with the water at the free end, where the pressure is zero. If the centre of the cross-section of the free end of the tube be joined to the centres of all the menisci, it Fig. 17- -Diagram tg illustrate Flow of Water along a Horizontal Tube connected with a Reservoir. will be found that the line is a straight line. The lateral pressure at any point of the tube is therefore proportional to its distance from the free end. Since the same quantity of water must pass through each cross-section of the horizontal tube in a given time as flows out at the open end, the kinetic energy of the liquid at every cross-section must be constant and equal to ^f/iv~, where v is the mean velocity (the quantity which escapes in unit of time divided by the cross-section) of the water at the free end. Just inside the orifice the total energy of a mass m of water is nigh ; just beyond it at the first vertical tube, nigh' + \mv^, where h' is the lateral pressure. On the assumption that between the inside of the orifice and the first tube, no energy has been transformed into heat (an assumption the more nearly correct the smaller the distance between it and the inside of the orifice is made), we have mgh = mgh' + \mv', i.e., \m'iP- = mg(Ji- h') In other words, the portion of the energy of position of the water in the reservoir which is transformed into the kinetic energy of the water flowing along the horizontal tube is measured by the difference between the height of the level of the THE CIRCULATION OF THE BLOOD AND LYMPH. 59 reservoir and the lateral pressure at the beginning of the horizontal tube — that is, the height at which the straight line joining the menisci of the vertical tubes intersects the column of water in the reservoir. Let H represent the height corresponding to that part of the energy of position which is transformed into the kinetic energy of the flow- ing water. H is easily calculated when the mean velocity of efflux is known. For v = v/2^H by Torricelli's theorem (since none of the energy corresponding to H is supposed to be used up in overcoming friction), or H = - " At the second tube the lateral pressure is only h". The sum of the visible kinetic and potential energy here is therefore ^//iv- + vigh" . A quantity of energy mg {h' — h") must have been transformed into heat owing to the resistance caused by fluid friction in the portion of the horizontal tube between the first two vertical tubes. In general the energy of position represented by the lateral pressure at any point is equal to the energy used up in over- coming the resistance of the portion of the path beyond this point. It has been found by experiment that v, the mean velocity of out- flow, when the tube is not of very small calibre, varies directly as the diameter, and therefore the volume of outflow as the cube of the diameter. In fine capillary tubes the mean velocity is proportional to the square, and the volume of outflow to the fourth power of the diameter (Poiseuille). If, for example, the linear velocity of the blood in a capillary of 10 /a in diameter is i mm. per sec, it will be four times as great (or 2 mm. per sec.) in a capillary of 20 yu. diameter, and one-fourth as great (or i mm. per sec.) in a capillary of 5 /x diameter, the pressure being supposed equal in all. The volume of outflow per second is obtained by multiplying the cross-section by the linear velocity. The cross-section of a circular capillary, 10 /* in diameter, is ''" (5 x y^Vit)^~' ^^y> Tirlinr ^'^' '^"'"- "^'^^ outflow will be jTrl^jj^ X ^T = TT-^]yj^jy cub. mm. per sec. The outflow from the capillary of 20 /x diameter would be sixteen times as much, from the 5 jx capillary only one-sixteenth as much. Some idea of the extremely minute scale on which the blood-flow through a single capillary takes place, may be obtained if we consider that for the capillary of 10 /x diameter a flow of 0-5^^0 cub. mm. per sec. would scarcely amount to i cub. mm. in six hours, or to i cc. in 250 days. When the initial energy is obtained in any other way than by means of a 'head' of water in a reservoir — say, by the descent of a piston which keeps up a constant pressure in a cylinder filled with liquid — the results are exactly the same. Even when the horizontal tube is distensible and elastic, there is no difference when once the tube has taken up its position of equilibrium for any given pressure, and that pressure does not vary. Take now the case of an intermittent pressure. \Mien this acts on a rigid tube, everything is the same as before. When the pressure alters, the flow at once comes to correspond with the new pressure. Water thrown by a force-pump into a system of rigid tubes escapes at every stroke of the pump in exactly the quantity in which it enters, for water is practically incompressible, and the total quantity present 6o A MANUAL OF PHYSIOLOGY. at one time in the system cannot be sensibly altered. In the intervals between the strokes the flow ceases ; in other words, it is intermittent. It is very different with a system of distensible and elastic tubes. During each stroke the tubes expand, and make room for a portion of the extra liquid thrown into them, so that a smaller quantity flows out than passes in. In the intervals between the strokes the dis- tended tubes, in virtue of their elasticity, tend to regain their original calibre. Pressure is thus exerted upon the liquid, and it continues to be forced oat, so that when the strokes of the pump succeed each other with sufficient rapidity, the outflow becomes continuous. This is the state of affairs in the vascular system. The intermittent action of the heart is toned down in the elastic vessels to a continuous steady flow. The Beat of the Heart. — In the frog's heart the contraction can be seen to begin about the mouths of the great veins which open into the sinus venosus. Thence it spreads in succession over the sinus, auricles, and ventricle, being propagated in all probability as a muscular wave, without the intervention of nerve-fibres. In the mammalian heart the starting-point of the contraction is likewise the mouths of the veins opening into the auricles, which are richly pro- vided with muscular fibres akin to those of the heart. But the wave advances so rapidly that it is difficult, if not im- possible, to trace in its course a regular progress from base to apex, although the ventricular beat undoubtedly follows that of the auricle, and the capillary electrometer indicates that, in a heart beating normally, the negative change asso- ciated with contraction begins at the base and then reaches the apex. It is not definitely known how in the mammal the beat of the ventricle is co-ordinated with that of the auricle. The alleged absence of muscular connection has led to a very general belief that the link is of nervous nature ; but recent work makes it possible that, at least in some animals, the contraction wave may spread, as in the frog's heart, along fibres, apparently muscular, which interpenetrate the ring of fibrous tissue between the auricles and ventricles (Kent). The most conspicuous events in the beat of the heart, in their normal sequence, are : (i) the auricular contraction or systole ; (2) the ventricular contraction or systole ; (3) the pause or diastole. The auricles, into which, and beyond THE CIRCULATION OF THE BLOOD AND LYMPH. 6i which into the ventricles, blood has been flowing during the pause from the great thoracic veins, contract sharply. The contraction begins in the muscular rings that surround the orifices of the veins, so that these, destitute of valves as they are, are sealed up for an instant, and regurgitation of blood into them is prevented. The filling of the ventricles is thus completed ; their contraction begins either simul- taneously with the relaxation of the auricles or a little before it, the mitral and tricuspid valves being at the same time floated up so as to cover the auriculo-ventricular orifices, and prevent the backward flow of blood from the ventricles to the auricles. The free edges of the segments of the valves are kept close against each other by the pressure of the blood in the contracting ventricle, and prevented from being pushed up into the auricle by the chordae tendineae attached to the papillary muscles, which contract along with the ventricle, and, in spite of the shortening of the latter, keep the chordae taut. During their contraction, or systole, the ventricles change their shape in such a way that the cross-section — which in the relaxed state is a rough ellipse with the major axis from right to left — becomes approximately circular, and they then form a right circular cone. As soon as the pressure of the blood within the con- tracting ventricles exceeds that in the aorta and pulmonary artery respectively, the semilunar valves, which at the beginning of the ventricular systole are closed, yield to the pressure, and blood is driven from the ventricles into these arteries. The ventricles are more or less completely emptied during the contraction, which seems still to be maintained for a short time after the blood has ceased to pass out. The contraction is followed by sudden relaxation, regurgitation of the blood from the aorta and pulmonary arteries being prevented by closure of the semilunar valves. The interval during which the whole heart is at rest — i.e., the interval between the end of the relaxation of the ventricles and the beginning of the systole of the auricles — constitutes the pause. The whole series of events is called a cardiac cycle or revolution (see * Practical Exercises,' p. 150). 62 A MANUAL OF PHYSIOLOGY. It will be easily understood that the time occupied by any one of the events of the cardiac cycle is not constant, for the rate of the heart is variable. If we take about 70 beats a minute as the average normal rate in a man, the ventricular systole will occupy about '3 second ; the ventricular diastole, including the relaxation, about '5 second. The ventricular systole may be divided into three periods of pretty nearly equal length : a period during which the pressure is still insufficient to cause the opening of the semilunar valves ; a period during which, these valves being open, the blood is forced into the arteries ; and a further period during which the ventricle remains contracted. The systole of the auricle is one-third as long as that of the ventricle. This rhythmical beat of the heart is the ground phe- nomenon of the circulation. It reveals itself by certain tokens — sounds, surface-movements or pulsations, alterations of the pressure and velocity of the blood, changes of volume in parts — all periodic phenomena, continually recurring with the same period as the heart-beat, and all funda- mentally connected together. And if we hold fast the idea that when we take a pulse-tracing, or a blood-pressure curve, or a plethysmographic record, we are really investigating the same fact from different sides, we shall be able, by following the cardiac rhythm and its consequences as far as we can trace them, to hang upon a single thread many of the most important of the physical phenomena of the circulation. The Sounds of the Heart, — When the ear is applied to the chest, or to a stethoscope placed over the cardiac region, two sounds are heard with every beat of the heart ; they follow each other closely, and are succeeded by a period of silence. The dull booming ' first sound ' is heard loudest in a region which we shall afterwards have to speak of as that of the ' cardiac impulse ' (p. 64) ; the short, sharp ' second sound ' over the junction of the second right costal cartilage with the sternum. There has been much discussion as to the cause of the first sound. That a sound corresponding with it in time is heard in an excised bloodless heart when it contracts, is certain ; and therefore the first sound cannot be exclusively THE CIRCULATION OF THE BLOOD AND LYMPH. 63 due, as some have asserted, to vibrations of the auriculo- ventricular valves when they are suddenly rendered tense by the contraction of the ventricles, for, of course, in a bloodless heart the valves are not stretched. Part of the sound must accordingly be associated with the muscular contraction, as such. As we shall see (Chap. IX.), the sound caused by a contracting muscle is probably, in part at least, a resonance tone of the ear ; and therefore there is no diffi- culty in understanding how a simple non-tetanic contraction like that of the heart should give rise to a ' muscular' sound of definite pitch. But there is undoubtedly a valvular as well as a muscular factor in the first sound ; and, indeed, there is reason to believe that the valvular note is the essential part of the sound, which perhaps acquires its peculiar booming character from the resonance tones of the ear, and possibly of the chest-wall, set up by the muscular contraction. Some observers (Rutherford and Hay- craft), have been able to distinguish in the first sound the valvular and the muscular elements, the former being higher in pitch than the latter, but a minor third below the second sound. Further, when the mitral valve is prevented from closing by experimental division of the chordae tendinea, or by pathological lesions, the first sound of the heart is altered or replaced by a ' murmur.' This evidence is not only decisive as regards the physiological question, but of great practical interest from its bearing on the diagnosis of cardiac disease. It may be added that the point of the chest-wall at which the first sound is heard loudest is also the point at which a changed sound or murmur connected with disease of the mitral valve is most distinctly heard. The sound is, therefore, best conducted from the mitral valve along the heart to the point at which it comes in contact with the wall of the chest. Changes connected with disease of the tricuspid valve are heard best in the third to the fifth interspace just to the right of the sternum, and over the right border of that bone. The second sound is caused by the vibrations of the semi- lunar valves when suddenly closed. The sharpness of its note is lost, and nothing but a rushing noise or bruit can be 64 yl MANUAL OF PHYSIOLOGY. heard, when the valves are hooked back and prevented from closing. It is altered, or replaced by a murmur when the valves are diseased. As there is a mitral and a tricuspid factor in the first sound, so there is an aortic and a pul- monary factor in the second. The place where the second sound is best heard (over the junction of second right costal cartilage and sternum) is that at which any change pro- duced by disease of the aortic valves is most easily recog- nised. The sound is conducted up from the valves along the aorta, which comes nearest to the surface at this point. Changes connected with disease of the pulmonary valves are most readily detected over the second left intercostal space near the edge of the sternum. The first sound is 'systolic' — that is, it occurs during the Fig. i8.— Diagram of Makey's Cakoiogkai'H. A, knob attaclied to flexible membrane tied over end of metal bnx — the knob is placed over the apex beat ; C is the folded edge of the membrane ; H is the tube communicating with a recording tambour. ventricular systole; the second is 'diastolic,' beginning at the commencement of the diastole. The Cardiac Impulse. — A surface-movement is seen, or an impulse felt, at every cardiac contraction in various situa- tions where the heart or arteries approach the surface. The pulsation, or impulse, of the heart, often somewhat loosely styled the apex-beat, is usually most distinct to sight and touch in a small area lying in the fifth left intercostal space, an inch and a half to the sternal side of a vertical line drawn through the left nipple. It is due to the systolic hardening of the ventricles, which are here in contact with the chest- wall, the contact being at the same time rendered closer by their change of shape, and by a slight movement of rotation of the heart from left to right during the contraction (' Prac- tical E.xercises,' p. 152). The very apex of the heart does not correspond with the position of the cardiac impulse, but lies THE CIRCULATION OF THE BLOOD AND LYMPH. 65 somewhat lower in the chest. Even in health the position of the impulse varies somewhat with the position of the body and the respiratory movements. In disease its displacement is an important diagnostic sign, and may be very marked, especially in cases of effusion of fluid into the pleural cavity. Various instruments, called cardiographs, have been devised for magnifying and recording the movements produced by the cardiac impulse. Marey's cardiograph consists essenti- ally of a small chamber, or tambour, filled with air, and closed at one end by a flexible membrane carrying a button, Fig. ig. — Cakuiogram takkn w rm Makey's Cakdiograph. A, auricular systole ; V, ventricular systole ; D, diastole. Tlie arrow shows the direction in which the tracing is to be read. which can be adjusted to the wall of the chest. This receiv- ?w^ tambour is connected by a tube with a nTor^/;/^ tambour, the flexible plate of which acts upon a lever writing on a travelling surface— a uniformly-rotating drum, for example — covered with smoked paper. Any movement communicated to the button forces in the end of the tambour to which it is attached, and thus raises the pressure of the air in it and in the recording tambour ; the flexible plate of the latter moves in response, and the lever transfers the movement to the paper. The tracing, or cardiogram, obtained in this way shows a small elevation corresponding to the auricular systole, succeeded by a large abrupt rise corresponding to the beginning of the first sound, and caused by the ven- tricular systole. The rise is maintained, with small secondary oscillations, for about '3 of a second in a tracing from a normal man, then gives way to a sudden descent, that marks the relaxation of the ventricles, the beginning of the second 5 66 A MANUAL OF PHYSIOLOGY. sound, and the closure of the semikinar valves. An interval of about "5 second elapses before the curve begins again to rise at the next auricular contraction. Endocardiac Pressure. — The function of the heart is to maintain an excess of pressure in the aorta and pulmonary artery sufficient to overcome the friction of the whole vascular channel, and to keep up the flow of blood. So long as the semilunar valves are closed, most of the work of the contracting ventricles is expended in raising the pressure of the blood within them. At the moment when blood begins to pass into the arteries, nearly all the energy of this blood is potential ; it is the energy of a liquid under \ '.! ■ V \ J ; ^ 1 Aur: 1 ^ r\r \ ^ i H \ f' V ; : / 1 1, 1 1 i i ■ ;l '■■J y^^^~< V _^^ ~^~^\ Vtnt:\ K \ >~-_--^ AS VS D Fig. 2o.— CURVE.S ok Endocakdi.\c Pressure takem with Cardiac Sound.s. Aur., auricular curves ; Vent., ventricular curves ; AS, period of auricular systole ; VS, of ventricular systole ; D, diastole. pressure. During a cardiac cycle the pressure in the cavities of the heart, or the endocardiac pressure, varies from moment to moment, and its variations afford important data for the study of the mechanics of the circulation. Chauveau and Marey obtained tracings of the variations of endocardiac pressure by means of their cardiac sound. This consists of an ampulla of thin indiarubber, supported on a framework and communicating with a long tube, which is connected with a recording tambour. The sound is pushed through the jugular vein till the ampulla lies in the right auricle or ventricle (of a horse), or through the carotid THE CIRCULATION OF THE BLOOD AND LYMPH. 67 and aorta till it lies in the left ventricle. Another form of sound has two ampullae, placed at such a distance from each other that when one is in the right ventricle the other is in the auricle of the same side. Each ampulla communicates by a separate tube in the common stem of the instrument with a recording tam.bour, and the writing points of the two tambours are arranged in the same vertical line. When any change in the blood-pressure takes place, the degree of compression of the ampullae is altered, and the change is transmitted along the air-tight connections to the recording tambours. Simultaneous records of the changes in the blood-pressure in the right auricle and ventricle, obtained in this way, indicate a sudden rise of the auricular pressure corresponding with the auricular systole, followed by a sudden fall. This is represented on the ventricular curve Fig. 21. — Diagram of Cardiac Sound for Simultaneous Rkgistratkjn ok Endocardiac Pressure in Auricle and Ventricle. A, elastic ampulla for auricle ; V for ventricle ; T, tubes connected with recording tambours. by a smaller elevation, which shows that the pressure in the ventricle has been raised somewhat by the blood driven into it from the auricle. Then follows immediately a great and abrupt increase of ventricular pressure, the result of the systole of the ventricle. This elevation remains for some time at the maximum, and then the curve suddenly sinks as the ventricle relaxes. Near the bottom of the descent there is a slight elevation, due, as Marey supposes, to the closure of the semilunar valves, which causes a better-marked and simultaneous elevation in the curve of aortic pressure when this is registered by means of a sound passed into the aorta through the carotid artery. Both the auricular and ven- tricular curves now begin again to rise slowly, showing a gradual increase of pressure as the blood flows from the 68 A MANUAL OF PHYSIOLOGY. great veins into the auricle, and through the tricuspid orifice into the ventricle. This slow rise continues till the next auricular systole. A tracing of the cardiac impulse, taken at the same time by means of a cardiograph, follows the curve of ventricular pressure with considerable closeness, showing the same slow ascent during diastole, the same slight elevation corre- sponding to the auricular systole, a great and sustained rise during the contraction of the ventricle, and even a slight indication of the closure of the semilunar valves. Marey states that before closure of the semilunar valves, especially when the arterial blood-pressure has been lowered, as b}^ running for a few minutes or by nitrite of amyl, and the discharge of blood from the ventricles is, therefore, rendered abrupt, secondary waves (p. 72) set up in the pulmonary artery and the aorta by that discharge may react through the unclosed orifices upon the ventricles, and cause small undulations in the endocardiac pressure, visible also on the tracings of the cardiac impulse. The method of Chauveau and Marey is well suited for recording changes of pressure, but not so suitable for giving absolute measurements, although by experimental graduation of the instruments these, too, can be obtained. Roy and Rolleston used a lever, connected with a piston working in a cylinder, as a recording apparatus. The endo- cardiac pressure was directly communicated to the piston by connecting the cylinder with the interior of the heart either by means of a cannula introduced through one of the great vessels, or by a hollow needle or trocar pushed through the ventricle or auricle. For certain purposes it is important to know the maximum and minimum pressure in the heart during a cardiac cycle, and with this object Goltz and Gaule constructed their maximum and minimum manometer. This consists of an ordinary mercurial manometer (p. 80), with a valve in the connection between it and the heart. This valve can be arranged so as to oppose the passage of blood from the mano- meter towards the heart, while it allows it to pass in the opposite direction. The apparatus then acts as a maximum THE CIRCULATION OF THE BLOOD AND LYMPH. 69 manometer. If the direction of the valve is reversed, it acts as a minimum manometer. Hurthle has lately improved upon this by constructing a manometer that allows both the maximum and the minimum pressure to be read at the same time. Goltz and Gaule found in the dog during the sj^stole a maximum pressure in the left ventricle of (in round numbers) 140 mm. of mercury, and in the right ventricle and auricle 60 mm. and 20 mm. respectively. A minimum pressure of —50 to — 20 mm. was seen in the left ventricle, and a smaller minimum pressure in the right ventricle and right auricle. Part of this negative pressure may be ascribed to the general fall of pressure in the thoracic cavity when the chest expands in inspiration (Chap. III.). Whether the heart itself, and particularly the left ventricle, has any power of aspiration when it suddenly relaxes, has been much dis- cussed. Some have denied altogether the existence of such a power, but it would seem that, in a vigorous heart at any rate, a negative pressure or suction is really exerted, even after the thorax has been opened and the influence of the respirator}^ movements eliminated. The Pulse. — At each contraction of the heart, a quantity of blood, probably varying within rather wide limits (p. 106), is forced into the already-full aorta. If the walls of the bloodvessels were rigid, it is evident (p. 59), that exactly the same quantity would pass at once from the veins into the right auricle. The work of the ventricle would all be spent within the time of the systole, and only while blood was being pumped out of the heart would any enter it. Since, however, vessels are extensible, some of the blood forced into the aorta during systole is heaped up in the arteries, beyond which, in the capillaries, with their rela- tively great surface, the chief resistance to the blood-flow lies. The arteries are accordingly distended to a greater extent than before the systole, and, being elastic, they keep contracting upon their contents until the next systole over-distends them again. In this way, during the pause the walls of the arteries are executing a kind of elastic systole, and driving the blood on into the capillaries. The work done by the ventricle is, in fact, partly stored up as 70 A MANUAL OF PHYSIOLOGY. potential energy in the tense arterial wall, and this energy is being continually transformed into work upon the blood during the pause, the heart continuing, as it were, to con- tract by proxy during its diastole. Thus, the blood pro- gresses along the arteries in a series of waves, to which the name of ' blood-waves ' or ' pulse-waves ' may be given, "Wherever the pulse-wave spreads it manifests itself in various ways — by an increase of blood-pressure, an increase in the mean velocity of the blood-flow, an increase in the volume of organs, and by the visible and palpable signs to which the name of pulse is commonly given in a restricted sense. The intermittence in the flow with which the pulse- wave is necessarily associated is at its height at the begin- ning of the aorta. In middle-sized arteries, such as the radial, it is still well marked, but it dies away as the capil- laries are reached, and only under special conditions passes on into the veins. The pulse was well known to the Greek phj'sicians, and used by them to a certain extent as an indication in practical medicme. Harvey demonstrated with some clearness the relation of the pulse to the contraction of the heart, but Thomas Young was the first to form a proper conception of it as the outward token of a wave propagated from heart to periphery. When the finger is placed over a superficial artery like the carotid, the radial or the temporal, a throb or beat is felt, which, without measurement, seems to be exactly coinci- dent with the cardiac impulse. In certain situations the pulse can be seen as a distinct rhythmical rise and fall of the skin over the vessel. The throbbing of the carotid, especially after exertion, is familiar to everyone, and the beat of the ulnar artery can be easily rendered visible by extending the hand sharply on the wrist. When the pulse is felt by the finger, it is not the expansion, but the hardening of the wall of the vessel due to the increase of arterial pressure, that is perceived ; and even a superficial artery when embedded in soft tissues so that it cannot be compressed, gives no token of its presence to the sense of touch. Sometimes an artery is longitudinally extended by THE CIRCULATION OF THE BLOOD AND LYMPH. 71 the pulse-wave, and this extension may be far more con- spicuous than the lateral dilatation. This is particularly seen when one point of the vessel is fixed and a more distal point offers some obstruction to the blood-flow, as at a bifur- cation, or in an artery which has been ligatured and divided. By means of the sphygmograph, the lateral movements of the arterial wall, or, rather, in man, the movements of the skin and other tissues lying over the bloodvessel, can be magnified and recorded. It would be very unprofitable to enumerate all the sphygmographs which ingenuity has in- vented and found names for. The first rude attempt to magnify the movements of the pulse was made by loosely attaching a thin fibre of glass or wax to the skin with a little lard, in order to demonstrate the venous pulse which appears under certain conditions. Vierordt improved on Fig. 22. — Scheme of Makey's Sphygmograph. A, Toothed wheel connected with axle H, and gearing into toothed upright B ; C, ivory pad which rests over bloodvessel and is pressed on it by moving G, a screw passing tiirough tlie spring J ; E, writing lever attached to axle H, and moved by its rotation ; E writes on D, a travelling surface moved by clockwork F. this by using a counterpoised lever writing on a blackened surface. But the inertia of the lever was so great that the finer features of the pulse were obscured. In all modern sphygmographs there is a part, usually button-shaped, which is pressed over the artery by means of a spring, as in Marey's and Dudgeon's sphygmographs, or by a weight, or by a column of liquid. In Marey's instrument, the button acts upon a toothed rod gearing into a toothed wheel, to which a lever, or a system of levers, is attached. The lever has a writing-point which records the movement on a smoked plate, or a plate covered with smoked paper, drawn uni- formly along by clockwork. Brondgeest's pansphygmograph is a particular application of Marey's tambours, for receiving and registering the movement of the pulse,, as is Marey's 72 A MANUAL OF PHYSIOLOGY own ' sphygmograph of transmission.' (' Practical Exer- cises,' p. 159.) In a normal pulse-tracing (Fig. 23) the ascent is abrupt and unbroken ; the descent is more gradual, and is inter- rupted by one, two, or even three or more, secondary wave- lets. The most important and constant of these is the one marked 3, which has received the name of the dicrotic wave. Usually less marked, and sometimes absent, is the wavelet 2 between the dicrotic elevation and the apex of the curve. It is generally termed the predicrotic wave. Following the dicrotic wave are sometimes seen one or more ripples, which have been called elastic elevations. 1M(J. 2j. — I'L'L.sK 'JKACINGS. I, Primary elevation; 2, predicrotic or first tidal wave; 3, dicrotic wave. The depression between 2 and 3 is the dicrotic or aortic notcii ; 3 is better marked in B than in A. C, dicrotic pulse with low arterial pressure ; D, pulse with higii arterial pressure — summit of primary elevation in the form of an ascending plateau. E, systolic anacrotic pulse ; the secondary \\avelet a occurs during the upstroke corresponding to the ventricular systole. F, presystolic anacrotic pulse ; a occurs just before the systole of the ventricle. This is a rarer form of anacrotism. a may sometimes be due to the auricular systole when the aortic valves are incompetent. In the explanation of the pulse-tracing, a fundamental fact to be borne in mind is the elasticity of the vessels. When a wave of increased pressure passes along a rigid tube with open ends, it dies away at the ends, and is followed by no secondary waves. But when the tube is elastic, the primary wave is necessarily followed by secondary waves, the whole system passing through a series of vibrations to regain its original position. The period of these vibrations being sensibly constant for a given condition of the system, it will depend upon the length of this period, the interval THE CIRCULATION OF THE BLOOD AND LYMPH. 73 between two successive strokes of the pump, and the rate at which the ampHtude of the vibration dechnes, how many secondary wavelets will be seen on a given pulse-curve. Such secondary waves of oscillation, produced in an artificial scheme of elastic tubes attached to a valveless pump, are propagated in the same direction and with the same velocity as the primary wave, and there seems to be little doubt that the secondary waves of the pulse-curve, or at least the dicrotic wave, are due, in part at any rate, to oscillations of this kind. The dicrotic wave is always separated by the same interval of time from the primary elevation, from what- ever part of the arterial system the tracing may be taken. This can only be explained by supposing that it has the same point of origin, and travels with the same velocity and in the same direction as the primary wave, just as a wave of oscillation would do. It seems scarcely possible to maintain any longer the peripheral origin of this wave, and the only question remaining is, in what manner precisely it arises at the central end of the arterial system. As to this, several views have been held, (i) Some say that the contraction of the over-distended aorta upon the blood sets up a wave of increased pressure, which is intensified by the sudden closure of the semilunar valves, towards the end of the ventricular systole or the beginning of diastole. (2) Others maintain that the column of blood in the aorta tends still to move on, in virtue of its inertia, after the outflow from the left ventricle has suddenly ceased, and that a diminution of pressure, accompanied with a corresponding contraction of the aorta, takes place behind it. This contraction, as always happens in an elastic system, goes too far, and is followed by an expansion, which is propagated as the dicrotic wave. (3) Stress has recently been laid on the part played by the sudden relaxation of the ventricle in diastole in the production of the dicrotic wave. While the semi- lunar valves are still for an instant incompletely closed, the contents of the aorta are supposed to be sucked back towards the heart by the aspiration of the relaxing ventricle. A wave of diminished pressure, represented in the pulse- curve by the ' aortic notch,' and followed by a com- 74 A MANUAL OF PHYSIOLOGY. pensatory elevation, the dicrotic wave, is thus set up (Pick). On the whole, it seems best to consider the dicrotic wave as a secondary oscillation, reinforced, perhaps, by the sudden closure of the semilunar valves ; while the predicrotic wave is probably an oscillation of a similar character, but perhaps without a valvular element. The prominence of the dicrotic wave varies with the abruptness of discharge of the ventricle and the extensibility of the arteries. The conditions are usually favourable when the arterial pressure is low ; for then the heart is able to empty itself more rapidly, and the vessels, being already only moderately stretched, are easily distended further. And, in fact, an exaggeration of the dicrotic wavelet may be artificially produced by nitrite of amyl, a drug which lessens the blood-pressure by dilating the small arteries. A strong heart-beat and low blood-pressure present the ideal conditions for a marked dicrotic pulse. On the other hand, in certain diseases associated with a high arterial pressure the dicrotic elevation almost disappears. Atheromatous arteries, being very inextensible, do not allow a dicrotic pulse. Since the pulse represents a periodical increase and diminution in the amount of distension of an artery at any point, the line joining all the minima of the pulse-curve will vary in its height above the base-line, or line of no pressure, according to the amount of permanent distension, i.e., permanent blood-pressure, which the heart in any given circumstances is able to maintain. Any circumstance that tends to lessen the permanent distension will cause a fall of the line of minima, and any circumstance tending to increase the distension will cause that line to rise. If, for example, the arm be raised while a pulse-tracing is being taken from the wrist, the line of minima falls because the permanent pressure in the radial artery is diminished. The form of the pulse-curve varies in the different arteries,and therefore in making comparisons the same artery should be used. When the wave of blood only enters an artery slowly, the ascending part of the curve will be oblique. This is THE CIRCULATION OF THE BLOOD AND LYMPH. 75 normally the case in a pulse-curve of a distant artery, such as the posterior tibial. The height of the wave is also less than in an artery nearer the heart, such as the carotid, or even the axillary, where the primary elevation is relatively abrupt. Anacrotic Pulse. — As a rule, the ascent of the tracing is unbroken by secondary waves, but in certain circumstances these may appear on it. This condition, which, when well marked at any rate, may be considered pathological, is called anacrotism (Fig. 23). It is seen when the discharge of the left ventricle into the aorta is slow and difficult — e.g., in old people whose arteries have been rendered less extensible by the deposit of lime-salts in their walls (atheroma), and in cases where the orifice of the aorta has been narrowed from disease of the semilunar valves (aortic stenosis). Since these conditions are in general associated with hypertrophy and dilatation of the left ventricle, the slow emptying of the ventricle is, perhaps, partly due to the greater quantity of blood which it contains. In whatever way the delay in the emptying of the ventricle is brought about, the most probable explanation of the anacrotic pulse is that the delay affords time for one or more secondary waves to be developed in the arterial system before the summit of the curve has been reached, and that these are superposed upon the long-drawn primary elevation. In aortic insufficiency, where the left side of the heart is never cut off entirely from the aorta, the auricular impulse is marked on the pulse-curve as a distinct elevation ; and this gives rise to a peculiar kind of anacrotic pulse, especially in the arteries nearest the heart (Fig. 23, F). Frequency of the Pulse. — This depends upon a great variety of circumstances : I. Age and sex. The average normal rate for an adult male is about 72 beats per minute, for a female about 80. At all ages the pulse is somewhat quicker in the female. At the end of foetal life the rate is given as 144-133 ; from birth till the end of first year, 140-123; from 10 to 15 years, gi-76; from 20 to 25 years, 73-69. It remains at this till 60 years, and increases again somewhat in old age. 76 A MANUAL OF niYSIOLOGY. 2. Size. In persons of the same sex and age the rate is greater in short than in tall people. 3. Position of the body. The rate of the pulse is greater in the standing than in the sitting posture, and greater in the latter than in the recumbent position. And this is true even when muscular action is as far as possible eliminated by fastening the person to a board. 4. Muscular activity increases the rate. 5. The taking of food increases the rate. 6. It is greatly influenced by psychical events. 7. The time of day has an effect, which seems to be independent both of muscular exertion and of meals. The rate sinks from morning till mid-day, then rises, and sinks again tovvards evening. We shall see later on that there is a similar diurnal variation of the temperature, but may remark here that the daily maxima and minima of the pulse-rate precede a little those of the temperature. 8. The rate is affected by respiration in a manner to be described later (Chap. III.). g. Increase of temperature increases the rate, though this is less marked in the intact body than in the isolated heart. Various Characters of the Pulse. — Certain terms which have come down from the older medicine, and are still used clinically to describe various conditions of the circulation as investigated by feeling the pulse, must here be briefly touched on : ' Hard ' pulse {pulsus diirns). Here the mean blood- pressure is high, the vessels are considerably distended, and the pulse therefore feels hard. With a ' soft ' pulse {pulsus mollis) the mean blood-pressure is low. With a 'quick' pulse {pulsus celer) the artery is rapidly distended by the pulse-wave. With a ' slow ' pulse {pulsus tardus) the distension is slow. The terms 'strong' pulse {pulsus furtis) and 'weak ' pulse {pulsus debilis) refer to the amount by which the pulse-wave increases the blood-pressure at the point. 'Large' pulse {pulsus ma gnus) and ' small 'or 'thready ' pulse {pulsus parvus) refer to the increase in the quantity of blood which every pulse-wave causes in the vessel. THE CIRCULATION OF THE BLOOD AND LYMPH. 77 The ' force of the pulse ' is a phrase which is often ambiguously used, sometimes apparently as synonymous with * strength,' and sometimes with * size,' as above defined. In fact, the quantitative information obtained by feeling the pulse with the finger is far inferior in precision to the qualitative notion which that time-honoured proceeding affords. The * force of the pulse ' does not necessarily correspond with the force of the heart. It depends partly on the suddenness with which the pulse-wave distends the artery, partly on the amount of this distension in relation to the previous permanent distension, and to some extent on the calibre of the vessel. Other things being equal, the pulse in a large vessel will feel stronger than that in a smaller vessel. This last factor accounts for the inequality in the force of the pulse which is not infrequently found between the tv/o radials even of a healthy person. Rate of Propagation of the Pulse-wave. — When pulse-tracings are taken simultaneously at two points of the arterial system unequally distant from the heart, by two sphygmographs whose writing-points move in the same vertical straight line, it is found that the ascent of the curve begins later at the more distant, than at the nearer point. Since waves like the pulse-wave travel with approximately the same velocity in different parts of an elastic system like the arterial 'tree,' this 'delay' must be due to the difference in the length of the two paths. The difference in length can be measured ; the time-value of the 'delay' can be deduced from the rate of movement of the recording surface ; dividing the length by the time, we arrive at the rate of propagation of the pulse-wave. This rate has been found to be about 8*5 metres per second in man in the arteries of the upper limb, and g'5 metres in those of the lower limb, the difference being due to the smaller distensibility of the latter. The mean velocity of the pulse-wave would correspond to not much less than 500 miles in twenty-four hours, or about the same as the speed of a fast Atlantic liner or of a wave of the sea in a strong gale. The velocity of the pulse-wave must not be confounded with that of the blood-stream itself, which is not more than one-thirtieth as great. A ripple passes 78 A MANUAL OF PHYSIOLOGY. over the surface of a river at its own rate — a rate that is independent of the velocit}' of the current. The passage of the ripple is not a bodily transference of the particles of water of which at any given moment the wave is com- posed, but the propagation of a change of relative position of the particles. The mere fact that the ripple can pass up stream as well as down is sufficient to illustrate this. The pulse-wave does not, however, correspond in every respect to a ripple on a stream, for the bodily transfer of the blood depends upon the series of blood-waves which the heart sets travelling along the arteries. Every particle of blood is advanced, on the whole, by a certain distance with every pulse-wave in which for the time it takes its place. But no particle continues in the front of the pulse-wave from beginning to end of the arterial system. In fact, the true path of a particle of blood is perhaps something like Fig. 24, Fig. 24. — Path of a Particle of Blood (Webek). an oscillation in an ellipse, combined with a movement of translation. The ' delay ' or 'retardation ' of the pulse (the interval, say, between the beginning of the ascent of the carotid and radial curves) is practically constant in the same individual, not only in health, but also in most diseases. But the retardation is markedly increased when the pulse- wave has to pass through a portion of an artery, whose lumen is either greatly widened (aneurism), or greatly con- stricted (endarteritis obliterans). The velocity of the pulse-wave has sometimes been de- duced by comparing a tracing of the cardiac impulse with a pulse-tracing taken at the same time from a distant artery. But, as we have seen in dealing with the action of the heart, the ventricle does not at the very beginning of its contraction acquire sufficient force to cause the opening of the semi- lunar valves. The pulse, therefore, even in the aorta, must lag behind the ventricular pulse ; and the amount of this THE CIRCULATION OF THE BLOOD AND LYMPH. 79 ' lag ' must be subtracted from the total retardation. But since the aortic ' lag,' unlike the retardation, between two arteries, varies greatly even in health, depending as it does on the arterial blood-pressure, this method of determining the velocity of the pulse-wave is not satisfactory. The Blood-pressure Pulse. — In man it is only possible to trace the pulse-wave along the arteries by movements of the walls of the vessels transmitted through the overlying tissues. In animals the changes of pressure that occur in the blood itself can be directly registered, and these changes Fig. 25. — Diagram of Mkkcukiai. Kymograph. The record is taken on the endless strip of paper K, which is made to revolve at a uniform rate ; D is a float carrying a writing point ; C is tiie manometer, the difference of level of the mercury (//i,'^) in the two limbs of which measures the blood-pressure ; A is a pressure bottle filled with sodium carbonate or magnesium sulphate solution and connected by the fle.xible tube B with the manometer ; F is the bloodvessel ; G, the con- nectiug cannula. may be spoken of as the blood-pressure pulse. At bottom, as already pointed out, the phenomenon is exactly the same as that we have been dealing with in our study of the external pulse. We are only now to follow, by a more direct, and in some respects a more perfect method, the same wave of blood along the same channel. Measurement of the Blood-pressure. — Hales was the first to measure the blood-pressure. This he did by connecting a tall glass tube with the crural artery of a horse. The height to which the blood rose in the tube indicated the pressure 8o A MANUAL OF PHYSIOLOGY. in the vessel. Poiseuille, nearly half a century later, applied the mercury manometer, which had already been used in physics, to the measurement of blood-pressure. Ludwig and others improved this method by making the manometer self-registering by means of a float in the open limb, sup- porting a style which writes on a revolving drum, the whole arrangement being called a kymograph. (For the method of taking a blood-pressure tracing, see p. 154.) Owing to the relatively great amount of work required to produce a given displacement of the mercury, a manometer of this kind does not readily follow rapid changes of pressure, and the mercurial column, once displaced, continues to execute vibrations of its own, which are compounded with Fig. 26. — DiAGKA.M of Kick's Spring Manometer. A, hollow spring filled with alcohol. Its open end B is covered with a membrane and is fixed to the upright F ; the other end C is free to move, and is connecied with a system of levers, which move the writing point D; E is the cannula, which is connected with the bloodvessel. When the pressure in the spring is increased it tends to straighten itself. the true oscillations of the blood-pressure. Accordingly the mercurial manometer is better suited for measuring the mean blood-pressure, or for recording changes in the pressure which last for some time, than for following the rapid varia- tions of the pulse-wave. For the latter purpose, one of the class of elastic manometers is required. Of these the best known, and "most deserving to be known, are Fick's spring THE CIRCULATION OF THE BLOOD AND LYMPH 8i manometer (adapted from Bourdon's pressure-gauge) (Fig. 26), and especially the instruments recently introduced by Hiirthle, which are probably the most perfect manometers yet constructed for the investigation of the finer details of the blood -pressure pulse, whether in the heart or the arteries. Hiirthle's spring manometer consists of a small drum covered with an indiarubber membrane loosely arranged so as not to vibrate with a period of its own. The drum is connected with the blood- vessel, and the blood-pressure is transmitted to a steel spring bv means of a metal disc fastened on the membrane. The spring acts on a writing lever. The instrument is so constructed that for a given change of pressure the quantity of liquid displaced is as small as possible, and it is on this that its capacity to follow sudden variations of pressure chiefly depends. "iP\G. 27.— Curves of Rlood-pkessure taken with a Spring Manometer fk(.m THE Carotid Artery of a Dog (HUrthle). When I was taken the blood pressure was high ; 2 corresponds to a medium ; 3 to a low, and 4 to a very low blood pressure ; p is the primary elevation— this and the succeeding elevations between /and a are called systolic waves ; the systolic waves are followed by a marked elevation d, which corresponds to the dicrot'c pulse-wave. A blood-pressure tracing taken from an artery with a manometer of this sort almost exactly agrees with the tracing of a good sphygmograph applied to the correspond- ing artery on the opposite side. There is a very large increase of pressure during the systole — far greater than is indicated by the mercury manometer. This is especially the case when the permanent or minimum pressure is low. In the rabbit the pulsatory variation is one-third to one- 6 82 A MANUAL OF PHYSIOLOGY. fourth of the minimum pressure, and in the dog still more — generally at least one-half — the greater variation being connected with the slower rate of the heart. In the dog the pressure often rises as much as 50 mm. of Hg daring the systole, and with a low minimum pressure and slow pulse-rate the systolic pressure may be more than double the minimum (Hiirthle). Fick found also, by means of his spring manometer, that the pulsator}- variations of blood-pressure were greater than the respiratory variations (p. 84), although in the records of the mercury manometer the reverse appears often to be the case. The form of the blood-pressure pulse-curve varies with the mean blood-pressure ; but the dicrotic wave is always marked on it, preceded by one or more oscillations falling within the period of the systole, and followed by one or more within the period of diastole. When the blood- pressure is low, the first or primary elevation is the highest of the whole curve (Fig. 27). When the blood-pressure is high, the maximum falls later, coinciding with one of the secondary systolic waves, but always preceding the dicrotic wave ; and the curve assumes an anacrotic character. That all the secondary oscillations, including the dicrotic wavelet, are of central, and not of peripheral origin, may be shown by recording the blood-pressure simultaneously at two points of the arterial system at different distances from the heart — e.g., in the crural and carotid arteries. The secondary waves are found, by measuring the tracings, to reach the more distal point later than the more central ; therefore they cannot arise by reflection at the peripheral portions of the arterial system. That the dicrotic wave is not an artificial phenomenon, due to the methods employed to register the blood-pressure, was very clearly shown by Landois, who allowed the blood issuing from a divided artery to strike a moving surface, and found a well-marked dicrotic elevation on the curve so- obtained, in addition to the primary elevation. There were also indications of other secondary oscillations. The rate of escape of the blood was nearly 50 per cent, greater at the maximum than at the minimum pressure. THE CIRCULATION OF THE BLOOD AND LYMPH. 83 The wave of increased pressure, as it runs along the arterial system, carries with it wherever it arrives an increase of potential energy. But this excess of potential energy is continually being worn down, owing to the friction of the vascular bed ; and although in the comparatively large arteries the loss of energy is not great, it rapidly increases as the arteries approach their termination, and begin to branch. For not only is the total surface, and therefore the friction, increased with every bifurcation, but the mere change of direction and division of the wave cannot take place without loss of energy. For this reason the fluc- tuations of blood-pressure are greater in the large arteries near the heart than in arteries smaller and more remote: in the wide and much-branched capillary bed the pulse- wave disappears altogether, and the blood-pressure becomes Fig. 28. — Bi.ooD-PREssuRE Tracing. The horizontal straight line intersecting the curves is the line of mean pressure. relatively constant or permanent. And it is for some pur- poses convenient to look upon the blood-pressure in the arteries as made up of a permanent element, with pulsatory oscillations superposed on it. Since no portion of the arterial system is more than partially emptied in the interval between two blood-waves, the minimum or permanent pres- sure is always positive — i.e., always above that of the atmo- sphere. The only reason for this is that the beats of the heart succeed each other so rapidly that the successive waves overlap or ' interfere,' and are only separated at their crests. If the heart is stopped while a blood-pressure tracing is being taken — and we shall see later on how this can be done (p. 121) — the minimum line of the tracing goes on falling towards the zero -line. When the heart begins beating again, the pressure-curve rises, not abruptly, but by suc- cessive leaps, each corresponding to a beat of the heart, 84 A MANUAL OF PHYSIOLOGY. and each overtopping its predecessor, till the old line ot minimum or of mean pressure is again reached. The mean arterial blood - pressure is the permanent pressure plus one-half of the average pulsatory oscillation. In a blood-pressure tracing the line of permanent pressure joins all the minima; the line of maximum pressure joins all the maxima ; the line of mean pressure is drawn between them in such a way that of the area included between it and. the blood-pressure curve as much lies above as below it (Fig. 28). As has been said, a tracing taken with a mercury manometer gives approximately the mean blood- pressure. Each beat of the heart is represented on it by a single elevation of no great size, sometimes not amounting to more than one-twentieth of the height of the curve above the line of zero or atmospheric pressure. The small oscil- lations due to. the heart-beat are superposed upon much longer, and often, as registered in this way, larger waves, caused by the movements of respiration. The line of mean pressure intersects the respiratory waves midway between crest and trough (Fig. 28). The following table shows how the blood-pressure may vary in different kinds of animals. Carotid rHorse - - - 150 — 200 mm. Hg Sheep - - - 1 50 — 200 I Dog - - - 160 — 180 Rabbit - - - 100 Goose - - - 160 .Duck - - - 140 fFrog - - - 30 Aorta-| Tortoise - - -30 lEel - - - 55 The mean arterial pressure has been found to be approxi- mately the same in animals of the same species, irrespective of size. Even in warm-blooded animals of different species there is no very obvious relation of size and blood-pressure. This has been supposed by some to indicate that the resist- ance in the small vessels — which, as we shall see, makes up the chief part of the total vascular resistance — does not vary greatly in the different kinds of warm-blooded animals. In man the blood-pressure has been estimated by adjust- THE CIRCULATION OF THE BLOOD AXD LYMPH. 85 ing over an artery the thin and yielding membrane of a capsule containing liquid, and connected with a manometer. The height of the column of mercury just required to prevent the pulse-wave from passing is taken as approxi- mately equal to the maximum blood-pressure. A slight deduction must, however, be made on account of the resistance to compression of the artery itself and the tissues over it. In the radial artery of a healthy man the blood- pressure may, perhaps, average 150 mm. of mercury. In the anterior tibial artery of a boy whose leg was to be amputated the blood-pressure, measured by means of a manometer connected directly with the artery, was found to vary from 100 to 160 mm. Hg, according to the position of the body and other circumstances. In a woman sixty years old, in good health, the following measurements were obtained : June 28 - - - 126 — 130 mm. Hg „ 29 - - 126—136 „ Aug. 3 - - - 132—144 „ 7 - - - 134—140 „ 12 - - - 136—144 „ (Zadek.) Such measurements on man, so far as they can be trusted, show that the mean blood-pressure in one and the same artery may vary for a considerable time only within com- paratively narrow limits. The blood-pressure can be artificially lowered by copious haemorrhage, but it must be copious. Conversely, the direct injection of a considerable quantity of blood into a vein will cause a rise of blood-pressure, which, however, soon passes off. We shall return to this when discussing the influence of nerves upon the circulation (p. 138). The ligation or compression of arteries is another mechanical means of increasing the general blood-pressure. The position of the body affects the pressure in any par- ticular artery. This has led to the distinction of two factors in the blood-pressure, the hydrostatic and the hydrodynamic elements. The hydrostatic portion of the pressure is due to the weight of the column of blood acting on the vessel ; the hydrodynamic portion of the pressure is due to the work 86 A MA NUA L OF PH YSIOL O G Y. of the heart. If a dog be securely fastened to a holder arranged in such a way that the animal can be placed vertically, with the head up or down, and the mean blood- pressure in the crural artery be measured in the two posi- tions, there will be a considerable difference. For when the legs are uppermost the heart has to overcome the weight of the column of blood rising above it to the crural artery ; when the head is uppermost the action of the heart is reinforced by the weight of the blood. And if no change were produced in the action of the heart, or in the general resistance of the vascular path, by the change of position, this difference would be equal to the pressure of a column of blood twice as high as the straight-line distance between the cannula and the point of the arterial system at which the pressure is the same with head up as with head down (indifferent point). But in animals to which the upright position is normal (monkey) and in man the influence of changes of posture on the circulation is almost completely compensated by the action of vaso-motor nerves (p. 128), especially those that govern the abdominal vessels, and of the nerves that regulate the work of the heart (Hill). When this compensa- tion is destroyed, as in paralysis of the vaso-motor centre by chloroform, the circulation may be profoundly influenced by the position of the body : elevation of the head may lead to cerebral anaemia, syncope and even death ; elevation of the legs, and particularly the abdomen, may restore the sinking pulse by filling the heart and the vessels of the brain. In animals that go on all fours compensation is very imperfect even under normal conditions. If a chloralized dog be fastened on a board which can be rotated about a horizontal axis passing under the neck, the blood-pressure in the carotid artery falls greatly when the animal is made to assume the vertical position with the head up, and rises when the head is m.ade to hang down. So great may the fall of pressure be in the former position that death may occur if it be long maintained. The Velocity-Pulse. — We have seen that the circulation in the arteries takes place in the form of a series of waves of THE CIRCULATIOX OF THE BLOOD AND LYMPH. 87 blood travelling from the heart towards the periphery. The particles in the front of the pulse-wave are constantly changing, but since every section of the arterial tree is successively distended, every section contains more blood while the pulse-wave is passing over it than it contained immediately before. And since there is always a fairly free passage for this blood towards the periphery, there is a bodily transfer on the whole of a certain quantity with every wave. The translation of the blood, instead of being entirely intermittent, as it would be in a rigid tube or in an elastic system with a slow action of the central pump, is, in part, constantly going on ; for a portion of a blood-wave is always passing through every section of the arterial channel. Thus, we arrive at the same distinction as to the onward move- ment of the blood itself as we previously reached in regard to the blood-pressure, the distinction between the constant or permanent factor of the velocity and the periodical factor, which we may call the velocity-pulse. The Velocity of the Blood. — By the velocity or rate of flow of a river we should mean, if the flow were uniform through- out the whole cross-section, the rate of movement of any given portion or particle of the water. If we could identify a portion of the water, we could determine the velocity by measuring the distance travelled over by that portion in a given time. If the velocity was uniform over the channel, then we could predict the actual time which would be required to traverse any fractional part of the measured distance. If, however, the velocity of the current changed from point to point, then we could only deduce from our observation the mean rate of the river for the measured distance. To determine the actual rate for any given portion of this distance over which the rate was uniform, we should have to make a separate observation for this portion alone. But as soon as we pass from an ideal frictionless river to an actual stream, in which the water at the bottom and near the banks flows more slowly than that in the middle and on the surface, we are in every case restricted to the notion of 88 A MANUAL OF PHYSIOLOGY. mean velocity. We may distinguish between the velocity of different parts of the current, between that of the mid-stream and the side current, the bottom and the surface layers; but when we consider the river as a whole, we take cognizance only of the mean or average velocity. And at any cross- section this may be defined as the volume of water passing per hour, or whatever the unit of time may be, divided by the cross-section of the current. It is evident that this does not enable us to determine the actual velocity of any given particle of the water at any given moment within a measured interval ; nor does it tell us whether or not the average velocity of the current has itself undergone varia- tions within the period of observation. We have dwelt upon this point because the measurement of the velocity of the blood, to which we must now turn, involves the same considerations. Within the smaller vessels, as the microscope shows us, and as we should in any case expect from what we know of fluid motion, the blood- current, apart from the periodical variations in its velocity due to the action of the heart, varies in speed from point to point of the same cross-section. The layer next the periphery of the vessel, the so-called peripheral plasma layer or Poiseuille's space, moves more slowly than the central portion, the axial stream. In fact, we must suppose that in the large as well as in the small vessels the layer just in contact with the vessel-wall is at rest, while the stratum internal to this slides on it and has its velocity diminished by the friction. The next layer again slides on the last, but since this is already in motion, its velocity is not so much diminished, and so on. The velocity must therefore in- crease as we pass towards the axis of the bloodvessel, and reach its maximum there (p. 57). Again, the velocity must be altered wherever an alteration occurs in the width of the bed, that is, in the total cross- section of the vascular system ; for since as much blood comes back in a given time to the right side of the heart as leaves the left side, the same quantity must pass in a given time through every cross-section of the circulation. Wherever the total section of the vascular tree increases, THE CIRCULATION OF THE BLOOD AND LYMPH. 89 the blood-current must slacken ; wherever it diminishes, the current must become more rapid. Now the total section increases as we pass from the heart along the branching arteries, and reaches its maximum in the capillary region. It gradually diminishes again along the veins, but never becomes so small as in the arterial tract. We must, therefore, expect the mean velocity to be greatest in the large arteries, less in the veins, and least in the arterioles, capillaries and venules. Although in strictness we are only at present con- cerned with the arteries, it will be well to consider here what a change of velocity at any part of the vascular channel really implies. To say that when the channel widens the velocity diminishes, is not to explain the meaning of this diminution. A diminution of velocity implies a diminution of kinetic energy, and it is necessary to know what becomes of the energy which disappears. The stock of energy imparted by the contraction of the heart to a given mass of blood con- stantly diminishes as it passes round from the aorta to the right side of the heart, for friction is constantly being over- come and heat generated. This energy, as we have seen, exists in a moving liquid in two forms, potential and kinetic, the former being measured by the lateral pressure, the latter varying directly as the square of the velocity. Whenever the velocity, and therefore the kinetic energy, of a given mass of the blood is diminished without a corresponding increase in the potential energy, some of the total stock of energy must have been used up to overcome resistance (p. 58). In a uniform, rigid, horizontal tube, as has been already remarked, the velocity, and consequently the kinetic energy, is the same at every cross-section of the tube, while the potential energy, represented by the lateral pressure, diminishes regularly along the tube. When the calibre of the tube varies, it is different. Suppose, for instance, that the liquid passes from a narrower to a wider part, the velocity must diminish in the latter. The kinetic energy of visible motion which has disappeared must have left something in its room. Here there are three possibilities: (i) The kinetic energy which has dis- appeared may be just enough to overcome the extra friction in the wider i^art of the tube due to eddies and consequent change of direction of the lines of flow ; in this case the potential energy of a given mass of the liquid will be the same at the beginning of the wider part as in the narrower part. The lost kinetic energy will have been transformed into heat. (2) The kinetic energy which has 90 A MANUAL OF PHYSIOLOGY. disappeared may be greater than is enough to overcome the extra resistance ; a portion of it must therefore have gone to increase the potential energy, and the lateral pressure will be greater in the wide than in the narrow part. (3) The lost kinetic energy may be less than enough to overcome the extra resistance ; in this case both the lateral pressure and the velocity will be less in the wide than in the narrow part. It has been experimentally shown that when a narrow portion of a tube is succeeded by a considerably wider portion, case (2) holds ; and the liquid may, under these conditions, actually flow from a place of lower to a place of higher lateral pressure. In the vascular system the conditions are not the same. The v^idening of the bed which takes place as we proceed in the direction of the arterial current is not due to the widen- ing of a single trunk, but to the branching of the channel into smaller and smaller tubes. In the larger arteries the increase of resistance is so gradual that both the potential and the kinetic energy diminish only slowly, and the lateral pressure and velocity are not much less in the femoral artery than in the aorta or carotid. But in the capillary region the friction increases so much that although the velocity, and therefore the kinetic energy, is greatly less than in the arteries, the amount of kinetic energy lost is not upon the whole equivalent to the energy consumed in overcoming the extra resistance ; the potential energy of the blood is also drawn upon, and the lateral pressure falls sharply in the capillary region, as well as the velocity. Where the capillaries open into the veins, the lateral pressure again sinks abruptly, while the velocity begins to increase, till in the largest veins it is probably about half as great as in the aorta. Where does the extra kinetic energy of the blood in the veins come from ? To say that the vascular channel again contracts as the blood passes from the capillaries into the veins, and that, since the same quantity must ilow through every cross-section of the channel, the velocity must neces- sarily be greater in the narrower than in the wider part, does not answer the question. The greater portion of the kinetic energy of the arterial blood is, as we have seen, destroyed, or, rather, changed into an unavailable form, into heat, in the capillary region. The mean velocity of the blood in the THE CIRCULATION OF THE BLOOD AND LYMPH. 91 capillaries is not more than -^y to tt^o of the velocity in the aorta ; the kinetic energy of a given mass of blood in the capillaries cannot therefore be more than {^\^Y, or xoo^oo of its kinetic energy in the aorta. In the veins, taking the velocity at half the arterial velocity, the kinetic energy of the mass would be one-fourth of that in the aorta, or at least 10,000 times as great as in the capillary region. This extra kinetic energy comes partly from the transformation of some of the potential energy of the blood. The resistance in the veins is very small compared with that in the capillaries; less of the potential energy represented by the lateral pressure at the end of the capillary tract is required to overcome this resistance, and some of it is converted into the kinetic energy of visible motion, the lateral pressure at the same time falling somewhat abruptly. Contributory sources of kinetic energy in the veins are the aspiration caused by the respiratory movements and the pressure caused by muscular contraction in general, which, thanks to the valves, always aids the flow towards the heart. From these two sources new energy is supplied, to reinforce the remnant due to the cardiac systole (p. 164). Measurement of the Velocity of the Blood. — i. Direct Observa- tion.— (a) This method can be applied to transparent parts by observing the rate of flow of the corpuscles under the microscope. But it is only where the blood moves slowly, as in the capillaries, that the method is of use. (b) Part of the path of the blood through a large vessel may be artificially rendered transparent by the introduction of a glass tube, of approximately the same bore as the vessel (Volkmann). The tube is filled with salt solution, and the blood admitted by means of a stop-cock at the moment of observation. The time which the blood takes to pass from one end of the tube to the other is noted, and the length divided by the time gives the velocity of the blood in the tube. If the calibre of the tube is the same as that of the artery, this is also the velocity in the vessel ; but if the calibre is different, a cor- rection would have to be made. The method is not a good one, as the long tube introduces a considerable amount of extra resistance. 92 A MANUAL OF PHYSIOLOGY 2. Ludwig's Stromuhr. — This instrument measures the quantity of blood which passes in a given time through the vessel at the cross-section where it is inserted. It consists of a U-shaped tube, with the limbs widened into bulbs, but narrow at the free ends, which are connected with a metal disc. By rotating the instrument, these ends can be placed alternately in communication with a cannula in the central, and another in the peripheral portion of a divided artery ; or they can be placed so that none of the blood passes i'lG. 29. -.SlKO.MUHR OF LUUVVIG AND DuGlEL. A, B, glass bulbs ; a, a melal disc, to which A and B are attached, and which can be rotated on the disc d ; E, F, cannula attached to 6, and connected with the peripheral and central ends of a divided bloodvessel. At the beginning of the experiment, A and the junction between A and B are filled with oil ; B is filled with normal saline or defibrinated blood: a being turned into the position shown in the figure, the blood passes through F and D into A, and the oil is forced into B ; as soon as the blood has reached the mark /;/, the disc a, with the bulbs, is rapidly rotated, so that C is now opposite F. The blood now passes into B, and the oil is again driven into A ; when the oil has reached D, reversal is again made, and so on. through the bulbs, but all goes by a short-cut. One limb of the instrument is filled with oil, and the other with de- fibrinated blood. The limb containing the oil is first put into communication with the central end, and that contain- ing the blood with the peripheral end of the artery. The blood rushes in and displaces the oil into the other limb, the defibrinated blood passing on into the circulation. As soon THE CIRCULATION OF THE BLOOD AND LYMPH. 93 as the blood has reached a certain height, indicated by a mark, the instrument is reversed, and the oil is again dis- placed into the limb it originally occupied. This process is repeated again and again, the time from beginning to end of an experiment being carefully noted. The number of times the blood has filled a bulb in that period, the capacity of the bulb and the cross-section of the vessel being known, all the data required for calculating the velocity of the blood in the vessel have been obtained. Suppose, for example, that the capacity of the bulb up to the mark is 5 CO., and that it is filled twelve times in a minute, the quantity flowing through the cross-section of the artery is i cc, or 1,000 cub. mm. per second. Let the diameter of the vessel be 3 mm., then its ^\ = ^ = 7-06 sq. mm. The velocity is 1000 , > = 14T mm. per second. 7 'GO ' Various improvements in this method have been made, such as graphic registration of the reversals of the stromuhr. 3. A tube or box, in which swings a small pendulum, is inserted in the course of the vessel. The pendulum is deflected by the blood, and the amount of the deflection bears a relation to the velocity of the stream (Vierordt's hasmatachometer ; Chauveau and Lortet's nmch more per- fect dromograph) (Fig. 30). 4. Pitofs Tubes. — If two vertical tubes, a and b, of the form shown in Fig. 31, be inserted into a horizontal tube in which liquid is flov.'ing in the direction of the arrow, the level will be higher in a than would be the case in an ordinary side- tube without an elbow ; in b it will be lower. For the moving liquid will exert a push on the column in a, and a pull on that in b. The amount of this push and pull will vary with the velocity, so that a change in the latter will correspond to an alteration in the difference of level in the two tubes. Instruments on this principle have been con- structed by Marey and Cybulski, the former registering the movements of the two columns of blood by connecting the tubes to tambours provided with writing levers, the latter by photography (Fig. 32). 94 A MANUAL OF PHYSIOLOGY. Of these methods, 3 and 4 are alone suited for the study of the velocity-pulse, that is, the change of velocity occurring with every beat of the heart. The curves obtained by Chauveau's dromograph agree closely with blood-pressure tracings taken by a spring manometer, and with records of the external pulse obtained by a sphygmograph. There is a primary increase of velocity corresponding with the ventri- cular systole, and a secondary increase corresponding with the dicrotic wave. Like all the other pulsatory phenomena, Fiu. 30. — Chauveau's Ukomogkaph. A, tube connected with bloodvessel ; B, metal cylinder in communication with A. The upper end of B has a hole in the centre, which is covered by a membrane, m, through which a lever, C, passes ; C has a small disc/, at its end, which projects into the lumen of A and is deflected in the direction of the blood-stream through A. The deflection is registered by a recording tambour in communication by the tube E with a tambour D, the flexible membrane of which is connected with the lever or pendulum C. the velocity-pulse disappears in the capillaries, and is only present under special conditions in the veins. Just as we can distinguish between the permanent or minimum blood-pressure and its pulsatory increase, so we can speak of a permanent and a pulsatory element in the velocity of the blood. The mean velocity, like the mean blood-pressure, is more variable in the large arteries near the heart than in the smaller and more distant arteries.' Dogiel found in measure- ments taken with the stromuhr (a good instrument for the THE CIRCULATION OF THE BLOOD AND LYMPH. 95 estimation of mean velocity), within a period of two minutes, velocities ranging from over 200 mm. to under 100 mm. per second in the carotid of the rabbit, and from over 500 mm. to less than 250 mm. in the carotid of the dog. Chauveau, Fig. 31.— Bitot's Tubes. with the dromograph, found the velocity in the carotid of a horse to be 520 mm. per second during systole, 150 mm. during diastole, 220 mm. during the period of the dicrotic wave. Fia. 32. — Cybulski's Arrangement for Recording Variations in the Velocity of the Blood. A, tube connected with central, B with peripheral end of divided bloodvessel. The blood stands higher in the tube C than in D. A beam of light passing ilirough the meniscus in both tubes is focussed by the lens L on the travelling photographic plate, E. The velocity at any moment is deduced from the height of the meniscus m the two tubes C and D. Fick and v. Kries attempted to calculate, from plethysmo- graphic tracings obtained from the hand or arm, the velocity of the blood in the arteries of man ; and although it cannot 96 A MANUAL OF PHYSIOL OG v. be said that as yet we have sufficient data for an accurate estimate, we shall not probably be far wrong in taking the mean arterial velocity as about 250 mm. per second, or rather over half a mile per hour. ' The rivers of the blood ' are, even at their fastest, no more rapid than a sluggish stream. A red corpuscle, moving at the maximum rate, would only cover about 13 miles in twenty-four hours, and would require five years to go round the world. The Volume-pulse. — When the pulse-wave reaches a part it distends its arteries, increases its volume, and gives rise to what may be called the volume-pulse. This may be readily recorded b}' means of a plethysmograph, an instru- FiG. 33.— Plethysmograph for Arm. F, float attached by A to a lever which records variations of level of the water in B, and therefore variations in the volume of the arm in the glass vessel C. The tubulure at the upper part of C is closed when the tracing is being taken. ment consisting essentially of a chamber with rigid walls which enclose the organ, the intervening space being filled up with liquid (Fig. 33). The movements of the liquid are transmitted either through a tube filled with air to a record- ing tambour, or directly to a piston or float acting upon a writing lever. Special names have been given to plethys- mographs adapted to particular organs ; for example, Roy's oncometer for the kidney. The method has been successfully applied to the investigation of circulatory changes in man, a finger, a hand or an entire limb being enclosed in the plethysmograph. With a fairly sensitive arrangement, every beat of the heart is represented on the tracing by a primary elevation and a dicrotic wave. The general appearance of THE CIRCULATION OF THE BLOOD AND LYMPH. 97 the curve is very similar to that of an ordinary pulse-tracing, though there are some differences of detail, especially in the time relations. A volume-pulse has been actually ob- served not only in limbs and portions of limbs, but also (in animals) in the spleen, kidney and brain. In the soft tissues of the mouth and pharynx, too, a volume-pulse can be detected by changes in the pressure of the air in the respira- tory passages (' Practical Exercises,' p. 159). Doubtless the weight of an organ would also show a pulse corresponding to the beat of the heart, if it could be isolated from the surrounding tissues (except for its vascular connec- tions), and attached to a recording balance, as could probably be done with a kidney. Further, it is possible that the temperature, at least of the superficial parts, is altered with every beat of the heart. For the amount of heat given off by the blood to the skin increases with its mean velocity, and therefore, although the difference may not be measureable except under special con- ditions, more heat is presumably given off during the systolic increase of velocity than during the diastolic slackening. In fact, with a very sensitive instrument (bolometer, or resist- ance thermometer, Chap. VIII.) applied directly to an ex- posed artery, indications of a change of temperature of the vessel-wall with each beat of the heart have been observed. And this, along with other considerations, suggests that, at any rate in certain situations and under certain conditions, there may even be a pulse of chemical change ; that is, a slight and as yet doubtless inappreciable ebb and flow of metabolism corresponding to the rhythm of the heart. The Circulation in tlie Capillaries. — From the arteries the blood passes into a network of narrow and thin-walled vessels, the capillaries, which in their turn are connected with the finest rootlets of the veins. Physiologically, the arterioles and venules must for many purposes be included in the capillary tract, but the great anatomical difference — the presence of circularly-arranged muscular fibres in the arterioles, their absence in the capillaries — has its physio- logical correlative. The calibre of the arterioles can be altered by contraction of these fibres under nervous in. 98 A MANUAL OF PHYSIOLOGY. fluences ; the calibre of the capillaries, although it varies passively with the blood-pressure, and is possibly to some extent affected by active contraction of the endothelial cells, cannot be under the control of vaso-motor nerves acting through muscular fibres. Harve}^ had deduced from his observations the existence of channels between the arteries and the veins. Malpighi was the first to observe the capillary blood-stream with the microscope, and thus to give ocular demonstration of the truth of Harvey's brilliant reasoning. He used the lungs, mesentery and bladder of the frog. The web of the frog, the tail of the tadpole, the wing of the bat, the mesentery of Fig. 34. — Diagram to Illustrate the .Slope of Pressure along THE Vascular System. A, arterial ; C, capillary ; V, venous tract. The interrupted line represents the line of mean pressure in the arteries, the wavy line indicating that the pressure varies with each heart-beat. The line passes below the abscissa a.xis (line of zero or atmospheric pressure) in the veins, indicating that at the end of the venous system the pressure becomes negative. the rabbit and rat, and other transparent parts, have also been frequently employed for such investigations. From the apparent velocity of the corpuscles and the degree of magnification, it is easy to calculate the velocity of the capillary blood -stream. It has been estimated at from •2 to '8 mm. per second in different parts and different animals. The comparative slowness of the current and the dis- appearance of the pulse are the chief characteristics of the capillary circulation. The explanation we have already found in the great resistance of the narrow and much- branched vessels. Although the average diameter of a THE CIRCULATION OF THE BLOOD AND LYMPH. 99 capillary is only about 10 /x (5 to 20 yu, in different parts of the body), the number of branches is so prodigious that the total cross-section of the systemic capillary tract has been estimated at 500 to 700 times that of the aorta. The total cross-section of the vascular channel gradually widens as it passes away from the left ventricle ; in the capillary region it undergoes a great and sudden increase ; at the venous end of this region the cross-section is again somewhat abruptly contracted, and then gradually lessens as the right side of the heart is approached ; but the united sectional area of the great thoracic veins is greater than that of the aorta. The blood-pressure in the capillaries has been measured by weighting a small plate of glass laid on the back of one of the fingers behind the nail, until the capillaries are just emptied, as shown by the paling of the skin (v. Kries), or by observing the height of a column of liquid that just stops the circulation in a transparent part (Roy and Graham Brown). The last-named observers found that a pressure of 100 to 150 mm. of water (about 7 to 11 mm. of Hg) was needed to stop the circulation in the capillaries and veins of the frog's web ; that is, about a third of the blood- pressure in the frog's aorta. The pressure in the capillaries at the root of the nail in man varies from 30 to 50 mm. of mercury. Under certain conditions the pulse-wave may pass into the capillaries and appear beyond them as a venous pulse. Thus, we shall see that when the small arteries of the submaxillary gland are widened, and the vascular resistance lessened, by the stimulation of certain nerves, the pulse passes through to the veins. And, normally, a pulse may be seen in the wide capillaries of the nail-bed — especially when they are partially emptied by pressure — as a flicker of pink that comes and goes with every beat of the heart. We have seen that the lateral pressure at any point of a uniform rigid tube through which water is flowing is propor- tional to the amount of resistance in the portion of the tube between this point and the outlet. In any system of tubes the sum of the potential and kinetic energy must diminish loo A MANUAL OF PHYSIOLOGY. in the direction of the flow ; and although the problem i& complicated in the vascular system by the branching of the channel and the variation in the total cross-section, yet theory and experiment agree that in the larger arteries the lateral pressure diminishes but slowly from the heart to the periphery, the resistance being small compared with the resistance of the whole circuit. In the capillary region the vascular resistance abruptly increases ; the velocity (and therefore the kinetic energy) abruptly diminishes, and the lateral pressure falls much more steeply between the begin- ning and the end of this region than between the heart and its commencement. In the veins only a small remnant of resistance remains to be overcome, and the lateral pressure Fig. 35.— Relation of Blood-pressure, Velocity, and Cross-Section. Blood-pressure P, velocity of blood V, and total cross-section S, in the arteries A, capillaries C, and veins V. must sink again rather suddenly about the end of the capil- lary tract. Fig. 35 shows by a rough diagram the manner in which the pressure, velocity and cross-section probably change from part to part of the vascular system. The Circulation in the Veins, — The slope of pressure, as we have just explained, must fall rather suddenly near the beginning and near the end of the capillary tract. It con- tinues falling as we pass along the veins, till the heart is again reached. In the right heart, and in the thoracic portions of the great veins which enter it, the pressure may be negative — that is, less than the atmospheric pressure. And since nowhere in the venous system is the pressure more than a small fraction of that in the arteries, its THE CIRCULATION OF THE BLOOD AND LYMPH. loi measurement in the veins is correspondingly difficult, because any obstruction to the normal flow is apt to artificially raise the pressure. A manometer containing some lighter liquid than mercury, such as water or a solution of magnesium sulphate, is usually employed, in order that the difference of level may be as great as possible. In the sheep the pressure was found to be 3 mm. (Hg) in the brachial, and about II mm. in the crural ; in the dog's portal vein about 10 mm. The venous pressure being so low, or, in other words, the potential energy which the systole of the heart imparts to the blood being so greatly exhausted before it reaches the veins, other influences begin here appreciably to affect the blood -stream : 1. Contraction of the Muscles. — This compresses the veins in the neighbourhood, and since the blood is compelled by the valves, if it moves at all, to move towards the heart, the venous circulation is in this way helped. 2. Aspiration of the Thorax. — In inspiration the intra- thoracic pressure, and therefore the pressure in the great thoracic veins, is diminished, and blood is drawn from the more peripheral parts of the venous system into the right heart (p. 164). 3. Aspiration of the Heart. — When the heart, after its contraction, suddenly relaxes, it is said that for a little time the endocardiac pressure becomes negative, and blood is sucked into it, just as when the indiarubber ball of a syringe is compressed and then allowed to expand. Although there has been a great deal of discussion as to this aspirating power of the heart, the best of the recent observations seem to show that such a power does to some extent exist — at least for the vigorously-contracting left ventricle. Of course, it is only the relaxation of the right ventricle which could directly affect the venous circulation. 4. Every change of position of the limbs, as in walking, helps on the venous circulation (Braune), and this inde- pendently of the muscular contraction. When the thigh of a dead body is rotated outwards, and at the same time extended, a manometer connected with the femoral vem shows a negative pressure of 5 to 10 mm, of water. When I02 A MANUAL OF PHYSIOLOGY. the opposite imovements are made, the pressure becomes positive. It follows from the number of casually-acting influences which affect the blood-flow in the veins that it cannot be yjQxy regular or constant. We have seen that in the great arteries there is a considerable variation of velocity and of pressure with every beat of the heart ; and although this variation is absent from the veins, since normally the pulse does not penetrate into them, the venous flow is, never- theless, as a matter of fact, more irregular than the arterial. So that if it is difficult to give a useful definition of the term ' velocity of the blood ' in the case of the arteries, it is still more difficult to do so in the case of the veins. Where voluntary movement is prevented, one potent cause of variation in the venous flow is eliminated ; and in curarized animals certain observers have found but little difference between the mean velocity in the veins and in the corresponding arteries. Others have found the velocity in the veins considerably less, which is indeed what we should expect from the fact that the average cross-section of the venous system is greater than that of the arterial system. To sum up, we may conclude that, upon the whole, the blood passes with gradually-diminishing velocity from the left ventricle along the arteries ; it is greatly and somewhat suddenly slowed in the broad and branching capillary bed ; but the stream gathers force again as it becomes more and more narrowed in the venous channel, although it never acquires the speed which it has in the aorta. To complete the account of the circulation in the veins, it must be added that in some healthy persons, but more fre- quently and more distinctly in cases of incompetence of the tricuspid valve, a venous pulse may be seen in the jugular vein ; but this pulse travels from the heart against the blood- stream, not with it. The Circulation Time. — Hering was the first who attempted to measure the time required by the blood, or by a blood- corpuscle, to complete the circuit of the vascular system. He injected a solution of potassium ferrocyanide into a vein (generally the jugular), and collected blood at intervals from THE CIRCULATION OF THE BLOOD AND LYMPH. 103 the corresponding vein of the opposite side. He then tested, by means of a ferric salt (FeoCl,,), for the presence of the ferrocj-anide in the serum of his samples of blood. The first one which contained the ferrocyanide corresponded to the time when the injected salt had just completed the circulation. This method was improved by Vierordt, who arranged a number of cups on a revolving disc below the vein from which the blood was to be taken. In these cups samples of the blood were received, and the rate of rotation of the disc being known, it was possible to measure the interval between the injection and appearance of the salt with considerable accuracy. Hermann modified the method by allowing the blood to play upon a revolving drum covered with a paper soaked in ferric chloride, and by using the less poisonous sodium ferrocyanide for injection. The recently-introduced electrical method gives us the means of measuring the circulation time in individual organs, and of repeating the observations an indefinite number of times on the same animal. A cannula, connected with a syringe containing a solution of sodium chloride (usually a 2 to 5 per cent, solution), is tied into a vein — say, the jugular. Suppose that the time of the circulation from the jugular to the carotid is required — that is, practically the time of the lesser or pulmonary circulation. A small portion of one carotid artery is isolated, and laid on a pair of (hook-shaped) un-polarizable electrodes,* insulation from the underlying tissues being secured by slipping a piece of thin sheet-indiarubber below the electrodes. The electrodes are connected up in the usual Wheatstone's bridge*!" arrange- ment for measuring resistance, and the bridge is balanced with a weak current. The image having come to rest on the scale of the galvanometer, a definite small quantit}' of the salt solution is injected from the syringe. It moves on with the velocity of the blood, and, reaching the portion of the artery on the electrodes, causes a diminution of the electrical resistance. This disturbs the balance of the bridge, and the * See Chap. IX., Physical Introduction. f Ibid. I04 A MANUAL OF PHYSIOLOGY image at once begins to move. The time from the beginning of injection to the beginning of the deflection is the circula- tion time from jugular vein to carotid artery ; and this can be read off by a stop-watch, which is released at the moment of injection, and stopped as soon as the image begins to move. The circulation time of an organ like the kidney can be measured by putting a pair of electrodes under the renal -yi^^^cnivcl'^^'' Fig 36 -Mfasurement of the Pulmonary Circulation Time in Rabbit by Injection ok Methylene Blue. artery and another under the renal vein, and reading off the circulation time from the point of injection first to the one and then to the other. The difference gives the circulation time through the kidney. The circulation time from jugular to jugular of the horse has been found to be about 30 seconds (Hering and Vierordt). In a 2-kilo rabbit the time of the THE CIRCULATION OF THE BLOOD AND LYMPH. 105 lesser circulation varies from 2 to 3 seconds, from jugular to jugular 5 to 7 seconds ; the longest paths are through the kidney, the portal circulation, and the lower limbs. Section of vaso-constrictor nerves (p. 123) diminishes, and stimulation increases, the circulation time of the correspond- ing vascular tract. Another method of measuring the circulation time is to inject a solution of a pigment — e.g., methylene blue — at a given point of the vascular system, and to measure the time it takes to arrive at any other point (Practical Exercises, p. 156). If the average weight of blood contained in an organ is w, and the average circulation time through that organ t^, then the quantity of blood passing through the organ in time t may be taken as zc'-. Similarl}^ if W is the weight of all the blood in the body, and T,^ the average time in which the T whole of the blood makes a complete circuit, W^ is the quantity passing through each ventricle in time T. Taking the average time required by the whole of the blood to com- plete the circulation as about a minute in a 70-kilo man (probably a minute and a quarter would be nearer the truth), the quantity of blood as 5 kilos, and the mean pressure in the aorta as 250 mm. of mercury, we possess data for calculating the daily work done by the left ventricle on the blood. Up to the time when the semilunar valves are opened, the work done by the ventricles is spent in raising the intra- ventricular pressure till it is sufficient to overcome the pressure in the aorta. If a vertical tube were connected with the left ventricle, the blood would rise till the column was of the same weight as a column of mercury of equal section and 250 mm. high. This column of blood would be about 3*2 metres in height. If a reservoir were placed in com- munication with the tube at this height, a quantity of blood equal to that ejected from the ventricle would at each systole pass into the reservoir ; and the work which the blood thus collected would be capable of doing, if it were allowed to fall to the level of the heart, would be equal to the work io6 A MANUAL OF PHYSIOLOGY. expended by the heart in forcing it up. Thus, in i minute the work of the left ventricle would be equal to that done in raising 5 kilos of blood to a height of 3*2 metres — that is, 16 kilogramme-metres ; in 24 hours it would be 23,040 — say 23,000 kilogramme-metres. Taking the mean pressure in the pulmonary artery at one-third of the aortic pressure, we get for the daily work of the right ventricle about 7,000 kilogramme -metres. The work of the two ventricles is thus about 30,000 kilogramme-metres, which is enough to raise a weight of half a stone from the bottom of the deepest mine in the world to the top of its highest mountain, or to raise the man himself to more than twice the height of the spire of Strasburg Cathedral. By friction in the bloodvessels this work is almost all changed into its equivalent of heat, namely, about 70,000 small calories (see Chap. VIII.). The total heat production of the heart is pro- bably at least four or five times this amount ; for the most economically working muscle does not probably convert into work more than one-fourth or one-fifth of the chemical energy expended during contraction. Further, since the contraction of the heart is always maximal (p. iii),and there is reason to believe that the quantity of blood ejected at a single systole by the left ventricle (being dependent upon the inflow from the pulmonary veins, and therefore upon the inflow into the right side of the heart from the systemic veins) varies widely, some of the mechanical effect of the contraction must be wasted when the quantity is less than the ventricle is capable of expelling. If 5 kilos of blood pass through the heart in one minute with the average pulse-rate of 72 per minute, the quantity ejected by either ventricle with every systole will be = 69 grm., or "]! cc. This is much less than the estimate of Vierordt ; but the calculations of recent observers, based on direct measurements of the blood-flow in dogs (Stolnikow) and rabbits (Tigerstedt), show that Vierordt's figure is too high. In the middle of last century, Passavant calculated the discharge, or ' contraction-volume,' as it is called, of the left ventricle at 46*5 grm., which is probably somewhat too low. THE CIRCULATION OF THE BLOOD AND LYMPH. 107 The Relation of the Nervous System to the Circulation. So far we have been considering the circulation as a purel}- physical problem. We have spoken of the action of the heart as that of a force-pump, and perhaps to a small extent that of a suction-pump too. We have spoken of the blood- vessels as a system of more or less elastic tubes through which the blood is propelled. We have spoken of the re- sistance which the blood experiences and the pressure which it exerts in this system of tubes, and we have considered the causes of this resistance, the interpretation of this pressure, and the physical changes in the vascular system that may lead to variations of both. But so far we have not at all, or only incidentally and very briefly, dealt with the physiological mechanism through which the physical changes are* brought about. We have now to see that although the heart is a pump, it is a living pump ; that although the vascular system is an arrangement of tubes, these tubes are alive ; and that both heart and vessels are kept constantly in the most delicate poise and balance by impulses passing from the central nervous system along the nerves. In many respects, and notably as regards the influence of nerves on it, we may look upon the heart as an expanded, thickened and rhythmically-contractile bloodvessel, so that an account of its innervation may fitly precede the descrip- tion of vaso-motor action in general. The Relation of the Heart to the Nervous System. — A very simple experiment is sufficient to prove that the beat of the heart does not depend on its connection with the central nervous system, for an excised frog's heart may, under favourable conditions, of which the most important are a moderately low temperature, the presence of oxygen and the prevention of evaporation, continue to beat for days. The mammalian heart also beats for a time after removal from the body. But although this proves that the heart can beat when separated from the central nervous system, it does not prove that nervous influence is not essential to its action, io8 A MANUAL OF PHYSIOLOGY. for in the cardiac substance nervous elements, both cells and fibres, are to be found. The Intrinsic Nerves of the Heart. — In the heart of the frog there is a group of nerve-cells in the sinus venosus near its junction with the right auricle (Remak's ganglion). The vagus, or rather the vago-sympathetic nerve (for in the frog the vagus is joined a little below its exit from the skull by the sympathetic), enters the heart along the superior vena cava (pp. 147, 148). In passing through the sinus, the true vagus fibres, or some of them, which have hitherto been medullated, are believed to make junction with these ganglion cells, and to pursue their course beyond them as non-meduUated fibres. Nerve fibres pass in two main bundles down the anterior and posterior portions of the auricular septum to two groups of ganglion cells (Bidder's ganglion), from which fine nerve- branches can be traced for a short distance into the sub- stance of the ventricle. In the mammalian heart nerve-cells and fibres are also present, though their distribution has been less studied than in the heart of the frog. Now, it was long supposed that the presence of ganglion cells was the clue to the explanation of the automatic con- traction of the heart. They were looked upon as centres from which impulses were sent out at regular intervals to the cardiac muscular fibres. ' But the importance of the ganglia in this relation diminished when it was known that the ganglion-free apex of the frog's heart could pulsate rhythmically under certain conditions when isolated from the rest of the organ by section ; that the apex which was still anatomically connected with the heart, but brought to rest by the crushing of an intermediate zone of tissue, could also be caused to beat again with a rhythm of its own, par- ticularly by raising the pressure inside the heart ; that the " heart " preparation, made by tying a frog's heart on a cannula by a ligature round the auricle or sinus, although it contains ganglia, remained in standstill for some time after isolation from the higher parts of the heart, and was affected by internal pressure and nutritive liquids of different kinds, much in the same way as the ganglion-free apex ; and that the isolated ventricle of a heart from which Bidder's ganglia THE CIRCULATION OF THE BLOOD AND LYMPH. 109 had been removed could also be brought to rhythmical pulsation. We know further that the bulbus aorta; in the frog, which seems to contain no ganglion cells, can be made to pulsate ; that strips of the ventricle of the tortoise, also free from ganglia, can be made to beat rhythmically ; that the rhythmical contractions of the smooth muscle of the ureter of the rabbit and dog are affected by distension much as the cardiac muscle is ; and finally that even ordinary skeletal muscle can contract in a rhythmical manner under the stimulus of a certain tension and in certain saline solutions.' We can hardly doubt in view of these facts that the automatic rhythmical contraction of the heart is a property of the cardiac muscle, a property also possessed, though in much smaller degree, by muscular tissue in other parts of the vascular system, e.g., in the vessels of the rabbit's ear, and the veins of the bat's wing. We have seen that there is a normal order or sequence in which the different parts of the heart contract, the contrac- tion beginning both in the frog and in the mammal at the base and travelling more or less rapidly towards the apex. It would seem that the muscular tissue of the part of the heart in which the beat begins has a higher rhythmical power than the rest of the cardiac muscle, and that normally the contraction is only propagated, not originated, by the lower portion of the heart. But under certain conditions the normal sequence can be reversed. In the heart of the skate, e.g., it is easy by stimulating the bulbus arteriosus to cause a contraction passing from bulbus to sinus. Not only may the normal sequence be changed in the entire heart, but any part of the heart may apparently have its rhythmical power exalted by appropriate means, so that it can be brought to beat rhythmically when isolated from the rest of the heart. On the other hand, the power of propagating the contraction may be artificially interfered with — increased by heat, diminished by cold, abolished by pressure or fatigue. If, e.g., a frog's heart is supported by a clamp fixed in the auriculo-ventricular groove, and the clamp is tightened or the ventricle cooled, while the auricle is at the ordinary tem- no A MANUAL OF PHYSIOLOGY. perature, or if the auricle is heated while the ventricle is at the ordinary temperature, only every second or third auricular beat will be followed by a ventricular beat (p. 146). Stannius' Experiment (p. 149). — If in a frog's heart a ligature is tied firmly at the junction of the sinus with the right auricle, or if a section is made through the junction, the auricles and ventricle stop beating for a time, while the sinus generally continues to pulsate. Direct stimulation of the quiescent portion of the heart causes a beat or a series of beats. A second ligature or section at the auriculo-ven- tricular junction causes the ventricle to pulsate while the auricle still remains at rest. But occasionally both auricle and ventricle, or only the auricle, may begin to beat. Opinion is divided as to the meaning of these phenomena. To Gaskell and his followers the most probable explanation of the standstill caused by the first ligature is that the lower portion of the heart, when cut off from the sinus in which the beat normally originates, needs some time for the development of its rhythmical power to the point at which an independent rhythm can be maintained. For in the heart of the tortoise, in which a similar temporary standstill of the auricles and ventricle occurs when the former are detached from the sinus, the circulation of a blood solution through the coronary vessels or the application of atropia, both of which, according to Gaskell, increase the rhythmical power of the cardiac muscle, prevent or remove the stand- still. The effects following the second Stannius' ligature are supposed to be due to stimulation of the muscular tissue by the ligature. But it is difficult to explain why the second ligature should stimulate the ventricle in preference to the auricles, and why the first ligature should apparently not stimulate the muscular tissue at all. Another view is that the first ligature stimulates the in- hibitory mechanism (vagus fibres) at the junction of the sinus and auricle, a position in which it is specially sensitive to stimuli. This causes inhibition of the whole of the heart below the ligature. The second ligature cuts off the ven- tricle from the inhibitory impulses, while leaving the auricle still under their influence. THE CIRCULATION OF THE BLOOD AND LYMPH, in In addition to its marked power of rhythmical contraction, the cardiac muscle is distinguished from ordinary skeletal muscle by other peculiarities. The most striking of these is that ' it is everything or nothing with the heart ;' in other words, the contraction is always maximal ; a weak stimulus, if it can produce a beat at all, causes as great a contraction as a strong stimulus. Another peculiarity is that a true tetanus of the cardiac muscle cannot be obtained at all, or only under very special conditions. When the ventricle of a frog's heart is stimulated by a rapid series of induction shocks its rate is generally increased, but there is no definite relation between the number of stimuli and the number of beats. Many of the stimuli are ineffective. In the same way a portion of the heart, such as the apex of the ventricle, when stimulated in the quiescent condition by an interrupted current, responds by a rhythmical series of beats and not by a tetanus. It is evident that the cardiac muscle, like ordinary striped muscle, is for some time after excitation incapable of responding to a fresh stimulus, i.e., there is a refractory period. But this is immensely longer in cardiac than in skeletal muscle. It is, however, shorter for strong than for weak stimuli, and is markedly diminished by raising the temperature of the heart. So that stimulation of the heated heart with a series of strong induction shocks may cause a tetaniform condition, if not a typical tetanus. The contraction of the normally beating heart is really a simple contraction and not a tetanus. The capillary electro- meter shows only the electrical changes corresponding to a single contraction ; and when the nerve of a nerve-muscle preparation is laid on the heart, the muscle responds to each beat by a simple twitch and not by tetanus (p. 152). Like ordinary skeletal muscle, the cardiac muscle is at first benefited by contraction, so that when the apex is stimulated at regular intervals, each contraction is somewhat stronger than the preceding one. To this phenomenon the name of the staircase or ' treppe ' has been given from the appearance of the tracings (see Chap. IX.). The Extrinsic Nerves of the Heart. — By its nerves the heart is brought into relation with the grey matter in the medulla 112 A MANUAL OF PHYSIOLOGY. oblongata, for the vagus takes origin here. The sym- pathetic fibres which act upon the heart come off in the frog from the upper part of the spinal cord by a branch from the third nerve to the sympathetic ganglia, and thence find their way along the sympathetic cord to its junction with the vagus, in company with which they run down to the heart. We shall first consider the function of these nerves in the frog, and then pass on to the extrinsic nerves of the mammalian heart. When the vago-sympathetic in the frog or toad is cut, and its peripheral end stimulated, the heart in the vast majority Fig. 37 (aftek Fostek).— Diagram oi- Extrinsic Nerves of Frog's Heart. Ill, 3rd spinal nerve ; AV, annulus of Vieussens ; X, roots of vagus ; IX, glosso- pharyngeal nerve ; VS, combined vagus and sympathetic ; i, 2 and 3, the ist, 2nd and 3rd sympathetic ganglia. The dark line indicates the course of the sympathetic fibres. The arrows show the direction of the augmentor impulses. of cases is stopped or slowed, or its beat is distinctly weakened without, it may be, any marked slowing. In other words, the rate at which the heart was working before the stimulation is greatly diminished, or reduced to zero. Such an effect, a diminution of the rate of working, we call Inhibi- tion. What precise form the inhibition shall take, whether the stoppage shall be complete or partial, appears to depend partly upon the strength of the stimulus used, and partly upon the state of the heart itself. Some hearts it may be impossible to stop with weak stimulation, although other signs of inhibition may be distinct, while they are readily THE CIRCULATION OF THE BLOOD AND LYMPH. 113 stopped by stronger stimulation. In other cases the strongest stimulation may not produce complete standstill. Again, a heated heart may be more readily brought to stand- still by stimulation of the vagus than a heart at the ordinary temperature or a cooled heart. But there are other points of importance to be noted in regard to this inhibition : (i) It does not begin for a little time after stimulation has begun. In other words, there is a distinct latent period; and the length of this latent period Fig. 38. — Tracing from Frog's Heart. A, auricular. V, ventricular tracing. Sinus stimulated (primary coil 70 mm. from secondary). Heart at temperature 11 -2° C. Complete standstill. The time tracing between tlie curves marks intervals of two seconds. is related to the phase of the heart's contraction at which the stimulus is thrown in, and to the rate at which the heart is beating. As a general rule the heart makes at least one beat before it stops. (2) The inhibition does not continue indefinitel}-, even if stimulation of the nerve is kept up. Sooner or liter, and usually, in fact, after an interval of a few seconds, the heart begins again to beat if it has been completely stopped, or to quicken its beat if it has only been slowed, or to strengthen 8 114 A MANUAL OF PHYSIOLOGY. it if the inhibition has only weakened the contraction, and it soon regains its old rate of working. Not only so, but very often there follows a longer or shorter period during which the heart works at a greater rate than it did before the inhibition, and this greater rate of working may be manifested by increased frequency of beat, or increased strength of beat, or by both. When the temperature of the heart is low, increased frequency ; when it is high, increased strength, is generally seen during this period of secondary augmentation. The term augmentation is the converse of in- hibition. During augmentation the rate of working of the Fig. 39. — Frog's Heart. Vagus Stimulated. Temperature of heart 8" C. , 78 mm. between the coils. Diminution in force of auricle and ventricle, but not complete standstill. Time tracing shows two-second intervals. heart is greater than the normal. * Secondary ' augmenta- tion is an augmentation following on inhibition, whether there is any causal relation between the two or not. How is inhibition produced ? By the direct action of the nerve-fibres on the cardiac muscle, or through the interven- tion of linkage arrangements such as nerve-cells ? The battle which has been fought for a good many years over these questions cannot be said to be yet ended, although from the action of various poisons it is most probable that the cells on the course of nerve-fibres in the heart are rather THE CIRCULATION OF THE BLOOD AND LYMPH. 115 stations where the fibres lose their medulla, and where possibly other anatomical changes and rearrangements occur, than important intermediate mechanisms which essentially modify the physiological impulses falling into them, and shape the visible results that follow those impulses. Thus, after nicotine has been injected subcutaneously, or painted directly on the heart, stimulation of the vago-sympa- thetic causes no inhibition ; it may cause augmentation. But stimulation of the junction of the sinus and auricle still causes inhibition, as in the normal heart. Ciirara, conine, and other drugs, resemble nicotine in this respect. Atropia and its allies, such as datnrinc, not only abolish the inhibitory effect of stimulation of the vagus trunk, but also that of stimulation of the junction of sinus and auricle. Muscarine, a poison contained in certain mushrooms (p. 149), causes diastolic arrest of the heart, which, when the circulation is intact, becomes swollen and engorged with blood. This action takes place in a heart already poisoned with nicotine or one of its congeners, but not in a heart under the influence of atropia or its allies. And a heart brought to standstill by muscarine can be made to beat again by the application of atropia, although not by nicotine. Pilocarpine has much the same action as muscarine. These facts may be explained as follows : Nicotine paralyzes not the very ends of the vagus, but the ganglia through which its fibres pass. Stimulation of the sinus, which is practically stimulation of the vagus fibres between the ganglion cells and the muscular fibres, is therefore effective, although stimulation of the nerve-trunk is not (Langley). On the other hand, the atropia group paralyzes the nerve-endings themselves, so that neither stimulation of the sinus nor of the nerve-trunk can cause inhibition. Muscarine, on the contrary, stimulates the vagus fibres between the nerve-cells and the muscle, or the actual nerve- endings, and thus keeps the heart in a state of permanent inhibition, which is removed when atropia cuts out the nerve-endings. It is quite in accordance with this, that muscarine has no effect on a heart whose vagus nerves, as occasionally happens, have no inhibitory power. ii6 A MANUAL OF PHYSIOLOGY. Some observers have supposed that although muscarine and pilocarpine in large doses do act on the nervous structures of the sinus, their primary and chief action is to depress the rhythmical power of the muscle, which atropia, on the other hand, increases. Curara and nicotine, they say, do not affect the muscle of the heart, but only interrupt the conductivity of the fibres of the vagus, and therefore direct stimulation of the sinus is still able to cause inhi- bition. But it would seem that the power of a stimulus like an interrupted current to cause inhibition of muscular action, Fig. 40. — Fkog s Heart. Sympathetic stimulated (30 mm. between the coils). Temperature 12°. Maiked increase in force. Only auricular tracing reproduced. Time trace, two-second intervals. independently of inhibitory nerves, has been too hastily assumed. For in the snail's heart and other structures in which it was asserted that inhibition could be directly produced by a series of induction shocks, the presence of inhibitory nerves has been lately shown (Ransom), and this discovery cuts away part of the ground on which the assumption was based. We have now to consider the cause of the secondary augmentation, which so often follows inhibition when the vago-sympathetic is stimulated in the frog. THE CIRCULATION OF THE BLOOD AND LYMPH. 117 There is no doubt that the greater part of the augmenta- tion, at any rate, is due to the action of the sympathetic, accelerator, or, as it is better to call them (since mere acceleration is not the only consequence of their stimulation), aiigmentor fibres in the mixed nerve. This is shown (i) by stimulating the pure vagus roots within the skull, and there- fore above the junction of the sympathetic fibres. \\'hen this is done electrically, a very difficult experiment, or when the medulla is stimulated by the application of a crystal of salt, the inhibition lasts far longer than when the mixed Fig. 41. A is a curve representing in an experiment the rate of the heart before stimulation of the sympathetic, and B the maximum rate after stimulation, the number of beats per 100" being laid off along the vertical, and the temperature along the horizontal axis. C is a curve showing the ratio of the frequency aiter, to that before stimulation of the sympathetic. D shows the absolute amount of acceleration at the various temperatures, the ordinates being the excess of the rate after, over that before stimula- tion. trunk is stimulated ; and secondary augmentation is absent, or only feebly marked. (2) When the peripheral end of the vago-sympathetic on one side, and the upper or cephalic end of the sympathetic on the other, are alternately and equally stimulated, the curve of primary augmentation {i.e., augmentation beginning without a preceding inhibition) caused by sympathetic stimulation bears a remarkable resemblance to the curve of secondary augmentation following stimulation of the mixed nerve. ii8 A MANUAL OF PHYSIOLOGY. (3) When the vago-sympathetic is stimulated weakly there is little or no secondary augmentation. Now, it is known that the augmentor fibres require a comparatively strong stimulus to cause any effect when they are separately excited, whereas a weak stimulus will excite the inhibitory fibres. Putting these facts together, we conclude that when the sympathetic fibres are not stimulated, the secondary augmen- tation is slight or wanting. Fig. 42. — Frog's Hkakt. Ventricle beating very feebly. Vagus stimulated (60 mm. between coils). Marked augmentation of ventricular beat (V). In the tortoise the inhibitory and augmentor fibres seem to run, in great part at least, separately. The two vagi have not the same inhibitory power in this animal, the right being, as a rule, more effective than the left ; but marked secondary augmentation follows stimulation of neither. It is a noteworthy fact that the inhibition caused by stimulation of the vago-sympathetic in the frog runs its THE CIRCULATION OF THE BLOOD AND LYMPH. 119 course apparently without being affected by the simultaneous augmentor effect, which lies latent until the end of the inhibition, and then bursts out and completes its own curve. It is not like the passing of two waves through each other, but rather like the stopping of one wave until the other has passed by. It seems as if augmentation cannot develop itself in the presence of inhibition, at least until the latter is nearly spent. The inhibition caused by a weak stimulus takes precedence of the augmentation caused by a strong Frc. 43.— Diagram of Cardiac Nerves in the Dog (after Foster). II, III, second and third dorsal nerves ;" SA, subclavian artery; AV, annulus of Vieussens ; ICG, inferior cervical ganglion ; CS, cervical sympathetic ; i, first thoracic or stellate ganglion of the sympathetic ; 2, second thoracic ganglion ; Ac, accelerator or augmentor fibres passing off towards the heart ; X, roots of vagus ; XI, roots of spinal accessory; JG, jugular ganglion; GTV, ganglion trunci vagi; In., inhibitory fibres passing off towards the heart. stimulus, although it never permanently suppresses nor even diminishes it. Occasionally in the frog, stimulation of the vago-sym- pathetic causes, not inhibition, but augmentation from the first (primary augmentation). This is especially liable to occur if the preparation has been long worked with and much exposed ; and in many of these cases inhibitory power can be restored by moistening the nerve or the heart, or by raising the temperature of the latter (Fig. 42). 120 A MANUAL OF PHYSIOLOGY. Stimulation of the central end of a peripheral nerve, or of the central end of one vagus, the other being intact, may cause reflex inhibition. Mechanical stimulation of the intes- tines, as by striking with a knife-handle or pinching, will also cause reflex inhibition. In mammals (and in what follows we shall restrict ourselves to the dog, cat and rabbit, as it is in these animals that the subject has been chiefly studied) the inhibitory fibres run down the vagus in the neck and reach the heart by its cardiac branches. They are not, however, derived from the roots of the vagus itself, but from the inner branch of the spinal accessory, which joins the vagus. The augmentor fibres leave the spinal cord in the anterior roots of the second and third thoracic nerves, and possibly to some extent by the fourth and fifth. Through the corresponding white rami communicantes they reach the sympathetic cord, and running up through the stellate ganglion (first thoracic), and the annulus of Vieussens, which surrounds the sub- clavian artery, to the inferior cervical ganglion, they pass off to the heart by separate ' accelerator ' branches taking origin either from the annulus or from the inferior cervical ganglion. In the dog the vagus and cervical sympathetic are, in the great majority of cases, contained in a strong common sheath, and pass together through the inferior cervical ganglion. After opening this sheath, they may with care be separated, the fibres running in distinct strands and not mixed together as in the vago-sympathetic of the frog. For some distance below the superior cervical ganglion the cervical sympathetic is not connected with the vagus, and here the nerves may be separately stimulated without any artificial isolation, but the electrodes must be very well insulated, as the available length of nerve is small. In the rabbit, cat, horse, and some other mammals, the vagus and sympathetic run a separate course in the neck. The effects of stimulation of the vagus or vago-sym- pathetic in the mammal are very much the same as in the frog, except that secondary augmentation is far less marked and often altogether absent. In the mammal the inhibitory THE CIRCULATION OF THE BLOOD AND LYMPH. 121 fibres have no direct action on the ventricle. It beats more slowly when the auricle is slowed, but this is only because in the normally beating heart the ventricle takes the time from the auricle. The strength of the ventricular contractions is not at all diminished even when the auricle is beating very feebly during inhibition. When the auricle is completely stopped, which does not occur so readily as in the frog, the ventricle stops for a short time, but soon begins to beat again with an independent rhythm of its own. In the frog the ventricle is directly affected by stimulation of the vagus, Fig. 44. — Blood-pkessuke Tracing (Rabbit). Vagus stimulated at i. Stimulus stronger in B than in A (Hiirthle's sphygmo- manometer). and the force of its beats is diminished independently of the inhibitory effects in the auricles (' Practical Exercises,' pp. 152, 154)- Stimulation of the accelerator nerves in the dog causes increase in the force of both the auricular and ventricular contraction, and, as a rule, in addition, some increase in the rate of the beat. When the central end of a nerve like the sciatic is stimu- lated, the usual result is a pure augmentor effect of the same type as that produced by direct stimulation of the accelera- tor nerves themselves. Sometimes, however, the augmenta- 122 A MANUAL OF PHYSIOLOGY. tion is abruptly followed by a typical vagus action. Here the reflex inhibitory effect seems to break in upon and cut short the reflex augmentor effect. When the central end of one vago-sympathetic is excited, the corresponding nerve on the opposite side being intact, pure inhibition is the result (Roy and Adami). In the rabbit, stimulation by ammonia of the fibres of the trigeminal nerve which confer common sensation on the mucous membrane of the nose causes reflex inhibition of the heart (Filehne). Fainting in man may be due to reflex inhibition of heart or arterioles (p. 139). Some have credited the vagus with a trophic or restorative action (anabolic action), and have argued that the natural consequence of inhibition is a stage of increased efficiency and working power when the inhibition has passed away. Similarly, the action of nerves like the augmentor nerves of the heart, has been spoken of as a katabolic action — an action which increases for the time the destructive tissue changes underlying such physiological processes as muscular contraction, but is followed by its natural complement, a temporary exhaustion. But it must be remembered that this distinction is not as yet based upon any very solid foundation of actuaIl3'-observed and easily-interpreted facts, while to some of the facts brought forward in its favour undue importance has been given. For instance, a positive electrical variation has been seen in the quiescent auricle of the tortoise on stimulating the vagus, and a negative variation in the quiescent frog's ventricle on stimulating the cardiac sympathetic, neither of these variations apparently being accompanied with an}' sensible mechanical change. It has been argued from this (on the assumption that the negative variation observed when most excitable tissues, muscle and nerve, for example, are stimulated, is the expression of destructive metabolic changes or katabolism), that the vagus has the power of causing constructive (anabolic) changes, and the augmentor nerves the power of causing destructive (katabolic) changes, apart from mechanical effects. But all that we really know is that electrical changes and chemical changes can both be evoked in living tissues. We are quite ignorant of the relation between the two. THE CIRCULATION OF THE BLOOD AND LYMPH. 123 To complete our account of the effects of stimulation of the cardiac nerves, it may be added that excitation of the medulla oblongata causes standstill of the heart in diastole, but not if both vagi be cut. In this case it causes quicken- ing of the heart's action. The vagus appears normally to be in constant action, and always keeps the heart, so to speak, in hand by means of impulses passing down from the so-called cardio-inhibitory centre in the medulla. A proof of this is that section of both vagi (in the dog) is followed by a great increase in the rate of the heart. Section of one vagus causes little or no increase, for the other is able of itself to control the heart. In animals, such as the rabbit, with a very rapidly-beating heart, division of the vagi may have no effect on the rate of the heart. In the frog it is disputed whether division of both vagi affects the rate or not. The augmentor fibres are not constantly in action, for section of them is not necessarily, nor, as a matter of fact, often, if at all, followed by a diminution in the frequency or force of the heart's beat. It is a remarkable fact that although in the vast majority of individuals the will has no influence whatever on the rate or force of the heart, except, perhaps, indirectly through the respiration, some persons have the power, by a voluntary effort, of markedl}' accelerating the pulse. In one case of this kind it was noticed that perspiration broke out on the hands and other parts of the body when the heart was voluntarily accelerated. The gentleman, a medical practi- tioner, could not describe how he felt when he was bringing about the change. He was unable to keep up the effort for more than a short time, and the pulse-rate quickly went back to normal. Vaso-motor Nerves, — Just as the muscular walls of the heart are governed by two sets of nerve-fibres, a set which keeps down the rate of working and a set which may increase it, the muscular walls of the vessels are under the control of nerves which have the power of diminishing their calibre (vaso-constrictor), and of nerves which have the power of increasing it (vaso- dilator). All nerves that affect the 124 A MANUAL OF PHYSIOLOGY. calibre of the vessels, whether vaso-constrictor or vaso- dilator, are included under the general name vaso-nwtor. It is not every part of the vascular system which is controlled to any appreciable extent by vaso-motor nerves. So far as we know at present, vaso-motor nerves influence chiefly the small arteries. Although nerve-fibres have been seen sur- rounding capillaries, nothing is known of any change of lumen occurring in these vessels as a direct result of the action of nerves going to them. Nor has the existence of vaso-motor nerves for veins, except the portal system, been proved up to this time by any clear and unambiguous ex- periment, although there are grounds on which it has been argued that in some animals, at least, the nervous system does govern the calibre or ' tone ' of the whole venous tract. These grounds will be mentioned in the proper place. Meanwhile, before describing the distribution of the best- known tracts of vaso-motor fibres, we must first glance at the principal methods by which our knowledge of this subject has been attained. (i) In superficial and translucent parts inspection is sufficient. Paling of the part indicates constriction ; flushing, dilatation of the small vessels. This method has been much used, sometimes in conjunction with (2) in such parts as the balls of the toes of dogs or cats (when there is little or no pigment present), the ear of the rabbit, the conjunctiva, the mucous membrane of the mouth and gums, the web of the frog, the wing of the bat, the intestines, uterus, and other internal organs. (2) Observation of changes in the temperature of parts. This method has been chiefly used in investigating the vaso- motor nerves of the limbs, the thermometer bulb being fixed between the toes. In such peripheral parts the temperature of the blood is normally less than that of the blood in the internal organs, because the opportunities of cooling are greater. The effect of a freer circulation of blood (dilatation of the arteries) is to raise the temperature ; of a more re- stricted circulation (constriction of the arteries), to lower it. (3) Measurement of the blood-pressure. If we measure the arterial blood-pressure at one point, and find that THE CIRCULATION OF THE BLOOD AND LYMPH. 125 stimulation of certain nerves increases it without affecting the action of the heart, we can conclude that upon the whole the tone of the small vessels has been increased. But we cannot tell in what region or regions the increase has taken place ; nor can we tell whether it has not been accompanied by diminution of tone in other tracts. But if we measure simultaneously the blood-pressure in the chief artery and chief vein of a part such as a limb, we can tell from the changes caused by section or stimulation of nerves whether, and in what sense, the tone of the small vessels within this area has been altered. For example, if we found that the lateral pressure in the artery was diminished, while at the same time it was increased in the vein, we should know that the ' resistance ' between artery and vein had been lessened, and that the blood now found its way more readih' from the artery into the vein. If, on the other hand, the venous pressure was diminished, and the arterial pressure simultaneously increased, we should have to conclude that the vascular resistance in the part was greater than before. If the pressure both in artery and vein was increased, we could not come to any conclusion as to local changes of resistance without knowing how the general blood-pressure had varied. It is also sufficient to measure the blood-pressure simul- taneously at two points of the arterial path by which blood reaches the part, provided that there is a distinct difference in the pressure at the two points. The ratio of the two pressures will not be altered by any general change of blood-pressure due to changes in the action of the heart ; any alteration in the ratio will indicate a change in the peripheral vascular resistance in the part beyond the more distal of the two manometers. Let the vertical lines AD, BE be proportional to the lateral blood- pressure at any given time at two points, A and B, near the begin- ning and end of the arterial portion of a given vascular circuit. Let AB represent the resistance of the path between i\ and B, and lay off on the horizontal axis a distance BC proportional to the resistance of the rest of the path. The pressure at C, the end of the venous path, being taken as zero, the line joining D and E must pass through C (see Fig. 17). Now let the blood-pressure be increased while the 126 A MANUAL OF PHYSIOLOGY. peripheral resistance is unchanged ; that is, let the increase of pressure be due to increase in the work of the heart. Let AD', BE' represent the new pressures. D'E' must still pass through C, since at C the lateral pressure is zero. XT u • •, . , AD AC AD' ^ . , Now, by similar triangles, :^=, = ^^— = ~~—- ; that is, the ratio between the pressures at A and B will not be changed unless AC — vanes. If BC (which includes the resistance that chiefly varies, the resist- AC ance of the small vessels) is altered, the ratio -57^, and therefore the ratio of the blood-pressure at A and B, will be changed. On this principle, Hurthle has studied the changes in the circulation of the brain by inserting manometers into the central end of the divided common carotid and the peri- FiG. 45. pheral end of the internal carotid. The former shows the lateral pressure in the aorta, the latter that in the circle of Willis. (4) The measurement of the velocity of the blood in the vessels of the part. This may be done by the stromuhr or dromograph, or by allowing the blood to escape from a small vein and measuring the outflow in a given time, or, without opening the vessels, b}^ estimating the circulation time (p. 104). When changes in the general arterial pressure are eliminated, slowing of the blood-stream through a part corresponds to increase of vascular resistance in it; increase in the rate of flow implies diminished vascular resistance. Sometimes the red colour of the blood issuing from a cut vein, and the visible pulse in the stream, indicate with certainty that the vessels of the organs have been dilated. THE CIRCULATION OF THE BLOOD AND LYMPH. 127 (5) Alterations in the volume of an organ or limb are often taken as indications of changes in the calibre of the small vessels in it. We have already seen how these alterations are recorded by means of a plethysmograph (p. 96). The brain is enclosed in the skull as in a natural plethys- mograph, and changes in its volume may be registered by connecting a recording apparatus with a trephine hole. The Chief Vaso-motor Nerves. — The first discovery of vaso- motor nerves was made in the cervical sympathetic. When this nerve is cut, the corresponding side of the head, and especially the ear, become greatly injected owing to the dilatation of the vessels. This experiment can be very readily performed on the rabbit, and the changes in the ear can be easily seen. The ear on the side of the cut nerve becomes redder and hotter than the other ; the vessels are seen to be dilated, and many vessels formerly invisible come into view. The slow rhythmical changes of calibre, which in the normal rabbit are very characteristically seen in the middle artery of the ear, disappear for a time after section of the sympathetic, although they ultimately again become visible (' Practical Exercises,' p. 155). Stimulation of the cephalic end of the cut sympathetic causes a marked constriction of the vessels and a fall of temperature on the same side of the head. From these facts we know that the cervical sympathetic in mammals contains vaso-constrictor fibres for the side of the head and ear, and that these fibres are constantly in action. Certain parts of the eye, and the salivary glands, larynx, oesophagus, and thyroid gland, are also supplied with vaso-motor (con- strictor) nerves from the cervical sympathetic. It has been asserted that the cervical sympathetic con- tains vaso-constrictor fibres for the corresponding half of the brain and its membranes, although fibres of this kind also reach it by other routes ; but this has been disputed, and some observers have even gone so far as to deny that the vessels of the brain have any vaso-motor nerves (Roy and Sherring- ton). To say the least, their existence must still be regarded as ' not proven.' That the nerve contains some dilator fibres seems proved by the fact that stimulation of the 128 A MANUAL OF PHYSIOLOGY. cephalic end in the dog causes flushing of the mucous mem- brane of the mouth on the same side. The vaso-motor fibres of the head run up in the cervical sympathetic, and then pass into various cerebral nerves, of which the fifth or trigeminus is the most important. The trigeminus nerve contains vaso-constrictor nerves for various parts of the eye (conjunctiva, sclerotic, iris), and for the mucous membrane of the nose and gums, and section of it is followed by dilatation of the vessels of these regions. The lingual branch of the trigeminus contains vaso-motor fibres for the tongue, and apparently both vaso-constrictor and vaso-dilator. In some animals, the rabbit for instance, the ear derives part of its vaso-motor supply directly from the cerebro- spinal system, through the great auricular nerve, as well as through the cervical sympathetic. Another great vaso-motor tract, the most influential in the body, is contained in the splanchnic nerves, which govern the vessels of many of the abdominal organs. Section of these nerves causes an immediate and sharp fall of arterial pressure. The intestinal vessels are dilated and overfilled with blood. As a necessary consequence of their immense capacity, the rest of the vascular system is underfilled, and the blood-pressure falls accordingly. Stimulation of the peripheral end of the splanchnic nerves causes a great rise of blood-pressure, owing to the constriction of vessels in the intestinal area. We therefore conclude that in the splanchnics there are vaso-motor fibres of the constrictor type, and that impulses are constantly passing down them to maintain the normal tone of the vascular tract which they command. But it is a very important fact that this constrictor influence may be abolished or lessened reflexly through a nerve connected with the heart, which for this reason has received the name of the depressor nerve (p. 156). The depressor (ramus cardiacus of the vagus) is easily found in the rabbit as a slender nerve running quite close to the sympathetic in the neck, and a little to its inner side. It generally arises by two branches, one from the vagus, and another from the superior laryngeal. It is the afferent nerve THE CIRCULATION OF THE BLOOD AND LYMPH. 129 of the heart. Stimulation of its peripheral end has no effect, but stimulation of the central end causes a marked fall of arterial blood-pressure, due largely, at any rate, to dilatation of the vessels in the great area ruled by the splanchnic. If the splanchnics have been previously cut, stimulation of the depressor does not cause a fall of blood-pressure. If the animal is not under an anaesthetic, there may also be signs of pain when the central end of the depressor is excited. In the normal body the nerve is supposed to cause a reflex diminution of pressure when from any cause it has become so great as to embarrass the action of the heart. In the dog the depressor fibres are not anatomically isolated from Fjg. 46.— Diagram of Depkessok Nerve in Rabbit. X, vagus; SL, superior laryngeal branch of vagus ; D, depressor fibres. The arrows show the course of the impulses that affect the blood-pressure. those of the vagus, while in rare cases inhibitory fibres for the heart have been found in the depressor of the rabbit. The best-known examples of vaso-dilator nerves are the chorda tympani and the nevvi erigeiitcs. The chorda tympani ■contains vaso-dilator and secretory fibres for the sub- maxillary and sublingual salivary glands, and its action has been deeply studied in the dog (Heidenhain, Langley, etc.). With the secretory fibres we have at present nothing to do ; and the whole subject will have to be returned to, and more fully discussed in Chapter IV. But a most marked vascular change is produced by stimulation of the peripheral end of the divided chorda tympani nerve. The glands flush red ; .more blood is evidently passing through their vessels. 9 I30 A MANUAL OF PHYSIOLOGY. Allowed to escape from a divided vein, the blood is seen to be of bright arterial colour and shows a distinct pulse. The small arteries have been dilated by the action of the vaso-motor fibres in the nerve. The resistance being thus reduced, the blood passes in a fuller and more rapid stream through the capillaries into the veins, and on the way there is not time for it to become completely venous. These vaso-dilator fibres are apparently not in constant action, for section of the nerve, as a rule, produces little or no change. Vaso-constrictor fibres pass to the salivary glands from the cervical sympathetic, along the arteries, and Fig. 47. — Blood-pkessuke Tracing (Rabbit), (Hg Manometer). Central end of depressor stimulated at i ; stimulation stopped at 2. Time trace seconds. stimulation of that nerve causes narrowing of the vessels and diminution of the blood-flow, sometimes almost to complete stoppage. Section of the nerve has no obvious effect. The nervi erigenUs are the nerves through which erection of the penis is caused. When they are divided there is no effect, but stimulation of the peripheral end causes dilatation of the vessels of the erectile tissue of the organ, which becomes overfilled with blood. During stimulation of these nerves, the quantity of blood flowing from the cut dorsal THE CIRCULATION OF THE BLOOD AND LYMPH. 131 vein of the penis may be fifteen times greater than without stimulation. It spurts out in a strong stream, and is brighter than ordinary venous blood (Eckhard). The nervi erigentes can be excited reflexly by mechanical stimulation of the glans penis, but only so long as the nervus pudendus is intact. This nerve therefore is the path by which the afferent impulses pass up to the erection centre in the lumbar cord. Stimulation of the peripheral end of the nervus pudendus causes constriction of the vessels of the penis, so that it contains fibres which are the antagonists of the nervi erigentes (Loven). The Vaso-motor Nerves of Muscle. — When the motor nerve of the mylo-hyoid muscle of the frog, which can be observed under the microscope, is cut, the vessels are seen to dilate. On stimulation of the peripheral end of the cut nerve, they dilate still more, and this effect is not abolished when con- traction of the muscle is prevented by curara (Gaskell). Accordingly it has been argued that although vaso-constrictor fibres may be present in muscular nerves, they are over- borne by the vaso-dilators, and that this is of use to the contracting muscle, which requires a free flow of blood to supply it with food materials and to carry off its waste products. In the mammal, apparently, this experiment has not been confirmed ; widening of the vessels of a completely curarized muscle on stimulation of its motor nerve has not been demonstrated. But when the muscle is thrown into con- traction, the average flow of blood through it is increased, apart from the initial increase due to the compression of the muscular veins. The outflow of blood from the main vein of one of the muscles used in mastication in the horse was found to be three times as great during voluntary work with it (in chewing) as in rest. It has been suggested that the muscular vessels are widened in contraction, not through vaso-motor nerves, but by the direct action of the acid products of the active muscle itself, since it has been found that very dilute acids (lactic acid, e.g.^ cause general dilata- tion of the small vessels. A similar explanation has been extended to the dilatation of the vessels of the brain during 132 A MANUAL OF PHYSIOLOGY. cerebral activity by some of those who deny the existence of vaso-motor nerves for that organ. The nerves of the extremities supply two leading tissues with vaso-motor fibres, skin and muscle. Since these are not necessarily, nor even probably, affected in the same way and to the same extent, data drawn from observation of the skin cannot be applied off-hand to the muscles, nor can data drawn from the behaviour of the muscles be generally expected to hold good for the skin. Now some observers have used changes of temperature or changes of colour in the balls of the toes, that is, chiefly cutaneous signs, as the sole index of vaso-motor changes in the entire limb. Others have relied altogether upon alterations of volume, which are chiefly an index of the state of the muscles. So we need not be surprised that there has been a good deal of controversy, not only as to the facts observed, but as to the deductions to be drawn from them. In the web of the frog it can be seen that section of the sciatic nerve is followed by dilatation, perhaps preceded by transient contraction, of the arteries, and stimulation by constriction. The dilatation does not last, however, more than twelve to twenty-four hours, as a rule. By means of a tiny plethysmograph adapted to the leg of a frog, it has been found that stimulation of the sciatic causes either shrinking or swelling of the limb according to the frequency and strength of the stimulus (Ellis). In mammals (cat), simple increase of volume of the limb never appears with medium, strong and frequent stimulation of the peripheral end of the cut sciatic. Usually the result is first decrease and then increase of volume. In general, weak and slow stimuli favour the preponderance of dilatation ; strong and frequent stimuli, that of constriction. There is a distinct latent period between beginning of stimulation and beginning of change of volume of the limb. This is less for constriction (i*5 seconds) than for dilatation (3-5 seconds). The dilata- tion may outlast the stimulation by several minutes ; the constriction usually ends with it (Bowditch and Warren). Dastre and Morat found, by recording the lateral blood- pressure in the crural artery of the dog, and at the same THE CIRCULATION OF THE BLOOD AND LYMPH. 133 time observing the colour of the balls of the toes, that when the peripheral end of the sciatic was tetanized, there was a predominance of the constrictor action, for the blood- pressure rose. But the skin was now pale, now red, show- ing that dilators were in evidence, too. The anterior crural is also preponderatingly constrictor. The truth seems to be that in the nerves of the ex- tremities both vaso-constrictor and vaso-dilator fibres are present ; but the former, under ordinary conditions, pre- ponderate, so that section of the sciatic or the brachial is generally followed by flushing of the balls of the toes and rise of temperature, stimulation by paling and fall of tem- perature. The temperature of the limb at the time of stimulation of the nerve seems to affect the result. If the limb is cold and the vessels contracted, dilatation and rise of temperature are more likely to be caused by stimulation of the peripheral end of the sciatic ; if the limb is warm and the vessels dilated, constriction and fall of temperature are more likely to be the result (Bernstein). The dilatation which follows section of the sciatic is not permanent in mammals any more than in the frog. It generally passes off in a few days, and as the nerve de- generates, stimulation of its peripheral stump more readily causes dilatation than constriction (Kendall and Luchsinger, etc.). The vaso-motor fibres for the fore limb (dog) issue from the cord in the anterior roots of the third to the eleventh dorsal nerves, and for the hind limb in the anterior roots of the eleventh dorsal to the third lumbar. Stimulation of most of these roots causes constriction of the vessels, but stimulation of the eleventh dorsal may cause dilatation (Bayliss and Bradford). Vaso-motor Nerves of the Lungs. — There has been much discussion as to the existence of vaso-motor nerves for the lungs. The cervical sympathetic contains none. The vagus probably contains none. Stoppage of respiration has been seen to cause a rise of pressure in the pulmonary artery, and that independently of rise of pressure in the aortic system 134 A MANUAL OF PHYSIOLOGY. (Lichtheim and Badoud), indicating increased vascular re- sistance in the pulmonary area. Stimulation of the upper half of the dorsal cord, or peripheral stimulation of the anterior dorsal nerve-roots from the second to the seventh, causes a relatively great rise of pressure in the pulmonary artery, a relatively small rise in the aorta (Bradford and Dean). This, again, seems to indicate that the vascular resistance in the lungs is con- trolled by nervous impulses, and that pulmonary vaso-motor nerves pass out from the upper half of the dorsal cord. But all observers are agreed that the vaso-motor mechanism for the pulmonary vessels is far less perfect than that which controls the systemic circulation. Course of the Vaso-motor Nerves. — In the dog the vaso-con- strictors pass out as fine medullated fibres (i'8 to 3*6 /i in diameter) in the anterior roots of the second dorsal to about the second lumbar nerves (Gaskell). They proceed by the M^hite rami communicantes to the lateral sympathetic ganglia, where, or in more distal ganglia such as the inferior mesenteric, they lose their medulla, and now pass by various routes to their final destination. Their course to the head has been already described. To the limbs they are distributed in the great nerves (brachial plexus, sciatic, etc.), which they reach from the sympathetic ganglia by the grey rami communicantes. The outflow of vaso-dilator fibres does not seem to be restricted to any particular part of the cord, but their exist- ence has been most clearly demonstrated in nerves springing from those regions of the cerebro-spinal axis from which vaso-constrictor fibres do not arise, and where, therefore, we have not to contend with the difficulty and doubt of mixed effects. The dilator fibres of the chorda tympani for the submaxillary gland and the anterior part of the tongue, and of the tympanic branch of the glossopharyngeal nerve for the parotid gland, pass out in the corresponding cranial nerves. They pursue a direct course to their destination without entering the sympathetic, and only lose their medulla near their peripheral distribution. Similarly the dilator fibres of the nervi erigentes leave the cord in the THE CIRCULATION OF THE BLOOD AND LYMPH. 135 anterior roots of the second and third sacral nerves, and pass on to the periphery without joining nerve-cells. The exact path of the vaso-dilator fibres of the hmbs and of the abdominal viscera, which come off from the same part of the cord as the vaso-constrictors, has not been absolutely settled, although there is no doubt that they, too, come out in the anterior roots. It is probable that their path is upon the whole similar to that of the constrictor fibres. We have thus tried to trace the vaso-motor nerves from the cerebro-spinal axis to the bloodvessels which they control ; it still remains to define the portion of the central nervous system to which these scattered threads are related, which holds them in its hand and acts upon them as the needs of the organism may require. Now, experiment has shown that there is one very definite region of the spinal bulb which has a most intimate relation to the vaso-motor nerves. If while the blood-pressure in the carotid is being registered, say, in a curarized rabbit, the central end of a peripheral nerve like the sciatic is stimulated, the pressure rises so long as the bulb is intact, this rise being largely due to the reflex constriction of the vessels in the splanchnic area. If a series of trans- verse sections be made through the brain, the rise of pressure caused by stimulation of the sciatic is not affected till the upper limit of the bulb is almost reached. If the slicing is still carried downwards, the blood-pressure sinks, and the rise following stimulation of the sciatic becomes less and less. When the medulla has been cut away to a certain level, only an insignificant rise or none at all can be obtained. The portion of the medulla the cutting away of which exerts an influence on the blood-pressure, and its increase by reflex stimulation, extends from a point 4 to 5 mm. above the point of the calamus scriptorius to within i to 2 mm. of the corpora quadrigemina (Owsjannikow). Other observers give narrower limits. Stimulation of the medulla causes a rise, destruction of this portion of it a fall, of general blood- pressure. There is evidently in this region a nervous ' centre ' so intimately related, if not to all the vaso-motor 136 A MANUAL OF PHYSIOLOGY. nerves, at least to such very important tracts as to deserve the name of a vaso-motor centre. Experiment has shown that this is much the most influential centre, and it is usually called the chief or general vaso-motor centre. But there are subsidiary centres all along the cord, and while a very large number of the constrictor fibres are related to the chief centre in the medulla, some are either normally under the control of subordinate centres, or may in special circum- stances come to be dominated by them. Thus, in the frog it is possible to go on destroying more and more of the cord from above downwards, and still to obtain reflex vaso-motor effects, as seen in the vessels of the web, by stimulating the central end of the sciatic nerve. Although these effects indeed diminish in amount as the destruction of the cord proceeds, yet a distinct change can be caused when only a small portion of the cord remains intact. Similarly, in the mammal evidence has been obtained of the existence of ' centres ' at various levels of the cord, capable of acting as vaso-motor centres after the chief centre in the bulb has been cut off". It is possible that normally their action is subordinated to the higher centre. The central connections of the vaso-dilator fibres appear to be more scattered than those of the vaso-constrictors. The vaso-motor centre, as we have seen, is influenced reflexly through afferent nerves. It can also be stimulated directly by venous blood. In asphyxia the blood-pressure first rises owing to stimulation of the vaso-motor centre and the consequent constriction of the small arteries. If respira- tion is not recommenced, the centre soon becomes paralyzed, and the blood-pressure falls (Figs. 48 and 49, and p. 155). Further, the vaso-motor centre may discharge automatic impulses ; that is, impulses arising apparently without external stimuli. If, for instance, in a curarized animal the artificial respiration is stopped, the respiratory waves of the blood-pressure curve of course cease, but other waves of a longer period may appear (Traube-Hering curves), the blood- pressure slowly rising and falling in response, apparently, to rhythmical impulses from the vaso-motor centre (Fig. 62, p. 169). THE CIRCULATION OF THE BLOOD AND LYMPH. 137 By means of the vaso-motor nerves and the centres by which they are governed, the distribution of the blood in the different parts of the bod}^ is being constantly controlled, so that to a certain degree of approximation no organ has too much, and none too little. The activity of the organs is always shifting with the calls upon them. Now, it is the actively-digesting stomach and the actively-secreting glands of the alimentary tract which must be fed with a full stream of blood, to supply waste and to carry away absorbed nutri- ment. Again, it is the working muscles of the legs or of the arms which need the chief blood supply. And again, it may be the brain. But wherever the call may be, the vaso-motor mechanism is able, in health, to answer it by bringing about Fig. 48.— Rise ok Blood-pressuke in Asphyxia (in Rabbit). Respiration stopped at i. Interval between 2 and 3 (not reproduced) 44 seconds, during wiiich the blood-pressure steadily rose. At 4, respiration resumed. Time tracing marks seconds. a widening of the small arteries of the part which needs more blood, and a compensatory narrowing of the vessels of other parts whose needs are not so great. This seems to be effected, in some instances, at least, by impulses travelling up the afferent nerves of the part in which dilatation of the vessels is to be brought about. The usual effect of stimulation of the afferent fibres of the tibial or great auricular nerve, for example, is to cause a rise of general blood-pressure, due to a constriction of the small arteries in wide regions of the body. But in the part itself to which the afferent fibres belong (the portion of the leg supplied by the tibial, and the ear, in the examples chosen). 138 A MANUAL OF PHYSIOLOGY. not constriction, but dilatation, takes place; and both changes favour an increased supply of blood to the part. In virtue of the great power of accommodation which the vascular system, as controlled by the vaso-motor mechanism, possesses, a mean blood-pressure, which varies within fairly narrow limits, is maintained in health. And so long as the vaso-motor arrangements are intact, the total quantity of blood in an animal may be greatly increased or diminished (2 or 3 per cent, of the body-weight in a dog) without appreciably affecting the arterial pressure. From this we ^^ fi ^H\ <^— ^ ' » I ' I ' i 1 1 » t ' ' ' 1 ' I ' » 1 ' I t 1 I I t t t t 1 > I I I I I It 1 M I I i Fig. 49.— Blood-pressure Tracing from a Dog Poisoned with Alcohol. The respiratory centre being paralyzed, respiration stopped, and the typical rise of blood-pressure in asphy.xia took place. The pressure had again fallen, and total paralysis of the vaso-motor centre was near at hand, when at A the animal made a single respiratory movement. The quantity of oxygen thus taken in was enough to restore the vaso-motor centre, and the blood-pressure again rose. This was re- peated five or six times. can deduce the practical lesson, that blood-letting is useless as a means of lowering the general arterial pressure, while it need not be feared that transfusion of a considerable quantity of blood, or of salt solution, in cases of severe haemorrhage will dangerously increase the pressure. And from the physiological point of view the term ' haemorrhage' includes more than it does in its ordinary sense. For as dirt to the sanitarian is * matter in the wrong place,' haemorrhage to the physiologist is blood in the wrong place. Not a drop of blood may be lost from the body, and yet death may occur from haemorrhage into the pleural or the THE CIRCULATION OF THE BLOOD AND LYMPH. 139 abdominal cavity, into the stomach or intestines, into extra- vascular spaces anywhere. Not only so, but a man may bleed to death into his own bloodvessels ; in shock, as well as in ordinary fainting or syncope, the blood which ought to be circulating through the brain, heart and lungs may stagnate in the dilated vessels of the splanchnic area. We have still to answer the question, how it is that the vaso- motor nerves act upon the muscular fibres of the arterioles. This is a question quite analogous to the one already discussed with regard to the inhibitory and aug- mentor nerves of the heart. And, as in the case of the cardiac nerves, two theories have been held : (i) that the vaso-motor nerves act on the muscular fibres directly ; and (2) that they act through intermediate peripheral organs, probably of ganglionic nature. In favour of the second view it has been urged that it is difficult to explain the recovery of vascular tone which, as a rule, soon takes place after section of a nerve, such as the sciatic, except on the assumption that there are peripheral tonic centres, and also that the hypothesis of an intermediate mechanism simplifies the explanation of vaso-dilatation or vaso-inhibition. Nevertheless, in the absence of any anatomical evidence in favour of the existence of such centres, and in face of the fact that so far none of the sporadic ganglia (such as the submaxillary ganglion, spinal ganglia, etc.) have been found to possess reflex functions, opinion in favour of (i) has been steadily gaining ground. And although we cannot say how, at bottom, a vaso - inhibitory (dilator) or cardio- inhibitory nerve brings about relaxation of muscular fibres, we are just as much in the dark as to the process by which contraction is caused by vaso-constrictor nerves, or augmentor nerves of the heart, or indeed by the motor nerves of ordinary skeletal muscle. Yet in the last case nobody thinks of postulating independent or semi - independent centres between the end of the nerve-fibre and the beginning of the muscular fibre. Vaso-Motor Nerves of Veins. — Like arteries, veins have plexuses of nerve fibres in their walls, and contract in response to various stimuli. In some cases, e.g., in the wing I40 A MANUAL OF PHYSIOLOGY. of the bat, rhythmical contractions of the veins are strikingly displayed, but they do not seem to depend on the nervous system, as they persist after section of the brachial nerves. Up to a very recent date the only fact, and it was not decisive, which seemed to indicate the existence of vaso-motor nerves for veins was an experiment of Goltz. He found in the frog that repeated blows on the abdomen with a spatula, the animal being held vertically, caused the heart to become empty and the blood to gather in the distended veins. This is due to a relaxation of the walls of the veins, which gradually regain their tone and force the blood on into the heart. The maintenance and recovery of this venous tone, according to Goltz, depends on the integrity of the spinal cord and bulb. In 1892 Mall showed that vaso-constrictor fibres for the veins of the portal area exist in the splanchnic nerves. They issue from the spinal cord by the nerve- roots of the third to the eleventh dorsal nerves, but chiefly in the fifth to the ninth dorsal (Bayliss and Starling). But the branches of the vena portae are functionally arteries rather than veins, and we must not without special proof extend Mall's results to ordinary veins. The Lymphatic Circulation. — As has already been mentioned, some of the constituents of the blood, instead of passing back to the heart from the capillaries along the veins, find their waj^ by a much more tedious route along the lym- phatics. The blood - capillaries are everywhere in very intimate relation with lymph-capillaries, which are simply irregular spaces, more or less completely lined with epithe- lioid cells, in the connective-tissue that everywhere accom- panies and supports the bloodvessels. The constituents of the blood-plasma are filtered through, or, as some say, secreted by the capillary walls into the lymph spaces, and there form the clear liquid known as lymph, from which the cells of the tissues take up food, and into which they discharge waste products. The lymph spaces are connected with more regular lymphatic vessels, provided with numerous valves, and with lymphatic glands at intervals on their course. These fall into larger trunks, and finally the greater part of the lymph reaches the blood again by the thoracic THE CIRCULATION OF THE BLOOD AND LYMPH. 141 duct, which opens into the venous system at the junction of the left subclavian and internal jugular veins. The lymph from the right side of the head and neck, the right extremity, and the right side of the thorax with its viscera, is collected by the right lymphatic duct, which opens at the junction of the right subclavian and internal jugular veins. The open- ings of both ducts are guarded by semilunar valves, which prevent the reflux of blood from the veins. Serous cavities like the pleural sacs, are really large lymph spaces, and they are connected through small openings, called stomata, with lymphatic vessels. The rate of flow of the lymph in the thoracic duct is very small compared with that of the blood in the arteries — only about four mm. per second, according to one observer. The factors which contribute to the maintenance of the lymph flow are : (i) The pressure under which it passes from the capil- laries into the lymph spaces. The pressure in the thoracic duct of a horse may be as high as twelve mm. of mercury ; in the dog it may be less than one mm. (2) The contraction of muscles increases the pressure of the lymph by compressing the lymphatics, and the valves only permit of movement in the direction of the normal current. Even passive movements of the limbs increase the flow of lymph through their ducts. vSubstances may be sucked into the lymphatics of the central tendon of the diaphragm from the peritoneal cavity through the stomata in the serous layer ; even by passive movements of the diaphragm in a dead rabbit the lymphatics may be injected with a coloured solution placed on its peritoneal surface. The contractions of the intestines, and especially of the villi, are of importance in keeping up the movement of the chyle. (3) The movements of respiration aid the flow. At ever)'' inspiration the pressure in the great veins near the heart becomes negative, and lymph is sucked into them. (4) In some animals rhythmically-contracting muscular sacs or hearts exist on the course of the lymphatic circula- tion. The frog has tvvo pairs, an anterior and a posterior, of these lymph hearts, and they are also found in reptiles. It is possible that in animals without localized lymph hearts 142 A MANUAL OF PHYSIOLOGY. the smooth muscle, which is so conspicuous an element in the walls of the lymphatic vessels, may aid the flow by rhythmical contractions. An excessive transudation of lymph gives rise to the condition known as cedema, or when it involves the whole body, anasarca. CEdema may be experimentally caused by h'gature of the veins of a part. Here the increase of blood- pressure in the capillaries is a factor in causing the increased transudation ; but it is not the only one, for the rise of capil- lary blood-pressure produced by dilatation of the arterioles when vaso-dilator nerves are stimulated, or vaso-constrictor nerves cut, does not cause oedema. Probably the inter- ference with the blood-flow after ligature of the veins damages the capillary walls in such a way that they are more readily permeable. In disease oedema may be caused either by mechanical obstruction to the venous flow, as in valvular disease of the heart, or cirrhosis of the liver, or by alteration in the quality of the blood, as in Bright's disease of the kidney. PRACTICAL EXERCISES ON CHAPTER II. I. Microscopic Examination of the Circulating Blood. — (i) Take a tadpole and lay it on a glass slide. Cover the tail with a large cover-slip, and examine it with the low power (Leitz, oc. III., obj. 3). Generally the tail will stick so closely to the slide, and the animal will move so little, that a sufficiently good view of the circulation can be obtained. If there is any trouble, destroy the brain with a needle. Observe the current of the blood in arteries, capillaries and veins. An artery may be easily distinguished from a vein by looking for a place at which the vessel bifurcates. In veins the blood flows towards the points of bifurcation, in arteries away from them. Sketch a part of a field. To Pith a Frog. — Wrap the animal in a towel, bend the head forwards with the index finger of one hand, feel with the other for the depression at the junction of the head and backbone, and push a narrow-bladed knife right down in the middle line. The spinal cord will thus be divided with little bleeding. Now push into the cavity of the skull a piece of pointed lucifer match. The brain will thus be destroyed. The spinal cord can be destroyed by passing a blunt needle down inside the vertebral canal. (2) Take a frog and pith its brain only, inserting a match to prevent bleeding. Pin the frog on a plate of cork into one end of which a glass slide has been fastened with sealing-wax. Lay the web of one PRACTICAL EXERCISES. 143 of the hind-legs on the glass and gently separate two of the toes, if necessary by threads attached to them and secured to the cork plate. Put the plate on the microscope-stage and fasten by the clips (see pp. 18, 88). 2. Anatomy of the Frog's Heart. — Expose the heart of a pithed frog by pinching up the skin over the abdomen in the middle line, dividing it with scissors up to the lower jaw, and then cutting through the abdominal muscles and the bony pectoral girdle. The external abdominal vein, which will be observed on reflecting the skin, can be easily avoided. The heart will now be seen enclosed in a thin membrane, the pericardium, which should be grasped with fine- pointed forceps and freely divided. Connecting the posterior surface of the heart and the pericardium is a slender band of connective tissue, the fraenum. A ligature may be passed around this with a threaded curved needle and tied, and then the fraenum may be divided posterior to the ligature. The anatomical arrangement of the various parts of the heart should now be studied. Note the single ventricle with the buluus arteriosus, the two auricles, and the sinus, venosus, turning the heart over to see the latter by means of the ligature. Observe the whitish crescent at the junction of the sinus, venosus and the right auricle. 3. The Beat of the Heart. — Note that the auricles beat first, and then the ventricle. The ventricle becomes smaller and paler during its systole, and blushes red during diastole. Count the number of beats of the heart in a minute. Now excise the heart, lifting it by means of the ligature, and taking care to cut wide of the sinus venosus. Place the heart in a small porcelain capsule on a little blotting-paper moistened with normal saline. Observe that it goes on beating. Put a little ice or snow in contact wiih the heart, and count the number of beats in a minute. The rate is greatly diminished. Now remove the ice and blotting-paper, cover the heart with normal saline, and heat, noting the temperature with a thermometer. Observe that the heart beats faster and faster as the temperature rises. At 40° C. to 43° C. it stops beating in diastole (heat standstill). Now at once pour off the heated liquid, and run in some cold normal saline. The heart will begin to beat again. 4. Cut off the apex of the ventricle a little below the auriculo- ventricular groove. The auricles, with the attached portions of the ventricle, go on beating. The apex does not contract spontaneously, but can be made to beat by stimulating it mechanically (by pricking it with a needle) or electrically. Divide the still contracting portion of the heart by a longitudinal incision. The two halves go on beating. 5. Heart-tracings. — (i) Fasten a myograph-plate (Fig. 50) on a stand. Take a long light lever consisting of a straw or a piece of thin chip, armed at one end with a writing-point of parchment- paper, supported near the other end by a horizontal axis, and pierced not far from the axis by a needle carrying on its point a small piece of cork or a ball of sealing-wax. A counterpoise is adjusted on the short arm of the lever in the form of a small leaden weight. Cover a drum with glazed paper and smoke it. The paper must be put on 144 A MANUAL OF PHYSIOLOGY. so tightly that it will not slip. To smoke the drum, hold it by the spindle in both hands over a fish-tail burner, depress the drum in the flame, and rotate rapidly. Avoid putting on a heavy coating of Ccu\J:tyf>oiiC Fic. 50. — Arrangement for obtaining a Heart-tracing from a Frog. smoke, as a more delicate tracing is obtained when the paper is lightly smoked. The speed of the drum can be varied by putting in or taking out a small vane. Arrange an electro-magnetic time- marker for writing seconds (Fig. 51). Pith a frog (brain only), Fig. 51.— Electro-magnetic Time-marki':i{ connected with Metronome. The pendulum of the metronome carries a wire which closes the circuit when it dips into either of the mercury cups, Hg. expose the heart, and put under it a cover-slip to give it support. Pin the frog on the myograph-plate, and adjust the foot of the lever to rest on the ventricle or the auriculo-ventricular junction. Bring PRACTICAL EXERCISES. 145 the writing-point of the lever and that of the time-marker vertically under each other on the surface of the drum. Set off the drum at the slow speed (say, a centimetre a second). When the lever rests on the auriculo-ventricular junction, the part of the tracing corre- sponding to the contraction of the heart will be broken into two portions, representing the systole of the auricles and ventricle re- spectively. Cut the paper off the drum with a knife and carry it to the varnishing trough, holding the tracing by the ends with both Fig. 52.— Apparatus for obtaining a Simultaneous Tracing of Auricular AND Ventricular Contractions (Chadburn). hands, smoked side up. Immerse the middle of it in the varnish, draw first one end and then the other through the varnish, let it drip for a minute into the trough, and fasten it up with a pin to dry. (2) Heart Tracing, with Sitnultatieous Record of Auricular and Ventricular Contractions. — {a) For this purpose two levers may be arranged, one resting on the auricle, the other on the ventricle, the writing points being placed in the same vertical straight line on the drum. A convenient form of apparatus is shown in Fig. 52. 10 1 46 A MANUAL OF PHYSIOLOGY {b) Gaskell's Method (a modification of). — Attach a silk ligature to the very apex of the ventricle. Divide the fraenum, cut the aoria across close to the bulbus, pinch up a tiny portion of the auricle and ligature it. Remove the intestines, liver, lungs, etc., care being taken in cutting away the liver not to injure the sinus. Then remove the lower jaw, and cut away the whole of the body except the head, part of the oesophagus and the tissue connecting it with the heart. Fix the head in a clamp sliding on an ordinary stand. The heart is held Kl F^<^- 53-— Arkangemknt for Recording Auricular and Vkntricular Contractions. C, clamp holding the heart at tlie auriculo-ventricular groove. I', pulley round which a thread attached to the apex of the ventricle passes to the lever L ; 1., lever connected with auricle. The rest of the arrangement is for studying the influence of temperature on the heart and its nerves, G being a vessel filled with normal saline solution in which the heart is immersed ; R, an inflow tube from a reservoir containing salt solution at the temperature required ; O', an outflow tube by which G may be emptied into the beaker B' ; O, a tube passing to the beaker B to prevent overflow from G ; T, a thermometer. at the auriculo-ventricular junction in a Gaskell's clamp supported on a separate stand. The thread connected with the ventricle is brought round a pulley and attached to a lever above the heart. The auricle is connected with another lever. The writing points of the two levers are arranged in a vertical line on the drum. The small pulley must be oiled from time to time to prevent friction (Fig- 53)- PRACTICAL EXERCISES. 147 6. Dissection of the Vagus and Cardiac Sympatlietic Nerves in the Frog. — (i) Put the tissues in the region of the neck on the stretch by passing into the gullet a narrow test-tube or a thick glass rod moistened with water, and by pinning apart the anterior limbs. On clearing away a little connective tissue and muscle with a seeker, three large nerves will come into view. The upper is the glosso- pharyngeal, the lower the hypoglossal ; the vagus crosses diagonally between them (Fig. 54). Parallel to the vagus trunk, and separated from it by a thin muscle and a bloodvessel, lies its laryngeal branch. The vagus should be traced up to the ganglion situated on it near its exit from the skull. Glass rod Glo sso^haryn ^cal Hypoc/lossi \Lari^nqeal branch of -1^ Vagus iHearl Luna Fig. 54. — The Rel.a.tions of the Vagus in the Fkog. (2) Then cut away the lower jaw, dividing and reflecting the membrane covering the roof of the mouth. At the junction of the skull and the backbone will be seen on each side the levator anguli scapulae muscle (Fig. 55). Remove this muscle carefully with fine forceps, clear away a little connective tissue lying just over the upper cervical vertebrc^, and the sympathetic chain, with its ganglia, will be seen. Pass a fine silk thread beneath the sympathetic about the level of the large brachial nerve, by means of a sewing needle which has been slightly bent in a flame and fastened in a handle. Tie the ligature, divide the sympathetic below it, and isolate it carefully with fine scissors up to its junction with the vagus ganglion. 148 A MANUAL OF PHYSIOLOGY 7. Stimulation of the Vagus in the Frog. — Make the same arrangements as in 5 (i), but, in addition, set up an induction machine arranged for an interrupted current (Fig. 56), with a simple key in the primary circuit and a short-circuiting key in the secondary. Attach the electrodes to the short-circuiting key, push the secondary coil up towards the primary until the shocks are distinctly felt on the tongue when the Neef's hammer is set going and the short-circuiting key opened. Pith the brain of a frog, expose the heart, dissect out the vagus on one side, ligature it as high up as possible, and divide above the ligature. P'asten the electrodes on the cork plate by means of an indiarubber band, and lay the vagus on them. Set the drum Fig. 55. —Relation of the Symi'Athetic to the Vagus in the Fkog. I, 2, 3, 4 are spinal nerves. off (at slow speed). After a dozen heart-beats have been recorded, stimulate the vagus for two or three seconds by opening the short- circuiting key. If the nerve is active, the heart will be slowed, weakened, or stopped. In the last case the lever will trace an un- broken straight line ; but even if the stimulation is continued the beats will again begin. 8. Stimulation of the Junction of the Sinus and Auricles. — After a sufficient number of the observations described in 7 have been taken with varying time and strength of stimulation, take the writing- PRACTICAL EXERCISES. 149 points off the drum, apply the electrodes directly to the crescent' at the: junction of the sinus venosus with the right auricle, and stimulate. The heart will be affected very much in the same way as by stimulation of the vagus, except that during the actual stimulation its beats may be quickened and the inhibition may only begin after the electrodes have been removed (Fig. 38, p. 113). 9. Effect of Muscarine and Atropia. — Paint on the sinus venosus with a small camel's-hair brush a very dilute solution of muscarine. The heart will begin to beat more slowly, and will soon stop in diastole. Now apply a dilute solution of sulphate of atropia to the sinus. The heart will again begin to beat. Stimulation of the vagus v.'ill now cause no inhibition of the heart, because its endings have been paralyzed by atropia. (Muscarine has also been applied to the heart, but it could be shown by a separate experiment that atropia by itself has the same effect on the vagus endings.) (P. 115.) 10. Stannius' Experiment. — Pith a frog. Expose the heart in the way described under 2. Ligature the fr^enum, and use the thread to manipulate the heart. With a curved needle pass a moistened thread Fig. 56. — Ark.yngement oi' Induction Machine xok Tetanu.s. B, battery ; K, simple key ; P, primary coil ; S, secondary coil. between the aorta and the superior vena cava, and tie it round'^the junction of the sinus and right auricle. The auricles and ventricle stop beating as soon as the ligature is tightened. The sinus venosus goes on beating. Now separate the ventricle from the rest of the heart by an incision through the auriculo-ventricular groove. The ventricle begins to beat again, the auricle remaining quiescent in diastole (p. 1 10). ir. Stimulation of Cardiac Sympathetic Fibres in the Frog.— (i) /;/ the vagosympathetic after the ifihibitory fibres have been cut out by atropia. — -Arrange everything as in 7. Paint a dilute solution of atropia on the sinus. Stimulation of the vagus, which is really the vago-sympathetic (see Fig. 55), will now cause, not inhibition, but augmentation (increase in rate or force, or both), since the endings of the inhibitory fibres have been paralyzed by atropia. The strength of stimulating current required to bring out a typical augmentor effect is greater than that needed to stimulate the inhibitory fibres. (2) By direct stimulation of the cervical sympathetic. — Make the same arrangements as in n (i), but dissect out the sympathetic on ISO A MANUAL OF PHYSIOLOGY. one side in the manner described in 6 (2), and do not apply atropia to the heart. Lay the sympathetic on very fine and well-insulated electrodes, and stimulate. (To insulate electrodes the points may be covered with melted paraffin. When the paraffin has cooled, a narrow groove, just sufificient to lay bare the wires on the upper side, is made in it, and the nerve is laid in this groove.) (Fig. 40, p. 116.) Experiments 7, 11 (i) and 11 (2) will be rendered more exact by connecting a second electro-magnetic signal with a Pohl's com- mutator without cross-wires (Fig. 57), in such a way that the circuit is interrupted at the instant when stimulation begins. 12. The Action of the Mammalian Heart. — Inject under the skin of a dog i cc. of a i per cent., or \ cc. of a 2 per cent. Fig. 57.— Arrangement for Recording the Beginning and End of Stimulation. C, Pohl's commutator without cross wires ; B, battery in circuit of primary coil P; B', battery in circuit of electro-magnetic signal T ; K, simple key in primary circuit ; S, secondary coil. When the bridge of the commutator is tilted into the position shown in the figure, the primary circuit is closed and the circuit of the signal broken. solution of morphia hydrochlorate for every kilogram of body-weight. A medium-sized dog weighing about 10 or 12 kilograms should receive about 5 cc. of the 2 per cent, solution. As soon as the morphia has taken effect (in 15-30 minutes), fasten the animal on a holder (as in Fig. 81), pushing the mouth-pin behind the canine teeth and screwing the nut home. In the meantime select a tracheal cannula of suitable size, and get ready instruments for dissection ■ — one or two pairs of artery-forceps, a pair of artery- clamps (bulldog pattern), two or three glass cannuL-e of various sizes for bloodvessels, twenty strong waxed ligatures, sponges, hot water, a towel or two, and a pair of bellows to be connected with the tracheal cannula when the chest is opened. Arrange an induction- coil and electrodes for a tetanizing current. With scissors curved on the flat clip away the hair from the front of the neck and the anterior surface of one thigh below Poupart's ligament. Put the hair carefully PRACTICAL EXERCISES. 151 away, and remove all the loose hairs with a wet sponge so that they may not get into the wounds. If the animal is not fully anaesthetized, give ether. Insert a glass cannula into the central end of the femoral vein, through which i or 2 cc. of the 2 per cent, solution of morphia may be injected when necessary by pushing the needle of the hypo- dermic syringe through the indiarubber tube on the cannula. Feel for the femoral artery, cut down over it, and with forceps or a blunt needle separate the femoral vein from it for about an inch. Pass two un- waxed ligatures under the vein, and tie a loose loop on each. Put a pair of bulldog forceps on the vein between the ligatures and the heart. Now tie the lower (distal) ligature, and cut one end short. The piece of vein between it and the bulldog forceps is thus distended with blood, and this facilitates the next step. With fine- pointed scissors make a snip in the wall of the vein. The cannula, which has a piece of indiarubber tubing on its wide end, should have been previously filled with normal saline solution, which is prevented from running out by a pair of bulldog forceps or a screw clamp on the tubing. Now push the cannula through the slit in the vein, and tie the upper ligature firmly round the neck of the cannula. To put a Cannula in the Trachea. — The hair having been clipped in the middle line of the neck and the skin shaved, a mesial incision is to be made, beginning a little below the cricoid cartilage, which can be felt with the finger. The trachea is then cleared from its attachments by forceps or a blunt needle, and two strong ligatures are passed beneath it. A single loop is placed on each of those. Raising the trachea by means of the upper ligature, the student makes a longitudinal incision through two or three of the cartilaginous rings, inserts the cannula, and ties the lower ligature firmly around it. It is well also, though not necessary, to tie the upper ligature, and additional security may be obtained by tying together the ends of the two ligatures around the vertical portion of the cannula. Clip off the hair on each side of the sternum. Make an incision on each side through the skin and down to the costal cartilages about two inches from the edge of the breast-bone, and long enough to expose about four costal cartilages (say 3rd to 6th). With a curved needle pass double waxed ligatures round the cartilages, and tie firmly to compress the intercostal vessels. Then pass a double waxed ligature under the upper portion of the sternum, and tie. The bellows should now, if not before, be connected with the tracheal cannula by an indiarubber tube. One student should take sole charge of the arti- ficial respiration, which ought to be begun as soon as the chest has been opened, and continued at the rate of about twenty inflations per minute. It will often be a good plan to close the side opening of the tracheal cannula with the finger during inflation, and to open it when the air is to be allowed to escape. The costal cartilages and sternum are rapidly cut through with scissors between the double ligatures, the artificial respiration being suspended for an instant, as each cut is made, to avoid wounding the lungs. The lower part of the sternum is turned down like the lid of a box, tied out of the way or cut off altogether, and the heart, enclosed in the pericardium, 152 A MANUAL OF PHYSIOLOGY. comes into view. If the ligatures round the sternum have not properly compressed the internal mammary arteries, haemorrhage from the central ends may now occur. In this case they must be seized with artery-forceps and ligatured. A cotton thread is now passed with a suture-needle through each side of the pericardium, which is then stitched to the chest-wall and opened. The following observations and experiments should now be made : {a) Note the various portions of the heart, right and left ventricles, right and left auricles, with the auricular appendices. Feel the heart with the hand, and observe that the right ventricle is softer and has thinner walls than the left, and that the auricles are softer than the ventricles. Note how all the parts of the heart harden in the hand during systole and soften during diastole (pp. 60-64). ip) Pith a frog (brain and cord), dissect out the sciatic nerve on one side up to the sacral plexus. Cut off the whole leg. Drop the cut end of the nerve on the heart, and hold the preparation so that the nerve touches the heart also by its longitudinal surface. At each cardiac beat the nerve is stimulated by the action current (Chap. XL), and the muscles of the leg contract. {c) Dissect out the vago-sympathetic in the neck of the dog. The guide to the nerve is the carotid artery. Feel for the artery a little external to the trachea, cut down on it, open the common sheath, isolate the vago-sympathetic for about an inch, pass two ligatures under it, tie them, and divide between the ligatures. The peripheral and central end of the nerve may now be successively stimulated. Stimulation of the peripheral end causes slowing of the heart or stoppage in diastole. Feel that it softens when it stops. It soon begins to beat again. Stimulation of the central end of the vago- sympathetic may or may not cause inhibition. If it does, expose the other vago-sympathetic, divide it, and repeat the stimulation of the central end. There will now be no inhibition of the heart. Inci- dentally it may be seen that stimulation of the central end of the vagosympathetic causes strong, though, of course, with opened chest, abortive, respiratory movements. {d) Lay the electrodes on the heart, and stimulate it with a strong interrupted current. The character of the contraction soon becomes profoundly altered. Shallow irregular contractions flicker over the surface, with a kind of simmering movement suggestive of a boiling pot (delirium cordis, fibrillar contraction). Now kill the animal by stopping the artificial respiration. {e) Make a dissection of the cervical sympathetic up to the superior cervical ganglion, and down through the inferior cervical ganglion to the stellate or first thoracic ganglion. Make out the annulus of Vieussens and the cardiac sympathetic (accelerator) branches going off from the annulus or the inferior cervical ganglion to the cardiac plexus (Fig. 43 ; see also p. 120). 13. Action of the Valves of the Heart.— Study the action of the valves of the ox-heart in the artificial scheme. Connect the ox-heart provided with the pump P and bottle B, as shown in Fig. 58. The cavity of the heart is illuminated by means of a small electric lamp. PRACTICAL EXERCISES. 153 the wires of which pass in at A. When the piston of the pump is pushed down, water is forced through the aorta D along the tube T Fig. 58.— Arrangement to Illustrate Action of Cardiac Valves in the Heart of an Ox (Qad). C, glass window in left auricle ; D, window in aorta ; E, tube inserted through apex of heart into left ventricle and connected with pump P ; A, side tube on E, through which wires are connected with a tiny incandescent lamp in the ventricle ; W, water in bottle B ; T, T' tubes. (For comparison, use human heart with valvular lesion.) into the bottle, and flows back again into the left auricle by the tube T'. During each stroke of the pump the auriculo-ventricular 154 ^l MANUAL OF PHYSIOLOGY. valve is seen through the glass disc inserted into C to close, and the semilunar valves are seen through the glass in D to open. When the piston is raised, the semilunar valves are seen to be closed and the auriculo-ventricular valve to be opened. 14. Cardiogram. — Smoke a drum, and arrange a recording tambour and a time-marker beating quarter-seconds to write on it (Fig. 51). Apply the button of a cardiograph (Fig. 18) over your own cardiac impulse, and fasten it round the body by a string. Connect the cardiograph by an indiarubber tube with the recording tambour. Set the drum off at a fast speed, take a tracing, and varnish it. Compare with Fig. 19, and measure out the time-value of the various events in the cardiac revolution as indicated on the cardiogram. 15. Blood-pressure Tracing. — («) Put a dog under morphia (p. 150). Set up an induction-machine arranged for an interrupted current. Fill the connecting-tubes and one limb of the manometer with saturated solution of sodium carbonate or 25 per cent, magnesium sulphate. All air may be got out of the manometer by inserting a T-piece between it and the tube which is to connect it with the artery. The stem of the T has a short piece of indiarubber tube on it, closed by a pinchcock. A syringe filled with the sodium carbonate solution is attached to the connecting-tube or the horizontal limb of the T-piece, and the solution is injected till the mercury in the nearer limb of the manometer has sunk to within an inch of the bend. The pinchcock is now suddenly opened for an instant, and some air escapes. The manoeuvre is repeated as often as may be necessary. When all the air is out, get up a pressure of about 10 cm. of mercury — i.e., let the difference of level in the two limbs of the manometer be 10 cm.— and clamp the tubes (see Fig. 25, p. 79). Now smoke a drum, and arrange the writing-point of the mano- meter-float so that it will write on the drum without undue friction. In the same vertical line below it adjust the writing-point of a time- marker beating seconds. Next, fasten the animal on a holder, back down. Give ether, if necessary, and insert a tracheal cannula. (The tracheal cannula is not absolutely required for the experiment, but it is convenient, as the animal is more under control, and artificial respiration can be begun at any moment, should this be necessary.) Insert a glass cannula into the central (cardiac) end of the carotid artery (p. 45). Leaving the bulldog forceps on the artery, slip the short india- rubber tube of the cannula on to the glass tube which connects with the manometer, seeing that both are quite full of liquid, so that no air may be enclosed. Now take off the bulldog forceps, and allow the drum to revolve at slow speed. The writing-point of the manometer-float will trace a curve showing an elevation for each heart-beat, and longer waves due to the movements of respiration. {b) Now isolate the vago-sympathetic nerve in the neck. Ligature doubly, and cut between the ligatures. Stimulate first the peripheral (lower) and then the central (upper) end, and note the effect on the blood-pressure curve. (c) Expose and divide the other vago-sympathetic while a tracing PRACTICAL EXERCISES. 155 is being taken. Again stimulate the central end of the nerve, and observe whether there is any effect. {d) Expose the sciatic nerve in one leg. This is very easily done as follows. The leg having been loosened from the holder, the foot is seized by one hand and lifted straight up, so as to put the skin of the thigh on the stretch. An incision is now made in the middle line on the posterior aspect of the thigh, the skin and sub- cutaneous tissue being divided at one sweep. The muscles are separated in the line of the incision with the fingers, and the sciatic nerve comes into view lying deeply between them. Place a double ligature on it, and divide between the ligatures. Stimulate the upper (central end) ; the blood-pressure probably rises, and the heart may be accelerated. Stimulate the peripheral end of the nerve ; there is little change in the blood-pressure and none in the rate of the heart. (e) Note, incidentally, that stimulation of the central end of the vago-sympathetic or of the sciatic may cause increase in the rate and depth of the respiratory movements. Dilatation of the pupil may also be caused, especially by stimulation of the vago-sympathetic. (/) Close the tracheal cannula so that air can no longer enter the lungs. In a very short time the blood-pressure curve begins to rise (rise of asphyxia). After some minutes the pressure falls, and finally becomes zero ; i.e., the level of the mercury is the same in the two limbs of the manometer (or, rather, the mercury in the distal limb is higher than that in the proximal limb by the amount needed to exactly balance the pressure of the column of sodium carbonate in the latter). Disconnect the arterial cannula from the manometer, and allow the writing-point to trace a horizontal straight line (line of zero pressure) on the drum (Figs. 48 and 49). 16. Section and Stimulation of the Cervical Sympathetic in the Rabbit. — Weigh out f gramme chloral hydrate. Dissolve in a little water and inject into the rectum of an albino rabbit. Put a pair of bulldog forceps on the anus to prevent escape of the solution. Set up an induction coil arranged for an interrupted current, and connect it through a short-circuiting key with electrodes. The preparations necessary for an operation with antiseptic precautions are supposed to have been previously made — the instruments, sponges, and liga- tures boiled in water ; the instruments then immersed in a 5 per cent, solution of carbolic acid, the sponges and ligatures in corrosive sublimate solution (o"i per cent.). The hands are to be washed, before the cutting operation begins, with soap and water, and then soaked in the corrosive solution. Fasten the rabbit on a holder, back downwards, as in Fig. 36. Clip off the hair on the anterior surface of the neck. Remove loose hairs with a wet sponge, shave the neck, and wash it thoroughly first with soap and water, and then with corrosive sublimate. Give ether if necessary. Make a longitudinal incision in the middle line over the trachea, beginning a little below the thyroid cartilage and extending downwards for an inch and a half. Feel for the carotid artery, expose, and raise it up. Two nerves will now be seen coursing beside the artery. The larger is the vagus, the smaller the sympathetic. 156 A MANUAL OF PHYSIOLOGY. A third and much finer nerve (the depressor, or superior cardiac branch of the vagus) may also be seen in the same position, but the student should neglect this for the present. Pass a ligature under the sympathetic, and tie it, the ear being held up to the light while this is being done, so that its vessels may be clearly seen. A transient constriction of the arteries may be seen at the moment when the nerve is ligatured. This is due to stimulation of the vaso-constrictor fibres. Then follows a marked dilatation of the bloodvessels due to paralysis of these fibres. The ear is flushed and hot. On stimula- tion of the upper (cephalic) end of the sympathetic with disinfected electrodes, the vessels are markedly constricted and the ear becomes pale and cold. The wound is now to be closed, the muscles being fiist brought together by a row of interrupted sutures, and then the skin by another row. Since it is difficult, if not impossible, to thoroughly disinfect the hair-follicles, and a suture passed through a septic follicle is apt to give rise to suppuration, subcutaneous stitches — i.e., stitches passed by a curved needle through the deep layer of the skin without coming through to the surface — may be employed. The wound is to be protected by a coating of collodion. No other dressing is required. The animal is now removed from the holder and put back to its hutch. The student must examine it at least once a day for the next week, and study the differences between the two ears (p. 127). 1 7. Stimulation of the Depressor Nerve in the Rabbit. — Set up the apparatus for a blood-pressure tracing as described in 15. Arrange an induction coil and electrodes for an interrupted current. Anaesthetize a rabbit with ^^ gramme chloral hydrate, and if neces- sary wiih ether. For blood-pressure experiments only small doses of chloral hydrate or chloroform can be given, as they affect the vaso- motor centre. Put the animal on the holder. Insert a cannula in the trachea and a glass cannula in the central end of the carotid artery. Isolate the depressor nerve. Put double ligatures on it, and divide between them. Connect the cannula in the carotid with the mano- meter and take a blood-pressure tracing. Stimulate the central (upper) end of the depressor. A marked fall of blood-pressure will be obtained. Stimulate the peripheral (lower) end ; no effect. Divide both vagi, and again stimulate the central end of the nerve. The blood-pressure again falls. Stimulation of the depressor must, therefore, lower the blood-pressure in some other way than by reflex inhibition of the heart. It is known that it does so by causing reflex dilatation of the small arteries, especially in the abdominal (splanchnic) area. Close the tracheal cannula, and obtain another tracing, showing the effect of asphyxia. Varnish the tracings (see Fig- 47)- Autopsy. — Dissect the nerve that has been stimulated up to the origin of the superior laryngeal branch of the vagus, to make sure that it is the depressor (Fig. 46). 18. Determination of the Circulation-time. — {a) Begin with an artificial scheme (Fig. 59). Fill the syringe with a o"2 per cent, solution of methylene blue. Allow the water to flow from the bottle PR A CTICA L EXER CISES. 157 by loosening the clamp. Inject a definite quantity of the methylene- blue solution, and with a stop-watch observe how long it takes to pass from the point of injection to the end of the glass tube filled with beads. Make ten readings of this kind and take the mean. Then raise the bottle so as co increase the rate of flow of the water, and repeat the observations. The ' circulation-time ' will be found to be diminished. This corresponds to an increase of blood-pressure Fig. 59.— Artificial Scheme to Illustrate Method of Measuring the Circulation Time. B, bottle containing water, the rate of outflow of which is regulated by screw clamp a ; S, syringe filleil with methylene-blue solution, connected with T-piece A ; M, beaker containing methylene-blue solution ; h, c, screw-clamps ; C, T-piece, inserted in the course of the flexible tube E, and connected with the glass tube 'V, which is filled with beads ; F, outflow tube. The clamp c having been closed and i^ opened, the syringe is filled with the methylene-blue solution, b is then closed, c opened, and a definite quantity of the solution injected into the system. The time from the beginning of in- jection till the appearance of the blue at G is measured with thestop-watcti. due to increased activity of the heart without change in the calibre of the bloodvessels. Next, leaving the bottle in its present position, diminish the outflow by tightening the clamp ; the circulation-time will be increased. This corresponds to an increase of blood- pressure due to diminution in the calibre of the small arteries. {b) Fill the syringe with methylene-blue solution (0*2 per cent, in normal saline), as in {a). Keep the solution warmed to 40° C. by 158 A MANUAL OF PHYSIOLOGY. immersing the small beaker containing it in a water-bath, or heating over a bunsen with a small flame. Weigh a rabbit, and inject f gramme chloral into the rectum. Fasten it on a holder, back downwards (Fig. 36, p. 104). Clip off the hair on the front of the neck, and after giving ether if the animal shows the least sign of pain, make an incision i^- inches long in the middle line, beginning a little way below the cricoid cartilage. Reflect the skin and isolate the external jugular vein, which is quite superficial. Carefully separate about | inch of the vein from the surrounding tissue, and pass two ligatures under it, but do not tie them. Compress the vein with a pair of bulldog forceps between the heart and the ligatures. Now tie the uppermost of the two ligatures (that next the head), but only put a single loose loop on the other. The piece of vein between the upper ligature and the bulldog is now dis- tended with blood. With fine-pointed scissors make a small slit in the vein, taking great care not to divide it completely, and insert the cannula, previously filled with normal saline, which is retained by means of a pair of bulldog forceps on the short piece of india- rubber tubing attached to it. Tie the loose ligature firmly over the neck of the cannula. Expose the carotid on the other side, isolate it for f inch, clear it carefully from its sheath, slip under it a strip of thin sheet indiarubber, and between this and the artery a little piece of white glazed paper. Connect the cannula in the jugular with the T-piece attached to the syringe. Care must be taken that no air remains in the cannula or its connecting tube, as an animal not unfrequently dies instantaneously when a bubble of air is injected into the right heart. Now take off the bulldog from the vein, and make a series of observations on the pulmonary circulation-time. ^I'he animal must be so placed that a good light falls on the carotid. If necessary, the light of a gas-flame may be concentrated on it by a lens. The student holds the stop-watch in one hand, and injects a measured quantity of the methylene-blue solution with the other. Uniformity in the quantity injected is secured by fastening on the piston of the syringe a screw-clamp, which stops the piston at the desired point. The observation consists in setting off the watch at the moment when injection begins and stopping it when the blue appears in the carotid. After each injection the screw-clamp or pinchcock on the tube con- nected with the cannula must be tightened, the other opened, and the syringe refilled. Creat care must be taken never to open the two clamps at the same time, as in that case blood may regurgitate through the jugular and fill the syringe, or methylene blue may be sucked into the circulation. As many observations as possible should be taken, and the mean determined. The circulation-time observed is approximately that of the lesser circulation, the time taken by the blood to pass from the left ventricle to the carotid being negligable. Autopsy. — Observe particularly the state of the lungs, whether the bladder is distended or not, and whether any of the serous cavities or the intestines contain much liquid ; so as to determine, if possible, by what channel the water injected into the blood may have been PRACTICAL EXERCISES. 159 eliminated. The specific gravity of the blood may also be tested at the beginning and end of the experiment. 19. SphygmograpMc Tracings. — Attach a Marey's sphygmograph (Fig. 22, p. 71) to the arm. Fasten a smoked paper on the plate D. Apply the pad C of the sphygmograph to the wrist over the point where the pulse of the radial artery can be most distinctly felt. Adjust the pressure by moving the screw G. The writing-point of the lever E will rise and fall with every pulse-beat. When everything is satisfactorily arranged, set off the clockwork which moves the plate D, and a pulse-tracing will be obtained. Study the changes which can be produced in the form of the pulse curve — [a) by raising the arm above the head and letting it hang at the side, {h) by com- pressing the brachial artery at the bend of the elbow, {c) by altering the pressure of the pad. Varnish the tracings after marking on them the conditions under which they were obtained. 20. Plethysmographic Tracings.--Connect the vessel C (Fig. t^i^ p. 96) with B, place the arm in it, and adjust the indiarubber band to make a watertight connection. Fill C with water at body tem- perature. Adjust a writing-point carried by the float A to write on a drum, and close the upper tubulure of C with a cork. The quantity of blood in the arm is increased with every systole of the left ventricle, diminished in diastole. The float will therefore rise when the ventricle contracts, and sink when it relaxes. Or C may be connected by an indiarubber tube with a recording tambour writing on the drum. Adjust a time-marker to write half or quarter seconds. Mark and varnish the tracings. CHAPTER II I. RESPIRATION. Respiration in its widest sense is the sum total of the processes by which the ultimate elements of the body gain the oxygen they require, and get rid of the carbonic acid they produce. Comparative. — In a unicellular organism no special mechanism of respiration is needed ; the oxygen diffuses in, and the carbonic acid diffuses out, through the general surface. The simple wants of such multicellular animals as the coelenterates, the group to which the sea anemone belongs, are also supplied by diffusion through the ectoderm from and into the surrounding water, and through the endoderm from and into the contents of the body-cavity and its ramifications. But in animals of more complex structure special arrangements become necessary, and respiration is broken up into two stages : (i) external respiration, an interchange between the air or water and a circulating medium or blood as it passes through richly vascular skin, gills, tracheae, or lungs ; and (2) internal respiration, an interchange between the blood, or lymph, and the cells. In the lower kinds of worms respiration goes on solely through the skin, under which plexuses of bloodvessels often exist, but in some higher worms there are special vascular appendages that play the part of gills. The Crustacea also possess gills, while in the other arthro- poda respiration is carried on either by the general surface of the body (in some low forms), or more commonly by means of tracheae, or branched tubes surrounded by blood spaces and communicating externally with the air and internally by their finest twigs with the individual cells. Most of the mollusca breathe by gills, but a few only by the skin. Among vertebrates the fishes and larval amphibians breathe by gills, but most adult amphibians have lungs. The skin, too, in such animals as the frog has a very important respiratory function, more of the gaseous exchange taking place through it than through the lungs. One small group of fishes, the dipnoi, has the peculiarity of RESPIRATION. i6l possessing both gills and a kind of lungs, the swim-bladder being surrounded with a plexus of bloodvessels and taking on a respiratory function. In all the higher vertebrates the respiration is carried on by lungs ; the trifling amount of gaseous interchange which can possibly take place through the skin is not worth taking into account. The lungs are to be regarded as developed from outgrowths of the alimentary canal, beginning near the mouth. The object of all special respiratory arrangements being, in the. first instance, to facilitate the gaseous exchange between the sur- rounding medium (air or water) and the blood, a prime necessity of a respiratory organ, be it skin, gill, trachea, or lung, is a free supply of blood, in vessels so fine and thin that diffusion readily takes place into them and out of them. But a free supply of blood would be of no avail if the medium to which the blood gave up its carbonic acid and from which it drew its oxygen was not bemg constantly and sufficiently renewed. Sometimes the natural currents of the water or the air are of themselves sufficient to secure this renewal ; in other cases, artificial currents are set up by cilia, or special bailing organs, like the scapho- gnathites of the lobster. In all the higher animals active move- ments, by which air or water is brought into contact with the respira- tory surfaces, are necessary ; and it is possible that such movements take place even in the trachea of insects and other air-breathing arthropoda. Fishes, by rhythmical swallowing movements, take in water through the mouth and pass it over the gills and out by the gill-slits, while the frog distends its lungs by swallowing air. Physiological Anatomy of the Respiratory Apparatus. — In man the respiratory apparatus consists of a tube (the trachea) widened at its upper part into the larynx, which contains the special mechanism of voice, and communicates through the nose or mouth with the external air. Below, the trachea divides dendritically into innumerable branches, the ultimate divisions of which are called bronchioles. Each bronchiole breaks up into several wider passages, or infundibula, the walls of which are everywhere pitted with recesses or alcoves, called alveoli. The trachea and larger bronchi are strengthened by hyaline cartilage in the form of incomplete rings, connected behind by non-striped muscular fibres, which also exist in the intervals between the rings. The middle-sized bronchi within the lungs have the cartilage in the form of detached pieces in the outer portion of the wall, while nearer the lumen lies a complete ring of non-striped muscle. II 1 62 A MANUAL OF PHYSIOLOGY. In the bronchioles, no cartilage is present, but the circu- larly-arranged muscular fibres still persist, and also form a thin layer in the infundibula. In the air-cells, or alveoli, however, there are no muscular fibres. Their walls consist essentially of a network of elastic fibres, continuous with a similar layer in the infundibula and bronchioles, and covered on the side next the lumen by a single layer of large, clear epithelial scales, with here and there a few smaller and more granular polyhedral cells. From the larynx to the bronchioles the mucous mem- brane is ciliated on its free surface, the cilia lashing upwards so as to move the secretion towards the larynx and mouth. In the infundibula the ciliated epithelium begins to disappear, and is absent from the alveoli. Part of the nasal cavity and the upper part of the pharynx are also lined with ciliated epithelium. Mucous glands are present in abundance in the upper portions of the respiratory passages, but disappear in the smaller bronchi. Blood-supply of the Lungs. — The quantity of blood traversing the lungs bears no proportion to the amount required for their actual nourishment. Small, however, as this latter quantity is, it cannot apparently be derived from the vitiated blood of the right ventricle, but is obtained directly from the aortic system by the bronchial arteries. These are dis- tributed with the bronchi, which they supply as well as the connective-tissue of the interlobular septa running through the substance of the lung, the pleura lining it and the walls of the large bloodvessels. Most of the blood from the bronchial arteries is returned by the bronchial veins into the systemic venous system, but some of it finds its way by anastomoses into the pulmonary veins. The branches of the pulmonary artery are also distributed with the bronchi, and break up into a dense capillary net- work around the alveoli. From the capillaries veins arise which, gradually uniting, form the large pulmonary veins that pour their blood into the left auricle. The same quantity of blood must, on the whole, pass per unit of time through the lesser as throus:h the greater circu- RE SPINA TION. 163 lation, otherwise equilibrium could not exist, and blood would accumulate either in the lungs or in the systemic vessels. But it does not follow that at each heart-beat the output of the two ventricles is exactly equal. If, indeed, the capacity of the lesser circulation were constant, the quantity driven out at one systole by the right ventricle would be the same as that ejected at the next by the left ventricle. But it is known that the capacity of the pulmonary vessels is altered by the movements of respiration and probably in other ways, so that it is only on the average of a number of beats that the output of the two ventricles can be supposed equal. The time required by a given small portion of blood, e.g. by a single blood-corpuscle, to complete the round of the lesser circulation, is much less than the average time needed to complete the systemic circulation. In the rabbit the ratio is probably about i : 5. Since all the blood in a vascular tract must pass out of it in a period equal to the circulation time, the average quantity of blood in the lungs and right heart of a rabbit must be about one-fifth of that in the systemic vessels. On the assumption that the same proportion holds for a inan, not less than three-quarters of a kilo out of the five kilos of blood in a seventy kilo man must be contained in the lesser circulation, and four kilos and a quarter in the greater. This corresponds sufficiently well with calculations from other data. For example, the average weight of the lungs in three persons, executed by beheading, was 457 grm. (Gluge). The average weight of the lungs in a great number of persons who had died a natural death was 1024 grm. (Juncker). The weight of the pulmonary tissue alone in the first set of cases must be less than 457 grm., for the lungs of a person who has bled to death are never bloodless. In a dog killed by bleeding from the carotid one-quarter of the weight of the lungs consisted of blood. Assuming the same pro- portion for the decapitated individuals, we get 343 grm. as the net weight of the blood-free lungs. Deducting this from 1024 grm., we arrive at 681 grm. as the average quantity of blood in the lungs. Adding to this the quantity i64 A MANUAL OF PHYSIOLOGY. in the right side of the heart (p. io6), we get, in round numbers, 750 grm. as the amount in the lesser circulation. It is true that in the living body the conditions are not the same as after death ; but it is probable that in a large number of cases taken at random the differences would be approximately equalised. At any rate, it is interesting that from data so different we should reach results so accordant. It has been further calculated — but here the data are much less certain — that the total area of the alveolar surface of the lungs of a man is 200 square metres, of which 150 square metres are occupied by capillaries. The average thickness of this immense sheet of blood has been reckoned to be equal to the diameter of a red blood-cor- puscle, or, say, 7'5/i.. This would give 1,125 c.c. as the quantity of blood in the lungs, which is doubtless somewhat too high an estimate. If we take the total circulation time as 75 seconds (p. 105), = 240 kilos of blood will pass through the lungs in an hour, or 5,760 kilos (say, 5,000 litres) in twenty-four hours. This would fill a cubical tank in which the man could just stand upright with the lid closed. Mechanical Phenomena of Respiration. The lungs are enclosed in an air-tight box, the thorax ; or it may be said with equal truth that they form part of the wall of the thoracic cavity, and the part which has by far the greatest capacity of adjustment. The alveolar surface of the lungs is in contact with the air ; the space enclosed between their pleural surface, the diaphragm and the walls of the chest is the thoracic cavity. This is sub- divided into two lateral (pleural) sacs and a mesial space (the mediastinum), which is partially filled up by the heart and great bloodvessels. The external surface of the chest- wall and the alveolar surface of the lungs are subjected to the pressure of the atmosphere, to which the pressure in the thoracic cavity (intra-thoracic pressure) would be exactly equal if its boundaries were perfectly yielding. But in RESPIRA TION. 165 reality the intra-thoracic pressure is always normally some- thing less than this. For even the lungs, the least rigid part of the boundary, oppose a certain resistance to distension, and so hold off, as it were, from the thoracic cavity a portion of the alveolar pressure ; and in any given position of the chest the intra-thoracic pressure is equal to the atmospheric pressure minus this elastic tension of the lungs. Since the lungs are very distensible, and, further, since blood can pass more freely into the chest when the pressure in it is reduced, there cannot in any position of the chest- walls exist an actual thoracic cavity. Wherever such a cavity would tend to form the lungs are pressed in and fill up every space ; and this goes on until the intra-thoracic pressure, plus the elastic tension of the lungs, is equal to the pressure of the air in the pulmonary alveoli. Whenever, therefore, the movements of the chest-walls tend to diminish the intra-thoracic pressure, and to increase the capacity of T is a bottle from which the bottom has been removed ; D a flexible and elastic membrane tied on the bottle, and capable of being pulled out by the string S so as to increase the capacity of the bottle. L is a thin elastic bag representing the lungs. It communicates with the external air by a glass tube fitted airtight through a cork in the neck of the bottle. When D is drawn down, the pressure of the external air causes L to expand. V/hen the string is let go, L contracts again, in virtue of its elasticity. Fig. 60.— Scheme to Illustk.-\te the Movement.s of the Lungs in the Chest (.after Rutherford). the thoracic cavity, the lungs must be distended, and air must enter them. Whenever the movements of the chest- walls tend to increase the intra-thoracic pressure, and to diminish the capacity of the thoracic cavity, the lungs, thanks to their elasticity, contract so as still exactly to fill up the available space, and air is forced out of them. In inspiration the first happens, in expiration the second. In inspiration the capacity of the chest is increased (i) by the contraction of the diaphragm, which closes it below. In i66 A MANUAL OF PHYSIOLOGY. the state of relaxation this muscle forms a sort of l^at dome with the convexity upwards. It is composed of a central tendon with a ring of muscle round it. When the muscular fibres contract the whole diaphragm is somewhat flattened, and, especially at the position of the muscular ring, a wedge- shaped depression is formed. In this way the vertical diameter of the thorax is lengthened, and the lungs, keeping always in contact with the diaphragm, are elongated. The apex of the lung probably moves very slightly, or not at all. (2) The ribs and the lower part of the sternum are elevated. The elevation of the ribs is caused (a) by the levatores costarum muscles, w^hich pass from them to the transverse processes of the vertebrae above ; (b) by the external intercostal muscles, which fill up the space between adjacent ribs from the necks to the junction of the bony ribs with the costal cartilages ; and (c) by the inter-cartilaginous part, at least, and possibly by the whole, of the internal intercostals. The scalene muscles may be felt to be tense in a lean person during inspiration. Their function is to fix the first and second ribs (scalenus anticus and medius, the first ; scalenus posticus, the second rib), and so to afford a fixed line for the intercostals to work from on the lower ribs. Since the ribs slant downwards and forwards, they raise the sternum when they are elevated, and an increase in the antero-posterior diameter of the chest takes place. This is favoured by the fact that the length of the ribs increases from above downwards from the first to the eighth. There is a certain amount of twisting of the ribs during their elevation, so that the lower edge is directed more to the side than before ; and this, along with their change of position, causes an increase in the lateral diameter of the chest. In normal expiration no muscles are called into action. The muscles which have brought the chest-wall into the inspiratory position cease to contract, and, in virtue of their elasticity and weight, the walls of the chest and the dia- phragm return to their old position. The elasticity of the lungs comes also into play, and they shrink until their tension RESPIRATIOiY. 167 is equal to the difference between the atmospheric and the intra-thoracic pressure. In forced inspiration all the muscles which can elevate the ribs may be thrown into contraction, as well as other muscles which give these fixed points to act from. During a paroxysm of asthma, for example, the patient may grasp the back of a chair with his hands, so as to fix the arms and shoulders and allow the pectoral and serratus magnus to raise the ribs. Similarly in forced expiration all the muscles are used which can depress the ribs, or increase the intra-abdominal pressure and push up the diaphragm. Even in ordinary respiration the larynx moves, rising in expiration and sinking in inspiration. In forced breathing the glottis widens with each inspiration, particularly its posterior portion (glottis respiratoria). The alse nasi also move in forced respiration, and in some people in ordinary breathing. Hitherto we have always spoken of the pressure of the air in the lungs, the intra-alveolar pressure, as being that of the atmosphere. This is only strictly the case when the chest-walls, and therefore the lungs, have ceased to move. While expansion is going on, the intra-alveolar pressure (and the pressure in the air-passages generally) is less than that of the atmosphere ; while contraction is going on, it is more. In both cases the farther a point is from the external air, the greater is the difference. By percussing the chest, and marking the limits of the lungs in the expirator_v and inspiratory position, it may be demonstrated in the human subject that in inspiration the lungs enlarge from above downwards, and also from side to side, the inner edges moving nearer to the middle line, and more of the left lung coming between the heart and the anterior wall of the chest. By means of auscultation — that is, listening over the chest either directly with the ear, or, much better, with a stetho- scope— changes in the lungs or bronchi may be recognised and localized. The sound given over the whole of the general substance of the lung in the normal state is the so-called vesicular sound, a soft breezy murmur, which has 1 68 A MANUAL OF PHYSIOLOGY. been compared to the rustling of the wind through distant trees. It is only heard in health during inspiration, and the very beginning of expiration, and is louder in children than in adults. Around the larger bronchi and the trachea a blowing sound is heard. Normally this is not recognised over the greater portion of the lung, but in certain diseases in which the alveoli are filled up with exudation, this bronchial or tubular breathing may be heard over a large area, the vesicular sound being now suppressed, and the bronchial sound being better conducted by the consolidated tissue than by the portions of the lung that still contain air. Fig. 6i.— -Scheme of Tambour (Brondgeest's) for Recording Respiratory Movements. C, a metal capsule connected airtight with B, A, two caoutchouc membranes, the chamber formed by which can be inflated by means of the tube and stopcock E. The tube D connects the space H with a registering tambour provided with a lever. The membrane A is applied to the chest, round which the ine.xtensible strings F are tied. At every expansion of the chest the pressure in H is increased, and the increase of pressure is transmitted to the registering tambour. The mechanical changes which occur in respiration may be studied : (i) By registering the movements of a single point, or the variations in a single circumference, of the boundary of the thoracic cavity. In animals a graphic record of the move- ments of a point of the diaphragm may be obtained by placing the end of a lever between its lower surface and the liver, through an incision in the abdominal wall (Kronecker). In man changes in the circumference of the chest at any level can be recorded by means of a tambour so adjusted that expansion of the chest increases the pressure of the air RE SPINA TION. 169 in the tambour. This tambour is connected with another (recording tambour) provided with a writing lever (Marey's pneumograph, Sanderson's stethometer, Brondgeest's pan- sphygmograph). (Fig. 61.) (2) By recording the changes of pressure produced in the air-passages by the respiratory movements. This can be done by connecting a cannula in the trachea of an animal with a recording tambour in the manner described in the Practical Exercises, p. 230. The changes of pressure may be measured by connecting a manometer with the trachea, or in man with the nostril. (3) By recording the changes of pressure which occur in the thoracic cavity during respiration. Fig. 62. The upper 'racing is a record of tlie respiratory movements in a rabbit, taken with Kronecker's iever between the diaphragm and liver. The lower curve i.s a blood- pressure tracing showing large oscillations (like Traube-Hering waves). E, expiration ; I, inspiration. Time trace, seconds. The animal was imder the influence of gelsemin. When the respiratory movements are studied in any of these ways it is found that there is practically no pause between the end of inspiration and the beginning of expira- ation, and that expiration takes somewhat longer time than inspiration, the ratio varying from 7 : 6 to 3 : 2, according to age, sex, and other circumstances. The frequency of respiration is by no means constant even in health. The mere thinking about it will modify it. In the adult 15 to 20 respirations per minute may be I70 A MANUAL OF PHYSIOLOGY. taken as about the normal. In young children the frequency may be twice as great (new-born child, 40 to 50 ; child from I to 5 years old, 20 to 30 per minute). It is greater in a female than in a male of the same age. A rise of temper- ature increases it, and this is probably one of the causes of the increased rate of respiration in fever ; 150 respirations per minute have been seen in a dog with a high temperature. Sudden cooling of the skin, exercise, and various emotional states increase the rate, and sleep diminishes it. The will can alter the frequency and depth of respiration for a time, and even stop it altogether, but in about a minute the desire to breathe becomes imperative. Cato's assertion that he could kill himself at any time ' merely by holding his breath, is only a proof that he was a better philosopher than physiologist. In animals the rate can be greatly affected by section and stimulation of certain nerves ; but to this we shall return when we come to consider the general subject of the influence of nerves on respiration. Many drugs affect the respiration ; for instance, pituri and nicotin cause, in various animals, a quickening and deepening at first, followed, if the dose has been large, by slowing and ultimate cessation. There is generally a fairly constant ratio (i to 4 or i to 5 in man) between the frequency of respiration and the rate of the heart. Types of Respiration. — Although increase in the capacity of the thorax is essential for inspiration, this is not brought about in all mammals, nor even in women and men, in the same way. The rabbit, in its normal breathing, uses only the dia- phragm in inspiration, and the same muscle, along with some of the muscles of the abdominal wall (external oblique), in expiration. The ribs remain at rest. This is a perfect type oi diapliragmatic or abdominal breathing. Women use the ribs more than the diaphragm. They have, therefore, the costal or thoracic type of respiration, while men incline more to the abdominal type. In ab- dominal respiration the movements of inspiration commence at the diaphragm, and spread to the lower ribs and the RESPIRA TION. 171 lowest portion of the sternum. In costal respiration the upper ribs begin the movement, and are followed by the abdomen. This is the ordinary mode in women (Hutchin- son). In full-blooded North American Indians abdominal breathing is most common among the women, and the same is true of Chinese women (Mays and Kellogg, quoted by Sewall). It is, therefore, probable that the predominance of the costal type among the women of European races is not connected with child-bearing, but with dress. In forced respiration, when the need for air is urgent, costal breathing always becomes prominent, for by eleva- FiG. 63.— Diagram of Spirometer. A, vessel filled with water. B, glass cylinder with scale C, swung on pulleys and counterpoised by weights W. D, tube for breathing through. tion of the ribs the capacity of the chest can be much more enlarged than by any movements of the diaphragm. The total quantity of air expired, or, what comes to the same thing, the alteration in the capacity of the chest during expiration, can be measured by means of a spirometer, which consists of an inverted graduated glass bell dipping by its open mouth into water and balanced by weights. The vessel is sunk till it is full of water, the air being allowed to escape by a cock. The expired air is now permitted to 172 A MANUAL OF PHYSIOLOGY. enter it through a tube, and displaces some of the water. The spirometer is adjusted so that the level of the water inside and outside is the same, and then the volume of air contained in it is read off. This gives the volume of the expired air at atmospheric pressure. Similarly, by breathing air from the spirometer the amount inspired can be measured. About 500 c.c. of air are taken in and given out at each respiration in quiet breathing. This is called tidal air. It amounts to 35 pounds by weight in 24 hours, or enough to fill, at atmospheric pressure, a cubical box with a side of 8 feet. With the deepest possible inspiration 2,000 c.c. more can be taken in ; this is called complemental air. By a forced expira- tion 1,500 c.c. can be expelled besides the tidal air; and to this quantity the name of supplemental or reserve air has been l/ital Cajmcity I CojnpU mental aii- Tidal air Supplemental air Residual air Fig. 64. — Diagram to Illustrate the Relative Amount of Complemental, Tidal, Supplemental, and Residual Air. given. After the deepest expiration there always remain about 700 or 800 c.c. of air in the lungs, and this is called the residual air. After a normal expiration following a normal inspiration there remains in the lungs stationary air to the amount of about 2,500 c.c. The residual air may be measured by causing a person, starting immediately after the deepest possible expiration, to breathe out and in several times into a vessel (a spirometer) filled with hydrogen, till it can be assumed that the hydrogen and the residue of air in the lungs have been completely mixed. Knowing the quantity of hydrogen originally contained in the vessel, we can calculate from the percentage at the end of the experiment the quantity of air with which it has been mixed, that is, the residual air (Davy). Let V be the quantity of hydrogen in the spirometer at first, and / the percentage amount in it at the end of the experiment. Let x be the volume of residual air in the lungs at the beginning. RESPIRA TION. 1 73 Then, since the quantity of hydrogen remains unchanged after the mixture, ^ (jc + V) = V, 100 . ^,_V(ioo-/) p ' Suppose V = 4,oooc.c., and / = 85 per cent., 12,000 , we get x= = about 705 c.c. 17. But some carbonic acid would be given off by the lungs, and some oxygen, and perhaps hydrogen, absorbed, during the experiment, and therefore slight corrections might have to be made. The coefficient of ventilation, that is, the ratio of the quantity of air taken in at each mspiration to the quantity already in the lungs, has been estimated at about \ or ,}. The term vital or respiratory capacity is applied to the quantity of air which can be expelled by the deepest expira- tion following the deepest inspiration, and amounts in an adult of average height to 3,500 or 4,000 c.c. The maximum quantity of air which the lungs can contain is evidently equal to vital capacity plus residual air. At one time the vital capacity was thought to be capable of affording valuable information in the diagnosis of chest disease ; but little stress is now laid upon it, as it varies from so many causes. It is greater in mountaineers than in the inhabitants of lowland plains. It is evident from the figures we have given that in ordinary breathing only a small proportion of the air in the lungs comes in direct at each inspiration from the atmosphere, and only a small proportion escapes into the atmosphere at each expiration. The greater part of the air in the lungs is simply moved a little farther from the upper respiratory passages, or a little nearer them ; and fresh oxygen reaches the alveoli, as carbonic acid leaves them, mainly by diffusion, aided by convection currents due to inequalities of temperature, and to the churning which the alternate expansion and shrinking of the lungs, and the pulsations of their arteries, must produce. But that some of the tidal air strikes right down to the alveoli, is evident enough. For the respiratory ' dead space ' — that is, the capacity of the upper air passages and the bronchial tre 174 A MANUAL OF PHYSIOLOGY. down to the infundibula — is onlv 140 cc, or one-third of the amount of the tidal air. (Zuntz, Loewy.) The immense extent of the pulmonary surface, and the extreme thinness of the layer of blood in the capillaries of the lungs, facilitate the interchange between the gases of the blood and the gases of the alveoli. Respiratory Pressure. — As we have already remarked, the pressure in the alveoli and air passages is less than that of the atmosphere while the inspiratory movement is going on, greater than that of the atmosphere during the expira- tory movement, and equal to that of the atmosphere when the chest-walls are at rest. When the external air-passages are closed, e.g., by connecting a manometer with the mouth and pinching the nostrils, or with one nostril, the other and the mouth being closed, the greatest possible variations of pressure are produced. In the deepest inspiration under these conditions a negative pressure of about 75 mm. of Hg {i.e., a pressure less than that of the atmosphere by this amount) has been found, and in deep expiration a positive pressure of 100 mm. of Hg {i.e., a pressure greater than that of the atmosphere by this amount). (Bonders.) But with ordinary respiratory movements, the variations of pressure as measured by this method do not exceed 5 to 10 mm. of Hg above or below the pressure of the atmosphere. When the external openings are not obstructed, as, for example, when the lateral pressure is taken in the trachea of an animal by means of a cannula with a side tube con- nected with a manometer, still smaller values have been found (2-3 mm. of Hg as the positive expiratory pressure, and I mm. as the negative inspiratory pressure in dogs). But since the respiratory passages are abruptly narrowed at the glottis, the variations of pressure must be much greater below than above it. Intra-Thoracic Pressure. — This is the pressure in the cavity of the chest — in the pleural sacs, for instance, or within the pericardium. It has been measured, in animals, by attach- ing a trocar, pushed through the pericardium, or a tube passed into the oesophagus, with a manometer. In the deepest expiration the lungs are never completely RESPIRATION. 175 collapsed ; their elastic fibres are still stretched ; and the tension of these acts in the opposite direction to the external atmospheric pressure, and diminishes by its amount the pressure inside the thoracic cavity. In the dead body Bonders measured the value of this tension, and therefore of the negative pressure of the thorax, by tying a mano- meter into the trachea, and then causing the lungs to collapse by opening the chest. It varied from 7"5 mm. of Hg in the expiratory position to 9 mm. in the inspiratory. With deep inspiration in the living rabbit it may amount, how- ever, to 20 mm. of Hg (Rosenthal), and in man to as much as 30 mm. The reason why the lungs collapse when the chest is opened is that the pressure is now equal on the pleural and alveolar surfaces, being in both cases that of the atmosphere. There is therefore nothing to oppose the elasticity of the lungs, which tends to contract them. So long as the chest is unopened the pressure on the pleural surface of the lungs is less than that on the alveolar surface, and the elastic tension can only cause them to shrink until it just balances this difference. In intra-uterine life, and in stillborn children who have never breathed, the lungs are completely collapsed (atelectic), and there is no negative intra-thoracic pressure. They are kept in this condition by adhesion of the walls of the bronchioles and alveoli. If the lungs have been once inflated, this adhesion ceases to act, and they never com- pletely collapse again. Relation of Respiration to the Nervous System. — The respira- tory movements are entirely dependent on the nervous system ; and the ' centre ' which presides over them is situated in the spinal bulb. It is a bilateral centre — that is, it has two functionally symmetrical halves, one on each side of the middle line ; and each of these halves seems to have to do more particularly with the respiratory muscles of its own side, for destruction of one-half of the spinal bulb causes paralysis of respiration only on that side. Anatomically the respiratory centre has not been sharply localized ; but it lies higher than the vaso-motor centre. It is brought into 176 A MANUAL OF PHYSIOLOGY. relation with the muscles of respiration by efferent nerves. The phrenic nerves to the diaphragm, and the intercostal nerves to the muscles which elevate the ribs, are the most important of those concerned in ordinary breathing. It is further related to afferent nerves, of which the most in- fluential is the vagus (particularly its pulmonary fibres), with its superior laryngeal branch. But almost any afferent nerve may powerfully affect the respiratory centre ; and it is also influenced by fibres passing to it from the higher parts of the central nervous system. Section of the spinal cord in animals above the origin of the phrenic nerves causes complete paralysis of respiration and consequent death ; and in man fracture of an}' of the four upper cervical vertebras is, as a rule, instantly fatal. But in one case respiration was carried on, and life main- tained for thirty minutes, merely by the contraction of the muscles of the neck and shoulders in a man entirely para- lysed below this level (Bell). Section of the cord just below the origin of the phrenics leaves the diaphragm working, although the other respiratory muscles are paralyzed. A case has been recorded of a man in whom, from disease of the spine in the lower cervical region, all the ribs became completely immovable. He was able to lead an active life, and to carry on his business, although he breathed entirely by his diaphragm and abdominal muscles (Hilton). Section of both phrenics paralyzes the diaphragm, but respiration still goes on by means of the muscles which act upon the ribs. The phrenic nuclei in the two halves of the cord are connected across the middle line. For when a hemisection of the cord is made between this level and the respiratory centre in the medulla respiratory impulses are still able to reach both phrenic nerves. In some animals both halves of the diaphragm go on contracting. But when, as usually happens, this is not the case, and the diaphragm on the side of the hemisection has ceased to act, it at once begins to contract again when the opposite phrenic nerve is cut, and the respiratory impulse, descending from the bulb, is blocked out from the direct, and forced to follow the crossed path. It has been shown that the cross- RESPIRATION. i-jj ing takes place at the level of the phrenic nuclei, and nowhere else (Porter). When one vagus is divided there is little or no change in the respiratory movements. Half an inch of one vagus nerve has been excised in removing a tumour, and the patient showed no symptoms whatever (Billroth), But section of both vagi generally (not invariably) causes re- spiration to become for a time much deeper and slower, the one change just compensating the other, so that the total amount of air taken in and given out, and the amount of carbonic acid eliminated, are not altered. Gad has shown that the effect is really due to the loss of impulses that normally ascend the vagi, not to any irritation of the cut ends. For a nerve can be frozen without exciting it ; and when a portion of each vagus is frozen the respiration is affected in precisely the same way as when the nerves are divided. A similar change follows the blocking of the paths connect- ing the respiratory centre with the brain above, by injection of paraffin wax into the common or internal carotid. The bloodvessels supplying the nerve-fibres which connect the respiratory centre with the brain may in this way be closed by artificial emboli. The nerves lose their function, as if they had been cut ; no impulses now reach the respiratory centre from above ; and the respiration becomes markedly slowed and deepened, just as happens when the vagi are divided. Where only the vagus or these ' higher paths,' but not both, are cut off, the respiration remains regular, although deep, and in course of time tends to resume its original type. But when both paths are cut, the character of the respiration is entirely changed ; periods of rapid and spas- modic breathing alternate with periods of complete cessation, till the animal dies (Marckwald). From these facts it appears that the periodic automatic discharges of the respiratory centre are being continually controlled and modified by impulses passing up the vagus or down from the brain, but especially up the vagus. When the vagus is severed the control of the higher paths becomes more complete, and is sufficient still to keep the breathing 12 178 A MANUAL OF PHYSIOLOGY. regular. When the higher paths are cut off, the vagus of itself is able to regulate the discharge. But when both are gone the respiratory centre, freed from control, passes into a condition of alternate spasm and exhaustion. The continuous excitation of the regulating vagus fibres is brought about either by mechanical stimulation of the nerve- endings in the lungs, due to the alternate stretching and shrinking, or to chemical stimulation depending on the state of the blood. Gentle excitation of the central end of the cut vagus below the origin of the superior laryngeal causes quickening of respiration ; stronger stimulation causes arrest of respiration in the inspiratory phase. These statements tlG. 65. — Kl.bPlKATOKY 'iKAClNGb (DoG A, normal; B, effect of stimulation of the central end of tlie vagus; C, effect of section of both vagi. (Tracing taken with ariangement shown in Fig. 81.) Time- iracing marks seconds. are based on the usual effects of excitation of the nerve with induction shocks. But the result seems to depend to some extent on the nature of the stimuli used. For chemical stimulation {e.g., with a solution of potassium chloride) and the closure of an ascending voltaic current {i.e., a current passing towards the head in the nerve) always bring about slowing of the respiratory movements or expi- ratory standstill. Stimulation of the central end of the cut superior laryn- geal, if not too strong, causes slowing of the respiration ; if strong, arrest of respiration in expiratory standstill. RESPIRATION. 179 The same effect may be produced by stimulation of the vagus trunk above the point where it is joined by the superior laryngeal. These facts may be readily demon- strated by opening the abdomen in a rabbit, and observing the lungs through the thin diaphragm (Gad). They have been more than once unintentionally illustrated on man. In one case the left vagus trunk was included in a ligature with the common carotid. The respiratory movements immediately stopped, the pulse was slowed, and death occurred in 30 minutes (Rouse). The superior laryngeal fibres do not appear to be constantly in action, as section of both nerves has no effect on respiration. Any source of irritation in the larynx may stimulate these fibres and produce a cough, which may be also caused by irritation of the pulmonary fibres of the vagus. The cutaneous nerves, and especially those of the face (fifth nerve), abdomen and chest, have a marked influence on respiration. Cold suddenly applied to the skin gene- rally, but not always, accelerates the respiratory movements. The respiratory centre is greatly affected by the quality of the blood which circulates through it. It is stimulated by blood deficient in oxygen, the actual stimulating sub- stance being, perhaps, an easily oxidizable body which rapidly disappears from properly oxygenated blood (Pfliiger). That the poorly oxygenated blood acts directly on the spinal bulb, is supposed to be shown by the fact that want of oxygen still produces dyspnoea (p. 180) when the brain has been cut away above it, the cord severed below the origin of the phrenics, and all nerves, except the latter, connected with the region between the two planes of sections divided.* The common doctrine, that excess of carbonic acid in the blood has less effect on the respiratory centre than deficiency of oxygen, is not in accordance with the recent work of Haldane and Smith. These authors believe that excess of carbonic acid is the important factor in the production of the hyperpnoea caused by breathing air vitiated by respiration. * The conclusion is doubtless correct, but this experiment is not decisive. For the phrenic nerves themselves contain afferent fibres, through which the respiratory centre might have been affected. i8o A MANUAL OF PHYSIOLOGY. Be this as it may, when the gaseous interchange from any cause becomes insufficient, the respiratory movements are exaggerated, and ultimately every muscle which can directly or indirectly act upon the chest-walls is called into play in the struggle to pass more air into and out of the lungs. To a lesser and greater degree of this exaggeration of breathing the terms Hyperpncea and Dyspncea have been respectively applied. If the gaseous interchange remains insufficient, or is altogether prevented, asphyxia or suffocation sets in. Sometimes in man impending asphyxia from loss of function by a part of the lungs, as in pneumonia, may be warded off by inhalations of oxygen. Increase in the tem- perature of the blood circulating through the spinal bulb, as when the carotid arteries of a dog are laid on metal boxes through which hot water is kept flowing, also causes dyspnoea (heat-dyspncea). In man the increased temperature of the blood in fever is probably connected with the increase in the rate of respiration. The physiological opposite of dyspnoea is apncea. This condition may be produced in an animal by rapid artificial respiration. For some seconds, in a successful experiment, after the artificial respiration is stopped, the animal remains without breathing. The apnoeic state seems to be due partly to an excess of oxygen in the arterial blood or in the lungs, partly to some nervous effect produced through the vagi on the respiratory centre. Possibly the pulmonary nerve- endings of the vagi are affected mechanically by the inflation ; for rapid and repeated inflation of the lungs with hydrogen may cause apnoea (Traube). The venous blood in apncea is, if anything, poorer in oxygen than normal venous blood. Although the chief respiratory centre undoubtedly lies in the medulla oblongata, it appears that under certain condi- tions impulses to the respiratory m.uscles may originate in the spinal cord. Thus, in young mammals (kittens, puppies), especially when the excitability of the cord has been in- creased by strychnia, in birds and in alligators, movements, apparently respiratory, have been seen after destruction of the brain and spinal bulb. Effect of Chloroform on the Respiratory Centre. — The cause RESPIRA TION. l8i of the deaths from chloroform which, at rare intervals, startle the operating theatre of every great hospital where this anaesthetic is used, has been, on account of its extreme practical interest, the subject of prolonged discussion and experiment. Is it the heart that fails ? Or is it the respiration ? The answer of what is known as the ' Edin- burgh School ' is that the respiration (in physiological terms, the respiratory centre) is always first paralysed. Their golden rule of doctrine in chloroform administra- tion is, ' Watch the respiration ; the heart will take care of itself — a rule which, however, in 'Edinburgh' practice does not exclude careful observation of the pulse. This view, having the merit of simplicity, has been widely adopted. It has been lately upheld by a scientific commis- sion appointed by the Nizam of Hyderabad for the special purpose of investigating the question with the aid of modern physiological methods. But the conclusions of the Hydera- bad Commission, valuable as they are, seem to have been too absolutely drawn. For it has been shown by a number of observers (MacWilliam, Gaskell and Shore, etc.) that chloroform undoubtedly may paralyse the heart without affecting the respiration, and further, that the paralysis of the vaso-motor centre, and the consequent withdrawal of blood from the heart and brain to the dilated splanchnic area, may be an important factor in bringing about a fatal result (p. 86). A second table might therefore be added to the ' Edinburgh law' : 'Watch the breathing; watch the pulse. If the heart threatens to fail for want of blood, fill it by raising the legs and compressing the abdomen.' Cheyne-Stokes' Respiration is the name given to a peculiar type of breathing, marked by pauses of many seconds alternating with groups of respirations. In each group the movements gradually increase to a maximum amplitude, and then become gradually shallower again, till they cease for the next pause. The cause is unknown. The phenomenon is not peculiar to pathological conditions, although it often occurs in certain diseases of the brain, and although pressure on the spinal bulb may produce it. But it is also seen, more or less perfectly, in normal sleep, especially in children, and i82 A MANUAL OF PHYSIOLOGY. in morphia and chloral poisoning. A periodic change in the activity of the respiratory centre, corresponding to the change in the vaso-motor centre which is credited with the production of Traube-Hering oscillations in the blood- pressure (p. 136), has been suggested as the cause, but there is no certainty as to this. In frogs, Cheyne-Stokes' breathing has been observed as the result of interference with the circulation in the spinal bulb, ' drowning,' or ligature of the aorta, and also as a con- sequence of removal of the brain, or parts of it (hemispheres and optic thalami) (Langendorff, Sherrington, etc.). Section Pneumonia. — Alterations in the rhythm of respira- tion are not the only effects that follow division of both vagi. In certain animals, at least, this operation is incompatible with life. Changes of a pneumonic nature are set up in the lungs, and death occurs after an interval that varies with the nature of the animal. In the rabbit, as a rule, life is not prolonged for more than twenty-four hours (p. 232). The precise significance of the pulmonary lesion is obscure. But it would seem that paralysis of the laryngeal and oesophageal muscles, with the consequent entrance of food, foreign bodies, and perhaps bacteria, into the lungs, is re- sponsible to a great extent. And when only a partial palsy of the glottis is produced by dividing the right vagus below the origin of the recurrent laryngeal and the left, as usual, in the neck, pneumonia does not occur. It is impossible, however, to suppose that in any case the loss of two such nerves as the vagi, which supply so many important organs, should not of itself profoundly affect the whole animal economy. Peculiarly modified, but more or less normal respiratory acts are coughing, sneezing, yawning, sighing and hiccup. A cough is an abrupt expiration with open mouth, which forces open the previously closed glottis. It may be excited reflexly from the mucous membrane of the respiratory tract or stomach through the afferent fibres of the vagus, from the back of the tongue or mouth, and (by cold) from the skin. Sneezing is a violent expiration in which the air is chiefly expelled through the nose. It is usually excited reflexly RESPIRATION. 1S3 from the nasal mucous membrane through the branch of the fifth nerve which supphes it. Pressure on the course of the nasal nerve will often stop a sneeze. A bright light sometimes causes a sneeze, and so in some individuals does pressure on the supra-orbital nerve, when the skin over it is slightly inflamed. Yawnino^ is a prolonged and very deep inspiration, some- times accompanied with stretching of the arms and the whole body. It is a sign of mental or physical weariness. A ^igli is a long-drawn inspiration, followed by a deep e.xpiration. Hiccup is due to a spasmodic contraction of the diaphragm, which causes a sudden inspiration. The abrupt closure of the glottis cuts this short and gives rise to the characteristic sound. The following readings of the intervals between successive spasms were obtained in one attack : 13 sees., 12 sees., 15 sees., g sees., 14 sees., etc. The mere fi.xing of the attention on the observations soon stopped the hiccup. Chemistry of Respiration. Our knowledge of this subject has been entirely acquired in the last 200 years, and chiefly in the last century. Boyle showed by means of the air-pump that animals die in a vacuum, and BernouilH that fish cannot live in water from which the air has been driven out by boiling. Mayow, of Oxford, seems to a considerable extent to have anticipated Black, who in 1757 demonstrated the presence of carbonic acid in expired air by the turbidity which it causes in lime water. A most fundamental step was the discovery of oxygen by Priestley in 1771, and his proof that the venous blood could be made crimson, like arterial, by being shaken up with oxygen. Lavoisier discovered the composition of carbonic acid, and applied his discovery to the explanation of the respira- tory processes in animals, the heat of which he showed to be generated like that of a candle by the union of carbon and oxygen. He made many further important experiments on i84 A MANUAL OF PHYSIOLOGY. respiration, publishing some of his results in 1789, vhen the French Revolution, in which he was to be one of the most distinguished victims, was breaking out. He made the great mistake, however, of supposing that the oxidation of the carbon takes place in the blood as it passes through the lungs. That this is not the case was sufficiently proved as soon as it was known that the blood which comes to the lungs from the right heart is highly charged with carbonic acid. As to the actual seat of oxidation, we shall have something to say in another part of this chapter (p. 203). There are two main lines on which research has gone in trying to solve the chemical problems of the respiration : (i) The analysis and comparison of the inspired and expired air, or, in general, the investigation of the gaseous inter- change between the blood and the air in the lungs. (2) The analysis and comparison of the gases of arterial and venous blood, of the other liquids, and of the solid tissues of the body, with a view to the determination of the gaseous inter- change between the tissues and the blood. We shall take these up as far as possible in their order. The methods which have been used for comparing the composition of inspired and expired air are very various. (i) Breathing into one spirometer and out of another, the inspired and expired air being directed by valves. The contents of the spirometers are anah^zed at the end of the experiment (Speck). (2) A small apparatus, much on the same principle, was used for rabbits by Pfliiger and his pupils. A cannula in the trachea was connected with a balanced and self-adjust- ing spirometer containing oxygen, and the inspired and expired air separated by caustic potash valves, which absorbed the COo. The amount of oxygen used could be read off on the spirometer, and the amount of COj produced estimated in the liquid of the valves. (3) Larger and more elaborate arrangements, such as Pettenkofer's great respiration apparatus, in which a man can remain for an indefinite period, working, resting, or sleep- irjg. Smaller chambers of the same kind have also been RESPIRATION. 185 used for animals. In Pettenkofer's apparatus air is drawn through by an engine, its volume being measured by a gasometer. But as it would be far too troublesome to analyze the whole of the air coming from the chamber, a sample stream of it is constantly drawn off, which also passes through a gasometer, through drying tubes containing sulphuric acid, and through tubes filled with baryta water. The baryta solution is titrated to determine the quantity of COo; the increase in weight of the drying tubes gives the quantity of aqueous vapour. A similar sample stream of the air before it passes into the chamber is treated exactly in the same way, and from the data thus got the quantity of carbonic acid and aqueous vapour given off can readily be ascertained. But the oxygen has to be calculated by differ- ence, and all the errors fall upon it. (4) Haldane and Pembrey have elaborated a gravimetric method, which is the most suitable of any, at least for small animals. It depends upon the absorption of COo by soda lime. See Practical Exercises, p. 455. The expired air is at or near the body temperature, is saturated with watery vapour, and contains about 4 per cent, more carbonic acid and 4 to 5 per cent, less oxygen than the inspired. There may be in addition in expired air small quantities of hydrogen or ammonia, but these are probably derived from the alimentary canal, either directly or after absorption into the blood. The volume of the expired air, owing to its higher temperature and excess of watery vapour, is somewhat greater than that of the inspired air, but if it be measured at the temperature and degree of saturation of the latter, the volume is somewhat less. Since the oxygen of a given quantity of carbonic acid would have exactly the same volume as the carbonic acid itself at a given temperature and pressure, it is clear that the deficiency is due to the fact that all the oxygen which is taken up in the lungs is not given off as carbonic acid ; some of it, going to oxidize hydrogen, reappears as water. The quotient of the volume of oxygen given out as carbonic acid by the volume of o.xygen taken in is the respiratory quotient. It shows what proportion of the oxygen is used to oxidize carbon. It may i86 A MANUAL OF PHYSIOLOGY. approach unity on a carbo-hydrate diet, which contains enough oxygen to oxidize all its own hydrogen to water. With a diet rich in fat it is least of all ; with a diet of lean meat it is intermediate in amount. For ordinary fat con- tains no more than one-sixth, and proteids not one-half, of the oxygen needed to oxidize their hydrogen. In man on a mixed diet the respiratory quotient may be taken as "8 or 'g. So long as the type of respiration is not changed, the respiratory quotient may remain constant for a wide range of metabolism. In hibernating animals, how- ever, the respiratory quotient becomes very small during winter sleep (as low as -4), the output of carbonic acid faUing far more than the consumption of oxygen. On the other hand, in excised mammalian muscles at a low temperature the consumption of oxygen is lessened to a greater extent than the production of carbonic acid, and the respiratory quotient may be as high as 3*2 (Rubner). Muscular work increases the respiratory quotient, because carbo-hydrates are chiefly used up. In starvation the respiratory quotient diminishes, the production of carbonic acid falling off at a greater rate than the consumption of oxygen, for the starving organism lives on its own fat and proteids, and has only a trifling carbo-hydrate stock to draw upon. In a diabetic patient, fed on a diet of fat and proteid alone, the respirator}' quotient was only o"6 to 0*7, just as in a starving man. In an average man weighing 70 kilos the mean produc- tion of carbonic acid is about 800 grammes (400 litres) in 24 hours, and the mean consumption of oxygen about 700 grammes (490 litres) (Pettenkofer and Voit). But there are very great variations depending upon the state of the body as regards rest or muscular activity, and on other circumstances. In hard work the production of carbonic acid was found to rise to nearly 1,300 grammes, and in rest to sink to less than 700 grammes, the consumption of oxygen in the same circumstances increasing to nearly 1,100 grammes and diminishing to 600 grammes. In rest, in moderate exertion, and in hard work, the production of carbonic acid was found to be nearly proportionate to the RESPIRATION. 187 numbers 2, 3 and 6, respectively. In a case of diabetes the consumption of oxygen was 50 per cent, greater than in a healthy man, corresponding to the higher heat-equivalent of the food of the diabetic patient (Weintraud and Laves). Taking 400 litres per 24 hours, or 17 litres per hour, as the mean production of CO., by an average male adult at rest or doing only light work, we can calculate the quantity of fresh air which must be supplied to a room in order to keep it properly ventilated. It has been found that when the carbonic acid given off in respiration amounts to no more than 2 parts in 10,000 in the air of an ordinary room, the air remains sweet. When the carbonic acid given off reaches 4 parts in 10,000, the room feels distinctly, and at 6 in 10,000 disagreeably, close, while at 9 parts in 10,000 it is oppressive and almost in- tolerable. This has been supposed to be due chiefly to organic matter exhaled from the lungs, for pure carbonic acid added alone in similar proportions to the air of a room has not the same bad effect. Recent observations, however, seem to show that it is probably not the small quantity of organic matter given off by the lungs of healthy persons which causes either the odour or the ill-effects of a close room. Both are perhaps due to the products of slow putrefactive processes constantly going on, under favour- able conditions, on the walls, floors or furniture, but only becoming perceptible to the sense of smell when ventila- tion is insuflicient. In a small, newly-painted chamber, presumably free from such impurities, it was not until the carbonic acid reached 3 to 4 per cent, that discomfort began to be felt and the respiration to be quickened. No close odour could be detected (Haldane and Lorrain Smith). Nevertheless, experience has shown that it is a good working rule for ventilation to take the limit of permissible respiratory impurity at 2 parts of CO.2 per to, 000 ; and the 17 litres of carbonic acid given off in the hour will require 85,000 litres (or 3,000 cubic feet) of air to dilute it to this extent. This is the quantity required for the average male adult per hour. For men engaged in active labour, as in factories or mines, twice this amount may not be too much. 1 88 A MANUAL OF PHYSIOLOGY. Yov women and children less is required than for men. If a room smells close, it needs ventilation, whatever be the proportion of carbonic acid in the air. It must be remembered that in permanently-occupied rooms mere increase in the size will not compensate for in- complete renewal of the air, although it may be easier to ventilate a large room than a small one without causing draughts and other inconveniences. But as few apartments are occupied during the whole 24 hours, a large room which can be thoroughly ventilated in the absence of its inmates has a distinct advantage over a small one in its great initial stock of fresh air. The cubic space per head in an ordinary dwelling-house should be not less than 28 cubic metres or 1,000 cubic feet. The quantity of carbonic acid given off is not only affected by muscular work, but also by everything which influences the general metabolism. In males it is greater than in females (in the latter there is a temporary increase during pregnancy), and greater in proportion to the body-weight in the young than the old. This depends, partly at least, on the fact that the metabolism is relatively more active in a small than in a large organism. The taking of food increases it, chiefly in consequence of the increased mechanical and chemical work performed by the alimentary canal and the digestive glands. Sleep diminishes the pro- duction of COo partly owing to the rest of the muscles, and partly to the absence of external stimuli. Even a bright light is said to cause an increase in CO2 production and oxygen consumption ; but recent experiments have cast doubt on the statement (C. Ewald). The external tempera- ture influences the production of carbonic acid. In poikilo- therinal animals (such as the frog), the temperature of which varies with that of the surrounding medium, the production of carbonic acid, on the whole, diminishes as the external temperature falls, and increases as it rises. In homoiothermal animals, that is, animals with constant blood temperature, external cold increases the production of carbonic acid and the consumption of oxygen. But if the connection of the nervous system with the muscles has been cut out by RESPIRA TWN. curara, the warm-blooded animal behaves like the cold- blooded (Pfliiger and his pupils in guinea-pig and rabbit). These interesting facts will be returned to under Animal Heat (p. 437). Cold-blooded animals produce far less carbonic acid, and consume far less oxygen, per kilo of body-weight than warm-blooded. The following table shows the relation between the body- weight and the excretion of carbonic acid in man : Age. Weight ill kilos. CO., excreted per kilo per hour. (35 Male^^ i 9;6_ Female |;7 65 82 577 22 •51 gramme •4^ •59 ■92 557 23 ■45 •fc8 „ The next table illustrates the difference m the intensity of metabolism in different kinds of animals, a difference, how- ever, largely dependent upon relative size : Species. O.xvijen absorbed per Respiratory Quotient 1 kilo per hour. CO.. 0., (inCO.,). 0. °^ 0,. 1 Small song-bird 1 1 '3 gramme -yS Fowl I '3 •93 Dog - - ri8 75 Cat - I '00 „ 77 Horse •56 ., ■97 Sheep ■49 •98 Frog •084 „ •63 Forced respiration, although it will temporarily increase the quantity of carbonic acid given off by the lungs, does not sensibly affect the production ; it is only the store of already formed carbonic acid in the body which is drawn upon. The amount of oxygen taken up is little altered by changes in the movements of respiration except for a very short time. igo A MANUAL OF PHYSIOLOGY. How it is that the depth of the respiration may affect the rate at which carbonic acid is eliminated we can only under- stand when we have examined the process by which the gaseous interchange between the blood and the air of the alveoli is accomplished ; and before doing this it is necessary to consider the condition of the oxygen and carbonic acid in the blood. The Gases of the Blood. Physical Introduction. — The structure of matter is molecular; that is, it is made up of molecules beyond which it cannot be divided without altering its essential character. A molecule may consist of two or more particles of matter (atoms) bound to each other by chemical links. The kinetic theory of matter supposes the molecules of a substance to be in constant motion, frequently colliding with each other, and thus having the direction of their motion changed. In a gas the mean free path, that is, the average distance which a molecule travels without striking another, is comparatively long, and far more time is passed by any molecule without an encounter than is taken up with collisions. Although the average velocity of the molecules is very great, these collisions will produce all sorts of differences in the actual velocity of different molecules at any given time. Some will be moving at a greater, some at a slower rate, than the average ; while some may be for a moment at rest. If the gas is in a closed vessel the molecules will be constantly striking its sides and rebounding from them. If a very small opening is made in the vessel, some molecules will occasionally hit on the opening and escape altogether. If the opening is made larger, or the experi- ment continued for a longer time with the small opening, all the molecules will in course of time have passed out of the vessel into the air, while molecules of the oxygen, nitrogen, and argon of the air, will have passed in. In a gas, then, not enclosed by impenetrable boundaries, there is no restriction on the path which a molecule may take, no tendency for it to keep within any limits. When two chemically indifferent gases are placed in contact with each other, diffusion will go on till they are uniformly mixed. The diffusion of gases may be illustrated thus : Suppose we have a perfectly level and in every way uniform field divided into two equal parts by a visible but intangible line, the well-known whitewash line, for instance. On one side of the line place 500 blind men in green, and on the other 500 blind men in red. At a given signal let them begin to move about in the field. Some of the men in green will pass over the line to the 'red' side ; some of the men in red will wander to the 'green' side. Some of the men may pass over the line and again come back to the side they started from. But, upon the whole, after a given interval has elapsed, as many green RESPIRATION. 191 coats will be seen on the red side as red coats on the green. And if the interval is long enough there will be at length about 250 men in red and 250 in green on each side of the boundary-line. When this state of equilibrium has once been reached, it will henceforth be maintained, for, upon the whole, as many red uniforms will pass across the line in one direction, as will recross it in the other. In a liquid it is very different ; the molecule has no free path. In the depth of the liquid no molecule ever gets out of the reach of other molecules, although after an encounter there is no tendency to return on the old path rather than to choose any other ; so that any molecule may wander through the whole liquid. Although the average velocity of the molecules is much less in the liquid state than it would be for the same substance in the state of gas or vapour (gas in presence of its liquid), some of them may have velocities much above the average. If any of these happen to be moving near the surface and towards it, they may overcome the attraction of the neighbouring molecules and escape as vapour. But if in their further wanderings they strike the liquid again, they may again become bound down as liquid molecules. And so a constant inter- change may take place between a liquid and its vapour, or between a liquid and any other gas, until the state of equilibrium is reached, in which on the average as many molecules leave the liquid to be- come vapour as are restored by the vapour to the liquid, or as many molecules of the dissolved gas escape from solution as enter into it. For the sake of a simple illustration, let us take the case of a shallow vessel of water originally gas-free, standing exposed to the air. It will be found after a time that the water contains the atmo- spheric gases in certain proportions — in round numbers, about yj^ of its volume of oxygen and ./„ of its volume of nitrogen (measured at 760 mm. Hg and o°C.). Now, let a similar vessel of gas-free water be placed in a large air- tight box filled with air at atmospheric pressure, and let the oxygen be all absorbed before the water is exposed to the atmosphere of the box. The latter now consists practically only of the nitrogen of the air, and its pressure will be only about four-fifths that of the external atmosphere. Nevertheless, the quantity of nitrogen absorbed by the water will be exactly the same as was absorbed from the air. If the box was completely exhausted, and then a quantity of oxygen, equal to that in it at first, introduced before the water was exposed to it, the pressure would be found to be only about one-fifth that of the external atmosphere ; but the quantity of oxygen taken up by the water would be exactly equal to that taken up in the first experiment. Two well-known physical laws are illustrated by our supposed experiments.- (i) In a mixture of gases 2vhich do fiot act chemically on each other the pressure exerted by each gas {called the partial pies- sure of the gas) is the same as it nwuld exert if the others ivere absent. (2) The quantity (tnass) of a gas absorbed by a liquid which does not act chemically upon it is proportional to the partial pressure of the gas. 192 A MANUAL OF PHYSIOLOGY. It also depends upon the nature of the gas and of the liquid, and on the temperature, increase of temperature in general diminishing the quantity of gas absorbed. It is to be noted that when the volume of the absorbed gas is measured at a pressure equal to the partial pressure under which it was absorbed, the same volu/ne of gas is taken up at every pressure. Suppose, now, that a vessel of water, saturated with oxygen and nitrogen for the partial pressures under which these gases exist in the air, is placed in a box filled with pure nitrogen at full atmospheric pressure. As we have seen, there is a constant interchange going on between a liquid which contains gas in solution and the atmosphere to which it is exposed. Oxygen and nitrogen molecules will there- fore continue to leave the water ; but if the box is large, few oxygen molecules will find their way back to the water, and ultimately little oxygen will remain in it. In other words, the quantity of oxygen absorbed by the water will become again proportional to the partial pressure of oxygen, which is now not much above zero. On the other hand, molecules of nitrogen will at first enter the water tn larger number than they escape from it, for the pressure of the nitrogen is now that of the external atmosphere, of which its partial pressure was formerly only four-fifths. In unit volume of the gas above the water there will be 5 molecules of nitrogen for every 4 molecules in the same volume of atmospheric air. Therefore on the average 5 nitrogen molecules will in a given time get entangled by liquid molecules for every 4 which came within their sphere of attrac- tion before. On the whole, then, the water will lose oxygen and gain nitrogen, while the atmosphere of the air-tight box will gain oxygen and lose nitrogen. If, now, the partial pressures of oxygen and nitrogen under which the water had been originally saturated were unknown, it is evident that by exjjosing it to an atmosphere of known composition, and afterwards determining the changes produced in the composition of that atmosphere by loss to, or gain from, the gases of the water, we could find out something about the original partial pressures. If, for example, the quantity of oxygen in the atmosphere of the chamber was increased, we could conclude that the partial pressure of oxygen under which the water had been saturated was greater than that in the chamber at the beginning of the experiment. And if we found that with a certain partial pressure of ox\gen in the atmosphere of the chamber there was neither gain nor loss of this gas, we might be sure that the partial pressure (the temperature being supposed not to vary) was the same when the water was saturated. We shall see later on how this princi[jle has been applied to determine the partial pressure of oxygen or carbonic acid which just sufifices to prevent blood, or any other of the liquids of the body, from losing or gaining these gases. This pressure is evidently equal to that exerted by the gases of the liquid at its surface, which is sometimes called their ' tension '; for if it were greater, gas would, upon the whole, pass into the blood ; and if it were less, gas would escape from the blood. Thus, the te?isioti of a gas in solution in a liquid is equal to the partial RESPIRA TION. 193 pressure of that gas in an atmosphere to 7vhich the liquid is exposed ^which is Just sufficient to prevent gain or loss of the gas by the liquid (p. 200). The following imaginary ex[)eriment may further illustrate the meaning of the term ' tension ' of a gas in a liquid in this connection : Suppose a cylinder filled with a liquid containing a gas in solution, and closed above by a piston moving air-tight and without friction, in contact with the surface of the liquid (Fig. 66). Let the weight of the piston be balanced by a counterpoise. The pressure at the surface of the liquid is evidently that of the atmosphere. Now, let the whole be put into the receiver of an air-pump, and the air gradu- ally exhausted. Let exhaustion proceed until gas begins to escape from the liquid and lies in a thin layer between its surface and the piston, the quantity of gas which has become free being very small in proportion to that still in solution. At this point the piston is acted upon by two forces which balance each other, the pressure of P, frictionless piston ; L, liquid in cylinder ; G, gas beginning to es- cape from liquid. F is exactly counterpoised. In addition to ttie manner described in tiie te.\t, the ex- periment may be supposed to be per- formed thus. Let ihe weight, \V, be determined which, when the receiver is completely exhausted, suffices just to keep the piston in contact with the liquid. The pressure of the gas is tlien just counterbalanced by \V ; and if S is the area of the cross- section of the piston the pressure of W the gas per unit of area is Or it S the piston is hollow, and mercury be poured into it so as just to keep it in contact with the liquid, the height of the column of mercury required is also equal to the pressure or tension of the gas. Fig. 66.— Im.vginary Experiment to Illustrate 'Tension' of a Gas in .a. Liquid. the air in the receiver acting down, and the pressure of the gas escap- ing from the liquid acting upwards. If the pressure in the receiver is now slightly increased, the gas is again absorbed. The pressure at which this just happens, and against which the piston is still sup- ported by the impacts of gaseous molecules flying out of the liquid, while no pressure is as yet exerted directly between the liquid and the piston, is obviously equal to the pressure or tension of the gas in the li(juid. From the above principles it follows that a gas held in solution may be extracted by exposure to an atmosphere in which the partial pressure of the gas is made as small as possible. Thus, oxygen can be obtained from liquids in which it is simply dissolved by putting them in an atmosphere of hydrogen or nitrogen, in which the partial pressure of oxygen is zero, or in the vacuum of an air-pump, in 13 194 A MANUAL OF PHYSIOLOGY. which it is extremely small. Heat also aids the expulsion of dis- solved gases. Some gases held in weak chemical union, like the Fig. 67. — Scheme of Gas-pump. A, the blood bulb ; B, the froth chamber ; C, the drying tube ; D, fixed mercury bulb ; E, movable mercury bulb connected by a flexible tube with D ; F, eudiometer ; G, a narrow delivery tube'; i. 2, 3, 4, taps, 4 being a three-way tap. A is filled with blood by connectins: the tap i by means of a tube with a bloodvessel, laps i and 2 are then closed. The rest of Ihe apparatus from B to D is now exhausted by raising E, with tap 4 turned so as to place E only in communication with G, till the mercury fills D. Tap 4 is now turned so as to connect C with D and cut off G from D, and L is lowered. I'he mercury passes out of D, and air passes into it frorii B and C. Tap 4 is again turned so as to cut off C from D and connect G and D. E is raised, and the mercury passes into D and forces the air out through G, the end of which has not hitherto been placed under F. This alternate raising and lowering of E is continued till a manometer connected between C and 4 indicates that the pressure has been sufficiently reduced. The tap 2 is now opened ; the gases of the blood bubble up into the froth chamber, pass through the rirvin^-tube C, which is filled with pumice- stone and sulphuric acid, and enter D. The end of G is placed under the eudiometer F, and bv raising E, with tap 4 turned so as to cut off C, the gases are forced out through G and collected in F. The movements required for exhaustion can be re- peated several times till no more gas comes off. The escape of gas from the blood is facilitated by immersing the bulb A in water at 40°-50° C. loosely-combined oxygen of oxyhaemoglobin, can be obtained by dis- sociation of their compounds when the partial pressure is reduced. RESPIRATION. 195 More stable combinations may require to be broken up by chemical agents — carbonates, for instance, by acids. Extraction of the Blood-gases. — This is accomplished by exposing blood to a nearly perfect vacuum. The gas- pumps which have been most largely used in blood analysis are constructed on the principle of the Torricellian vacuum. A diagram of a simple form of Pflliiger's gas-pump is given in Fig. 67. The gases obtained are ultimately dried and collected in a eudiometer, which is a graduated glass tube with its mouth dipping into mercury. The carbonic acid is estimated by introducing a little caustic potash to absorb it. The diminution in the volume of the gas contained in the eudiometer gives the volume of the carbonic acid. The •oxygen may be estimated by putting into the eudiometer more than enough hydrogen to unite with all the oxygen so as to form water, and then, after reading off the volume, exploding the mixture by means of an electric spark passed through two platinum wires fused into the glass. One-third of the diminution of volume represents the quantity of ox}'gen present. It can also be estimated by absorption with potas- sium pyrogallate. The remainder of the original mixture of blood-gases, after deduction of the carbonic acid and oxygen, is put down as nitrogen (with, no doubt, a small proportion of argon). For the sake of easy comparison, the observed volume of gas is always stated in terms of its equivalent at a standard pressure and temperature (760 mm., or some- times on the Continent i metre, Hg, and 0° C). In dog's blood, which has been up to this time chiefly in- vestigated, there are considerable variations in the quantitj* of oxygen and carbonic acid which can be extracted ; and this is particularl}' true of the venous blood, as might naturally be expected, since even to the eye it varies greatly according to the vein it is obtained from, the rapidity of the circulation, and the activity of the tissues which it has just left. On the average, Volumes of Oo COo N2 100 \olumes of ar'erial blood yield - - - 20 40 1-2 „ mixed venous blood (from right heart) yield 10-12 47 1-2 reduced to 0° C. and 760 mm. Hg. 196 A MANUAL OF PHYSIOLOGY. The blood gains about twice as many volumes of O^ per cent, as the air loses in the lungs, for about twice as much air (by volume) as blood passes into them (pp. 164, 172, 185). Average venous blood contains 7 or 8 per cent, by volume less oxygen, and 7 or 8 per cent, more carbonic acid, than arterial blood. But even arterial blood is not quite saturated with oxygen ; it can generally still take up one-tenth to one- fifteenth of the quantity contained in it. When the gases are not removed from blood immediately after it is drawn, its colour becomes darker, and it yields more carbonic acid and less oxygen than if it is evacuated at once (Pfliiger). From this it is concluded that oxidation goes on in the blood for some time after it is shed. The oxidizable substances appear, however, to be confined to the corpuscles, which suggests that ordinary metabolism simply continues for some time in the formed elements of the shed blood, and that the disappearance of oxygen is not due to the oxidation of substances which have reached the blood from the tissues. The Distribution of the Gases in the Blood. — The oxygen is nearly all contained in the corpuscles. A little oxygen can be pumped out of serum ('i to '2 per cent, by volume), but this follows the Henry-Dalton law of pressures ; that is, it comes off in proportion to the reduction of the partial pressure of the oxygen in the pump, and is simply in solution. When blood is being pumped out, very little oxygen comes off till the pressure has been greatly reduced, and then at a certain point it is disengaged with a burst. This shows that it is not simply absorbed, but is united by chemical bonds to some constituent of the blood. The same thing is seen when defibrinated blood is saturated at the ordinary air temperature with oxygen at different pressures. The quantity taken up diminishes but slowly as the pressure is reduced, till at about 40 mm. of Hg the curve cf saturation begins to fall abruptly towards the abscissa line, showing that the quantity of oxygen which the blood can now take up, under the diminished pressure,, rapidly becomes very small (Bert). It is found that a solution of pure haemoglobin crystals RESPIRATION. 197 behaves towards oxygen just like blood ; and there is no doubt that the body in blood with which the oxygen is loosely united is haemoglobin. We may suppose that at the ordinary temperature and partial pressure of oxygen (the partial pressure of oxygen when haemoglobin is exposed to 21 the air will be, at 760 mm. atmospheric pressure, x 760, or I59"6 mm.) some oxygen is continually escaping from the bonds by which it is tied to the haemoglobin ; but on the whole an equal number of free molecules of oxygen, coming within the range of the haemoglobin molecules, are entangled by them, and thus equilibrium is kept up. If now the atmospheric pressure, and therefore the partial pressure of oxygen, is reduced, the tendency of the oxygen molecules to break off from the haemoglobin will be unchanged, and as many molecules on the whole will escape as before ; but even after a considerable reduction of pressure the haemo- globin, such is its avidity for oxygen, will still be able to seize as many atoms as it loses. The more, however, the partial pressure of the oxygen is diminished — that is to say, the fewer oxygen molecules there are in a given space above the haemoglobin — the smaller will be the chance of the loss being made up by accidental captures. At a certain pressure the escapes will become conspicuously more numerous than the captures ; and the gas-pump will give evidence of this, although it could give us no information as to mere mole- cular interchange, so long as equilibrium was maintained. The higher the temperature of the haemoglobin is, the greater will be the average velocity of the molecules, and the greater the chance of escape of molecules of oxygen. The ' dissociation tension ' of oxyhaemoglobin, or the partial pressure of oxygen at which the oxyhaemoglobin begins to lose more oxygen than it gains, is raised by raising the tempera- ture. At the temperature of the body it is more than 80 mm. of Hg for haemoglobin only nine-tenths saturated (Bert). In ordinary venous blood there is still much oxygen — so much that it gives the spectrum of oxy-haemoglobin. It is only in the blood of asphyxia that oxygen disappears. The Carbonic Acid of the Blood. — Blood freed from gas 198 A MANUAL OF PHYSIOLOGY. absorbs carbonic acid, partly in proportion to the pressure, and partly independently of it. Some of the carbonic acid must therefore be simply dissolved ; some, and this the greater part, is chemically combined. The serum contains a larger percentage of carbonic acid than the clot, but this percentage is not great enough to allow us to assume that the whole of the carbonic acid is confined to the serum. Some of it must belong to the corpuscles. Since the serum contains alkalies (especially soda), it is natural to suppose that the combined carbonic acid must exist chiefly as carbonate or bicarbonate of sodium. That there is something more, however, is shown by the fact that from defibrinated blood the whole of the carbonic acid can in time be pumped out without the addition of an acid to displace it from the bases with which it is combined. It is hardly necessary to say that this could not be done with a solution of sodium carbonate. From serum a great deal, but not the whole, of the carbonic acid can be likewise pumped out. The residue is set free on the addition of an acid, phosphoric acid, e.g. The most satisfactory explanation seems to be that in the serum there exist substances which can act as weak acids in gradually driving out the carbonic acid, when its escape is rendered easier by the vacuum, but which, nevertheless, do not affect litmus paper (since the reaction of serum is alkaline). The quantity of these, however, is so small that a portion of the carbonic acid remains in the serum. The proteids of the serum, such as serum-globulin, can act as weak acids, and may contribute to the driving out of the carbonic acid. When defibrinated blood is pumped out, the whole of the carbonic acid can be removed, apparently because sub- stances of an acid nature pass from the corpuscles into the liquid part of the blood and help to break up the carbonates. In the red corpuscles a portion of the carbonic acid may be in combination with alkalies. We know that the cor- puscles contain alkalies, for the alkalinity of ' laked ' blood (pp. 25, 45), in which the red corpuscles have been broken up, is found to be greater than that of unlaked blood, unless RESPIRA TION. 1 99 a long time is allowed in the case of the latter for the alkalies of the corpuscles to reach the acid used in titration (Loewy). But there is reason for believing that a weak compound of carbonic acid can be formed with haemoglobin; for a solution of haemoglobin absorbs more of this gas than water, and the quantity absorbed is not proportional to the pressure. The haemoglobin of the corpuscles may therefore hold a portion of the carbonic acid in combina- tion. Even ordinary venous blood can take up much more carbonic acid than it actually contains. When blood is saturated with carbonic acid and then separated into serum and clot, the serum is found to yield more gas than the clot ; but if the serum and clot are separately saturated, the latter takes up more carbonic acid than the former. From this it is argued that a substance combined with carbonic acid must in blood saturated with the gas pass out of the corpuscles into the serum. This cannot be haemoglobin, for it remains in the corpuscles, but it may ver}' well be an alkali, combined with the carbonic acid, and thus set free from its connection with the haemo- globin. And, as a matter of fact, under the circumstances described, it has been found that alkalies, as well as certain food-substances (proteid, fat and sugar), do pass from the clot into the serum (Zuntz, Hamburger), and chlorine from the serum into the corpuscles (Lehmann). On the other hand, when blood is saturated with oxygen, alkalies and the food-substances mentioned pass out of the serum into the corpuscles. Hamburger has extended these observations to living blood, and has shown that the plasma of venous blood has more alkali, proteid, sugar and fat than the plasma of arterial blood. In the pulmonary capillaries, ac- cording to him, food-substances go over, under the influence of oxygen, from the plasma to the corpuscles. In the systemic capillaries the blood becomes loaded with carbonic acid, and therefore the corpuscles give up proteids, etc., to the plasma, which accordingly has a greater supply of food- substances to offer to the tissues than the plasma of arterial blood itself. In both cases he sees in this interchange an arrangement by which oxidation is favoured. \\'hatever -co A MANUAL OF PHYSIOLOGY. may be thought of this view — and ic is a serious objection to it that the amount of oxidation which can be supposed to take place in the red corpuscles is small — the current theory, that the corpuscles are simply passive carriers of oxygen, and exercise no further influence on the plasma, breaks down in face of the facts. We must admit that an active and many-sided commerce exists between them and the liquid in which they float. The nitrogen of the blood is simply absorbed. The tension or partial pressure of a gas in the blood can be conveniently ascertained by means of an apparatus called the aerotonometer (Pfliiger, Strassburg). The blood is made to pass directly from the vessel to two tubes, which it traverses at the same time, the stream being divided between them ; it then passes out again. The tubes are warmed to the bod}' temperature ; one of them is filled "with a gaseous mixture having a greater, and the other with a mixture having a smaller, partial pressure, say of COo, than is expected to be found in the blood. As the latter runs in a thin sheet over the walls of the tubes, it loses COg to the one and takes up COo from the other. From the alteration in the proportion of the COo in the two tubes, it is easy to calculate the partial pressure of that gas in the blood ; that is, the partial pressure which it would be necessary to have in the tubes in order that the blood might pass through them without losing or gaining carbonic acid (p. 192). The pressure of oxygen in arterial blood was given by Strassburg as about 30 mm. of Hg in the dog, and in venous blood as something like 20 mm. But the careful recent experiments of Bohr make it necessary to treble or quadruple these numbers. He allowed the blood to flow through an apparatus constructed and worked much in the same way as Ludwig's stromuhr (p. 92) and inserted in the course of an artery. In the instrument the blood came into contact with a gaseous mixture of known composition. The pressure of carbonic acid in arterial blood we may take at 10 to 40 mm., in venous blood at 30 to 50 mm., according to the results of different observers. RESPIRATION. 20 1 Whenever the venous blood has to pass through a region in which the pressure of carbonic acid is kept lower than in itself, it will begin to lose carbonic acid by diffusion. If the pressure of oxygen in this region is at the same time higher than in the venous blood, some of it will be taken up. And to bring about these results no physiological force need be invoked ; only physical processes will, under the assumed conditions, be required. Now, we know that in the lungs carbonic acid is given off from the blood, and oxygen taken up by it. We have, there- fore, to inquire what the partial pressures of these gases are in the alveoli, and whether they are so related to the cor- responding partial pressures in the blood that a simple process of dissociation and diffusion will be sufficient to explain pulmonary respiration. The percentage of carbonic acid in expired air cannot tell us the pressure of that gas in the alveoli, for it includes the air in the upper part of the respiratory tract. But it gives us a minimum value, below which it is not conceivable that the alveolar partial pressure can lie, for we cannot imagine that any air in the respiratory tract can be richer in carbonic acid than that of the alveoli. Now, Vierordt found with the deepest possible expiration a little over 5 per cent, of carbonic acid in the expired air. From this it seems justifiable to conclude that in man the partial pressure of carbonic acid in the alveoli may be at least one-twentieth of an atmosphere or 38 mm. of Hg. In animals, samples of the alveolar air have been drawn off directly (Wolffberg) by means of Pfliiger's pulmonary catheter. This consists of two tubes, one within the other. The inner tube, which is a fine elastic catheter, projects free from the other for a little distance at its lower end. The outer tube terminates in an indiarubber ball, which can be inflated so as to block the bronchus into which it is passed, and cut off the corresponding portion of the lung from communication with the outer air. A sample of the air below the block can be drawn off through the inner tube. In this way the proportion of carbonic acid in the alveoli of the dog was found to be only about 3"S per cent., corre- 202 A MANUAL OF PHYSIOLOGY. spending to a partial pressure of about 29 mm. of Hg. But this would be undoubtedly too high, owing to the im- possibility of interchange with the external atmosphere, and would represent the partial pressure of the carbonic acid in the blood rather than in the alveolar air under normal conditions. For gaseous equilibrium is soon established between blood and air separated only by a thin membrane like the alveolar wall. In Bohr's experiments the tension of the carbonic acid in the air of the lungs in dogs varied from 5*8 to 34*6 mm. of Hg, while in arterial blood, taken at the same time, it usually ranged from 10 to 38 mm., and was often less than in the alveolar air. If we accept these results, we seem shut up to the con- clusion that, in part at least, this gas does not pass through the walls of the alveoli by diffusion, but by an active process of secretion in the cells which line them (Miiller, Bohr). Others have suggested that the absorption of oxygen favours the liberation of COo by increasing the avidity of the haemo- globin for alkalies with which the CO., is combined. As we have seen, alkalies do actually pass from the plasma into the corpuscles under the influence of oxygen ; and it may be that this is a process auxiliary to secretion and diffusion of COo into the alveoli. As to the oxygen, there is the same difficulty, for its partial pressure in the alveoli is not always, under normal conditions, as high as, or higher than, that of the arterial blood which leaves the lungs. Indeed Bohr found that, in the majority of his observations, the oxygen tension was distinctly greater in the blood than in the pulmonary air. And the fact observed by Biot and Moreau, that the gas of the swim- bladder in fishes consists chiefly of oxygen, and the further fact demonstrated by Bohr, that gas ceases to accumulate in the organ when the branches of the vagi going to it are cut, are additional evidence in favour of the view that there is, besides diffusion, an element of selective secretion in the interchange of gases through the pulmonary membrane. The lungs, then, are the portal b}^ which oxygen enters the blood, and through which carbonic acid is cast out. We RESPIRA TION. 203 have now to see what becomes of the oxygen, and how and where the carbonic acid arises. The suggestion which hes nearest at hand, and which, as a matter of fact, was first put forward, is that the oxygen does not leave the blood at all, but that it meets with oxidizable substances in it, and unites with their carbon to form carbonic acid. While there is a certain amount of truth in this view, oxygen, as already mentioned, being to some extent taken up by freshly-shed blood, and also by blood under other conditions, to oxidize bodies, other than haemo- globin, either naturally contained in it or artificially added, there is no doubt that the tissues themselves are the busiest seats of oxidation. This is shown by the presence of carbonic acid in large amount in lymph and other liquids which are, or have been, in intimate relation with tissue elements ; by its presence, also in considerable amount, in the tissues themselves — in muscle, for instance ; by its con- tinued and scarcely lessened production not only in a frog whose blood has been replaced by normal saline solution, but in excised muscles ; and by the remarkable connection between the amount of this production and the functional state of those tissues. Lymph, bile, urine, and the serous fluids, contain very little oxygen, but so much carbonic acid that the pressure of that gas in all of them is greater than in arterial blood, while in lymph alone (taken from the large thoracic duct) has it been found less than that of venous blood ; and it is extremely probable that lymph gathered nearer the primary seats of its production (the spaces of areolar tissue) would show a higher proportion of carbonic acid. Strassburg found that with a pressure of carbonic acid in the arterial blood of 21 mm. of Hg, the pressure in bile was 50 mm., in peritoneal fluid 58 mm., in urine 68 mm., in the surface of the empty intestine 58 mm. Saliva, pancreatic juice, and milk, also contain much carbonic acid, and only a little, if any, oxygen. From muscle (to facilitate pumping, the muscle is minced, and often warmed) no free oxygen at all can be pumped out, but as much as 15 volumes per 100 of carbonic acid, some 204 A MANUAL OF PHYSIOLOGY. of which is free, that is, is given up to the vacuum alone, while some of it is fixed, and only comes off after the addi- tion of an acid, such as phosphoric acid. If the muscle be left long in the pump putrefaction begins to appear, and this causes a discharge of carbonic acid which may last indefinitely. Muscle may be safely taken as a type of the other tissues in regard to the problems of internal respiration. It is instructive, therefore, to observe that the great scarcity of oxygen in the parenchymatous liquids which bathe the tissues, here in the tissues themselves deepens into actual famine. The inference is plain. The active tissues are greedy of oxygen ; as soon as it enters the muscle it is seized and ' fixed ' in some way or other. The traces of oxygen in the lymph cannot therefore be journeying away from the muscle; they must have come from another source, and this can only be the blood. Could we gather lymph for analysis directly from the thin sheets which lie between the blood capillaries and the tissues, we might find more oxygen present as well as more carbonic acid. But if we did find more oxygen, it would still be oxygen in transit from the capillaries towards places where the partial pressure of oxygen is less. In the lymph, the pressure is kept low by the avidity of the tissues with which it is in contact, and possibly by the existence in it of oxidizable substances v/hich have come from the tissues. In the tissues there is no partial pressure at all, because the oxygen which reaches them is at once stowed away in some compound, in which it has lost the properties of free ox3'gen. Assuming, then, that at least a great part of the oxidation and consequent production of carbonic acid goes on in the tissues, we have yet to follow the steps of the process, as far as we can, in the light of our knowledge of the respiration of muscle. Respiration of Muscle. — Three methods have been used to determine the respiratory changes going on in resting muscle, or to compare them with those in the excited state : (i) The excised muscles of cold-blooded animals are exposed for a considerable time to an atmosphere of known RESPIRATION. 205 composition in a small chamber ; and the changes in this atmosphere are then determined (G. Liebig, Matteucci, Hermann), (2) Samples of the blood coming to and leaving a muscle of a warm-blooded animal may be taken in its natural position, and the gases analyzed and compared (Ludvvig, Chauveau and Kaufmann). (3) Artificial circulation may be kept up through a muscle or group of muscles ; for example, through one or both hind- limbs of a dog. In the newest forms of apparatus for artificial circulation the blood is oxygenated in a special chamber from a graduated cylinder containing oxygen, and the carbonic acid collected in baryta or caustic potash valves. The oxygen consumption can be read off from the cylinder, and the production of carbonic acid estimated by titrating from time to time samples of the baryta water or potash (Von Frey and Gruber, and Jacobi). (Fig. 68.) By the first of these methods a very remarkable fact, among others, has been brought to light. It has been found that a frog's muscle is capable of going on producing carbonic acid, and that at an undiminished rate, in the entire absence of oxygen, when the chamber, for instance, is filled with nitrogen or other indifferent gas. Not only so, but it can be made to contract many times and to perform a comparatively large amount of work in this oxygen- free atmosphere, and to produce a correspondingly large quantity of carbonic acid. This leads us to the very important con- clusion that the carbonic acid does not arise, so to speak, on the spot, from the immediate union of carbon and oxygen. Oxygen is essential to muscular life and action. But a stock of it is apparently taken up by the muscle, and stored in some compound or compounds which are broken down during muscular contraction, and more slowly during rest, carbonic acid in both cases being one of the end products. It is very possible that there may be an ascending series of bodies through which oxygen passes up, and a descending series through which it passes down, before the final stage is reached. When muscle goes into rigor (Chap. IX.) — and this is A MANUAL OF PHYSIOLOGY • . 1) OJ c i> • ' a> _: ■ ^ ■! ■= -c^._ = " ° "3 - . 'U o (u _• c y « tij . rr u w* > c^ c^ " ■■ '^ >-ja_x: — ^ t3 J Oh _ OJ D O ^ ■ ^ ^ n ;^ f- O rt "V — D D ~ C M S t/i w — u ^ u rt 03 ^ C "^ = • - oi „ |<^ o 5 rt ^ 3 o " I" i: . c r- JJ ■« r -■- -^ "o ■" 5 >- t^ ^ m — . rt-; C 03 'X rt > as tiO = - o « g ^ sz^/ ■ n-r 1) ^ — O — .E-c' ^ — o oj i: ._ J-i ^ . _ fj _ 1- M ri n RESPIRATION. 207 most strikingly seen when the rigor is caused by raising the temperature of frog's muscle to about 40° or 41° C. — there is a sudden increase in the quantity of carbonic acid given off. Moreover, in an isolated muscle the total quantity of carbonic acid obtainable during rigor is less if the muscle has been previously tetanized, and less, it is said, by just the amount given out during the contractions (Hermann). From this it has been argued that the hypothetical substance (inogen), the decomposition of which yields carbonic acid in contraction, is also the substance which decomposes so rapidly in rigor; that a given amount of it exists in the muscle at the time it is removed from the influence of the blood ; and that this can all explode either in contraction or in rigor, or partly in the one and partly in the other. Many of the older experiments made by method (2) are too inexact to yield more than qualitative results, and the same is true of some of the researches with the more primi- tive and imperfect methods of artificial circulation. The mere difference of colour between the venous and arterial blood of a muscle, or other active organ, is sufficient to show that oxygen is taken up and carbonic acid given out by it to the blood. This is the case in muscles at rest (Bernard and many others), and even in muscles with artificial circulation after they have become inexcitable. In active muscles more oxygen is used up and more carbonic acid produced than in the resting state. Chauveau and Kaufmann in their experiments on one of the muscles used by the horse in feeding, found that the consumption of oxygen and the production of carbonic acid might be three times as great in activity as in rest. In the submaxillary salivary gland there was also an increase of carbonic acid during activity but not proportion- ally so great as in muscle. In the active brain it is not easy to demonstrate any increase at all (Hill). For excised mammalian muscles (hind-limbs of dog), as has been said, the respiratory quotient increases when the temperature is reduced. As the temperature is raised, the opposite effect is observed. Stimulation of the muscle causes a rise in both oxygen consumption and carbonic acid pro- 2o8 A MANUAL OF PHYSIOLOGY. duction, but proportionally more in the former, and the respiratory quotient diminishes. When the excised muscle begins to deteriorate in the course of some hours, the con- sumption of oxygen falls off more quickly than the production of carbonic acid. All this goes to show that the two processes are to a great extent independent of each other. At the higher tempera- tures, during muscular contraction, and when the vitality of the muscle is still but little impaired, the conditions are relatively favourable to the chemical changes in which oxygen is combined. Low temperature, rest, and diminished vitality, are relatively favourable to the splitting up of sub- stances which yield carbonic acid. But it must be re- membered that in the intact organism the conditions are different (p. i86). The Influence of Respiration on the Blood-pressure. — We have Fig. 69. The upper tracing shows the respiratory movements in a rabbit ; the next tracing is the blood-pressure curve: I, inspiration ; E, expiration, including the pause; time trace (the lowest) shows seconds. already stated, in treating of arterial blood-pressure (p. 84), that a normal tracing shows a series of waves corresponding with the respiratory movements. When the respiratory movements are recorded simul- taneously with, and immediately below the pressure curve, it is seen that although the mean blood-pressure is falling for a short time at the beginning of inspiration, it soon reaches its minimum, then begins to rise, and continues rising during the rest of this period. At the commencement of expiration it is still rising, but soon reaches its maximum, begins to fall, and continues falling through the rest of the expiratory phase. The explanations given of this phenomenon are many, but RESPIRA TION. 209 they may all be grouped into two divisions, in which nervous and mechanical influences are respectively invoked as the chief cause. Theory of Nervous Influences. — Everybody admits that in certain animals (the dog, for instance), and in man under certain conditions, the rate of the heart is greater during in- spiration, especially towards its end, than in expiration ; and this is due to nervous influence, for the difference disappears after division of both vagi. Now, it might be said that the rise of blood-pressure during the latter part of inspiration is simply caused by the increased rate of the heart, which, as we know, can raise the blood-pressure. Nevertheless, this is not the explanation, for the respirator}' oscillations persist after section of the vagi, and they are seen in animals like the rabbit, in which little or no variation in the rate of the heart is connected with the phases of respiration. Then, again, it has been stated that in weakly curarized dogs which are still able to carry on rudimentary move- ments of respiration, full-sized respiratory oscillations of the blood-pressure, with the usual increase of the heart's rate during inspiration, coincide with these rudimentary move- ments. Now, the latter cannot have an appreciable in- fluence on the intra-thoracic pressure or on the volume of the lungs, the changes in which are the two great factors in the mechanical explanations ; and therefore the theorv that the cardio-inhibitory centre in the bulb is stimulated at the same time as the respiratory centre was advanced. The persistence of the oscillations after section of the vagi cannot, however, be reconciled with this. Quite a number of observers have supposed that rhyth- mical discharges from the vaso-motor centre, either automatic or due to stimulation of the centre by the venous blood, and causing a periodic increase and diminution in the peripheral resistance, are responsible for the respiratory oscillations. A great difficulty in the way of this explana- tion is that the Traube-Hering curves (p. 136) are not, unless under special conditions (Fredericq), synchronous with respiratory movements, nor, when both exist together, with respiratory oscillations of pressure. 14 2IO A MANUAL OF PHYSIOLOGY. Mechanical Theories. — While admitting that nervous influences may have some share, we fall back upon the mechanical changes as the chief factor ; and of these there are two of special importance : (i) the changes of intra- thoracic pressure, (2) the changes of vascular resistance in the lungs. The intra-thoracic pressure, which, as we have seen, is always less than that of the atmosphere, unless during a forced expiration when the free escape of air from the lungs is obstructed, diminishes in inspiration and increases in expiration. The great veins outside the chest, the jugular veins in the neck, for example, are under the atmospheric pressure, which is readily transmitted through their thin walls, while the heart and thoracic veins are under a smaller pressure. The venous blood both in inspiration and ex- piration will, therefore, tend to be drawn into the right auricle. In inspiration the venous flow will be increased, since the pressure in the thorax is diminished ; and upon the whole more venous blood will pass into the right heart during inspiration than during expiration. But all the blood which reaches the right heart during an inspiration is at once sent into the lungs, although not even the first of it can have passed through to the left side of the heart at the end of the inspiration, since the pulmonary circulation time is longer than the time of a complete inspiration at any ordinary rate (three to four seconds in a small dog, two to three seconds in a rabbit). The increase in the quantity of blood pumped into the pulmonary artery will, if not counter- acted by other circumstances, tend to raise the blood- pressure in the artery and its branches, and therefore at once to accelerate the outflow through the pulmonary vein. This will be greatly aided if at the same time the vascular resistance in the lungs is reduced, as there seems good reason for believing is the case. The increased blood-flow into the left ventricle will of course correspond to better filling of the systemic arteries ; that is, to a rise of arterial blood-pressure. In expiration the contrary will happen. Less blood will be dra'svn into the right heart, less will be pumped into the RESPIRATION. 211 pulmonary artery, in which the pressure will, of course, fall. The outflow into the left auricle will thus be diminished — all the more as in the expiratory phase the vascular resist- ance in the lungs is increased — and the systemic arterial pressure will be lowered. Now, this is just what is seen on the blood-pressure curve, except that in both cases the change is somewhat belated, and does not coincide exactly with the commencement of the inspiration or the expiration. But this delay may be explained on several grounds. First, we cannot expect the curve of pressure to alter its course quite suddenly, at the very moment when the respiration changes its phase ; for the change in the blood-flow through the lungs must require time to establish itself, in the face of the opposite tendency to which it succeeds. The same is true of the systemic arteries, in which at the end of expiration the movements of the blood associated with the falling pressure are going on. It is impossible that they can be checked at once ; inertia must carry them on into inspiration. The negative pressure of the thorax acts also on the aorta, although, on account of the greater thickness of its walls, to a much smaller extent than on the thoracic veins. The diminution of pressure in inspiration tends to expand the intra-thoracic aorta, and to draw blood back out of the systemic arteries, while expiration has the opposite effect. And although the hindrance caused in this way to the flow of blood into the arteries during inspiration, and the acceleration of the flow during expiration, cannot be great, the tendency will be to diminish the pressure in the one phase and increase it in the other. As soon as the changes of pressure produced by alterations in the flow of venous blood into the chest and through the lungs are thoroughly established, the slight arterial effect will be overborne ; but before this happens, that is, at the beginning of inspiration and expiration, it will be in evidence, and will help to delay the main change. Another factor in this delay may be found in the changes of vascular resistance and capacity which take place in the lungs when they pass from the expanded to the collapse 1 condition. 212 A MANUAL OF PHYSIOLOGY. According to the most careful of recent observations, the expansion of the lungs in natural respiration causes a widening of the pulmonary capillaries, with a consequent increase of their capacity and diminution of their resistance, (De Jager). This is supported by experiments on the rabbit, in which the vessels at the base of the heart were ligatured either at the height of inspiration or the end of expiration, so as to obtain the whole of the blood in the lungs. It was found that the lungs invariably contained more blood in inspiration than in expiration (Heger and Spehl). During inspiration, as we have seen, the right ventricle is sending an increased supply of blood into the pulmonary artery; but before any increase in the outflow through the pulmonary veins can take place, the vessels of the lung must be filled to their new capacity. The first effect, then, of the lessened vascular resistance of the lungs in inspiration is a temporary falling off in the outflow through the aorta, and therefore a temporary fall of arterial pressure. As soon as a more copious stream begins to flow through the lungs, this is succeeded by a rise. In like manner the first effect of expiration, which increases the resistance and diminishes the capacity of the pulmonary vessels, is to force out of the lungs into the left auricle the blood for which there is no room. This causes a temporary rise of arterial blood-pressure, succeeded by a fall as soon as the lessened blood-flow through the lungs is established. In artificial respiration oscillations of blood-pressure, synchronous with the movements of the lungs, are also seen, even when the thorax is opened. In the latter case there are, of course, no variations of intra-thoracic pressure, and the oscillations must be connected with the changes in the pulmonary circulation. The respiratory waves differ in certain respects from those in natural breathing, as might be expected from the very different mechanical conditions. During inspiration (inflation) there is first a small rise and then a large fall of pressure. In expiration (collapse) there is first a slight fall and then a great rise. RESPIRATION. 213 The meaning of this is clearly seen when artificial respira- tion is stopped at the height of inflation (Fig. 70). The arterial blood-pressure then falls rapidly, and continues low until the stock of oxygen is exhausted and the rise of asphyxia begins. When the respiration is stopped in collapse, instead of a fall a steady rise of pressure occurs (as in Fig. 48, p. 137). This ultimately merges in the .elevation due to asphyxia, which shows itself sooner than in inflation, since the lungs contain less air. The difference in the course of the blood-pressure curve in the two cases immediately after stoppage of respiration cannot, however, depend on this latter circumstance. It is undoubtedly due Fig. 70. — Effect on Blood-pressure of Inflation of the Lungs (Rabbit). Artificial respiration stopped in inflation at i. Interval between 2 and 3 (not repro- duced) 51 seconds, during which the curve was almost a straight line. Time-tracing shows seconds. to the fact that in artificial inflation the vascular capacity and resistance of the lungs are less than in collapse. When the tracheal cannula is closed in natural respiration, no initial fall of pressure takes place (Fig. 71). To sum up the causes of the respiratory oscillations in the arterial blood-pressure : The changes of intra-thoracic pressure and of the vascular resistance in the lungs seem the most important factors, but nervous influences may also play a subordinate part. The respiratory oscillations in the veins, as might be expected, run precisely in the opposite direction to those in the arteries, and so do the Traube-Hering curves. The increased flow from the veins to the thorax during inspira- 214 A MANUAL OF PHYSIOLOGY. tion lowers the pressure in the jugular vein, while it increases the pressure in the carotid. The constriction of the small bloodvessels to which the Traube-Hering curves are due increases the blood-pressure in the arteries, because it increases the peripheral resistance to the blood-flow ; in the veins it lowers the pressure, because less blood gets through to them. Accordingly, when the Traube-Hering curve is ascending in the carotid, it is descending in the jugular. The effects of breathings condensed and rarefied air are — (i) mechanical, shown chiefly by changes in the circulation, in the blood-pressure, for instance ; (2) chemical. The mechanical effects differ according to whether the whole body, or only the respiratory tract, is exposed to the Fig. 71.— Bi.ooo-pressure Tracing (Rabbit, undkr Chloral). Natural respiration stopped at I in inspiration, at E in expiration. The mean'blood ■ pressure is scarcely altered ; but the respiratory waves become much larger owing to the abortive efforts at breathing. Time-tracing shows seconds. altered pressure. When the trachea of an animal is con- nected with a chamber in which the pressure can be raised or lowered, it is found that at first the arterial blood-pressure rises as the pressure of the. air of respiration is increased above that of the atmosphere. But a maximum is soon- reached ; and when respiration begins to be impeded, the pressure falls in the arteries and increases in the veins. When the pressure of the. air- in the chamber is diminished a little below that of the atmosphere, there is a slight sinking of the arterial blood-pressure, which rises if the air-pressure is further diminished (Einbrodt). It is. clear that any change of the air-pressure which tends to diminish the intra-thoracic pressure will favour the RESPIRATION. 215 venous return to the heart, and therefore, if the exit of blood from the thorax is not proportionally impeded, the filling of the arteries. An increase in the intra-alveolar pressure must tend on the whole to increase, and a diminu- tion in it to lessen, the pressure inside the thorax, which always remains equal to the intra-alveolar pressure, minus the elastic tension of the lungs. Breathing compressed air should, therefore, under the conditions described, be upon the whole unfavourable to the venous return to the heart and to the filling of the arteries, and the arterial pressure should fall ; while breathing rarefied air should have the opposite effect. But a very great diminution of the intra-thoracic pressure is not necessarily favourable to the circulation. Certain chest diseases have been treated by the use of apparatus by which the patient is made to breathe either compressed or rarefied air ; or to inspire air at one pressure and to expire into air at another pressure. And it has, upon the whole, been found, in agreement with theory, that con- densed air cannot help the circulation however it is applied, but always hinders it ; while rarefied air aids the circulation both in inspiration and in expiration. But the increased work of the inspiratory muscles may counterbalance the advantage. Valsalva's experiment, which is performed by closing the mouth and nostrils after a previous inspiration, and then forcibly trying to expire, is an imitation of breathing into compressed air. The intra-thoracic pressure is raised, it may be, to considerably more than that of the atmosphere; the venous return to the heart is impeded, and may be stopped ; and the pulse curve is altered in such a way as to indicate first an increase and then a decrease of the arterial blood- pressure. Mailer's experiment, which should be bracketed with Valsalva's, consists in making, after a previous expiration, a strong inspiratory effort with mouth and nostrils closed. Here the intra-thoracic pressure is greatly diminished, more blood is drawn into the chest, and upon the whole effects opposite to those of Valsalva's experiment are produced. Neither experiment is quite free from danger. When the whole body is subjected to the changed 2i6 A MANUAL OF PHYSIOLOGY, pressure, as in a balloon or on a mountain, in a diving-bell or a caisson used in building the piers of a bridge, the conditions are very different. For the blood-pressure, the intra-thoracic pressure, and the intra-alveolar pressure, all fall together when the pressure of the atmosphere is diminished, and all rise together when it is increased. It is possible not only to live, but to do hard manual labour, at very different atmospheric pressures. There are towns on the high tablelands of the Andes, and in the Himalayas, where the barometric pressure is not more than 20 inches, yet the inhabitants feel no ill effects. And in the caissons of the Forth Bridge the workmen were engaged in severe toil under a maximum pressure of over three atmospheres, while in the caissons of the St. Louis Bridge in America a maximum pressure of more than four atmospheres was reached, which however, proved fatal in a few cases. When the air-pressure is diminished below a certain limit, death takes place from asphyxia,, more or less gradual according to the rate at which the pressure is reduced. The haemoglobin cannot get or retain enough oxygen to enable it to perform its respiratory function ; its dissociation tension is no longer balanced by an equal or greater partial pressure of oxygen in the air. The quantity of carbonic acid in the blood is also lessened. These belong to the chemical effects of changes of pressure in the air of respiration. To such changes, as well as to the cold, some of the deaths in high balloon ascents must be attributed. Messrs. Glaisher and Coxwell reached the height of 36,000 feet ; the former became unconscious at 29,000 feet, but recovered during the descent. The suddenness of a change of pressure has a good deal to do with the symptoms it produces, as was shown at the Forth Bridge, where the men were more liable to troublesome symptoms while passing through the air-lock connecting the caissons with the external air than either in the caissons themselves or outside. When pressure is very suddenly lowered, bubbles of nitrogen, disengaged in the blood, may form emboli and cause death. Bert discovered the singular fact that in pure o-xygen at a RESPIRATION. 217 pressure of three atmospheres, which corresponds to air at fifteen atmospheres, animals die in convulsions. The con- sumption of oxygen and elimination of carbonic acid are both much diminished. Even seeds and vegetable organisms generally are killed in a short time ; and an atmosphere of pure oxygen, equal to five atmospheres of air, hinders the development of eggs. Cataneous Respiration. — It has already been remarked that a frog survives the loss of its lungs for some time, respira- tion going on through the skin. Indeed, it has been calculated that in the intact frog as much as three-quarters of the total gaseous interchange is cutaneous. In mammals the structure of the skin is very different, and respiration can only go on through it to a very slight extent. The amount of carbonic acid excreted in man, although only about 4 grm. or 2 litres in twenty-four hours, is much greater than cor- responds to the quantity of oxygen absorbed through the skin. It has been asserted, and no doubt with justice, that some at least of the carbonic acid given off is due to putrefactive processes taking place on the surface of the body. Such processes seem also responsible in part for the heavy odour of a ' close ' room. For no harmful products appear to be exhaled from the skin when it is properly cleansed. In spite of the romantic statements to the contrary in ancient and modern books, the whole of the skin may be coated with an impermeable varnish without any ill effects. The entire surface of the body of a patient with cutaneous disease was covered with tar and kept covered for ten days. There was not the least disturbance of any normal function (Senator). The harmful effects of varnishing the skin in animals are due, not to retention of poisonous substances, but to increased heat loss. Varnishing does not hurt large animals like dogs, but kills rabbits, which have a relatively great surface and a delicate skin. The danger of widespread superficial burns is well known. But it is not due to diminished excretion by the skin, for death occurs when large cutaneous areas remain uninjured. The patient nearly always dies when a quarter of the whole skin is burnt ; yet the remaining three-quarters may surely be con- 2i8 A MANUAL OF PHYSIOLOGY. sidered capable, from all analogy, of making up the loss by increased activity. One kidney is enough to eliminate the products of the nitrogenous metabolism of the whole body. It is difficult to see why the excretion of the trifling amount of solid matter in the perspiration should be interfered with by the loss of 25 per cent, of the sweat-glands. The real explanation of the serious effects of extensive superficial burns is perhaps the excessive irritation of the sensory nerves, which may lead to changes in the nervous centres, or reflexly in other organs. Some observers have supposed that the chemical changes in the damaged tissue, for example in the blood-corpuscles, may be the cause of death (Hunter). Voice and Speech. Voice. — Sounds of various kinds are frequently produced by the movements of animals as a whole, or of individual organs. The muscular sound, the sounds of the heart and of respiration, we have already had to speak of. Such sounds may be considered as purely accidental as the foot- fall of a man or the buzzing of a fly. The wings of an insect beat the air, not to cause sound, but to produce motion ; the respiratory murmur is a mere indication that air is find- ing its way into the lungs, it is in no way related to the oxidation of the blood in the pulmonary capillaries. But in many of the higher animals mechanisms exist which are specially devoted to the utterance of sounds as their prime and proper end. In man the voice-producing mechanism consists of a triple series of tubes and chambers : (i) The trachea, through which a blast of air is blown ; (2) the larynx, with the vocal cords, by the vibrations of which sound waves are set up ; and (3) the upper resonance chambers, the pharynx, mouth, and nasal cavities, in which the sounds produced in the larynx are modified and in- tensified, and in which independent notes and noises arise. The larynx is a cartilaginous box, across which are stretched, from front to back, two thin and sharp-edged membranes, the (true) vocal cords. In front the cords are RESPIRA TION. 219 attached to the thyroid cartilage, one a little to each side of the middle Hne ; behind, they are connected to the vocal or anterior processes of the pyramidal arytenoid cartilages. The thyroid and the two arytenoids are mounted upon a cartilaginous ring, the cricoid, on which the former can rotate about a transverse horizontal axis, the latter around a vertical axis. The thyroid can thus be depressed by the contraction of the crico-thyroid muscle, and the vocal cords stretched. By the pull of the posterior crico-arytenoid muscles, attached to the external or muscular processes of the arytenoid cartilages, the vocal processes are rotated outwards, the cords separated from each other or abducted, and the chink Fig. 72. — Diagrammatic horizontal section ok Larynx to show the direction ok pull ok THE Posterior Crico- arytenoid Muscles, which abduct the Vocal Cords. Dotted lines show position in abduction. Fig. 73. — Direction of PULL OF the Lateral Crico-Arytenoids, which adduct the Vocal Cords. Dotted lines show position in adduction. between them, the rima glottidis, widened. When the vocal processes are approximated by contraction of the lateral crico-arytenoid muscles and the consequent forward move- ment of the muscular processes, the vocal cords are brought closer together, or adduded, and the rima is narrowed. The transverse or posterior arytenoid muscle, which connects the two arytenoid cartilages behind, also helps by its contrac- tion to narrow the glottis by shifting the cartilages on their articular surfaces somewhat nearer the middle line. Running in each vocal cord,, and, in fact, incorporated with its elastic tissue, is a muscle, the thyro-arytenoid, the external portion 220 A MANUAL OF PHYSIOLOGY. of which may to some extent cause inward rotation of the vocal processes and adduction of the cords ; but the main function, at least of its inner part, is to alter the tension of the cords. The diagrams in Figs. 72 and ']'^ illustrate the action of the abductors and adductors of the vocal cords. The crico-thyroid muscle and the deflectors of the epi- glottis are supplied by the superior laryngeal branch of the vagus, which also contains the sensory fibres for the mucous membrane of the larynx above the vocal cords. All the other intrinsic muscles are supplied by the recurrent laryn- geal branch of the vagus. It receives these motor fibres from the spinal accessory; and supplies sensory fibres to the mucous membrane of the larynx below the vocal cords and to the trachea. The voice is produced, like the sounds of a reed instru- ment, by the rhythmical interruption of an expiratory blast of air by the vibrating vocal cords. When a bell is struck vibrations are set up in the metal, which are communicated to the air. It is not the same with the vibrations of the vocal cords ; if they were plucked or struck, they would only produce a feeble note. The air in the mouth, pharynx, and larynx is the real sounding body ; a pulse of alternate rare- faction and condensation is set up in it by the interference, at regular intervals, of the vocal cords with the expiratory blast. Forced abruptly from their position of equilibrium as the blast begins, they almost immediately regain and pass below it, in virtue of their elasticity, and continue to vibrate as long as the stream of air continues to issue in sufficient strength. The sound waves thus set up spread out on every side, impinge on the tympanic membrane, set it quivering in response, and give rise to the sensation of sound. We may say, in a word, that the whole exquisite mechanism of cartilages, ligaments, and muscles, has for its object the production of a sufficient pressure in the blast of air driven through the windpipe by an expiratory act, and of a suitable tension in the vibrating cords. An approxima- tion of the cords, a narrowing of the glottis, is essential to the production of voice ; with a widely-opened glottis the RESPIRATION. 221 air escapes too easily, and the necessary pressure cannot be attained. The pressure in the windpipe was found in a woman with a tracheal fistula to be about 12 mm. Hg for a note of medium height, about 15 mm. for a high note, and about 72 mm. for the highest possible note. The period of vibration of structures like the vocal cords depends on their length and tension ; the shorter, thinner, more tense and less dense a stretched string is, the greater is the vibration frequency, the higher the note. In the child the cords are short (6 to 8 mm.), in woman longer (10 to 15 mm. when slack, 15 to 20 mm. when stretched), in man longest of all (15 to 20 mm. in the relaxed, and 20 to 25 mm. in the stretched position") ; and the lower limit of the voice is fixed by the maximum length of the relaxed cords. i\ boy or a woman cannot utter a deep bass note, because their vocal cords are relatively short, and do not vibrate with sufficient slowness. It is true that by the action of the crico-thyroid muscle the cords can be lengthened, and that the maximum length in a woman approaches or exceeds the minimum length in a man. But the lengthening of the vocal cords in one and the same individual is always accompanied by other changes — increase of tension, decrease of breadth and thickness — which tell upon the vibration frequency in the opposite way, and more than compensate the effect of the increase of length. So that when the highest notes are uttered, the cords are not onl}' in the position of greatest tension, but also in the position of greatest length. The range of an ordinary voice is 2 octaves ; by training 2h octaves can be reached ; but in exceptional cases a range of 3, and even 3!, octaves has been known. The pitch of a note, while it depends chiefly, as has been said, on the tension of the vocal cords, rises and falls some- what with the strength of the expiratory blast ; the highest notes are only reached with a strong expiratory effort. The intensity of all sounds is determined by the strength of the blast, for the amplitude of vibration of the vocal cords is proportional to this. Besides pitch and intensity, the ear can still distinguish the quality or timbre of sounds ; and the 222 A MANUAL OF PHYSIOLOGY. explanation is as follows : Two simple tones of the same pitch and intensity, that is, the sounds caused by two air- waves of the same period and amplitude — of the same fre- quency and height, if these terms seem simpler — would appear absolutely identical to the sense of hearing; just as the aerial disturbances on which they depend would be absolutely alike to any physical test that could be applied. But no musical instrument ever produces sound-waves of one definite period, and one only ; and the same is true of the voice. When a stretched string is displaced in any way from its position of rest, it is set into vibration ; and not only does the string vibrate as a whole, but portions of it vibrate independently and give out separate tones. The tone corresponding to the vibration period of the whole string is the lowest of all. It is also the loudest, for it is more difficult to set up quick than slow vibrations. The ear therefore picks it out from all the rest ; and the pitch of the compound note is taken to be the pitch of this, its funda- mental tone. The others are called partial or over-tones, or harmonics of the fundamental tone, their vibration frequency being twice, three times, four times, etc., that of the latter. Now, the fundamental tone of a compound note or clang produced by two musical instruments may be the same, while the number, period and intensity of the har- monics are different; and this difference the ear recognises as a difference of timbre or quality. The timbre of the voice depends for the most part on partial tones produced or intensified in the upper resonance chambers. A great deal of our knowledge as to the mode and mechanism of the production of voice has been acquired by means of the laryngoscope (Fig. 74). This consists of a small plane mirror mounted on a handle, which is held at the back of the mouth in such a position that a beam of light, reflected from a larger concave mirror fastened on the fore- head of the observer, is thrown into the larynx of the patient. The observer looks through a hole in the centre of the large mirror ; and a reversed image of the interior of the larynx is thus seen in the small mirror, the arytenoid cartilages appearing in front, the thyroid behind, and the RESPIRATION. 223 vocal cords stretching between. The small mirror is warmed to body temperature before being introduced, so as to prevent the condensation of moisture on it. And the tendency to retch which is caused by contact of the instru- ment with the soft palate may be removed or lessened by the application of a solution of co'caine. Examined with the laryngoscope during quiet respiration, the glottis is seen to be moderately, though not widely, open. Although the portion between the arytenoid carti- lages has received the name of glottis respiratoria, in con- tradistinction to the glottis vocalis between the vocal cords, Fig. 74. — Diagram of Laryngoscope. the rima in its whole extent from front to back is really con- cerned in the respiratory act. In expiration the vocal cords come nearer to the middle line, and the glottis is narrowed ; in deep inspiration they are widely separated, and the rings of the trachea, and even its bifurcation, may be disclosed to view. When a sound is produced, a note sung, for example, the cords are approximated (Figs. 75 and 76) ; and with a high note more than with a low. The essential difference between the production of notes in the lower register, or chest voice, and in the higher 224 A MANUAL OF PHYSIOLOGY. register, or falsetto, has been much debated. The lowest notes which can be uttered by any given voice are chest notes, the highest are falsetto notes ; but there is a debatable land common to both registers, and medium notes can be sung either from the chest or from the head. Chest notes impart a vibration or fremitus to "the thoracic walls, from the reso- nance of the lower air-chambers, the trachea and bronchi ; and this can be distinctly felt by the hand. In head notes or falsetto the resonance is chiefly in the upper cavities, the pharynx, mouth, and nose. As to the mechanical conditions in the larynx, there is a pretty general agreement that during the Fig. 75. — Position of the Glottis preliminary to THE utterance OF SOUND. rs, false vocal cord ; ri, true vocal cord ; ar, arytenoid carti- lage ; b, pad of the epiglottis. Fig. 76. — Position of open Glottis. /, tongue ; e, epiglottis ; ae, ary- epiglottidean fold ; c, cartilage of Wrisberg ; ar, arytenoid cartilage ; 0, glottis ; V, ventricle of Morgagni ; ti, true vocal cord ; ts, false vocal cord. production ot falsetto notes the vocal cords are less closely approximated than in the sounding of chest notes. The escape of air is consequently more rapid in the head voice, and a falsetto note cannot be maintained so long as a note sung from the chest. But it is only the anterior part of the rima glottidis that is wider in the falsetto voice ; the whole of the glottis respiratoria, and even the posterior portion of the glottis vocalis, are closed during the emission of falsetto notes. Oertel has stated, and the statement has been confirmed by others, that the free edge of the vocal cord alone vibrates in the falsetto voice, one or more nodes or motionless lines parallel to the edge being formed by the contraction of the RESPIRATION. 225 internal part of the thyro-arytenoid muscle, which thus acts like a stop upon the cord. Approximation of the vocal cords may take place in certain acts unconnected with the production of voice. Thus, a cough, as has already been mentioned, is initiated by closure of the glottis. During a strong muscular effort, too, the chink of the glottis is obliterated, and respiration and phonation both arrested. The object of this is to fix the thorax, and so afford points of support for the action of the muscles of the limbs and abdomen. But consider- able efforts can be made even by persons with a tracheal fistula. Speech. — Ordinary speech is articulated voice — voice shaped and fashioned by the resonance of the upper air cavities, and jointed together by the sounds or noises to which the varying form of these cavities gives rise. Here we come upon the fundamental distinction between vowels and consonants. Vowels are musical sounds ; consonants are not musical sounds, but noises — that is to say, they are due to irregular vibrations, not to regularly recurring waves, the frequency of which the ear can appreciate as a definite pitch. This difference of character corresponds to a differ- ence of origin : the vowels are produced by the vibrations of the vocal cords ; the consonants are due to the rushing of the expiratory blast through certain constricted portions of the buccal chamber, where a kind of temporary glottis is estab- lished by the approximation of its walls. One of these ' positions of articulation ' is the orifice of the lips ; the consonants formed there, such as p and b, are called labials. A second articulation position is between the anterior part of the tongue and the teeth and hard palate. Here are formed the dentals t, d, etc. The ordinary English r, and the r of the Berwickshire and East Prussian ' burr,' also arise in this position through a vibratory motion of the point of the tongue. The third position of articulation is the narrow strait formed between the posterior portion of the arched tongue and the soft palate. To the consonants arising here the name of gutturals has been given. They include k, g, the Scottish ch, and the uvular German r. The latter is 15 226 A MANUAL OF PHYSIOLOGY. produced by a vibration of the uvula. The aspirated h is a noise set up by the air rushing through a moderately wide glottis, and some have therefore included the glottis as a fourth articulation position for consonants. As we have said, the vowels are produced by vibrations of the vocal cords, but they owe their special timbre to the reinforcement of certain overtones by the resonating cavities, the shape and fundamental tone of which are different for each vowel. When a vowel is whispered, the mouth assumes a characteristic shape, and emits the fundamental tone proper to the form and size of the particular * vowel-cavity,' not as a reinforcement of tones set up by the vibrations of the vocal cords, but in response to the rush of air through them, either in expiration or inspiration; just as a bottle of given shape and size gives out a definite note when the air which it contains is set in vibration, by blowing across its mouth. A whisper, in fact, is speech without voice ; the larynx takes scarcely any part in the production of the sounds ; the vocal cords remain apart and comparatively slack ; and the expiratory blast rushes through without setting them in vibration. The fundamental tone of the ' vowel-cavity ' may be found for each vowel by placing the mouth in the position necessary for uttering it, then bringing tuning-forks of different period in front of it, and noting which of them sets up sympathetic resonance in the air of the mouth, and so causes its sound to be intensified. The fundamental tone is lowest for u. Next comes o ; then a ; then e ; while i is highest of all. A simple illustration of this may be found in the fact that when the vowels are whispered in the order given, the pitch rises. Such is the explanation of the difference of the vowels in quality which was first given by Helmholtz. Universally accepted for a time, it has been in recent years assailed by Hermann, who bases his criticisms (i) on microscopic ex- amination of curves obtained by the Edison phonograph, and (2) on the results of his phono-photographic method. (The record of an Edison phonograph is magnified by a system of levers, the last of which carries a small mirror, on which RESPIRA TION. 227 a beam of light is allowed to strike. The reflected beam falls on a moving drum covered with sensitive paper. Thus the movements of the mirror are greatly exaggerated and photographed.) Hermann has come to the conclusion that the mouth does not act as a mere resonator, but that for each vowel, in addition to the fundamental note due to the vibration of the vocal cords, the pitch of which is, of course, variable, one or, it may be, two other notes, not necessarily harmonics of the laryngeal note, and of constant or nearly constant pitch, are directly produced by the passage of the expiratory blast through the mouth. For example, the buccal note for a is in the middle of the second octave of the laryngeal note, the buccal notes for c in the beginning of the second and the end of the third octave. The fact that it is by no means difficult to sing and whistle at the same time shows the possibility of Hermann's view, that a fixed tone can be generated in the mouth by the inter- mittent stream of air issuing from betv/een the vibrating vocal cords, just as a tone is generated in a pipe by blowing into or over it (Griitzner). When n or 0 is sounded, the buccal cavity has the form of a wide-bellied flask with a short and narrow neck for «, a still shorter but wider neck for 0. For i the tongue is raised and almost in contact with the palate, and the cavity of the mouth is shaped like a flask with a long narrow neck and a very short belly. For e the shape is similar, but the neck is not so narrow. For a the vowel-cavity is intermediate in form between that of u and i, being roughly funnel-shaped, and the mouth is rather widely opened (Figs. 77 to 79). When the vowels are being uttered, the soft palate closes the entrance to the nasal chambers completely, as may be shown by holding a candle in front of the nose, or trying to inject water through the nares. If the cavities of the nose are not completely blocked oft", the voice assumes a nasal character in pronouncing certain of the vowels ; and in some languages this is the ordinary and correct pronunciation. Many animals have the power of emitting articulated sounds ; a few have risen, like man, to the dignity of sentences, but these only by imitation of the human voice. 228 A MANUAL OF PHYSIOLOGY. Both vowels and consonants can be distinguished in the notes of birds, the vocal powers of which are in general higher than those of mammalian animals. The latter, as a rule, produce only vowels, though some are able to form consonants too. The nervous mechanism of voice and speech will have to be again considered when we come to study the physiology of the brain and spinal cord. But the curious physiological antithesis between the functions of abduction and of adduc- tion of the vocal cords may be mentioned here. The abductor muscles are not employed in the production of voice; they are associated with the less specialized, the less skilled and pur- FiG. 77. Fig. 78. Fig. 79. posive function of respiration. The adductor muscles are not brought into action in respiration ; they are associated with the highly-specialized function of speech. Corresponding to this difference of function, we find that the adductors only are represented in the cortex of the brain, the abductors in the medulla oblongata. Stimulation of an area in the lower part of the ascending frontal convolution, near the fissure of Rolando, in the macaque monkey, causes adduction of the vocal cords, never abduction. Stimulation of the medulla oblongata (accessory nucleus) causes abduction, never adduction (Horsley and Semon). The skilled adductor function is, therefore, placed under control of the cortex. The vitally important, but more mechanical, abductor RESPTRA TION. 2,29 function is governed by the medulla. The abductor move- ments are more likely to be affected by organic disease, the adductor movements by functional changes. But the distinction between the two groups of muscles is not entirely due to a difference of central connections; for Hooper has found that in an animal deeply narcotized with ether, stimulation of the recurrent laryngeal nerve causes invariably abduction of the vocal cords ; in an animal slightly narcotized, adduction. Lesions of the medulla oblongata are often accompanied by marked changes in the character of the voice and the power of articulation. Section or paralysis of the superior laryngeal nerve causes Fig. 80.— Diagram of Vocal Cords in Paralyses of the Larynx. a, Paralysis of both inferior laryngeal nerves. The vocal cords have taken up the ' mean ' position, b. Paralysis of right inferior laryngeal nerve. An attempt is being made to narrow the glottis for the utterance of sound. The right cord remains in its ' mean ' position, c. Paralysis of the abductor muscles only, on both sides. The cords are appro.ximated beyond the ' mean ' position by the action of the adductors. the voice to become hoarse, and renders the sounding of high notes an impossibility, owing to the want of power to make the vocal cords tense. Stimulation of the vagus within the skull causes contraction of the crico-thyroid muscle and increased tension of the cords. Section or paralysis of the inferior laryngeal nerves leads to loss of voice or aphonia, and dyspnoea (Fig. 80). Both adductor and abductor muscles are paralyzed ; the vocal cords assume their mean position — the position they have in the dead body — and the glottis can neither be narrowed to allow of the production of a note, nor widened during inspiration. It is said, how- ever, that young animals, in which the structures around the 230 A MANUAL OF PHYSIOLOGY. glottis are more yielding than in adults, can still utter shrill cries after section of the inferior laryngeals, the contraction of the crico-thyroid muscle alone being able, while increasing the tension of the cords, to draw them together. Strong stimulation of the inferior laryngeal causes closure of the glottis, for although it supplies both abductors and adductors, the latter prevail. With weak stimulation, in young animals, and when the nerve is cooled, the abductors carry off the victory, and the glottis is opened. Interference with the connections on one side, between the higher cerebral centres and the medulla oblongata, as by rupture of an artery and effusion of blood into the posterior portion of the internal capsule (giving rise to hemiplegia, or paralysis of the opposite side of the body), is not followed by loss of voice ; the laryngeal muscles on both sides are still able to act. In stammering, spasmodic contraction of the diaphragm interrupts the effort of expiration. The stammerer has full control of the mechanism of articulation, but not of the expiratory blast. His larynx and lips are at his command, but not his diaphragm. To conquer this defect he must school his respiratory muscles to calm and steady action during speech. The stutterer, on the other hand, has full control of the expiratory muscles. His diaphragm is well drilled, but his lips and tongue are insubordinate. PRACTICAL EXERCISES ON CHAPTER III. I. Tracing of the Respiratory Movements. — {a) Set up the arrangement shown in Fig. Si, and test wlicther it is air-tight. Have also in readiness an induction machine and electrodes arranged for an interrupted current. Anaesthetize a dog with morphia and ether (p. 150). Insert a cannula into the trachea (p. 151), and connect it with the large bottle by a tube. Connect the bottle with a record- ing tambour adjusted to write on a drum, and regulate the amount of the excursion of the lever by slackening or tightening the screw- clamp. Set the drum off at slow speed, and take a tracing. {I)) Then disconnect the cannula from its tube. Dissect out the PR A CTICA L EXERCISES. vago-sympathetic in the lower part of the neck, pass a ligature under it, but do not tie it. Connect the cannula again with the bottle, and while a tracing is being taken ligature the vagus. Then stimulate its central end with weak shocks, marking the time of stimulation on the drum. Repeat the stimulation with strong shocks, and observe the results. {c) Again disconnect the cannula. Isolate the superior laryngeal branch of the vagus, which will be found coursing inwards to the larynx at the level of the thyroid cartilage. Ligature the nerve, and 232 A MANUAL OF PHYSIOLOGY. divide it between the larynx and the h'gature. Reconnect the cannula. Take a tracing first with weak and then with strong stimulation of the central end of the superior laryngeal. {d) Disconnect the cannula, and isolate the vagus on the other side. While a tracing is being taken, divide it. The respiratory movements will probably at once become deeper and less frequent. {e) Isolate the sciatic nerve (p. 155), ligature it, and cut below the ligature. Stimulate its central end while a tracing is being taken. The respiratory movements will be increased. (/) Insert a glass cannula with a rectangular elbow into the carotid artery. While a tracing is being taken, allow the blood to flow. Dyspnoea and exaggeration of the respiratory movements will be seen when a considerable quantity of blood has been lost. Mark and varnish the tracings. In the whole of this experiment the cannula is to be disconnected, except when the lever is actually writing on the drum, in order that the period during which the animal must breathe into the confined space of the bottle may be diminished as much as possible. 2. Measurement of the Quantity of Water and Carbonic Acid given off in Respiration. — (See Practical Exercises on Chapters VII. and VIII.) This experiment may be performed here, or with those on Chapters VII. and VIII. , as is most convenient. 3. Section of both Vagi. — Proceed as in Experiment 16, p. 155, but use an ordinary rabbit ; and instead of cutting the sympathetic, pass threads under both vagi, divide them, and sew up the wound. An induction coil is not required, unless the student has any diffi culty in deciding which nerve is the vagus. The point may be at once settled by stimulating the nerves before division. Stimulation of the vagus will cause slowing or stoppage of the heart, and there- fore of the pulse in the carotid, and quickening of respiration. Stimulation of the sympathetic will have neither of these effects. At the moment of section the student should observe whether there is any change in the frequency and depth of the respiratory move- ments. The animal must be looked at once at least on the day of the operation, and its behaviour carefully observed. Early next morning it should be again seen, as it does not usually live much more than twenty-four hours. Make an autopsy, observing especially the state of the lungs. Harden portions of the lungs that appear to contain the most exudation in Miiller's fluid (ten times as much fluid as tissue). Change the fluid next day, and again at the end of a week. In three or four weeks wash out the Miiller's fluid under the tap, and transfer the tissue to 90 per cent, alcohol. After a few days it is to be prepared for cutting by being passed successively through absolute alcohol (two days), absolute alcohol and ether mixture (two days), thin celloidin (two or three days), thick celloidin (one day). Fasten on vulcanized wood-fibre and cut sections with a sliding microtome, moistening the knife with 80 per cent, alcohol. Stain, mount, and examine under the microscope. Note the exudation in the alveoli, and make drawings. Write a report of your complete experiment. Pla,te ir . ^■^'^ Mucous alveolus SeroiiK alveolus !•• ^^ f* v_ V \«'*^**«rA -^^Q - Crescent! of Qia ^ Supporting connective tissue 1. Section of submaxillary gland showing both mucous and serous alveoli, X 250. (Stained with hsBmatoxyUn.) ;^ '^^ffli. %y' Be/ore secretion {resting) * -'•«■ 2. Section of seroas gland, x 300. (Stained with borax carmine.) Mucous cells Crescents of \\r fHanazzi . . i^ (very large) Connective tissue ^ acinus Interm''diate duel _> 0> f-^ '^ "v leading from acini of gland "' ^ «.' ~ ^ ^^^ jSfood-vcMet Dttct (intralobular) to intralobular duct 3. Section of mucous gland (after secretion), x 300. (Stained with picrocarmine.) Yfciit, ITe wi.-aji chr. iitk . CHAPTER IV. DIGESTION. In the last chapter we have described the manner in which the interchange of gases between the tissues and the air is carried out. We have now to consider the digestion and absorption of the soHd and Hquid food, its further fate in relation to the chemical changes or metabolism of the tissues, and finally the excretion of the waste products by other channels than the lungs. Logically, we ought to take metabolism after absorption and before excretion, tracing the food through all its vicissi- tudes from the moment when it enters the blood or lymph till it is cast out as useless matter by the various excretory organs. Unfortunately, however, the steps of the process are as yet almost entirely hidden from us ; we know only the beginning and the end. We can follow the food from the time it enters the alimentary canal till it is taken up by the tissues of absorption ; and we have really a fair know- ledge of this part of its course. We can collect the end products as they escape in the urine, or in the breath, or in the sweat ; and our knowledge of them and of the manner in which they are excreted is considerable. But of the wonderful pathway by which the dead molecules of the food mount up into life, and then descend again into death, we catch only a glimpse here and there. Only the introduction and the conclusion of the story of metabolism are at present in our possession in fairly continuous and legible form. We will read these before we try to decipher the handful of torn leaves which represents the rest. 234 ^ MANUAL OF PHYSIOLOGY. Comparative. — In the lowest kinds of animals, such as the Amceba, there is neither mouth, nor alimentary canal, nor anus : the food, wrapped round by pseudopodia, is taken in at any part of the animal with which it happens to come in contact ; it is digested within the cell-substance, and the part of it which is useless for nutrition is cast out again at any part of the surface. Coming a little higher, we tind in the Ccelenterates a mouth and alimentary tube, which opens into the body-cavity, where a certain amount of digestion seems to take place, and from which the food is absorbed either through the cells of the endoderm, or, as in Medusa, by means of fine canals, which radiate from the body-cavity into its walls, and form part of the so-called gastro vascular system. In the Echinodermata we have a further development, a complete alimentary canal with mouth and anus, and entirely shut off from the body- cavity. In many Arthropods it is possible already to distinguish parts corresponding to the stomach, and the small and large intes- tines of higher forms, the digestive glands being represented by organs which in some groups seem to be homologous with the liver, and in others with the salivary glands of the higher vertebrates. A few Molluscs seem in addition to possess a pancreas. Among Vertebrates fishes hvae the simplest, and birds and mam- mals the most complicated, alimentary system. In the lowest fishes the stomach is only indicated by a slight widening of the anterior part of the digestive tube. In water-living Vertebrates there are no salivary glands. In Birds the oesophagus is generally dilated to form a crop, from which the food passes into a stomach consisting of two parts, one pre-eminently glandular (proventriculus), the other pre- eminently muscular (ventriculus). Among Mammals a twofold division of the stomach is distinctly indicated in rodents and cetaceae, but this organ reaches its greatest complexity in ruminants, which possess no fewer than four gastric pouches. The differentiation of the intestine into small and large intestine and rectum is more distinct, both anatomically and functionally, in Mammals than in lower forms ; but there are marked dift'erences between the various mammalian groups both in the relative size of the several parts of the digestive tube, and in the proportion between the total length of the alimentary canal and the length of the body. In general, the canal is longest in herbivora, shortest in carnivora. Thus, the ratio between length of body and length of intestine is in the cat i : 4, dog I : 6, man i : 5 or 6, horse 1:12, cow i : 20, sheep i : 27. The relative capacity of the stomach, small intestine, and large intestine, is in the dog 6 : 2 : i'5, in the horse i : 3*5 : 7, in the cow 7:2:1. The area of the mucous surface of the alimentary canal is very con- siderable, in the dog more than half that of the skin, the surface of the small intestine being three times that of the stomach and four times that of the large intestine. In the horse the mucous surface has twice the area of the skin. Anatomy of the Alimentary Canal in Man. — The alimentary canal is a muscular tube, which, beginning at the mouth, DIGESTION. 235 runs under the various names of pharynx, oesophagus, stomach, small intestine, large intestine, and rectum, till it ends at the anus. Its walls are largely composed of muscular fibres ; its lumen is clad with epithehum, and into it open the ducts of glands, which, morphologically speaking, are involutions or diverticula formed in its course. In virtue of its muscular fibres it is a contractile tube ; in virtue of its epithelial lining and its special glands it is a secreting tube ; in virtue of both it is fitted to perform those mechanical and chemical actions upon the food which are necessary for digestion. Its inner surface is in most parts richly supplied with bloodvessels, and in special regions beset with pecu- liarly-arranged lymphatics ; by both of these channels the alimentary tube performs its function of absorption. From the beginning of the oesophagus to the end of the rectum the muscular wall consists, broadly speaking, of an outer coat of longitudinally-arranged fibres, and a thicker inner coat of fibres running circularly or transversely around the tube. Between the layers lies a plexus of non-medullated nerves and nerve-cells (Auerbach's plexus). In the stomach the longitudinal fibres are found only on the two curvatures, and a third incomplete coat of oblique fibres makes its appear- ance internal to the circular layer. In the large intestine, again, the longitudinal fibres are chiefly collected into three isolated strands. In the pharynx the typical arrange- ment is departed from, inasmuch as there is no regular longitudinal layer; but the three constrictor muscles repre- sent to a certain extent the great circular coat. The muscles of the mouth and of the pharynx are of the striped variety. So is the muscle of the upper half of the oesophagus in man and the cat, and of the whole oesophagus in the dog and the rabbit. In the rest of the alimentary canal the muscle is smooth, except at the very end, where the external sphincter of the anus is striped. In certain situations the circular coat is developed into a regular anatomical sphincter, a definite muscular ring, whose function it is to shut one part of the tube off from another (sphincter pylori), or to help to close the external opening of the tube (internal sphincter of anus). Elsewhere a tonic contraction of a 236 A MANUAL OF PHYSIOLOGY. portion of the circular coat, not anatomically developed beyond the rest, creates a functional sphincter (cardiac sphincter of stomach). Throughout the greater part of the digestive tract the peritoneum forms a thin serous layer, external to the muscular coat. Internally the muscular coat is separated from the mucous membrane, the lining of the canal, by some loose areolar tissue containing bloodvessels, lymphatics and nerves (Meissner's plexus), and called the submucous coat. Between the mucous and submucous layers, but belonging to the former, in the whole canal below the beginning of the oesophagus, is a thin coat of smooth muscular fibre, the muscularis mucosae, consisting in some parts, e.g., in the stomach, of two, or even three, layers. Between this and the lumen of the canal lie the ducts and alveoli of glands, sur- rounded by bloodvessels and embedded in adenoid or lymphoid tissue, which in particular regions is collected into well-defined masses (solitary follicles, Peyer's patches, tonsils), extending, it may be, into the submucous tissue. In the mouth, pharynx and oesophagus, the glands lie in the submucosa, as do the glands of Brunner in the duodenum ; everywhere else they are confined to the mucous membrane proper. Between the openings of the glands the mucous membrane is lined with a single layer of columnar epithelial cells, sometimes (in the small intestine) arranged along the sides of tiny projections or villi. At the ends of the alimen- tary canal, viz., in the mouth, pharynx and oesophagus, and at the anus, the epithelium is stratified squamous, and not columnar. The purpose of food is to supply the waste of the tissues and to maintain the normal composition of the body. In the body we find a multitude of substances marked off from each other, some by the sharpest chemical differences, others by characters much less distinct, but falling upon the whole into a few fairly definite groups. Thus, there are bodies like serum-albumin, serum-globulin, myosin, and so on, which are so much alike that they can all be placed in one great class, diS proteids. Then we have bodies like glycogen and dextrose, vastly simpler in their composition, and DIGESTION. ■2-yi belonging to the group of carho-liydratcs. Then, again, fats of various kinds are widely distributed in normal animal bodies ; and inorganic materials, such as water and salts, are never absent. Now, although it is by no means necessary that a sub- stance in the body belonging to one of these great groups should be derived from a substance of the same group in the food, it has been found that no diet is sufficient for man unless it contains representatives of all ; a proper diet must include proteids, carbo-hydrates, fats, inorganic salts and water. These proximate principles have to be obtained from the raw material of the food-stuffs ; it is the business of digestion to sift them out and to prepare them for absorption. This preparation is partly mechanical, partly chemical. The water and salts and some carbo-hydrates, such as dextrose, are ready for absorption without change. Fats are, for the most part, only mechanically altered. Indiffu- sible carbo-hydrates, like starch and dextrin, are changed into diffusible sugar, and the natural proteids into diffusible peptones. Mechanical division of the food is an important aid to the chemical action of the digestive juices. We shall see that this mechanical division forms a great part of the work of the stomach, but it is normally begun in the mouth, and it is of consequence that this preliminary stage should be properly performed. I. The Mechanical Phenomena of Digestion. Mastication. — It is among the mammalia that regular mastication of the food first makes its appearance as an important aid to digestion. The amphibian bolts its fly, the bird its grain, and the fish its brother, without the ceremony of chewing. In ruminating mammals we see mastication carried to its highest point ; the teeth work all day long, and most of them are specially adapted for grinding the food. The carnivora spend but a short time in mastication; their teeth are in general adapted rather for tearing and cutting than for grinding. Where the diet is partly animal and partly vegetable, as in man, the teeth are fitted for all 238 A MANUAL OF PHYSIOLOGY. kinds of work ; and the process of mastication is in general neither so long as in the purely vegetable feeders, nor so short as in the carnivora. In man there are two sets of teeth : the temporary or milk- teeth, and the permanent teeth. The milk-teeth are twenty in number, and consist on each side of four incisors or cutting-teeth, two canines or tearing-teeth, and four molars or grinding-teeth. The central incisors emerge at the seventh month from birth, the other incisors at the ninth month, the canines at the eighteenth, and the molars at the twelfth and twenty-fourth month respectively. Each tooth in the lower jaw appears a little before the corresponding one in the upper jaw. Each of the milk-teeth is in course of time replaced by a permanent tooth, and in addition the vacant portion of the gums behind the milk set is now filled up by twelve teeth, six on each side, three above and three below. These twelve are the permanent molars ; they raise the number of the permanent teeth to thirty-two. The permanent teeth which occupy the position of the milk molars now receive the name of premolars. The first tooth of the permanent set (the first true molar) appears at the age of 6|- years, the last molar, or wisdom tooth, does not emerge till the seventeenth to the twenty-fifth year. In mastication the lower jaw is moved up and down, so as to alternately separate and approximate the two rows of teeth. It has also a certain amount of movement from side to side, and from front to back. The masseter, temporal and internal pterygoid muscles raise, and the digastric, with the assistance of the mylo- and genio-hyoid, depresses, the lower jaw. The external pterygoids pull it forward when both contract, forward and to one side when only one contracts. The lower fibres of the temporal muscle retract the jaw. The buccinator and orbicularis oris muscles prevent the food from passing between the teeth and the cheeks and lips. The tongue keeps the food in motion, works it up with the saliva, and finall}' gathers it into a bolus ready for deglutition. 'That mastication may be properly performed, the teeth must be sound ; and that they may remain sound, they should be kept clean. DIGESTION. 239 For the particles of food that adhere to the teeth after a meal become the feeding-ground of bacteria, whose acid products injuriously affect the enamel, and often by corroding it expose the dentine. Entrance is thus afforded to the micro-organisms of caries, which, although they cannot live on enamel with its small proportion of organic matter, flourish upon dentine, and especially upon the contents of the pulp cavity when this is at length opened. In addition to the deformity and the loss of distinctness in speech which extensive destruction of the teeth entails, a vast number of cases of foul breath are entirely due to filthy and carious teeth. And since in most countries bad breath subtracts more from the sum of human happiness than bad laws, there is perhaps, even in this relation alone, no single hygienic measure that costs so little andyields so much as the thorough and systematic cleansing of the mouth. But the proper care of the teeth is by no means of merely i^sthetic interest ; it is of great importance for the maintenance of health. In many cases of severe and even serious dyspepsia, the cause of the mischief lies no deeper than the mouth, and the patient needs, not physic for his stomach, but filling for his carious teeth. And although no physician at the present day can take all medicine for his province as Bacon took all knowledge, every man who busies himself with the treatment of alimentary diseases (and how few diseases are not in some degree alimentary !) should know enough about the teeth to be able to tell when a patient has mistaken the doctor's door for the dentist's.' Deglutition. — This act consists of a voluntary and an involuntary stage. During the former the anterior part of the tongue is pressed against the hard palate so as to thrust the bolus through the isthmus of the fauces. As soon as this has happened and the food has reached the posterior portion of the tongue, it has passed beyond the control of the will, and the second or involuntary stage of the process begins. This stage may be divided into two parts : (i) pharyngeal, (2) oesophageal — both being reflex acts. During the first the food has to pass through the pharynx, the upper portion of which forms a part of the respiratory tract, and is in free communication with the larynx during ordinary breathing. It is therefore necessary that respiration should be inter- rupted and the larynx closed while the food is being moved through the pharynx. But that the interruption may be short, the food must be rapidly passed over this perilous portion of its descent. The pharynx is accordingly provided with rapidly-contracting striped muscle ; and that none of 240 A MANUAL OF PHYSIOLOGY. its purchase may be lost, the pharyngeal cavity is cut off from the nose and mouth as soon as the bolus has entered it. The soft palate is raised by the levator palati ; at the same time the upper part of the pharynx, narrowed by the contraction of the superior constrictor, comes forward to meet the soft palate, closes in upon it, and so prevents the food from passing into the nasal cavities. The pharynx is cut off from the mouth by the closure of the fauces through the contraction of the palato-pharyngeal muscles which lie in their posterior pillars. The larynx is pulled upwards and forwards by the contraction of the thyro-hyoid muscle, and the elevation of the hyoid bone by the muscles which connect it to the lower jaw. The glottis is closed by the approximation of the vocal cords and the arytenoid cartilages, assisted it may be by the epiglottis. But this organ can hardly play the great part which has been assigned to it in closing the larynx, since swallowing proceeds in the ordinary way when it is absent. The morsel of food, grasped by the middle and lower constrictors as it leaves the back of the tongue, passes rapidly and safely over the closed larynx, the process being accelerated by the pulling up of the lower portion of the pharynx over the bolus by the action of the palato- and stylo-pharyngei. The second or oesophageal portion of the involuntary stage is a more leisurely performance. The bolus is carried along by a peculiar contraction of the muscular wall of the oesophagus, which travels down as a wave, pushing the food before it. When the food reaches the lower end of the gullet the tonic contraction of that part of the tube is for a moment relaxed, apparently by reflex inhibition, and the morsel passes into the stomach. There are certain remarkable peculiarities which dis- tinguish this peristaltic movement of the oesophagus from that of other parts of the alimentary canal. It is far more closely related to the nervous system, and, unlike the peristaltic contraction of the intestine, can pass over any muscular block caused by ligature, section, or crushing, so long as the nervous connections are intact. But division of the oesophageal nerves causes, as a rule, stoppage of DIGESTION, 241 oesophageal movements ; although under certain circum- stances an excised portion of the tube may go on contracting in the characteristic way after removal from the body. Again, the peristaltic wave when artificially excited seems always under normal conditions to travel down the oesophagus, never to spread upwards or in both directions, as may happen in the intestine. In vomiting, however, there must be a reverse peristalsis. Stimulation of the mucous membrane of the pharynx will cause reflex movements of the oesophagus, while stimulation of its own mucous membrane is ineffective. From these facts we learn that although the muscle of the oesophagus may possess a feeble power of spontaneous peristaltic contraction, yet this is usually in abeyance, or at least overmastered by nervous control ; so that impulses, passing from a nerve centre and travelling down in regular progression along the oesophageal nerves, excite the muscular fibres in succession from the upper to the lower end of the tube. The centre for the whole involuntary stage (both pharyngeal and oesophageal) of deglutition lies in the upper part of the medulla oblongata, a little above the respiratory centre. When the brain is sliced away above the medulla deglutition is not affected, but if the upper part of the medulla is removed, the power of swallowing is abolished. In man disease of the spinal bulb interferes far more with deglutition than disease of the brain proper. Normally the afferent impulses to the centre are set up by the contact of food or saliva with the mucous membrane of the posterior part of the tongue, the soft palate and the fauces, the nerve-channels being the superior laryngeal, the pharyngeal branches of the vagus, and the palatal branches of the fifth nerve. Artificial stimulation of the central end of the superior laryngeal will cause the movements of degluti- tion independently of the presence of food or liquid ; but if the central end of the glosso-pharyngeal nerve be stimulated at the same time, the movements do not occur. The glosso- pharyngeal is therefore able to inhibit the deglutition centre, and it is probably owing to the action of this nerve that in a series of efforts at swallowing, repeated within less than a 16 242 A MANUAL OF PHYSIOLOGY. certain short interval (about a second), only the last is successful. The efferent nerves of the reflex act of deglutition are the hypoglossal to the tongue and the thyro-hyoid and other muscles concerned in raising the larynx ; the glosso-pharyn- geal, vagus, facial and fifth to the muscles of the palate, fauces, and pharynx ; and the vagus to the larynx and oesophagus. Section of the vagus interferes with the passage of food along the oesophagus ; stimulation of its peripheral end causes oesophageal movements. Movements of the Stomach and Intestines. — Here the peri- staltic movements become much more independent of the nervous system, and much more dependent upon the con- tinuity of the muscular tissue than in the oesophagus. In the stomach the arrangement of the muscular fibres is such that the peristaltic waves do not, as a rule, travel right down from the cardiac to the pyloric end, but spread out in a more irregular fashion, giving rise to the so-called churning move- ments. When the stomach is empty it is contracted and at rest. The presence of food causes churning movements to begin, which, feeble at first, become stronger and stronger as digestion proceeds. By these movements the food is worked up thoroughly with the gastric juice. Kept in constant circulation, it gradually becomes reduced to a semi-liquid mass, the chyme, which is at intervals driven against the pylorus by strong and regular peristaltic con- tractions of the lower end of the stomach, the sphincter relaxing from time to time by a sort of reflex inhibition to admit the better-digested portions into the duodenum. The peristaltic movements of the small intestine are the most typical of their kind. Normally, the constriction travels always down the tube, squeezing the contents before it, and the wave ends at the ileo-csecal valve, which separates the small intestine from the large. But under certain conditions, a reverse or anti-peristalsis is set up even in the intact body, and by artificial stimulation it is easy to excite peristaltic waves, which travel in both directions. The movements of the large intestines do not differ essentially from those of the small. They start at the ileo-csecal valve and travel down- DIGESTION. 243 wards, but do not normally reach the rectum, which, except during defsecation, remains at rest. Influence of Nerves on the Gastro-intestinal Movements. — As we have said, these movements are much less closely dependent on the nervous system than are those of the oesophagus ; they can go on when the nervous connections are cut ; they cannot spread when the continuity of the muscle is destroyed, and the mere presence of food will excite them when reflex action has been excluded by section of the nerves. Nevertheless, the nervous system does exercise some influence in the way of regulation and control, if not in the way of direct initiation of the movements, and the swallowing or even the smell of food has been observed to strengthen the contractions of a loop of intestine severed from the rest, but with its nerves still intact. The vagus is the efferent channel of this reflex action : stimulation of its peripheral end may cause movements of all parts of the alimentary canal from oesophagus to large intestine, and may strengthen movements already going on ; but section of it does not stop them, nor hinder the food from causing peristalsis wherever it comes. It is only the distant and reflex action of food which division of the vagi can abolish ; and we do not know to what extent the movements of normal digestion are directly excited, and to what extent they are reflex. The splanchnic nerves contain fibres by which the intestinal movements can be inhibited, but they are certainly not always in action, for section of these nerves has no distinct effect upon the movements, in spite of the vascular dilatation which it causes. On the other hand, stimulation of the peripheral end of the cut splanchnic usually, but by no means invariably, causes arrest of the peristalsis. Occasionally, however, it has the opposite effect. We have no evidence that the ganglion-cells in the walls of the alimentary canal are either automatic or reflex centres for its movements. The lower part of the large intestine is influenced by the sacral nerves (second, third and fourth sacral in the rabbitV, and^by certain lumbar nerves, in the same way as the higher parts of the alimentary canal, and particularly the small 244 ^ MANUAL OF PHYSIOLOGY. intestine, are influenced by the vagus and the splanchnics. Stimulation of these sacral nerves within the spinal canal causes contraction, tonic or peristaltic, of the descending colon and rectum ; stimulation of the lumbar nerves or of the portions of the sympathetic into which their visceral fibres pass (lumbar sympathetic chain from second to sixth ganglia, or the rami from it to the inferior mesenteric ganglia), causes inhibition of the movements, preceded, it may be, by a transient increase. Stimulation of the sacral nerves causes or increases the contraction of both coats of the descending colon and rectum, stimulation of the lumbar nerves inhibits both. And in the small intestine the same law holds good ; the two coats are contracted together by the action of the vagus, or inhibited together by that of the splanchnics (Langley). With the establishment of these facts an in- genious theory, originated by V. Basch and adopted by Gaskell, falls to the ground. They supposed that the same nerve which causes contraction of the circular coat in all tubes whose walls are made up of two layers of muscle, also contains fibres that bring about inhibition of the longitudinal coat, and vice^ versa. It was suggested that in this way antagonism between the two coats was pre- vented. Some drugs, such as strychnia, stimulate peristaltic move- ments by acting through the central nervous system ; others, like nicotine and muscarine, by acting directly on the intes- tine. Atropia antagonizes the action of muscarine, and morphia that of nicotine, in both cases by local influence ; but after morphia the intestinal walls are steadily contracted, not relaxed. An isolated loop of intestine, fed with properl}^ oxygenated blood, remains altogether, or nearly, at rest ; if the blood is allowed to become venous, vigorous movements begin. Defaecation is partly a voluntary and partly a reflex act. But in the infant the voluntary control has not yet been developed ; in the adult it may be lost by disease ; in an animal it may be abolished by operation, and in each case the action becomes wholly reflex. In the normal course of DIGESTION. 245 events, the rectum, which is empty and quiescent in the intervals of defsecation, is excited to contraction as soon as fasces begin to enter it through the sigmoid flexure, and the sensations caused by their presence give rise to the desire to empty the bowels. This desire may for a time be resisted by the will, or it may be yielded to. In the latter case the abdominal muscles are forcibly contracted, and the glottis being closed, the whole effect of their contraction is ex- pended in raising the pressure within the abdomen and pelvis, and so driving the faeces from the colon to the rectum. The sphincter ani is now relaxed by the inhibition of a centre in the lumbar portion of the spinal cord, through the activity of which the tonic contraction of the sphincter is normally maintained. This relaxation is partly voluntary, the im- pulses that come from the brain acting probably through the medium of the lumbar centre ; but in the dog, after section of the cord in the dorsal region, the whole act of defaeca- tion, including contraction of the abdominal muscles and relaxation of the sphincter, still takes place, and here the process must be purely reflex. The contraction of the levatores ani helps to resist over-distension of the pelvic floor and to pull the anus up over the faeces as they escape. Vomiting. — We have seen that under normal conditions the movements of the alimentary canal always tend to carry the food in one definite direction, along the tube from the moljth to the rectum. The peristaltic waves generally run only in this direction, and, further, regurgitation is prevented at three points by the cardiac and pyloric sphincters of the stomach and the ileo-caecal valve. But in certain circum- stances the peristalsis may be reversed, one or more of the guarded orifices forced, and the onward stream of the intestinal contents turned back, In obstruction of the bowel, the faecal contents of the large intestine may pass up beyond the ileo-caecal valve, and, reaching the stomach, be driven by an act of vomiting through the cardiac orifice ; in what is called ' a bilious attack,' the contents of the duodenum may pass back through the pylorus and be ejected in a similar way ; or, what is by far the most common case, the contents of the stomach alone may be expelled. 246 A MANUAL OF PHYSIOLOGY. Vomiting is usually preceded by a feeling of nausea and a rapid secretion of saliva, which perhaps serves, by means of the air carried down with it when swallowed, to dilate the cardiac orifice of the stomach, but may be a mere by-play of the reflex stimulation bringing about the act. The dia- phragm is now forced down upon the abdominal contents, the glottis closed, and the abdominal muscles strongly con- tracted. At the same time the stomach itself contracts, the cardiac orifice relaxes, and the gastric contents are shot up into the pharynx, and issue by the mouth or nose. Either the stomach alone or the diaphragm and abdominal muscles alone, or the diaphragm and stomach together, without the abdominal muscles, can carry out the act of vomiting. For an animal in which the phrenic and intercostal nerves have been cut can still vomit ; so can an animal whose stomach has been replaced by a bladder ; and Hilton saw that a man who lived fourteen years after an injury to the spinal cord at the height of the sixth cervical nerve, which caused com- plete paralysis below that level, could vomit, though with great difficulty. In a young child, in which very slight causes will induce vomiting, the stomach alone contracts during the act. The nerve centre is in the medulla oblongata. It may be excited by many afferent channels : irritation of the fauces or pharynx, of the stomach or intestines (as in strangulated hernia), of the liver or kidney (as in cases of gallstone or renal calculi), of the uterus or ovary, and of the brain (as in cerebral tumour), are all capable of causing vomiting by impulses passing from them to the vomiting centre. The vagus nerve in man certainly contains afferent fibres by the stimulation of which this centre can be excited, for it has been noticed that when the vagus was exposed in the neck in the course of an operation, the patient vomited whenever the nerve was touched (Boinet, quoted by Gowers). In meningitis, vomiting is often a prominent symptom, and is sometimes due to irritation of the vagus nerve by the inflammatory process. Some drugs act as emetics by irritating surfaces in which efficient afferent impulses may be set up, the gastric mucous DIGESTION. 247 membrane, for example ; sulphate of zinc and sulphate of copper act mainly in this way. Apomorphia, on the other hand, stimulates the centre directly, and this is also the mode in which vomiting is produced in certain diseases of the medulla oblongata. The efferent nerves for the diaphragm are the phrenics, for the abdominal muscles the intercostals. The impulses which cause contraction of the stomach pass along the vagi. Dilatation of the cardiac orifice is brought about partly by the shortening of muscular fibres^ which spread out upon the stomach from the lower end of the oesophagus, perhaps partly by nervous inhibition. II. The Chemical Phenomena of Digestion. The chemical changes wrought in the food as it passes along the alimentary canal are due to the secretions of various glands, which line its cavities, or pour their juices into it through special ducts. These secretions owe their power for the most part to substances present in them in very small amount, but which, nevertheless, act with extraordinary energy upon the various constituents of the food, causing profound changes without being themselves used up, or their digestive power affected. These marvellous and as yet mysterious agents are the unformed or un- organized ferments — unorganized because, unlike some other ferments, such as yeast, their action does not depend upon the growth of living cells. Their chemical nature has not been exactly made out ; some of them at least do not appear to be proteids. But it is doubtful whether even one of the ferments of the digestive juices has as yet been satisfactorily isolated, and at present it is only by their effects that we recognise them. Some of them act best in an alkaline, some in an acid medium ; they all agree in having an ' optimum ' temperature, which is more favourable to their action than any other ; a low temperature suspends their activity, and boiling abolishes it for ever. The action of all of them seems to he hydrolyiic ; i.e., it is accompanied with the taking up of the elements of water by the substance acted upon. The accumulation of the products of the action first checks and then arrests it. 248 A MANUAL OF PHYSIOLOGY. Beside these unformed ferments, certain formed ferments, or micro-organisms, are present in parts of the alimentary canal, and even in normal digestion contribute to the changes brought about in the food ; while under abnormal conditions they may awaken into troublesome, and even dangerous, activity. It is possible that many of these act by producing unorganized ferments, and that the distinction between the two kinds of ferments is rather superficial. It is now necessary to consider in detail the nature of the various juices yielded by the digestive glands, and the mechanism of their secretion, so far as it is known to us. Since it is along the digestive tract that glandular action is seen on the greatest scale, this discussion will practically embrace the nature of secretion in general. And here it may be well to say that, although in describing digestion it is necessary to break it up into sections, a true view is only got when we look upon it as a single, though complex, process, one part of which fits into the other from beginning to end. It is, indeed, the duty of the physiologist, wherever it is possible to insert a cannula into a duct and to drain off an unmixed secretion, to investigate the properties of each juice upon its own basis ; but it must not be forgotten that in the body digestion is the joint result of the chemical work of five or six secretions, the greater number of which are actually mixed together in the alimentary canal, and of the mechanical work of the gastro-intestinal walls. The Chemistry of the Digestive Juices. (i) Saliva. — The saliva of the mouth is a mixture of the secretions of three large glands on each side, and of many small ones. The large glands are the parotid, which opens by Stenson's duct opposite the second upper molar tooth ; the submaxillary, which opens by Wharton's duct under the tongue ; and the sublingual, opening by a number of ducts near and into Wharton's. The small glands are scattered over the sides, floor, and roof of the mouth, and over the tongue. Two types of salivary glands, the serous or albuminous and the mucous, are distinguished by structural characters and DIGESTION. 249 by the nature of their secretion ; and the distinction has been extended to other glands. The parotid of many, if not all, mammals is a purely serous gland ; it secretes a watery juice with a general resemblance in composition to dilute blood-serum. The submaxillary of the dog and cat is a typical mucous gland ; its secretion is viscid, and contains mucin. The submaxillary gland of man is a mixed gland ; mucous and serous alveoli, and even mucous and serous cells, are intermingled in it (Plate II.). The submaxillary of the rabbit is purely serous. The sublingual is in general a mixed gland, but with far more mucous than serous alveoli. The mixed saliva is a somewhat viscous, colourless liquid of alkaline reaction and low specific gravity (average about 1005). Besides water and salts, it contains mucin (entirely from the submaxillary, the sublingual and the small mucous glands of the mouth), to which its viscidity is due, traces of serum-albumin and serum-globulin (chiefly from the parotid), and a ferment — ptyalin. The salts are calcium carbonate and phosphate (often deposited as 'tartar' around the teeth, occasionally as salivary calculi in the glands and ducts), sodium and potassium chloride, and usually, but not always, a trace of sulphocyanide of potassium, detected by the red colour which it strikes with ferric chloride. The total solids amount only to five or six parts in the thousand. A great deal of carbonic acid can be pumped out from saliva, as much as 60 to 70 cc. from 100 cc. of the secretion, i.e., more than can be obtained from venous blood. Only a small proportion of this is in solution, the rest existing as carbonates. Under the microscope epithelial scales, leuco- cytes (the so-called salivary corpuscles), bacteria, and portions of food, maybe found. All these things are as accidental as the last — they are mere flotsam and jetsam, washed by the saliva from the inside of the mouth. The quantity of saliva secreted in the twenty-four hours varies a good deal. On an average it is from i to 2 litres. (Practical Exercises, p. 322.) Besides its functions of dissolving sapid substances, and so allowing them to excite sensations of taste, of moistening the food for deglutition and the mouth for speech, and of cleansing the teeth after a meal, saliva, in virtue of its 250 A MANUAL OF PHYSIOLOGY. ferment, ptyalin, is amylolytic ; that is, it has the power of digesting starch and converting it into maltose, a reducing sugar. In man the secretion of any of the three great saHvary glands has this power, although that of the parotid is most active. In the dog and cat, on the other hand, parotid saliva has little or no action on starch ; while in animals like the rat and the rabbit it is highly active, although in the last-named animal the submaxillary saliva is almost powerless. In the horse, sheep, and ox, the saliva secreted by all the glands seems equally inactive. A watery or glycerine extract of a gland whose natural secre- tion is active also possesses amylolytic power. Starch-grains consist of granulose enclosed in envelopes of cellulose. Only the granulose is acted upon by ptyalin, and hence unboiled starch, in which the cellulose envelopes are intact, is but slowly affected by saliva. When starch is boiled, the envelopes are ruptured, and the granulose passes into imperfect solution, yielding an opalescent liquid. If a little saliva be added to some boiled starch solution v/hich is free from sugar, and the mixture be set to digest at a suitable temperature (say 40° C), the solution in a very short time loses its opalescence and becomes clear. It still, however, gives the blue reaction with iodine ; and Trommer's test (p. 323) shows that no sugar has as yet been formed. The change is so far purely a physical one ; the substance in solution is soluble starch. Later on the iodine reaction passes gradually through violet into red ; and finally iodine causes no colour change at all, while maltose is found in large amount, along with isomaltose, a sugar having the same formula as maltose, but differing from it in the melting point of the crystalline compound formed by it with phenyl hydrazine (p. 370). Traces of dextrose, a sugar which rotates the plane of polarization less than maltose, but has greater reducing power, are produced by the further action of the saliva on maltose itself. When a small quantity of ferment acts for a short time, the production of isomaltose is favoured. The production of maltose and dextrose is favoured by the action of a large quantity of ferment for a long time (Kiilz and Vogel). DIGESTION. 251 The red colour indicates the presence of a kind of dextrin called erythrodextrin ; the violet colour shows that at first this is still mixed with some unchanged starch. Soon the erythrodextrin disappears, and is succeeded by another dextrin, which gives no colour with iodine, and is therefore called achroodextrin. This is partly, but in artificial digestion never completely, converted into maltose, and can always at the end be precipitated in greater or less amount by the addition of alcohol to the liquid. It is probable that a whole series of dextrins is formed during the digestion of starch. Some of these may appear as forerunners of the sugar, others merely as concomitants of its production. The latter may never pass into sugar ; and it is certain that sugar may appear before all the starch has been converted into achroodextrin. When the sugar is removed as it is formed, as is approximately the case when the digestion is performed in a dialyser, the residue of unchanged dextrin is less than when the sugar is allowed to accumulate (Lea). In ordinary artificial digestion, for instance, under the most favourable circumstances at least 12 to 15 per cent, of the starch is left as dextrin ; in dialyser digestions the residue of dextrin may be little more than 4 per cent. This goes far to explain the complete digestion of starch which apparently takes place in the alimentary canal, a digestion so complete that although soluble starch and dextrin may be found in the stomach after a starchy meal, they do not occur in the intestine, or only in minute traces. Here the amylolytic ferment of the pancreatic juice, which, as we shall see, is essentially the same in its action as ptyalin, only more powerful, must be able to effect a very complete conversion. It is impossible with our present knowledge to represent the entire process by a chemical equation. If we look only to the final product, the equation (C,Hi,0,)« + ^H.O = I (CioH.p,,) Starch. Water. Maltose. or will represent the change in natural and complete digestion. The molecule of starch being taken as some unknown multiple, a, of the 2 52 A MA NUA L OF PH Y BIOLOGY \ group CgHjf,Or,, the first equation suits the case of a being an even number, and the second that of a being an odd number. If we accept 4 per cent, as the minimum residue of unchanged dextrin in the best artificial digestion, or, in other words, if we suppose that of 25 parts of starch 24 are changed into maltose, and i remains as dextrin, our equation, taking the dextrin molecule as a multiple b of CgHjoOj, will be : 25(QHi„0,-,). + 1 2aH,0 = 1 2a(CioHooOn) + ^ (QH.oO,), Starch. Water. Maltose. Dextrin. for the case where - is a whole number. If - is not a whole b 0 number, we should have to clear of fractions by multiplying both sides by — , where ui is the greatest common measure of a and b. m We should thus get : 25 A(C,HioO,)„ +i2a^ H.O = 1 2«i(C,.,H.,..0ii) + -{C,YL^,0:)^ m III ' III " III Starch. Water. Maltose. Dextrin. It is a notable fact that amylolytic ferments are not confined to the animal body. Diastase, which is present in all sprouting seeds, and may be readily extracted by water from malt, forms maltose and dextrin from starch. Its optimum temperature, however, is about 65° C, while that of ptyalin is about 40° C. Salivary digestion goes on best in a neutral or slightly alkaline medium. It can, however, still proceed when the medium is made faintly acid ; but an acidity equal to that of a 'I per cent, solution of hydrochloric acid stops it completely, although the ferment is still for a time able to act when the acidity is sufficiently reduced. Strong acids or alkalies permanently destroy it. These facts are of con- sequence, for they show that in the mouth, where the reaction is alkaline, the conditions are favourable to salivary digestion ; while in the stomach, where, as we shall see, it is acid during the greater part of digestion, the conditions are not so favourable, but may be, on the contrary, inimical. Although the food stays but a short time in the mouth, there is no doubt that, in man at least, some of the starch is there changed into sugar (p. 323). But this does not seem to be the case in all animals. Something depends on the amylolytic activity of the saliva, and something upon the DIGESTION. 253 form in which the starchy food is taken, whether it is cooked or raw, enclosed in vegetable fibres or exposed to free admixture with the secretions of the mouth. It is important to note here that hydrolytic changes of very much the same nature as those produced by ptyalin can be brought about in other ways. If starch is heated for a time with dilute hydrochloric or sulphuric acid, it is changed first into dextrin, and then into a form of reducing sugar, which, however, is not maltose, but dextrose. If maltose is treated with acid in the same way, it is also changed into dextrose. When glycogen (p. 381) is boiled with dilute oxalic acid at a pressure of three atmospheres, isomaltose and dextrose are formed (Cremer). We shall see later on that the action of other ferments can also be to a certain extent imitated by purely artificial means. In fact, some of the ferments accomplish at a comparatively low temperature what can be done in the laboratory at a higher temperature, and by the aid of what we may call more violent methods. (2) Gastric Juice. — The Abbe Spallanzani was the first to recognise the chemical powers of the gastric juice, and to give the secretion its name, but it was by the careful and convincing experiments of Beaumont that the foundation of our exact knowledge of its composition and action was laid. It is difficult to speak without enthusiasm of the work of Beaumont, if we consider the difficulties under which it was carried on. An army surgeon stationed in a lonely post in the wilderness that was then called the territory of Michigan, a thousand miles from a university, and four thousand from anything like a physiological laboratory, he was accidentally called upon to treat a gun-shot wound of the stomach in a Canadian voyageur, Alexis St. Martin. When the wound healed a permanent fistulous opening was left, by means of which food could be introduced into the stomach and gastric juice obtained from it. Beaumont at once perceived the possibilities of such a case for physiological research, and began a series of experiments on digestion. After a while, St. Martin, with the wandering spirit of the voyageur, returned to Canada without Dr. Beaumont's consent and in his absence. Beaumont traced him, with great difficulty, by the aid of the Hudson Bay Company's officials, induced him to come back, provided for his family as well as for himself, and proceeded with his investigations. A second time St. Martin went back to his native country, and a second 254 ^4 MANUAL OF PHYSIOLOGY. time the zealous investigator of the gastric juice, at heavy expense, secured his return. And although his experiments were necessarily less exact than would be permissible in a modern research, the modest book in which he published his results is still counted among the classics of physiology. The production of artificial fistuk^ in animals, a method that has since proved so fruitful, was first suggested by his work. Gastric juice when obtained pure, as it can be from an accidental fistula in man, or by passing a tube through the oesophagus into the stomach, or by mechanically stim.u- lating the mucous membrane of the stomach of a fasting dog through an artificial gastric fistula, is a thin, colourless liquid of low specific gravity (1002 to 1005) and distinctly acid reaction. The total solids average about 5 parts per thousand, about one half being inorganic salts, chiefly sodium and potassium chloride. Two ferments are present : pepsin, which changes proteids into peptones ; and rennin, which curdles milk. The acidity is due to free hj^drochloric acid, the proportion of which in man is usually something like •2 per cent., but more in the dog ("3 to -5 per cent.). It is said that in cancer of the stomach the free h3'drochloric acid is replaced by lactic acid. That in normal gastric juice the acidity is not due to lactic acid, can be shown by Uffelmann's test. The reagent is a dilute solution of carbolic acid to which a trace of ferric chloride has been added (say a drop of a i per cent, ferric chloride solution to 5 cc. of a I per cent, carbolic acid solution). The blue colour of the mixture is turned yellow by lactic acid, but not by dilute hydrochloric acid; normal healthy gastric juice does not affect it, therefore its acidity is not caused by free lactic acid. More than this, it is not caused by an organic, but by an inorganic acid, for congo-red, methyl violet, phloroglucin-vanilhn, and some other coloured organic sub- stances, are altered in colour by dilute mineral acids, while much stronger organic acids do not affect them ; gastric juice, in which the acid is decidedly dilute, readily causes the change, therefore its acidity is due to a mineral acid. Finally, when the bases and acid radicals of the juice are quantitatively compared, it is found that there is more chlorine than is required to combine with the bases ; the DIGESTION. 255 excess must be present as free hydrochloric acid. The quantity of gastric juice secreted is very great ; it has been estimated at as much as 5 to 10 htres in twenty four hours, or five times as much as the quantity of saHva secreted in the same time. But such estimates are loose and uncertain. The great action of gastric juice is upon proteids. In this two of its constituents have a share, the pepsin and the free acid. One member of this chemical copartner}^ cannot act without the other ; peptic digestion requires the presence both of pepsin and of acid ; and, indeed, an active artificial juice can be obtained by digesting the gastric mucous membrane with '2 per cent, hydrochloric acid. A glycerine extract of a stomach which is not too fresh also possesses peptic powers ; but it requires the addition of a sufficient quantity of acid to render them available. Well-washed fibrin obtained from blood is a convenient proteid for use in experiments on digestion. Since the blood contains traces of pepsin, the fibrin should be boiled to destroy any which may be present. If we place a little fibrin in a beaker, cover it with '2 per cent, hydrochloric acid, add a small quantity of pepsin or of a gastric extract, and put the beaker in a water-bath at 40° C, the fibrin soon swells up and becomes translucent, then begins to be dissolved, and in a short time has dis- appeared (see Practical Exercises, p. 324). If we examine the liquid before digestion has proceeded very far, we shall find chiefly acid-albumin in solution ; later on, chiefly albumoses ; and still later, chiefly peptones. From this we conclude that acid-albumin is a stage in the conversion of fibrin into albumose, and albumose a half-way house between acid-albumin and peptone. Similar, but not identical, intermediate substances occur in the digestion of the other proteids, as well as in that of bodies like gelatin, which are not true proteids, but which pepsin can digest. The generic name of proteose has been proposed for bodies of the albumose type, the term albu- mose itself being reserved for such intermediate products of the digestion of albumin ; while those of fibrin are called fibrinoses ; of globulm, globuloses ; of casein, caseoses, and 256 A MAXUAL OF PHYSIOLOGY. SO on. Probably the peptones produced from different pro- teids are also not absolutely identical. Beyond peptone gastric digestion does not go. Indeed, in no case does the whole of the original proteid, in an artificial digestion, ever reach the stage of peptone; although the pancreatic juice, as we shall see later on, can spHt up peptone itself into substances which are no longer proteid. Since the subject of proteid digestion must come up again, it will be well to postpone any closer discussion of the process till we can view it as a whole. In the meantime it is only necessary to repeat that pepsin alone cannot digest proteids at all. Its action requires the presence of an acid ; in a neutral or alkaline medium peptic digestion stops. As in the case of other ferments, there is a certain temperature at which pepsin acts best, an 'optimum' temperature (35° to 40° C, or about that of the body). At 0° C. it is inactive, except in cold-blooded animals (frog). Boiling destroys it. Dilute acid alone does not dissolve coagulated proteids like boiled fibrin, or does so only with extreme slowness. Uncoagulated proteids, however, are readily changed by it into acid-albumin ; and by the prolonged action of acids, especially at a high temperature, further changes may be caused in all proteids, apparently of much the same nature as those produced in peptic digestion. But, under the ordinary conditions of natural or artificial gastric digestion, it may be said that the acid alone does little until it is aided by the ferment, just as the ferment alone does nothing without the aid of the acid. One striking difference, how- ever, there is : the acid is used up during the process; the ferment is little, if at all, affected. Although hydrochloric acid acts most powerfully, other acids, such as lactic, phos- phoric, or sulphuric, can replace it. The milk-curdling ferment, rcnnin, is obtained in large amount in an extract of the fourth stomach of the calf, which has long been used in the manufacture of cheese. It exists in the healthy gastric juice of man, but disappears in cancer of the stomach and in chronic gastric catarrh. It can be separated from pepsin by precipitating an extract of calf's stomach with mae^nesium carbonate in DIGESTION. 257 powder, which carries down the pepsin, but leaves the rennin in the supernatant hquid. The curdHng of milk by rennin is essentially a coagulation of casein. It seems to be produced by the splitting up of a more complex body, caseinogen, into two substances, one of which, casein, is insoluble (in the presence of calcium phosphate, but not otherwise), and forms the curd ; while the other, whey- proteid, is soluble, and passes into the whey. Dilute acid will of itself precipitate casein, and the presence of acid in the gastric juice helps the action of the milk -curdling ferment. That a ferment is really concerned in the process is, however, shown by the fact that the juice, after being made neutral or alkaline, still curdles milk, and that this power is destroyed by boiling. The optimum temperature is the same as that of the other ferments of the digestive tract, about 40° C. (p. 325). As to the exact function which the milk-curdling ferment of the gastric juice performs in digestion, we have no precise knowledge. It seems superfluous if we suppose that the free acid is able of itself to do all that the ferment does along with it. But there is evidence that the curd produced by the ferment is more profoundly changed than the pre- cipitate caused by dilute acids ; for the latter may be redissolved, and then again curdled by rennin, while this cannot be done with the former. We may suppose, then, that the ferment is capable of effecting changes more favourable to the subsequent action of the pepsin upon the casein than those which the acid alone would effect. Or it may be that the ferment acts in the early stages of digestion before much acid has been secreted. We do not know whether the curd- ling of milk renders it easier for the watery portion to be absorbed by the walls of the stomach. If this were the case, it would be a raison d'etre for early curdling, since milk is a very dilute food, and the immense proportion of water in it might weaken the gastric juice too much for rapid diges- tion of the proteids. On fats and carbo-hydrates gastric juice has no action, although it wifl dissolve the proteid constituents of fat-cells, and the proteid substances which keep the fat-globules of 17 258 A MAXCAL OF PHYSIOLOGY. milk apart from each other ; while swallowed saliva will continue to act on starch in the stomach, so long as the acidity is not too great. Healthy gastric juice has no action on cane-sugar, but when there is much mucus present, it seems to contain a ferment which changes this sugar into dextrose, or into a mixture of dextrose and levulose (' invert ' sugar). (3) Pancreatic Juice. — Pancreatic juice, bile, and intestinal juice, of which the first two only are important, are all mingled together in the small intestine, and act upon the food, not in succession, but simultaneously. But by artificial fistulae in animals they can all be obtained separately; and occasionall}' some of them can be procured through accidental fistulae in the human subject. Pancreatic juice, as obtained from a dog, by means of a cannula tied in the duct of Wirsung through an opening in the linea alba, is a clear, viscid liquid of distinctly alkaline reaction. It differs notabh' from saliva and gastric juice in its high specific gravity, and the large proportion of solids in it, which may be as much as 10 per cent., or, roughly speaking, about the same as in blood -plasma. About 9 per cent, of the solids are organic (serum-albumin, a peculiar kind of alkali-albumin, and various ferments), and rather less than i per cent, inorganic (chiefly sodium car- bonate, to which the alkaline reaction is due, and sodium chloride). Traces of fats and soaps, and, if the juice is not perfectly fresh, leucin, tyrosin and peptone, produced by the digestion of its own proteids, may also be present. When the juice is heated to near the boiling-point, a copious precipitate of coagulated albumin is formed. The fresh juice coagulates spontaneously, especially at a low tempera- ture; but the coagulum is soon digested. Possibly cold hinders the destructive power of the juice on the factors necessary for coagulation more than it restrains the process of clotting. The quantity of pancreatic juice secreted during the twenty-four hours in an average man has been estimated at 200 to 300 cc. An artificial pancreatic juice can be made by extracting the pancreas, which must not be too fresh (p. 278), with water or glycerine. DIGESTION. 259 Pancreatic juice contains four ferments: (i) A proteolytic or proteid-digesting ferment, trypsin ; (2) an amylolytic fer- ment, amylopsin ; (3) a fat- splitting or lipolytic ferment, steapsin ; (4) a milk-curdling ferment. The last cannot be considered as taking any practical share in digestion, since it can never happen that milk passes through the stomach without being curdled. Trypsin, to a certain extent, corresponds with pepsin in its action on proteids. But it has two remarkable peculiarities : it acts energetically in an alkaline as well as in a not too acid medium (a very slight amount of digestion may go on in distilled water) ; and its action does not stop at the peptone stage — it can split up peptones into leucin and tyrosin, crystalline nitrogenous substances very different from proteids. If fibrin is digested at a temperature of 40° C. with a i per cent, solution of sodium carbonate, to which a little pancreatic extract or juice has been added, along with a trace of thymol to prevent putrefaction, it is gradually eaten away without swelling up and becoming transparent as it does in peptic digestion ; but some granular debris is always left (p. 326). This undigested residue is soluble in i per cent, sodium hydrate, and consists of anti-albumid. It is never entirely dissolved in any artificial digestion ; in natural digestion, on the contrary, it is never found ; just as some dextrin always remains when ptyalin has done its utmost upon starch outside the body, while in the intestine little or no dextrin can be detected. When the undigested residue is filtered off, the solution may still contain : (i) a substance or substances having resemblances both to alkali-albumin and to globulin, (2) albumoses, (3) peptone, (4) leucin and tyrosin. It will depend on how far the digestion has been carried whether, and in what quantity, any one of these bodies is present. The order in which they appear and their relative amount at different stages of the digestion show that the alkali- albumin and albumoses are, like the acid-albumin and albumoses of peptic digestion, mainly, at any rate, inter- mediate substances through which proteid passes on its 26o A MANUAL OF PHYSIOLOGY. way to peptone ; and there is no reason to believe that up to this point there are any essential differences between the action of trypsin and pepsin. In both cases the action seems to consist in a splitting up of the complex proteid with assumption of water, so that each successive product is further hydrated than the last ; nor is it, as yet at least, possible to point out any radical distinction between the peptone of gastric and the peptone of pancreatic digestion. It is not necessary to suppose that the further splitting up of some of the peptone by trypsin into leucin and tyrosin is an action differing in kind so much as in degree from that which leads to the formation of peptone both in tryptic and in gastric digestion. Trypsin is in almost all respects a more powerful ferment than pepsin ; it can do most things which pepsin can do, and a few things which pepsin cannot do : but it can do nothing which is not right in the line of peptic digestion. Thus, a pancreatic digest almost always contains less albumose than a peptic digest ; more of the albumose is carried on to the further stage of peptone by the more powerful ferment ; but we ascribe this not to a peculiar property, but to a more energetic action on the common lines. And when this action suffices to push the peptone still farther along the downward path, it is not necessary to assume that an influence radically different from that of pepsin is at work. This argument is strengthened when we find that without a ferment at all, by the prolonged action of various agents which cause hydration, such as dilute acids or alkalies, or oxidizing substances like ozone, peptones first, and ultimately leucin and tyrosin, may be formed from ordinary proteids. In fact, it would seem that when the complex proteid molecule is split up by proteolytic ferments, or by other and not too violent agents, there are certain favourite ' sets ' or combinations into which its constituents are apt to fall, no matter how the decomposition may be brought about, bodies of the fatty and of the aromatic series being especially constant and conspicuous among the products. Leucin, for instance, is amido-caproic acid, in which amidogen (NHo) has replaced one atom of H in the fatty acid, and tyrosin is an DIGESTION. 261 amidated aromatic acid (p. 326). So we may perhaps con- sider the proteid molecule as partly built up out of fatty acid and aromatic groups united with amidogen. Only a portion of the peptones formed in tryptic digestion are broken up into leucin and tyrosin; and the same is true of the peptones formed in peptic digestion when submitted to the further action of trypsin. As much as 8 to 10 per cent, of leucin, and 2 to 4 per cent, of tyrosin, may be produced in artificial tryptic digestion of fibrin (Lea, Kiihne). Kiihne believes that every natural proteid consists of two elements as regards the products into which it may be split by digestion — a hemi element and an anti element. Each of these gives rise to a series of bodies, so that we have a hemi series and an anii series. Thus, albumin consists of hemi- albumin and anti-albumin. When digested by pepsin or trypsin, hemi-albumin gives rise eventually to hemi-albumose, and this to hemipeptone, while anti-albumin in like manner passes through the stage of anti-albumose to that of anti- peptone. Further than this peptic digestion does not go, but trypsin can split up the hemipeptone, whether formed by its own action or by that of pepsin, into leucin and tyrosin, while it does not affect the antipeptone. As to the method in which the ferments bring about these profound changes, and the role played by the auxiliary acid or alkali, we are almost completely in the dark. Wurtz has supposed that papain, a ferment obtained from the juice of the fruit of the Carica papaya, which acts powerfully on pro- teids in much the same way as trypsin, unites temporarily with the proteid — with fibrin, for instance — and after the hydration of the latter is complete, is again set at liberty, and free to act on some more of the unchanged fibrin. He compares its action with that of some inorganic bodies, such as sulphuric acid, a small quantity of which may cause the hydration of a large amount of certain substances b}^ forming temporary compounds with them, and being then set free to act again. In peptic digestion, however, the hydrochloric acid seems certainly to be used up. In the gastric juice it is perhaps united to the pepsin ; and it is capable of forming combinations with all proteids, the lower proteids, such as 262 A MANUAL OF PHYSIOLOGY. peptone, combining with a greater proportion of the acid than the higher, such as fibrin or albumin. In all that we have hitherto said regarding tryptic diges- tion we have supposed that putrefaction has been entirely prevented. If no antiseptic is added to a tryptic digest, it rapidly becomes filled with micro-organisms, and emits a very disagreeable faecal odour ; and now various bodies which are not found in the absence of putrefaction make their appearance. Such are indol, skatol, and phenol, as well as the unknown substance to which the fsecal odour is due. They are not true products of tryptic digestion, but are formed by the putrefactive micro-organisms, which can themselves break up proteids into leucin and tyrosin, and readily change tyrosin into indol. Amylopsin, the sugar-forming ferment of pancreatic juice, changes starch into dextrin and maltose, just asptyalin does; but it is much more powerful, and readily acts on raw starch as well as boiled. Steapsin splits up neutral fats into glycerine and the corresponding fatty acids. The latter unite with the alkalies of the pancreatic juice and the bile to form soaps, which aid in the emulsification of fats. In this important process, so essential to digestion, bile acts as the helpmate of pancreatic juice ; together they effect much more than either or both can accomplish by separate action. (4) Bile. — Bile is a liquid the colour of which varies greatly in different groups of animals, and even in the same species is not constant, depending on the length of time the bile has remained in the gall-bladder and other circumstances. When it is recognised that the colour depends on a series of pigments, which are by no means stable, and of which one can be caused to pass into another by oxidation or reduction, this want of uniformity will be easily intelligible. The fresh bile of carnivora is golden red ; the bile of herbivorous animals is in general of a green tint, but, when it has been retained long in the gall-badder, may incline to reddish brown. Human bile is generally described as being of a reddish or golden yellow colour, but it is doubtful whether DIGESTION. 263 this is true of the perfectly fresh secretion, for bile flowing from a fistula has been observed to be green (Robson, Copeman and Winston). That of a monkey taken from the gall-bladder immediately after death is dark green, but if left a few hours in the gall-bladder it is brown, the green pigment having been reduced. This would seem to indicate that human bile, originally green, may alter its colour in the interval which must elapse before it can usually be obtained after death. Bile, as obtained from accidental fistulse in otherwise healthy persons, has a much lower specific gravity than pancreatic juice (1008 to loog). The composition of human bile is approximately as follows : Water 982 Solids: Mucin and pigments - 1-5^ Bile-salts - 7-5 Lecithin and soaps - I V18 Cholesterin •5 Inorganic salts - - rs) It will be observed that no proteids are enumerated in this table ; bile contains none, and it is unlike all the other digestive juices in this respect. Mucin is scarcely to be looked upon as a normal con- stituent of bile ; it is not formed by the actual bile-secreting cells, but by mucous glands in the walls and goblet-cells in the epithelial lining of the larger bile-ducts, and especially of the gall-bladder. The mucin of human bile is a true mucin, but that of ox-bile is a nucleo-albumin ; that is, it may be considered as a compound of nuclein (a complex body rich in phosphorus) and an albumin. By peptic digestion the proteid element is changed into albumoses and peptone, while the nuclein remains unaltered. Although bile (or at least free bile-acids) has in itself considerable antiseptic power, the mucin causes it rapidly to putrefy. It may be removed by precipitation with alcohol or dilute acetic acid. Bile-pigments. — -It has been said that these form a series, but only two of the pigments of that series appear to be present in normal bile, bilirubin and biliverdin. In human bile as usually obtained the former, in herbivorous bile and that of some cold-blooded animals, such as the frog, the 264 A MANUAL OF PHYSIOLOGY. latter, is the chief pigment. But in fresh human bile biliverdin may be chiefly present, and bilirubin can be extracted in large amount from the gallstones of cattle ; while in the placenta of the bitch biliverdin is present in quantity, although, as in all carnivora, it is either absent from the bile or exists in it in comparatively small amount. All these facts show that the two pigments are readily interchange- able. Bilirubin is best obtained from powdered red gallstones by dissolving the chalk with hydrochloric acid, and extract- ing the residue with chloroform, which takes up the pig- ment. From this solution, on evaporation, beautiful rhombic tables or prisms of bilirubin separate out; and the crystals are finer when the solution also contains cholesterin than when it is pure. Biliverdin can be obtained from the placenta of the bitch by extraction with alcohol. It is insoluble in chloroform, and by means of this property it may be separated from bilirubin when the two happen to be present together in bile. Biliverdin can also be formed from bilirubin by oxidation. By the aid of active oxidizing agents, such as yellow nitric acid (which contains some nitrous acid), a whole series of oxidation products of bilirubin is obtained, beginning with biliverdin, and passing through bilicyanin, a blue pigment, to choletelin, a yellow substance. It is possible that there are other intermediate bodies. This is the foundation of Gmelifi's test for bile-pigments (see Practical Exercises, p. 328). The positive pole of a galvanic current causes the same oxidative changes, the same play of colours, while the reducing action of the negative pole reverses the effect, if the action of the positive electrode has not gone too far. Starting from biliverdin, the negative pole causes the green to pass through yellowish-green into golden-yellow, and ultimately into pale yellow, indicating a series of bodies formed by reduction of the biliverdin. These reactions can also be used for the detection of bile-pigments. By the reducing action of sodium amalgam, or of tin and hydro- chloric acid, on bilirubin, but not apparently by electrolysis, hydro- bilirubin is obtained. This is identical with the ' febrile ' urobilin of some pathological urines, and with stercobilin, a pigment found in the faeces from birth onwards, although not in the meconium (p. 311), and therefore probably derived from the normal bile-pigment by reduction in the intestine itself, where reducing substances due to DIGESTION. 265 the action of micro-organisms are never absent in extra-uterine life. The changes occurring in oxidation and reduction of the bile-pigment may be partially represented as follows : (C3,H3,N,0,) 4- O, = (Q,H,,N,0,), + 2O, = (C3,H3,N,Oi,) ; Bilirubin. Biliverdin. Choletelin. 2(C3oH36NA) - Oo + 4H,0 = 2(C3,H3,NA.2H,0). Bilirubin. Hyurobilirubin. Judging from the analogy of the blood-pigment — from which, as we shall see, the bile-pigment is derived, and the changes in which, through oxidation and reduction, have a certain superficial resemblance to those which bilirubin undergoes when it is converted into biliverdin, and which biliverdin undergoes when it passes back again to bilirubin — -we might have expected bile to possess a characteristic spectrum. This, however, is not the case. The bile of most animals shows no bands at all. The fresh bile of certain animals, the ox, for instance, does show bands — a strong one over C, and two weaker bands, one of which is just to the left of D, and the other to the right of it, but nearer D than E. The two last bands grow stronger when the bile is allowed to stand for twenty-four hours, and in about three days, in warm weather, a fourth sharp band may appear between C and B. But none of these bands are due to the normal bile-pigment, and they are not essentially changed when this is oxidized or reduced by electrolysis. MacMunn attributes the spectrum of the bile of the ox and sheep to a body which he calls cholohaematin, and which does not belong to the bile-pigments proper. Of the derivatives of the bilirubin set, only the lowest and the highest members, hydro- bilirubin and choletelin, are described as giving absorption spectra. The Bile-salts. — These are the sodium salts of two acids, glycocholic and taurocholic. In human bile both are present, but the former in greater quantity than the latter. In the bile of the dog and cat only taurocholic acid is found ; in that of the carnivora generally it is by far the more im- portant of the two acids ; in the bile of herbivora there is much more glycocholic than taurocholic acid. Both acids are made up of a non-nitrogenous body, cholic or cholalic acid, and a nitrogenous body, glycin in glyco- cholic, and taurin in taurocholic acid. The decomposition of the bile -acids into these substances is effected by boiling them with dilute acid or alkali, a molecule of water being taken up ; thus — C,,H,3N0, + H.O = C0H5NO0 -F C.,,H,o05 ; Glycocholic acid. Glycin. Cholic acid. C00H45NSO7 4- HoO = C0H7NSO3 + Cs^H^.O^. Taurocholic acid. Taurin. Cholic acid. Taurocholic acid is much more easily broken up than glyco- cholic ; even boiling with water is sufficient. 266 A MANUAL OF PHYSIOLOGY. Glycin is amido-acetic acid, taurin is amido-isethionic acid, an atom of the hydrogen of the acid being in each case replaced by NH.2. A notable difference between glycocholic and taurocholic acid is that the latter contains sulphur. The whole of this belongs to the taurin. Traces of cholic acid, probably formed by the action of putrefactive products on the bile -salts, are found in the intestines, especially in the lower portion. Pettenkofers test for bile-acids (Practical Exercises, p. 327), accidentally discovered in examining the action of bile upon sugar, depends upon three facts : (1) That cholic acid and furfurol give a purple colour when brought together ; (2) that the bile-salts yield cholic acid when acted upon by sulphuric acid ; (3) that when cane-sugar is decomposed by strong sulphuric acid, furfurol is formed. Since a similar colour is given when the same reagents are added to a solution containing albumin, it is necessary to remove this, if present, from any liquid which is to be tested for bile-acids. Lecithin and cholestcrin are by no means peculiar to bile. They are found in almost all the liquids of the body, and are especially important constituents of the nervous substance. The former is a crystallizable fat of a peculiar nature, con- taining nitrogen and phosphorus. It is unstable, and when heated with baryta-water it yields a soap, barium stearate, which is precipitated, and two other substances, neurin and glycerin-phosphoric acid, which remain in solution. Cholestcrin is a triatomic alcohol. It is best obtained from white gallstones, of which it is the chief, and sometimes almost the sole, constituent (see Practical Exercises, p. 328). The chief inorganic salt of bile is sodium chloride. The phosphoric acid of the ash comes partly from the phosphorus of organic compounds (lecithin and bile-mucin), the sulphuric acid from the sulphur of taurin, the sodium largely from the bile-salts. Iron is a notable inorganic constituent of bile, although it exists only in traces, in the form of phosphate of iron ; manganese is also present. 100 cc. of fresh bile yields 50 to 100 cc. of carbonic acid, part of which is in solution and part combined with alkalies. DIGESTION. 267 The quantity of bile secreted in twenty-four hours in an average man is probably from 750 cc. to a litre. The great action of the bile in digestion is undoubtedly the emulsification of fats, and this it accomplishes, not by itself, but in conjunction with the pancreatic juice. No completely satisfactory explanation has been given of the precise nature of this partnership, but it is certain that the fat-splitting ferment of the pancreatic juice, on the one hand, and the bile-salts on the other, contribute largely to the total action. An alkaline solution, a solution of sodium carbonate, e.g., is unable of itself to emulsify a perfectly neutral oil ; but if some free fatty acid be added, emulsification is rapid and complete. Now, there is no doubt that here a soap is formed by the action of the alkali on the fatty acid, and there is equally little doubt that the formation of the soap is an essential part of the emulsification. But it is not clear in what manner the soap acts, whether by forming a coating round the oil-globules, or by so altering the char- acter of the solution in which it is dissolved that they no longer tend to run together. However this may be, in pancreatic juice we have the two conditions present which this simple experiment shows to be necessary and sufficient for emulsification ; we have a ferment which can split up neutral fats and set free fatty acids, and an alkali which can combine with those acids to form soaps. Accordingly, pancreatic juice is able of itself to form emulsions with perfectly neutral oils. It is possible that the proteid con- stituents of pancreatic juice, and particularly a substance resembling alkali-albumin, may have a share in emulsifica- tion. In bile, on the contrary, although the alkaU is present, there is no fat-splitting ferment, and according to the latest experiments, bile alone has no emulsifying power. But we now come to a remarkable fact : this inert bile when added to pancreatic juice greatly intensifies its emulsifying action, and a solution of bile-salts has much the same effect as bile itself. The fact is undoubted, but the explanation is obscure. What it is that bile or bile-salts can add to the pancreatic juice which so increases its power of emulsification, we do not know. It is indeed true that the bile, in virtue of its 268 A MANUAL OF PHYSIOLOGY. alkaline salts, can, in presence of a free fatty acid, rapidly form an emulsion. But the pancreatic juice itself contains a con- siderable quantity of sodium carbonate. A part of the effect of the bile seems to be due to its favour- ing in someway the fat-splitting action of the pancreatic juice. The capacity of dissolving soaps, which is a property of the bile-salts, would undoubtedly be important if it were shown that the comparatively small emulsifying power of pancreatic juice by itself is due to its want of solvent power for the soaps which it forms, and especially if it were shown that soaps such as the alkaline stearates produced in the digestion of ordinary fatty food, which are soluble in water, were much less soluble in the pancreatic secretion. However the mutual action of the two juices on the digestion of fats may be explained, there is no doubt that they are equally necessary. For in some diseases of the pancreas fat often appears in the stools, and this token of imperfect digestion of the fatty food may be confirmed by the wasting of the patient ; and the same occurs when the bile is prevented by obstruction of the duct or by a biliary fistula from entering the intestine. The white stools of jaundice owe their colour, not to the absence of bile-pigment, but to the presence of fat, for the normal colour of fasces is due to hasmatin and sulphides of iron. In suckling children it is not uncommon to see the faeces white with fat. This is a less serious symptom than in adults, and perhaps betokens merely that the milk in the feeding-bottle is undiluted cow's milk, which is twice as rich in fat as human milk, and ought to be mixed with an equal quantity of water. Bidder and Schmidt found that the chyle in the thoracic duct of a normal dog contained 3*2 per cent, of fat. In a dog with the bile-duct ligatured the proportion fell to 0-2 per cent. Bile has been credited with a physical power of aiding the passage of fat through membranes, and it has been inferred that this has an important bearing on the absorption of fat from the intestine. But the inference does not follow from the statement, and the statement has been itself denied. On proteids bile has no digestive action. The addition DIGESTION, 269 of it to a gastric digest causes a precipitate of acid-albumin (parapeptone), albumose, and pepsin. The precipitate is soluble in excess of bile, or of a solution of bile-salts, but the pepsin has no longer any power of digesting proteids. Part of the bile-acids is also thrown down by the acid of the digest. It has been vaguely, and almost helplessly suggested, in the laudable endeavour to find functions for the bile, that by neutralising the chyme bile prepares it for the action of the pancreatic juice. But since the contents of the small intestine are acid throughout the whole of digestion, it is evident that the excess of bile required to neutralise the chyme and redissolve the precipitated proteids does not actually exist. And it is difficult to see in what way the precipitation of a substance can prepare the way for its digestion. The whole discussion is, indeed, an illustration of the hazard that is run in transferring without great care the results of digestion in vitro to the normal and natural processes in the alimentary canal. Although bile has a feebly amylolytic action, this is not to be included among its specific powers, for a diastatic ferment in small quantities is widely diffused in the solids and liquids of the body. Succus Entericus. — This is the name given to the special secretion of the small intestine, which is supposed to be a product of the Lieberkuhn's crypts and of Brunner's glands. In order to obtain it pure, it is of course necessary to prevent admixture with the bile, the pancreatic juice, and the food. This is done by dividing a loop of intestine from the rest by two transverse cuts, the abdomen having been opened in the linea alba. The cofitinuity of the digestive tube is restored by stitching the portion below the isolated loop to the part above it ; one end of the loop is sutured to the lips of the wound in the linea alba, and the other being ligatured, the whole forms a sort of test-tube opening externally (Thiry's fistula). Or both ends are made to open through the abdominal wound (Vella's fistula). Another method is to make a single opening in the intestine, and by means of two indiarubber balls, one of which is pushed down, and the other 270 A MANUAL OF PHYSIOLOGY. up through the opening, and which are afterwards inflated, to block off a piece of the gut from communication with the rest. The intestinal juice so obtained is a thin yellowish liquid of alkaline reaction. Its specific gravity is about loio. It contains a small amount of proteids, and about the same proportion of inorganic salts as most of the liquids and soHds of the body, namely "7 or '8 per cent.; but its com- position seems to be far from constant. It has been credited with various digestive powers ; in fact, according to one or two enthusiastic observers, it would almost seem to sum up in itself the actions of all the other digestive juices, and to possess besides a peculiar activity of its own. But we need not hesitate to say that in the work of digestion it plays at most a very subordinate part. The sodium carbonate which it contains may aid in the emulsion of fats. A ferment called invertin — which is not introduced with the food or formed by bacterial action as has been suggested, since it occurs in the aseptic intestine of the new-born child — changes cane-sugar into a mixture of dextrose and levulose, both reducing sugars, but rotating the plane of polarization in opposite directions, as indicated by their names ; some maltose may be changed into dextrose. But here the catalogue of the powers of the succus entericus ceases ; on proteids and starch it has little or no action. Having now finished our review of the chemistry of the digestive juices, our next task is to describe what is known as to their secretion — the nature of the cells by which it is effected and their histological appearance in activity and repose, and the manner in which it is called forth and controlled. III. The Secretion of the Digestive Juices. The digestive glands are formed originally from involu- tions of the mucous membrane of the alimentary canal, the salivary glands from the epiblast, the others from the hypoblast. Some are simple unbranched tubes, in which there is either no distinction into body and duct as in Lieberkiihn's crypts in the intestines, or in which one or more of the tubes open into a duct, as in the glands of the DIGESTION. 271 cardiac end of the stomach. Some are branched tubes, several of which may end in a common duct ; such are the glands of the pyloric end of the stomach, and the Brunner's glands in the duodenum. In others the main duct ramifies into a more or less complex system of small channels, into each of the ultimate branches of which one or more (usually several) of the secreting tubules or alveoli open. The salivary glands and the pancreas belong to this class of compound tubular or racemose glands, and so does the liver of such animals as the frog. But in the latter organ the typical arrangement is obscured in the higher vertebrates by the predominance of the portal bloodvessels over the system of bile-channels as a groundwork for the grouping of the cells. In every secreting gland there is a vascular plexus outside the cells of the gland-tubes, and a system of collecting channels on their inner surface ; and in a certain sense the cells of every gland are arranged with reference to the blood- vessels on the one hand, and the ducts on the other. But in the ordinary racemose glands the blood-supply is mainly required to feed the secretion ; the cells of the alveoli have either no other function than to secrete, or if they have other functions, they are not such as to entail a great disproportion between the size of the cells and the lumen of the channels into which they pour their products. For both reasons the relation of the grouping of the cells to the duct-system is very obvious, to the blood-S3'Stem very obscure. In the liver the conditions are precisely reversed. We cannot suppose that the manufacture of a quantity of bile less in volume than the secretion of the salivary glands, though certainly containing far more solids, requires an immense organ like the liver, and a tide of blood like that which passes through the portal vein. And, as we shall see, the liver has other functions, some of them certainly of at least equal im- portance with the secretion of bile, and one of them evidently requiring from its very nature a bulky organ. Accordingl}', both the richness of the blood-supply and the size of the secreting cells are out of proportion to the calibre of the ultimate channels that carry the secretion away. The so-called bile-capillaries, which represent the lumen of 272 A MANUAL OF PHYSIOLOGY. the secreting tubules, are mere grooves in the surface of adjoining cells ; and the architectural lines on which the liver lobule is built are (i) the interlobular veins which carry blood to it ; (2) the rich capillary network which separates its cells and feeds them ; (3) the central intra-lobular vein which drains it. Thus a network of cells lying in the meshes of a network of blood-capillaries takes the place of a regular dendritic arrangement of ducts and tubules ; and in accord- ance with this the bile - capillaries, instead of opening separately into the ducts, form a plexus with each other within the hepatic lobule. The ducts and secreting tubules of all glands are lined by cells of columnar epithelial type, but the type is most closely preserved in the ducts. In none of the digestive glands is there more than a single complete layer of secreting cells. But the alveoli of the mucous salivary glands show here and there a crescent-shaped group of small deeply-staining cells (crescents of Gianuzzi) outside the columnar layer (Plate II., I, 3), and between it and the basement membrane, while the gland-tubes of the cardiac end of the stomach have in the same situation a discontinuous layer of large ovoid cells, termed parietal from their position, oxyntic (or acid-secreting) from their supposed function (Fig. 82). The serous salivary glands, the pancreas, the pyloric glands of the stomach, the Lieberkiihn's crypts, have but a single layer of epithelium ; and since there is no hepatic cell which is not in contact with at least one bile-capillary, the liver may be regarded as having no more. Remarkable histological changes, evidently connected with changes in functional activity, have been noticed in most of the digestive glands. In discussing these, it will be best to omit for the present any detailed reference to the liver, since, although there are histological marks of secretive activity in this gland as well as in others, and of the same general character, they are accompanied, and to some extent overlaid, by the microscopic evidences of other functions (p. 382). The serous salivary glands and the pancreas can be taken together ; so can the cardiac and pyloric glands of the stomach ; the mucous salivary glands must be considered separately. DIGESTION. 273 Changes in th.e Pancreas and Parotid during Secretion. — The cells of the alveoli of the pancreas or parotid during rest, as can be seen by examining thin lobules of the former between the folds of the mesentery in the living rabbit, or fresh teased preparations of the latter, are filled with fine granules to such an extent as to obscure the nucleus. In the parotid the whole cell is granular, in the pancreas there is still a narrow clear zone at the outer edge of the cell which contains few granules or none ; in both, the divisions between the cells are very indistinct, and the lumen of the alveolus cannot be made out. During activity the granules seem to be carried from the outer portion of the cell towards the lumen, and there discharged ; the clear outer zone of Fig. 82. — Serous Glands in 'Loaded' and 'Discharged' state. A, rabbit's pancreas, ' loaded' (resting) ; A', ' discharged' (active), (observed in the living animal) (Kiihne and Lea). B, loaded ; B', discharged, alveolus of parotid (fresh preparations), (Langley). the pancreatic cell grows broader and broader at the expense of the inner granular zone, until at last the latter may in its turn be reduced to a narrow contour line around the lumen. In the uniformly clouded parotid cell a similar ■change takes place ; a transparent outer zone arises ; and, after prolonged secretion, only a thin edging of granules may remain at the inner portion of the cell. In both glands the outlines of the cells become more clearly indicated, and a distinct lumen can be now recognised. The cells are smaller than they are during rest, and in the pancreas they stain more readily with carmine and other protoplasmic dyes, the outer zone always staining more deeply than the 18 2/4 A MANUAL OF PHYSIOLOGY. inner, as is the case with the same zone in the resting pancreatic cell (Plate II., 2). When the glands are hardened with alcohol, or most of the ordinary hardening reagents, the appearances in the serous salivary cells differ from those described, for the granules, unlike those of the pancreatic cells, are destroyed by the treatment, and the two zones in the discharged gland are not distinguishable by any difference in the depth of the carmine stain. But in the rabbit's parotid after secretion caused by prolonged stimulation of the sympathetic the whole cell stains more deeply than the loaded cell, and its nucleus is large and spherical, and contains well-marked nucleoli ; in contrast to the small shrivelled nucleus of the resting cell, in which nucleoli are indistinct or absent. Now, carmine being a protoplasmic dye, it is fair to conclude that depth of stain is proportional to amount of protoplasm present. The deeper stain of the outer rim of the pancreatic cell during rest indicates that here the protoplasm pre- dominates over the dead and unstained products of its activity, which are accumulated in the rest of the cell. The increase of the deeply-staining zone during secretion shows that these products are being moved towards the lumen of the alveolus, and that the relative amount of protoplasm in the outer zone is being increased, although the absolute size of the cell may be diminished. The deeper stain of the parotid cell after sympathetic stimulation, as well as the changes in the nucleus, indicate regeneration of protoplasm as much as ehmination of non-protoplasmic elements, for in the dog changes similar to those in the rabbit are caused, although the amount of secretion on stimulation of the sympathetic is very small, and generally only sufficient to block the ducts without appearing externally. The dis- appearance of granules from without inwards during activity suggests that these are manufactured products eliminated in the secretion. Changes in the Glands of the Stomach during Secretion, — The mucous membrane of the stomach is covered with a single layer of columnar epithelium, largely consisting of mucigenous goblet-cells. It is studded with minute pits, into which DIGESTION, 275 open the ducts of the peptic and pyloric glands, the ducts being lined with cells just like those of the general gastric surface. The peptic or cardiac glands have short ducts, into each of which open one to three gland-tubes seldom branched. The ducts of the pyloric glands are longer, and the secreting tubules, which also open by twos or threes into the ducts, are i^% "-^-^ 3:r-H^ $M^' ^ % Vv^v Fig. 83.— The Gastric Glands.— On the left cardiac, right pyloric (Ebstein). branched. The secreting parts of both kinds of glands are lined by short columnar, finely granular cells ; and in the pyloric tubules no others are present. But, as we have said, in the peptic glands there are besides large ovoid cells scattered at intervals like beads between the basement membrane and the lining or chief cells. 276 A MANUAL OF PHYSIOLOGY. The histological changes connected with secretion do not differ essentially from those described in the pancreas and the parotid, but there is much greater difficulty in making observations on the living, or at least but slightly altered, cells. During digestion the granules seem to disappear from the outer part of the chief cells, both in the peptic and pyloric glands, leaving a clear zone, the lumen being bor- dered, as before, by a granular layer. The ovoid cells swell up, so as to bulge out the membrana propria, but no definite changes in their contents, such as those observed in the other cells, have been made out. Changes in Mucous Glands during Secretion. — In the mucous salivary and other mucous glands similar, but apparently more complex, changes occur. During rest the cells which line the lumen may be seen in fresh, teased preparations to be more granular than when the gland has been previously excited to active secretion ; but there is no very distinct differentiation into two zones. But that a discharge of material takes place from these cells is shown by their smaller size in the active gland. That the material thus discharged is not protoplasmic is indicated by the behaviour of the cells to protoplasmic stains such as carmine. The resting cells around the lumen stain but feebly, in contrast to the deep stain of the demilunes, while the discharged cells take on the carmine stain much more readily. Further, when a resting gland is treated with various reagents (water, dilute acids, or alkalies), the granules swell up into a transparent substance apparently identical with mucin, which appears to fill the meshes of a fine protoplasmic network. In ordinary alcohol -carmine preparations only the network and nucleus are stained ; the latter, small and shrivelled, is situated close to the outer border of the cell. When a discharged gland is treated in the same way there is proportionally more ' protoplasm ' and less of the clear material, what remains of the latter being chiefly in the inner portion of the cell, while the nucleus is now large and spherical, and not so near the basement membrane (Plate II., i and 3). Everything, therefore, points to the granules in what we DIGESTION. 277 may now call the mucin-forming cells as being in some way or other precursors of the fully-formed mucin; manufactured during ' rest ' by the protoplasm and partly at its expense, moved towards the lumen in activity, discharged as mucin in the secretion. Not only is the protoplasm lessened in the loaded cell and renewed after activity, but it seems that many of the mucigenous cells may be altogether broken down and discharged, their place being supplied by proliferation of the small cells of the demilunes. But the fact on which we would specially insist is that the granules of the resting mucigenous cell may be looked upon as a mother-substance from which the mucin of the secretion is derived ; they are not actual, but potential, mucin. So in the pancreas, the serous salivary glands, and the glands of the stomach, there is every reason to believe that the granules which appear in the intervals of rest, and are moved towards the lumen and discharged during activity, are the precursors, the mother-substances, of important con- stituents of the secretion. These granules are sharply marked off from the protoplasm in which they lie and by which they are built up. By every mark, by their reaction to stains, for instance, they are non-living substance, formed in the bosom of the living cell from the raw material which it culls from the blood, or, what is more likely, formed from its own protoplasm, then shed out in granular form and secluded from further change. The proteolytic power of an extract of the pancreas, or the gastric mucous membrane, seems to be, roughly speaking, in proportion to the quantity of granules present in the cells. Therefore it is concluded that the granules are related in some way to trypsin and pepsin. But we should greatly deceive ourselves if we supposed that granules of this nature in gland-cells are necessarily related to the production of ferments. The mucigenous granules have no such significance. Most digestive secre- tions contain proteid constituents, with which the granules may have to do, as well as with ferments. And bile, a secretion which contains no mucin, no proteids, and no ferments, as essential constituents, is formed in cells with 278 A MANUAL OF PHYSIOLOGY. granules so disposed and so affected by the activity of the gland as to suggest some relation between them and the process of secretion. In the liver -cells of the frog, in addition to glycogen and oil-globules, small granules may be seen, especially near the lumen of the gland tubules ; they diminish in number during digestion, when the secre- tion of bile is active, and increase when food is withheld and secretion slow. And in Brunner's glands, as well as in the pyloric glands, many of the granules, as seen in fasting dogs (Savas), appear to be of fatty nature. It is possible that these represent the fat which is known to be excreted into the alimentary canal (pp. 320, 322, 389). The granules in the ferment - forming glands are not composed of the actual ferments, and, indeed, the actual ferments are present in the secreting cells only in small amount, if at all, as is shown by the following facts : A glycerine extract of a fresh pancreas has hardly any effect on proteids ; a similar extract of a stale pancreas is very active. Therefore the fresh pancreas is devoid of trypsin. But it contains a substance which can readily be changed into trypsin ; and this substance is soluble in glycerine, for the inert extract becomes active when it is treated with dilute acetic acid, or even when it is diluted with water and kept at the body-temperature. If the fresh pan- creas be first treated with dilute acetic acid, and then with glycerine, the extract is at once active. All this goes to show that in the fresh pancreas not trypsin, but a mother-substance, which has been named trypsinogen, is present, and that the latter yields trypsin, gradually when the pancreas is simply allowed to stand, more rapidly when the dilute acid is used. The natural secretion of the gland is active when the gland- cells contain no ferment, therefore during secretion the trypsinogen must be changed into trypsin. Similarly, a glycerine extract of a fresh gastric mucous membrane is inert as regards proteids, or nearly so. But if the mucous membrane has been previously treated with dilute hydrochloric acid, the glycerine extract is active, as is an extract made with acidulated glycerine. Here we must assume the existence in the gastric glands of a mother- DIGESTION. 279 substance, pepsinogen, from which pepsin is formed. Only the chief cells of the cardiac and pyloric glands are believed to manufacture the pepsin-forming substance. The ovoid cells of the former are supposed to secrete the hydrochloric acid. The evidence on which this belief is based is as follows : The pyloric glands, which contain only chief cells, secrete pepsin, but no acid. The pyloric portion of the stomach has been isolated, the continuity of the alimentary canal restored by sutures, and the secretion of the pyloric pocket collected. It was found to be alkaline, and contained pepsin. The glands of the frog's oesophagus, which contain only chief cells, secrete pepsin, but no acid. It seems fair to conclude that the chief cells of the cardiac glands in the mammal secrete none of the free hydrochloric acid, but certainly some of pepsin. But it does not follow that all the pepsin is formed by these cells, although it would seem that all the hydrochloric acid must be secreted by the only other glandular elements present, the ovoid or ' border ' cells. And, indeed, the glands in the fundus of the frog's stomach, which are composed only of ovoid cells, while secreting much acid, also form some pepsin, although far less than the oesophageal glands. The rennet ferment, according to Langley, is formed in the chief cells, and has a precursor or zymogen like the others. A glycerine or watery extract of the salivary glands always contains active amylolytic ferment, if the natural secretion is active. So that if ptyalin is preceded by a zymogen in the cells, it must be very easily changed into the actual ferment. The Quantitative Estimation of Ferment Action. — Since we have as yet no certain method of freeing ferments from impurities, our only quantitative test is their digestive activity. And since a very small quantity of ferment can act upon an indefinite amount of material if allowed suf- ficient time, we can only make comparisons when the time of digestion and all other conditions are the same. If we find that a given quantity of one pancreatic extract, acting on a given weight of fibrin, dissolves it in half the time required by an equal amount of another pancreatic extract, or dissolves twice 28o A MANUAL OF PHYSIOLOGY. as much of it in a given time, we conclude that the digestive activity of the trypsin is twice as great in the first extract as in the second, or, as it is sometimes more loosely put, that the one contains twice as mucn trypsin as the other. A convenient method of estimating the rate at which the fibrin disappears is to use fibrin stained with carmine. As solution goes on, the dye colours the liquid more and more deeply, and by comparing the depth of colour at any time with standard solutions of carmine, the quantity of the dye set free, and therefore of the fibrin digested, can be approxi- mately arrived at. The relative amounts of actual ferment and of zymogen, or mother-substance, in a digestive gland can also in some cases be calculated, but not with any great exactness. If, for instance, a gastric mucous membrane is extracted with glycerine until a further extract has little or no proteolytic power, and then treated with dilute hydrochloric acid, the ready-formed pepsin will be all in the glycerine extract ; the pepsinogen will be represented by the ferment in the acid extract ; and the digestive power of the two can be com- pared as above described. Another method, applicable to the peptic ferment, depends on the fact that a i per cent, solution of sodium carbonate, acting for a very short time (say half a minute), destroys pepsin, but not pepsinogen. By determining the digestive power before and after this treatment, we can gain some idea of the relative quantity of pepsin and pepsinogen originally present. We have spoken more than once of the gland-cells as manufacturing their secretions, and it is now necessary to consider in a few words how far this notion of their being living laboratories, and not merely passive filters, is correct. It is evident that everything in the secretion must, in some form or other, exist in the blood which comes to the gland, and in the lymph which bathes its cells. No glandular cell, if we except the leucocytes, which in some respects are to be considered as unicellular glands, dips directly into the blood ; everything a gland-cell receives must pass through the walls of the bloodvessels ; the blood supplies the lymph, and the DIGESTION. 281 lymph nourishes the cell. And since lymph is practically diluted blood-plasma, anything which we find in the secre- tion and do not find in the blood must have been elaborated by the gland from raw material brought to it by the latter ; but it does not follow that a constituent of the secretion which is also found in the blood has been merel}- passed through the cell. For example, we find a small amount of pepsin in the blood, but there is no reason whatever to believe that this is the source of the pepsin secreted by the gastric glands. On the contrary, it is possible that some of it is taken up by the blood from these glands, while some of it at least may be formed by the leucocytes, which perhaps require it for the further digestion of the food they take in from the blood, or as one of the weapons with which they attack and destroy injurious bacteria. Many facts may be brought forward to prove that the characteristic constituents of the bile, the bile-pigments and bile-acids, are formed in the liver, and not merely separated from the blood. Bile-pigment has indeed been recognised in the normal serum of the horse, and bile-acids in the chyle of the dog, but only in such minute traces as are easily accounted for by ab- sorption from the intestine. Frogs live for some time after excision of the liver, but no bile -acids are found in the blood or tissues. But if the bile-duct be liga- tured, bile-acids and pigments accumulate in the body, being absorbed by the lymphatics of the liver, as was shown p,^. 84.._h.ematoidin. by Ludwig and Fleischl in the dog. If the thoracic duct and the bile-duct are both ligatured, no bile- acids or pigments appear in the blood or tissues. In mammals excision of the liver is impracticable ; and life cannot be maintained for any length of time after ligature of the portal vein, since this throws the whole intestinal tract out of gear. And although after an artificial communication has been made between the portal and the left renal vein or the inferior cava, the portal may be tied and the animal live for months (Eck), the hepatic circulation is not completely interrupted. In birds, however, there exists a communicating branch between the portal vein and a vein (the renal-portal) which passes from the posterior portion of the body to the kidney, and there breaks up into capillaries ; and not only may the portal be tied, but the liver may be completely destroyed without immediately killing the animal. In the hours of life that still remain to it no accumulation of biHary substances takes place in the blood or tissues. A further 282 A MANUAL OF PHYSIOLOGY. indication that bile-pigment is produced in the Hver is the fact that the hver contains iron in relative abundance in its cells (p. 328), and eliminates small quantities of iron in its secretion. Now bile- pigment, which contains no iron, is certainly formed from blood- pigment, which is rich in iron, for hsematoidin (Fig. 84) a crystalline derivative of haemoglobin found in old extravasations of blood, especially in the brain, is identical with bilirubin. The seat of formation of bile-pigment must therefore be an organ peculiarly rich in iron. The existence of hcemotoidin, however, shows that bile- pigment maj, under certain conditions, be formed outside of the hepatic cells. The occurrence of biliverdin in the placenta of the bitch points in the same direction. But the pathological evidence in favour of the pre-formation of the biliary constituents tends rather to shrink than to increase. For many cases of what used to be considered ' idiopathic ' or ' hematogenic ' jaundice, i.e., an accumulation of bile-pigments and bile-acids in the tissues, due to defective elimination by the liver, are now known to be caused by obstruction of the bile-ducts and consequent re-absorption of bile ('obstructive' or 'hepatogenic' jaundice). But if substances such as the ferments, mucin, hydrochloric acid, the bile-salts and bile-pigments, are undoubtedly manu- factured in the gland-cells, it is different with the water and inorganic salts which form so large a part of every secretion. No tissue lacks them ; no physiological process goes on without them ; they are not high and special products. As we breathe nitrogen which we do not need because it is mixed with the oxygen we require, the secreting cell passes through its substance water and salts as a sort of by-play or adjunct to its specific work. But this is not the whole truth. The gland-cell is not a mere filter through which water and salts pass in the same proportions as they exist in the liquids from which the cell draws them. The secretions of different glands differ in the nature, and especially in the relative proportions, of their inorganic constituents ; and the secre- tion of one and the same gland is by no means constant in this respect, as we shall have to note more especially when we come to deal with the influence of the nervous system on secretion (p. 292). The proteid substances, such as serum-albumin and globulin, common to blood and to some of the digestive secretions, take a middle place between the constituents that are undoubtedly manufactured in the cell and those which seem by a less special and laborious, though a DIGESTION. 283 selective, process to be passed through it from the blood. Their absence from bile, and, as we shall see, from urine, their abundance in pancreatic and scantiness in gastric juice, point to a closer dependence upon the special activity of the gland-cell than we can suppose necessary in the case of the salts. Although it is in the cells of the digestive glands that the power of forming ferments is most conspicuous, it is by no means confined to them. It seems to be a primitive, a native power of protoplasm. Lowly animals, like the amoeba, lowly plants, like bacteria, form ferments within the single cell which serves for all the purposes of their life. The ferment-secreting gland-cells of higher forms are perhaps only lop-sided amoebae, not so much endowed with new properties as disproportionately developed in one direction. The contractility has been lost or lessened, the digestive power has been retained or increased ; just as in muscle the power of contraction has been developed, and that of digestion has fallen behind. The muscle-cell and the cartilage-cell are parasites, if we look to the function of digestion alone. They live on food already more or less prepared by the labours of other cells ; and it is a universal law that in the measure in which a power becomes useless it disappears. But the presence of pepsin in the white blood- corpuscles, the parasites as well as the scavengers of the blood, and of am.ylolytic ferments in many tissues, should warn us not to conclude that the power of forming ferments belongs exclusively to any class of cells. And it is possible that food-substances absorbed from the blood are further elaborated by ferment action within the tissues themselves ; while many facts show that the power of contraction is widely diffused among structures whose special function is very different, and a few point to its possession in some degree even by glandular epithelium. On the other hand, it must be remembered that none of the digestive glands absorb food directly from the alimentary canal to be then digested within their own cell-substance ; the ferments which they form do their work outside of them ; their cells feed also upon the blood. 284 A MANUAL OF PHYSIOLOGY. Why are the Tissues of Digestion not affected by the Digestive Ferments ? — This is the place to mention a point which has been very much debated, though never satisfactorily ex- plained : Why is it that the stomach or the small intestine does not digest itself? This is really a part of a wider question : Why is it that living tissues resist all kinds of influences, which attack dead tissues with success ? The living leucocyte destroys bacteria by which the dead leucocyte is broken up ; it kills and digests them by sub- stances formed within itself, but its own living protoplasm is not digested. Or if the battle goes the other way, the bacteria kill the leucocyte, and break it up, perhaps, by the aid of ferments of their own manufacture which affect it but not them. The amoeba digests food in its cell-substance, but does not digest itself. The pancreatic cell produces ferments which ruin it soon after death, but are perfectly harmless during life. The pancreatic juice acts with great intensity upon proteids, but the living pancreas and the living intestinal wall are immune to it. When we ascribe these things to the resistance of living tissues, we play wath words. Is this a general resistance of all living tissues, or a specific resistance of certain tissues to certain influences ? Are all living tissues, or only the gastric and intestinal walls, shielded from the attack of the digestive ferments? and if all living tissues are protected, are they protected against all ferments, or only against those pro- duced by themselves or by the organism of which they form a part, against comparatively inactive ferments, or equally against the most powerful ? That all living tissues cannot withstand the action of the gastric juice has been shown by putting the leg of a living frog inside the stomach of a dog ; the leg is gradually eaten away (Bernard). It is scarcely to the point to say that it has first been killed and then digested. Why is the stomach- wall not first killed and then digested? When the wall has been injured by caustics or by an embolus, the gastric juice acts on it. But the living epithelium that covers it is able to resist the action of the acid and pepsin, which destroy the tissues of the frog's leg. The alkalinity of the blood has DIGESTION. 285 nothing to do with the explanation, for the frog's blood is also alkaline, and the cells that line the pancreatic ducts are preserved from the pancreatic juice, which is intensely active in an alkaline medium. In the gland-cells of the pancreas the protoplasm is, no doubt, shielded from digestion by the existence of the ferment in an inert form as zymogen ; and it is possible that this is the reason, or at least one of the reasons, for the existence of the mother-substance. A certain amount of protection may be afforded to the walls of the stomach by the thin layer of mucus which covers the whole cavity, for mucin is not affected by peptic digestion. And a mucous secretion seems in some other cases to act as a protection to the walls of hollow viscera whose contents are such as would certainly be harmful to more delicate membranes, e.g., in the urinary bladder, large intestine, and gall-bladder. Still, however important such a mechanical protection may be, it does not explain the whole matter, and it is necessary to suppose that the gastric epithelium has some special power of resisting the gastric juice, possibly by turning any of the ferment which may invade it into an inert substance like the zymogen, or by opposing its entrance as the epithelium of the bladder opposes the absorption of urea. That each membrane becomes accustomed, and, so to speak, ' immune,' to the secretion normally in contact with it is certain ; but this is not a general, but a special, vital action. What living tissues but the lining of the urinary tract or of the large intestine could bear the constant contact of urine or faeces ? When urine is extravasated under the skin or the contents of the alimentary canal burst into the peri- toneal cavity, they are still in contact with a living surface, but with a surface much less fitted to resist them than that by which they are normally enclosed ; and the consequences are often disastrous. Leucocytes thrive in the blood, but perish in urine ; blood does not harm the living cells of the vessels, but kills a muscle whose cross section is dipped in it. The defensive, or rather in some cases offensive, liquids secreted by many animals are harmless to the tissues which produce and enclose them : a caterpillar investigated by Poulton secretes a liquid sometimes containing 40 per cent. 286 A MANUAL OF PHYSIOLOGY . of formic acid, but the mere contact of this would kill most cells. The so-called saliva of Octopus macropus contains a substance fatal to the crabs and other animals on which it preys. The blood of the viper contains an active principle similar to that secreted by its poison-glands, but its tissues are not affected by this substance, so deadly to other animals. The Influence of the Nervous System on the Digestive Glands. The greater part of our knowledge of this subject has been gained by the study of the salivary glands, and especially .—Scheme of the Nerves of the Salivary Glands. SM and SL, submaxillary and sublingual glands ; P, parotid ; V, fifth nerve ; VII, facial; GP, glosso-pharyn- geal ; L, lingual ; CT, chorda tympani ; CL, chordo-'iingual ; D, submax- iUary (Wharton's) duct ; C, ganglion cell of so-called submaxillary ganglion in the chordo-lingual triangle, con- nected with a nerve fibre going to sublingual gland ; C", ganglion cell in hilus of submaxillary gland ; SSP, small superficial petrosal branch of thefacial ; OG, otic ganglion; JN, Jacobson's nerve ; C', ganglion cells in superior cervical ganglion (SG) connected with sympa- thetic fibres going to paro- tid, submaxillary and sub- lingual glands. the submaxillary and sublingual, which lie superficially and are easily exposed. (i) The Influence of Nerves on the Salivary Glands. — All the salivary glands have a double nerve-supply, from a cerebral nerve and from the sympathetic (Fig. 85). The fibres from the latter run in the cervical sympathetic, pass through the superior cervical ganglion, and reach the glands along their bloodvessels. Langley has shown, by means of nicotin (p. 289), which paralyzes nerve-cells much more readily than nerve- fibres, that the sympathetic fibres for the submaxillary and sublingual, and, indeed, for the head in general in the dog and cat, are connected with nerve-cells in this ganglion, but not between it and their termination, or between it and their DIGESTION. 287 origin from the spinal cord. In the dog the chorda tympani branch of the facial nerve carries the cerebral supply of the sublingual and submaxillary glands. It joins the lingual branch of the fifth nerve, runs in company with it for a little way, and then, breaking off, after giving some fibres to the lingual, passes, as the chorda tympani proper, along Wharton's duct to the submaxillary gland. In the hilus of this gland most of its fibres become connected with nerve- cells and lose their medulla in them, a few having lost it before entering the hilus, and a few doing so deeper in the gland. The lingual, the chorda tympani proper, and Wharton's duct form the sides of what is called the chordo- lingual triangle. Within this triangle are situated many ganglion cells, a special accumulation of which has received the name of the submaxillary ganglion. This, however, should rather be called the sublingual ganglion, since its cells, as well as the others in the chordo-lingual triangle, are connected with fibres going to the sublingual gland, which become non-medullated after joining the nerve-cells. The sublingual gland receives its cerebral fibres partly from branches given off from the lingual in the chordo-lingual triangle after the chorda tympani proper has separated from it, and joining the nerve-cells within that triangle, partly from the chorda itself in the terminal portion of its course. These statements rest on anatomical and physiological evidence. The latter we shall return to. The cerebral fibres for the parotid (in the dog) pass from the tympanic branch of the glosso- pharyngeal (Jacobson's nerve) through connecting filaments to the small superficial petrosal branch of the facial, with this nerve to the otic ganglion, and thence by the auriculo-temporal nerve to the gland. When in the dog a cannula is placed in Wharton's duct, and the saliva collected (p. 324), it is found that stimulation of the peripheral end of the divided chorda causes a brisk flow of watery saliva, and at the same time a dilatation of the vessels of the gland, which we have already described in dealing with vaso-motor nerves (p. 129). That the increased secretion is not due merely to the greater blood-supply, and the consequent increase of capillary pressure, is shown 288 A MANUAL OF PHYSIOLOGY. by the injection of atropia, after which stimulation of the nerve, although it still causes dilatation of the vessels, is not followed by a flow of saliva. Further, mere increase of pressure could not in any case of itself account for the secretion, since it has been found that the maximum pressure in the salivary duct, may, during stimulation of the chorda, much exceed the arterial blood-pressure (Ludvvig). In one experiment, for example, the pressure in the carotid of a dog was 125 mm., in Wharton's duct 195 mm. Hg. Even in the head of a decapitated animal a certain amount of saliva may be caused to flow by stimulation of the chorda, but too much may easily be made of this. And since the blood is the ultimate source of the secretion, we could not expect a permanent or copious flow in the absence of some circulation, even if the gland-cells could continue to live. In fact, when the circulation is almost stopped by strong stimulation of the sympathetic, the flow of saliva caused by excitation of the chorda is at the same time greatly lessened or arrested, even though the sympathetic itself possesses secretory fibres. So that, while there is no doubt that the chorda tympani contains fibres whose function is to increase the activity of the gland-cells, its vaso-dilator action is, under normal conditions, closely connected with, and, indeed, auxiliary to, its secretory action, although the former does not directly produce the latter. This is only a particular case of a general physiological law, that an organ in action always receives more blood than the same organ in repose, or, in other words, that the tissues are fed according to their needs. The contracting muscle, the secreting gland, is flushed with blood, not because an increased blood-flow can of itself cause contraction or secretion, but because these high efforts require for their continuance a rich supply of what blood brings to an organ, and a ready removal of what it takes away. The quantity of blood passing through the parotid of a horse when it is actively secreting during mastication may be quadrupled (Chauveau). The parallel between the muscle and the gland is drawn closer when it is stated that electrical changes accompany secretion (see Chapter XL), and that the rate of production of carbonic acid and consumption of DIGESTION. 289 oxygen rises during activity. Tlie temperature of the saliva flowing from the dog's submaxillary during stimulation of the chorda has been found to be as much as i'5° C. above that of the blood of the carotid, although with the gland at rest no constant difference could be found (Ludwig). But such measurements are open to many fallacies ; and while there is no doubt that more heat is produced in the active than in the passive gland, it will not be surprising, when the vastly increased blood-flow is remembered, that no difference of temperature between the incoming and outgoing blood has been satisfactorily demonstrated, although we must assume that such a difference exists. How the secretory fibres of the chorda end in the gland we do not know. We can hardly doubt that they must be connected with the secreting cells, although Pfliiger's obser- vations, which seemed to establish this connection, have not been confirmed. In the 'salivary glands' of the cockroach, however, nerve-fibres have been shown to end in the cells. Effect of Nicotine on Nerve-cells. — It has already been mentioned that most of the fibres of the chorda tympani proper become con- nected with ganglion-cells, and lose their medulla inside the sub- maxillary gland, only a few having already lost it by a similar connection with ganglion-cells in the chordo-lingual triangle : and it is now necessary to say something of the physiological method by which this knowledge has chiefly been gained, especially as it has proved to be of great value in the investigation of the nervous paths in many parts of the body. When a suitable dose of nicotine is injected into a vein, or a suitable solution locally applied, it is possible to paralyze for a longer or shorter time the ganglion-cells on the course of peripheral nerves, without affecting the nerve-fibres. The question as to whether efferent fibres are connected with nerve- cells between a given point and their peripheral distribution, can be answered by observing whether any effect of stimulation is abolished by nicotine. The precise position of the nerve-cells can be determined by stimulating the nerve at points nearer and nearer to its termina- tion, and noting the part at which stimulation first becomes effective ; this must be peripheral to the nerve-cells, or some of them. Now, it is found that, after the injection of nicotine (25 to 30 mg. in a dog weighing 6 kilos), stimulation of the chorda tympani proper or of the chordo-lingual nerve causes no secretion from the submaxillary gland; but stimulation of the hilus of the gland is followed by a copious secretion — as much, if the stimulation is fairly strong, as was caused by excitation of the nerve before injection of nicotine. That this is due neither to any direct action on the gland-cells, nor to stimula- 19 290 A MANUAL OF PHYSIOLOGY. tion of the sympathetic plexus on the submaxillary artery, but to stimulation of chorda fibres beyond the hilus, is shown by the fact that after atropia has been injected in sufficient amount to paralyze the nerve endings of the chorda, but not of the sympathetic, stimula- tion of the hilus causes little or no flow of saliva. The application of nicotine solution to the chordo-lingual triangle does not affect the sub- maxillary secretion caused by stimulation of the chordo-lingual nerve, even in cases where a few secretory fibres for the submaxillary do not leave the chordo-lingual nerve in the chorda tympani proper, but are given off to the chordo-lingual triangle. This shows that none of the ganglion-cells in the triangle are connected with the cerebral secretory fibres o f the submaxillary gland. By observations of the same kind they are known to be connected with fibres going to the sublingual. In a similar way, by observing the effects of stimulation of the chorda on the bloodvessels before and after the application of nicotine, it has been found that the vasodilator fibres are connected with ganglion-cells in the same positions as the secretory fibres (Langley). The sympathetic, as has been already indicated, contains both vaso-constrictor and secretory fibres for the salivary glands. If the cervical sympathetic in the dog is divided, and the cephalic end moderately stimulated, a thick viscid and scanty saliva flows from the submaxillary and sublingual ducts, while the current of blood through the glands is diminished. As a rule, no visible secretion escapes from the parotid, but microscopic examination shows that many of the ductules are filled with fluid, which is apparently so thick as to plug them up (Langley) ; while the cells show signs of * activity.' When the chorda and sympathetic are stimulated together, the former prevails so far, with moderate stimulation of the latter, that the submaxillary saliva is secreted in considerable quantity, and is not particularly viscid ; it is, however, richer in organic matter than is the chorda saliva itself. When the chorda is weakly, and the sympathetic strongly excited, the scanty secretion (if there is any) is of sympathetic type, thick and rich in organic matter. With strong stimulation of both nerves, the secre- tion is plentiful and watery ; with stimulation just strong enough to cause secretion when applied separately to either nerve, there is no secretion when it is applied simultaneously to both. All this refers to the dog. In this animal, then, there DIGESTION. 291 seems to be a certain amount of physiological antagonism between the secretory action of the two nerves. But it differs in one respect from the antagonism between their vaso- motor fibres ; for with strong stimulation the constrictors of the sympathetic always swamp the dilators of the chorda, while the secretory fibres of the chorda appear to prevail over those of the sympathetic. And in all probability this apparent secretory antagonism is very superficial ; and what- ever interference there may be between the two nerves is not due to the one annulling the influence of the other on the gland-cells, but to the cells being called by them to different labours, in general complementary to each other, and only incompatible in so far as the working power of the cells may not be able to respond at the same time to large demands from both sides. For the sympathetic always adds something to the common secretion when there is a secretion at all, this something being represented by an increase in the percentage of organic matter. Not only so, but the sympathetic effect persists after stimulation has been stopped ; and excitation of the chorda after previous stimulation of the sympathetic causes a flow of saliva richer in organic matter than would have been the case if the sympathetic had not been stimulated. Indeed, the distinction between chorda and sympathetic saliva, which, by taking account of the parotid as well as the submaxillary and sublingual glands, has been generalized into a distinction between cerebral and sympathetic saliva, and which holds good in the dog and the rabbit, breaks down before a wider induction. For in the cat the sympathetic saliva of the submaxillary gland is more watery than the chorda saliva (Langley), which, however, is by no means viscid; and the two secretions differ far less than in the dog. In accordance with this functional similarity, there is a much smaller difference in the action of atropia on the two sets of fibres in the cat than in the dog, although even in the cat the sympathetic is less readily paralyzed than the chorda. In their secretory action there is not even an apparent antagonism in the cat, minimal stimulation of both nerves together causing as much secretion as would be produced if 292 A MANUAL OF PHYSIOLOGY. both were separately excited. Further, even in the dog, after prolonged stimulation of the sympathetic, the sub- maxillary saliva is no longer viscid, but watery, the propor- tion of solids, and especially of organic solids, being much lessened, as it also is in chorda saliva after long excitation. When the cerebral nerve of the resting gland is excited, it is found that up to a certain limit the percentage of organic matter increases with the strength of stimulation ; this is also true of the inorganic solids. But there is a striking difference when the experiment is made on a gland after a long period of activity ; here increase of stimulation causes no increase in the percentage of organic material, while the inorganic solids are still increased. In both cases the absolute quantity of water, and therefore the rate of flow of the secretion, is augmented. All this points to the same conclusion as the microscopic appearances in the gland-cells, that the cells during rest manufacture the organic constituents of the secretion, or some of them, and store them up, to be discharged during activity. The water and the inorganic salts, on the other hand, seem rather to be secreted on the spur of the moment, so to speak, and not to require such elaborate preparation. And it has been found that the quantity of organic substances is much more nearly proportional to the strength of the stimulus applied to the secretory nerve-fibres than is the quantity of water and salts, which varies also with the blood-supply. In order to explain the difference between the cerebral and sympathetic secretion, Heidenhain has supposed the existence of two kinds of secretory fibres, (i) fibres having to do with the secretion of the water and salts, {2) fibres having to do with the secretion of the organic material. In such animals as the dog, the cerebral nerve (the chorda in the case of the submaxillary and sublingual glands) contains many fibres of group (i), comparatively few of group (2) ; the sympathetic contains few of (i), many of (2). Heidenhain's second set of fibres is supposed only to promote the changes by which already formed organic matter passes into solution, and leaves the cells in the secretion. They may, since they DIGESTION. 293 favour the breaking down and removal of material from the cell, with more propriety be called katabolic secretory, than trophic fibres as Heidenhain originally proposed. Langley's experiments indicate that Heidenhain's hypothesis must be completed by assuming the existence of a third group of fibres which have to do with the building up of fresh substance by the gland-cells. These would appro- priately be called anabolic secretory fibres. The chorda may therefore contain no less than four physiological groups of nerve-fibres : 1. Secretory for water and salts. 2. Katabolic secretory | ^^.^^^ ^^^ ^^^^^.^ material. 3. Anabolic secretory J 4. Vaso-dilator. But it must be remembered that we have no proof of the distinct anatomical existence of these different kinds of fibres ; and Langley has shown that in the cat's chorda atropia acts simultaneously on all the secretory fibres ; the moment it paralyzes one group all are paralyzed. If they were anatomically distinct, it might have been supposed that atropia in a certain dose would pick out one or other group, and leave the rest still active. It is conceivable that the differences between chorda and sympathetic saliva are due, not to the nerve-fibres, but to the end organs with which they are connected ; that is, the two nerves may supply, not the same, but different gland- cells. And it is well known that even after prolonged stimulation of the chorda or chordo-Hngual alone, some alveoli of the dog's submaxillary gland remain in the ' resting ' state ; after stimulation of the sympathetic alone, the number of unaffected alveoli is much greater ; while after stimulation of both nerves, no alveolus seems to have escaped change. However suggestive these facts may be, they will not as yet bear the weight even of a hypothesis of salivary secretion. And, indeed, we know nothing of a division of labour between the cells of a gland, except when there are obvious anatomical distinctions. Thus, the sub- maxillary gland in man contains both serous and mucous acini, and mucin-making cells are scattered over the ducts 294 A MANUAL OF PHYSIOLOGY. of most glands, and, indeed, on nearly every surface which is clad with columnar epithelium. In these cases we cannot doubt that one constituent — mucin — of the entire secretion is manufactured by a portion only of the cells. In the cardiac glands of the stomach, too, the ovoid cells, in all probability, yield the whole of the acid of the gastric juice. But, so far as we know, every hepatic cell is a liver in little. Every cell secretes fully-formed bile ; every cell stores up, or may store up, glycogen. So it is with the alveoli of the pancreas ; one cell is just like another ; all apparently perform the same work ; each is a unicellular pancreas. (But see p. 415.) Paralytic Secretion. — When the chorda tympani is divided, a slow ' paralytic ' secretion from the submaxillary gland begins in a few hours, and continues for a long time accom- panied by atrophy of the gland. There is also a secretion of the same kind from the submaxillary on the opposite side, but it is less copious. This is called the ' antilytic ' secretion. The cause of the secretion has not been fully made out. If within two or three days of division of the chorda the sympathetic on the same side is cut, the paralytic secretion stops ; and it is concluded that up to this time it is maintamed by impulses passing along the sympathetic to the gland from the secretory centre in the bulb, the excitability of which has been in some way increased by division of the chorda. But if section of the sympathetic is not performed for several days, it has no effect on the paralytic secretion, which at this stage seems to depend on local changes in the gland itself. Section of the sympathetic alone causes neither secretion nor atrophy, nor does removal of the superior cervical ganglion. The histological characters of the gland-cells during paralytic secretion are those of ' rest.' Reflex Secretion of Saliva. — The reflex mechanism of salivary secretion is very mobile, and easily set in action by physical and mental influences. It is excited normally by impulses which arise in the mouth, especially by the contact of food with the buccal mucous membrane and the gustatory nerve-endings. The mere mechanical movement of the jaws, even when there is nothing between the teeth, or only DIGESTION. 295 a bit of a non-sapid substance like indiarubber, causes secretion. The vapour of glacial acetic acid or ether gives rise to a rush of saliva, as does gargling the mouth with distilled water. The smell, sight, or thought of food, and even the thought of saliva itself, may act on the salivary centre through its connections with the cerebrum, and make ' the teeth water,' A copious flow of saliva, reflexly excited through the gastric branches of the vagus, is a common precursor of vomiting ; the introduction of food into the stomach also excites salivary secretion. The centre is situated in the medulla oblongata, stimulation of which causes a flow of saliva. The two chief afferent paths to the salivary centre are the lingual branch of the fifth and the glosso-pharyngeal ; but stimulation of many other nerves may cause reflex secretion of saliva. In experimental stimulation, the sole efferent channel seems to be the cerebral nerve-supply of the glands. After section of the chorda, no reflex secretion by the submaxillary gland can be caused, although the sympa- thetic remains intact. The statement that after division of the chordo-lingual a reflex secretion could be obtained from the submaxillary gland, the so-called submaxillary ganglion being supposed to act as ' centre,' has been com- pletely disproved ; and indeed, as we have seen, the chorda fibres for the submaxillary gland are not even connected with the cells of the ganglion. Nor do we know of any peripheral or sporadic ganglion which can act as a reflex centre. In most animals and in man the secretion of saliva is strictly intermittent, but the parotid of the sheep is said to be always active. The salivary centre can also be inhibited, especiall}- by emotions of a painful kind — for instance, the nervousness which often dries up the saliva, as well as the eloquence, of a beginner in public speaking, and the fear which sometimes made the medieval ordeal of the consecrated bread pick out the guilty. (2) The Influence of Nerves on the Gastric Glands. — Like saliva, gastric juice is not secreted continuously, except in animals, such as the rabbit, whose stomachs are never empty. The 296 A MANUAL OF PHYSIOLOGY. normal and most efficient stimulus is the presence of food in the stomach. Faintly alkaline liquids, such as saliva, excite an active secretion, but it is only very early in digestion, before the reaction of the gastric contents has become distinctly acid, that swallowed saliva can have any effect. Mechanical stimulation of the gastric mucous membrane causes a certain amount of secretion, but not a great deal. Ko nerve has been shown with certainty to have any influence over the gastric glands. So that at first thought there is much to suggest that these are normally stimulated in a more direct manner than the salivary glands, perhaps by the local action of food substances reaching the cells by a short-cut from the cavity of the stomach, or in a more roundabout way by the blood. And it might be very plausibly argued that the gastric glands are favourably situated for direct stimulation, while the salivary glands are not ; and that the great function of saliva being to aid deglutition, an almost momentary, and at the same time a perilous act, it is necessary to provide by nervous mechanism for an immediate rush of secretion at any instant, while it is not important whether the gastric juice is poured out a little sooner or a little later, and therefore it is left to be called forth by the more tardy and haphazard method of local action. Nevertheless, on looking a little closer, w^e find that this does not exhaust the subject, and that the gastric secre- tion can be influenced by events taking place in distant parts of the body, just as the salivary secretion can. In a boy whose cesophagus was completely closed by a cicatrix, the result of swallowing a strong alkali, and who had to be fed by a gastric fistula, it was found that the presence of food in the mouth, and even the sight or smell of food, caused secretion of gastric juice (Richet) ; and in dogs with the oesophagus divided so that nothing could pass through it to the stomach, a similar result was obtained (Pawlow). Here there must have been some nervous mechanism at work. The secretion can hardly have been excited by the direct action of food products absorbed from the mouth and circulating in the blood — an explanation which has been given of the secretion seen in an isolated portion of the DIGESTION. 297 cardiac end of the stomach during the digestion of food in the rest. What the nervous channels are through which these effects are produced has not been clearty made out. After division of the sympathetic fibres going to the stomach, and also the vagi, gastric secretion is still caused by the intro- duction of food into the stomach, so long as the latter nerves are cut below the origin of their cardiac and pulmonary branches, and disturbance of the heart and respiration thus avoided (Heidenhain). Not only so, but the vascular dilatation, which accompanies the activity of the gastric as well as the salivary glands, and is shown by flushing of the mucous membrane of the stomach, is not interfered with by section of the vagi in the position mentioned. The most probable conclusion would seem to be that, while a great part must be assigned to the local effects of the food, and the action of the products of digestion absorbed into the blood on the gland-cells or on nervous centres, these may be supplemented and controlled by a truly reflex mechanism. (3) The Influence of Nerves on the Pancreas. — Our knowledge of the influence of nerves on the pancreas is a little more definite, but not much. Stimulation of the medulla oblongata causes or increases secretion even after section of the vagi. Stimulation of the central end of the vagus and of other nerves inhibits the secretion ; the inhibition caused by vomiting is probably due to impulses ascending the vagus. These facts point to the existence of a reflex mechanism, but neither has the centre been located nor the afferent and efferent paths definitely ascertained. The natural secretion of pancreatic juice is by no means so intermittent as that of saliva. In the rabbit the pancreatic, like the gastric, juice flows continuously. In a well-fed dog it is probable that it seldom stops altogether, for it was found that after a meal it took from twenty to twenty-four hours for the flow to cease entirely. It begins abruptly as soon as the food enters the stomach, probably through reflex impulses originating in the gastric mucous membrane, rises in two or three hours to a maximum, then falls till the fifth or sixth hour, after which it mounts again about the ninth or tenth hour to a second lower maximum, and then, 298 A MANUAL OF PHYSIOLOGY. gradually diminishing, ultimately stops. During activity the bloodvessels of the gland are dilated ; but we have as yet no precise information as to the vaso-motor nerves which govern them. When the nerves of the pancreas, which pass to it from the solar plexus along the vessels, are divided, ' paralytic ' secretion of thin watery juice takes place. There is one ver}' remarkable difference between the normal secretion of pancreatic juice and of saliva : the pressure of the latter in the submaxillary duct may, as we have seen, greatly exceed the arterial blood-pressure, without reabsorption and consequent oedema of the gland occurring; but the secretory Fig. 86. — Rate of Secketion of Pancreatic Juice. S shows the variation in tlie rate of secretion of the pancreatic juice in a clog ; P, the variation in the percentage of solids in the juice. It will be seen that the maxima of S fall at the same time as the minima of P. The numbers along the horizontal axis are hours since the last meal. pressure of the pancreatic cells is very low, not more than a tenth of that of the salivary glands. GEdema begins before a manometer in the duct shows a pressure of 20 mm. of Hg. (4) The Influence of Nerves on the Secretion of Bile. — Although bile is secreted constantly, it only passes at intervals into the intestine. For the liver in most animals, unlike every other gland except the kidney, has in connection with it a reservoir, the gall-bladder, in which its secretion accumulates, and from which it is only expelled occasionally. We have therefore to distinguish the bile-secreting from the bile-expelling mechanism. Of the direct influence of nerves on either we have scarcely any knowledge, scarcely even any guess which is worth m.entioning here. It is true the secretion of bile may be distinctly affected by the section DIGESTION. 299 and stimulation of nerves which control the blood-supply of the stomach, intestines, and spleen, for the quantity of blood passing by the portal vein through the liver depends upon the quantity passing through these organs, and the rate of secretion is closely related to the blood-supply. In this way stimulation of the medulla oblongata, the spinal cord, and the splanchnic nerves stops or slows the secretion of bile by constricting the abdominal vessels ; and the same effect can be reflexly produced by the excitation of afferent nerves. The muscular fibres of the gall-bladder and the larger bile-ducts are thrown into contraction by stimulation of the spinal cord. It is possible that this takes place naturally in response to reflex impulses from the mucous membrane of the duodenum, for the application of dilute acid to the mouth of the bile-duct causes a sudden flow of bile, and the acid contents of the stomach, when projected through the pylorus into the intestine, have a similar effect. The pressure under which the bile is secreted is remark- ably small, the maximum being no more than 15 mm. of Hg. But small as this is, it is higher than the pressure of the portal blood, and therefore the liver ranges itself with the high-pressure salivary glands rather than with the low- pressure pancreas. But although the biliary pressure is high relatively to that of the blood with which the secreting cells are supplied, it is absolutely very low ; and this is a point of practical importance, for a comparatively slight obstruction to the outflow, even such as is offered by a congested or inflamed condition of the duodenal wall about the mouth of the duct, may be sufficient to cause reabsorption of the bile through the lymphatics, and consequent jaundice. Of course complete plugging of the duct by a biliary calculus is a much more formidable barrier, and inevitably leads to jaundice, just as ligature of a salivary duct, in spite of the great secretory pressure, inevitably causes oedema of the gland. When food passes into the stomach, there is at once a sharp rise in the rate of secretion of bile. A maximum is reached from the fourth to the eighth hour — that is, while the food is in the intestine ; there is then a fall, succeeded by 300 A MANUAL OF PHYSIOLOGY. a second smaller rise about the fifteenth or sixteenth hour, from which the secretion gradually declines to its minimum. Upon the whole, the curves of secretion of pancreatic juice and bile show a fairly close correspondence, which lends additional support to the view derived from their chemical and physical properties, that in digestion they are partners in a common work. We do not know in what way the rate of secretion of bile is influenced by digestion, although it has been conjectured that the first abrupt rise may be started by reflex nervous action, and that later on absorbed food products may directly Fig. 87. — Rate of Secretion of Bile. S shows how the rate of secretion of bile falls in a dog when a biliary fistula is first made, and the bile thus prevented from entering the intestine ; P shows the fall in the percentage of solids. The numbers along the horizontal axis are quarters of an hour since bile began to escape through the fistula. The numbers along the vertical axis refer only to curve S, and represent the rate of secretion in arbitrary units. excite the hepatic cells. Rutherford found that when the mucous membrane of the stomach and duodenum is irritated by a substance like gamboge, there is no increase in the rate of secretion of the bile, notwithstanding the greatly increased flow of blood through the intestinal vessels which the irritation causes. This tells in favour of the direct influence of substances derived from the food rather than of any important reflex action. (5) The Influence of Nerves on the Secretion of Intestinal Juice. — As to the influence of nerves on the secretion of the succus entericus, our knowledge is almost limited to a single experiment, and that an inconclusive one. Moreau placed four ligatures on a portion of the small intestine, so as to DIGESTION. 301 form three compartments separated from each other and from the rest of the gut. The mesenteric nerves going to the middle loop were divided, and the intestine returned to the abdomen. After some time a watery secretion was found in the middle compartment, little or none in the others. But we cannot say whether this is a true ' paralytic ' secretion, or whether it depends simply on the vascular dilatation caused by section of the vaso-con- strictor nerves. Effect of Drugs on the Digestive Secretions. — A small dose of atropia, as has been said, abolishes the secretory action of the chorda tympani. This it does apparently by paralyzing the nerve-endings ; the nerve-cells are not paralyzed, for the sympathetic can still cause secretion. Pilocarpine is the physiological antagonist of atropia, and restores the secre- tion which atropia has abolished. In small doses it causes a rapid flow of saliva, its action being, partly at least, a peripheral action, for it persists after all the nerves going to the salivary glands have been divided. Atropia and pilocarpine act similarly on some of the other digestive glands, the former paralyzing the pancreatic secretion, the latter increasing the secretion of gastric, and probably of intestinal, juice ; but atropia does not stop the secretion caused by division of the intestinal nerves. Physostigmine, nicotine and muscarine act on the whole like pilocarpine. The action of a host of drugs on the secretion of bile has been investigated by various observers, but till something like unanimity has been reached, it world not be profitable to go into details here. Some drugs seem to act directly upon the hepatic cells, or on nerves supplying them, others refiexly by stimulating the mucous membrane of the intestine. Summary. — Here let us sum up the most important points relating to the secretion of the digestive juices. They arc all formed by the activity of gland -cells originally derived from the epithelial lining of the alimentary canal. The organic constituents or their precursors {including the mother-substances of the ferments') are prepared in the intervals of rest — absolute in some glands, relative in others — and stored up in the form of granules, which 302 A MANUAL OF PHYSIOLOGY. during activity are moved towards the lumen of the gland tubules, and there discharged. At the same time the secreting proto- plasm is regenerated, either by an increase in the substance of the actually secreting cells {pancreas, serous salivary glands), or, when these have been completely broken doivn {mucons salivary glands), by proliferation of other cells. The nerves of the salivary glands are, as regards their origin, (a) cerebral, {/>) sympathetic ; the former group is vaso-dilator, the latter vaso-constrictor — both are secretory. Secretion of saliva depends strictly on the nervous system. That nerves influence the pancreatic secretion is made out, but nothing definite is known as to the nervous paths. As regards the gastric and intestinal glands and the liver, it has not been proved that their secretive activity is at all under the control of the nervous system, except in so far as the latter may indirectly govern it through the blood- supply, although various circumstances suggest the probability of a more direct action. In all the glands the blood-flow is increased during activity — in some {salivary glands) this is known to be caused through nerves. In the salivary glands electromotive changes accompany the active state, while more heat is produced, more CO., given off, and more 0., used up, during secretion than during rest. In the other glands we may assume that the same occurs. IV. Digestion as a Whole. Having discussed in detail the separate action of the digestive secretions, it is now time to consider the act of digestion as a whole, the various stages in which are co-ordinated for a common end. The solid food is more or less broken up in the mouth and mixed with the saliva, which its presence causes to be secreted in considerable quantity. Liquids and small solid morsels are shot down the open gullet without contraction of the constrictors of the pharynx, and reach the stomach in a comparatively short time ('fV second) ; while a good-sized bolus is grasped by the constrictors, then by the oesophageal walls, and passed along by a more deliberate peristaltic contraction. Beau- mont saw, in the case of St. Martin, that the oesophageal orifice of the stomach contracted firmly after each morsel DIGESTION. 303 was swallowed, and so did the gastric walls in the neigh- bourhood of the fistula when food was introduced by this opening. Two sounds may be heard in man on listening in the region of the stomach or oesophagus during degluti- tion of liquids, especially when, as generally happens, they are mixed with air. The first sound occurs at once, and is supposed to be due to the sudden squirt of the liquid along the gullet ; the second, which is heard after a distinct interval, seems to be caused by the forcing of the fluid through the Fig. -Skckktion of Pepsin. C shows the quantity of pepsin in the mucous membrane of the cardiac end of the stomach at different times during digestion ; P, the quantity of pepsin in the mucous membrane of the pyloric end ; S, the quantity of pepsin in the secretion of the cardiac glands. The numbers marked along the horizontal a.xis are hours since the last meal. .About five hours after the meal S reaches its maximum. From the very beginning of the meal C falls steadily down to the tenth hour, and then begins to rise, i.e. , the gland- cells of the cardiac end of the stomach become poorer in pepsin as secretion proceeds. cardiac orifice of the stomach by the contraction of the oesophagus. Chemical digestion in man begins already in the mouth, a part of the starch being there converted into dextrins and sugar (maltose), as has been shown by examining a mass of food containing starch just as it is ready for swallowing (p. 323). This process is no doubt continued during the passage of the food along the oesophagus. The first morsels of a meal which reach the stomach find it free from gastric juice, or nearly so. They are alkaline 304 A 31 AN UAL OF PHYSIOLOGY. from the admixture of saliva ; and the juice which is now beginning to be secreted, in response to the presence of the food, and to reflex excitement starting in the mouth, is for a time neutrahzed, and amylolytic digestion still permitted to go on. For about ten minutes after digestion has begun there is no free hydrochloric acid in the stomach, although some is combined with pro- teids, and at least during this period the ptyalin of the swallowed saliva will be able to act. But as the meal goes on, the successive portions of food which arrive in the stomach will find the conditions less and less favourable for amylolytic digestion ; and, upon the whole, a considerable proportion of the starches must escape complete conversion into sugar until they are acted upon by the pancreatic juice. This is particularly the case with unboiled starch, as con- tained in vegetables which are eaten raw ; and, indeed, we know that sometimes a certain amount of starch may escape even pancreatic digestion, and appear in the faeces. Mean- while, even during the short amylolytic stage of gastric digestion, pepsin and hydrochloric acid are already being poured forth ; the latter is entering into a peculiar combina- tion with the proteids of the food ; and long before the end of an ordinary meal peptic digestion is in full swing. The movements of the stomach increase, and eddies are set up in its contents, which carry the morsels of food with them, and throw them against its walls. In this way not only are the contents thoroughly mixed, and fresh portions of food constantly brought into contact with the gastric juice, but a certain amount of mechanical disintegration is brought about ; and this is aided by the digestion of the gelatin-yielding connective tissue which holds together the fibres of muscle and the cells of fat, and the digestible structures in vegetable tissue which enclose starch granules. If milk has formed a portion of the meal, the casein will have been curdled soon after its entrance into the stomach, by the action of the rennet ferment alone when the milk has been taken at the beginning of digestion before the gastric contents have become distinctly acid, by the acid and rennin together when it has been taken later. The casein DIGESTION. 305 and other proteids of milk, like the myosin and other proteids of meat, and the globulins, phytovitellins, and other proteids of bread and of vegetable food in general, are all acted upon by the pepsin and hydrochloric acid, yielding ultimately peptones ; while variable quantities of acid- albumin and proteoses may escape this final change, and pass on as such into the duodenum. In the dog, indeed, a meal of flesh has been found to be almost entirely digested to the peptone stage while still in the stomach, leaving little for the pancreatic juice to do. But we may safely assume that, in the case of a man living on an ordinary mixed diet, much of the food proteids passes through the pylorus chemically unchanged, or having undergone only the first steps of hydration. For, even a few minutes after food has been swallow^ed, the pyloric sphincter may relax and allow the stomach to propel a portion of its contents into the intestine; and such relaxations occur at intervals as digestion goes on, although it is not for several hours (three to five) that the greater portion of the food reaches the duodenum. During this time the acidity has at first been constantly increasing, although for about half an hour after the short amylolytic stage the hydrochloric acid has combined, as it is formed, with the proteids of the food. The combination, however, does not prevent it from causing an acid reaction, although up to this time no free acid is present. Then comes a stage where the hydrochloric acid has so much increased that, after combming with all the proteids, some of it remains over as free acid. Soon, however, the total acidity begins to fall, the fully-digested proteids being continually absorbed in the form of peptones, which are only found in traces, if at all, in the chyme. This fall continues till the third or fourth hour, the proportion of free to combined acid continuing, nevertheless, to rise, since nearly all that is now secreted remains free. Easily-diftusible bodies, such as sugars and some of the organic crystalline constituents of meat, e.g. kreatin, will also pass through the gastric mucous membrane into the blood. The substances which reach the duodenum are : (i) the whole of the fats, with no chemical and little physical 20 3o6 A MANUAL OF PHYSIOLOGY. change. But the digestion in the stomach of the envelopes and protoplasm of the cells of adipose tissue, and of the proteid which keeps the fat of milk in emulsion, prepares the fats for what is to follow in the intestine. (2) All the proteids which have not been carried to the stage of peptone, and perhaps some peptone. (3) All the starch and dextrins — and glycogen, if any be present — which have not been converted into maltose, and possibly a little maltose. (4) Elastin, nuclein, cellulose, and other sub- stances not digestible or digestible only with difficulty in gastric juice. (5) The constituents of the gastric juice itself, including pepsin. The ptyalin of the saliva has been already digested and destroyed. It must be remembered that all this time, even from the beginning of digestion, a certain amount of pancreatic juice has been finding its way into the duodenum in response to that distant action of the food which we have discussed, and the reflex nature of which we have not been able either definitely to admit or altogether to reject. The secretion of bile, too, always going on, has quickened its pace, and the gall-bladder is getting more and more full as the meal proceeds, and gastric digestion begins. When the acid chyme, a grayish liquid, turbid with the debris of animal and vegetable tissues — with muscular fibres, fat globules, starch granules, and dotted ducts — gushes through the pylorus and strikes the duodenal wall, a rush of bile takes place, which perhaps precipitates some of the soluble consti- tuents— parapeptones, proteoses (albumoses), and pepsin — as a granular coating on the surface of the mucous membrane. The pepsin, although afterwards redissolved along with the rest of the precipitate, is thus rendered inert, and prevented from destroying the trypsin already present in the duodenum, as it would otherwise do, since the reaction of the chyme still remains acid. By-and-by, as bile and pancreatic juice continue to be poured out, the reaction becomes less acid though never alkaline unless for a short time in the duode- num, and the trypsin begins its work upon the proteids. The undigested proteids are all carried on to the stage of peptone, much of this being absorbed as it is formed, some DIGESTION. 307 even in perfectly normal digestion, in the dog at least, being further split up into leucin and tyrosin. The common statement that the contents of the intestine are alkaHne is certainly incorrect. Trypsin, like pepsin, performs its work, for the most part, at any rate, in an acid medium. The reaction in the duodenum may possibly become alkaline for a time, when the inflow of bile and pancreatic juice is at its height. But the lactic acid produced by the action of micro-organisms on the sugar in the intestine more than neutralizes the alkaline substances in these secretions, and the acidity of the chyme continually increases as it passes down the gut. We are not without other examples of digestive juices destined to act in a medium with an opposite reaction to their own. The ' saliva ' of Octopus macropus, strongly acid though it is, contains a proteolytic ferment which in vitro acts, like trypsin, better in a neutral or alkaline, than in an acid solution. The pepsin of the (in itself) alkaline secretion of the pyloric end of the stomach becomes a constituent of the acid gastric juice ; and it may, perhaps, be con- sidered a morphological accident, so to speak, that the oxyntic cells of the cardiac end should mingle their acid products with the (pre- sumedly) alkaline secretion of the chief cells in the lumen of each gland-tube, instead of being massed as a separate organ with a special duct. In the lower portions of the small intestine bacteria of various kinds are present and active ; and it is not unlikely that even throughout its whole length a certain range of action is permitted to them, checked by the acidity of the chyme, and perhaps by the antiseptic properties of the bile. The stomach, with its acid contents, forms during the greater part of gastric digestion a valve or trap to cut' off the upper end of the intestine from the bacteria-infested regions of the mouth and pharynx, and to destroy the micro-organisms swallowed with the food and saliva. The occasional presence in vomited matter of sarcinae or regularly arranged groups of micrococci, generally four to a group, shows that under abnormal conditions the gastric contents are not perfectly aseptic ; and even from a normal stomach active micro-organisms of various kinds can be obtained. But upon the whole there is no doubt that the acidity of the gastric juice is an important check on bacterial activity during the first part of digestion, and in the upper portion of the alimentary canal. And, indeed, Koch has shown that the acidity of the gastric juice of a guinea-pig is suiBcient to kill the comma bacillus 3o8 A MANUAL OF PHYSIOLOGY. of cholera. Normal guinea-pigs fed with cholera bacilli were unaffected. But if the gastric juice was neutralized by an alkali before the administration of the bacilli the guinea- pigs died. It has been supposed by some that this bactericidal action is the chief function of the stomach, and the question has been asked, why we should attribute any digestive im- portance to the secretion of that viscus, smce the pancreatic juice can do all that the gastric juice does, and some things which it cannot do ? Further, it has been shown that a dog may live five years after complete excision of the stomach, comport himself in all respects like a normal dog, and when killed for autopsy show every organ in perfect health (Czerny). But if this is to be admitted as evidence against the digestive function of the stomach, it is just as good evidence against the bactericidal function, particularly as it has in addition been lately shown that even putrid flesh has no harmful effect on a dog after excision of the stomach, any more than on a normal dog. And, indeed, the reasoning is fallacious which assumes that what may happen under abnor- mal conditions must happen when the conditions are normal. For nothing is impressed more often on the physiological observer than the extraordinary power of adaptation, of making the best of everything, which the animal organism possesses. Doubtless, a dog without a stomach will use to the best advantage the digestive fluids that remain to him ; and the pancreatic juice may be adequate to the task of complete digestion. So, too, a man from whom the surgeon has removed a kidney, or a testicle, or a lobe of the thyroid gland, may be in no respect worse off than the man who possesses a pair of these organs. But what do we deduce from this ? Not surely that the excised thyroid, or testicle, or kidney was useless, or the gastric juice inactive, but that the organism has been able to compensate itself for their loss. The lower end of the small intestine is not cut off by any bacteria-proof barrier from the large intestine, in which putrefaction is constantly going on. So that micro-organisms may be able to work their way above the ileo-csecal valve, even against the downward peristaltic movement. But even DIGESTION. 309 if this were not the case a few bacteria or their spores, passing through the stomach with the food, would be enough to set up extensive changes as soon as they reached a part of the ahmentary canal where the conditions were favourable to their development. Indeed, from the time when the lirst micro-organism enters the digestive tube soon after birth, it is never free from bacteria ; and their multiplication in one part of it rather than another depends not so much on the number originally present to start the process, as on the conditions which encourage or restrain their increase. The fact that the reaction in the intestine is acid renders it difficult to apply the results of experiments made under artificial conditions (p. 327), to the explanation of the changes undergone by the fats in actual digestion. They may, to a small extent, be broken up into their fatty acids and glycerine by the fat-splitting ferment of the pancreatic juice. The acids may form soaps with alkalies wherever they meet them in the intestinal contents, or even in the mucous membrane. The soaps may aid the emulsifi- cation of the fats which we know takes place in the small intestine as a preparation for their absorption by the villi (p. 328). The starch and dextrine which have escaped the action of the saliva are changed into maltose by the pancreatic juice. A little dextrine may be absorbed as such (Bleile). The succus entericus plays no very important part, although, as an alkaline liquid, it doubtless aids in establish- ing the reaction favourable to intestinal digestion. It will invert any cane-sugar which may reach the intestine ; but it cannot be doubted that cane-sugar may be absorbed by the stomach, being inverted either by a ferment in the mucus lining that viscus, or on its way through the gastric walls. Upon the whole no great amount of water is absorbed in the small intestine, or at least the loss is balanced by the gain, for the intestinal contents are as concentrated in the duodenum as in the ileum. But as soon as they pass beyond the ileo-caecal valve, water is rapidly absorbed, and the contents thicken into normal fgeces, to which the chief con- tribution of the large intestine is mucin, secreted by the vast number of goblet-cells in its Lieberkiihn's crypts. 3IO A MANUAL OF PHYSIOLOGY. So far we have paid no attention to other than the soluble ferments of the digestive tract. It is now necessary to recognise that the presence of bacteria is an absolutely constant feature of digestion ; and although their action must in part be looked upon as a necessary evil which the organism has to endure, and against the consequences of which it has to struggle, it is not unlikely that in part it may be ancillary to the processes of aseptic digestion. Among the more important actions of bacteria on the proteid food-products in the intestines maybe mentioned the formation of indol, phenol, and skatol, the first having tyrosin for its precursor, and being itself after absorption the precursor of the indican in the urine ; the second being to a small extent thrown out with the faeces, but chiefly absorbed and eliminated by the kidneys as an aromatic compound of sulphuric acid ; the third passing out mainly in the faeces. From carbo-hydrates lactic acid is formed in increasing amount as the lower portion of the intestine is reached, so that the reaction, which is acid in the upper part of the tube, owing to the acidity of the chyme, in spite of the out- flow of bile and pancreatic juice remains acid in the ileum. In the dog, indeed, on a flesh diet, and therefore under con- ditions which leave little scope for lactic acid fermentation, the reaction of the whole of the small intestine has been found acid. But this is perhaps not constantly the case ; and when it does occur, it may be connected with the very thorough and almost exhaustive digestion of proteids, which, as we have already mentioned, the stomach of the dog is of itself able to accomplish, so that little being left for the intestine to do, little of the alkaline digestive juices are poured into it, and this little is swamped by the acid gastric contents. The large intestine is the chosen haunt of the bacteria of the alimentary canal ; they swarm in the faeces, and by their influence, especially in the caecum of herbivora, but also to a small extent in man, even cellulose is broken up, the final products being carbonic acid and marsh gas. The contents of the large bowel are generally acid from the products of putrefaction, although the wall itself is alkaline. DIGESTION. 311 Faeces. — In addition to the mucin secreted by the large intestine the faeces consist of indigestible remnants of the food, such as elastic fibres, spiral vessels of plants, and in general all vegetable structures chiefly composed of cellulose. They are coloured with a pigment, stercobilin, derived from the bile pigments, and identical with ' febrile ' urobilin, and with the urobilin which forms a common, though not an invariable constituent of bile itself, but different from the urobilin of normal urine. No bilirubin or biliverdin occurs in normal faeces, although pathologically they may be present. A small amount of altered bile acids and their products is also found ; and in respect to these, and to the altered pigments, bile is an excretion. And although its im- portant function in digestion, and the fact that the greater part of the bile salts is reabsorbed, show that in the adult it is very far from being solely a waste product, the equally cogent fact, that the intestine of the new-born child is filled with what is practically concentrated bile {meconium), proves that it is just as far from being purely a digestive juice. Skatol and other bodies, formed by putrefactive changes in the proteids of the food, are also present in the faeces ; but the faecal odour is not due to skatol, as has been supposed, since it is without smell when pure. Of the inorganic substances in fseces the numerous crystals of triple phosphate are the most characteristic. When the diet is too large, or contains too much of a particular kind of food, a considerable quantity of digestible material may be found in the faeces, e.g., muscular fibres and fat. CHAPTER V. ABSORPTION. Having thus traced the food in its progress along the alimentary canal, and sketched the changes wrought in it by digestion, we have next to consider the manner in which it is absorbed. Then, for a reason which has already been explained, instead of following its fate within the tissues, until it is once more cast out of the body in the form of waste products, it will be best to drop the logical order and pick up the other end of the clue — in other words, to pass from absorption to excretion, from the first step in metabolism to the closing act, and afterwards to return and fill in the interval as best we can. And here, first of all, it should be remembered that the epithelial surfaces, through which the substances needed by the organism enter it, and waste products leave it, are, physiologically considered, outside the body. The mucous membranes of the alimentary, respiratory and urinary tracts are in a sense as much external as the fourth great division of the physiological surface, the skin. The two latter surfaces are in the mammal purely excretory. Absorption is the dominant function of the alimentary mucous membrane, but a certain amount of excretion also goes on through it. The pulmonar}- surface both excretes and absorbs, and that in an equal measure. But it is by no means necessary that the surface through which oxygen is taken in and gaseous waste products given off should be buried deep in the body, and communicate only by a narrow channel with the exterior. Plate III. Fat globule in central lacteal y^&S* Villut Fat globules passing through umnar epitJielium — - -^ Circular muscular '~' "" coat 1. Section of frog's intestine to show absorption of fat, x 300. (Stained with picrocarmine and osmin ncid.^ Villi Oohlet cell with plug of mucin ► Capillary plcxu* More nighly magnified portion of villus .=- - - A LieberJciiJin'a crypt Circular musetilar coat /r^f^'As^'-^y^::: ,, I '' ,,= ,,' *l.^**^ Longitudinal muscular coat 2. Sectii^n of small intestine. Blood-vessels injected. (Stained with hasmatoxylin and eosin.) WestlTewman cirlitk. ABSORPTION. 313 In the frog the skin is largely an absorbing as well as an excreting surface ; oxygen passes freely in through it, just as carbonic acid passes freely out. In most fishes, and many other gill-bearing animals, the whole gaseous inter- change takes place through surfaces immersed in the sur- rounding water, and therefore distinctly external. In certain forms it has even been shown that the alimentary canal may serve conspicuously for absorption and excretion of gaseous, as well as liquid and solid substances. Still lower down in the animal scale, the surface of a single tube may perform all the functions of digestion, absorption and Carbon c, nitrogen w, hydrogen h, and oxygen o. L repre- sents the pulmonary surf^ice; K, the surface of the renal epithelium ; A, the ali- m e n t a r y canal ; S, the skin. Diagram of Absorption .\nd Excretion. excretion. Lower still, and even this tube is wanting, and everything passes in and out through an external surface pierced by no permanent openings. Indeed, even in man the functions of the various anatomical divisions of the physiological surface are not quite sharply marked off from each other. Though gaseous interchange goes on far more readily through the pulmonary membrane than anywhere else, swallowed oxygen is easily enough absorbed from the alimentary canal and carbonic acid given off into it ; and to a small extent these gases can also pass through the skin. Though water is excreted chiefly by the skin the pulmonary and the urinary surfaces, and on the whole absorbed chiefly from the digestive tract, there is no surface which in the twenty-four hours 314 ^i MANUAL OF PIIYSIOLOGV. pours out so much water as the mucous membrane of the stomach. Under normal conditions, it is true, by far the greater part of this is reabsorbed in the intestine, yet, in diarrhoea, whether natural or caused by purgatives, the intestines themselves may, instead of absorbing, contribute largely to the excretion of water. Again, although the solids of the excreta are normally given off in far the greatest quantity in the urine and faeces (only part of the latter is truly an excretion, since much of the faeces of a mixed diet has never been physiologically inside the body at all), yet salts are constantly, and urea occasionally, found in the excretions of the skin, and of the respiratory tract. Further, although the solids and liquids of the food are usually taken in by the alimentary mucous surface, it is possible to cause substances of both kinds to pass in through the skin ; and a certain amount of absorption may also take place through the urinary bladder. So that really it may be considered, from a physiological point of view, as more or less an accident that a man should absorb his food by dipping the villi of his intestine into a digested mass, rather than by dipping his fingers into properly pre- pared solutions, as a plant dips its roots among the liquids and solids of the soil ; or that he should draw air into organs lying well in the interior of his thorax, instead of letting it play over special thin and highly vascular portions of his skin ; or that the surface by which he excretes urea should be buried in his loins, instead of lying free upon his back. It has been already explained that, although digestion is a necessary preliminary to the absorption of most of the solids of the food, we are not to suppose that all the food must be digested before any of it begins to be absorbed. On the contrary, the two processes go on together. As soon as any peptone has been formed from the proteids, or sugar from the starch, they begin to pass out of the alimentary canal ; and by the time digestion is over, absorption is well advanced. Even in the mouth it has already begun, and it is con- tinued with far greater rapidity in the stomach. Here ABSORPTION. 315 peptones, sugar, and diffusible substances like alcohol, and the extractives of meat, which form an important part of most thin soups and of beef-tea, are undoubtedly absorbed. But it is in the small intestine that absorption reaches its height. The mucous membrane of this tube offers an immense surface, multiplied as it is by innumerable villi, and by the valvulae conniventes. Here the whole of the fat, much sugar and peptone, certain products of the further action of the unformed and formed ferments of the intestine on the food, and certain constituents of the bile are taken in. In the large intestine, as has been already said, water and soluble salts are chiefly absorbed. What now is the mechanism by which these various products are taken up from the digestive tube, and what paths do they follow on their way to the tissues ? Absorption is the Work of Cells. — Not so very long ago, it was supposed by many that the laws of osmosis held within them the complete explanation of physiological absorption. At that time the dominant note of physiology was an eager appeal to chemistry and physics to ' come over and help it '; and much more was expected from their aid than, as we see now, it was wise to hope for. The phenomena of the passage of liquids and dissolved solids through animal membranes, upon which the work of Graham had cast so much light, seemed to find their parallel in the absorptive processes of the alimentary canal. And when digestion was more deeply studied, facts appeared which seemed to show that its whole drift was to increase the solubility and diffusibility of the constituents of the food. Here then at last, it was thought, the phantom of ' vital action ' had been laid. Within the digestive tract at least there was no room left for any ' mystery of life.' But as time went on, and more was learnt of the phenomena of absorption and the powers of cells, the physical theory broke down, and the vitalistic theory again took its place. The mystery came back ; and it had to be confessed that here, as elsewhere, we were face to face with the processes of living matter, definite, well-ordered, and evidently guided by laws, but by laws which denied themselves to the modern physiologist with 3i6 A MANUAL OF THYSIOLOGY chemistry in one hand and physics in the other, as they had denied themselves to his predecessor, equipped only with his scalpel, his sharp eyes, and his mother-wit. To-day we have to confess that, just as secretion is not a physical filtration, so absorption is not osmosis. Both are undoubtedly aided by osmosis, perhaps by imbibition, but at bottom are the work of cells, and of cells with a selective power which we do not understand, and which is probably peculiar to living structures. Accordingly, we find that when the cells which line the intestine are weakened or destroyed, absorption from it is diminished or abolished ; and that in their normal state the}^ do not take up indiscriminately all kinds of a, layer of columnar epi- thelium cover- ing the villus — the outer edge of the cells is striated; b, cen- tral lacteal of villus ; c, un- striped muscu- lar fibres ; d, mucin -forming goblet-cell. Fig. 90. — Vkktical Section of a Villus (Cat) x 300. diffusible substances, nor absorb those which they do take up in the direct ratio of their diffusibility, nor do they reject everything which does not diffuse. Thus cane-sugar, not- withstanding its high diffusibility, is for the most part not taken up as such. Grape-sugar is absorbed in larger amount from a loop of intestine than sodium sulphate, although the latter is the more diffusible. Albumin, which does not pass through dead animal membranes, is to a certain extent taken up from a loop of intestine without change. But if it be true that the action of the columnar epithelium of the intestinal mucous membrane is governed by a secretive and selective ABSORPTION. 317 power, that makes use of purely physical processes, but is not mastered by them, the possibility must be admitted that in the cells of endothelial type which line the serous cavities, the lymphatics, the bloodvessels, the alveoli of the lungs, and the Bowman's capsules of the kidney (p. 342), the element of secretion is less marked, and more overshadowed by the physical factors. And it may very plausibly be urged that changes of considerable physiological complexity can only be wrought on substances that have to pass through a cell of considerable depth, while a mere film of protoplasm suffices for, and indeed favours, mechanical filtration and diffusion. We have already seen (p. 202), in the case of the lungs, that whatever the complete explanation may be of the gaseous interchange which takes place through the alveolar membrane, physical diffusion undoubtedly plays a certain part. We shall see, too (p. 348), that in the case of the kidney the endothelium of the Bowman's capsule, although by no means devoid of selective power, does seem to have allotted to it a simpler task than falls to the share of the ' rodded ' epithelium. Further, it has been stated that interchange between blood-serum, circulated artificially in the vessels of dogs and rabbits which have been dead for hours, and liquids introduced into the peritoneal cavity is essentially the same as in the living animal, and can be explained by the physical process of imbibition alone (Hamburger). Ligation of the thoracic duct has little effect on the fate of liquids injected into serous cavities, since the bloodvessels play the chief part in their absorption, just as strychnia, when injected under the skin — i.e., into the lymph-spaces of areolar tissue — is taken up by the blood and does not appear in the lymph. And if substances can pass, by physical processes alone, from the serous cavities, which are really expanded lymph-spaces, into the blood, and from the blood into serous cavities, it is natural to inquire whether anything else is con- cerned in the passage of the constituents of the lymph through the capillary walls. Formation of Lymph. — The teaching of Ludwig, that filtration is the great factor in the formation of lymph, was called in question by Heidenhain, whose theory of secretion at first bade fair to totally supplant the older view. But a reaction has set in. A zealous band of investigators has revived the old doctrine of filtration. The battle is once more being fought on equal terms ; and a rich harvest of new facts and new ideas has been the result of the controversy. One of the strongest arguments in favour of the secretion theory has been the existence of substances which, when injected into the blood, increase the flow of lymph, without affecting appreciably the arterial pressure. Heidenhain divides these so-called /y//ip/iagc\i;ues into two classes : (i) substances like peptone, leech-extract, extract of crayfish, egg-albumin, etc., which cause not only an increase in the rate of flow, but an increase in the specific gravity and total solids of the lymph ; (2) crystalloid substances, like sugar, salt, etc., which cause an increased flow of lymph more watery than normal. Starling has shown that although the lymphagogues of the second class do not raise the arterial pressure, they do, by attracting water from the 3i8 A MANUAL OF PHYSIOLOGY. tissues and thus causing hydrsemic plethora (an excess of blood of low specific gravity), bring about a marked rise of venous, and there- fore, what is the important thing for lymph filtration, of capillary pressure. The action of the first class of lymphagogues, which cannot be explained in this way because the pressure in the capillaries is not increased, he attributes to an injurious effect on the capillary endothelium (and especially on the endothelium of the capillaries of the liver, since nearly the whole of the increased lymph-flow comes from that organ), which increases its permeability. Starling's expla- nation is supported by various facts, but it is not easy to distinguish an increase of permeability produced by lymphagogues from an increase of secretive activity of the endothelial cells. Hamburger, too, has brought forward results which it is difficult to reconcile with a theory of filtration even for the second class of lymphagogues, and asks how it is possible that, through a purely physical process of filtration, liquid should pass from the tissue-spaces into the capillaries and at the same time from the capillaries into the tissue-spaces. Further, Heidenhain has shown that some time after injection of a crystalloid substance, like sugar, into the blood, a greater percentage of the substance may be found in the lymph than in the blood. Now, when a mixture of crystalloids and colloids is filtered through a thin membrane, the percentage of crystalloids in the filtrate is never, at most, greater than in the original liquid (Cohnstein). And although Cohnstein states that if time enough be allowed, the maxi- mum concentration of sodium chloride in the lymph, after intra- venous injection, becomes approximately the same as the maximum in the blood, this fact does not enable us to decide against the secretion and in favour of the filtration hypothesis. It ought to be remembered in this whole discussion that the epithelium of ordinary glands derives its supplies of material from the lymph. The vicissitudes of blood-pressure affect it only in a secondary and indirect manner. On the other hand, the endothelial cells which have to do with the formation of lymph are in direct contact with the blood. And it is interesting to observe that in this respect the glomeruli of the kidney and the alveoli of the lungs (if the endothelial lining of Bowman's capsule and the alveolar membrane are assumed to be complete) take a middle place between the glands proper and the quasi-glandular capillaries. The increase in the quantity of chyle flowing from the thoracic duct during digestion may be, on the mechanical theory, associated with the dilatation of the intestinal arterioles and the consequent increase of blood pressure in the capillaries of the splanchnic area in general, and of the liver in particular. But it may be equally well harmonized with the doctrine of secretion. In consequence of the quickened flow of lymph the number of lymphocytes in the blood is increased during digestion, a fact which ought to be remembered in enumerating the corpuscles for clinical purposes. Absorption of Fat. — Fats are absorbed, not in solution, but in a state of fine division, by the epithelial cells covering the ABSORPTIOy. 319 villi, and apparently by them alone. If an animal is killed during digestion of a fatty meal, these cells are found to contain globules of different sizes, which stain black with osmic acid, are dissolved out by ether, leaving vacuoles in the cell substance, and are therefore fat (Plate III., i). It is not known in what manner the cells take up the emulsified fat from the intestine, but it certainly passes into them, and not between them. When fat is found in the cement sub- stance between the cells, it has been mechanically squeezed out of them by the shrinking of the villi in preparation. Leucocytes have been asserted to be the active agents in the absorption of fat. They have been described as pushing their way between the epithelial cells, fishing, as it were, for fatty particles in the juices of the intestine, and then travelling back to discharge their cargo into the lymph. This view, however, is erroneous, and was based upon the assumption that the granules in certain leucocytes which are blackened by osmic acid were fat, which is not the case, as they are not soluble in ether. From the epithelial cells the fat passes into the spaces of the network of adenoid tissue that occupies the interior of the villus, from which it finds its way into the central lacteal, part of it being still more finely divided in its passage so as to form the so-called molecular basis of the chyle. The contraction of the smooth muscular fibres of the villus and the peristaltic movements of the intestinal walls alter the capacity of the lacteal chamber, and so alternately fill it from the lymph of the adenoid reticulum, and empty it into the lymphatic vessel with which it is connected. By this kind of pumping action the passage of fat and other sub- stances into the lymphatics is aided. In the dog no fat is absorbed by the bloodvessels, except perhaps a small quantity in the form of soaps ; it nearly all goes into the lacteals, and thence by the general lymph stream through the thoracic duct into the blood. And in man the chyle collected from a lymphatic fistula contained a large propor- tion of the fat given in the food (Munk). But this bare statement would be misleading if we did not add that the fat taken in can never be entirely recovered in the chyle collected 320 A MANUAL OF PHYSIOLOGY. from the thoracic duct. A portion of it disappears, and its fate is unknown. And even after Hgature of the thoracic duct a large proportion of a meal of fatty acids is absorbed from the intestine, by what channel is uncertain (Frank). A dog normally absorbs g — 21 per cent, of the fat in a meal in three to four hours ; 21 — 46 per cent, in seven hours; and 86 per cent, in eighteen hours (Harley). After excision of the pancreas not only is the absorption of fat abolished, but more fat can be recovered from the intestine than is given in the food. This at first sight paradoxical result is explained by the well-established fact that a certain amount of fat is normally excreted into the intestine. Absorption of Water, Salts, and Sugar. — The water, salts, and sugar pass normally into the rootlets of the portal vein, not into the chyle, for no increase in the quantity of these substances flowing through the thoracic duct takes place during digestion, while the sugar in the portal blood is increased after a starchy meal. In man not i per cent, of the sugar corresponding to the carbo-hydrates of the food could be recovered in the chyle escaping from a lymphatic fistula. But when a large amount of a dilute solution of sugar is introduced into the intestine some of it is taken up by the lacteals. Absorption of Proteids. — The precise path taken by the proteids remains obscure. Although a certain amount of egg-albumin, myosin, alkali-albumin, and other proteid sub- stances can be absorbed as such by the small, and even by the large intestine, there can be no doubt that the greater part of the proteids of the food is first changed into peptones. But peptones are found neither in the blood nor in the chyle, and, indeed, even when injected in small quantity into the blood they are excreted in the urine. When injected in larger amount thtey pass also into the lymph, from which they gradually reach the blood again, and are eventually, as before, eliminated by the kidneys. The clear inference is that they must be changed into one or both of the chief proteids of blood and chyle (serum-albumin and serum-globulin) in their passage through the intestinal wall. Such a change must presumably take place in cells, and the ABSORPTION. 321 only available cells in this locality are those which line the intestine, or the leucocytes which wander between them. Accordingly, both have been credited with the power of absorbing and transforming peptone, but the balance of evidence is in favour of the epithelial cells. We cannot, however, as in the case of the fat, single out any particular tracts of these cells as alone engaged in the absorption of peptone, or, indeed, of the diffusible substances in general. In all likelihood the cells covering the villi are actively con- cerned, but there is no valid reason for denying a share to the general lining of the stomach and small intestine, even including the Lieberkiihn's crypts, which morphologically form a kind of inverted villi. It is, indeed, true that the crypts do not take part in the absorption of fat, for no granules blackened by osmic acid occur in them during digestion of a fatty meal. But this is a ground for attributing to them other absorptive functions rather than for altogether denying to them a share in absorption, especially as it seems un- likely that the secretion of the comparatively scanty and relatively unimportant succus entericus should engross the whole activity of such an extensive sheet of cells. Even the large intestine, which possesses Lieberkiihn's crypts but no villi, is able to absorb not only peptones and sugar, but also undigested proteids; and although these are powers which can be rarely exercised in normal digestion, they form the physiological basis of the important method of treatment by nutrient enemata. Whether the proteids of the food and their digested products pass directly into the blood-capillaries which feed the portal system, or into the lacteals, or into both, has hardly been decided as yet by exact experiments ; but it is highly probable that at any rate a large proportion goes at once intC) the blood. For it has been shown that after ligature of the thoracic duct proteid substances are still absorbed from the intestine, and the urea corresponding to their nitrogen appears in the urine. And the proteids in the lymph flowing from a lymphatic fistula in man were not found to be sensibly increased during the digestion of proteid food (Munk). 21 322 A MANUAL OF PHYSIOLOGY. We may add to the proof of the varied powers of the cells of the intestinal wall given by the change which peptones undergo in their passage through them, the fact, already mentioned, that cane-sugar does not pass into the blood as such, but is first converted into dextrose, even in the absence of an inverting ferment, and the remarkable discovery of Munk, that fatty acids given by the mouth appear in the lymph of the thoracic duct as neutral fats, having somewhere or other, in all probability on their way through the epithe- lium of the gut, been combined with glycerine, although no free glycerine is known to occur in the body. Since, however, the amount of neutral fat recovered from the thoracic duct is not equivalent to more than one-third of the fatty acid given, it has been suggested that this synthesis of fat is only apparent, and that the whole of the fat which appears in the chyle after a meal of fatty acids comes from the fat excreted into the intestine (Frank), which is increased when fatty acids are given by the mouth. PRACTICAL EXERCISES ON CHAPTERS IV. AND V. I. Saliva. — Collection and Al icroscopic Examination of. Saliva. — Chew a piece of parafifin-wax, or inhale ether or the vapour of strong acetic acid. The flow of saliva is increased. Collect it in a porcelain capsule. Examine a drop under the microscope. It may contain a few flat epithelial scales from the mouth and a few round granular bodies, the salivary corpuscles, the granules in which often show a lively, dancing movement (Brownian motion). Filter the saliva to free it from air-bubbles, and perform the following experiments : (a) Test the reaction with litmus paper. It is usually alkaline. An acid reaction may indicate that bacterial processes are abnormally active in the mouth. {b) Add dilute acetic acid. A precipitate indicates the presence of mucin (p. 249). Filter. {c) Add a drop or two of silver nitrate solution. A precipitate soluble in ammonia, insoluble in nitric acid, proves that chlorides are present. {d) Add to another portion a few drops of dilute ferric chloride, and the same quantity to as much distilled water in a control test- tube. A red coloration is obtained, due to the presence of potassium sulpho-cyanide (KCNS). The colour is discharged by mercuric chloride. This reaction is not given by the saliva of most animals, nor bv that of some men. PRACTICAL EXERCISES. 323 {e) To the filtrate from {p) add Millon's reagent. A red coloration or precipitate shows that proteid is present. (/) Take some boiled starch mucilage, and test it for reducing sugar by Trommer's test. If no sugar is found, take three test-tubes, label them A, B, and C, and nearly half fill each with the boiled starch. To A add a little saliva, to B some saliva which has been boiled, to C an equal volume of 0*4 per cent, hydrochloric acid and a little saliva which has been neutralized, so as to make the strength of the acid in the mixture o'2 per cent., or the same as that of the gastric juice. Put the test-tubes into a water-bath at about 40° C. In a few minutes test the contents for reducing sugar. Abundance will be found in A, none in B, little, if any, in C. In B the ferment ptyalin has been destroyed by boiling ; in C its action has been in- hibited by the acid. If the test-tubes have been left long enough in the bath, no blue colour will be given by A on the addition of iodine, but a strong blue colour by B and C ; />., the starch will have completely disappeared from A. Trommer's Test for reducing Sugar. — To the liquid to be tested add a drop or two of dilute cupric sulphate, and then excess of caustic soda, and boil. The blue colour of the cupric hydrate gives place to a yellow or red (cuprous hydrate or oxide) if reducing sugar be present. Phenyl-hydrazine Test. — See p. 370. {g) Put some starch in a test-tube, add a little saliva, and hold in the hand or place in a bath at 40° C. On a porcelain slab place several separate drops of dilute iodine solution. With a glass rod add a drop of the mixture in the test-tube to one of the drops of iodine at intervals as digestion goes on. At first only the blue colour given by starch will be seen ; a little later a violet colour, due to the presence of erythrodextrin in addition to some unaltered starch ; a little later the colour will be reddish, the starch having disappeared, and the erythrodextrin reaction being no longer obscured ; later still no colour reaction will be obtained, the erythrodextrin having under- gone further changes, and only sugar (maltose, isomaltose, and perhaps a trace of dextrose) and achroodextrin — a kind of dextrin which gives no colour with iodine — being present. {h) Put a little distilled water in a porcelain capsule, and bring the water to the boil. Now put into the mouth some boiled starch paste, and move it about as in mastication. After half a minute spit the starch out into the boiling water. Divide the water into two portions. Test one for sugar, and the other for starch. Repeat the experiment, but keep the starch two minutes in the mouth. Report the result. {i) Starch solution to which saliva has been added is placed in a dialyser tube of parchment paper for twenty-four hours. At the end of that time the dialysate (the surrounding water) should be tested for sugar and for starch. Sugar will probably be found, but no starch. If no reaction for sugar is obtained, the dialysate should be concentrated on the water-bath, and again tested. (/) Stimulation of the Chorda Tympani. — Having previously studied 324 A MANUAL OF PHYSIOLOGY. the anatomy of the mouth and submaxillary region in the dog by dissecting a dead animal, put a good-sized dog under morphia (p. 150). Set up an induction-machine for a tetanizing current (p. 149). Fasten the dog on the holder, give ether if necessary, and insert a cannula in the trachea (p. 151). Then make an incision three or four inches long, through skin and platysma muscle, along the inner border of the lower jaw. Ligature doubly and divide such branches of the jugular vein as come in the way, except those belonging to the submaxillary gland. Feel for the facial artery, so as to be able to avoid it. Divide the digastric muscle about its anterior third, and clear it carefully from its attachments, in order to expose the submaxillary and sublingual ducts with the accom- panying nerves. Now ' ligature the lingual nerve before it enters the tongue, cut it peripherally to the ligature ; then separate it and the chorda tympani from the surrounding tissue,' and cut the chordo- lingual nerve (Fig. 85, p. 286) ' centrally to the point where the chorda is given off' (Langley). Then insert a suitable glass cannula with a rectangular elbow into the submaxillary duct, just as if it were a bloodvessel (p. 45). On stimulating the chorda, the flow of saliva through the cannula will be increased. It may be collected, and the experiments already made with human saliva repeated. If the experiment is successful, finish by stimulating the nerve to ex- haustion. Then harden both submaxillary glands in absolute alcohol, make sections, stain with carmine and compare them. 2. Gastric Juice — {a) Preparation of Artificial Gastric Juice. — Take a portion of the pig's stomach provided, strip off the mucous membrane (except that of the pyloric end), cut it into small pieces with scissors, and put it in a bottle with fifty times its weight of o"2 per cent, hydrochloric acid. Label and put in bath at 40° C. for twelve hours. Then filter. (Ji) Take another portion of the mucous membrane, cut it into pieces, and rub up with clean sand in a mortar. Then put it in a small bottle, cover it with glycerine, label, and set aside for two or three days. The glycerine extracts the pepsin. {c) Take five test-tubes. A, B, C, D, E, and in each put a little washed and boiled fibrin. To A add a few drops of glycerine extract of pig's stomach, and fill up the test-tube with o'2 per cent, hydrochloric acid. To B add glycerine extract and distilled water ; to C glycerine extract and i per cent, sodium carbonate ; to D 0-2 per cent, hydrochloric acid alone ; to E glycerine extract which has been boiled and 0*2 per cent, hydrochloric acid. Put up another set of five test-tubes in the same way, except that a few drops of a watery solution of a commercial pepsin is substituted for the glycerine extract. Label them A', B', C, D', E'. Into another test-tube put a little fibrin, and fill up with the filtered acid extract from {a). Label it F. Place all the test-tubes in a tumbler, and set them in a water-bath at 40° C. After a time the fibrin will have almost completely disappeared in A, A', and F, but not in the other test-tubes. Filter the contents of A, A', and F. PRACTICAL EXERCISES. 325 (d) Test the filtrate for the products of gastric digestion : (a) Neutralize a portion carefully with dilute sodium hydrate. A precipitate of acid-albumin may be thrown down. Filter. (fi) To a portion of the filtrate from (a) add excess of sodium hydrate and a drop or two of very dilute copper sulphate. A rose colour indicates the presence of proteoses or peptones. The cupric sulphate must be very cautiously added, because an excess gives a violet colour, and thus obscures the rose reaction. If still more cupric sulphate be added, blue cupric hydrate is thrown down, and nothing can be inferred as to the presence or the nature of proteids in the liquid. (7) Heat another portion of the filtrate from (a) to 30 ' C, and add crystals of ammonium sulphate to satura- tion. A precipitate of proteoses (albumoses) may be obtained. Filter off. (6) Add to the filtrate from (7) a trace of cupric sulphate and excess of sodium hydrate. A rose colour in- dicates that peptones are present. More sodium hydrate must be added than is sufficient to drive off all the ammonia of the ammonium sulphate, for the biuret reaction requires the presence of free alkali. A strong solution of the sodium hydrate should therefore be used, or the stick caustic soda. {e) To some milk in a test-tube add a drop or two of rennet extract, and place in a bath at 40° C. In a short time the milk is curdled by the rennin. (/) To obtain Normal Chyme. — Etherize a dog one and a half hours after a meal, and fasten it on a holder. Take a stomach-tube or large flexible catheter, and measure how far it must pass down from the mouth in order to reach the stomach. Put a mark at this point. Moisten the tube with water or a small quantity of vaseline, and push it steadily but gently down the oesophagus. If it is stopped before the mark is reached, its passage must be resisted by the tonic con- traction of the cardiac sphincter of the stomach (the lower part of the oesophagus'). Push the tube steadily on, and this will yield. Then, if no liquid issues, make firm pressure on the abdomen, or attach a large syringe to the tube, and suck the contents of the stomach up. (g) To obtain Pure Gastric Juice. — Put a fasting dog under ether, and fasten on the holder. Clip the hair and shave the skin in the middle line below the sternum. Make a longitudinal incision through the skin and subcutaneous tissue from the xiphoid cartilage downwards for 3 or 4 ^ . ^ , rn, V lu -n i; Fig. qi.— stomach-Cannula. inches. Ihe hnea alba will now be seen as a white mesial streak. Open the abdomen by an incision through 326 A MANUAL OF PHYSIOLOGY. it. Pull over the stomach towards the right, stitch it to the abdominal wall, open it, and insert a stomach-cannula (Fig. 91). By mechani- cally stimulating the mucous membrane of the stomach with a feather, or by the introduction of pieces of indiarubber, a flow of gastric juice can be caused. {h) Test the proteolytic and milk-curdling powers of the filtrate from the chyme obtained in (/), and of the pure juice obtained in {g). Both will dissolve fibrin, but probably neither will curdle milk when neutralized. For the gastric juice of many animals contains no rennin, although the fully-formed ferment or its zymogen may be present in the gastric mucous membrane. Examine a drop of the unfiltered chyme under the microscope. Partially digested fragments of food will be seen— muscular fibres, if meat has been given, or vegetable cells or milk globules. Filter, and proceed as in 2 {d). 3. Pancreatic Juice. — {a) Take a piece of the pancreas of an ox or dog which has been kept twenty-four hours at the temperature of the laboratory, and make a glycerine extract in the same way as in the case of the pig's stomach (2, b). Put in a small botde, and set aside for a day or two. {b) Put a little fibrin into each of six test-tubes, A, B, C, D, E, F. To A add a few drops of glycerine extract of pancreas, and fill up with I per cent, sodium carbonate solution ; to B add glycerine extract and distilled water ; to C glycerine extract and excess of o-i per cent, hydrochloric acid ; to D i per cent, sodium carbonate alone ; to E i per cent, sodium carbonate in which a few drops of glycerine extract of pancreas has been previously boiled ; to F glycerine extract and excess of 0*4 per cent, hydrochloric acid. Set up six test-tubes, A', B', C, D', E', F', in the same way, but substitute a few drops of a solution of commercial pancreatin for the glycerine extract. Put all the test-tubes in a tumbler, and place in a bath at 40° C. The fibrin will be gradually eaten away in A and A' by the action of the trypsin, but will not swell up or become clear before disappearing, as it does in dilute hydrochloric acid with glycerine extract of stomach. Filter the contents of these test-tubes. Neutralize the filtrate with dilute acid ; a precipitate will consist of alkali-albumin. If such a precipitate is obtained, filter it off and test the filtrate for proteoses and peptones as in 2 {d), p. 325. Digestion will also have taken place in C and C, but not in the other test- tubes (pp. 259, 307). {c) Lend?! and Tyrosin. — If pancreatic digestion be allowed to go on for some time, part of the peptone first formed may be broken up into leucin and tyrosin. If the 'digest' be neutralized to separate alkali-albumin, then filtered, and the filtrate concentrated and allowed to stand, a crop of tyrosin crystals will separate out, since tyrosin is only slightly soluble in watery solutions of neutral salts. These crystals having been filtered off, the proteoses (albumoses) and peptones can be precipitated together by alcohol, and afterwards separated, if that is desired, by redissolving the precipitate in water and throwing down the proteoses by saturation with ammonium sulphate. The alcoholic filtrate will contain any leucin that may be PRACTICAL EXERCISES. 327 present, since that body is moderately soluble in alcohol, as well as traces of tyrosin, which, however, is much less soluble in this medium. On concentration, crystals of both substances will be obtained. Tyrosin crystallizes characteristically from animal liquids in beautiful silky needles united into sheaves, leucin in the form of indistinct fatty-looking balls, often marked with radial strias and coloured with pigment (Figs. 99 and 100, p. 340). {d) Add a few drops of the glycerine extract to a test-tube con- taining starch mucilage, which has been previously found free from reducing sugar. Put in a bath at 40^ C. After a short time abundance of reducing sugar will be found, owing to the action of the ferment, amylopsin. ((?) To obtain Norvcal Pancreatic Juice. — Give a rabbit f grm. chloral hydrate per rectum. Put on a holder. Open the abdominal cavity by an incision in the linea alba 2^ inches long. Pull the duodenum, which will be found in the right hypochondrium, through the wound, and follow it down till its mesentery prevents it from coming out any farther. Here the pancreatic duct will be found. ' Resect two inches of the intestine at this point, leaving the mesenteric attachment, tie the cut ends of the intestine above and below, and drop them in the cavity, bringing the resected portion through the wound.' Open the resected piece of intestine opposite the mesenteric attachment, and spread it out on the abdominal wall. Clamp the ends to stop haemorrhage. Push into the pancreatic duct a small glass cannula through the papilla on which the duct opens. The juice begins to flow immediately, and the flow lasts four to six hours, although it is slow, and only a comparatively small quantity can be collected. The exposed intestine must be kept moist by pads of cotton-wool soaked in normal saline (Rachford). The animal must be killed as soon as the flow has ceased. The juice has an alkaline reaction. (/) With the juice so obtained perform the following experiments to demonstrate its fat-splitting action : Shake a little of it with neutral olive-oil ; the oil becomes acid owing to the formation of fatty acid. Take with a pipette a drop of the oil from the surface of the mixture of oil and pancreatic juice, and put it on a ^^ per cent, solution of sodium carbonate in a watch-glass. An emulsion is formed. Sodium carbonate and neutral olive-oil do not form an emulsion ; some fatty acid must be present. 4. Bile. — {a) Test the reaction of ox bile. It is alkaline. {b) Add dilute acetic acid. A precipitate of bile-mucin (really nucleo-albumin) falls down. Some of the bile-pigment is also pre- cipitated. Filter. (r) Dilute the filtrate from (b). Put a little of it into a porcelain capsule, add a few drops of strong sulphuric acid, and a drop or two of a dilute solution of cane-sugar. A purple colour appearing at once, or after gentle heating, shows the presence of bile-acids (Pet- tenkofer's reaction). Examine the purple liquid in a test-tube with a spectroscope (p. 49). Two absorption bands are seen, one between D and E, the other between E and F. 328 A MANUAL OF PHYSIOLOGY. {d) Add yellow nitric acid (containing nitrous acid) to a little bile on a white porcelain-slab. A play of colours, beginning with green and running through blue to yellow and yellowish-brown, indicates the presence of bile-pigment (Gmelin's reaction). (e) Cholesterin (Fig. 92). Preparation. — Extract a powdered gall- stone (preferably a white one) with hot alcohol and ether in a test-tube. Heat the test-tube in warm water. Put a drop of the extract on a slide. Flat crystals of cholesterin, often chipped at the corners, separate out. Carefully allow a drop of strong sulphuric acid and a drop of dilute iodine to run under the cover-glass. A play of colours — violet, blue, green, red— is seen. Evaporate a drop of the solution of choles- ^'*^^^Cryst\ls^^^'^'^ ^^^^" ^" ^ small porcelain capsule, add a drop of strong nitric acid, and heat gently over a flame. A yellow stain is left, which becomes red when a drop of ammonia is poured on it while it is still warm. (/) Preparation of Bile Salts from Bile. — Evaporate bile to a small bulk, mix the residue with animal charcoal, dry to a paste at 100° C, extract with absolute alcohol, and precipitate the solution with ether. The bile-salts separate as a mass of needle-shaped crystals, often in sheaf-like bundles. On dissolving the crystals in water, and adding dilute sulphuric acid to displace the bile-acids, the latter are precipitated as crystalline needles. {g) To demonstrate the Presetice of Iron in the Liver Cells. — Steep sections of liver in a solution of potassium ferrocyanide, and then in dilute hydrochloric acid. They become bluish from the formation of Prussian blue. Mount in glycerine or Farrant's solution. Blue granules may be seen under the microscope in some of the hepatic cells. {Ji) To some starch, shown to be free from sugar, add a little bile, and place in a bath at 40°. After a time test for reducing sugar. Report the result. 5. Microscopical Examination of Faeces. — Examine under the microscope the slides provided. Draw, and as far as possible deter- mine the nature of, the objects seen (p. 311). 6. Absorption of Fat. — Feed a rat or frog with fatty food ; kill the rat in three or four hours, the frog in two or three days. Strip off tiny pieces of the mucous membrane of the small intestine, and steep them in \ per cent, solution of osmic acid for forty-eight hours. Then tease fragments of the mucous membrane in glycerine, take off the glycerine with blotting-paper, mount in Farrant, and examine under the microscope. Other portions of the mucous membrane may be hardened for a fortnight in a mixture of two parts of Miiller's fluid and one part of a i per cent, solution of osmic acid. Sections are then made with a freezing microtome after embedding in gum. No process must be used by which the fat would be dissolved out (Schafer). Celloidin is inadmissible. PRACTICAL EXERCISES. 329 7. Time required for Digestion and Absorption of various Food Substances. — ( i ) Feed a dog which has previously fasted for 24 hours with a meal containing starch, milk and meat. After an hour and a half put it lightly under ether, partially evacuate the stomach as in 2 (/), p. 325, and perform the following experiments : {a) Examine a drop of the chyme under the microscope, and see whether any fat globules, muscular fibres or starch granules can be recognised. (/') Apply the tests given in 2 {d), p. 325, to the filtrate, and in addition test for reducing sugar. {c) In five hours from the beginning of the meal, or a little more if the animal has been sick after the ether, pass the tube again and empty the stomach completely. If it contains no liquid, attach a funnel to the tube and fill the stomach with water. The water is allowed to escape after a few minutes, and tested as in {b). (2) Feed a dog, after a 24 hours' fast, with starch (proved to be free from sugar), seasoned with salt and made up with a little lard or gravy. In 20 minutes evacuate the stomach, test for reducing sugar and for starch, and examine the liquid under the microscope for starch granules. (3) Feed a dog, cat, or white rat, kept without food for 24 hours, with a meal containing fat and a weighed amount of cane-sugar. After three or four hours put the animal under ether, open the abdomen in the linea alba, lift a loop of the small intestine gently up and observe the lacteals in the mesentery. Now kill the animal, tie the oesophagus, place double ligatures on the pyloric end of the stomach and the lower end of the small intestine, and divide between them. Cut out the stomach and intestine ; wash their contents into separate vessels: examine microscopically for fat; test for reducing sugar after filtration, and if any is present estimate its amount in a measured or weighed quantity of the liquid by titration with Fehling's solution (p. 370). Then boil an equal quantity of the liquid with one-twentieth of its volume of hydrochloric acid, and again estimate the reducing power. If this is markedly greater than before, some cane-sugar, which had escaped ' inversion,' must have been present. From the alteration in reducing power the amount of unchanged cane-sugar, if any, could be calculated. 8. Time required for Food to pass through the Alimentary Canal. — Feed a dog with bones. Keep in a special cage, and observe how long it takes before the easily-recognised white bone- fseces appear. CHAPTER VI. EXCRETION. We have now followed the ingoing tide of gaseous, liquid and solid substances within the physiological surface of the body. There we leave them for the present, and turn to the consideration of the channels of outflow, and the waste products which pass along them. In a body which is neither increasing nor diminishing in mass the outflow must exactly balance the inflow ; all that enters the body must sooner or later, in however changed a form, escape from it again. In the expired air, the urine, the secretions of the skin, and the fasces, by far the greater part of the waste pro- ducts is eliminated. Thus the carbon of the absorbed solids of the food is chiefly given off as carbonic acid by the lungs ; the hydrogen, as water by the kidneys, lungs and skin, along with the unchanged water of the food ; the nitrogen, as urea b\' the kidneys. The fasces represent chiefly unabsorbed portions of the food. A small and variable contribution is that of the expectorated matter, and the secretions of the nasal mucous membrane and lachrymal glands. Still smaller and still more variable is the loss in the form of dead epidermic scales, hairs and nails. The discharges from the generative organs are to be considered as excretions with reference to the parent organism, and so is the milk, and even the foetus itself, with respect to the mother. Excretion by the lungs and in the faeces has been already dealt with. All that is necessary to be said of the expectora- tion and the nasal and lachrymal discharges is that the first two generally contain a good deal of mucin, and are produced in small mucous and serous glands, the cells of which are of the same general type as those of the mucous and serous salivary glands. The lachrymal glands are serous like the parotid ; and the tears secreted by them contain some albumin and salts, but little or no mucin. The sexual secretions and milk will be best considered under Plate W. 3,. Crystals of phenyl glucosazone from urine. Mdlpighian tt^ 1. Crystals of uric acid from urine. Bowman's eaptule Interlobular artery 4. Section of cortex of injected kidney. Benal tubule 2. Crystals of ammonium urate from urine. 6. Section of medulla of injected kidney showing vasa recta and collecting tubules-. West.Ne-wman dirHth. EXCRETION. 331 reproduction (Chap. XIV.), so that there remain only the urine and the secretions of the skin to be treated here. I. Excretion by the Kidneys. The Chemistry of the Urine. — Normal urine is a clear yellow liquid of acid reaction, and with an average specitic gravity of about 1020, the usual limits being 1015 and 1025, although when water is taken in large quantities, or long withheld, the specific gravity may fall to 1005, or even less, or rise to 1035, or even more. The quantity passed in twenty-four hours is very variable, and is especially dependent on the activity of the sweat-glands, being, as a rule, greater in summer when the skin sweats much, than in winter when it sweats little. The average quantity for an adult male is about 1500 cc. (say, 50 02.). Composition of Urine. — It is essentially a solution of urea and inorganic salts, the proportion of the latter being about 1*5 per cent., or double the usual amount in physiological solids and liquids. Besides urea, there are other nitrogenous bodies in much smaller quantity, such as uric acid, hippuric acid, and kreatinin. Some of these at least are products of the metabolism of proteids within the tissues, and besides the inorganic salts there are certain organic bodies — indol, phenol, pyrokatechin, skatol — united with sulphuric acid, which are primarily derived from the products of the putre- faction of proteids within the digestive tube. In tabular form the composition of urine, and the total excretion by an average man of 70 kilos, may be given thus : Per 1000. In 24 h ours. Water - 960 1440 grammes. Solids - 40-43 60-65 1-1 Urea - 23 35 ] 075 0-5 1-5 J Uric acid ■ \ Hippuric acid - 1 1-8 -3775 grammes. Kreatinin -) Sodium ■\ 10 Potassium 9 2-5 Ammonia mi 075 Calcium and magnesiu 075 ■26"5 grammes. Chlorine -) 7 Phosphoric acid _ i_ 8 3"5 Sulphuric acid - -) 2 Mucus, pigment, etc. A MANUAL OF PHYSIOLOGY The acidity of urine is not due to free acid, for the tests which reveal the presence of free acid in a mixture, such as the precipitation of sulphur on the addition of sodium hyposulphite, and the change of colour of many organic substances, give a negative result when applied to urine. The acidity is chiefly due to the acid phosphates of sodium and potassium ; in a less degree to dissolved carbonic acid. The acidity is estimated by running into a given quantity of urine a dilute solution of caustic soda, which has been previously titrated with a pure acid solution (say, oxalic acid) of known strength, until a neutral reaction is just obtained. From the amount of caustic soda required the acidity can be calculated in terms of the standard acid. Normally the acidity of urine is about equal to that of a o'l per cent, solution of sulphuric acid. It diminishes dis- tinctly, or even gives place to alkalinity, during digestion when the acid of the gastric juice is being secreted, and rises and falls with the quantity of vegetable food in the diet. The urine of herbivora is alkaline, and turbid from precipitated carbonates and phosphates of earthy bases, while that of carnivora and of fasting herbivora, which are living on their own tissues, is strongly acid and clear. Normal Fig. 93.— Uric Acid. Fig. 94.— Calcium Oxalate. human urine may deposit urates soon after discharge, as they are more soluble in warm than in cold water. They carry down some of the pigment, and therefore usually appear as a pink or brick-red sediment. When urine is allowed to stand after being voided, what is generally described as ' acid fermentation ' occurs. The acidity gradually increases, owing apparently to the formation of lactic acid ; acid sodium urate is produced from the neutral urate, and comes down in the form of amorphous granules, while the liberated uric acid is deposited often in 'whetstone ' crystals, coloured yellow by the pigment (Fig. 93 ; Plate IV., i). Calcium oxalate may also be thrown down as ' envelope,' iN Crvst.\ls. of the kidney casts of the renal tubules are not uncommon. These tube-casts may be composed chiefly of red blood-corpuscles, or of leucocytes, or of the epithelium of the tubules, sometimes fattily degenerated, or of structureless proteid, or of amyloid substance. Abnormal crystalline substances, such as leucin, tyrosin, and cystin, may be on rare occasions found in urinary sediments ; but generally the unorganized deposits of pathological urine consist of bodies actually present in, or obtainable from, the normal secretion, but present in excess, either absolutely, or relatively to the solvent power of the urine. Sugar. — In diabetes mellitus, although the quantity of urine is greatly increased, its specific gravity is above the normal ; and this is due chiefly to the presence of sugar (glucose), which generally amounts to i to 5 per cent., but may in extreme cases reach 10 or even 15 per cent., more than half a kilogramme being sometimes given off" in twenty-four hours. The name of the tests for glucose is legion. They are mostly founded on its reducing action in alkaline solution. Hydrated oxide 340 A MANUAL OF PHYSIOLOGY. of bismuth (Boettcher), salts of gold, platinum and silver, indigo (Mulder), and a host of other substances, are reduced by glucose, and may be used to show its presence. The reduction of cupric salts (Trommer) and the formation of crystals of phenyl-glucosazone (Plate IV., 3) are perhaps the best established tests. (See Practical Exercises, p. 370). Proteids. — Serum -albumin and serum -globulin are the proteids most commonly found in pathological urine. Both are coagulated by heating the urine, slightly acidulated, if it is not already acid, or by the addition of strong HNO., in the cold. Proteoses (albumoses), and peptones, are also occasionally present, and may be recognised by the tests given in the Practical Exercises (p. 368). The pigments of blood and bile may be detected by the char- acters described in treating of these substances ; the spectrum of oxyhcemoglobin, or methtemoglobin, or any of the other derivatives of haemoglobin, with the formation of haemin crystals, would afford proof of the presence of the former, and Gmelin's test of the latter. The red blood-corpuscles, seen with the microscope, are the most decisive evidence of the presence of blood, as leucocytes in abundance are of the ]:)resence of pus. It should be remembered that pus in the urine of women has sometimes no significance except as showing that there has been an admixture of leucorrheal discharge from the vagina. (See Practical Exercises, pp. 49, 52, 328.) The Secretion of the Urine. — We have now to consider the mechanism by which the urine is formed in the kidney from the materials brought to it by the blood. And here the same questions arise as have already been discussed in the case of the salivary and other digestive glands : (i) Are the urinary constituents, or any of them, present as such in the blood? (2) If they do exist in the blood, are they separated from it by processes mainly physical or mainly vital — in other words, by filtration and diffusion, or by the selective action of living cells ? In the case of the digestive juices it has been seen that some constituents are already present in the blood, but that physical laws alone cannot explain the proportions in which they occur in the secretions, nor the conditions under which they are separated ; while other constituents — and these the more specific and important — are manufactured in the gland-cells. In the kidneys the conditions seem at first sight favourable to physical filtration, as opposed to physiological secretion. Urine has been described as essentially a solution of urea and salts, and both are ready formed in the blood. The EXCRETION. 341 arrangement of the bloodvessels, too, suggests an apparatus for filtering under pressure. Bloodvessels and Secreting Tubules of Kidney. — The renal artery splits up at the hilus into several branches, which pass in between the Malpighian pyramids, and form at the boundary of the cortex and medulla vascular arches, from Vessels of ffhmerulus Ejferen/ AHeren^ Bou?idaru Zone rf MeduUa Pap-illaru Zone / Ca/7i//ary plexus fo rme d v^^ bu e/y^erent vessels JJ Distal \^Conv-DluleJ -L -Proximal J ^' 'Glc meru hi s with Bowman's cartsule -~ubis can be felt. A little below this is the opening of the urethra. With the right hand the point of a flexible catheter of suitable calibre is directed along the finger, and after a little ' guess and trial ' it slips into the bladder, its entrance being announced by the escape of urine. When the animal is to be used in a long series of experiments an operation is sometimes performed first of all to render the urethral orifice more accessible. CHAPTER VII. METABOLISM, NUTRITION AND DIETETICS. We return now to the products of digestion as they are absorbed from the alimentary canal, and, still assuming a typical diet containing proteids, carbo-hydrates and fats, we have to ask, What is the fate of each of these classes of proximate principles in the body ? what does each contribute to the ensemble of vital activity ? It will be best, first of all, to give to these questions what roughly qualitative answer is possible, then to look at metabolism in its quanti- tative relations, and lastly to focus our information upon some of the practical problems of dietetics. I. Metabolism of Proteids. — The two chief proteids of the blood-plasma, serum-globulin and serum-albumin, must, as has been already pointed out, be recruited from proteids absorbed from the intestine and for the most part altered in their passage through the epithelium which lines it. What at bottom the reason and the mechanism of this alteration are, we do not know ; but we do know that it is imperative that peptone (or at least albumose), should not appear in quantity in the blood, for when injected it causes profound changes in that liquid, one expression of which is the loss of its power of coagulation, and is rapidly excreted by the kidneys, or separated out into the lymph. It is not definitely known whether the peptones formed in digestion yield, under the influence of the epithelial cells, both the chief proteids of the blood in the proportions in which they exist in the plasma, or only one of them, which is afterwards METABOLISM, NUTRITION AND DIETETICS. 373 and elsewhere partially changed into the other. However this may be, it cannot be doubted that the conversion of peptones, directly or indirectly, into the proteids of the blood-plasma forms the first recognisable step in the trans- formation of the greater part of the digested proteids. Living and Dead Proteids. — Now and again a living proteid molecule in the whirl of ilying atoms which we call a muscle-fibre or a gland-cell or a nerve-cell, falls to pieces. Now and again a molecule of proteid, hitherto dead, coming within the grasp of the molecular forces of the living substance, is caught up by it, takes on its peculiar motions, acquires its special powers, and is, as we phrase it, made alive. But it is not any difference in the kind of proteid which determines whether a given molecule shall become a part of one tissue rather than of another. For it is from the serum-albumin and serum-globulin of the blood that all the proteid material required to repair the waste of the body must ultimately be derived ; and a particle of serum-albumin may chance to take its place in a liver-cell and help to form bile, while an exactly similar particle may become a constituent of an endothelial scale of a capillary and assist in forming lymph, or of a muscular fibre of the heart and help to drive on the blood, or of a spermatozoon and aid in transferring the peculiarities of the father to the offspring. Indeed, although there are differences of detail, the broad lines of nutrition are the same for all tissues ; and just as a tomb or a lighthouse, a palace or a church, may be, and has been built with the same kind of material, or even in succession with the very same stones, so every organ builds up its own characteristic structure from the common quarry of the blood. In the case of the more highly developed tissues at least, ho mere change of food will radically alter structure ; a cell may be fed with different kinds of food, it may be over- fed, it may be ill-fed, it may be starved ; but its essential peculiarities remain as long as it continues to live. But in proportion as the advance of physiology has emphasized the dominant position of organization, it has taken away the hope of our ever being able to understand in what it is that the difference between the living and the dead cell, between living and dead proteid, or protoplasm, really consists. The speculation of Pliiiger, that the nitrogen of living proteid exists in the form of cyanogen radicals, whilst in dead proteid it is in the form of amides, and that the cause 374 A MANUAL OF PHYSIOLOGY. of the characteristic instabihty of the Hving substance — its prodigious power of dissociation and reconstruction — is the great intramolecular movement of the atoms of the cyanogen radicals, is very interesting and ingenious, but it remains, and is likely to remain, a speculation. And the same is true of the suggestion of Loew and Bokorny, that the endowments of living protoplasm depend on the presence of the unstable aldehyde group H-C = 0. Nor do the known differences of chemical composition in dead organs give any insight into the peculiarities of organization and function which mark off one living tissue from another. For so far as they do not depend upon differences in the dead plasma which interpenetrates the living substance, they only show that the latter does not split up quite in the same way at death in all the tissues, while the general similarity in the elementary composition of excitable structures leaves us free to imagine as great or as small a similarity as we please in the grouping of the atoms in the hving combinations. Be this as it may, the living proteid molecule, whatever function it may have been fulfilling in the organized elements of the body, has certainly a much greater tendency to fall to pieces than the dead proteid molecule. And it falls to pieces in a fairly definite way, the ultimate products, under the influence of oxygen, being carbonic acid, water and comparatively simple nitrogen- containing substances, which after further changes appear in the urine as urea, uric acid, hippuric acid, kreatinin and ammonia. We have no definite information as to the pro- duction of water from the hydrogen of the tissues, except what can be theoretically deduced from the statistics of nutrition (p. 406). A few words will be said a little farther on about the production of carbonic acid from proteids ; we have now to consider the seat and manner of forma- tion of the nitrogenous metabolites. And since in man and the other mammals urea contains by far the greater part of the excreted nitrogen, it will be well to take it first. Formation of Urea. — The starting-point of all inquiries into the formation of urea is the fact that it occurs in the blood, METABOLISM, NUTRITION AND DIETETICS. 375 although in very small quantities (2 to 4 parts per 10,000). Evidently, then, some, at least, of the urea excreted in the urine may be simply separated by the kidney from the blood ; and analysis shows that this is actually the case, for the blood of the renal vein is poorer in urea than that of the renal artery. If we knew the exact quantity of blood passing through the kidneys of an animal in twenty-four hours, and the average difference in the percentage of urea in the blood coming to and leaving them, we should at once be able to decide whether the whole of the urea in the urine reaches the kidneys ready made, or whether a portion of it is formed by the renal tissue. Although data of this kind are as yet too inexact and too incomplete to enable us, without other evidence, absolutely to say that all the urea is simply separated by the kidney, it is not difficult to see, from such rough measurements as have been made, that this is at least possible, if not probable. If we take the weight of the kidneys of a dog of 35 kilos at 160 grammes (o|-g-th of the body weight is the mean result of a great number of observations in man), and the average quantity of blood in them at rather less than one-fourth of their weight, or 35 grammes, and consider that this quantity of blood passes through them in the average time required to complete the circulation from renal artery to renal vein, or, say, ten seconds, we get about 300 kilos of blood as the flow through the kidneys in twenty-four hours. At '3 per 1,000, the urea in 300 kilos of blood would amount to 90 grammes. Now, Voit found that a dog of 35 kilos body-weight on the minimum proteid diet (500 grammes lean meat per day) which sufficed to maintain its weight, excreted 40 grammes urea in the twenty-four hours. If, then, the renal epithelium separated somewhat less than half of the 90 grammes urea offered to it in the circulating blood, the whole excretion in the urine could be accounted for, and the blood of the renal vein would still contain more than half as much urea as that of the renal artery. So that the whole of the urea in the urine viay be simply separated by the kidney from the ready-made urea of the blood. But it is necessary to add that urea may be formed to a small extent in the kidney itself; for when blood is caused to circulate through an excised * surviving ' kidney, urea accumulates in it to a certain extent, and apparently in greater amount than can be accounted for on the supposi- tion that it is merely washed out of the secreting cells. 27(-> A MANUAL OF PHYSIOLOGY. Another line of evidence leads us to the same conclusion : that the kidney is, at all events, not an important seat of urea-formation. When both renal arteries are tied, or both kidneys extirpated, in a dog, urea accumulates in the blood and tissues ; and, upon the whole, as much urea seems to be formed during the first twenty-four hours of the short period of life which remains to the animal as would under normal circumstances have been excreted in the urine. Where, then, is urea chiefly formed ? We should naturally look first to the muscles, which contain three-fourths of the proteids of the body ; but we should look there in vain for urea — not a trace is normally present. The liver contains a relatively large amount, and there is very strong evidence that it is the manufactory in which the greater part of the nitrogenous relics of broken-down proteids reach the final stage of urea. This evidence may be summed up as follows : (i) An excised ' surviving ' liver forms urea from ammonium carbonate mixed with the blood passed through its vessels, while no urea is formed when blood containing ammonium carbonate is sent through the kidney or through muscles. It is difficult, in the light of this experiment, to resist the conclusion that the increase in the excretion of urea in man, when salts of ammonia are taken by the mouth, is due to a similar action of the hepatic cells. (2) If blood from a dog killed during digestion is perfused through an excised liver, some urea is formed, which cannot be simply washed out of the liver-cells, because when the blood of a fasting animal is treated in the same way there is no apparent formation of urea (v. Schroeder). This suggests that during digestion certain substances which the liver is capable of changing into urea enter the blood in such amount that a surplus remains for a time unaltered. These substances may come directly from the intestine ; or they may be products of general metabolism, which is increased while digestion is going on ; or they may arise both in the intestine and in the tissues. Leucin — which, as we have seen, is constantly, or, at least, very frequently, present in the intestine during digestion — can certainly be changed METABOLISM, NUTRITION AND DIETETICS. 377 into urea in the body, and there is every reason to beheve that the change takes place in the liver, (3) Uric acid — which in birds is the chief end-product of proteid metabolism, as urea is in mammals — is formed in the goose largely, and almost exclusively, in the liver. This has been most clearly shown by the experiments of Min- kowski, who took advantage of the communication between the portal and renal-portal veins (p. 281) to extirpate the liver in geese. When the portal is ligatured the blood from the alimentary canal can still pass by the roundabout road of the kidney to the inferior cava, and the animals survive for six to twenty hours. While in the normal goose 50 to 60 per cent, of the total nitrogen is eliminated as uric acid in the urine, and only g to 18 per cent, as ammonia, in the operated goose uric acid represents only 3 to 6 per cent, of the total nitrogen, and ammonia 50 to 60 per cent. A quantity of lactic acid equivalent to the ammonia appears in the urine of the operated animal, none at all in the urine of the normal bird. The small amount of urea in the normal urine of the goose is not affected by extirpation of the liver. And while urea, when injected into the blood, is in the normal goose excreted as uric acid, it is in the animal that has lost its liver eliminated in the urine unchanged. (4) In acute yellow atrophy, and in extensive fatty de- generation of the liver, urea may almost disappear from the urine, and be replaced by leucin and tyrosin. If it be granted, as in the face of the evidence it must, that the liver plays an important part in the formation of urea, we have still to ask what the materials are upon which it works, and in what organs they are formed before being brought to the liver. To the latter question it may be at once replied that proteid metabolism, although its final stages may be worked out in the hepatic cells, must go on in all the organized elements of every tissue. The living substance everywhere contains proteid ; proteid is every- where and at all times breaking down. In the muscles especially nitrogenous substances on the road to urea must be constantly produced. Can we lay our finger on any such intermediate substances ? Can we with certainty state 37« A MANUAL OF PHYSIOLOGY. that any of the separate links of the chain of proteid metabolism, except the first and the last, have actually been discovered, identified, and labelled ? The answer is that a whole series of bodies containing nitrogen, simpler than proteids and with a greater proportion of oxygen, more complex and less oxidized than urea, has been found in muscle and other tissues ; but we cannot say definitely that any or all of them, although they are undoubtedly stages in the downward course of worn-out proteids, have arisen the one from the other, or must necessarily pass into the form of urea before being finally excreted. Such substances are : Guanin, Cr,Hr,N-0 ... ... In the pancreas, liver, and muscles. Sarkin, or hypoxanthin, CjH^N^O In spleen, liver, muscles, and bone-marrow. In spleen, liver, muscles, brain, pancreas, and in the urine. In liver, spleen, lungs, pan- creas, brain, and in urine. Kreatin, C4H9N3O2I In muscles, blood, brain. Xanthin, C^H4N402 Uric acid, C5H4N4O3 The increase in the proportion of oxygen from guanin to uric acid is very striking, and particularly the regular series formed by hypoxanthin, xanthin and uric acid ; and Bunge has suggested that the first three may be stages on the way to uric acid or urea. But kreatin is the substance of this class which exists in greatest amount in the body, muscle containing from 0*2 to 0*4 per cent, of it ; and the total quantity of nitrogen present at any given time as kreatin is not only greater than that of the nitrogen present in urea, but greater than the whole excretion of nitrogen in twenty- four hours. To kreatin, then, we should naturally look first, among all these nitrogenous metabolites, in our search for a forerunner of urea. But there is a difficulty in accepting it as such, for although in the laboratory kreatin can be changed into kreatinin, and kreatinin into urea, there is no proof that in the body anything more than the first step in this process is accomplished. When kreatin is introduced into the intestine, it appears in the urine, not as urea, but METABOLISM^ NUTRITION AND DIETETICS. yj^ as kreatinin ; injected into the blood, it is excreted without change by the kidneys. Uric acid is, indeed, very closely related to urea, and can be made to yield it b}' oxidation outside the body. Not only so, but it is excreted as urea when given to a mammal by the mouth, and it replaces urea as the great end-product of nitrogenous metabolism almost wholly in the urine of birds and reptiles, partially in the human subject in leukaemia, and possibly to some extent in gout. But none of these things can be admitted as evidence that in the normal metabolism of mammals uric acid lies on the direct line from proteid to urea. Then, again, the amido-acids, leucin, glycin and aspara- ginic acid, when given by the mouth, increase the output of urea, so that the leucin formed in the intestine during digestion is probably, in part at least, a precursor of urea. And since leucin and tyrosin are very widely spread in the solids and liquids of the body, it has been asserted that the amido-acids are the form in which nitrogen leaves the tissues to be converted into urea in the liver. But it is against this view that there is not enough carbon in proteids to convert their nitrogen into amido-acids (Bunge). Lea has suggested that the amido-acids and the amidated aromatic acid, tyrosin, have quite another significance than that of intermediate steps in the downward metabolism of proteids — that they are destined, in fact, to take part in synthetic processes within the liver — that they are on the up, and not on the down, grade. And he points out, in support of this view, that even when the urea in the urine is increased by the administration of these bodies, the increase does not cor- respond to the whole of their nitrogen : a part of it is there- fore devoted to other purposes in the body. The conclusion of the whole matter is that, if anyone chooses to assert that the proteids of the tissues fall by a single descent nearly to the stage of urea, there is as yet little real evidence to contradict him. What is certain is that /row some tissues, and notably from muscle, the nitrogen does not pass out in the form of urea, that [it appears in the urine inainly as urea, and that the change is effected to a large extent, but not exclusively, in the liver. 38o A MANUAL OF PHYSIOLOGY. Uric acid, like urea, is separated from the blood by the kidneys, not to any appreciable extent formed in them. In birds it can be detected in normal blood ; in man in the blood and transudations of gouty patients, in whose joints and ear-cartilages it often forms concretions. ' Chalk- stones ' may contain more than half their weight of sodium urate. The spleen yields a small quantity of uric acid, which may be increased by blowing air through a mixture of splenic pulp and calf's blood. The fantastic theory that the presence of uric acid in large amount in the urine of birds was due to deficiency of oxidation is happil}^ now defunct, and need not detain rs here. Hippuric acid can undoubtedly be produced in the kidney. If an excised kidney is perfused with blood containing benzoic acid, or, better, benzoic acid and glycin, hippuric acid is formed. In herbivora no hippuric acid exists in the blood ; it is present in large quantities in the urine ; it must therefore be manufactured in the kidney, not merely separated by it. It is not known how the nitrogenous glycin, which combines with the benzoic acid derived from vegetable food, appears on the spot where it is wanted to form hippuric acid, since glycin has not been found anywhere in the tissues. It is, however, a constituent of glycocholic acid, and may be derived from that part of the bile which is reabsorbed. Kreatinin can be so readily obtained from kreatin out- side the body that it is very tempting to suppose that the kreatinin of the urine is manufactured by the kidney from the kreatin of muscle carried to it by the blood. It seems, however, more likely that some, at any rate, of the kreatinin of the urine is derived from ready- formed kreatin in the food. But we have little definite knowledge on the subject. Formation of CO^ front Proteids. — We cannot say whether carbonic acid is normally produced at the moment when the nitrogenous portion of the proteid molecule splits off, or whether a carbonaceous residue may not still hang together and pass through further stages before the carbon is fully oxidized. We shall see that under certain condi- tions some of the carbon of proteids may be retained in the body as glycogen or fat ; and this suggests that in all METABOLISM, NUTRITION AND DIETETICS. 381 cases it may run through intermediate products as yet unknown, before being finally excreted as carbonic acid. 2. Metabolism of Carbo-hydrates — Glycogen. — The carbo- hydrates of the food, passing into the blood of the portal vein in the form of dextrose, are in part arrested in the liver, and stored up as glycogen in the hepatic cells, to be gradually given out again as sugar in the intervals of digestion. The proof of this statement is as follows : Sugar is arrested in the liver, for during digestion, espe- cially of a meal rich in carbo-hydrates, the blood of the portal contains more sugar than that of the hepatic vein. In the liver there exists a store of sugar-producing material from which sugar is gradually given off to the blood, for in the intervals, of digestion the blood of the hepatic vein contains more sugar (2 parts per 1,000) than the mixed blood of the body or than that of the portal vein (i to i"5 part per 1,000). And when the circulation through the liver is cut off in the goose, sugar rapidly disappears from the blood (Minkowski). The nature of the sugar-forming substance is made clear by the following experiments : (i) A rabbit after a large carbo- hydrate meal, of carrots for instance, is killed, and its liver rapidly excised, cut into small pieces, and thrown into acidu- lated boiling water. After being boiled for a few minutes, the pieces of liver are rubbed up in a mortar and again boiled in the same water. The opalescent aqueous extract is filtered off from the coagulated proteids. No sugar, or only traces of it, are found in this extract ; but another carbo- hydrate, glycogen, an isomer of starch giving a port-wine colour with iodine and capable of ready conversion into sugar by amylolytic ferments, is present in large amount. (2) The liver after the death of the animal is left for a time in situ, or, if excised, is kept at a temperature of 30° to 40° C, or for a longer period at a lower temperature ; it is then treated exactly as before, but no glycogen, or comparatively little, can now be obtained from it, although sugar (dextrose) is abundant. The inference plainly is that after death the hepatic glycogen is converted into dextrose by some influence which is restrained or destroyed by boiling. This influence may be due to an unformed ferment or to the direct action of 382 A MANUAL OF PHYSIOLOGY. the liver-cells, for both unformed ferments and living tissue elements are destroyed at the temperature of boiling water. And the post-mortem change is to be regarded as an index of a similar action which goes on during life : sugar in the intact body is changed into glycogen ; glycogen is constantly being changed into sugar. (See Practical Exercises, p. 454.) (3) With the microscope, glycogen, or at least a substance which is very nearly akin to it, which very readily yields it, and which gives the characteristic port-wine colour with iodine, can be actually seen in the liver-cells. The liver of a rabbit or dog which has been fed on a diet containing much carbo-hydrate is large, soft, and very easily torn. Its large size is due to the loading of the cells with a hyaline material, which gives the iodine reaction of glycogen, and is dissolved out by water, leaving empty spaces in a network of cell-substance. If the animal, after a period of starvation, has been fed on proteid alone, only a little glycogen is found in the shrunken liver-cells ; if the diet has been wholly fatty, no glycogen at all may be found. In the liver-cells of the frog in winter-time, a great deal of this hyaline material — this glycogen, or perhaps loose glycogen compound — is present ; in summer, little or none. The difference is very remarkable if we consider that in winter frogs have no food for months, while summer is their feeding-time ; and at iirst seems inconsistent with the doctrine that the hepatic glycogen is a store laid up from surplus sugar, which might otherwise be swept into the general circulation and excreted by the kidneys. But it has been found that the ' summer ' condition of the hepatic cells can be produced merely by raising the temperature of the air in which a winter frog lives ; at 20° or 25° C. glycogen disappears from its liver. Conversely, if a summer frog is artificially cooled, a certain amount of glycogen accumulates in the liver. The meaning of this seems to be that at a low temperature, when the wheels of life are clogged and metabolism is slow, some substance, possibly dextrose, is produced in the body in greater amount than can be used up, and that the surplus is stored as glycogen ; just as in plants starch is put by as a reserve which can be METABOLISM, NUTRITION AND DIETETICS. 383 drawn upon — which can be converted into sugar — when the need arises. When a fasting dog is made to do severe muscular work glycogen soon disappears from its liver. When a dog is starved but allowed to remain at rest, the glycogen still vanishes, although it takes a longer time ; and at a period when there is still plenty of fat in the body, there may not be a trace of hepatic glycogen left. The glycogen which is usually contained in the muscles also disappears early during hunger. These facts have been taken to indicate that glycogen and the sugar formed from it are the readiest resources of the starving and working organism. The fat of the body is a good security, which, however, can only be gradually realized ; its organ-proteids are long-date bills, which will be discounted sparingly and almost with a grudge ; its glycogen, its carbo-hydrate reserves, are consols, which can be turned into money at an hour's warning. Glycogen is drawn upon for a sudden demand, fat for a steady drain, proteid for a life-and-death struggle. While the liver in the adult may thus be looked upon as the main storehouse of surplus carbo-hydrate, depots of glycogen seem to be formed, both in adult and foetal life, in other situations where the strain of function or of growth is exceptionally heavy — in the muscles of the adult (0*3 to 0*5 per cent, of the moist muscle), in the placenta, in the developing muscles of the embryo (as much as 40 per cent, of the solids). .,^, 1 -^ ^ 1 J 1 . J ^1 i Fig. 108.— Cells OF Pla- Although it cannot be doubted that centa containing Gly- much of the hepatic glycogen leaves the cogen. liver as sugar, there is no proof that it all does so. It is known that fat may be formed from carbohydrates (p. 391) ; and globules of oil are often conspicuous among the contents of liver-cells, side by side with glycogen. It is possible, therefore, that some of the glycogen may represent a half- way house between sugar and fat, or, since fat can also be formed from proteid, and a purely proteid diet produces some glycogen, a half-way house between proteid and fat. 384 A MANUAL OF PHYSIOLOGY. That glycogen may be produced from proteids even during starvation is shown by the following experiment : A fasting animal was put under the influence of strychnia to remove all glycogen from the liver. Then the strychnia spasms were cut short by chloral, and the animal allowed to sleep for eighteen hours. At the end of that time a considerable amount of gl3^cogen was found in the liver and muscles, and this must have come from the proteids of the body. Pavy has put forward the heterodox view that the glycogen formed in the liver from the sugar of the portal blood is never reconverted into sugar under normal conditions, but is changed into some other substance or substances, and he denies that the post-mortem formation of sugar in the hepatic tissue is a true picture of what takes place during life. But in spite of the brilliant manner in which he has defended this thesis both by argument and by experiment, it must be said that the older doctrine of Bernard, which in the main we have followed above, is supported by such a cloud of modern witnesses that it seems to be firmly and finally established. Fate of the Sugar, — What, now, is the fate of the sugar which either passes right through the portal circulation from the intestine without undergoing any change in the liver, or is gradually produced from the hepatic glycogen ? "When the proportion of sugar in the blood rises above a certain low limit (about 3 or 4 parts per 1,000), some of it is excreted by the kidneys (Practical Exercises, p. 455). A large meal of carbohydrates is frequently followed by a temporary glycosuria, but something seems to depend upon the form in which the sugar-forming material is taken. Miura, for example, after an enormous meal of rice (equivalent to 6-4 grammes ash- and water-free starch per kilo of body-weight), which, as he mentions, tasked even his Japanese powers of digestion to dispose of, found not a trace of sugar in the urine. Glucose, cane-sugar and lactose, on the other hand, when taken in large amount, were in part excreted by the kidneys, as was also the case with levulose and maltose in a dog (Practical Exercises, p. 455). But, except as an occasional phenomenon, such an ex- cretion is inconsistent with health ; and therefore in the normal body the sugar of the blood must be either destroyed or transformed into some more or less permanent constituent of the tissues. The transformation of sugar into fat we have already mentioned, and shall have again to discuss ; it only takes place under certain conditions of diet, and no more than METABOLISM, NUTRITION AND DIETETICS. 385 a small proportion of the sugar which disappears from the body in twenty-four hours can ever, in the most favourable circumstances, be converted into fat. Accordingly, it is the destruction of sugar which concerns us here, and there is every reason to believe that this takes place, not in any particular organ, but in all active tissues, especially in the muscles, and to a less extent in glands. It has been asserted that the blood which leaves even a resting muscle, or an inactive salivary gland, is poorer in sugar than that coming to it ; and the conclusion has been drawn that in the metabolism of resting muscle and gland sugar is oxidized, the carbon passing off as carbonic acid in the venous blood. This is indeed extremely likely, for we know that when the skeletal muscles of a rabbit or guinea-pig are cut off from the central nervous system by curara, the pro- duction of carbonic acid falls much below that of an intact animal at rest ; and the carbon given off by such an animal on its ordinary vegetable diet can be shown, by a compari- son of the chemical composition of the food and the excreta, to come largely from carbo-hydrates. But, considering the relatively feeble metabolism of muscles and glands when not functionally excited, the large volume of blood which passes through them, the difficulty of determining small differences in the proportion of sugar in such a liquid, the possibility that even in the blood itself sugar may be destroyed, or that it may pass from the blood, without being oxidized, into the lymph, too much weight may easily be given to the results of direct analysis of the in-coming and out-going blood. And although the recent results of Chauveau and Kaufmann, obtained in this way, fit in fairly well with what we have already learnt by less direct, but more trustworthy, methods, they cannot be accepted as yielding exact quantitative information. They found that in one of the muscles of the upper jaw of the horse the quantity of grape-sugar used up during activity (chewing movements) was 3'5 times as much as in the same muscle at rest, and this corresponded with the deficit of oxygen in the blood entering the muscle, and with the excess of carbonic acid in the blood leaving it. More dextrose was also destroyed in 25 386 A MANUAL OF PHYSIOLOGY. the active than in the passive parotid gland of the horse, but the excess per unit of weight of the organ was far less than in muscle. Diabetes. — In the disease known as diabetes mellitus, sugar accumulates in the blood, and is discharged by the kidneys, and it has been supposed that a derangement in the gly- cogenic function of the liver is the cause of this accumula- tion and of this discharge. An artificial and temporary diabetes, in which the sugar in the urine undoubtedly arises from the hepatic glycogen, can, indeed, be caused by punc- turing the medulla oblongata in a rabbit at or near the region of the vaso-motor centre (p. 455). If the animal has been previously fed with a diet rich in carbo-hydrates — that is, if it has been put under conditions in which the liver con- tains much glycogen — the quantity of sugar excreted by the kidneys will be large. If, on the other hand, the animal has been starved before the operation, so that the liver is free or almost free from glycogen, the puncture will cause little or no sugar to appear in the urine. That nervous influences are in some way involved is shown by the absence of diabetes if the splanchnic nerves, or the spinal cord above the third or fourth dorsal vertebra, be cut before the puncture is made. But sometimes these operations are themselves followed by temporary diabetes. Section of the vagi has no effect either in causing glycosuria of itself or in preventing the ' puncture ' diabetes, although stimulation of the central ends of these and of other afferent nerves may cause sugar to appear in the urine. Curara, morphia, phlorizidin (p. 455), and other substances, also cause diabetes. But phlorizidin diabetes differs from 'puncture' diabetes in this, that it can be produced in an animal free from glycogen, and is accompanied by extensive destruction of proteids. Although several of the operations which lead to this temporary glycosuria undoubtedly bring about changes in the hepatic circulation, it is as yet impossible to say whether the whole phenomenon is at bottom a vaso-motor effect, or is due to direct nervous stimulation of the liver-cells, or to withdrawal of such stimulation or control. Recent experiments point to the pancreas as intimately METABOLISM, NUTRITION AND DIETETICS. 387 concerned in the metabolism of sugar. Excision of this organ in dogs causes permanent diabetes (v. Mering and Minkowski), which is prevented if a portion of the pancreas be left, or if it be transplanted under the skin of the ■abdomen (p. 415). In the natural diabetes of man it is possible that in some •cases the sugar coming from the alimentary canal passes entirely or in too large amount through the liver, owing to a deficiency in its power of forming glycogen. But it is remarkable that levulose may be entirely used up in the tissues of a diabetic patient, or of a dog rendered diabetic by extirpation of the pancreas, while dextrose, which is so closely allied to it, and from which an identical form of glycogen is produced, is promptly cast out by the kidneys. And in many cases when carbo-hydrates are completely, or almost completely, omitted from the food, sugar, probably ! - - - Skin over biceps ----- „ „ head of tibia - - - - ,, immediately below xiphoid cartilage ,, over sternum - . . - On hair (boy) - . . . - Under hair over sagittal suture (boy) Shaved skin of neck (rabbit) On hair ,, ,, - - ,, between eyes „ 36-25 33'5-34' oV 35' 31 9 347 33"2 30' 337-34- 36-5 31-5 307 Artificial Surfaces. vl^'^' (Surface of trousers over thigh R""'^"^ J „ coat over arm ^ - temperature, 17-5° waistcoat 287-237 26-8 26- Variations in the Temperature. — The internal temperature, as has been already said, is not strictly constant. It varies with the time of day ; with the taking of food ; with age ; to a slight extent with violent changes in the external temperature, such as those produced by hot or cold baths ; and possibly with sex. The daily curve of temperature shows a minimum in the early morning (two to six o'clock), and a maximum in the evening (five to eight o'clock) (Fig. 117). It will be remarked that the daily variations of temperature and those of the pulse-rate (p. 76) correspond to a considerable extent ; and it is of scientific, and perhaps of practical, interest that the early morning, when the temperature and pulse-rate are at their minimum, is often the period at which the flagging powers of the sick give way. From two to six o'clock in the morning the daily tide of life may be said to reach low-water mark. Even in a fasting man the diurnal tem- perature-curve runs its course, but the variations are not so great. The taking of food of itself causes an increase of temperature, although in a healthy man this rarely amounts to more than half a degree. The rise of tempera- ture is certainly due in part to the increased work of the ali- 45: A MANUAL OF PHYSIOLOGY. mentary canal, but may also be connected with the increase of metabolic activity which the entrance of the products of digestion into the blood brings about. The solution of the solids of the food by the digestive juices is associated with absorption of heat, as has been observed in artificial digestion, and even in a case of gastric fistula. The in- creased heat-production, however, is more than sufficient to prevent any fall of body temperature from this cause. As to the relation of age and sex to temperature, it is only necessary to remark that the mean temperature of the young child is some- what higher, and that of the old man some- what lower, than that of the vigorous adult ; but a point of more importance is the relative imperfection of the heat-regulation in infancy and age, and the greater effect of accidental circum- stances on the mean temperature. Thus, old people and young children are specially liable to chills, and a fit of crying may be sufficient to send up the temperature of a baby. The temperature of women is generally a little higher than that of men, and is also, perhaps, somewhat more variable. After death the body cools at first rapidly, then more slowly (Fig. 1 1 8). But occasionally a post-mortem rise of temperature may take place. In certain acute diseases (like tetanus) associated with excessive muscular contraction this has been especially noticed; in bodies wasted by prolonged illness it does not occur. Nearly an hour after death, in a case of tetanus, the temperature was found to be 45*3'^ (Wun- derlich). In dogs a slight post-mortem rise may be demon- strated, especially when the body is wrapped up ; but when an animal has been long under the influence of anaesthetics. Fig. 117. — Curve showing the Dah.v V'akia- TiON OF Body Temperature. ANIMAL HEAT. 453 no indication whatever of the phenomenon may be obtained. The explanation of post-mortem rise of temperature is to be found : (i) In the continued metaboHsm of the tissues for some time after the heart has ceased to beat, for the cell dies Fig. ii8. — CuKVK tH' < Time marked along horizontal, and temperature along vertical axis. .■\t a ether and chloroform given to kill animal ; death, as indicated by stoppage of the heart, took place at h. The dotted line shows the course the curve would have taken if death had oc- curred at the mo- ment the anaes- thetics were given. Air of room 17 6^ IKK IJKATH (GUINE.\-PIG) harder than the body. (2) In the diminished loss of heat, due to the stoppage of the circulation. (3) Possibly to a small extent in physical changes (rigor mortis, coagulation of blood) in which heat is set free. PRACTICAL EXERCISES ON CHAPTERS VII. AND VIII. I. Glycogen — (i) Preparatioii. — {a) Place in a mortar some fine sand and a mi.xture of equal volumes of saturated solution of mercuric chloride and Esbacfi's reagent.* Put one or two oysters in the mortar, rub up thoroughly, and let the mass stand till (b) and {c) have been done, stirring it occasionally. Then filter and precipitate the glycogen from the filtrate with alcohol. Filter again, wash the precipitate on the filter with a little alcohol, dissolve it in i or 2 cc. of water, and test for glycogen as in (b). The mercuric chloride and Esbach's reagent are added to precipitate the proteids, which are more completely thrown down in this way than by the methods used in {b) and {c) (Huizinga). {b) Cut an oyster into two or three pieces, throw it into boiling water, and boil for a minute or two. Rub up in a mortar with clean * Esbach's reagent is a solution of 10 grm. picric acid and ?.o grm. citric acid in a litre of water. 454 ^ MANUAL OF PHYSIOLOGY. sand, and again boil. Filter. Precipitate any proteids which have not been coagulated, by adding alternately a drop or two of hydrochloric acid and a few drops of potassio -mercuric iodide so long as a precipitate is produced. Only a small quantity of these reagents will be required, as the greater part of the proteids has been already coagulated by boiling. Filter if any precipitate has formed. The tiltrate is opalescent. Precij^itate the glycogen from the filtrate (after con- centration on the water-bath if it exceeds a few cc. in bulk) by the addition of four or five times its volume of alcohol. Filter off the precipitate, wash it on the filter with alcohol, and dissolve it in a little water. To some of the solution add a drop or two of iodine ; a reddish-brown (port wine) colour is produced, which disappears on heating, returns on cooling, is removed by an alkali, restored by an acid. Add saliva to some of the glycogen solution, and put in a bath at 40° C. In a few minutes reducing sugar (maltose) will be found in it by Trommer's test (p. 323). Note that dextrin gives the same colour with iodine as glycogen does. Dextrin is also precipitated by alcohol, but a greater pro- portion must be added to cause complete precipitation. Digest a solution of sugar-free dextrin with saliva at 40° C. Reducing sugar is formed, but the digestion is neither so rapid nor so complete as in the case of glycogen. ic) Cut another oyster into pieces, throw it into boiling water acidulated with dilute acetic acid, and boil for a few minutes. Rub up in a mortar with sand, boil again, and filter. Test a portion of the filtrate with iodine for glycogen. Precipitate the rest with alcohol, filter, dissohe the precipitate in water, and test again for glycogen. (2) Deeply etherize a dog or rabbit 5 hours after a meal rich in carbo- hydrates (t'.i,'-., rice and potatoes). Fasten it on a holder. Clip off the hair over the abdomen in the middle line. Make a mesial in- cision through the skin and abdominal wall from the ensiform car- tilage to the pubis. The liver will now be rapidly cut out [by the demonstrator] and divided into two portions, one of which will be [distributed among the class and] treated as in {a) or {b) ; the other will be kept for an hour at a temperatuie of 40° C, and then sub- jected to processes {a) or {b). Little, if any, sugar and much glycogen will be found in the portion which w^as boiled imme- diately after excision. Abundance of sugar will be found in the portion kept at 40" C. ; it may or may not contain glycogen. 2. Glycosuria. — (i) Weigh a dog (female by preference) or rabbit. Give morphia to the dog or chloral to the rabbit, as described on pp. 150,155. Fasten on a holder, and etherize. Insert a glass cannula into the femoral or saphena vein of the dog, or into the jugular of the rabbit (p. 151). Fill a large syringe with a 2 per cent, solution of dextrose (glucose) in normal saline, connect it with the cannula by means of an indiarubber tube, taking care that there are no air- bubbles in the tube, and shnuly inject as much of the solution as will amount to \ to | grm. sugar per kilo of body-weight. Tie the vein, remove the cannula, and in half an hour evacuate the bladder bypassing a catheter in the case of a bitch (p. 371), by pressure in the PRACTICAL EXERCISES. 455 case of a rabbit, and in the case of a male dog ; if pressure on the abdomen fails, by tapping the bladder with a trocar pushed through the linea alba (supra-pubic puncture). In an hour again draw off the urine. Test both specimens for sugar. In this experiment, the opportunity may also be taken to demon- strate that egg-albumin, when injected into the blood, is excreted by the kidneys, a clear solution containing albumin and sugar being injected. (2) Phloridziii Diabetes. — Dissolve \ grm. of phloridzin in warm water, and inject it subcutaneously into a small dog (female). Or \ grm. may be injected into a rabbit. Obtain a sample of the urine at the end of some hours, and test for sugar. If none is present, wait for another interval, and again test the urine, and so on. This experiment can also be performed without risk on man. One grm. of phloridzin has been injected twice a day without dis- turbing the individual. Much sugar is found in the urine, but it disappears the day after the administration of phloridzin is stopped. The phloridzin may also be given by the mouth, but more is required, and it is not very easily absorbed, and often causes diarrhcea (v. Mering). (3) Puncture Diabetes. — Anaesthetize a rabbit with ether, and fasten it (belly down) on a holder. Put a pad or a roUed-up towel under the neck so as to raise the back of the head. Divide the skin over the occipital protuberance down to the bone. Make a iv;/^?// trephine hole just behind the protuberance. Push in through the cerebellum a thin glass rod drawn out to not too sharp a point in the blowpipe flame. Hold the rod so that it will bisect the line joining the ex- ternal openings of the two ears, and send it in till it is felt to have met the basilar bone. Empty the bladder in an hour, and test for sugar by Trommer's (p. 323) and the phenyl hydrazine test (p. 370). (4) Alimentary Glycosuria. — The urine having been tested for sugar for two successive days, and none being found, {a) a large quantity of cane-sugar is to be taken in the form which is most agreeable to the student. The urine of the next twenty-four hours is to be collected and measured. A sample of it is then to be tested for reducing sugar by Trommer's and the phenyl hydrazine test. If any sugar is found, the reducing power of a definite quantity of the urine is to be determined by titration with Fehling's solution (p. 370) (u) before and (/i) after boiling with hydrochloric acid (p. 329). Or {b) a large meal of rice or arrowroot, sweetened with as much dextrose as the observer can induce himself to swallow, is to be taken, and the urine treated as in (a). {c) If experiments {a) and {b) are both unsuccessful, they may be repeated on a dog. 3. Estimation of the Quantity of Water and of Carbonic Acid given oS {Halda He's Method). — Apparatus: see Fig. it 9. Connect the apparatus with the water-pump. Allow a negative pressure of 5 or 6 inches of water to be established in it, as shown by the rise of water in the bell-jar, B. Then close the open tube of carbonic acid bottle i, and clamp the tube between the water-pump and the 456 A MANUAL OF PHYSIOLOGY. bell-jar. If the negative pressure is maintained, the arrangement is air-tight. Now weigh bottle 3 and bottles 4 and 5, the last two together. Place a cat in the respiratory chamber, connect the chamber directly with the water-pump, and test whether it is tight. Fig. 119. — Haldane's Apparatus for Measuring the Quantity of CO2 AND Aqueous Vapour given off by an Ani.mal. A, chamber into which the animal is put ; i and 4, Woulff' s bottles filled with soda-lime to absorb CO^ ; 2, 3, and 5, Woulff' s bottles filled with pumice-stone soaked in sulphuric acid to absorb watery vapour ; B, glass bell-jar suspended in water, by means of which the negative pressure is known ; P, water-pump which sucks air through the apparatus ; i and 2 are simply for absorbing the CO:; and H2O of the ingoing air. Then lake the stopper out of bottle i, and adjust the rate at which air is drawn through the apparatus. Let the ventilation go on for a few minutes, then insert bottles 3, 4, and 5 again. Note the time exactly at this point, and after an hour disconnect 3, 4, and 5, and again weigh. The difference of the two weighings of 3 shows the A, soda lime; B, sulphuric acid tube ; C, wooden frame, in which A and B are supported by wires (/; b, wire hook, which grips the glass tube firmly, and by means of which the tubes are lifted out of the frame in order to be weighed ; a, short piece of glass tubing, by taking out which the absorption tubes are disconnected from the rest of the apparatus ; e, glass tube going off to animal chamber. The right hand glass tube of B should not touch the sulphuric acid as depicted. KiG. 120.— Absorption Tubes for CO.. and Moisture. quantity of water given off by the animal in an hour ; the difference in the combined weight of 4 and 5, the quantity of carbonic acid. Weigh the cat, and calculate the amount of water and of carbonic given off per kilo per hour. PRACTICAL EXERCISES. 457 For the student it is more convenient to use smaller animals. The mouse may be taken as an example of a warm-blooded animal, and the frog of a cold-blooded. Adapt the apparatus described by Haldane and Pembrey for estimating small quantities of CO., (Lor- rain Smith and Wesbrook). Instead of the Woulff's bottles use wide test-tubes connected as in Fig. 120. For the animal chamber use a small beaker. Close the mouth of the beaker with a very carefully- fitted cork which has been boiled in parafifin. The inlet and outlet tubes of the chamber are to be introduced through this cork. The holes for these are to be bored with the greatest care, and the tubes to be put in while the cork is still hot from boiling in paratifin. Also insert a thermometer about 6 inches long registering from 0° C. to 45° C. Modeller's wax is to be used finally to render all the junctions air-tight. Add to the series of tubes described in the apparatus a single tube containing baryta-water. This is placed after the tube 5, and so arranged that the air-current bubbles through the water. As long as the absorption of CO. is complete, the baryta-water remains clear. Beyond this a water-bottle should be placed to act as a valve and to indicate the negative pressure in the apparatus. It can be most simply constructed by using a cylinder of stout glass tubing in a wide-mouthed bottle containing some water, the inlet and outlet tubes passing through a paraffined cork which seals the upper end of the cylinder. Before making an observation, test whether the apparatus is air- tight, as explained above, after introducing the animal into the chamber, sealing the latter with wa.x, and connecting it with the absorp- tion tubes. But a negative pressure of 2 or 3 inches of water is a sufficient test for the small ai)paratus. To make an observation, set the air-current going at the desired rate. Allow it to run for a few minutes till the COo which has accumulated during the testing has been swept out. At a time which has been decided on and noted, stop the current by disconnecting the water-pump. Disconnect and stopper up the animal chamber, and weigh it as quickly as possible. Connect up again, using only recently-weighed absorption-tubes, and finally connect with the water-pump and allow the current to pass for a definite period, say an hour. If a consecutive series of observations is to be made, two sets of tubes should be prepared for use during alternate periods. Use in each case two soda-lime tubes, the most recently filled one being placed second of the two. The soda-lime should not be too dry, or absorption is not sufficiently rapid. The following facts are made out in the observa- tion : {a) The loss of weight by the animal chamber (chiefly loss by the animal), {b) The gain of the sulphuric acid tube in HoO. {c) The gain of the soda-lime tubes in CO^. If we compare total loss and total gain, we find they do not corre- spond, the gain being always greater than the loss. What is gained contains a surplus, therefore, and this can only be oxygen which has 458 A MANUAL OF PHYSIOLOGY. been absorbed by the animal and added to the H and C of its substance to form H^O and COo- Calculate the respiratory quotient (p. 185). The following series of experiments should be done with this apparatus : (i) Observe the amount of gaseous exchange per kilo and hour at room temperature in : («) A cold-blooded animal (frog), (/'') a warm-blooded animal (mouse), {c) Calculate the respiratory quotient in each case. (2) Observe : {a) The effect of exercise in increasing, and of rest in diminishing, the total gaseous exchange (p. 1 88); {b) the effect of food in increasing the total gaseous exchange ; {c) the effect of different kinds of food (carbo-hydrates, proteids, etc.) on the respiratory quotient (p. 186). (3) Observe the reaction of: («) A cold-blooded animal, (b) a warm-blooded animal, to changes in temperature of the surrounding air, as shown in the rise and fall of the gaseous exchange. For this, arrange round the beaker a water-jacket through which a current of water flows. Allow cold water to flow through the jacket for half an hour, and read off the temperature of the chamber (say 10° C). For the next half-hour heat the water in the jacket till the air of the chamber is at 30° C. Lastly, take another observation of a cold period. Compare the exchange for the three periods (p. 437). 4. Measurement of the Quantity of Heat given off in Respiration. — This may be done approximately as follows : Put in the inner copper vessel. A, of the respiration calorimeter (Fig. 114, p. 426'^ a measured quantity of water sufficient to completely cover the series of brass discs. Place A in the wider outer cylinder, the bottom of which it is prevented from touching by pieces of cork. The outer cylinder hinders loss of heat to the air. Suspend a thermometer in the water through one of the holes in the lid. In the other hole place a glass rod to serve as a stirrer. Read off the temperature of the water. Put the glass tube connected with the apparatus in the mouth, and breathe out through it as regularly and normally as possible, closing the opening of the tube with the tongue after each expiration and breathing in through the nose. Continue this for 5 to 10 minutes, taking care to stir the water frequently. Then read off the tem- perature again. If W be the quantity of water in cc, and / the observed rise of temperature in degrees Centigrade, W/ equals the quantity of heat, expressed in small calories (p. 420), given off by the respiratory tract in the time of the experiment, on the assumptions (i) that all the heat has been absorbed by the water, (2) that none of it has been lost by radiation and conduction from the calorimeter to the surrounding air. Calculate the loss in twenty-four hours on this basis ; then repeat the experiment, breathing as rapidly and deeply as possible, so as to increase the amount of ventilation. The quantity of heat given off will be found to be increased. In an experiment of short duration (2) is approximately fulfilled. As to (i), it must be noted that in the first place the metal of the calorimeter is heated as well as the water, and the water-equivalent of the apparatus must be added to the weight of the water (p. 421). The water-equivalent is determined by putting a definite weight of water at PR A CTICA L EXERCISES. 459 air temperature T into the calorimeter, and then allowing a quantity of hot water at known temperature T' to run into it, stirring A,ell, and noting the temperature of the water when it has ceased to rise. Call this temperature T". Enough hot water should be added to raise the temperature of the calorimeter about 2" C. The quantity run in is obtained by weighing the calorimeter before and after the hot water has been added. Suppose it is m. Let the mass of the cold water in the calorimeter at first be M, and let M' = the mass of water which would be raised 1° C. in temperature by a quantity of heat sufficient to increase the temperature of all the metal, etc., of the calori- meter by 1° ; in other words, the water-equivalent of the calorimeter. 'I'he mass m of hot water has lost heat to the amount of in (T'-T"), and this has gone to raise the temperature of a mass of water M and metal equivalent to a mass of water M' by (T'' — T) de- grees. . •. ;// (T' - T") = M(T" - T) + M'(T" - T). Everything in this equation except M' is known, and .•. M', the water-equivalent of the calori- meter, can be deduced, and must be added in all exact experiments to the mass of water contained in it. Secondly, all the excess of heat in the ex- pired over that in the inspired air is not given off to the calorimeter, for the air passes out of it at a slightly higher temperature than that of the atmosphere. At the beginning of the experiment this excess of temperature is zero. If at the end it is i'^ C, the mean excess is o*5° C. Now, when respiration is carried on in a room at a temperature of 10° C, the expired air has its temperature increased by nearly 30° C. About ,./y of the heat given off by the respiratory tract in raising the temperature of the air of respiration would accordingly be lost in such an experiment. But since the portion of the heat lost by the lungs which goes to heat the expired air is only 1 of the whole heat lost in respiration (p. 425), the error would only amount to -A,-^ of the whole, and this is negligible. Thirdly, the air leaves the calorimeter saturated with watery vapour at, say, io"5°, while the inspired air is not saturated for 10" C. Now, the quantity of heat rendered latent in the evaporation of water sufficient to saturate a given quantity of air at 40° C. (the expired air is saturated for body temperature) is six times that required to saturate the same quantity of air at 10°. If, then, the inspired air is half saturated, the error under this head is J., or 8i per cent. If the inspired air is three-quarters saturated, the error is ttj, or about 4 per cent. If the air is fully saturated before inspiration, as is the case when it is drawn in through a water-valve (Fig. 121) by a tube fixed in one nostril, the only error is that due to the slight excess of temperature of the air leaving the calorimeter over that of the inspired air. The latent heat of the aqueous vapour in saturated air at 10-5° C. is about ^ijjth more than the latent heat of the aqueous vapour in t'lG. 121. — PiOTTI.E AR- RANGED FOR Water- valve. 46o A MANUAL OF PHYSIOLOGY. the same mass of saturated air at io° C., or about ^i^ of the latent heat in saturated air at 40°. The error in this case would therefore be under i per cent. The tubes must be wide and the bottle large. 5. Variations in the Quantity of Urea excreted, with Variations in the Amount of Proteids in the Food. — The student should put himself, or somebody else if he can, for two days on a diet poor in proteids, then (after an interval of forty-eight hours on his ordinary food) on a diet rich in proteids. A suitable table of diets will be supplied. The urine should be collected on the six days of the period of experiment, on the day before it begins, and on the day after it ends. Small samples of the mixed urine of the twenty-four hours for each of these eight days should be brought to the laboratory, and the quantity of urea determined by the hypobromite method. The volume of the urine passed in each interval of twenty-four hours being known, tlie total excretion of urea for the twenty-four hours can t)e calculated, and a curve plotted to show how it varies during the period of experiment. 6. Nitrogenous Metabolism. — For the study of nitrogenous balance experiments on a mouse will be found the simplest. Break up into small particles a quantity of dog - biscuit sufficient to feed the mouse during the whole experiment. Estimate by several analyses the proportion of nitrogen in the dog-biscuit. Use Kjeldahl's method, as described on p. 365, but substitute for the sulphuric acid employed for oxidation a mixture of sulphuric and phosphoric acids (i part phos- phoric to 5 parts sulphuric), as this oxidizes more quickly than sul- phuric alone. Boil with this for i to li hours. Keep the biscuit in an air-tight vessel to prevent change of weight by drying. For animal chamber use a cylindrical glass vessel, and place in it a stage of wire netting on which the mouse may remain. The urine and faeces fall through the wire netting, and are collected on the bottom of the glass vessel. If the laboratory be cold, the mouse must be kept in an incubator at about 20° C. Begin the observations by finding the quantity of biscuit needed to keep the weight of the mouse constant. When this has been obtained, feed the mouse and collect the urine and faeces for analysis at the same time each day for three or four successive days. Compare the analysis of food and excreta. 7. Thyroidectomy. — Study the anatomy of the neck and the rela- tions and blood-supply of the thyroid glands in a dog used for some previous experiment. (i) Then select a half-grown dog, weigh it, inject morphia subcu- taneously (p. 150), and fasten on the holder back down. Clip the hair from the neck, and shave a wide space on each side of the middle line. Scrub with soap and water, and then with corrosive sublimate solution. All sponges, instruments, ligatures, etc., must have been previously boiled ; the instruments are immersed in 5 per cent, carbolic acid solution, everything else in the corrosive solution. The hands and nails must be carefully cleansed and washed with corrosive, A longitudinal incision is made through the skin and subcutaneous tissue in the middle line of the neck, beginning a little below the pro- PRACTICAL EXERCISES. 461 jecting thyroid cartilage. By separating the longitudinal muscles just external to the trachea on one side, the corresponding thyroid lobe will be seen as an oval red body. It is now to be carefully freed from its attachments ; all vessels connected with it are to be tied with double ligatures, and divided between the ligatures. In tying the superior thyroid artery (a short large vessel coming off from the carotid), care must be taken not to put the ligatures too near its origin, as the rapid current in the carotid may prevent closure of the vessel by clot, and secondary haemorrhage may occur some days after the operation. The thyroid lobe is thus shelled out of the tissues in which it lies. If an isthmus is present (the isthmus connects the two lobes across the front of the trachea), it must also be removed. All bleeding having been stopped, the wound is washed out with corrosive solution, and the muscles brought together over the trachea by a row of interrupted sutures, which should not be drawn too tightly. The wound in the skin is then closed by a similar row, preferably of subcutaneous sutures (see p. 156). Collodion is painted over the wound, and the animal is returned to its cage. It should be kept for a week, or, better, a fortnight, and examined care- fully during that time. Probably, unless the wound has become infected, its behaviour will be perfectly normal. (2) The second part of the experiment, which consists in removing the remaining thyroid lobe, is now to be performed just as in (i). The animal must be examined next morning, and then twice a day for the following week, as the symptoms of cachexia strumipriva generally come on very rapidly in young dogs, and death may even ensue within two days. Trembling of the limbs, associated with insta- bility of movement, spasms resembling those of tetany, sometimes passing into general epileptiform convulsions, and progressive emacia- tion, are the most marked symptoms. The animal must be weighed daily, the temperature taken in the rectum, the thermometer being always pushed in to the same distance ; and it will also be well to determine the number of the red corpuscles in samples of the blood (p. 48). A record of the experiment from the operation to the autopsy must be kept. At the autopsy search must be made to see whether the thyroid was completely removed, and whether any accessory thyroids exist. Such are occasionally found in the form of small reddish masses, either in the neck or within the chest in the neighbourhood of the aorta. If any are found, they must be hardened in alcohol and sections made. Portions of the muscles, spleen, and central nervous system are also to be preserved ; and it is to be observed whether the pituitary body has undergone any increase in size or other change (pp. 416, 417). 8. Thyroidectomy with Thyroid Feeding. — Some of the members of the class should modify experiment 7 by feeding the animal, as soon as symptoms have appeared, with fresh sheep's thyroid glands or commercial thyroid extracts, and noting any alleviation of the symptoms. If, as only rarely happens, they disappear, the animal is to be allowed to live for a considerable time, then killed by chloroform, an autopsy made, and portions of the tissues hardened and compared with those from experiments done as in 7. CHAPTER IX. MUSCLE. It is impossible to understand the general physiology of muscle and nerve without some acquaintance with electricity. It would be out of place to give even a complete sketch of this preliminary but essential knowledge here ; and the student is expressly warned that in this book the elementary facts and principles of physics are assumed to be part of his mental outfit. But in describing some of the electrical apparatus most commonly used in the study of this portion of our subject, it may be useful to recall the physical facts involved. Batteries. — The Daniell cell is perhaps better suited for physio- logical work than any other voltaic element, although for special purposes Bunsen, Grove, Leclanche, and bichromate of potassium batteries may be employed. A, outer vessel ; B. copper ; C, porous pot ; D, zinc rod ; D IS supposed to be raised a little so as to be seen. Fig. 122.— Daniell Cell. The Daniell is a two-fluid cell. Saturated solution of sulphate of copper is contained in an outer vessel, and a dilute solution of sulphuric acid in a porous pot standing in the copper sulphate solu- tion. The latter is kept saturated by a few crystals of copper sulphate. A piece of sheet-copper, generally bent so as to form a hollow cylinder, dips into the sulphate of copper, and a piece of amalga- mated zinc into the contents of the porous pot. Inside the cell the current (the positive electricity) passes from zinc to copper ; outside, MUSCLE. 463 from copper to zinc. The copper is called the positive, the zinc the negative, pole. When the current is passed through a tissue, the electrode by which it enters is termed the anode, and that by which it leaves the tissue the kathode. The anode is, therefore, the elec- trode connected with the copper of the Daniell's cell; the kathode is connected with the zinc. Potential— Ctirrent Strength — Resistance. — We do not know what in reality electricity is, but we do know that when a current flows along a wire energy is expended, just as energy is expended when water flows from a higher to a lower level. Many of the phenomena of current electricity can, in fact, be illustrated by the laws of flow of an incompressible liquid. The difference of level, in virtue of which the flow of liquid is maintained, corresponds to the difference of electrical level, ox potential^ in virtue of which an electrical current is kept up. The positive pole of a voltaic cell is at a higher potential than the negative. When they are connected by a conductor, a flow of electricity takes place, which, if the difference of level or potential were not constantly restored, would soon equalize it, and the current would cease ; just as the flow of water from a reservoir would ulti- mately stop if it was not replenished. If the reservoir was small, and the discharging-pipe large, the flow would only last a short time ; but if water was constantly being pumped up into it, the flow would go on indefinitely. This is practically the case in the Daniell cell. Zinc is constantly being dissolved, and the chemical energy which thus dis- appears goes to maintain a constant difference of potential between the poles. Electricity, so to speak, is continually running down from the place of higher to the place of lower potential, but the cistern is always kept full. The difference of electrical potential between two points is called i\\Kt electromotive force ; and from its analogy with difference of pressure in a liquid, it is easy to understand that the intensity or strength of t/ie current, that is, the rate of flow of the electricity between two points of a conductor, does not depend upon the electromotive force alone, any more than the rate of discharge of water from the end of a long pipe depends alone on the difference of level between it and the reservoir. In both cases the resistance to the flow must also be taken account of. With a given difference of level, more water will pass per second through a wide than through a narrow pipe, for the resistance due to friction is greater in the latter. In the case of an electrical current, a wire connecting the two poles of a Daniell's cell will represent the pipe. A thick short wire has less resistance than a thin long wire ; and for a given difference of potential, of electric level, a stronger current will flow along the former. But for a wire of given dimensions, the intensity of the current will vary with the electromotive force. The relation between electromotive force, strength of current, and resistance were experimentally determined by Ohm, and the formula C = ^, which expresses it, is called Ohm's Law. It states that the current varies directly as the electromotive force, and inversely as the resistance. 464 A MANUAL OF PHYSIOLOGY Although we do not know in what electrical resistance consists, it may be defined as that property of a conductor in virtue of which a flow of electricity cannot be kept up through it without the expendi- ture of energy. In treating of the circulation of the blood, we have already seen that the flow of a liquid along a tube involves the expenditure of energy to overcome the friction of the liquid molecules on each other, and that this energy is transformed into heat (p. 58). In like manner electrical energy is transformed into heat whenever a current flows along a wire. The heat produced in a circuit in which no external work is done is exactly equal to the energy which has dis- appeared in the transference of the electricity from the place of higher to the place of lower potential : just as the heat produced in the flow of a liquid is equal to the difference in its total energy at the beginning and end of the path. If C is the current strength, and E the electromotive force, the energy represented by the transference of electricity in time / is EC/, or (since E = CR by Ohm's Law), C^R/; and this represents the heat produced in the circuit when no work is done. For the measurement of electrical quantities a system of units is necessary. The common unit of resistance is the ohm, of current the ampere, of electromotive force the 7'olt. The electromotive force of a Daniell's cell is about a volt. An electromotive force of a volt, acting through a resistance of an ohm, yields a current of one ampere ; but the current produced by a Daniell's cell, with its poles connected by a wire of i ohm resistance, would be less than an ampere, because the internal resistance of the cell itself, that is, the resistance of the liquids between the zinc and the copper, must be added to the external resistance in order to get the total resistance, which is the quantity represented by R in Ohm's Law. Measurement of Resistance. — To find the resistance of a con- ductor, we compare it with known resistances, as a grocer finds the Fig. 123.— Whf.atstone's Bridge. Fig. 124.— Diagram of Resistance Box. weight of a packet of tea by comparing it with known weights. The Wheatstone's bridge method of measuring resistance depends on the fact that if four resistances, AB, AD, BC, CD, are connected, as in Fig. 123, with each other, and with a galvanometer G and a battery F, A B Bf ^ no current will flow through the galvanometer when -- ^ — — . ^ AD CD MUSCLE. 465 For when no current passes through the galvanometer, B and D are at the same potential. Let the fall of potential from C to B or from C to D be a ; then, since the total fall of potential from C to A must be the same along either of the paths CBA or CDA, the fall from B to A must be equal to that from 1) to A. Call this ]i. Now, the fall of potential which takes place in any given portion of a circuit is to the whole fall of potential in the circuit as the resistance of the given portion is to the whole resistance. That is, a BC a + /?~BC + AB' ^ AB . . a_BC a+^^'BC + AB' ■■ ^"AB" a CD BC CD AB BC Similarly: ^^ = ^^^ '. .^3 = ^. or ^^^^^y In making the measurement, a resistance-box, containing a large number of coils of wire of different resistances, is used (Fig. 124). The resistances corresponding to AB and AD, called the arms of the Fig. 125. — Scheme of Wiedemann's Galvanometer (with telescope reading). 'T, telescope ; S, scale ; M, mirror ; w, ring magnet suspended between the two galvanometer coils G, the distance of which from in can be varied ; F, fibre suspending mirror and magnet. bridge, may be made equal, or may stand to each other in a ratio of I : 10, I : 100, etc. Then, the unknown resistance being CD, BC is adjusted by taking plugs out of the box till, on closing the current, there is either no deflection, or the deflection is as small as it is possible to make it with the given arrangement. Galvanometer. — A galvanometer is an instrument used to detect a current, to determine its direction, and to measure its intensity. Since, by Ohm's law, electromotive force, resistance, and current strength are connected together, any one of them may be measured by the galvanometer. A galvanometer of the kind ordinarily used in physiology consists essentially of a small magnet suspended in the axis of a coil of wire, and free to rotate under the influence of a current passing through the coil. The most sensitive instruments 30 466 A MANUAL OF PHYSIOLOGY. possess a small mirror, to which the magnet is rigidly attached. A ray of light is allowed to fall on the mirror, from which it is reflected on to a scale ; and the rotation of the mirror is magnified and measured by the excursion of the spot of light on the scale. In the Thomson galvanometers the magnet is very light. A strip or two of magnetized watch-spring does very well. The magnet is 'damped,' that is, its tendency, when once displaced, to go on oscillating about its new position of equilibrium is overcome by enclosing it in a narrow air space. In the Wiedemann instrument the magnet is heavier (Fig. 125). It swings in a chamber with copper walls. Every movement of the magnet ' induces ' currents in the co]:)per ; these tend to oppose the movement, and so ' damping ' is obtained. It is usual to read the deflections of the Wiedemann galvanometer by means of a telescope. An inverted scale is placed over the telescope at a distance of, say, a metre from the mirror ; an upright image of the scale is formed in the telescope after reflection from the mirror, and with every movement of the latter the scale divisions appear to move correspondingly. The method of reading by a telescope can be applied to any mirror galvanometer, and is often extremely con- venient in physiological work. Sometimes a small scale is fastened on the mirror itself, and observed directly through a low-power microscope. A suspended magnet, if no other magnets are near, takes up a definite position under the influence of the earth's magnetism ; its long axis, in the position of rest, lies in a vertical plane, called the plane of the magnetic meridian at the given place. The ' marked ' or north pole points north, the south pole south. If the magnet is dis- turbed from this position, it tends to return to it as soon as the dis- turbing force ceases to act. If, for instance, the north pole is displaced in an eastward direction, the earth's magnetism will produce a couple (a pair of parallel forces acting in opposite directions), one member of which may be considered to pull the north pole towards the west, and the other to pull the south pole towards the east. Displacement of the magnet, then, is opposed by this couple ; and where the dis- placing force is small, that is, the current passing through the galva- nometer weak, as is usually the case in physiological observations, it becomes important to reduce the effect of the magnetism of the earth, in other words, the strength of the magnetic field, as much as possible. This can be done by bringing a magnet into the neigh- bourhood of the galvanometer with its north pole pointing north. This pole, which is the one attracted by the earth's north pole, is magnetized in the opposite sense ; and by properly adjusting its distance from the galvanometer magnet, the influence of the earth on the latter can be almost neutralized, and the system made nearly ' astatic' In many galvanometers the magnets attached to the mirror form an ' astatic ' pair (Fig. 126). Two small magnets of nearly equal strength are connected to a light slip of horn or an aluminium wire, with their poles in opposite directions. The earth's magnetism affects them oppositely, so that the resultant action is nearly zero. It is not possible to make the magnets exactly equal in strength, nor is it MUSCLE. 467 126. — ASTAIIC Paik Ol' MAGNP'.TS. Fig. 128. — Co.MPt:NSATCR. liG. 127. — Diagram ok Rheocord (AFTER DU BOIS-REYMOND'S MODEL). Description of Fig. 126. — SN and XS are the magnets, fi.xed to the vertical piece P. M is a mirror. The arrow-heads show the direction of a current which deflects both magnets in the same direction. Description of Fig. 127. — I. to VII. are pieces of brass connected with the wires a to / in such a way that by taking out any of the brass pUigs i to 5, a greater or less resistance may be interposed between the binding screws A and B. The two wires a are connected by a slider s, filled with mercury or otherwise making contact between the wires. The current from the battery B' divides at A and B, part of it passing through the rheocord, part through N, the nerve, muscle, or other conductor which forms the alternative circuit. When a suflficient resistance R is interposed in the chief circuit to make the total strength of the current independent of changes in the resistance of the rheocord, the strength of the current passing through N will vary inversely as the resistance of the rheocord. When all the plugs are in, and the slider close up to A, there is practically no resistance in the rheocord, and all the current passes across the brass pieces and plugs to B, and thence back to the battery. As s is moved further away from A, the resistance of the rheocord is increased more and more, and the intensity of the current passing through N becomes greater and greater. The scale S shows the length of wire interposed for any position of f, and this gives a rough measure of the fraction of the current passing through N. When p'ug i or 2 is taken out, a resistance equal to that of the two wires a is interposed ; plug 3, twice that of a/ plug 4, five times ; plug 5, ten times. Description of Fig. 128. — W is a wire stretched alongside a scale S. A battery B is connected to the binding screws at the ends of the wire. A pair of unpolarisable electrodes are connected, one with a slider moving on the wire, the other through a galvanometer with one of tlie terminal binding screws. In the Fig. a nerve is shown on the elec- trodes, one of which is in contact with an uninjured portion, the other with an injured part. The slider is moved until the twig of the compensating current just balances the demarcation current of the nerve and the galvanometer shows no deflection. 468 A MANUAL OF PHYSIOLOGY. desirable, for then the system would not tend to come to rest in any definite position, and the zero point would be constantly shifting. Either one or both magnets may be surrounded by the galvanometer coils. If both are so surrounded, each must be within a separate coil, and the current must pass in opposite directions in the two coils, otherwise they would neutralize each other. The deflection of a magnet by a current of given strength is pro- portional to the number of turns of wire around it. Where an increase in the number of turns does not sensibly cut down the current, as in experiments on tissues like nerves, whose resistance is large in comparison with that of the galvanometer, an instrument with a great number of turns of wire, that is, a high-resistance galvanometer, is suitable. The resistance of the galvanometers generally used in electro-physiology varies from 3,000 or 4,000 ohms up to 5 times as much. A rheocord is an instrument by means of which a current may be divided, and a definite portion of it sent through a tissue (Fig. 127). A compensator is simply a rheocord from which a branch of a current is led off, to balance or 'compensate' any electrical dif- ference in a tissue, like that which gives rise to the current of rest of a muscle, for example (Fig. 128). An electrometer is an instru- ment for measuring electromotive force, that is, differences of electric potential. Lippmann's capillary electrometer is being more and more employed in physiology. A simple form can be conveniently made as follows. A glass tube is drawn out to a capillary at one end and filled with mercury. The tube is inserted into a small parallel - sided glass bottle, and fastened in its neck with a plug of sealing-wax. The bottle is partially filled with 10 to 20 per cent, sulphuric acid, under which the capillary dips. By means of a small pressure-bottle filled with mercury, and connected with the glass tube, a little mercury is forced through the capillary so as to expel the air in it. When the pressure is lowered again, sulphuric acid is drawn up, and now lies in the capillary in contact with the meniscus of the mercury. A platinum wire fused through the tube dips into the mercury. Another, passing through the sealing- wax, makes contact with the sulphuric acid through some mercury at the bottom of the bottle. The bottle is fastened on the stage of a microscope, the capillary brought into focus, and the meniscus adjusted by raising or lowering the pressure-bottle. When the platinum wires are connected with points at different potential, the mercury and Fig. 129. — Diagram of a simple form OF Capillary Elfxtrometer. B, parallel-sided glass bottle containing sulphuric acid, S ; Hg, mercury in glass lube, the capillary end of which projects into B; E, E', platinum wires; T, tube filled with mercury, and connecting the capillary with a pressure bottle ; C, capil- lary magnified. MUSCLE. 469 sulphuric acid receive charges at their surfaces of contact in the capillary tube, by which the equilibrium previously existing between the three surface-tensions (between mercury and glass, between sulphuric acid and glass, between sulphuric acid and mercury) and the hydrostatic pressure of the mercury is disturbed, and the mercurial meniscus moves along the capillary. If the mercury is connected with a surface at a higher potential than that in con- nection with the sulphuric acid, the meniscus moves towards the point of the capillary, and 7nce versa. It consists (i) of a small table carrying a parallel- sided glass vessel con- taining mercury and sul- phuric acid. {2) The capillary tube, which can be moved in two direc- tions at right angles to each other, and so ad- justed in the field of the microscope. (3) A pres- sure-vessel, and a mano- meter connected with it for measuring the pressure. {4) Two binding - screws connected by wires to the mercury in the capillary tube and in the parallel- sided vessel. The binding- screws can be short-cir- cuited by closing the friction-key shown at the right side of the figure, thus preventing any dif- ference of electromotive force between two points connected with the screws from affecting the electro- meter. Fig. 130. — Capillary Electkomktek (aktek Frey ; Petzold, Leipzig), .■\s arranged FOR Mounting on the Microscope Stage. Induced Currents. — When a coil of wire in which a current is flowing is brought up suddenly to another coil, a momentary current is developed in the stationary coil in the opposite direction to that in the moving coil. Similarly, if instead of one of the coils being moved a current is sent through it, while the other coil remains at rest in its neighbourhood, a transient oppositely-directed current is set up in the latter. When the current in the first coil is broken, a current in the same direction is induced in the other coil. Du Bois-Reymond's Sledge Inductorium (Fig. 131). — This consists of. two coils, the primary and the secondary, the former having a comparatively small number of turns of fairly thick copper wire, the latter a large number of turns of thin wire. The object of this is that the resistance of the primary, which is connected with one or more voltaic cells, may not cut down the current too much ; while the currents induced in the secondary, having a high electromotive 470 A MANUAL OF PHYSIOLOGY. force, can readily [jass through a high resistance, and are directly proportional in intensity to the number of turns of the wire. By means of various binding-screws and the electro-magnetic interrupter, or Neef's hammer, shown in the figure and explained below it, the current can be made once in the primary or broken once, or a constant alternation of make and break can be kept up. We can thus get a single make or break shock in the secondary, or a series of shocks, sometimes called an interrupted current. Such a series of stimuli can also be got by making and breaking a voltaic current at any given rate. A ' self-induced ' current can also be obtained from a single coil ; for instance, from the primary coil alone of the induction apparatus. The reason of this is, that when a current begins to flow through any turn of a coil of wire, it induces in all the other turns a current in the opposite direction, and, when it ceases to flow, a current in the same Fig. 131.— Du Bois-Rkymoxd's Inductorium. B, primary, B', secondary, coil ; H, guides in \v?iich B' slides, with scale ; D, electro- magnet ; E, vibrating spring ; ;, wire connecting wire of D to end of primary ; v, screw with platinum point, connected with other end of primary ; A, A', binding screws to which are attached the wires from battery. A' is connected with the wire of the electro- magnet D, and through it and i with the primary. direction as itself. The former current, ' the make extra shock,' being in the opposite direction to the inducing current, is retarded in its development, and reaches its maximum more slowly than the break extra shock. But, as we shall see, the suddenness with which an electrical change is brought about is one of the most important factors in electrical stimulation, and, therefore, the break extra shock is a much more powerful stimulus than the make. Owing to these self- induced currents, the stimulating power of a voltaic stream may be much increased by putting into the circuit a coil of wire of not too great resistance. The self-induction of the primary also affects the stimulating power of the currents induced in the secondary ; the shock induced in the secondary by break of the primary current is a stronger stimulus than that caused at make of the primary. The reason is, that with a MUSCLE. 471 given distance of primary and secondary, and a given intensity of the voltaic current in the primary, the abruptness with which the induced current in the secondary is developed depends upon the rapidity with which the primary current reaches its maximum at closing, or its minimum (zero) at opening. Now, the make extra current retards the development of the primary current, while in the opened circuit of the primary coil the current intensity falls at once to zero. The inequality between the make and break shocks of the secondary coil can be greatly reduced by means of Helmholtz's wire. Connect one pole of the battery with v (Fig. 131), and the other with x^'. Join A and A' by a short, thick wire. With this arrange- ment the primary circuit is never opened, but the current is alter- nately allowed to flow through the primary, and short-circuited when the spring touches v. The ' make ' now corresponds to the sudden increase of intensity of the current in the primary when the short-circuit is removed, and the 'break' to its sudden decrease when the short-circuit is established. In both cases self-induced Fig. 132. — Unpolakizable Electkuuks. .\, liook-shaped ; B, U-tubes ; C, straight. D, clay in contact with tissue ; S, saturated zinc sulphate solution ; Z, amalgamated zinc wire. currents are developed, and, therefore, both shocks are weakened. But the opening stimulus is now slightly the weaker of the two, because the opening extra shock has to pass through a smaller resistance (the short-circuit) than the closing extra shock (which passes by the battery), and therefore opposes the decline of current intensity on short-circuiting, more than the closing shock opposes the increase of current intensity on long-circuiting through the primary. By means of wires connected with the terminals of the secondary coil and leading to electrodes, a nerve or muscle may be stimulated ; and it is usual to connect the wires to a short-circuiting key (Fig. 134), by opening which the induced current is thrown into the tissue to be stimulated. For some purposes the electrodes may be of platinum ; but all metals in contact with moist tissues become polarized when currents pass through them, that is, have decom- position products of the electrolysis of the tissues deposited on them. And as any slight chemical difference, or even perhaps a difference of physical state, between the two electrodes will cause them and the tissues to form a battery evolving a continuous current, it is often desirable to use unpolarizabk electrodes. 472 A MANUAL OF PHYSIOLOGY. Unpolarizable Electrodes. — Some convenient forms of these are represented in Fig. 132. A piece of amalgamated zinc wire dips into saturated zinc sulphate solution contained in the upper part of a glass tube. The lower end of the tube may be straight, but drawn out so as to terminate in a not very large opening, or it may be bent into a hook, in the bend of which a hole is made. Before the tube is filled with the zinc sulphate solution, the lower part of it is plugged with china clay made up with normal saline. The clay just projects through the opening, and thus comes in contact with the tissue. When these electrodes are properly set up, there is very little polariza- tion for several hours, but for long experiments, U-shaped tubes, filled with saturated zinc sulphate solution, are better. The amalgamated zinc dips into one limb, and a small glass tube filled with clay, on which the tissue is laid, into the other. Pohl's Commutator (Fig. 133) consists of a block of paraffin or wood with six mercury cups, each in connection with a binding-screw (not shown in the figure). Cups i and 6, and 2 and 5 are connected by copper wires, which cross each other without touching. The bridge consists of a glass or vulcanite cross-piece a, to which are attached two wires bent into semicircles, each connected with a straight wnre dipping into the cups 3 and 4 respectively. With the bridge in the position shown in the figure, a current coming in at 4 would pass out by the wire connected with i, and back iiG. 133.— Pohl's Com- again by that connected with 2, in the MUT \TOK . "^ direction shown by the arrows. When the bridge is rocked to the other side so that the bent wires dip into 5 and 6, the direction of the current is reversed. The cross-wires may be taken out altogether, and the commutator used to send a current at will through either of two circuits, one connected with 1 and 2, and the other with 5 and 6. Du Bois-Reymond's Short-circuiting Key. — A cheap and convenient form is shown in Fig. 134. Time-Markers — Electric Signal. — It is of importance to know the time relations of many physiological phenomena which are graphically recorded ; for example, the contraction of a skeletal muscle or the beat of a heart. For this purpose a tracing showing the speed of the travelling-surface in a given time is often taken simultaneously with the record of the movement under investigation. For a slowly- moving surface it is sufficient to mark intervals of one or two seconds, and this is very readily done by connecting an electro-magnetic marker (such as the electric signal of Deprez) with a circuit which is closed and broken by the seconds' pendulum of an ordinary clock (Fig. 135) or a metronome (Fig. 51, p. 144). For shorter intervals a tuning-fork is used, which makes and breaks a circuit including an electro-magnetic marker, or writes on the drum directly by means of a writing-point attached to one of the prongs. MUSCLE. 473 In all the great functions of the body we find that muscular movements play an essential part. The circulation and the respiration, the two functions most immediately essential to life, are kept up by the contraction and relaxation of muscles. The movements of the digestive canal, the regulation of the blood-supply to its glands and to all parts of the body, and that immense class of movements which we call voluntar}-, are all dependent upon muscular action, which, again, is indebted for its initiation, continuance, or control, to impulses passing along the nerves from the nerve-centres. Hitherto we have not gone below the surface fact, that Fig. 134. — Du Bois-Revmond's Key. Fig. 135. — TiMi:-.M.\KKEK. Arrangement formarking 2" intervals. D, seconds pendulum, with platinum point E soldered on; A, mercury trough, into which E dips at end of its swing; B, Daniell cell ; C, electro-magnets, which draw down writing lever F when the current is closed by E dipping into A ; G, spring (or piece ot" indiarubber), which raises F as soon as current is broken. muscular fibres have the power of contracting, either auto- matically, or in response to suitable stimuli. In this chapter and the two next we shall consider in detail the general properties of muscle, nerve, and the other excitable tissues. Lying deeper than the peculiarities of individual muscles, muscular tissue has certain common properties, physical, chemical, and physiological. The biceps muscle flexes the arm upon the elbow, and the triceps extends it. The external rectus rotates the e3'eball outwards. The inter- costal muscles elevate the ribs. The sphincter ani seals up by a ring-like contraction the lower end of the alimentary 474 ^i MANUAL OF PHYSIOLOGY. canal. These actions are very different, but the muscles that carry them out are at bottom very similar. And it cannot be doubted that the functional differences are due entirely, or almost entirely, to differences of anatomical con- nection, on the one hand with bones and tendons, on the other with the nerve-cells of the spinal cord and brain. The common properties in which all the skeletal muscles agree are the subject-matter of the general physiology of striated muscle. The cardiac muscle differs more, both in structure and in function, from the skeletal muscles than these do among themselves ; the smooth muscle of the intestines and blood- vessels still more. But every muscular fibre, striped or unstriped, resembles every other muscular fibre more than it does a nerve-fibre or a gland-cell or an epithelial scale. The properties common to all muscle make up the general physiology of muscular tissue. A nerve-fibre is at first sight very different from a muscular fibre. It has diverged more widely from the primitive type of undifferentiated protoplasm. It has lost the power of contraction, or contractility, but it retains, in common with the muscle-fibre, susceptibility to stimulation, or excitability, the capacity for growth, and to a limited extent the capacity for reproduction. This inheritance of primitive properties, retained alike by both tissues, is the basis of the general physiology of muscle and nerve. The electrical organ of the torpedo or the Malapterurus is intermediate in some respects between muscle and nerve, and has properties common to both. In the gland-cell the chemical powers of native proto- plasm have been specialized and developed. Contractility has been, in general, entirely lost ; but excitability remains. The properties shared in common by muscle, nerve, electrical organ, gland, and certain other structures, make up the general physiology of the excitable tissues. Amoeboid movement is the most primitive, the least elaborated form of contraction. An amoeba may be seen under the microscope to send out pseudopodia, or processes, of its substance and to retract MUSCLE. 475 them, and it is even able by such movements to change its place. Stimulation with induction shocks causes the whole of the processes to be drawn in. and the amoeba to gather itself into a ball. This illustrates a universal property of protoplasm, excitability, or the power of responding to certain external influences, or stimuli, by manifestations of the peculiar kind which we distinguish as vital or physiological. Certain of the white blood-corpuscles behave like the amoeba ; and we have already dwelt upon some of the important functions fulfilled by such amoeboid movement in the higher animals and in man. But a great distinction between this kind of contraction and that of a muscular fibre is that it takes place in any direction. Cilia. — Cilia possess a higher and more specialized grade of contractility. They are very widely distributed in the animal kingdom ; and analogous structures are also found in many low plants, such as the motile bacteria. In the human subject ciliated epithelium usually con- sists of several layers of cells, the most superficial of which are pear-shaped, the broad end being next the surface and covered with extremely fine processes, or cilia, about 8/x in length, which are planted on a clear band. It lines the respiratory passages, the middle ear and Eustachian tube, the Fallopian tubes, the uterus above the middle of the cervix, the epididymis, where the cilia are extremely long, and the central cavity of the brain and spinal cord. Ciliary motion can be very readily studied by placing a scraping from the palate of a frog, or a small portion of the gill of a fresh-water mussel under the microscope in a drop of normal saline solution. The motion of the cilia is at first so rapid that it is impossible to make out much, except that a stream of liquid, recognised by the solid particles in it, is seen to be driven by them in a constant direction along the ciHated edge. When the motion has become less quick, which it soon does if the tissue is deprived of oxygen, it is seen to consist in a swift bending of the cilia in the direction of the stream, followed by a slower recoil to the original position, which is not at right angles to the surface, but sloping streamwards. All the cilia on a tract 476 A MAXUAL OF PHYSIOLOGY. of cells do not move at the same time ; the motion spreads from cell to cell in a regular wave. The energy of ciliary motion ma}- be considerable, although far inferior to that of muscular contraction. The work which cilia are capable of performing can be calculated by removing the membrane, fixing it on a plate of glass, cilia outwards, putting weights on the glass plate, and allowing the cilia, like an immense number of feet, to carry it up an inclined plane. Bowditch found in this way that the cilia on a square centimetre of mucous membrane did nearly 7 gramme-millimetres of work per minute (equal to the raising of 7 grammes to a height of a millimetre). Since the cilia in the respiratory tract all lash upwards, they must play an important part in carrying up foreign particles taken in with the air, and the mucus in which they are entangled, as well as pathological products. Engelmann found that the energy of ciliary motion increases as the temperature is raised up to about 40° C, after which it diminishes quickly. Overheating causes cilia to come to rest, but if the temperature has not been too high, and has not acted too long, they recover on cooling. Structure of Muscle. — The structure of striped muscle has long been the enigma of histology ; and the labours of many distinguished men have not sufficed to make it clear. On the contrary, as investigations have multiplied, new theories, new interpretations of what is to be seen, have multiplied in proportion, and a resolute brevity has become the chief duty of a writer on elementary physiology in regard to the whole question. The muscle-fibre, the unit out of which the anatomical muscle is built up, is surrounded by a structureless mem- brane, the sarcolemma. The length and breadth of a fibre var}' greatl}' in different situations. The maximum length is about 4 cm. ; the breadth may be as much as 70 fx and as little as 10 IX. The fibre shows alternate light and dark stripes, the latter being doubly, the former only singly, re- fractive (p. 485). As to the interpretation of this appearance there has been much discussion. It was supposed by some that a membrane (Krause's membrane) stretched across the MUSCLE. 477 fibre in the middle of each light disc, dividing it into a number of compartments. Kiihne, however, was fortunate enough to find one day a nematode worm in the interior of a fibre. He followed its movements, and saw it pass along the fibre with perfect freedom, ignoring Krause's membrane ; so that if such a partition exists, it must either be incomplete, or much more easily ruptured than the sarcolemma. As to the nature of the contents of the sarcolemma, Bowman described the dark disc as being composed of sarcous elements or prisms of contractile substance. Schafer has recently described the contractile elements as fine columns (sarcostyles) divided by septa into segments (sarcomeres). Each sarcomere contains a sarcous element with a clear fluid at its ends, which produces the appearance of the light stripe. During contraction this fluid is squeezed into fine longi- tudinal canals, which pierce the sarcous elements. Other observers, using chloride of gold as a stain, have asserted that an apparent network, brought out by that reagent, and which is stated to be connected with the nuclei or muscle-corpuscles, is the contractile part of the fibre. But this view has met with great opposition ; and the substance stained by the gold is probably only interstitial material. On the whole, it seems to be clearly made out that the contents of the muscle-fibre consist of two functionally different sub- stances, a contractile substance, and an interstitial, perhaps nutritive, non-contractile material of more fluid nature. The contractile substance is arranged as longitudinal fibrillae (sar- costyles) embedded in interfibrillar matter (sarcoplasm). Smooth muscle-fibres are spindle-shaped, and, unlike the fibres of striped muscle, contain only a single nucleus. Cardiac muscle has been already described (p 56). Nearly all our knowledge of the physiology of muscle has been gained either from striped skeletal muscle or from the muscle of the heart, and chiefly from the former. Of non- striped muscle we know comparatively little except by in- ference, owing to the difficulty of obtaining it in sufficient quantity and in suitable preparations for experiments. In what follows we always refer to ordinary skeletal muscle, unless it is otherwise stated. 478 A MANUAL OF PHYSIOLOGY. Physical Properties of Muscle — Elasticity. — All bodies may have their shape or volume altered by the application of force. Some require a large force, others a small force, to produce a sensible amount of distortion. The elasticity of a body is the property in virtue of which it tends to recover its original form or bulk when these have been altered. Liquids and gases have only elasticity of volume ; solids have also elasticity of form. Most solids recover perfectly, or almost perfectly, from a slight deformation. The limits of distortion within which this occurs are called the limits of elasticity, and they vary greatly for different substances. Living muscle has very wide limits of elasticity ; it may be deformed — stretched, for example — to a very considerable extent, and yet recover its original length when the stretch- ing force ceases to act. The extensibility of a body is measured by the ratio of the increase of length, produced by unit stretching force per unit of area of the cross-section, to the original length of a uniform rod of the substance. , . Is If e is the extensibility, ^=, ^, where / is the increase of length, L the original length, s the cross-section, and F the stretching force. LF The reciprocal of this, - ' is called Young's modulus of elasticity, or the co-efificient of elasticity. Suppose we wish to compare the ex- tensibility of two substances. Let A and B be strips or rods of the substances, the length of A being 500 mm., that of B 1,000 mm. ; the cross-section of A, 100 sq. mm., of B, 200 sq. mm. Let the elon- gation produced by a weight of i kilo be 10 mm. in each. Then the •u-r. c A • 10x100 , , r Ti • 10x200 extensibility of A is =2 ; and that of B is =2 ; ^ 500 X I 1,000 X I ' that is, the substances are equally extensible. Living muscle is very extensible ; a small force per unit area of cross-section of a prism of it will produce a com- paratively great elongation. The extensibility, however, diminishes continually with the elongation, so that equal increments of stretching force produce always less and less extension. If, for instance, the sartorius or semimem- branosus of a frog be connected with a lever writing on a blackened surface, and weights increasing by equal amounts MUSCLE. 479 be successively attached to it, the recording surface being- allowed to move the same distance after the addition of each weight, a series of vertical lines, representing the amount of each elongation, will be traced. When the lower ends of all the vertical lines are joined by a smooth curve, it is found to be a hyperbola with the concavity upwards (Fig. 136). This is a property common to living and dead muscle and to other animal structures, such as arteries. Marey's method, in which the weight is continuousl}' in- creased from zero and then continuously decreased to zero again by the flow of mercury into and out of a vessel attached to the muscle, gives directly the hyperbolic curve of extensibility. The elongation of a steel rod or other inorganic solid is proportional within limits to the extending force per unit of cross-section ; and a curve plotted with the weights for abscissae and the amounts of elongation for ordinates would be a straight line. But this is not a fundamental distinction between animal tissues, and the materials of unorganized nature, as some writers seem to suppose. For when the slow after- ^ , "^ . 1 . 1 r 11 r •^"-'- 136.— Curves of Extensi- elongation which follows the first bility. rapid increase in length in the . m, of muscle ; s, of an ordinary ■^ ^ , , inorganic solid. loaded, excised muscle is waited for, the curve of extensibility comes out a straight line (Wundt), and within limits this is also the case for human muscles in the intact body. And although a steel rod much more quickly reaches its maximum elongation for a given weight when loaded, and its original length when the weight is removed, than does a muscle, time is required in both cases and the difference is one of degree rather than of kind. Dead muscle is less extensible and much less elastic than living. In the state of contraction the extensibility is in- creased in frog's m.uscle ; but Bonders and Van Mansveldt have found that contraction causes little difference in the muscles of a living man, although fatigue increases the ex- 48o A MANUAL OF PHYSIOLOGY. tensibility. The great extensibility and elasticity of muscle must play a considerable part in determining the calibre of the vessels, and in lessening the shocks and strains which the heart and the vascular system in general are called upon to bear, and must contribute much to the smoothness with which the movements of the skeleton are carried out, and immensely reduce the risk of injury to the bones as well as to the muscles themselves, the tendons and the other soft tissues. And not only is smoothness gained, but economy also ; for a portion of the energy of a sudden contraction, which, if the muscles were less extensible and elastic, might be wasted as heat in the jarring of bone against bone at the joints, is stored up in the stretched muscle and again given out in its elastic recoil. The skeletal muscles, too, are even at rest kept slightly on the stretch, braced up, as it were, and ready to act at a moment's notice without taking in slack. This is shown by the fact that a transverse wound in a muscle * gapes,' the fibres being re- tracted, in virtue of their elasticity, towards the fixed points of origin and insertion. If a muscle is so overweighted that it cannot contract, it elongates slightly on stimulation (Wundt). This has by some been held to indicate that the increase of extensibility associated with contraction still occurs in the excited state when actual contraction is mechanically prevented. In the further study of muscle it is necessary first of all to consider the means we have of calling forth a contraction — in other words, the various kinds of stimuli. Stimulation of Muscle. — A muscle may be excited or stimulated either directly or through its motor nerve ; and the stimulus may be electrical, mechanical, chemical, or thermal. Electrical stimuli are by far the most commonly used, and will be discussed in detail. A prick, a cut, or a blow are examples of mechanical stimuli. A fairly strong solution of common salt or a dilute solution of a mineral acid will act as chemical stimuli, which always tend to cause, not a single contraction, but a tetanus. Sudden cooling or heating acts as a stimulus for muscle, but thermal stimulation is somewhat uncertain. In all artificial stimula- MUSCLE. 481 tion there is an element of sudden or abrupt change, of shock, in other words ; but we cannot tell in what the * natural ' or ' physiological ' stimulus to muscular contraction in the intact body really consists, nor how it differs from artificial stimuli. All we know is that there must be a wide difference, and that our methods of excitation must be very crude and inexact imitations of the natural process. Direct Excitability of Muscle. — ^The famous controversy on the existence of 'independent muscular irritability' has now passed into oblivion, and has no further interest except for the antiquaries of science, if such exist. The direct excitability of muscle in the modern sense is very different from the question which occupied Haller and his contemporaries. What the modern physiologists have been called upon to decide is whether muscular fibres can be caused to contract except by an excitation that reaches them through their nerves. In this sense there can exist no doubt that muscle is directly excitable, and the proofs are as follows : (i) The ends of the frog's sartorius contain no nerves, the apex of the frog's heart contains neither nerves nor nerve- cells, yet both respond to direct stimulation. (2) Certain chemical stimuli — ammonia, for instance — do not act on nerve, but excite muscle. (3) When the motor nerves of a limb are cut they degenerate, and after a certain time stimulation of the nerve-trunk causes no muscular contrac- tion, while the muscles, although atrophied, can be made to contract by direct stimulation. (4) Finally, there is the celebrated curara experiment of Claude Bernard, which is described in a somewhat modified form in the Practical Exercises, p. 543. A ligature is tied firmly round one thigh of a frog, omitting the sciatic nerve ; then curara is injected, and in a short time the skeletal muscles are paralyzed. That the seat of the paralysis is not the muscles themselves is shown by their vigorous response to direct stimulation. The ' block ' is not in the nerve-trunk, nor above it in the central nervous system, for the ligatured leg is often drawn up — that is, its muscles are contracted, although the poison has circulated freely in the sacral plexus and the 31 482 A MANUAL OF PHYSIOLOGY. spinal cord. Further, if the nerve of the Hgatured leg be prepared as high up above the ligature as possible, where the curara must undoubtedly have reached it (just above the ligature the nerve has been isolated and the circulation in it more or less interrupted), stimulation of it will cause con- traction of the muscles of the limb ; while excitation of the other sciatic is ineffective. It can be also shown, by means of the negative variation or current of action (p. 557), that a nerve-trunk on which curara has acted remains excitable, and capable of conduct- FiG. 137.— Tonic Compaction of Muscle during Passage of Constant Current. Two sartorius mucles of frof^ connected by pelvic attachment?. Current from 12 small Daniell cells in series passed through their whole length. Current closed at 7n, opened at b. Time trace, two-second intervals. ing the nerve-impulse. The conclusion, therefore, is that the curara paralyzes neither nerve-fibre nor muscular fibre, but the link between the two which we call the nerve- ending. In coming to this conclusion, the assumption is made that the nerve-fibres within the muscle, since they are anatomically similar to those in the nerve-trunk till near their terminations, are similarly affected by curara. We must carefully remember that the * nerve-endings ' which are paralyzed by curara do not necessarily, nor even pro- bably, coincide exactly with the ' nerve-endings ' of histology. Still, it is significant that the histological differences between the nerve-terminations in striped and smooth muscle should correspond to a physiological difference in the action of MUSCLE. 48: curara on them. This drug paralyzes the nerve-endings in smooth muscle — the muscles of the bronchi, for in- stance— with much greater difficulty than those in ordinary skeletal muscle, and the same is true of the vagus-endings in the heart. The action of curara gives us the means of stimulating muscle directly ; when electrical currents are sent through a non-curarized muscle, there is in general a mixture of direct and indirect stimulation, for the nerve-fibres within the muscle are also excited. Induced currents stimulate nerve more readily than muscle. Voltaic currents may excite a muscle whose nerves have degenerated, while induced currents are entirely without effect. For direct stimulation, a curarized frog's sartorius or semi-membranosus is generally used on account of their long parallel fibres ; for indirect excitation, a muscle-nerve Curve from frog's gastroc- nemius. At M constant cur- rent closed, at B broken. Contracture continues after opening of current. Time trace, two - second intervals. Fig. 138.— To.mc Co.ntkactio.n dcking .\nd after flow. preparation, composed of a frog's gastrocnemius with the sciatic nerve attached to it, is commonly employed, as it is easy to isolate the muscle without hurting its nerve. Stimulation by the Voltaic Current. — While the current con- tinues to pass through a nerve without any sudden or great change in its intensity, there is no stimulation, and the muscle connected with the nerve remains at rest. The same is generally true of muscle when the current is passed directly through it. But here the constancy of the rule is 484 A MANUAL OF PHYSIOLOGY. far more frequently broken by exceptional results than in nerve, especially if the current is at all strong, when a state of tetanus is very apt to show itself during the whole time of flow (Wundt) (Fig. 138) ; and a similar condition, the so-called galvanotomts, is normally seen in human muscles when traversed by a stream of considerable intensity. For nerve, and with these qualifications for muscle, too, we may lay down the law that the voltaic current stimulates at make and at break, but not during its passage. Or, generalizing this a little, since it has been shown that a sudden increase or decrease in the strength of a current already flowing also acts as a stimulus, we may say that the voltaic current stimulates only when its intensity is suddenly and sufficiently increased or diminished, but not while it remains constant. A second law of great theoretical importance is that at make the stimidation occurs only at the cathode ; at break only at the anode ; and that the make is stronger than the break contrac- tion. This is true both for muscle and nerve, but it is most directly and simply demonstrated on muscle. A long parallel-fibred curarized muscle is supported about its middle ; the two ends, which hang down, are connected with levers writing on a revolving drum, and a current is sent longitudinally through the muscle. It is not difficult to see from the tracings that at make the lever attached to the cathodic end moves first, and that the other lever only moves when the contraction started at the cathode has had time to reach it in its progress along the muscle. Similarly, at break the lever connected with the anodic end moves first. The Muscular Contraction. — When a muscle contracts, its two points of attachment, or, if it be isolated, its two ends, come nearer to each other; and in exact proportion to this shortening is the increase in the average cross-section. The contraction is essentially a change of form, not a change of volume. The most delicate observations fail to detect the smallest alteration in bulk (Ewald). Living fibres kept contracted by successive stimuli can be examined under the microscope ; or fibres may be ' fixed ' by reagents like osmic MUSCLE. ■485 acid, and sometimes a very good opportunity of studying the microscopic changes in contraction is given by a group of fibres in which the 'fixing' reagent has caught a wave of contraction, and, so to speak, pinned it down. It is then seen that the process of contraction in the fibre is a miniature of that in the anatomical muscle. The individual fibres shorten and thicken, and the sum-total of this shorten- ing and thickening is the muscular contraction which we see with the naked eye. The phenomena of the muscular contraction may be classified thus : (i) Optical, (2) Me- chanical, (3) Thermal, (4) Chemical, (5) Sonorous, (6) Elec- trical. Fjg. 139. — Diagram 01 Striped Muscle. Here a muscular fibre is sup- posed to be fixed in contraction at one part C The figure is only a rough diagram. The left hand half is supposed to be looked at in ordin.-iry, and the right hand halfinpolnrised light. A is the dim and B the light stripe of the uncontracted fibre. Fig. 140. — Living Muscular I-ihki: (kkom Gkotrupes stercorarius). I, In ordinary; 2, in polarised light. (Van Gehuchten. ) In living muscle (at least in fibres which are not extended) in contrast to dead nmscle after treatment with reagents, the doubly refract- ing or anisotropous substance is present in the greater part of the fibre ; and with crossed nicols the position of the singly refracting or isotropous material is indicated only by narrow transverse black lines or rows of dark dots. (i) Optical Phenomena. — The shortening occurs in both stripes, and their appearance changes, chiefly through the increasing dimness of the light disc, so that what is the lighter in the relaxed becomes the darker in the contracted fibre. This curious phenomenon is known as the ycvcysoI of the stripes. That the doubly refractive substance, how- ever, does not change its place is shown by the fact that in polarized light there is no reversal. A ray of ordinary light consists of vibrations of the ether in all planes at right angles to the direction of the ray. In a ray of plane polarized light all the particles vibrate in one plane. A ray of light which has been polarized by a Nicol's prism cannot pass through 486 A MANUAL OF PHYSIOLOGY. another Nicol's prism with its principal plane at right angles to that of the first. If the second or analyzing prism be rotated so that the principal planes are no longer at right angles, some of the light will pass through. The same effect is produced if, without altering the original ' crossed ' position of the nicols, a substance capable of rotating the polarized ray is introduced between the prisms. The dark disc of the uncontracted fibre contains such a doubly refracting substance, and, therefore, stands out as a light area in the otherwise dark field of the crossed nicols. In the contracted fibre the stripe which appears light occupies the same position as in the relaxed fibre. A rough illustration will perhaps tend to make this point clearer. Suppose that a string fixed at one end is set vibrating in various directions by a twisting movement. If the string has to pass through a narrow vertical slit, e.g., between two fingers held vertically, all vibrations except those in the vertical plane will be extinguished ; but vertical vibrations will be able to pass beyond the slit. The movement may be said to be plane polarized, and the effect of the slit corresponds to that of the first nicol. Now make the string pass also through a horizontal slit ; the vertical vibrations will now be extinguished too— in other words, none of the move- ments will pass beyond the ' crossed ' slits. This corresponds to the dark field of the crossed nicols. But if the vertical vibrations which have passed the first slit could be in any way changed into horizontal vibrations, they would no longer be extinguished by the second. This would correspond to rotation of the plane of polarization through 90°. A ray of light polarized by the first nicol will, if its plane of polariza- tion be rotated through 90°, pass entirely (except for loss by ordinary reflection and absorption) through the second. If the angle of rota- tion is less than 90", a portion will pass through. (2) Mechanical Phenomena. — The muscular contraction may be graphically recorded by connecting a muscle with a lever which is moved either by its shortening or by its thickening. The lever writes on a blackened surface, which must travel at a uniform rate if the form and time-relations of the muscle-curve are to be studied, but may be at rest if only the height of the contraction is to be recorded. The whole arrangement for taking a muscle-tracing is called a myograph (Fig. 163). The duration of a ' twitch ' or single contraction (including the relaxation) of a frog's muscle is usually given as about one-tenth of a second, but it may vary considerably with temperature, fatigue, and other circumstances. It is measured by the vibrations of a tuning-fork written imme- diately below or above the muscle curve. When the muscle is only slightly weighted, it but very gradually reaches its original length after contraction, a period of rapid relaxation MUSCLE. 487 being followed by a period of ' residual contraction,' during which the descent of the lever towards the base line becomes slower and slower, or stops altogether some distance above it. Latent Period. — If the time of stimulation is marked on the tracing, it is found that the contraction does not begin simultaneously with it, but only after a certain interval, which is called the latent period. This can be measured by means of the pendulum myo- FiG. 141. — Spring Myockaph. A, B, iron uprights, between which are stretched the guide-wires on which tlie travelHng plate a runs ; k, pieces of cork on the guides to gradually check the plate at the end of its excursion, and prevent jarring; b, spring, the release of which shoots the plate along ; h, trigger-key, which is opened by the pin d on the frame of the plate. graph or the spring myograph, in both of which the carrier of the recording plate opens, at a definite point, in its passage, a key in the primary coil of an induction machine, and so causes a shock to be sent through the muscle or nerve, which is connected with the secondary. The precise point at which the stimulus is thrown in can be marked on the tracing by carefully bringing the plate to the position in which the key is just opened, and allowing the lever to trace here a vertical line (or, rather, an arc of a circle). The portion of the time-tracing between this line and a parallel 488 A MANUAL OF PHYSIOLOGY. line drawn through the point at which the contraction begins, gives the latent period. Fig. 142. — Penpulum Myograph. At the left as seen from the side, at the right as seen from the front. A, bearings on which the pendulum swings ; P, pendulum ; G, G', glass plates carried in the frames T, T' ; a, pin which opens tne trigger-key. The key, when closed, is in cuntact with c, and so completes the circuit of the primary coil. Helixiholtz measured the length of the latent period by means of the principle of Pouillet, that the deflection of a magnet by a current of given strength and of very short duration is proportional to the time during which the current MUSCLE. 489 acts on the magnet. He arranged that at the moment of stimulation of the muscle a current should be sent through a galvanometer, and should be broken by the contraction of the muscle the moment it began. In this way he obtained the value of ^ffir second for the latent period of frog's muscle. The tendency of later observations has been to make the latent period shorter. Burdon Sanderson finds that the change of form probably begins in muscle with direct stimulation in twit second after, and the electrical change (p. 559) simultaneously with, the excitation. It is known that the apparent latent period depends upon the re- sistance which the muscle has to overcome in beginning its contraction. A heavily-weighted muscle, for instance, can- not begin to shorten until as much energy has been developed as is necessary to raise the weight ; and its latent period Fig. 143. — CuKVK of a Sinci.k Mlscui.ak Contkaction ok Twitch taken UN Smoked Glass with Spring Myoguaph and Photographed. Vertical line A marks the point at which the muscle was stimulated ; time-tracing shows yiijth of a second (reduced). will be distinctly longer than that of unweighted or very slightly weighted muscles, such as those with which Sander- son worked. The maximum shortening, or 'height of the lift,' depends upon the length of the muscle, the direction of the fibres, the strength of the stimulus, the excitability of the tissue, and the load it has to raise. In a long muscle, other things being equal, the absolute shortening, and therefore the maximum height of the curve will be greater than in a short muscle; in a muscle with fibres parallel to its length — the sartorius,;_for instance — it will be greater than in a muscle like the gastrocnemius, with the fibres directed at various angles to the long axis. For stimuli less than maximal, the absolute contraction increases with the strength of stimulation, and a given stimulus will cause a greater contraction in a^muscle with 490 A MANUAL OF PHYSIOLOGY a given excitability than in a muscle which is less excitable. Finally, increase of the load per unit of cross-section of the muscle diminishes above a certain limit the ' height of the lift,' although below that limit it may increase it. Influences which affect the Time-relations of the Muscular Contraction. — Many circumstances affect the form of the muscle-curve and its time-relations. {a) Influence of the Load. — The first effect of contraction is to suddenly stretch the muscle, and the more the muscle is loaded the greater will this elongation be. So that at the beginning of the actual shortening part of the energy of contraction is already expended without visible effect, and Fk;. 144. — Influence of \a^.\\< 1, curve taken with unloaded lever trace Tuuth sec. (reduced). >N nil-. iMiKM (IK THE iMuSCLE CURVE. ■ 2, 3, 4, weight successively increased ; time- has to be recovered from the elastic reaction during the ascent of the lever. Then the inertia of the lever itself and of its load comes into play, and may carry the curve too high during the up-stroke and too low during the down-stroke. This can be minimized by making the lever very light, and attaching the weight close to the fulcrum, so that it has only a small range of movement, and never acquires more than a small velocity. The contraction of a muscle loaded by a weight which is not increased or diminished during the contraction is said to be iso-tonic, for here the tension of the muscle is the same throughout, and its length alters. When the miiscle is attached very near the fulcrum of the lever, so that it acts upon a short arm, while the long arm carrying the writing-point is prevented from moving much by a spring, the muscle can onl}' shorten itself very slightly; but MUSCLE. 491 the changes of tension in it will be related to those in the spring, and therefore to the curve traced by the writing- point. Such a curve is called iso-metric, since the length of the muscle remains almost unaltered. The maximum of the iso-metric curve (the maximum tension with practically constant length) is sooner reached than that of the iso- tonic (the maximum contraction with constant tension). From this it has been concluded that during contraction the co-efficient of elasticity of the muscle continuously diminishes (Fick), or, what comes to the same thing, its extensibility continuously increases. The ic'ork done by a muscle in raising a weight is equal to the product of the weight by the height to which it is raised. Beginning with no load at all, it is found that the weight can be increased up to a certain limit without diminishing the height of the contraction ; perhaps the height may even increase. Up to this limit, then, the work evidently increases with the load. If the weight i^; made still greater the contraction becomes less and less, but up to another limit the increase of weight more than compensates for the diminution of 'lift,' and the work still increases. Beyond this, further increase of weight can no longer make up for the lessening of the lift, and the work falls off till ultimately the muscle is unable to raise the weight at all. The manner of application of the weight has an influence on the work done by the muscle. If it is applied before the contraction begins, so that the muscle is already sti'etched at the moment of stimulation, a cause of error and un- certainty is introduced ; for it is known that mere stretching of muscle affects its metabolism, and therefore its functional power. So that it is usual in experiments of this kind to after-load the muscle — that is, to support the lever and its load in such a way that the weight does not come upon the muscle till contraction has just begun. The 'absolute con- tractile force ' of an active muscle may be measured on this principle by determining the weight which, brought to bear upon the miuscle at the instant of contraction, is just able to prevent shortening without stretching the muscle. It, of course, depends, among other things, on the cross-section 492 A MANUAL OF PHYSIOLOGY. of the muscle. Durinp^ the contraction the absolute force diminishes continuall}-, so that a smaller and smaUer weight is sufficient to stop any further contraction, the more the muscle has already shortened before it is applied. At the maximum of the contraction the absolute force is zero. Hence a muscle works under the most favourable conditions when the weight decreases as it is raised, and this is the case with many of the muscles of the body. During flexure of the forearm on the elbow, with the upper arm horizontal, a weight in the hand is felt less and less as it is raised, since Fig. 145. — Influence of Temi'ekatuke on the Muscle Curve. 2, air temperature; i, 25° — 30° C ; 3, 7° — 10° C ; 4, ice in contact with muscle. The 5ih curve s\as taken at a little above air temperature. its moment, which is proportional to its distance from the vertical through the lower end of the humerus, continually diminishes. (6) Influence of Tcmpcrahivc on the Miiscnlar Contraction. — Increase of temperature of the muscle up to a certain limit diminishes the latent period and the length of the curve, and increases the height of the contraction, but beyond this limit the contractions are lessened in height. Marked dimi- nution of temperature causes, in general, an increase in the MUSCLE. 493",. latent period and length, and a decrease in the height of the contraction. It is evident that much depends upon the normal temperature which we start from, and moderate cooling may increase the height of the curve. In the heart the effect of cold in strengthening the beat is often very marked. (c) Influence of rrevioua Stimulation. — If a muscle is stimu- lated by a series of equal shocks thrown in at regular Below is shown the arrangement with which the ' curve figured was obtained. A, femur with gHStrocnemius attached, supported in clamp ; C, metal hook with fine wire attaclied to lever. The wire is con- tinued alona; the lever and connected witlij ,a sewing- needle, the point of which just dips into, the mercury cup D. A wire from one pole of the Daniell cell E dips perma- nently into the mer- cury ; the wire B. from the other pole is attached to the upper end of the muscle or the clamp. When the lever F is. raised so as to with- draw the needle from the cup the muscle is stimulated. V/hen it rela.xesit is again stimulated as soon as the needle again touches the mercury, and so on till it is e.xhausted. Fig. T46.— Fatigl'k Cukvk ok Mt_-scLE (Frog's G.astuo- CNEMIUS). intervals, and the contractions recorded, it is seen that at first each curve overtops its predecessor by a small amount. This phenomenon, which is regularly seen in fresh skeletal muscle, although it was at one time supposed to be peculiarly a property of the muscle of the heart, is called the * staircase,' and seems to indicate that within 494 A MANUAL OF PHYSIOLOGY. limits the muscle is benefited by contraction and its ex- citability increased for a new stimulus. Soon, however, in an isolated preparation, the contractions begin to decline in height, till the muscle is at length utterly exhausted, and reacts no longer to even the strongest stimulation. A conspicuous feature of the contraction-curves of fatigued muscle is the progressive lengthening, which is much more marked in the descending than in the ascending period ; in other words, relaxation be- FiG. 147. — ' Staircase ' IN Skeletal ^■r^ ^ Muscle (Fkogj. comes more and more dimcult Stimulation by arrangement shown in and imperfcCt. It is bynO mcaUS '^' ^^ ' so easy to fatigue a muscle still in connection with the circulation as an isolated muscle. But even the latter, if left to itself, will to some extent recover, and be again able to contract, although exhaustion is now more readily induced than at first. Fig. 148. — 'Staircase' in Cardiac Muscle. Contraction.s recorded on a much more quickly moving drum than in Fig. 147. The contractions were caused by stimulating a heart reduced to standstill by the first Stannius' ligature (p. no). Tlie contractions gradually increase in height. What is the cause of muscular fatigue ? An exact answer is not possible in the present state of our knowledge, but we may fairly conclude that in an isolated preparation it is twofold : (i) The material necessary for contraction breaks down more quickly than it can be reproduced or brought to the place where it is required ; (2) waste products are MUSCLE. 495 formed by the active muscle faster than they can be removed. That even an isolated muscle has a certain store of the material needed for contraction which cannot be all exhausted at once, or which can to a certain extent be replenished by processes going on in the muscle, is shown by the beneficial effect of mere rest. That the accumulation of fatigue products has something to do with the exhaustion is shown by the fact that the muscles of a frog, exhausted in spite of Fig. 149.— Fatigi k Curve ok Skeletal Mlsci.k, {Gastrocnemius of frog, indirect stimulation) taken with arrangement shown in Fig. 163. Time tracing, -'^ of a second. the continuance of the circulation, can be restored by bleed- ing the animal, or washing out the vessels with normal saline solution, while injection of a watery extract of exhausted muscle into the bloodvessels of a curarized muscle renders it less excitable (Ranke). This observer supposed that it was specially the removal of the acid products of contraction (sarcolactic acid and acid potassium phosphate) which restored the muscle. Injection of arterial blood, or even of an oxidizing agent like potassium permanganate, into 496 A MANUAL OF PHYSIOLOGY. the vessels of an exhausted muscle also causes restoration (Kronecker). When a fatigued muscle responds no longer to indirect stimulation, it can still be directly excited. The seat of exhaustion must therefore be either the nerve-trunk or the nerve-endings. It is not the nerve-trunk which is first fatigued, for this still shows the negative variation on being excited. And if the two sciatic nerves of a frog or rabbit be stimulated continuously with interrupted currents of equal strength, while the excitation is prevented from reach- ing the muscles of one limb till those of the other cease to contract, it will be found that when the 'block' is removed the corresponding muscles contract vigorously on stimulation of their nerve. The passage of a constant current through a portion of the nerve or the application of ether between the point of stimulation and the muscles may be used to prevent the excitation from passing down (p. 545). The fatigue caused by voluntary muscular contraction may have its seat (i) in the muscle, (2) in the nerve-endings, (3) in the nerve-trunk, and (4) in the central nervous system. Elaborate experiments on this subject have been recently made (Mosso and Maggiora, Lombard) (p. 546). Lombard found that in his own case fatigue after volun- tary effort was chiefly central, and not in the muscles and nerves themselves. Electrical stimulation, either of a 'tired' muscle or of its nerve, was readily responded to at a time when voluntary contraction was impossible. But since at this time the voluntary power over untired muscles was com- plete, he suggests that part at least of the central fatigue may be in the lower spinal centres. Alcohol, food, rest, and moderate exercise increased the power of voluntary muscular work ; tobacco, hunger, high temperature, general and local fatigue diminished it. Mosso also observed that central fatigue might exist independently of fatigue of the peripheral organs. (i) The, Influence of Drugs on the Contraction of Muscle. — The total work which a muscle can perform, its excitability and the absolute force of the contraction, may all be altered either in the plus or the minus sense by drugs. But in con- MUSCLE. 497 nection with our present subject those drugs which con- spicuously alter the form and time-relations of the muscle- curve have most interest. Of these veratria is especially important. When a small quantity of this substance is injected below the skin of a frog, spasms of the voluntary muscles, well marked in the limbs, come on in a few minutes. These are attended with great stiffness of m.ovement, for while the animal can contract the extensor muscles of its legs so as to make a spring, they relax very slowly, and some time elapses before it can spring again. If it be killed before the reflexes are completely gone, the peculiar alterations in the form of the muscle-curve caused by veratria will be most marked. The poisoned muscle stimulated directly or through its nerve, contracts as rapidly as a normal muscle, while the height of the curve is as great, or Fig. 150. — Veratria Curve. Frog's gastrocnemius. even greater, but the relaxation is enormously prolonged (Fig. 150). This effect seems to be to a considerable degree dependent on temperature ; and it may temporarily disappear when the muscle is made to contract several times without pause. Barium salts, and in a less degree those of strontium and calcium, have an action on muscle similar to that of veratria (p. 547). (e) The individuality of the muscle itself has an influence on the muscle-curve. Not only do the muscles of different animals vary in the rapidity of contraction, but there are also differences in the skeletal muscles of the same animal. In the rabbit there are two kinds of striped muscle, the red and the pale (the semitendinosus is a red, and the adductor magnus a pale muscle), and the contraction of the former is markedly slower than that of the latter. In many fishes and birds, and in some insects, a similar 498 A MANUAL OF PHYSIOLOGY. difference of colour and structure is present, although a physiological distinction has not here been worked out. Even where there is no distinct histological difference, there may be great variations in the length of contraction. In the frog, for instance, the hyoglossus muscle contracts four or five times more slowly than the gastrocnemius. The wave of contraction, which in frogs' striped muscle lasts only about '07 second at any point, may last a second in the forceps muscle of the crayfish, though only half as long in the muscles of the tail. In the muscles of the tortoise the contraction is also very slow. The muscles of the arm of man contract more quickly than those of the Summation of Stimuli and Superposition of Contractions. — Hitherto we have considered a single muscular contraction I is the curve when only one stimulus is • hrown in ; 2, when a second stimulus acts at the time when curve 1 has nearly reached its maximum height. Fig. 151. — Superposition of Contrac- tions. as arising from a single stimulus, and we have assumed that the muscle has completed its curve and come back to its original length before the next stimulus was thrown in. We have now to inquire what happens when a second stimulus acts upon the muscle during the contraction caused by a first stimulus, or during the latent period before the contraction has actually begun ; and what happens when a whole series of rapidly-succeeding stimuli are thrown into the muscle. First let us take two stimuli separated by a smaller interval than the latent period (p. 548). If they are both maximal {i.e., if each by itself would produce the greatest amount of contraction of which the muscle is capable when excited by a single stimulus) the second has no effect what- MUSCLE. 499 ever, the contraction is precisely the same as if it had never acted. But if they are less than maximal, the contraction, although it is a single contraction, is greater than would have been due to the first stimulus alone ; in other words, the stimuli have been summed or added to each other during the latent period so as to produce a single result. Next let us consider the case of two stimuli separated by a greater interval than the latent period, so that the second falls into the muscle during the contraction produced by the first. The result here is very different : traces of two con- tractions appear upon the muscle-curve, the second curve being that which the second stimulus would have caused Fig. 152. — Tetanus. I, 5 stimuli per second ; 2, 15 per second ; 3, 15 per second, when muscle was more exhausted than in 2. alone, but rising from the point which the first had reached at the moment of the second shock (Fig. 151). Although the first curve is cut short in this manner, the total height of the contraction is greater than it would have been had only the first stimulus acted ; and this is true even when both stimuli are maximal. Under favourable circumstances, when the second curve rises from the apex of the first, the total height may be twice as great as that of the contraction which one stimulus would have caused (p. 548). Not only may we have superposition or fusion of two con- tractions, but of an indefinite number ; and a series of rapidly following stimuli causes complete tetanus of the muscle, which remains contracted during the stimulation, or till it is exhausted (Fig. 152). 500 A MANUAL OF PHYSIOLOGY. The meaning of a complete tetanus is readily grasped if, beginning with a series of shocks of such rapidity that the muscle can just completely relax in the intervals between successive stimuli, we gradually increase the frequency (p. 549). As this is done, the ripples on the curve become smaller and smaller, and at last fade out altogether. The maximum height of the contraction is greater than that pro- duced by the strongest single stimulus ; and even after com- plete fusion has been attained, a further increase of the frequency of stimulation may cause the curve still to rise. It is evident from what has been said that the frequency of stimulation necessary for complete tetanus will depend upon the rapidity with which the muscle relaxes ; and everything which diminishes this rapidity will lessen the necessary frequency of stimulation. A fatigued muscle may be tetanized by a smaller number of stimuli per second than a fresh muscle, and a cooled by a smaller number than a heated muscle. The striped muscles of insects, which can contract a million times in an hour, require 300 stimuli per second for complete tetanus, those of birds 100, of man 40, the torpid muscles of the tortoise only 3, The pale muscles of the rabbit need 20 to 40 excitations a second, the red muscles only 10 to 20 ; the tail muscles of the crayfish 40, but the muscles of the claw only 6 in winter and 20 in summer. The gastrocnemius of the frog requires 30 stimuli a second, the hyoglossus muscle only half that number (Richet). We see, then, that there is a lower limit of frequency of stimulation below which a given muscle cannot be com- pletely tetanized, and the question arises whether there is also an upper limit beyond which a series of stimuli becomes too rapid to produce complete tetanus, or, indeed, to cause contraction at all. We may be certain that every stimulus requires a finite time to produce an effect, and it is possible that if the duration of each shock were reduced below a certain minimum, without lessening at the same time the interval between successive excitations, no contraction would be caused by any or all of the stimuli in the series. But above this minimum there apparently lies a frequency of stimulation — at least, when the interval between the stimuli MUSCLE. 501 is reduced exactly in the same proportion as the duration — at which an interrupted current comes to act Hke a constant current, causing a single twitch at its commencement or at its end, but no contraction during its passage. As to this last limit, on the fixing of which much labour has been expended without any harmony of result, it un- doubtedly does not depend upon the frequency of stimula- tion alone ; the intensity of the individual excitations, the temperature of the muscle, and probably other factors affect it. For Bernstein found that with moderate strength of stimulus tetanus failed at about 250 per second, and was replaced by an initial contraction ; with strong stimuli at more than 1,700 per second, tetanus could still be obtained. Kronecker and Stirling, stimulating the muscle by a novel and ingenious method (by induced currents set up in a coil by the longitudinal vibrations of a magnetized bar of iron), saw complete tetanus even at 24,000 stimuli a second ; while V. Kries in a cooled muscle found tetanus replaced by the simple initial twitch at 100 stimuli per second, although in a muscle at 38° C. stimulation of ten times this frequency still caused tetanus. But it is doubtful whether the electrical method of stimulation is capable of solving the problem, because of the difficulty of being sure that the number of excitations is the same as the nominal number of shocks, all the more that even very short currents leave alterations of conductivity and excitability behind them (Sewall), which we shall have to discuss in another chapter (p. 524). It is only while the actual shortening is taking place that a tetanized muscle can do external work. But although during the maintenance of the contraction no work is done, energy is nevertheless being expended, for the metabolism of a muscle during tetanus is greater than during rest. Among other changes, the carbonic acid given off is increased, and lactic acid produced. And upon the whole a muscle is more quickly exhausted by tetanus than by successive single contractions, although there are great differences between different muscles. For example, the muscles which close the forceps of the crayfish or lobster have, as everyone knows, the power of most obstinate contraction. Richet tetanized S02 A MANUAL OF PHYSIOLOGY. one for over seventy minutes, and another for an hour and a half, before exhaustion came on, while a tetanus of a single minute exhausted the muscles of the crayfish's tail. The gastrocnemius of a summer frog kept up for twelve minutes, and a tortoise muscle for forty minutes. Continuous stimulation is not always necessary for the production of continuous contraction ; in some conditions a single stimulus is sufficient. A blow with a hard instru- ment may cause a dying or exhausted, and in thin persons even a fairly normal, muscle to pass into long-continued contraction. This so-called ' idio- muscular ' contraction seems to depend, in part at least, on the great intensity of the stimulus. The rate at which the wave of muscular contraction travels may be measured by stimulating the muscle at one end, and recording, by means of levers, the movements of two points of its surface as far apart from each other as possible. Time is marked on the tracing by means of a tuning-fork, and the distance between the points at which the two curves begin to rise from the base-line divided by the time gives the velocity of the wave. Another method is founded upon the measurement of the rate at which the negative variation (p. 557) passes over the muscle, this being the same as the velocity of the contraction-wave. In frog's muscle it is about three metres a second, or six miles an hour. Rise of temperature increases, fall of temperature lessens it. When a muscle is excited through its nerve the contrac- tion springs up first of all about the middle of each mus- cular fibre where the nerve-fibre enters it, and then sweeps out in both directions towards the ends. But so long is the wave, that all parts of the fibre are at the same time in- volved in some phase or other of the contraction. And this is the case even when the end of a long muscle like the sartorius is artificially stimulated. The wave of contraction in unstriped muscle lasts a relatively long time at any given point, and in tubes like the intestines and ureters, the walls of which are largely com- posed of smooth muscle arranged in rings, the wave shows MUSCLE. 503 itself as a gradually-advancing constriction travelling from end to end of the organ. There is no evidence that the con- traction of smooth muscular fibres is discontinuous — that is, composed of summated contractions like a tetanus ; it appears to be a greatly-prolonged simple contraction of the kind called ' tonic' An artificial stimulus, mechanical or elec- trical, causes, after a long latent period, a very definitely- localized contraction in a rabbit's ureter, which slowly spreads in a peristaltic wave in one or both directions along the muscular tube. Here, as in the cardiac muscle, the excitation passes from fibre to fibre, while in striped skeletal muscle only the fibres excited directly or through their nerves seem to contract. That the rhythmical contraction of the heart is not a tetanus has already been seen. It is a simple contraction, intermediate in its duration and other characters between the twitch of voluntary muscle and the tonic contraction of smooth muscle. The contraction both of unstriped and of cardiac muscle is lengthened and made stronger by distension of the viscera in whose walls they occur, just as a skeletal muscle contracts more powerfully against resistance. Voluntary Contraction. — It is often stated that the volun- tary contraction is a tetanus, but in favour of this belief there is very little direct evidence. One of the strongest buttresses of the theory of natural tetanus has been the muscle-sound. Discovered about eighty years ago, first by Wollaston and then by Erman, half a century passed away before it was investigated more fully by Helmholtz. The latter observer, confirming the results of his predecessors, put down the pitch of the low rumbling sound heard when the masseter contracts in closing the jaws at 36 to 40 vibra- tions per second. He found, however, that pieces of watch- spring vibrating about 19*5 times per second, were more affected, when attached to muscle thrown into voluntary contraction, than those that vibrated at a smaller or a greater rate. He therefore concluded that the fundamental tone of the muscle corresponded to this frequency, and that the sound heard was really its octave or first harmonic (p. 222), strengthened by the resonance of the ear. It seems 504 A MANUAL OF PHYSIOLOGY. to be now generally accepted that vibrations of various fre- quency, and even irregular oscillations, can give rise to the same resonance tone ; so that the muscle-sound does not really enable us to say much about the nature of the volun- tary contraction. But several observers (Schafer, Horsley, v. Kries) have noticed periodic oscillations, at the rate of 8 to 10 per second, in the curves taken from voluntarily contracted muscles, and from muscles excited through stimulation of the motor areas of the surface of the brain. And since this rate remains the same whether the motor cortex, the corona, radiata, or the spinal cord is excited, and, unlike the rate of response to excitation of peripheral nerves, is independent of the frequency of stimulation, it has Fig. 153.— Contractions caused ]Y Shmulation of the Spinal Cord. been supposed to represent the rhythm with which impulses are discharged from the motor cells of the cord. Other observers have seen a rhythm of 20 per second ; while Haycraft denies that regular oscillations occur at all, and thinks that irregularities in the contraction, connected with a want of co-ordination of all the fibres, cause the muscle-sound by drawing forth the resonance tone of the ear itself. Loven, however, found the rhythm of strychnia (Fig. 153) tetanus in the frog about 8 to 10 per second ; and asserted that by means of the capillary electrometer (p. 469) an electrical oscillation of 8 per second could be demon- strated in voluntarily contracted muscle. This last state- ment, if confirmed, would be strong evidence for the MUSCLE. 505 discontinuity of at least some voluntary contractions. But against it we must put the fact that secondary tetanus (p. 571) is not caused by muscle in voluntary contraction, except (and even this is doubtful) just at the beginning. This, indeed, is not incompatible with the existence of natural tetanus, since chemical stimulation, which certainly sets up a state of contraction analogous to experimental tetanus, does not cause secondary tetanus ; but we still lack a decisive proof that voluntary contraction is maintained by a strictly intermittent outflow of nervous energy, and not by a continuous outflow, which, it may be, remits and is re- inforced at intervals. In any case, some voluntary contrac- tions, namely the shortest possible, cannot be tetanic. For a voluntary movement can be executed in yV to TrV of a second, which, if we take the greatest frequency of dis- charge in natural tetanus that has been suggested, would allow time only for a single oscillation, caused by a single impulse. (3) Thermal Phenomena of the Muscular Contraction. — When a muscle contracts its temperature rises ; the production of heat in it is increased. This is most distinct when the muscle is tetanized, but has also been proved for single con- tractions. The change of temperature can be detected by a delicate mercury or air thermometer ; and, indeed, a thermometer thrust among the thigh-muscles of a dog may rise as much as i' to 2° C. when the muscles are thrown into tetanus. In the isolated muscles of cold-blooded animals the increase of temperature is much less ; and electrical methods, which are the most delicate at present known, have generally been used for its detection and measurement. They depend either upon the fundamental fact of thermo-elec- tricity, that in a circuit composed of two metals a current is set up if the junctions of the metals are at different temperatures : or upon the fact that the electrical resistance of a metallic conductor varies with its temperature. On the former principle the thermopile has been constructed (Fig. 154), on the latter the bolometer., or ^electrical-resistance thermometer.' Where no very fine differences of temperature are to be measured, a single thermo-junction of German silver and iron, or copper and ircn, is inserted into a muscle or between two muscles. But the electro- motive force, and, therefore, the strength of the thermo-electric current, is proportional for any given pair of metals to the number of 5o6 A MANUAL OF PHYSIOLOGY. junctions, and for delicate measurements it may be necessary to use several connected together in series. A thermopile of antimony- bismuth junctions gives a stronger current for a given difference of temperature than the same number of German silver-iron couples, but from its brittle nature is otherwise less convenient. The direction of the current in the circuit is such that it passes through the heated junction from bismuth to antimony, and from copper or German silver to iron. Knowing this direction, we are aware of the changes of temperature which take place from the move- ments of the mirror of the galvanometer with which the pile is con- nected. The galvanometer must be of low resistance, since the electromotive force of the thermo-electric currents is small, and a high resistance would cut down their intensity too much. A, a single copper- iron thermo - electric couple ; B, two pairs, one inserted into the tissue /', the other dip- ping into water in a beaker a. The tem- perature of the water may be adjusted so that the galvanometer shows no deflection. The tem- perature of the tissue is then the same as that of the water. Fig. 154. The muscle which is to be excited is brought into close contact with one junction or set of junctions, the other set being kept at constant temperature by immersing them in water, or covering them with muscle that is not to be stimulated. The image will now come to rest on the scale ; and excitation of the muscle will cause a movement indicat- ing an increase of temperature in it, the amount of which can be calculated from the deflection. In this way Helmholtz observed a rise of temperature of •14° to '18° C. in excised frogs' muscles when tetanized for a couple of minutes. Heidenhain, with a very delicate pile, found a rise of 'ooi" to '005' C. for a single contraction of a frog's muscle. On the assumption that the pile had time to take on the temperature of the muscle before there was any appreciable loss of heat, this would be equal to the production by every MUSCLE. 507 gramme of muscle of a thousandth to five-thousandths of a small calorie (p. 420) of heat. From Pick's observations we may take about three-thousandths of a small calorie as the maximum production of a gramme of frog's muscle in a single contraction. It is certain that when work is done by a muscle an equi- valent amount is subtracted from its sum-total of energy, and we might therefore expect that the heat produced in contraction should diminish as the work increases. But experiment does not fulfil this expectation. The manner and the rate of its expenditure of energy depend upon the conditions under which the muscle is placed. The mere stretching of a muscle increases its metabolism, and there- fore its heat-production ; and a stretched muscle, when caused to contract, produces more heat than if it had started without tension, and still more heat when it is fixed so that it cannot shorten during stimulation. This last fact does not, however, prove that the heat-production is greater when no work is done, because the tension increases during excitation when contraction is prevented, and we know that increase of tension alone causes more heat to be given out. For example, more heat is produced by a muscle when it contracts isometrically than when it contracts isotonically. When a muscle, excited by maximal stimuli, is made to lift continuously increasing weights, both the work done and the heat given out increase up to a certain limit. The muscle, as it were, burns the candle at both ends. This would be of itself enough to show that there is no fixed relation between the work and the heat-production; although the latter reaches its maximum somewhat sooner than the former. We have already seen that when a muscle is cooled, or fatigued, or poisoned with veratria or with suprarenal extract, the stress of the change falls chiefly upon the relaxation. This indicates that the relaxation is by no means a mere elastic recoil, but a physiological process as important as the contraction itself; and this conclusion is strengthened by the fact we have now to mention, that not only is heat produced during the actual shortening, but also during the 5o8 A MANUAL OF PHYSIOLOGY. relaxation. If a muscle is allowed to contract without raising any weight, and is loaded just at the top of its lift, so that the load acts only during relaxation, more heat is produced than when no weight is applied ; and the heavier the weight, the greater is the heat-production. This result seems to invalidate an experiment which has been quoted as proof that the work done by a muscle is represented by a deficit in the heat-production, as compared with that of another muscle contracting under the same conditions, but doing no work. Fick allowed a muscle to raise a weight, which was either removed at the height of the con- traction, or permitted to descend again with the muscle during relaxation. In the first case external work was done, for the weight caught at the top of the ' lift ' could be allowed to fall again to its old level and do work in its descent. In the second case no work was transferred beyond the muscle. Now, Fick actually found that the heat produced was greater in the second case than in the first ; and he argued from this that when a muscle does work, an equivalent quantity of energy is subtracted from that which would otherwise appear as heat. But the mere fact that one of the muscles was loaded during relaxation might account for the difference, as the load would increase the heat-produc- tion during the descent, apart from the transformation of its lost energy of position into heat through the ' shattering ' of the muscle. The fraction of the total energy transformed which appears as muscular work, varies with the conditions of the contraction. The greater the resistance, the larger is the proportion of the energy which appears as work, the smaller the proportion which appears as heat ; but even in the most favourable case, an excised frog's muscle never does work equal to more than \ of the heat given off. Generally the ratio is much less, and may sink as low as 4^. In the intact mammalian body it is probable that the muscles work at least as economically as the excised frog's muscle under the most favourable conditions ; for both experiment and calculation show (p. 430) that in a normal man not less than \, nor much more than \, of the whole energy transformed MUSCLE. 509 in the body is converted into work. But in any case the heat - producing mechanism and the work - producing mechanism of muscle are certainly in some respects distinct, and a variation in the activity of the one is not necessarily associated with a corresponding variation in the activity of the other. (4) Chemical Phenomena of the Muscular Contraction. — We as yet know but little regarding the chemical composition of living muscle, and are unlikely ever to know much, since most chemical operations cause the immediate death of the tissue. The composition of dead mammalian muscle may be stated, in round numbers, as follows, but there are considerable variations, even within the same species. Water ... 75 per cent. Proteids ... ... ... ... 20 ,, Fats ... ... ... ... 2 ,, •\T-» [Kreatin Nitrogenous (,,,. metabolites. Uj ,, . I^Hypoxanthin Carbohydrates.- o i^*^'^- -j ^ I^Sarcolactic acid Inosit I Salts, chiefly carbonate and phosphate of potassium, less than I per cent. There is more water in the muscles of young than of old animals (v. Bibra), and more in tetanized than in rested muscle (Ranke). The fats probably belong only to a small extent, if at all, to the actual muscle-fibres. In lean horse- flesh Pfliiger found only 0*44 per cent, of fat, o'35 per cent, of glycogen, and no sugar at all. The total nitrogen was 3'2i per cent, of the moist tissue. It would be natural to expect that the proteids, which bulk so largely among the solids of the dead muscle, and which are so obviously important in the living muscle, should be affected by contraction. But up to the present time no quantitative difference in the proteids of resting and exhausted muscle has ever been made out. The following chemical changes, however, have been definitely established. In an active muscle — 5IO A MANUAL OF PHYSIOLOGY. (a) More carbonic acid is produced. (d) More oxygen is consumed. (c) Sarcolactic acid is formed. (d) Glycogen is used up. (e) The substances soluble in water diminish in amount ; those soluble in alcohol increase. That the carbonic acid is not formed by direct oxidation, but by the splitting up of a substance or substances with which the oxygen has previously combined, is, as has already been shown (pp. 203, 205, 208), highly probable. For (to recapitulate) (a) no free oxygen exists in muscle. None can be pumped out. (b) A muscle isolated from the body will go on contracting for a long time in an atmosphere devoid of oxygen, e.g., in an atmosphere of hydrogen, (c) When artificial circulation is maintained through isolated muscles the amount of carbonic acid gas produced does not run parallel with the quantity of oxygen consumed. The latter is dependent on the temperature of the muscle, being increased when the muscle is heated, diminished when it is cooled. The production of carbonic acid, on the contrary, is, within a wide range, independent of the temperature. Formation of Sarcolactic Acid. — Reaction of Muscle. — To litmus paper fresh muscle is amphicroic, that is, it turns red litmus blue and blue litmus red. This is due, partly at least, to the phosphates. Monophosphate (tribasic phosphoric acid in which one hydrogen atom is replaced, say by sodium or potassium) reddens blue litmus, while diphosphate (where two hydrogen atoms are replaced) turns red litmus blue. And since the addition of an alkali changes some of the monophosphate into diphosphate, and the addition of an acid brings about the reverse effect, liquid containing phos- phates cannot be made neutral to litmus. It is therefore much better, in testing the reaction of muscle, to use litmoid or turmeric paper or phenolphthalein. Litmoid differs from litmus in not being affected by monophosphates. Diphosphates turn red litmoid blue (Rohmann). A cross - section of fresh muscle is about neutral to turmeric paper (sometimes faintly acid) while that of a rigid or tetanized muscle is distinctly acid, brown turmeric being turned strongly yellow. The sarcolactic acid pro- MUSCLE. 511 duced in rigor and activity is at once neutralized, as is shown by the fact that blue litmoid paper is not reddened, as it would be by free sarcolactic acid. The neutralization takes place at the expense of the sodium carbonate and disodium phosphate, the latter being changed into monophosphate, which, in part at least, causes the acid reaction to turmeric (Rohmann). Glycogen is the one solid substance which has been definitely proved to diminish in muscle during activity. It accumulates in a resting muscle, especially in a muscle whose motor nerve has been cut ; rapidly disappears from the muscles of an animal made to do work while food is withheld ; or from the muscles of an animal poisoned by strychnia, which causes violent muscular contractions. What substance is the sarcolactic acid formed from ? From what we know of the production of lactic acid both outside the body and in the intestine from carbo-hydrates, it might seem a most plausible suggestion that in the active muscle it comes from glycogen. But all the evidence points the other way ; e.g., in rigor mortis sarcolactic acid is pro- duced just as in muscular contraction. Not only so, but according to Ranke every isolated muscle has a certain maximum of acidity, which it reaches either through con- traction, or through rigor, or through contraction followed by rigor. Yet in rigor mortis the quantity of glycogen is un- altered (Boehm). The probability is that the sarcolactic acid is formed from proteid, perhaps by the action of a ferment. Source of the Energy of Muscular Contraction. — The facts just mentioned show that glycogen may be one of the sources of muscular energy, but it cannot be the only source, for its amount is too small. For example, the heart of an average man, which weighs 2S0 grammes, contains about 60 grammes solids, and among these not more than 1*5 grammes glycogen. In twenty-four hours it produces, even on a low estimate, at least 300,000 calories of heat, equivalent to the complete combustion of more than 70 grammes of glycogen. To supply this amount the whole store of glycogen in the heart would have to be used and replaced every half-hour. But the accumulation of glycogen 512 A MANUAL OF PHYSIOLOGY. is immensely slower in the muscles of a rabbit made glycogen- free by strychnia, and therefore we have to look around for some other source of energy to supplement the glycogen. We have already brought forward evidence (p. 401) that, under ordinary circumstances, not a great deal, at any rate, of the energy of muscular contraction comes from the proteids. Of carbohydrates, the only one except glycogen which is at all adequate to the task of supplying so much energy is the glucose of the blood. The quantity of blood passing through the coronary circulation has been estimated at 30 cc. per 100 grammes of cardiac muscle per minute (Bohr and Henriques), which would be equivalent for an average man to about 120 litres in twenty-four hours. This quantity of blood will contain at least 150 grammes of glucose, and 80 grammes will suffice to supply all the heat produced by the heart. Of proteids a little less than 70 grammes would be needed, of fat about 30 grammes. We see therefore how intense must be the metabolism that goes on in an actively contracting muscle. On any probable assumption as to the source of muscular energy a quantity of material equal to the whole of its solids must be used up by the heart in twenty-four hours. Or, to put it in another way, the heart requires not less than half its weight, possibly its weight, of ordinary solid food in a day. The body as a whole requires Jg- to ^V of its weight. To sum up : It is universally admitted that carbohydrates can yield energy for muscular work. It has been demon- strated by Zuntz and his pupils and by others that fat can do so. The experiments of Pfliiger, to which we have already alluded (p. 401) have shown that when an animal is fed on lean meat, the muscular work done is far too great to have come from non-proteid substances. We must conclude, therefore, that when carbohydrates and fats are plentiful in the food, the greater part of the energy of muscular contraction comes from them ; it comes on the other hand from proteids, when the carbohydrates and the fats are restricted, and the proteids plentifully supplied. Not only so, but these three groups of food substances yield muscular energy in isodynamic relation. In other words. MUSCLE. 513 a given amount of muscular work requires the expenditure of approximately the same quantity of chemical energy, whether it comes almost entirely from proteid, or chiefly from carbohydrates, or chiefly from fat. And this is what we should expect in a machine like the animal bod}^, endowed with such a marvellous power of adaptation, of making the best of everything. Rigor Mortis. — When a muscle is dying its excitability, after perhaps a temporary rise at the beginning, diminishes more and more until it ultimately responds to no stimulus, however strong. The loss of excitability is not in itself a sure mark of death, for, as we have seen, an inexcitable muscle may be partially or completely restored, but it is followed, or, where the death of the muscle takes place very rapidly, perhaps accompanied by a more decisive event, the appearance of rigor. The muscle, which was before soft and at the same time elastic to the touch, becomes firm ; but its elasticity is gone. The fibres are no longer translucent, but opaque and turbid. If s'hortening of the muscle has not been opposed, it will be somewhat contracted, although the absolute force of this contraction is small compared with that of a living muscle, and a slight resistance is enough to prevent it. The reaction is now distinctly acid. This is rigor mortis, the death-stiffening of muscle. An insight into the real meaning of this singular and sometimes sudden change was first given by the experiments of Kiihne. He took living frog's muscle, freed from blood, froze it, and minced it in the frozen state. The pieces were then rubbed up in a mortar with snow containing i per cent, of common salt, and a thick neutral or alkaline liquid, the muscle-plasma, was obtained by filtration. This clotted into a jelly when the temperature was allowed to rise, but at 0° C. remained fluid. The clotting was accompanied by a change of reaction, the liquid becoming acid. An equally good, or better, method is to use pressure for the extraction of the plasma from the frozen fragments of muscle. A low temperature is essential, otherwise the plasma will coagulate rapidly within the injured fibres. 514 A MANUAL OF PHYSIOLOGY. A similar plasma can be expressed from the skeletal muscles of warm-blooded animals (Halliburton), and with greater difficulty from the heart. Attempts to obtain it from smooth muscle have hitherto failed, possibly because of the unfavourable anatomical conditions. When the muscle, after exhaustion with water, is covered with a solution of a neutral salt, a 5 per cent, solution of magnesium sulphate or 10 per cent, solution of ammonium chloride being probabl}'- the best, a proteid passes into solution, which is identical with the myosin of the clotted plasma. If the solution is diluted it clots just as the muscle- plasma clots, and the clot can be dissolved and reproduced at will (Practical Exercises, p. 551). The addition of potas- sium oxalate does not prevent coagulation of muscle- extracts, as it does of blood and blood-plasma. From all this we gather that rigor mortis is essentially a clotting or coagulation of a substance which yields myosin. What this substance is we cannot tell. Some have sup- posed that in the living muscle there exists a body, niyo- sinogcn, which is the direct precursor of the myosin in the muscle-clot or within the fibres in rigor mortis, and which is related to it as fibrinogen is related to fibrin in the clotting of blood. It has even been assumed that this very myosin- ogen is formed when myosin is dissolved in a salt solution ; but this hypothesis is perhaps not backed by sufficient evidence. Why does coagulation of myosin occur at the death of the muscle ? To this question no clearer answer can be given than to the question why blood clots when it is shed. Just as a fibrin ferment is developed when blood begins to die, a myosin ferment, which aids coagulation, appears to be developed in dead or dying muscle. It has been suggested that myosin, sarcolactic acid and carbon dioxide, are all products of some complex body which breaks up both at the death of the muscle, and during contraction, and that, indeed, contraction is only a transient and removable rigor (Hermann). According to Hoppe-Seyler, it is greatly against this view that neither rigor mortis nor the extraction of the myosin with salt solution alters the doubly refractive substance, which is MUSCLE. 515 almost universally looked upon as the essentially contractile part of the muscle. Danilewski and others, however, have stated that the doubly refractive discs contain myosin. A great deal of the muscle substance remains after the myosin has been extracted as fully as possible by repeated ex- haustion with the salt solution. A dilute acid solution ("I per cent. HCl, ^.,i^.) may dissolve out ten times as much substance from muscle as a 10 per cent, solution of sodium chloride. Dilute acids or alkalies turn all the coagulable proteids, myosin included, into acid or alkali-albumin. Although it cannot be admitted that there is any funda- mental connection between rigor and contraction, there are some superficial resemblances. In both there is 1. Shortening. 3. Formation of fixed acid and CO.,. 2. Heat-production. 4. An electrical change (p. 556). Another analogy might be forced into the list by anyone who was determined to see only rigor in contraction : the rigor passes off as the contraction passes off, although the ' resolu- tion ' of a rigid muscle takes days, the relaxation of an active muscle a fraction of a second. The disappearance of rigor is not dependent on putrefaction ; it takes place when growth of bacteria is prevented (Hermann). Various influences affect the onset of rigor. Fatigue hastens it ; heat has a similar effect ; the contact of caffeine, chloroform and other drugs causes most pronounced and immediate rigor. Blood applied to the cross-section of a muscle first stimulates the fibres with which it is in contact, and then renders them rigid. But it is to be remembered that normally the blood does not come into direct contact even with the sarcolemma, much less with its contents. The effect of heat is of special interest. A skeletal muscle of a frog, like the gastrocnemius, if dipped into normal saline solution at 40° or 41° C. goes into rigor at once ; the frog's heart requires a temperature 3° or 4° higher ; the distended bulbus aortse can stand even a temperature of 48° for a short time. An excised mammalian muscle passes into immediate rigor at 45° to 50°. In heat rigor the reaction of the muscle becomes strongly acid, and the acidity is due to a fixed acid (sarcolactic), not to carbon dioxide, although the production 5i6 A MANUAL OF PHYSIOLOGY. of the latter is greatly increased. A small quantity of heat is produced, and the temperature of the muscle may be raised as much as t,V C. This is probably due chiefly to the increased chemical change, and only to a slight extent to the physical alteration in the myosin. Heat rigor is, in fact, a greatly accelerated rigor mortis, and the myosin, although clotted, is not rendered insoluble like a heat-coagulated proteid (p. 552). When muscle is suddenly raised to a temperature of 75° to 100° C, we have quite a different series of events. There is no acid reaction, no evolution of carbonic acid ; the muscle is indeed rigid, but true rigor has not taken place, and the rigidity is due to coagulation of the proteids by heat. Rigor is a change which cannot go on when once the com- paratively mobile substance of the living muscle, or of the muscle in the act of dying, has been converted into the stable form of coagulated proteid. No sarcolactic acid is pro- duced in scalded muscle, perhaps because the acid-forming ferment (p. 511) is killed by the high temperature. The so- called rigor caused by alcohol and by acids is a coagulation of the proteids, and not true rigor. No heat is produced, and no carbonic acid given off. In a human body rigor generally appears not earlier than an hour, and not later than four or five hours, after death. In exceptional cases, however, it may come on at once, and the annals of war and crime contain instances where a man has been found after death still holding with a firm grip the weapon with which he had fought, or which had been thrust into his hand by his murderer. It is related that after one of the battles of the American Revolutionary War some of the dead were found with one eye open and the other closed as in the act of taking aim. A high tem- perature favours a rapid onset ; a body wrapped up in bed will, other things being equal, become rigid sooner than a body lying stripped in a field. Muscular exhaustion, as we have said, is another favouring condition : hunted animals and the victims of wasting diseases go quickly into rigor. It is a rule, but not an invariable one, that rigor, when it comes on quickly, is short, and lasts longer when it comes MUSCLE. 517 on late. All the muscles of the body do not stiffen at the same time ; the order is usually from above downwards, beginning at the jaws and neck, then reaching the arms and finally the legs. After two or three days the rigor disappears in the same order. The position of the limbs in rigor is the same as at death ; the muscles stiffen without contracting. This can be strikingly shown on a newly-killed animal by cutting the tendons of the extensors of one leg and the flexors of the other ; when natural rigor comes on the legs remain just as they were. If heat rigor, however, is caused, the one leg becomes rigid in flexion and the other in extension. The Removability of Rigor. — It has been asserted that rigor can be removed and excitability restored. After in- terrupting the circulation in the hind-legs of rabbits by com- pression or ligation of the abdominal aorta, and so causing the muscles to become rigid, Brown-Sequard saw them recover their irritability when the blood was again allowed to reach them. He performed a similar experiment with artificial circulation through the hand of an executed criminal, and got a like result. But grave doubt has been cast upon these experiments by later observations, and it is now almost universally believed that no really rigid muscle has ever been restored, and that the apparent recovery which Brown-Sequard saw was due to the muscles not having been completely rigid. Heubel has, however, stated that the rhythmical contractions of the frog's heart can be restored by blood, after rigor has been caused by heat and in other ways ; and although we cannot transfer these results directly to skeletal muscle, they would show, if confirmed, that the question is not yet closed. CHAPTER X. NERVE. The voluntary movements are originated by impulses from the brain, which reach the muscles along their motor nerves. The involuntar}' movements are in many cases able to go on in the absence of central connections, but are normally under central control. Everywhere the connection between the brain and cord and the peripheral organs, be they muscles, glands, or sensory mechanisms, is made by nerve- fibres ; and these are called peripheral nerve-fibres to dis- tinguish them from the fibres of the central nervous system itself. An ordinary peripheral nerve like the sciatic is made up of a number of bundles of nerve-fibres. Connective tissue surrounds and separates the bundles, and also penetrates in fine septa within them and between the individual fibres, forming a framework for their support, and carrying the bloodvessels and lymphatics. Each medullated nerve-fibre (Plate V. i), consists of two sheaths enclosing an axis-cylinder, which runs from end to end of it without break, and is connected centrally, either directly or indirectly, with a nerve-cell. The axis cylinder is the essential conducting part of the fibre, for it is present in every nerve-fibre, and towards the periphery it is alone present. The innermost, and by far the thickest, of the sheaths is the medullary sheath, or white substance of Schwann, which is of fatty nature, and is blackened by osmic acid. It undergoes a kind of coagulation at death, loses its homogeneity, and shows a double contour. This sheath is not continuous, but is broken by constrictions of the outer sheath, called nodes of Ranvier, into numerous segments. The outer sheath, or neurilemma, is a thin, structureless envelope immediately external to the medulla. It invests the nerve-fibre, as the sarcolemma does the muscle-fibre. In each internodal segment immediately under the neurilemma lies a nucleus surrounded by a little protoplasm. Medullated fibres such NERVE. 519 as those described are by far the most numerous in the cerebro- spinal nerves ; but they are mixed with a few fibres which contain no white substance of Schwann, and are, therefore, called non- medullated (Plate V. i). In these the axis-cylinder is covered only by the neurilemma. In the sympathetic system the non-meduUated variety is present in greater abundance than the medullated. In the central nervous system the medullated fibres possess no neuri- lemma. So far as we know, the only function of nerve-fibres is to conduct impulses from nerve-centres to peripheral organs, or from peripheral organs to nerve-centres, or from one nerve-centre to another. /\nd in the normal body these impulses never, or only very rarely, originate in the course of the nerve-fibres ; they are set up either at their peripheral or at their central endings. By artificial stimulation, how- ever, a nerve-impulse may be started at any part of a fibre, just as a telegram may be despatched by tapping any part of a telegraph wire, although it is usually sent from one fi.xed station to another. The Nerve-impulse : its Initiation and Conduction. What the nerve-impulse actually consists in we do not know. All we know is that a change of some kind, of which the only external token is an electrical change, passes over the nerve with a measurable velocity, and gives tidings of itself, if it is travelling along efferent fibres (that is, out from the central nervous system), by the contraction or inhibition of muscle or by secretion ; if it is travelling along afferent fibres (that is, up to the central nervous system), by sensa- tion, or by reflex muscular or glandular effects. Whether the wave which passes along the nerve is a wave of chemical change, or a wave of mechanical (molecular) change, there is no definite experimental evidence to decide. That chemical changes go on in living nerve, we need not hesitate to assume ; and, indeed, if the circulation through a limb of a warm-blooded animal be stopped for a short time, the nerves lose their excitability. But the metabolism appears to be very slight compared with that in muscle or gland. Even in active nerve no measurable production of carbonic acid has ever been observed, nor, in fact, has any 520 A MANUAL OF PHYSIOLOGY. chemical or physical difference between the excited and the resting state ever been unequivocally made out. Neither in cold-blooded nor in mammalian nerves does there seem to be any sensible rise of temperature during stimulation. Stimulation of Nerve. — -With some differences, the same stimuli are effective for nerve as for muscle (p. 480) ; but chemical simulation is not in general so easily obtained. In fact, it is doubtful whether any great rehance should be placed on many of the observations hitherto made with this mode of excitation. For it has been shown that the current of rest of the nerve (p. 556), when a short-circuit is formed for it by a drop of any conducting liquid applied to a fresh cross- section (the usual method of experimenting on chemical stimulation), may of itself cause excitation (Hering). Griitzner uses equimolecular solutions for experiments on chemi- cal stimulation ; i.e., solutions which contain an equal number of molecules of the substances to be tested in a given volume of water. He has found that for motor nerves the halogen salts have a stimulating power in the order of their molecular weights ; e.g., Nal is stronger than NaBr, and NaBr than NaCl. Sensory nerves are much less susceptible to chemical stimulation. Bile or bile salts, for example, which stimulate motor nerves, have no effect on sensory. A sugar solution, which excites motor nerves, does not alter the rate of respiration when applied to the central end of the vagus, which, however, is excited by potassium chloride (p. 178). In non-narcotized animals reflex secretion of saliva is caused by stimulation of the central end of the lingual with sodium chloride (Wertheimer). Mechanical stimulation has been carried to great perfection by Heidenhain, and especially by Tigerstedt. By means of an instrument invented by the latter, not only may a regular tetanus be obtained, but the strength of the stimulus (fall of a weight) can be graduated with fair accuracy within a considerable range. He found that the smallest amount of work spent on a frog's nerve which would suffice to excite it was a little less than a gramme-millimetre — that is, the work done by a gramme falling through a distance of a milli- metre. No doubt a great part of this is wasted, as a much smaller quantit}^ of work done by an electrical current, which may be supposed to act more directly on the excitable constituents, suffices to stimulate a nerve. Thus, while the NERVE. 521 minimal mechanical stimulus may have a heat-equivalent of about -;- X — g gramme-degree, the heat-equivalent of the minimal electrical stimulus may easily be less than — X — — gramme-degree, or one-millionth part of the former. A kilogramme-degree is equivalent to 424 kilogramme-metres of work ; therefore, a gramme-millimetre of work is equivalent to — ■ gramme-degree, or, say, — x — r gramme-degree. This 424,000 D ° ^ 4-2 10' ° ° corresponds to Tigerstedt's minimum mechanical stimulus. A piece of nerve of 100,000 ohms resistance may be excited by a current passed for -^\^ second when the difference of potential between its ends is only yi^ of a volt. Taking the work done in this case as measured by the heat produced, we get work (W) = H rp J. = ^ ' where E is the electromotive force, / the time of flow of the J . current, J Joule's equivalent, and R the resistance. Expressing these in C.G.S. (centimetre — gramme — second) units, we have : -.,. \ioo>' 100 I I VV = = X 42x10*^x10^x100,000 4*2 10^'' as the work done bj' an electrical stimulus sufficient to excite a nerve. S. P. Langley has shown that the work done by the minimal, tiatiiral or specific, stimulus for the retina (green light) may be as little as — 1 erg* ; i.e., — - x - ,- gramme-degree, or 10,000 times less than 16* 4" 2 lo^'' the minimal electrical stimulus, on our assumptions, for the naked nerve-trunk of a frog. But these assumptions are quite rough, and it is possible that the energy of the minimum artificial stimulus is no greater than that of the minimum natural stimulus of the retina. The laws of electrical stiimilaiion for nerve are essentially the same as those we have already discussed for muscle (p. 484). The voltaic current stimulates a nerve, as it does a muscle, at closure and opening, and not in general during the flow, but the exceptions to this rule are far less frequent in nerve than in muscle. Induction shocks are relatively more powerful stimuli for nerve than the make or break of a voltaic current. The opposite, as we have seen, is true of muscle ; and, upon the whole, we may say that muscle is more sluggish in its response to stimuli, and is excited less easily by very brief currents, than nerve is. An apparent * Here we take an erg as equivalent to tuW gramme- centimetre. 522 A MANUAL OF PHYSIOLOGY. illustration of this difference is the fact that the nervous excitation has no measurable latent period, while muscular excitation has. But it is quite possible that, if the condi- tions of experiment were as favourable in nerve as in muscle, a sensible latent period might be found here too. In nerve as in muscle, strength of stimulus and intensity of response correspond within a fairly wide range, when we take the height of the muscular contraction as the measure of the nervous excitation. Superposition of stimuli, super- position of contractions, and complete tetanus, are caused by stimulating a muscle through its nerve, just as by stimulat- ing the muscle itself (p. 498). The excitability of nerve, as measured by the muscular response to stimulation, is increased, for induction shocks or voltaic currents of short duration, by rise of temperature up to about 30° C, and diminished by fall of temperature. It has been lately suggested that this increase of excitability is only apparent, and due to the strengthening of the current by diminution of the resistance, since the resistance of all animal tissues, like that of electrolytic conductors in general, diminishes as the temperature rises (Gotch). Cooling of the nerve, even to 5° C, increases the excitability for currents of long duration (several hundredths of a second). The con- ductivity for the nervous impulse — that is, the power of a portion of the nerve to conduct an impulse set up elsewhere — is undoubtedly increased by heat and diminished by cold. Drying of a nerve at first increases its excitability ; and the same is true of separation of a nerve from its centre. In the latter case the increase of irritability begins at the proximal end of the nerve, and travels towards the peri- phery. As time goes on, the excitability diminishes, and ultimately disappears in the same order (Ritter-Valli Law). At a certain stage it may be found that a given stimulus causes a smaller and smaller contraction the farther down the nerve — that is, the nearer to the muscle — it is applied. On this was based the now abandoned * avalanche theory,' according to which the impulse continually unlocked new energy as it passed along the nerve, and so gathered strength in its course like an avalanche. NERVE. 523 Electrotonus. — Although the constant current does not, unless it is very strong or the nerve very irritable, cause stimulation during its passage, it modifies profoundly the excitability and conductivity of the nerve. (In man a certain amount of tonic contraction — galvanotonns — is normally seen during the passage of a strong current through a nerve.) In the neighbourhood of the kathode Fig. 155. — DiA'.RAM of Changes of Kxcitabilitv anu CoNDUcrivriY produced IN a Nekve by a Voltaic Curkent. E, changes of excitability during the flow of the current, according to Pfliiger. The ordinates drawn from the abscissa axis to cut the curve represent the amount of the change. C(i), changes of conductivity during the flow of a moderately strong current. Conductivity greatly reduced around katliode ; little affected at anode. C(2), changes of conductivity during flow of a very .strong current. Conductivity reduced both in anodic and kathodic regions, but less in the former. C, changes of conductivity just after opening a moderately strong current. Conductivity greatly reduced in region which was formerly anodic ; little affected in region formerly kathodic. the excitability is increased (condition of katelectrotonus), while around the anode it is diminished (anelectrotonus). Immediately after the opening of the current these relations are for a brief time reversed, the excitability of the post- kathodic area (area which was at the kathode during the flow) being diminished, and that of the post-anodic in- creased. In the intrapolar area there is one point the excitability of which is not altered. This indifferent point, as 524 yl MANUAL OF PHYSIOLOGY. it is called, shifts its position when the intensity of the current is varied. These statements have been made on the strength of experiments in which the height of the muscular contrac- tion was taken as the index solely of the excitahility of the nerve at any given point. But it is now known, partly from observations on muscular contraction in which changes of excitability of the nerve were eliminated by proper choice of the point of stimulation, and partly from observations on the action stream (p. 556), that very striking altera- tions of conductivity are also produced by the constant current, which even outlast its i^ow. For all currents except the weakest the conductivity at the kathode and in its Fig. 156. — Katei.kcikotonu.s. Fig. 157. — ANhLECTKuioNUS. Weak tetanus of muscle (the right-hand Strong tetanus of muscle (left-hand elevation), greatly intensified in katelec- elevation), lessened in strength by an- trotonus of the motor nerve (ihe left-hand electrotonic condition of the motor nerve elevation). (right-hand elevation). immediate neighbourhood is diminished, and with currents still only moderately strong (xooWir ampere, e.g.) the block deepens into utter impassability. The conductivity at the anode is, during all this stage, but little affected, and is at any rate much higher than at the kathode, so that at the time of full kathodic block the nerve-impulse still freely passes through the region around the positive pole. With still stronger currents the conductivity here, too, begins to diminish, until at last the anode is also blocked ; but this is to be looked upon as merely an extension of the defect of conductivity which has been creeping along the intrapolar area from the kathode. After the opening of the current, the relation between kathodic and anodic conductivity is NERVE. 525 reversed, for now the post-kathodic region conducts the nerve-impulse relatively better than the post-anodic. The above facts serve to explain the manner in which the effects of stimulation of a nerve with the constant current vary with the strength and direction of the stream. These effects, so far as the contraction of the muscles sup- plied by the nerve is concerned, have been formulated in what has been somewhat loosely termed the law of contrac- tion. In this formula the direction of the current in the nerve is commonly distinguished by a thoroughly bad but now ingrained phraseology, as ascending when the anode is next the muscle, and descending when the kathode is next the muscle. Lazu of Contraction. Current. Ascending. Descending. M. 1 B. M. B. Weak - - 1 C Medium - i C C Strong - - — C C C c c Here M means ' make,' B, ' break,' of the current ; C means ' contraction follows.' The explanation generally given of the facts summed up in the ' law of contraction ' is as follows : Wherever there is an increase of excitability sufficiently rapid and sufficiently large, stimulation is supposed to take place ; where there is a fall of excitability, stimulation does not occur. Accord- ingly, at closure the kathode stimulates — the anode does not ; while at opening, the anode, at which the depressed excitability jumps up to normal or more, is the stimulating pole ; the kathode, at which it declines to normal or under it, is inactive. With a weak current^ (i) contraction only occurs at make, and (2) the direction of the current is indifferent. The explanation of the first fact is that the make is a stronger stimulus than the break, and when the current is weak enough the break is less than a mini- mal stimulus. No sensible change of conductivity is caused by weak currents, which suffices to explain (2). With a ' tnediiim ' current, contraction occurs at make and break with both directions. Here the break excitation is effective as well as the make. With anode next the muscle (ascending current), there is of course nothing to prevent the opening excitation, which starts 526 A MANUAL OF PHYSIOLOGY at the anode, from passing down the nerve and causing contraction ; and since there is no block around the anode or in the intrapoiar region with 'medium' currents, there is nothing to keep the closing (kathodic) excitation from reaching the muscle too. With the kathode next the muscle (descending current), the closing excita- tion, which starts from the kathode, has no region of diminished conductivity to pass through, nor has the opening (anodic) excitation, for the kathodic block, caused by moderately strong currents, is removed as soon as the current is broken. With ' strong ' currents there are only two cases of contraction out of the four, just as with ' weak,' but for very different reasons. There is a braek-contraction with ascending, and a make-contraction with descending current. With ascending current the anode is next the muscle, and the break-excitation starting there has nothing to hinder its course. The make-excitation, although as strong or stronger, has to pass through the whole intrapoiar region and over the anode, and here the conductivity is depressed and the nerve- impulse blocked. With descending current the kathode is next the muscle, and there is no hindrance to the passage of the make-excita- tion. The break-excitation, however, has to traverse the intra-polar region, and the anodic end of this area has a smaller conductivity immediately after opening than during the flow, while the kathodic end does not at once, after a strong current, become passable. The break-excitation, accordingly, cannot get through to the muscle. In all these cases of complete or partial block, during or after the flow of a constant current, the progress of the nerve-impulse, its gradual weakening, and final extinction can be very well shown by means of the action stream (p. 569). The above formula can only be verified upon isolated nerves, and, even for these, exceptional results are apt to be obtained as soon as the nerves begin to die. Some of the apparent irregularities, however, can be explained in accordance with the law of contraction ; for example, the obser- vations of Rosenthal and others on the effect of opening and closing a weak current, always of the same strength, at diff'erent stages in the dying of a nerve. Rosenthar s Law of Contraction for Dying Nerve, shown in the accompanying table, corresponds with the ordinary law if for ' weak ' ' medium,' and ' strong ' current we read ' first,' ' second,' and ' third ' stage. The explanation com- monly given is that the in- crease of excitability, which a nerve undergoes when it begins to die is equivalent to an in- crease of current strength ; so that a stream at first ' weak, after a time becomes 'medium,' and then ' strong.' But since the third stage persists not only after the Stage. Ascending. Descending. M. ! B. M. B. I. - II. - III. - C — c ; c — 1 c c i — c c c — NERVE. 527 excitability has begun again to decline, but usually till it is entirely gone, some supplement to the ordinary explanation for that stage is wanting ; and it is perhaps to be found in the fact that a weaker current suffices to cause complete block in exhausted than in fresh nerves. A formula similar to the law of contraction has been shown to hold for the inhibitory fibres of the vagus (Bonders), ' inhibition ' being substituted for ' contraction.' There is also some evidence that a similar law obtains for sensory nerves. The Law of Contraction for Nerves ' in Situ.' — When a nerve is stimulated without previous isolation — in the human body, for instance, through electrodes laid on the skin — the current will not enter and leave it through definite small portions of its sheath, nor will it be possible to make the lines of flow nearly parallel to each other and to the long axis of the nerve, as is the case in a slender strip of tissue when there is a considerable distance between the electrodes. A, an isolated nerve ; B, a nerve z'« situ. Secondary anodes ( + ) are formed where the current re-enters the nerve below the negative electrode, after passing tlirough the tissues in which it is embedded, and secondary kath- odes ( - ) where the current passes out of the nerve into the surround- ing tissues below the positive elec- trode. P'iG. 158. — Diagram of Lines of Flow OF A Current passing through a Nerve. On the contrary, even when a single electrode — say, the positive — is placed over the position of the nerve, and the other at a distance on some convenient part of the body, the current will enter the nerve by a broad fan of stream-lines cutting it more or less obliquely, and pass out again into the surrounding tissues ; so that both an anode (surface of entrance) and a kathode (still larger surface of exit) will correspond to the single positive pole. Similarly, the single negative electrode will correspond to a kathodic surface where the now narrowing sheaf of lines of flow enters the nerve, and a smaller anodic surface, where they emerge. If the two electrodes were on the course of the nerve, the stream- lines would still cut it in such a way that each electrode would correspond both to anode and kathode (Fig. 158). 528 A MANUAL OF PHYSIOLOGY. It is impossible under these circumstances to define the direction of a current in a nerve, or to connect direction with any specific effect. The terms ' ascending ' and * descending ' current are, therefore, meaningless. When we place one of the electrodes over the nerve and the other at a distance, the law oinal Nerves and their Roots after Section. — The shading shows the degenerated portions. second week. This consists in the outgrowth of new axis cylinders, in the form of fine fibres, from the ends of the divided axis cylinders of the central stump of the nerve. These push their way into and along the degenerated fibres, ultimately acquire a medullary sheath, and develop into complete nerve-fibres, restoring first sensation, and later on voluntary motion, to the paralyzed part. The process needs several months for its completion, even in warm-blooded animals. It takes place under the influence of the nutritive centre, and never occurs if the nerve is permanently separ- ated from its cell. It is a remarkable and as yet unex- plained fact that regeneration of the fibres of the central nervous system, at least in the higher animals, does not occur. NERVE. 535 The nutritive centre for the fibres of the posterior root of a spinal nerve — i.e., for the afferent fibres — is the ganghon on that root ; the centres for nearly the whole of the fibres of the anterior root lie in the spinal cord itself (p, 604). The proof of these statements is contained in Waller's experiments, which may be summarized as follows : (i) Section of the anterior root causes degeneration on the peripheral, but not on the central side of the lesion. Only the anterior root fibres in the mixed nerve degenerate. (2) Section of the posterior root above the ganglion causes degeneration of the central stump, but not of the portion still connected with the ganglion, nor of the posterior root fibres below the ganglion or in the mixed nerve. (3) Section of the posterior root below the ganglion causes degeneration of the fibres of the root below the section and in the mixed nerve, but not above it. (4) As has already been mentioned, section of the mixed nerve causes degeneration on the peripheral, but not on the central side of the lesion. A few fibres in the peripheral stump of the anterior root do not degenerate after its division, and a few fibres in the central stump do. These are * recurrent fibres ' (p. 615), which, leaving the spinal cord by the posterior root, run down the nerve for a short distance, and then pass upwards in the anterior root, probably to the pia mater and the connective tissue of the root. The nutritive, or trophic, centre of these fibres being the spinal ganglion, they do not degenerate so long as the connection with it is intact. Experimental section, or, in man, traumatic division or compression of a nerve, leads not only to its degeneration, but ultimately, if regeneration of the nerve does not take place, to degeneration of the muscles supplied by it as well. The muscle-fibres dv*'indle to a quarter of their normal diameter ; the stripes disappear ; the longitudinal fibrilla- tion fades out ; and at length only hyaline moulds of the fibres are left, filled and separated by fatty granules and globules, and surrounded by engorged capillaries. Amidst the general decay, the muscular fibres of the terminal 'spindles,' with which the afferent nerves of muscles are 536 A MANUAL OF PHYSIOLOGY. connected, alone remain unchanged (Sherrington). Certain diseases of the cord which interfere with the cells of the anterior horn cause degeneration of motor nerves, and ultimately of muscles. Muscles whose motor nerves have been separated from their trophic centres show, when a certain stage in degeneration has been reached, a peculiar behaviour to electrical stimula- tion, called the 'reaction of degeneration.' To the constant current the muscles are more excitable, and the contraction slower and more prolonged than normal ; to the induced current they are less excitable than normal, or not excitable at all. The closing anodic contraction is stronger than the closing kathodic — the opposite of the ordinary law. The nerves are inexcitable either to constant or induced currents. The reaction of degeneration is only obtained from paralyzed muscles when the paralyzing lesion is situated below the level of the cells of the anterior horn from which the motor nerves take origin. Accordingly, it is sometimes of use in localizing the position of a lesion. Trophic Nerves. — The fact that the proper nutrition of nerve-fibres is dependent on their connection with nerve- cells, has been by some writers generalized into the doctrine that all tissues are provided with ' trophic ' nerves, which, apart from any influence on functional activity, regulate the nutrition of the organs they supply. But the evidence for this view, when weighed in the balance, is found want- ing ; and it may be said that up to the present no unequivocal proof, experimental or clinical, has ever been given of the existence of specific trophic nerves. It is true that division of the trigeminus nerve within the skull is sometimes followed by cloudiness of the cornea, going on to ulceration, and ultimately inflammation and destruction of the eyeball. Ulcers also form on the lips and on the mucous membrane of the mouth and gums ; and the nasal mucous membrane on the side corresponding to the divided nerve becomes inflamed. But in this case the sensibility of the eye is lost, and reflex closure of the eyelids ceases to prevent the entrance of foreign bodies. The animal is no longer aware of the contact of particles of dust NERVE. 537 or bits of straw or accumulated secretion with the conjunc- tiva, and makes no effort to remove them. The lips being also without sensation, are hurt by the teeth, particularly as the muscles of mastication on the side of the divided nerve are paralyzed, and decomposed food, collecting in the mouth, and inhaled dust in the nose, will tend still further to irritate the mucous membranes. There is thus no more need to assume the loss of unknown trophic influences in order to explain the occurrence of the ulcerative changes than there is to explain the production of ordinary bed- sores, bunions or corns on parts peculiarly liable to pressure. And, as a matter of fact, if the eye be artificially protected, after section of the trigeminal nerve, the ophthalmia either does not occur or is much delayed. In man, too, a case has been recorded in which both the fifth and the third nerves were paralyzed. The eye was still shielded by the contraction of the orbicularis oculi supplied by the seventh nerve, as well as by the drooping of the upper eyelid that accompanies paralysis of the third. It remained perfectly sound for many months, till at length the tumour at the base of the brain which had affected the other nerves involved the seventh too. The eye was now no longer completely closed ; inflammation came on, and vision was soon permanently lost (Shaw). In another case a patient lived for seven years with complete paralysis of the fifth nerve, yet the eye remained free from disease and sight was unimpaired (Gowers). The so-called * trophic ' effects following division of both vagi we have already discussed (p. 182) so far as they are concerned with the respiratory system. The cardiac changes are perhaps secondary to the pulmonary, or due to the want of nervous restraint on the functional activity of the heart. The nutritive alterations in muscles and salivary glands after section of motor and secretory nerves seem to depend on functional and vaso-motor changes. In muscles they come on far too late to be due to the loss of * trophic ' nerve-fibres. Section of the cervical sympathetic in young rabbits and dogs is said to increase the growth of the ear and of the 538 A MANUAL OF PHYSIOLOGY. hair on the same side ; but it is impossible to separate these consequences from the vaso-motor paralysis ; and the same is true of the hypertrophy following section of the vaso-motor nerves of the cock's comb and of the nerves of bones. The statement has recently been made that on section of the superior laryngeal nerve in the horse the laryngeal muscles undergo rapid atrophy. This seemed to indicate either that the nerve contains efferent ' trophic ' fibres for the muscles, or that the activity of its afferent fibres has a profound influence on their nutrition. But it appears doubtful whether the alleged facts can be made good, and not less doubtful whether, in any case, they would justify the in- ferences that have been drawn from them. And Mott and Sherrington have found that, although section of the pos- terior roots in monkeys is followed after a time (three weeks to three months) by ulceration over certain portions of the foot, no corresponding lesions occur in the hand. They believe, therefore, that the lesions are not due to the with- drawal of a reflex trophic tone, but are accidental injuries in positions specially exposed to mechanical or microbic insults. Omitting the group of ' trophic ' nerves, and the even more pro- blematical ' thermogenic ' fibres, peripheral nerves may be classified as follows : f Smell. Nerves of special sensation -' tt :* Sight. Tactile sensation (per- haps including the nerves of muscular sense). Temperature. Pain, r Calibre of small arteries (pressor, depressor). Action of heart. Visceral movements. Respiratory move- ments. Glandular secretion. Ordinary skeletal I muscles. * It is not known whether the afterent portion of a reflex arc is always composed of fibres included in the first two categories, although undoubtedly in some cases it is. Centripetal or afferent fibres 2. Nerves of general sensation Possibly nerves other than those included under i and 2, concerned in reflex changes in PRACTICAL EXERCISES. 539 Centrifugal or efferent fibres I. Motor nerves for Skeletal muscles. Visceral „ fVaso-constrictor. Vascular „ - Cardio - augmen- \ tor. Erector muscles of hairs (pilo- motor fibres). (Visceral muscles. 2. Inhibitory nerves for-j 3. Secretory nerves. [Vascular fVaso-dilator. - Cardio- inhi- [ bitory. PRACTICAL EXERCISES ON CHAPTERS IX. AND X. I. Difference of Make and Break Shocks from an Induction Machine. — Connect a Daniell cell B (Fig. 122) with the two upper binding-screws of the primary coil P, and interpose a spring key K in the circuit. Connect a pair of electrodes with the binding- screws of the secondary coil (Fig. 160). Fig. 160. — .■\kk.\ngement of Coil for Single Shocks. Electrodes can be very simply made by pushing copper wires through two glass tubes, filling the ends of the tubes with sealing- wax, and binding them together with waxed thread. The projecting points may be filed, and the nerve laid directly on them, or they may be tipped with small pieces of platinum wire soldered on. {a) Push the secondary away from the primary, until no shock can be felt on the tongue when the current from the battery is made or broken with the key. Then bring the secondary gradually up towards the primary, testing at every new position whether the shock is per- ceptible- It will be felt first at break. If the secondary is pushed still further up, a shock will be felt both at make and at break. From this we learn that for sensory nerves the break shock is 540 A MANUAL OF PHYSIOLOGY. stronger than the make. The same can easily be demonstrated for motor nerves and for muscle. {b) Smoke a drum and arrange a myograph, as shown in Fig. 163. But omit the brass piece F, and do not connect the primary through the drum, as there shown, but connect it as in Fig. 160. Pith a frog (brain and cord), and make a muscle-nerve preparation. To make a Miisck-Ahrve Preparatiflu. — Hold the frog by the hind-legs ; the front part of the body will hang down, making an angle with the posterior portion. With strong scissors divide the back- bone anterior to this angle, and cut away all the front portion of the body, which will fall down of its own weight. Make a circular in- cision at the level of the tendo Achillis, and another at the lower end of the femur, through the skin. The sciatic nerve must now be dis- sected out, as follows : Remove the skin from the thigh, and, holding the leg in the left hand, slit up the fascia which connects the external and internal groups of muscles on the back of the thigh. Complete the separation with the two thumbs. Cut through the iliac bone, taking care that the blade of the scissors is well pressed against the bone, otherwise there is danger of severing the sciatic plexus. Now divide in the middle line the part of the spinal column which remains above the urostyle. A piece of bone is thus obtained by means of which the nerve can be manipulated without injury. Seize this piece of bone with the forceps, and carefully free the sciatic plexus and nerve from their attachments right down to the gastrocnemius muscle, taking care not to drag upon the nerve. The muscles of the thigh will con- tract, as the branches going to them are cut. This is an instance of mechanical stimulation. Now pass a thread under the tendo Achillis, tie it, and divide the tendon below it. Strip up the tube of skin that covers the gastrocnemius, as if the finger of a glove were being taken off. Tear through the loose connective between the muscle and the bones of the leg, and divide the latter with scissors just below the knee. Cut across the thigh at its middle. Fix the preparation on the cork plate of the myograph by a pin passed through the cartilaginous lower end of the femur, and attach the thread to the upright arm of the lever by one of the holes in it. Hang not far from the axis by means of a hook a small leaden weight (5 to 10 grammes) on the arm of the lever which carries the writing-point, and move the myograph plate or the muscle-nerve preparation until this arm is just horizontal. Fasten the electrodes from the secondary coil on the cork plate with an indiarubber band; lay the nerve on them ; and cover both muscle and nerve with an arch of blotting-paper moistened with normal saline, taking care that the blotting-paper does not touch the thread. Adjust the writing-point to the drum. Begin with such a distance between the coils that a break contraction is just obtained on opening the key in the primary circuit, but no make contraction. The lever will trace a vertical line on the stationary drum. Read off on the scale of the induction machine the distance between the coils, and mark this on the drum. Now allow the drum to move a little, still keeping the writing-point in contact with it ; then push up the secondary coil i centimetre nearer the primary, and close the key. PR A CTICA L EXER CISE S. 541 If there is a contraction, let the drum move a little before opening the key again, so that the lines corresponding to make and break may be separated from each other. If there is still no contraction at make, go on moving the secondary up, a centimetre (or less) at a time, till a make contraction appears. When the coils are still further approxi- mated, the make may become equal in height to the break con- traction, both being maximal, i.e., as great as the muscle can give with any single shock (Fig. 161). ■ ( 1 11 w w w 1 W \ \\\ MB 22 MB 20 M B 18 MB 16 M B 11*. MB 12 M B 10 ■ MB S M B 6 Fig. 161.— Contractio.ss caused by Make and Break Shocks fro.m ax Induction Machine. M, make ; B, brenk contractions. The numbers give the distance between the primary and secondary coils in centimetres. {c) Attach a thin insulated copper wire to each terminal of the secondary. Loop the bared end of one of the wires through the tendo Achillis, and coil the other round the pin in the femur, so that the shocks will pass through the whole length of the muscle. Repeat the experiment of {b), with direct stimulation of the muscle. ?. Stimulation of Nerve and Muscle by the Voltaic Current. — {a) Connect a Daniell cell through a key with a pair of electrodes on Fig. 162. — Simple Rheocord arranged to Send a Twig of a Current THROUGH .\ Muscle or Nerve. B, battery ; R, rheocord wire (German silver) ; S, slider formed of a short piece of thick indiarubber tubing tilled with mercury ; K, spring key ; W, \V, wires connected with electrodes. which the nerve of a muscle-nerve preparation lies. Observe that the muscle contracts when the current is closed or broken, but not during its passage. Connect the cell with a simple rheocord, as shown in Fig. 162, so that a twig of the current of any desired strength may be sent through the nerve. As the strength of the current is decreased by moving 54 2 A MANUAL OF PHYSIOLOGY. the slider S, it will be found that it first becomes impossible to obtain a contraction at break. The current must be still further reduced before the make contraction disappears, for the closing of a galvanic stream is a stronger stimulus than the breaking of it. The break or make contraction obtained by stimulating a nerve with an in- duction-machine must not be confused with the break or make contractions caused by the voltaic current. In the case of the induction-machine, the break or make applies merely to what is done in the primary circuit, not to what happens to the current actually passing through the nerve. The current induced in the secondary at make of the primary circuit is, of course, both made and broken in the nerve — made when it begins to flow, broken when the flow is •over ; the shock induced at break of the primary is also made and broken in the nerve. And although make and break of the actual stimulating current come very close together, the real make, here too, is a stronger stimulus than the real break. (/?) Repeat {a) with the muscle directly connected by thin copper wires, or better, unpolarizable electrodes (p. 579), to the cell. 3. Mechanical Stimulation. — Pith a frog. Cut away the anterior portion of the body, dissect out one sciatic nerve, and separate the leg to which it belongs from the other. Pinch the end of the nerve or prick the muscles, and they contract. 4. Thermal Stimulation. — Touch the nerve of the same prepara- tion with a hot wire ; the muscle contracts. The nerve is killed at the point of contact, but can be again stimulated by touching it with the wire lower down. 5. Chemical Stimulation.— {a) Cut off the injured portion of the nerve used in 3 and 4. Apply to the cut end a crystal of common salt, or let the nerve dip into a watch-glass containing a saturated solution of salt. In a short time the muscles supplied by the nerve begin to twitch, and soon enter into irregular tetanus. Cut off the piece of nerve in contact with the salt, and the tetanus stops. This shows that the seat of irritation is the portion of the nerve into which the salt has penetrated, and from which water has been withdrawn by osmosis. Contraction can also be caused by applying the salt directly to the muscles. \b) Wrap the leg in blotting-paper moistened with normal saline, and expose the nerve to the vapour of strong ammonia ; it will be killed, but not stimulated, for the muscles will not contract. Expose the muscles themselves to the ammonia, and contraction will occur. Accordingly muscle is stimulated by ammonia, while nerve is not. 6. Ciliary Motion. — Cut away the lower jaw of the same frog, and place a small piece of cork moistened with normal saline on the ciliated surface of the mucous membrane covering the roof of the mouth. It will be moved by the cilia down towards the gullet. Lay a small rule, divided into millimetres, over the mucous membrane, and measure with the stop-watch the time the piece of cork takes to travel over 10 millimetres. Then pour normal saline heated to 30° C. on the ciliary surface, rapidly swab with blotting-paper, and repeat the observation. The piece of cork will now be moved more PRACTICAL EXERCISES 543 quickly than before, unless the normal saline has been so hot as to injure the cilia. 7. Direct Excitability of Muscle — Action of Ciirara. — Pith the brain of a frog, and prevent bleeding by inserting a piece of match. Expose the sciatic nerve in the thigh on one side. Carefully separate it, for a length of half an inch, from the tissues in which it lies. Pass a strong thread under the nerve, and tie it tightly round the limb, excluding the nerve. Now inject into the dorsal or ventral lymph- sac a few drops of a i per cent, curara solution. As soon as paralysis is complete, make two muscle-nerve preparations, isolating the sciatic nerves right up to the vertebral column. Lay their upper ends on electrodes and stimulate ; the muscle of the ligatured limb will contract. This proves that the nerve-trunks are not paralyzed by curara, since the poison has been circulating in them above the ligature. The muscle of the leg which was not ligatured will contract if it be stimulated directly, although stimulation of its nerve has no effect. The muscular fibres, accordingly, are not paralyzed. The seat of paralysis must therefore be some structures physio- logically intermediate between the nerve-trunk and the muscular fibres (p. 481). 8. Graphic Record of a Single Muscular Contraction or Twitch. — Pith a frog (brain and cord), make a muscle-nerve preparation, and arrange it on the myograph plate, as in i [b). Lay the nerve on electrodes connected with the secondary coil of an induction machine arranged for single shocks. Introduce a short-circuiting key (Fig. 134) between the electrodes and the secondary coil, and a spring key in the primary circuit. Close the short-circuiting key, and then press down the spring key with the finger. Let the drum off (fast speed) ; the writing-point will trace a horizontal abscissa line. Open the short-circuiting key, and then remove the finger from the spring-key. The nerve receives an opening shock, and the muscle traces a curve. Now adjust the writing-point of an electrical tuning-fork (Fig. 163), vibrating, say, 100 times a second, to the drum, and take a time- tracing below the muscle-curve. Stop the drum, or take off the writing-point, the moment the time-tracing has completed one cir- cumference of the drum, so that the trace may not run over on itself. Cut off the drum-paper, write on it a brief description of the experi- ment, with the time-value of each vibration of the fork, the date, and the name of the maker of the tracing, and then varnish it. An exactly similar tracing can be obtained by directly stimulating the muscle (curarized or not). 9. Influence of Temperature on the Muscle-curve.— Pith a frog (brain and cord), make a muscle-nerve preparation, and arrange it on a myograph. Lay the nerve on electrodes connected through a short-circuiting key with the secondary coil of an induction-machine, or connect the muscle directly with the key by thin copper wires. Take a Daniell cell, connect one pole through a simple key with one of the upper binding-screws of the primary coil, and the other pole with the metal of the drum. A wire, insulated from the drum, but clamped on the vertical part of its support, and with its 544 A MANUAL OF PHYSIOLOGY M ■ T3 c < y c C M !?„* - w C c «: ^ .2 1) — bfl , -C rt Q} r" t- * ^- -*^^ W) * ?i i; i = u £,/> ^ 2 jr .5 i " i: 0''"- S (5 o ti : j2 IT o OJ H-^ S ■a ^ y oj bfl Ji « -^ £ -S d -= ^ ^. OJ C oc o aj! D 'J bn O ii 2 u in be ,. - *" o e I' w Ex: i; -a " 3>„ 5.2 O C he »^ o - ?.^ ■" - 5 I .^ - c s: ^ e o o D. 3 ^ - ;:: I- tu -S rt fa -c jr — •- O i; r^ 51 >- TO ^ >,^ c li « 0) •5 S ^ « =: 5 " the second opposed to it. But after the wave has v50me wruerb beem lO passed, the contacts are equipotential, as they were sunpOSC that an in- before ' (Burdon Sanderson). '■^ . crease of chemical ac- tivity must necessarily be at the bottom of both changes; in the dying muscle, it is said, the chemical changes must be increased, and we know that they are increased in the living active muscle. This may be so, but the electrical changes are very marked in injured and in active nerve, and here \Ve know nothing of measurable chemical changes. And warmed living muscle is positive to muscle less warm, although the metabolism must in general be more active in the former. It is, of course, quite clear that energy must be running down, for electrical currents capable of doing work are being produced ; but whether this energy comes from chemical changes or from physical changes, or from boih, or how much of it comes from either, we cannot tell. Others have said that there is really a subdued kind of more or less permanent excitation in the neighbourhood of the injured tissue, and that this explains the similarit}' . ELECTR 0-PH YSIOLOG F, . 565. of electrical condition in activity and injury. This pushes the inquiry a step further back, but does not touch the question of the nature of the changes underlying both action and injury. Physical explanations of the action current of muscle have been based on the hypothesis that in contraction variations in surface-tension, with accompanying electrical changes, occur at certain surfaces (surface of separation between light and dim discs, or between fluid contents and wall of sarcous capillary tubes). A great and decisive objection to these theories is that in nerve, so far as we know, no sensible mechanical change whatever takes place during excitation, and that differences of potential exist or may be developed in tissues of the most diverse structure. Polarization of Muscle and Nerve.* — We have already spoken of electrical excitation and of the changes of excitability caused by the passage of a constant current (p. 523). We are now to see that these physiological effects are accom- panied by, and indeed very closely related to, more physical changes which the galvanometer or electrometer reveals to us. When a current is passed by means of unpolarizable electrodes (Fig. 132, p. 471) through a muscle or nerve for several seconds, and the tissue thrown on to the galvano- meter immediately after this polarizing current is opened, a deflection is seen indicating a current (negative polarisation current) in the opposite direction. This negative polarization differs from the polarization of the electrodes seen after passage of a current through any ordinary elec- trolytic conductor, like dilute sulphuric acid. The latter is due to the deposition of hydrogen on the kathode and oxygen on the anode, the electrodes being converted for the time into the plates of a secondary battery. But in muscle, nerve and other animal tissues, as well as in vegetable structures, and indeed, to a certain extent, in unorganised porous bodies soaked with electrolytes, the polarization is not confined to the neighbourhood of the electrodes, but distributed all the way between them ; in other words, it is an internal polariza- tion depending on the separation of ions in the mass of the tissue. In muscle and nerve this internal negative polarization is very strongly marked ; and although it is not bound up with the life of the tissue, and may be obtained when this has become quite inexcitable, it is nevertheless dependent on the preservation of the normal structure, for a boiled muscle shows but little negative polarization. * The portions in small type on pp. 563-570 may be omitted except by students interested in the subject or reading for a special purpose. 566 A MANUAL OF PHYSIOLOGY. When the polarizing current is strong, and its time of closure short, we obtain, on connecting the tissue with the galvanometer after opening the current, not a negative but a positive deflection, indicating a so-called positive polarization current in the same direction as that of the polarizing stream. The * positive polarization ' is only obtained when the tissue is living; and it is far more strongly marked in the anodic than in the kathodic region. There is, in fact, a great weight of evidence that the * positive polarization ' current is really an action stream, due to the opening excitation set up at the anode (p. 525). Suppose that the nerve in Fig. 176 is stimulated by the opening of the battery B, and that, immediately after, the nerve is connected with the galvano- meter G by the electrodes E, E^. Sup- pose, further, that the shaded region near the anode remains more excited for a short time than the rest of the nerve, and we have seen (p. 524) that after the opening of a strong current there is a defect of conductivity, espe- cially in the neighbourhood of the anode, which would tend to localize excitation. The portion of nerve at E being negative relatively to that at E^, an action current will pass through the galvanometer from Ej to E, and through the nerve in the same direc- tion as the original stimulating stream ; that is, it will have the direction of the positive polarization current. Under certain conditions a state of continuous excitation in the anodic region of a nerve is shown by a tetanus of its muscle {Ritter's tetanus, p. 583, and Fig. 177). Grutzner and Tigerstedt have put forward a different theory of the break contraction. They say it is really a closing contraction due to the closure of the negative polari- zation current through the tissue itself, as soon as the polarizing current is opened. In fact, they admit only one kind of electrical stimulus, the kathodic, or make. But this theory does not adequately take account of positive polari- zation, and there are also other objections to it. Fig. 176. — Diagram to show Distribution of ' Positive Polarization ' after open- ing Polarizing Current. B, battery ; G, galvanometer. The dark shading signifies that the excitation to which the positive polarisation current is due is greatest in the immediate neigh- bourhood of the anode, and fades away in the intrapolar region. ELECTRO-PHYSIOLOGY. 567 Electrotonic Currents. — During the flow of the polarizing current, there are very remarkable galvanoscopic evidences of the changes pro- duced by it. And although it is not possible directly to demonstrate polariz- ation in the region between the elec- trodes while the cur- rent continues to pass, this is easily done in the extrapo- lar regions, although much more readily 177.— RiTTERs Tetanus, on nerve than on muscle. If a current be passed from the battery (Fig. 178) in the direction indi- cated by the arrows, while a galvano- meter is connected with either of the extrapolar areas, as shown in the figure, a current will pass through the galvanometer, in the same direction in the nerve as the polarizing current, so long as the latter continues to flow. A strong voltaic current was passed for some time tlirough the nerve of a muscle-nerve prepara- tion. On opening the circuit, the muscle gave one strong con- traction, and then entered into irregular tetanus, which continued for four minutes. (Only the first part of the tracing is repro- duced.) Fig. 178.— Diagram showing Direction of the Extrapolar Electrotonic Currents. These currents are called electrotonic, and seem to depend on the spread of the polarizing stream along the nerve outside the electrodes, owing to a polarization taking place at the boundary between some part of the nerve-fibre which may be called a core, and another part which may be called a sJuath. The exact seat of this polarization is unknown ; it may be between axis-cylinder and medullary sheath, or between the latter and the neurilemma. In any case, such a polari- 568 A MANUAL OF PHYSIOLOGY. zation would practically act as a resistance to the direct passage of the current from the anode down into the ' core,' or from the core out to the kathode, and would cause it to spread longitudinally along the sheath in the extrapolar regions. On this view the electrotonic currents are really twigs of the polarizing stream. And, as a matter of fact, such currents can be produced on a model in which a platinum wire is surrounded with a sheath of saturated zinc sulphate solution. A current led into the latter tries, so to speak, to pass mostly by the good conducting wire. If this is not polarizable, if it is, e.g.., a zinc wire, there is little or no spreading of the current outside the elec- trodes ; it passes at once into the core, and so on to the other electrode. If, however, there is polarization when the current passes from the liquid into the wire, as is the case when the latter is platinum, the stream spreads longitudinally. And, indeed, we know that both nerve and muscle, and especially the former, are far more polarizable in the transverse than in the longitudinal direc- tion ; the apparent transverse resistance of nerve may be seven times the longitudinal resistance, and this is a condition which favours electrotonus. This physical electrotonus must be distinguished from the changes of excitability produced by the constant current, to which the name of electrotonus is also sometimes given. For although the decline in the intensity of the electrotonic currents as we pass away from the electrodes, has its ana- logue in the distribution of the electrotonic changes of ex- citability, and there are other facts which suggest a relation between the two, we are ignorant of the real nature of this relation. The electrotonic currents cannot spread beyond a ligature; they are stopped by anything which destroys the structure of the tissue. But this does not show that they are other than physical in origin, for what destroys the structure of the tissue destroys also, in great part at least, its capacity for polarization. Stimulation of a nerve while the polarizing current is flowing causes in general in the extrapolar regions a negative variation of the electrotonic current, but in the intrapolar region a positive variation. The latter is undoubtedly an action stream. Hermann has explained its direction on the assumption that the excitation diminishes in intensity as it approaches the kathode or recedes from the anode, and increases in intensity as it passes towards the anode or away from the kathode (law of polarization increment). But the fact that during the flow of a current the conductivity of the nerve is far more depressed around the kathode than near the anode afl"ords a sufificient explanation. ELECTRO-PHYSIOLOGY. 569 Fig. 179. — Diagram showing Direction of THE Stimulation Effect in the Intra- POLAK Region during the flow of the Polarizing Current. The nerve-impulse, starting from the stimulating electrodes S (Fig. 179), will pass over E, the anode, in greater intensity than over Ep the kathode ; and therefore, upon the whole, during tetanus E will be negative to Ej, and a current of action will be developed in the same direction as the polarizing current, and reinforcing it. When the kathodic block is complete, and the excitation has to pass over the kathode before reaching the intrapolar region, no effect is pro- duced by stimulation. The stimulation effects in the extrapolar regions are probably due partly to action currents, as is shown by the fact that when the polarizing current is strong enough to markedly de- press the conductivity in the neighbourhood of the anode, the variation becomes positive instead of negative when one of the galvanometer electrodes lies near the anode. For here the excitation coming from S passes Eo in far less intensity than Eg (Fig. r8o). E., is therefore, on the whole, during tetanus negative to E.,, and the direction of the action current in the nerve is from E3 to Eo. The negative variation in the extrapolar kathodic region could also be explained as an action current due to diminished conduc- tivity in the neighbourhood of the kathode. But the negative anodic variation cannot be an action current, unless we suppose that with the weaker polarizing currents the conductivity is increased around the anode ; and for this there is not sufficient proof. It is probable, therefore, that there is another factor mixed up with the currents of action, and in part opposing them. Some have supposed that the capacity for polari- zation between core and sheath is diminished during excitation, and that, accord- ingly, less of the current spreads beyond the elec- trodes, and an apparent negative variation is caused in the extrapolar regions by stimulation ; but there is no direct evidence for this. After the opening of the polarizing current, electromotive changes can, as we have seen, be recognised for a short time in the intrapolar area. This is also true of both extrapolar regions. The main after-current in the anodic region is in the opposite direction to the polarizing stream ; but this is, under certain circumstances, preceded by a very short kick of the galvanometer magnet in the same direc- Fig. 180. — Diagram to show Direction of the Positive Stimulation Effect in the Anodic Extrapolar Region during the FLOW of a strong POLARIZING CURRENT. 570 A MANUAL OF PHYSIOLOGY. tion. The kathodic after-current is in the same direction as the polarizing stream, and is, except with strong currents and a compara- tively long time of closure, much weaker than the main anodic. The latter is to be looked upon as having the same origin as the positive polarization current of the intrapolar region, a state of opening excitation around the anode ; in other words, it is an action current. The kathodic and the preliminary anodic after-currents are probably due to negative polarization. Stimulation of the nerve after opening the polarizing current causes well-marked effects ; in the intrapolar region the stimulation effect is in the opposite direction to the polarizing current ; in the extrapolar anodic area, in the same direction as the polarizing stream. In the extrapolar kathodic region, it is in the opposite direction, and, except with strong polarizing currents, and a more than momentary time of closure, less in amount than the stimulation effect in the anodic region. All these cases are readily explained by the fact that immediately after opening the polarizing current the conductivity of the nerve is more depressed in the anodic than in thekathodic region, although with strong currents it is depressed in both. An excitation reach- ing the extrapolar anodic area from S will pass over E3 in greater intensity than over E4 (Fig. 181). E4 will there- fore be positive to Eo, and the action current will go through the nerve in the direction of the arrow. An excitation reaching the kathodic extrapolar area from S' will arrive at E^. in greater intensity than at E^. The resultant action stream will therefore have the direction in the nerve from E^ to E5. And the effects in the intrapolar region can be similarly explained. A nerve may be stimulated by an electrotonic current produced in nerve-fibres lying in contact with it. A well- known illustration of this is the experiment known as the paradoxical contraction (Practical Exercises, p. 581). The current of action of a nerve can, however, under certain conditions, stimulate another nerve, as Hering has shown. This comes under the head of secondary contraction. But the best-known form of secondary contraction is where a nerve, placed on a muscle so as to touch it in two points Fig. 181.— Diagram showing the Direction of the Stimulation Effects after opening the Polar- izing Currents in the Anodic and Kathodic Extrapolar Regions (A and K), and in the Intrapolar Region Ej, E-j. ELECTRO-PHYSIOLOGY. 571 Secondary Contrac- tion. The nerve of muscle M touches muscle M' at a and b. Stimulation of the nerve of M' at S causes con- traction of M, (Fig. 182), is stimulated by the action-current of the muscle, and causes its own muscle to contract. A secondary tetanus can be obtained in this way by dropping a nerve on an artificially tetanized muscle. The beat of the heart causes usually only a single secondary contraction when the sciatic nerve of a frog is allowed to fall on it (p. 152). But when the diphasic variation is well marked, as it is in an un- injured heart, there may be a secondary contraction for each phase, i.e., two for each heart- beat. Excitation of one muscle ^'f^- 182 may in the same way cause secondary contraction of another with which it is in close contact. The electromotive phenomena of the heart and of the central nervous system are naturally included under those of muscle and nerve. Heart. — The current of action has been chiefly studied. In the frog's heart the variation shown by the capillary electrometer is diphasic. During the first phase the base is negative to the apex ; during the second phase the apex is negative to the base. The meaning of this is that the negative electrical change, like the contraction, starts at the base, and passes on to the apex. Sometimes a third phase is seen (triphasic variation), in which the base again becomes negative to the apex. It has been supposed that this is due to the contraction of the arterial bulb, which follows that of the rest of the heart. If the tissue is injured at either leading -off electrode, the corresponding phase disappears. In the uninjured mammalian heart, beating as far as possible under normal conditions, the sequence is the same, the diphasic variation showing first base negative to apex, then apex negative to base. Statements to the contrary seem to have been founded on observations of injured hearts, or hearts placed under abnormal conditions. For example, when the base of the heart is cooled, the 572 A M.ANUAL.OF PHYSIOLOGY. variation first becomes triphasic, the sequence of the relative nega- tivity being base — apex — base ; and finally diphasic with a sequence the reverse of the normal, the apex being first negative, then the base. An electrical change accompanies every beat of the human heart. Waller has shown how this may be demonstrated by means of the capillary electrometer. His f- .-.-.-« ^- -«»«^ experiments seemed to in- dicate a diphasic variation in which the apex first became negative to the base and the base then negative to the apex. From later work by Bayliss and Starling, how- ever, it would seem that this is incorrect, the variation being really triphasic, first base negative to apex, then apex negative to base, and then again base negative to apex. When the heart is directly stimulated by induction shocks at the rate of about three per second, an artificial rhythm is set up. The interval which elapses be- tween stimulation either of auricle or ventricle and the beginning of the electrical change is about y^^j of a second. Central Nervous System. — It was discovered by du Bois- Reymond that the spinal cord, like a nerve, shows a current of rest between longitudinal surface and cross-section, and that a current of action is caused by excitation. Setschenow stated that when the medulla oblongata of the frog was connected with a galvanometer, spontaneous variations occurred which he supposed due to periodic functional changes in its grey matter. Gotch and Horsley have made elaborate experiments on the spinal cord of cats and monkeys. Leading off from an isolated portion of the dorsal cord to the capillary electrometer, and then stimu- lating the motor cortex cerebri, they obtained a persistent negative variation followed by a series of intermittent varia- tions. This agrees remarkably with the muscular contrac- tions in an epileptiform convulsion started by a similar excitation of the cortex, which consist of a tonic spasm followed by clonic (interrupted) contractions, and suggests tlG. ia3. — l:,Ll-XTKO-CAKUlUGkAMS (ElN- HOVEn). — Lower led off in opposite way from upper. ELECTRO-PHYSIOLOGY. 573 that it is the nature of the cortical discharge which deter- mines the character of the convulsion. By means of the galvanometer the same observers have made investigations on the paths by which impulses set up at different points travel along the cord. To these we shall have to refer again (p. 619). On the currents of the cerebral cortex only a few experi- ments have hitherto been made by Caton, Beck, and Fleischl. But if well-marked changes of potential could be localized on the cortex as a result of stimulation of sensory fibres, the method would probably be of great value for tracing these to their central connections. Glandular Currents. — These have been studied with any care only in the submaxillary gland and in the skin, although the liver, kidney, spleen, and other organs, also show currents when injured. In the submaxillary gland the hilus is positive to an}- point on the external surface of the gland ; a current passes from hilus to surface through the gal- vanometer, and from surface to hilus through the gland (Fig. 184). When the chorda tympani is fig. 184.— cukkent of sub- 1 , , • , -J, , MAXILLARY GLAND. stmiulated with rapidly-succeed- ing shocks of moderate strength, there is a positive varia- tion; i.e., the surface becomes still more negative to the hilus. This variation can be abolished by a small dose of atropia, and then stimulation causes a slight negative variation. A further dose of atropia abolishes this, too. With slowly-interrupted shocks (not more than five per second) a large negative variation is caused, and no positive variation, and the same is true of rapid stimuli too weak to excite secretion. Single induction shocks cause a diphasic variation, the surface of the gland becoming first more negative and then more positive to the hilus, so that a positive deflection of the galvanometer is follow'ed by a negative. In nearly all circumstances stimulation of the sympathetic causes a negative variation. Bradford, to whom, and to 574 A MANUAL OF PHYSIOLOGY. Bayliss, we are indebted for our knowledge of this subject, explains the different behaviour of the chorda tympani to different kinds of stimulation as due to the existence in it of anabolic fibres, which increase the building up of the proper substance of the gland, in addition to the katabolic fibres (trophic and secretory of Heidenhain), which increase destructive metabolism (p. 292). Skin Currents. — So far as has been investigated, the in- tegument of all animals shows a permanent current passing in the skin from the external surface inwards. This is feebler in skin which possesses no glands. In skin contain- ing glands the current is chiefly, but not altogether, secre- tory. As such, it is affected by influences which affect secretion, a positive variation being caused by excitation of secretory nerves, e.g., in the pad of the cat's foot by stimula- tion of the sciatic. The deflection obtained when a finger of each hand is led off to the galvanometer, which was at one time looked upon as a proof of the existence of currents of rest in intact muscles, is due to a secretion current, and the variation seen during voluntary contraction of the muscles of one arm is certainly in part, and probably altogether, a secretion stream. Of more doubtful origin is the current of ciliated mucous membrane, which has the same direction as that of the skin of the frog and the mucous membrane of the stomach of the frog and rabbit — viz., from ciliated to under surface through the tissue, or from ciliated surface to cross-section, if that is the way in which it is led off. The current is strengthened by induction shocks, by heating, and in general by influences which increase the activity of the cilia. Some circumstances point to the goblet-cells in the membrane as the source of the current ; but, on the whole, the balance of evidence is in favour of the cilia being the chief factor (Engelmann), although the mucin-secreting cells may be concerned, too. Eye-currents. — If two electrodes connected with a galvano- meter are placed on the excised eye of a frog or rabbit, one on the cornea and the other on the cut optic nerve, it is found that a current of rest due to the injury passes in the ELECTRO-PHYSIOL OGY. 575 eye from optic nerve to cornea. The same is true if the anterior electrode is placed on the retina itself, the front of i^CiQ eyeball being cut away. There is nothing of interest in this; but the important point is that if light be now allowed to fall upon the eye, an electrical change is caused (Holmgren, Dewar and McKendrick), generally first a positive and then a negative varia- tion, succeeded by another positive movement when the light is cut off. The variation depends upon the retina alone, and does not occur when it is removed. Bleaching of the visual purple does not much affect the variation, so that it is not connected with chemical changes in this substance. And of the spectral colours, yellow light, which affects the visual purple comparatively little, causes the largest variation ; blue, the least ; but white light is more powerful than either. (For * visual purple' see Chapter XIII.) Electric Fishes. — Except lightning, the shocks of these fishes were probably the first manifestations of electricity observed by man. The Torpedo, or electrical ray, of the coasts of Europe was known to the Greeks and Romans. It is mentioned in the writings of Aris- totle and Pliny, and had the honour of being described in verse 1,500 years before Faraday made the first really exact investigation of the shock of the Gy//inoius, or electric eel of South America. The third of the electric fishes, Malapterurus electricus, although found in many of the African rivers, the Nile in particular, and known for ages, was scarcely investigated till forty years ago. In all these fishes there is a special bilateral organ immediately under the skin, called the electrical organ. It is in this that the shock is developed. It consists of a series of plates arranged parallel to each other. To one side of each plate a branch of the electrical nerve supplying each lateral half of the organ is distributed. This side of the plate during the shock becomes negative to the other (Pacini's rule), so that each half of the organ represents a battery of many cells arranged in series. The direction of the shock through the organ depends on the side of the plate to which the nerve-supply goes, and the arrangement of the plates with reference to the natural position of the animal. Thus, in Gymnotus the plates are vertical, and at right angles to the long axis of the fish, and the nerves are distributed to their pos- terior surface ; the shock accordingly passes in the animal from tail 576 A 3/ANUA/, OF PHYSIOLOGY. to head. In Malapterurus, although the arrangement of the plates is the same, the nerve supply is to the anterior surface ; for Max Schultze has shown that although the nerve appears to sink into the posterior surface, it really passes through a hole in the plate, and spreads out on its anterior face. The shock passes from head to tail. In Torpedo, the plates or septa dividing the vertical hexagonal prisms of which each lateral half of the organ consists are horizontal ; the nerve-supplv is to the lower or ventral surface ; and the shock Fig. iS6.— Diagram showing Direction of Shock in Gymnotus. passes from belly to back through the organ. In all electric fishes the discharge is interrupted ; an active fish may give as many as 200 shocks per second. The electrical nerve of Malapterurus is very peculiar. It consists of a single gigantic nerve-fibre on each side, arising from a giant nerve-cell. The fibre has an enormously thick sheath, the axis cylinder forming a relatively small part of the whole ; and the branches which supply the i:)lates of the organ are divisions of this single axis cylinder. The electromotive force of the shock of the Gymnotus may be very considerable; and even Torpedo and Mal- apterurus are quite able to kill other fish, their enemies or their prey. Indeed, Gotch has estimated the electromotive .force of I cm. of the organ of Torpedo at 5 volts, and Schonlein finds that the electromotive force of the whole organ may be equal to that of 31 Daniell cells, or o'oS volt for each plate, and it is one of the most interesting questions in the whole of electro-physiology, how they are protected from their own currents. There is no doubt that the current density inside the fish must be at least as great as in any part of the water surrounding it, and probably much greater. The central nervous system and the great nerves must be struck by strong shocks, yet the fish itself is not injured; nay more, the Fig. 187. — DIAGRAM SHOWING DiRLCTION OF Shock in Malapterurus. ELECTRO-PHYSIOLOGY. 577 young in the uterus of the viviparous Torpedo are unharmed. The only explanation seems to be that the tissues of electric fish are far less excitable to electrical stimuli than the tissues of other animals ; and this is found to be the case when their muscles or nerves are tested with galvanic or induction currents. It requires extremely strong currents to stimulate them ; and the electrical nerves are more easily excited mechani- cally, as by ligaturing or pinch- ing, than electrically. In general, too, the shock is more readily called forth by reflex mechanical stimulation of the Fig. i8S.— Diagram Shouixg Direc- skin than by electrical stimu- '"O'^' o^" Shock in Torpedo. lation. But that the organ itself is excitable by electricity, has been shown by Gotch. He proved that in Torpedo a current passed in the normal direction of the shock is strengthened, and a current passed in the opposite direction weakened, by an action-current in the direction of the shock. And indeed a single excitation of the electrical nerve is followed by a series of electrical oscillations in the organ, which gradually die away. Whether the electrical organ is the homologue of muscle or of nerve-ending, or whether it is related to either, has not been definitely settled. That curara does not affect the electrical organ in Torpedo, although it paralyzes the motor nerve endings, is, as far as it goes, against the nerve-ending theory. That there is a measurable latent period (about Tj^jjth second) cannot be considered as in favour of the muscle theory, for the latent period is probably deter- mined more by functional than by morphological considerations. The skate must now be added to the list of electric fishes. Although its organ is relatively small, and its electromotive force relatively feeble, yet it is in all respects a complete electrical organ. It is situated on either side of the vertebral column in the tail. The plates or discs are placed transversely and in vertical planes. The nerves enter their anterior surfaces ; the shock passes in the organ from anterior to posterior end. Gotch and Sanderson have estimated the maximum electromotive force of a length of i cm. of the electrical ora:an of the skate at about half a volt. PRACTICAL EXERCISES ON CHAPTER XI. I. Galvani's Experiment. — Pith a frog (brain and cord). Cut through the backbone above the urostyle, and clear away the anterior portion of the body and the viscera. Pass a copper hook beneath the two sciatic plexuses, and hang the legs by the hook on an iron tripod. If the tripod has been painted, the paint must be scraped away where the hook is in contact with it. Now tilt the tripod so that the legs come in contact with one of the iron feet. Whenever 11 578 A MANUAL OF PHYSIOLOGY. this happens, the current set up by the contact of the copper and iron is completed, the nerves are stimulated, and the muscles contract (p. 555). 2. Make a muscle-nerve preparation from the same frog. Crush the muscle near the tendo Achillis, so as to cause a strong demarcation current. Cut off the end of the sciatic nerve. Then lift the nerve with a small brush or thin glass rod, and let its cross-section fall on the injured part of the muscle. Every time the nerve touches the muscle a part of the demarcation current passes through it, stimulates the nerve, and causes contraction of the muscle (p. 555). 3. Make a muscle-nerve preparation. Lay it on a glass plate A, supported on a block of wood. Snip off the end of the nerve N, and arrange the cut surface on a pad of kaolin B, moistened with normal saline. Another pad B' is placed under the nerve a little way from its cut end. Both pads project down over the edge of the glass plate. A watch-glass C filled with normal saline solution is lifted up below the projecting ends till they are im- mersed. Whenever this happens, a circuit is completed for the demar- cation current of the nerve itself, by which it is stimulated, and the muscle M contracts (Fig. 189). 4. Secondary Contraction. — Make two muscle-nerve preparations. Lay the cross-section of one of the sciatic nerves on the muscle of the other preparation (Fig. 1 82, p. 571). Place under the nerve near its cut end a small piece of glazed paper or of glass rod, and let the longitudinal surface of the nerve come in contact with the muscle beyond this. Lay the nerve of the other preparation on electrodes connected with an induction machine arranged for single shocks, with a Daniell cell and a spring key in the primary circuit (Fig. 160). On closing or opening the key both muscles contract. Arrange the induction machine for an interrupted current. When it is thrown into one nerve, both muscles are tetanized ; the nerve lying on the muscle whose nerve is directly stimulated is excited by the action current of the muscle. 5. Demarcation Current and Current of Action with Capillary Electrometer. — (a) Study the construction of the capillary electro- meter (Fig. 130, p. 469). Raise the glass reservoir by the rack and pinion screw, so as to bring the meniscus of the mercury into the field. Place two moistened fingers on the binding-screws of the electrometer, open the small key connecting them, and notice that the mercury moves, a difference of potential between the two binding-screws being caused by the moistened fingers. {b) Demarcation Current. — Set up a pair of unpolarizable elec- trodes (F'ig. 132, p. 471). Fill the glass tubes about one-third full of Fig. 189. — Stimll.\tion of a Nerve BY ITS OWN Demarcation Current. PRACTICAL EXERCISES. 579 kaolin mixed with normal saline solution till it can be easily moulded. To do this, make a piece of the clay into a little roll, which will slip down the tube. Then with a match push it down until it forms a firm plug. Next put some saturated zinc sulphate solution in the tubes, above the clay, with a fine-pointed pipette. Fasten the tubes in the holder fixed in the moist chamber (Fig. 190). Now amal- gamate the small pieces of zinc wire, which are to be connected with the binding-screws of the chamber. To amalgamate zinc, dip it into dilute sulphuric acid till a clean surface is formed ; rub mercury over it with a piece of cloth or cotton- wool until the whole surface is bright, and then wash with water. The zincs are now placed in the tubes, dipping into the zinc sulphate. A piece of clay or blotting-paper moistened with normal saline is laid across the electrodes to complete the circuit between their Fig. 190.— Moist Chamber. E, unpolarizable electrodes supported in the cork C ; M, muscle stretched over the electrodes and kept in position by the pins .-^ B stuck in the cork plate P ; B, binding- screws connected with galvanometer or capillary electrometer. The other pair of binding-screws serves to connect a pair of stimulating electrodes inside the chamber with the secondary coil of an induction machine. points, and they are connected with the electrometer to test whether they have been properly set up. There ought to be little, if any, movement of the mercury on opening the side-key of the electro- meter. If the movement is large, the electrodes are 'polarized,' and must be set up again. The second pair of binding-screws in the chamber are connected with a pair of platinum-pointed electrodes on the one side, and on the other, through a short-circuiting key, with the secondary coil of an induction machine arranged for tetanus. Next pith a frog (cord and brain), and make a muscle-nerve pre- paration. Injure the muscle near the tendo Achillis. Lay the injured part over one unpolarizable electrode, and an uninjured part over the other. Put a wet sponge in the chamber to keep the air moist, and place the glass lid on it. Focus the meniscus of the mercury, and open the key of the electrometer ; the mercury will 58o A MANUAL OF PHYSIOLOGY. move, perhaps right out of the field. Note the direction of move- ment, and remembering that the real direction is the opposite of the apparent direction, and that when the mercury in the capillary tube is positive to the sulphuric acid, the movement is from capillary to acid, determine which is the positive and which the negative portion of the muscle (p. 556). {c) Action Cur)r?it. — Now fasten the muscle to the cork or parafiin plate in the moist chamber, without disturbing its position on the electrodes, by pins thrust through the lower end of the femur and the tendo Achillis. Lay the nerve on the platinum electrodes. Open the key of the electrometer, and let the meniscus come to rest. This happens very quickly, as the capillary electrometer has but little inertia. If the meniscus has shot out of the field, it must be brought back by raising or lowering the reservoir. Stimulate the nerve by opening the key in the secondary circuit ; the meniscus moves in the direction opposite to its former movement. {d) Repeat {l>) and {c) with the nerve alone, laying an injured part (crushed, cut, or over-heated) on one electrode, and an uninjured part on the other. Of course the nerve does not need to be pinned. Clean the unpolarizable electrodes, and be sure to lower the reser- voir of the electrometer ; otherwise the mercury may reach the point of the capillary tube and run out. In 5 a galvanometer may be used instead of the electrometer, the unpolarizable electrodes being connected to it through a short- circuiting key. The spot of light is brought to the middle of the scale by moving the control-magnet; or if a telescope-reading (Fig. 125, p. 465) is being used, the zero of the scale is brought by the same means to coincide with the vertical hair-line of the tele- scope, The short-circuiting key is then opened. 6. Action-current of Heart. — Pith a frog (brain and cord). Excise the heart, and lay the base on one unpolarizable electrode, and the apex on the other, having a sufficiently large pad of clay on the tips of the electrodes to ensure contact during the movements of the heart, or having little cups hollowed in the clay and filled with normal saline, into which the organ dips. Connect the electrodes with the capillary electrometer and open its key. At each beat of the heart the mercury will move (p. 571). 7. Electrotonus. — Set up two pairs of unpolarizable electrodes in the moist chamber. Connect two of them with a capillary electro- meter (or galvanometer), and two with a battery 'of three or four small Daniell cells, as in Fig. 178. Lay a frog's nerve on the electrodes. When the key in the battery circuit is closed, the mercury (or the needle of the galvanometer) moves in such a direction as to indicate that in the extrapolar regions parts of the nerve nearer to the anode are positive to parts more remote, and parts nearer to the kathode are negative to parts more remote. The direction of movement of the mercury (or galvanometer needle) must be made out first for one direction of the polarizing current. Then the latter must be reversed, and the movement of the mercury (or needle) on closing it again noted (p. 567). PRACTICAL EXERCISES. 5S1 8. Paradoxical Contraction. — Pith a frog (brain and cord). Dis- sect out the sciatic nerve down to the point where it sphts into two divisions, one for the gastrocnemius b^ and the other for the peroneal muscles a. Divide the peroneal branch as low down as possible, and make a muscle-nerve preparation in the usual way. Lay the central end of the peroneal nerve on electrodes connected through a simple key with a battery of two Daniell cells. When the peroneal nerve is stimulated the gastrocnemius muscle contracts. This result is not due to the current of action, for it is not obtained with mechanical stimulation of the nerve ; but it is not the result of an escape of current, for if the peroneal nerve be ligatured between the point of stimulation and the bifurcation, no contraction is obtained. The contraction is really due to a part of the electrotonic current set up in the peroneal nerve passing through the fibres for the gastrocnemius, where they lie side by side in the trunk of the sciatic. 9. Alterations in Excitability and Conductivity produced in Nerve by the Passage of a Voltaic Current through it. — {a) Set up two pairs of unpolarizable electrodes in the moist chamber. Connect a battery of two or three Daniell cells, arranged in series, through a simple key with the side-cups of a Pohl's commutator with Fig. 191. — Paradoxi- cal Contraction. Fig. 192. — Ark.angemen't for showing Ch.\nge.s ok Excitability produced by the voltaic current. M, muscle ; N, nerve ; Ej, Eo, electrodes connected with secondary coil S ; E3, E4, unpolarizable electrodes connected witli Pohl's commutator (with cross-wires) C ; B', ' polarizing' battery ; B, ' stimulating ' battery in primary circuit P; K, K", simple keys ; K', short-circuiting key. cross-wires in. Connect the commutator to one pair of the unpolar- izable electrodes ('the polarizing electrodes'), as in Fig. 192. The other pair of unpolarizable electrodes ('the stimulating electrodes') are to be connected through a short-circuiting key with the secondary of an induction machine arranged for tetanus. A single Daniell is put in the primary coil. Pith a frog (brain and cord), make a muscle- nerve preparation, pin the lower end of the femur to the cork plate 582 A MANUAL OF PHYSIOLOGY. in the moist chamber, attach the thread on the tendo Achillis to the lever connected with the chamber through the hole in the glass pro- vided for this purpose, and arrange the nerve on the electrodes so that the stimulating pair is between the muscle and the polarizing pair. By moving the secondary, seek out such a strength of stimulus as just suffices to cause a weak tetanus when the polarizing current is not closed. Set the drum off (slow speed), and take a tracing of the contraction. Then close the polarizing current with the Pohl's commutator so arranged that the anode is next the stimulating electrodes, />., the current ascending in the nerve. Again open the short-circuiting key in the secondary ; the contraction will now be weaker than before, or no contraction at all may be obtained. Allow the preparation 2 minutes to recover, then stimulate again, as a control, without closing the polarizing current. If the contraction is of the same height as at first, close the polarizing current with the bridge of the commutator reversed, so that the kathode is now next the stimulating electrodes. On stimulating, the contraction will now be increased in height. (See Figs. 156, 157, p. 524). (b) Arrange everything as in [a), except that one of the polarizing electrodes is placed at each end, and the two stimulating elec- trodes close together in the middle of the nerve. A large carbon resistance (say 500,000 ohms) is introduced into the circuit of the secondary coil, to prevent more than a very small fraction of the polarizing current from passing through the coil. Seek out the strength of stimulation which just causes contraction when the polarizing current is not closed. Now close the polarizing current in such a direction that the anode is between the stimulating electrodes and the muscle. If no contraction occurs on stimulation, push up the secondary towards the primary till the muscle contracts. Then stop stimulation, open the polarizing current, and allow an interval of two minutes. Now pass the polarizing current through the nerve in the opposite direction, so that the kathode is between the stimulat- ing electrodes and the muscle. No contraction will be obtained on exciting with the same strength of stimulus as caused contraction when the anode was next the muscle. The kathode has diminished the conductivity of the nerve ; and if four or five small Daniell cells are put on in the polarizing circuit, no contraction may be obtained, even with the coils close together, while the stimulus will still pass the anode and cause contraction. (c) Connect a galvanometer or capillary electrometer by unpolar- izable electrodes with a frog's sciatic nerve, as shown in Fig. 193, the cut end being on one electrode, the longitudinal surface on the other. Arrange two polarizing electrodes (unpolarizable), one at each end of the remaining portion of the nerve, and connected through a simple key and a commutator with cross-wires with a battery of two or three small Daniells. A pair of fine platinum, or a third pair of very fine-pointed unpolarizable electrodes is placed under the nerve mid- way between the two polarizing electrodes, and connected, through a large carbon resistance, with the secondary of an induction-machine arranged for tetanus. Let the mercury of the electrometer or the PR A CTICAL EXERCISES. 583 spot of light on the scale of the galvanometer (or the telescope image of the scale) come to rest when the demarcation current of the nerve is thrown in. On stimulating the nerve when the polarizing circuit is open, a movement of the mercury in the capillary electrometer or of the spot of light (or telescope image, as the case may be) in the galvanometer takes place (current of action). Now close the polariz- ing current in such a direction that the anode is next the leading-off electrodes. An action current is still indicated on stimulation. Re- verse the polarizing current so as to bring the kathode ne.xt the lead- ing-off electrodes. The excitation is now blocked by the kathode, and no movement of the mercury or of the spot of light takes place. 10. Pflugers Formula of Contraction (p. 525). — To demonstrate this, connect two unpolarizable electrodes, through a spring key and a commutator, with a simple rheocord (Fig. 162), so as to lead off a twig of a current from a Daniell cell. The unpolarizable elec- trodes are placed in a moist chamber. A muscle-nerve preparation B, ' polarizing' bat- tery ; C, Pohl's com- mutator with cross- wires ; El, Eo, unpolar- izable electrodes con- nected with C ; D, platinum electrodes connected with S, the secondary coil, through the large carbon resist- ance R ; B', battery in circuit of primary P ; E;i, E4, unpolarizable electrodes connected with Hg and H0SO4, the mercury and sul- phuric acid of the capillary electrometer ; K, K', simple keys ; K", a short-circuiting key ; N, nerve. Fig. 193. — Arrangement for showing, by means of THE Capillary Electrometer, th.\t the Kathode Blocks the Nerve-impulse. is arranged with the nerve on the electrodes and the muscle attached to a lever. The effects of make and break of a weak current, ascend- ing and descending, can be worked out with the simple rheocord. The effects of a medium current will probably be obtained with a single Daniell connected directly with the electrodes through a key. The effects of a strong current will be got when three or four Daniells are connected with the electrodes. Care must be taken to keep the preparation in a moist atmosphere, and more than one preparation may be needed to verify the whole formula. II. Hitter's Tetanus. — Lay the nerve of a muscle-nerve prepara- tion on a pair of unpolarizable electrodes connected through a simple key with a battery of three or four small Daniells. Connect the muscle with a lever. Pass an ascending current (anode next the muscle for a few minutes) through the nerve, and let the writing-point trace on a slowly-moving drum. When the current is closed there may be a single momentary twitch, or the muscle may remain some- 584 A MANUAL OF PHYSIOLOGY. what contracted (galvanotonus) as long as the current is allowed to pass, or it may continue to contract spasmodically ('closing tetanus '). When the current is opened the muscle will contract once, and then immediately relax, or there may be a more or less continued tetanus (Ritter's or ' opening tetanus '). If opening tetanus is ob- tained, divide the nerve between the electrodes: the tetanus continues. Divide it between the anode and the muscle : the tetanus at once disappears. This shows that the seat of the excitation which causes the tetanus is the neighbourhood of the anode (p. 567). That there is a state of excitation in this region after a voltaic current is opened may be shown electrically thus : 12. Positive Polarization. — Connect a pair of unpolarizable elec- trodes by double leads with a battery of twelve or fifteen small Daniells and a galvanometer or capillary electrometer, as in Fig. 194. A Pohl's commutator without cross-wires is introduced in such a way that when the bridge is in one direction the battery circuit is made and Ej, Eo, unpolarizable <'Iecirodes connected with the ' polarizing ' battery B through a Fohl's commutator 'without cross-wires) C; K, simple key; Hg and HJSO4, the mercury and sulphuric acid of the capillary electro- meter ; N, nerve ; K', key in electrometer circuit. Fig. 194. — Scheme for Demonstrating ' Posi- tive Polarization ' by the Capillary Electrometer. the galvanometer or electrometer circuit broken, and vice versa when the bridge is tilted in the other direction. A frog's nerve is laid on tile electrodes in the moist chamber, with its cut ends at the same distance from the electrodes (streamless arrangement), to eliminate as far as possible the demarcation current. The battery current is now passed for an instant through the nerve ; the commutator is at once reversed, and the electrometer or galvanometer shows a movement indicating that the anodic area is negative to the kathodic (' positive polarization '). The positive polarization current is in the same direction as the polarizing current. The positive polarization effect may be preceded by a 'kick' in the opposite direction ('negative polarization '). The negative polarization effect is much increased if the polarizing current be allowed to flow for some time. For accu- rate experiments it is better to employ two pairs of unpolarizable electrodes, one for leading in the polarizing current to the tissue, and the other for leading off the polarization current to the galvanometer or electrometer. 13. G-alvanotropism. — Place at each end of a rectangular trough PRACTICAL EXERCISES. 585 filled with tap-water a metallic plate, or a plate of carbon, connected through a commutator and key with the poles of a Grove or bichro- mate battery of several cells, or, if the laboratory is provided with a current from the street, with the switch through one or more incan- descent lamps. Put into the water a number of tadpoles, which should not be too young. When the current is closed, the tadpoles will arrange themselves in a definite way with their long axes in the direction of the lines of flow. Reverse the current, and they turn their heads in the opposite direction. Determine whether the head of the tadpole is turned towards or away from the anode, and report the result of your observation. If the current is taken from the laboratory supply, the anode may be known as the electrode at which least gas comes off, or at which a mixture of potassium iodide and starch becomes blue. CHAPTER XII. THE CENTRAL NERVOUS SYSTEM. In other divisions of our subject we have been able to follow to a greater or less extent the processes which take place in the organs described. The chemistry and the physics of these processes have bulked more largely in our pages than the anatomy and histology of the tissues them- selves. In dealing with the central nervous system we must adopt a method the very reverse of this. Its anatomical arrangement is excessively intricate. The events which take place in that tangle of fibre, cell, and fibril are, on the other hand, almost unknown. So that in the description of the physiology of the central nervous system we can as yet do little more than trace the paths by which impulses may pass between one portion of the system and another, and from the anatomical connections deduce, with more or less pro- bability, the nature of the physiological nexus which its parts form with each other and the rest of the body. And here it may be well to remark that, although for convenience of treatment we have considered the general properties of nerves in a separate chapter, there is not only no funda- mental distinction between the central nervous system and the outrunners which connect it with the periphery, but obviously a central nervous system would be meaningless and useless without afferent nerves to carry information to it from the outside, and efferent nerves along which its commands may be conducted to the peripheral organs. Plate V. 2. C'over-glasa preparation of spinal cord of ox, x 250. (Stained with methyl blue.) Axis-cylinder Dendritic processes Detached cuU-cylinder proeexi Large ^ ji^< ^'^'^^ multivolar rurve-eeU , >v , JxU-eyhnier proeena Anterior column, Anterior nerve-root Bipolar nerve-cell Capillary Ant. median fissure Nerve-ceUs of anterior comu Nerve-fibres of ' trhite "natter Posterior nerve-root -i'^3Cr '' ^ lac^isure / ■ >':i)n-mediMated ' iicrve-fibres \ I I I Nucleus Medullated nerve-fibres ---Neuril-emma ■ I'ledullary sltealU '_ ,NodeofBaneier c 1. Nerve-lioies of frog, teased in f osmic acid, x 300. (Stained -with hasmatoxylin.) --'^ I'osterior coMmn 3. Transverse section of spinal cord. (Stained with a.niline blue-black.) Sylvian fissure Internal carotid. Basilar artery - Medulla oblotigatu Anterior cerebral .Hiddle cerebral -Corpora mamillariii 4. Base of brain, with arteries injected. West,I^ewTna.Ti clir.litk THE CENTRAL .XERVOUS SYSTEM. 587 I. Structure of the Central Nervous System.* In unravelling the complex structure of the central nervous system, we avail ourselves of information derived (i) from its gross anatomy ; (2) from its microscopical anatomy ; (3) from its development ; (4) from what we may call, although the term is open to the criticism of cross-division, its physiological and pathological anatomy. The study of development enables us not only to determine the homology, the morphological rank, of the various parts of the brain and cord, but also, by comparison of animals of different grades of organization, sometimes to decide the probable function and physio- logical importance of a strand of nerve-fibres or a column of nerve- cells. It is of special importance in helping us to differentiate and to trace the various tracts or paths into which the white matter of the central nervous system may be divided. For the medullary sheath is not developed at the same time in all the tracts, and a strand of nerve-fibres without a medulla, e.g., the pyramidal tract (p. 598) at birth, is readily distinguished under the microscope. Then, again — and this is what we propose to include under the fourth head — experimental physiology and clinical and pathological observation throw light not only on the functions, but also on the structure, of the central nervous system. For instance, complete or partial section, or destruction by disease, of the white fibres of the cord or brain, or of the nerve roots, or removal of portions of the grey matter, is followed by degeneration in definite tracts. And since, as we have already seen, degeneration of a nerve-fibre is caused when it is cut off from the cell of which it is a process, the amount and distribution of such degeneration teaches us the extent and position of the central connections of the given tract. And, particu- larly in young animals, removal of peripheral organs — an eye or a limb — may be followed by atrophy of portions of the central nervous system immediately related to it. Certain tracts of white or grey matter are also differentiated from each other by the size of their fibres or cells. For example, the postero-median column of the spinal cord has small fibres, the direct cerebellar tract large fibres ; the pyramidal cells in what we shall afterwards have to distinguish as the 'leg area' (p. 65S) of the cerebral cortex are large ; those of the ' face area ' are comparatively small. Certain tracts may also be marked out by means of the electrical variation, which gives token of the passage of nervous impulses along them when portions of the central nervous system or peripheral nerves are stimulated (Horsley and Gotch). * It is unnecessary to say that a complete description of the structure of the brain and cord from the anatomical standpoint would be out of place in a book like this. As in the other divisions of our subject, a knowledge of anatomy is assumed on the part of the reader. 588 A MANUAL OF PHYSIOLOGY. Development of the Central Nervous System. — Very early in development (Fig. 195) the keel of the vertebrate embryo is laid down as a groove or gutter in the epiblast of the blastodermic area (Chap. XIV.). The walls of this * medullary groove ' grow inwards, and at length there is formed, by their coalescence, the ' neural canal ' (Fig. 196), which expands at its anterior end to form four cerebral IW) Fig. 195. — Formation of the Neural Canal .'Vt an Early Stage (After Hill). vesicles (Fig. 197). Thus there is a continuous tunnel from end to end of the primary cerebro-spinal axis ; and this persists in the adult as the central canal of the spinal cord and the ventricles of the brain, whose ciliated epithelium represents the epiblastic lining of the primi- tive neural canal.* From the wall of this canal is developed the cerebro-spinal axis, with the motor roots of the spinal nerves. The - ^tUkcLL CQyixaA Neural Canal at a Later Stage. ganglia on the posterior roots arise from a series of epiblastic thicken- ings arranged along the neural canal, but outside its wall. From both poles of each ganghon cell a process grows out, one towards the periphery, which forms a peripheral nerve-fibre, the other centrally * Gaskell and Bland Sutton regard the central canal as the representa- tive of the alimentary canal of the (crustacean) ancestors of the verte- brates. THE CENTRAL NERVOUS SYSTEM. 589 to connect the cell with the cord. From the after-brain is developed the medulla oblongata, from the hind-brain the cerebellum and pons, from the mid-brain the corpora quadrigemina and crura cerebri. The fore-brain, or primary fore- brain, gives rise of itself only to the third ventricle and optic thalamus, but an anterior cere- bral vesicle or secondary fore- brain buds off from it and soon divides into two chambers, from the roof of which the cerebral hemispheres, and from the floor the corpora striata, are derived. Their cavities persist as the lateral ventricles, which communicate with the third ventricle by the foramen of Monro. The olfactory tracts are formed as buds from the secondary fore-brain. To complete the story of the development of the brain, it may be added that the retina is really an expansion of its nervous substance. A hollow process, the optic vesicle, buds out on each side from the primary fore -brain. A button of epiblast, which after- wards becomes the lens, grows against the vesicle and indents it, so that it becomes cup-shaped, the inner concave surface of the cup representing the retina proper, the outer convex surface the choroidal epithelium. The stalk becomes the optic nerve. Histological Elements of the Central Nervous System. — The central nervous system is built up (i) of true nervous elements, (2) of supporting tissue. The nervous elements consist of nerve- fibres and nerve-cells, but the antithesis of a time-honoured distinc- tion must not lead us to forget that the essential part of a nerve- fibre, the axis-cylinder, is a process of a nerve-cell, and the medullary sheath perhaps a product of the axis-cylinder. For although each internode of the medullary sheath of a peripheral nerve-fibre has been supposed to be formed from a cell that, in the course of development, comes in contact with the axis-cylinder and ultimately encircles it, a similar origin can hardly be admitted for the medulla of the fibres of the spinal cord and brain, where indeed a segmental genesis seems excluded by the absence of the nodes of Ranvier, the internodal nuclei and the neurilemma. Only meduUated nerve-fibres are met with in the white matter of the cerebro-spinal axis. In diameter they vary from 5 /x to 20 /x. In Malapteriirus electricus the fibre in the cord which supplies Fig. 197. — Diagram to illustrate the Formation of the Cerebral Vesicles. A. I indicates the cavity of the secondary fore-brain (anterior cerebral vesicles), whicli eventually becomes the lateral ventricles. In B the secondary fore-brain has grown back- wards so as to overlap the other vesicles. I, first cerebral vesicle (primary fore-brain) ; II, second cerebral vesicle (mid -brain) ; III, third cerebral vesicle (hind - brain) ; IV, fourth cerebral vesicle (after-brain). 590 A MANUAL OF PHYSIOLOGY. the electrical organ is of immense size ; and in the anterior column of many fishes may also be seen a single gigantic fibre on each side with a diameter of nearly loo /x. It cannot be said that any relation between the functions of nervous fibres and their size has been definitely established. Many afferent fibres, it is true, are small — this is notably the case with the fibres of the posterior column and posterior root — and many motor fibres are large. But the distinc- tion can by no means be generalized, for the fibres of the cerebellar tract, which certainly are afferent, are among the largest in the spinal cord ; and the vasomotor fibres, which pass from the cord into the sympathetic, are smaller than the fibres of the posterior column. Even the motor nerve-fibres of striated muscles vary considerably in diameter, those of the tongue, e.g., being smaller than those of the muscles of the limbs. Further, the medullated fibres of the brain are, without reference to function, in general finer than the fibres of the cord. The cause of these differences in the size of nerve-fibres is quite unknown. It is more likely to be morphological than physiological. The grey matter, in addition to non-medullated fibres and fila- ments arising from the nerve-cells, contains also, as may be seen in preparations stained by Weigert's method,* great numbers of exceed- ingly fine medullated fibres, which form with the interlacing non- medullated filaments a plexus, or feltwork. Nerve-cells are the most distinctive histological feature of the grey nervous substance. Sown thickly in the cerebral cortex, the basal ganglia, the floor of the fourth ventricle, and the cervical and lumbar enlargements of the cord, they are scattered more sparingly wherever the grey matter extends. They also occur in the spinal ganglia and their cerebral homologues, in the ganglia of the sympa- thetic system and the sporadic ganglia in general. But wide as is their distribution and great as is the size of the individual cells, they yet make up but a small portion of the whole of the central nervous substance. And although it is not to be wondered at that objects so notable when viewed under the microscope should have struck the imagination of physiologists, it is probable that the very high powers which it is so common to attribute exclusively to them ought to be, in part at least, shared with the nervous plexus woven from their processes and of which they form the nodes. A cell from the anterior horn of the spinal cord (Plate V, 2), which may be taken as a typical nerve-cell, is a knot of granular, often fibrillated, protoplasm, apparently destitute of a cell-wall, but containing a large nucleus, inside of which lies a highly refractive nucleolus. Several processes— it may be five or six— pass off from the cell-body, one of which is distinguished from the rest by the fact that it does not branch. This process, which in favourable cases can be traced on till it becomes the axis-cylinder of a nerve- fibre, is called the axis-cylinder process. The rest break up into * Weigert's is a special method of staining axis-cylinders with haema- toxylin. THE CENTRAL NERVOUS SYSTEM. 591 fibrils at a little distance from the cell, and lose themselves in the surrounding network, which forms the greater portion of the ground- material of the grey substance, and in which the branching systems of neighbouring cells anastomose — at least in the sense that it is possible for impulses to pass across it from one cell-system to another, whether an actual anatomical continuity exists or not. All the nerve-cells of the cerebro-spinal axis agree with the cells of the anterior horn in the possession of an unbranched process, and one or more offshoots that branch into the plexus of the grey matter. The cells of the sympathetic and spinal ganglia are on a different footing (see p. 627). «- Another kind of cell which seems undoubtedly to be of a nervous nature is the ' granule-cell.' Granule-cells are much smaller than the nerve-cells we have been describing. Their processes are much less easily followed, but probably the cells are bipolar. They con- tain a relatively large nucleus (5 to 8 /x in diameter), with only a mere fringe of cell-substance. The nucleus, unlike that of a large nerve-cell, stains deeply with hrematoxylin. Some parts of the grey matter are crowded with these granule-cells, e.g., the so-called nuclear layer of the cerebellum and the substantia gelatinosa, or substance of Rolando, which caps the posterior horn in the cord. In other parts they are more thinly scattered, but probably they are as widely diffused as the large nerve-cells proper, and no extensive area of the grey matter is wholly without them. The layer of ciliated epithelium lining the central canal of the spinal cord and the ventricles of the brain in the lower animals and in early life in man, has also been considered by some as of nervous nature ; and the fact that the deep ends of the cells are continued into processes which pierce far into the grey substance lends weight to this opinion. The supporting tissue of the central nervous system consists partly of ordinary connective tissue derived from the mesoblast, and partly of a peculiar form of tissue derived from the epiblast, and called neuroglia. The whole cerebro-spinal axis is wrapped in four concentric sheaths. Next the walls of the bony hollow in which it lies is the dura mater. Next the nervous substance itself, following the convolutions of the brain and the fissures of the cord, and giving off bloodvessels supported in connective-tissue septa to both, is the pia mater. Between the dura and the pia, separated from the latter by a jacket of cerebro-spinal fluid, is the double layer of the arachnoid. The comparatively coarse processes that run into the nervous sub- stance from the pia mater are the main beams in the scaffolding of non-nervous material with which that substance is interwoven, and by which it is supported. The interstices are filled in by a thick set network of interlacing and often branching filaments, given off l;y the small-bodied cells of the neuroglia. In certain situations — for example, in the grey matter immediately beneath the floor of the ventricles (the ependyma, as it is called) — the processes of these cells are especially long, and run out from the attenuated cell-body like the arms of a microscopic crab or spider, and they have hence received 592 A MANUAL OF PHYSIOLOGY. the name of ' spider-cells,' or cells of Deiters. Golgi's method* of stain- ing brings the processes out with great sharpness. Another kind of connective tissue has been described as peculiar to the central nervous system, and as consisting only of a granular mass, entirely devoid of cells, filling in the spaces of the grey matter not occupied by the other elements. It is for this substance that some authors reserve the name of neuroglia. But it is by no means certain that the granular appearance seen in microscopic preparations is due to anything else than the cross-sections of fine connective-tissue fibrils or of the nervous plexus. General Arrangement of the White and Grey Matter in the Central Nervous System. — (i) Around the central canal, as we Fig. 198. — Neuroglia Cells (from a liuman embryo 30 cm. in length). The small cell on the rijjht is from the grey, the other two from the white substance: Golgi's method (Kolliker). have seen, a tube of grey matter sheathed with white fibres is developed. This tube, from optic thalamus to conus medul- laris, may be conveniently referred to as the central grey axis or stem, which, in the lowest vertebrates, e.g., fishes, is much the most important part of the central nervous system. (2) On the outer surface of the anterior portion of the neural axis, but not in the part corresponding to the spinal * The method depends upon the deposition of mercury in or around the cell-bodies and their processes in tissues which have been hardened in bichromate of potassium and then soaked in a solution of mercuric chloride. In Pal's improvement of Golgi's method a solution of sodic sulphide follows the mercuric chloride. THE CENTRAL NERVOUS SYSTEM. 593 cord, is laid down a second sheet of cortical grey matter. Between this and the primitive grey stem are interposed (a) the sheath of white fibres that clothes the latter, and connects its various parts, and {h) a new development of white matter (corona radiata, cerebellar peduncles), which serves to bring the cortex into relation with the primitive axis, and through it with the rest of the body. Although there are histological and developmental dif- ferences between the cerebral and the cerebellar cortex, we may, for some purposes, classify them together as cortical formations. And we may also include under this head the corpora striata, which, although generally grouped with the optic thalami and the other clumps of grey matter at the base of the brain, as the basal ganglia, are to be regarded as cortical in character. As we mount in the vertebrate scale, the cortex formation of the secondary fore-brain and hind- brain acquires prominence. In other words, the grey matter developed in the roof of the cerebral vesicles I. and III. (Fig. 197) (the grey matter of the cere- bral and cerebellar cortex) comes to overshadow the superficial grey matter hitherto present only in the roof of vesicle II. (in the corpora bigemina). And this cortex formation becomes larger in amount, and, in the case of the cerebral grey matter, more richly convoluted, the higher we ascend, until it reaches its culmination in man. As the anterior cerebral vesicles develop, they spread continually back- ward until at length the cerebral hemispheres cover over, and almost completely surround, the primary fore-brain, and the mid- and hind- brains, so that the anterior portion of the primitive stem comes, as it were, to be invaginated into the second wider tube of cortical grey matter. This development of the cortical grey substance is accompanied with a corresponding development of white fibres, for an isolated nerve-cell is no more conceivable than a railway-station the track from which leads nowhere in particular, or a harbour on the top of a hill. But it is to be particularly observed that the new forma- tion does not supplant the old, but works through and directs it. The cortex does not throw out its filaments to make direct junction with muscles and sensory surfaces. Such junction it finds already established between the primitive cerebro-spinal axis and the periphery. It joins itself on by new white substance to the cells of the central stem ; and we have reason to believe that no fibres pass 3S 594 A MANUAL OF PHYSIOLOGY. either from the periphery to the cortex, or from the cortex to the periphery, without being broken in the cells of this primitive grey tube. The fibres from the cortex of each cerebral hemisphere (corona radiata), radiating out like a fan below the grey matter, are gathered together into a compact leash as they sweep down through the isthmus of the brain in the internal capsule, to join the crura cerebri. The cortex of each cerebellar hemisphere, and the ribbed pouch of grey matter, known as the corpus dentatum, which is buried in its white core, are also connected by strands of fibres with the central stem and the cerebral mantle. The restiform body or inferior peduncle brings the cerebellum into communication with the spinal cord. The superior peduncle by one path, and the middle peduncle by another, connect it with the cerebral cortex. A great transverse commissure, the corpus callosum, unites the cerebral hemispheres across the middle line, while transverse fibres that pass into the pons, as well as other fibres that break through the middle lobe or worm, form a similar junction between the two hemispheres of the cere- bellum. The fibres of the nervous system may be divided into (i) fibres connecting the peripheral organs with nerve-cells in the central grey axis ; (2) fibres connecting nerve-cells in this central axis with cells in the external or cortical grey tube ; and (3) fibres linking cortex with cortex, or central ganglia with each other. Our first task is, therefore, to trace the peripheral nerves to their cells or centres in the nervous stem. And although there is reason to believe that the whole of the peripheral nerves, cerebral and spinal (with the exception of the olfactory and optic, which are rather portions of the brain than true peripheral nerves), form an unbroken morphological series, it will be well to begin with the spinal nerves, since their motor and sensory fibres are gathered into different and definite roots, whose course within the cord is, in general, more easily traced than the course of the cerebral root-bundles within the brain. Arrangement of the Grey and White Matter in the Spinal Cord. — The grey matter of the spinal cord is arranged on each side in a great unbroken column of roughly crescentic section (Plate V., 3), joined with its fellow across the middle line by a grey bar or bridge, which springs from the con- vexity of the crescent, and is pierced from end to end by the central canal. The anterior horn of the crescent. THE CENTRAL NERVOUS SYSTEM. 595 although it varies in shape at different levels of the cord, is, in general, broad and massive in comparison with the slender and tapering posterior horn. In the lower cervical and upper dorsal region a moulding or projection, forming a lateral horn, springs from the fluted outer side of the gre> substance. Within the grey matter nerve-cells are founds Ce fvi c al '^si Cells ofihe — anitrior Cornu^ -StiUing's Cervical niieleus _ Z att ral cell- colum n (column of the tnter- medtc-lateral trad) -Stillin^'s dorsal nucleus or Clarke's Column. Lumbar ^ Enlarffemenf ^ : -Scattered cells of intermedio -laUral trad. ^Stilling's '■Sacrctl nucleus Fig. 199.— Diagram of Grey Tracts of Cord. sometimes so regularly arranged that they form veritable cellular or vesicular strands. Of these the best marked are : (i) The tract or tracts made up by the celh of the anterior horn (Fig. 199), which practically run from end to end of the cord, swell out in the cervical and lumbar enlargements, where the cells are very numerous and of great size (70 ix to 140 /i in diameter), and contract to a thin thread in the 596 A MANUAL OF PHYSIOLOGY. thoracic region, where they are relatively few, scattered, and small. (2) Clarke s coluum, whose cells are situated at the inner side of the root of the posterior horn just where it joins on to the grey cross-bar. It gradually increases in size from above downwards, usually appearing first at the level of the seventh or eighth cervical nerve, attaining its maximum development at the eleventh or twelfth dorsal and disappearing altogether, as a continuous strand, at the level of the second or third lumbar nerves. The so-called cervical and sacral nuclei of Stilling, however, occupy the same position towards the upper and lower ends of the cord, and may be looked upon as isolated portions of Clarke's column. (3) A tract called the intcrinedio-lateral trad, which is best marked in the thoracic region, but extends also down into the lumbar swelling and up until it blends with certain cells of the anterior horn of the cervical cord. (4) The cells of tJie posterior horn are much less nume- rous and smaller than those of the anterior horn. Through- out the whole cord, however, two small groups of cells may be distinguished, one on the lateral and the other on the mesial side of the isthmus or neck of the horn a little in front of (i.e., ventral to) the edges of the substance of Rolando. The white matter of the cord is anatomically divided by the position of the nerve-roots and the anterior and posterior fissures into three columns on each side: the anterior, lateral, and posterior columns (Plate V., 3). The first two are often grouped together as the antero-lateral column. In the cervical region it may be seen with the microscope that the posterior white column is almost bisected by a septum running in from the pia mater towards the grey commissure. The inner half is called the postero-median column, or column of Goll ; the outer half the postero-external column, or column of Burdach (Fig. 200). No localization of any of the other conducting paths in the cord is possible by anatomical examination ; but by means of the develop- mental method and the method of degeneration the columns of Goll and Burdach can be followed throughout the cord, and several similar areas can be mapped out. We shall THE CENTRAL NERVOUS SYSTEM. 597 only mention those that are physiologically the most im- portant. When the spinal cord is divided, and the animal allowed to survive for a time, certain tracts are picked out by the degeneration of their fibres, although in every degenerated tract some fibres remain unaffected. We may distinguish the tracts that degenerate above the lesion (ascending de- FiKST Cervical. Antero-lateral ground-bundle Sixth Cervical. Direct pyramidal Antero-lateral, nscend- ing and debcending Crossed pyramidal Direct cerebellar Postero-external (BurdE.ch's) Postero-median (GoU's) Sixth Dorsal. . Folrih Lu.mbar. Fig. 200. — Diagrammatic Sfxtions of the Spinal Coro to show the Tract-s ok White M.atter at Different Levels. generation) from those that degenerate below the lesion (descending degeneration). Ascending- Tracts. — Above the lesion degeneration is found both in the posterior and the antero-lateral columns. Immediately above the section nearly the whole of the posterior column is involved. Higher up the degeneration clears away from Burdach's tract, and, shifting inwards, comes to occupy a position in the column of Goll. In the antero-lateral column two degenerated regions are seen, both at the surface of the cord, one a compact, sickle-shaped area extendinsf forwards from the neisrhbourhood of the line of 598 A MANUAL OF PHYSIOLOGY. •entrance of the posterior roots, and the other an area of scattered degeneration, embracing many intact fibres, and completing the outer boundary of the column almost to the anterior median fissure. The compact area is called the direct cerebellar tract, the diffuse area the antero-lateral ascend- ing tract, or tract of Gowers. Descending: Tracts. — When the cord is divided, say in the npper dorsal or cervical region, the following tracts de- generate below the lesion : (i) A small group of fibres close to the antero-median fissure, which has received the name of the direct pyramidal tract — pyramidal, because higher up in the medulla oblongata it forms part of the pyramid ; direct, because it does not cross over at the decussation of the pyramids, but continues down on the same side. (2) A tract of degenerated fibres in the posterior part of the lateral column. This is the lateral or crossed pyramidal tract, and is much larger than the direct. In the medulla it also lies within the pyramid, but, unlike the direct pyramidal tract, it crosses to the opposite side of the cord at the decussation. (3) A tract of scattered degeneration overlapping the tract of Gowers, and called the antero-lateral descending tract. When we have deducted the long ascending and descend- ing tracts which have been described, there still remains, both in the anterior and in the lateral column, a balance of white matter unaccounted for. This white substance, which does not degenerate for any great distance either above or below a lesion, is called the antero-lateral ground-bundle, and lies chiefly in the form of an incomplete ring around the anterior cornu. It is believed to consist of fibres which run only a comparatively short course in the cord, and serve to connect nerve-cells at different levels. The next question which arises is : How are the long tracts connected below, i.e., with the periphery, and above, i.e., with the higher parts of the central nervous system ? The answer to this question, partly derived from clinical records and partly from experimental results, is in the case of some of the tracts unexpectedly full and minute, though THE CENTRAL NERVOUS SYSTEM. 599 meagre in regard to others. But to render it intelligible it is necessary, first of all, to describe briefly — The Arrangement of the Grey and White Matter in the Upper Portion of the Cerebro-spinal Axis. — In the medulla oblongata the grey and white matter of the spinal cord is rearranged, and, in addition, new strands of fibres and new nuclei of grey substance make their appearance. Of these nuclei the most conspicuous is the dentate nucleus of the inferior olive, which, covered by a crust of white fibres, appears as a pro- jection on the anterolateral surface of the medulla. In front of the olive, between it and the continuation of the anterior median fissure, is another projection, the pyramid, which looks hke a pro- longation of the anterior column of the cord, but is made up of very different constituents. Dorsal to the olive is the restiform body or inferior peduncle of the cerebellum, and behind the restiform body lie two thin columns, the funiculus cuneatus, which continues the postero-ex- ternal column of the cord, and the funiculus gracilis, which continues the pos- tero-internal column. In these funiculi are developed respectively the nucleus cuneatus and the nucleus gracilis. The rearrangement of the consti- tuents of the cord is due mainly to two causes : (i) The opening up of the central canal to form the fourth ventricle, and the folding out, on either side, of the grey matter which lies posterior to it in the cord ; (2) the breaking up of the grey matter of the anterior horn by strands of fibres as they sweep through it from the lateral pyramidal tract to take up a position in the pyramid of the opposite side (decussation of the pyramids). The cerebro-spinal axis passes up from the medulla Fig. 201. — Diagrammatic Transvekse Section of Medulla Oblongata. 1?, nucleus gracilis; b, nucleus cuneatus; (■, arcuate fibres crossing the middle line from a and b to the fillet, d ; e, anterior median fissure. 6oo A MANUAL OF PHYSIOLOGY. through the pons, encircled and traversed by its transverse fibres of the middle cerebellar peduncle or commissure, which enclose everywhere between them numerous collections of nerve-cells (nuclei pontis). Enlarged by the accession of many of these fibres which come from the cortex of the cerebellum on the opposite side, as well as of fibres from the nuclei of the cranial nerves that take origin in this neigh- bourhood (fifth and eighth), the central nervous stem bifur- cates above the pons into the two diverging crura cerebri. From each crus a great sheet of fibres passes up between the optic thalamus and the caudate nucleus of the corpus stria- tum on the one hand, and the globus pallidus of the lenticular nucleus on the other, as the internal capsule, from which they are dispersed, in the corona radiata, to the cerebral cortex. Both in the upper part of the pons and in the crus a ventral portion, or crusta, containing the fibres of the pyramidal tract, and a dorsal portion, or tegmentum, can be dis- tinguished, the line of separation being marked in the crus by a collection of grey matter, called from its usual, though not invariable, colour the substantia nigra (Fig. 203). A portion of the tegmentum is continued below the optic thalamus. Coming back now to our question as to the connections of the long tracts of the cord, let us consider, first of all, The Connections of the Postero-median and Postero-external Columns. — When a single posterior root is divided, say in the dorsal region, between the cord and the ganglion, its fibres, as we have already seen (p. 535), degenerate above the section. If a series of microscopic sections of the spinal cord be made, well-marked degeneration will be found at the level of entrance of the root on the same side of the cord, while below that level there will be few, if any, degenerated fibres. Immediately above the plane of the divided root the degeneration will be confined to Burdach's column and to its external border. Higher up it will be found in the internal portion of Burdach's and the external rim of Goll's column. Still higher up the degenerated fibres will be confined to the postero-median column ; the postero- external will be entirely free from degeneration. THE CENTRAL NERVOUS SYSTEM. 60 1 When a number of consecutive posterior roots are cut, the whole of the postero-external column in the sections immediately above the highest of the divided roots will be found occupied by degenerated fibres, while Goll's column may be free from degeneration, or de- generated only at its outer border. Higher up degeneration will be found to have involved the whole of the postero-median column, and to have cleared away altogether from the postero-external. The degenera- tion in the column of Goll may be traced along the whole length of the cord to the medulla. The meaning of all this is clear. Many of the posterior root-fibres after entering the cord pass up for a short distance in the postero-external column, sweeping obliquely through it to gain the tract of Goll. In this tract they run right on to the medulla oblongata, to end in a collection of grey matter of the nucleus gracilis. 'When the cervical posterior roots are cut, many of the degenerated fibres remain in Burdach's column up to the medulla, where they make junction with the nucleus cuneatus. In the posterior column, then, the fibres of the posterior roots which do not suffer interruption in nerve-cells in the spinal cord are arranged in layers, the fibres from the lower roots being nearest the median fissure, and those from the higher roots farthest away from it. Section of the posterior roots causes no degeneration in any long path elsewhere than in the columns of Goll and Burdach. We may, therefore, conclude without hesitation that some of the fibres of the posterior roots ascend to the medulla in the posterior column of the cord without making junction with any cells until they reach the gracile and cuneate nuclei, where they end by breaking up into terminal brushes of fibrils or dendrites. The trophic cells of these fibres lie, for the most part at any rate, in the posterior root-ganglia. But if the statement be accepted that some fibres degenerate in the central stump of the root when it is cut below the ganglion, we must admit that a few of the fibres in the ascending tract of the posterior column may have their trophic centres nearer the periphery. Connections of the Direct Cerebellar Tract. — Since the direct cerebellar tract does not degenerate after section of the Fig. 202. — Posterior Roots ENTERING ^PINAL C'oKD (at the left of the figure). (From a preparation stained with aniline blue-black.) 6o2 A MANUAL OF PHYSIOLOGY. posterior nerve-roots, but does degenerate above the level of the lesion after section of the spinal cord, its trophic cells must be situated somewhere or other in the cord. Now, the cells of the anterior horn are known, in great part at any rate, to be connected with other tracts, so that there are left over, to all intents and purposes, only the scattered cells of the posterior horn and the vesicular column of Clarke. Now, it has been observed that the column of Clarke first becomes prominent in the lower dorsal region, and that in this same region the direct cerebellar tract begins. Further, axis- cylinder processes may be seen sweeping out from Clarke's column in the direction of the direct cerebellar tract, and although, in all probability, nobody has as yet been able definitely to follow any of those axis-cylinder processes into fibres of the tract, the evidence when put together is pretty strong that the cells of Clarke's column, or some of them at least, are their trophic cells. The tract runs right up to the cerebellum through the restiform body, without crossing and without being further interrupted by nerve-cells. The fibres of the restiform body end partly in the dentate nucleus of the cerebellum, partly in the vermis. Connections of the Antero-lateral Ascending Tract. — It is not known with any certainty with what cells in the spinal cord this tract is connected. All we can say is that none of its fibres can come directly from the posterior nerve-roots, since no degeneration is seen in the tract on section of the roots alone. It passes up through the medulla, where it perhaps makes junction with the cells of the lateral nucleus, a collection of grey matter in the lateral portion of the spinal bulb. Thence through the formatio reticularis it is supposed to reach the pons, and, turning back through the superior peduncle, ends in the cerebellum. The formatio reticularis is the mosaic of grey and white matter formed in the medulla by the interlacing of longitudinal and trans- verse fibres with each other and with the relics of the grey matter of the anterior horn. Its longitudinal fibres are derived from the fillet and from the remains of the anterior and lateral columns after the direct and crossed pyramidal tracts have taken up their position in the pyramid and the direct cerebellar tract has passed into the restiform body. The antero-lateral ascending tract seems to pass bodily into the formatio reticularis and to form part of its longitudinal fibres. The transverse fibres sweep in bold curves towards the raphe THE CENTRAL NERVOUS SYSTEM. 603 from the gracile and cuneate nuclei and the dentate nucleus of the olive. The reticular formation occupies the whole of the anterior and lateral portions of the medulla behind the pyramids and olivary bodies, and is continued upwards in the dorsal portion of the pons and crura. Through the gracile and cuneate nuclei, but particularly the latter, the postero-internal and postero-external columns of the cord are further connected on the one hand with the cerebellar cortex by fibres passing up in the restiform body of the same side, and on the other hand with the fillet by Fig. 203. — Di.-\GRAM.M.-'iTic Transverse Section of Crura Cerebri and Aqueduct of Sylvius. a. anterior corpora quadrig;emina ; b, aqueduct ; r, red nucleus ; d, fillet ; e, sub- stantia nigra ; /, pyramidal truer in tlie crusta of the crura cerebri ; g, fibres from frontal lobe of cerebrum ; h, fibres from temporo-occipital lobe ; /, posterior longi- tudinal bundle. fibres which sweep in wide arches (internal arcuate fibres) across the mesial raphe to the opposite side. The fillet is a well-marked bundle which is formed from those fibres and lies immediately behind the pyramid. Receiving fibres from other sources on its way, and giving off at least one strand to the cerebellum, it runs upwards in the dorsal or tegmental portion of the pons and crura cerebri, posterior to the formatio reticularis, with the longitudinal fibres of which it blends in the region below the optic thalamus. One well- marked strand of these longitudinal fibres receives the name of the posterior longitudinal bundle (Fig. 203). From the 6o4 A MANUAL OF PHYSIOLOGY. sub-thalamic region fibres stream out in all directions to join the corona radiata for distribution to the cerebral cortex. Connections of the Pyramidal Tracts, — When the cortex around the fissure of Rolando is destroyed by disease in man, or removed by operation in animals, it is found that in a short time degeneration has taken place in the fibres of the corona radiata which pass off from this area. The degenera- tion can be followed down through the genu and the anterior two-thirds of the posterior limb of the internal capsule (Fig. 204), and the crusta of the cerebral peduncle of the corresponding side into the medulla oblongata. Below the decussation of the pyramids it is found that the degenera- tion has involved the two pyramidal tracts, and only these — the crossed pyramidal tract on the side opposite the cortical lesion, the direct pyramidal tract on the same side — and that the cross-section of the two degenerated tracts goes on continually diminishing as we pass down the cord. (We overlook, for the moment, in the interest of simplicity of statement, the fact that in the monkey, at any rate, some degenerated fibres may be found in the crossed pyramidal tract on the same side as the lesion.) This is proof positive that the trophic cells of these tracts are situated in the cerebral cortex. The fact that the degeneration does not spread to the anterior roots is proof probable that nerve- cells intervene between the pyramidal fibres and the root- fibres. The results both of normal and morbid histology complete the proof, and enable us to identify the cells of the anterior horn as the cells in question. For (i) Axis-cylinder processes have been actually observed passing out from certain of the so-called motor cells of the anterior horn to become the axis-cylinders of fibres of the anterior root. (2) The only cells which are left after we deduct the scattered cells of the posterior horn and the cells of Clarke's column, which are believed to have other connections, are the cells of the anterior cornu. (3) An enumeration has been made in a small animal (frog) of the cells of the anterior horn and of the anterior root-fibres, and it has been found that the numbers agree in THE CE.\TRAL NERVOUS SYSTEM. 605 a remarkable manner. From all this it cannot be doubted that most, at any rate, of the cells of the anterior horn are connected with fibres of the anterior root. But since the number of fibres in the pyramidal tracts falls far short of the number of cells in the anterior horn, and of the number of fibres in the anterior roots, it is necessary to assume that one pyramidal fibre may be connected with several cells. (4) In the pathological condition known as anterior poliomyelitis, the cells of the anterior horn degenerate, and so do the anterior roots of the affected region, the motor fibres of the spinal nerves, and the muscles supplied by them. Connections of the Antero-lateral Descending Tract. — Degenera- tion is caused in this tract by a lesion in the cerebellum on the same side. The degeneration lessens as we pass down the cord. From this we conclude that the trophic cells of the antero-lateral descending tract lie in the cerebellum. It is said that some degenerated fibres are found in the anterior roots. This would point to a direct con- nection between the cortex of the cerebellum and the motor nerves, but the matter cannot as yet be considered beyond the pale of controversy. The descending antero-lateral tract passes down from the cerebellum in the restiform body. Thus far, then, we have been able to map out two great paths from the cerebral cortex to the periphery, one efferent, the other afferent, (i) The great eiferent or motor path, which, starting in the cortex around the fissure of Rolando, sweeps down the broad fan of the corona radiata, passes through the narrow isthmus of the posterior limb of the internal capsule into the crusta of the crus cerebri, and thence into the pyramid of the bulb. Here the greater part (usuall}^ about go per cent.) of the fibres decussate, appearing in the cervical cord as the massive crossed pyramidal tract of the opposite side. A few (usually about 10 per cent.) continue on the same side as the slender direct pyramidal tract ; but the breadth of this tract constantly diminishes as its fibres continue to decussate across the anterior white commissure, and to reinforce the crossed tract of the opposite side. The fibres of this crossed tract are, in their turn, continually passing off into the grey matter of the anterior horn, where they break up into fibrils or dendrites, and thus make connection (physiological if not 6o6 A MAXUAL OF PHYSIOLOGY. anatomical) with the fine nerve-plexus in the vicinity of the cells, whose axis-cylinder processes enter the anterior roots of the spinal nerves. The losses which it suffers as it passes along the cord may be partly compensated by the bifurcation of some of its fibres (geminal fibres), but ultimately the whole tract makes junction with the grey matter, and dwindles away as the lumbar region is reached (Fig. 200). It has been asserted that on their way down the cord the two crossed pyramidal tracts exchange some fibres with each other (recrossed fibres) ; and it was supposed that this would explain the escape in hemiplegia (paralysis of one side of the body) of those muscles which are accustomed to work with the corresponding muscles on the opposite side. But although there is no doubt that such muscles are innervated to some extent from both cerebral hemispheres, it is more probable that this is due to uncrossed than to recrossed fibres. (2) A great afferent or sensory path by which some, at least, of the impulses carried up through the posterior roots of the spinal nerves, after passing through various relays of nerve- cells, reach the cortex of the cerebellum ; or the upper portions of the central grey tube, the corpora quadrigemina and optic thalamus ; or, finally (both indirectly and by a more direct route which certain fibres of the fillet and the formatio reticularis follow through the tegmentum and the posterior limb of the internal capsule behind the motor fibres), the cerebral cortex itself. The efferent path from the cortex of the brain is broken by but one relay of nerve-cells, the motor cells of the anterior horn. The afferent path is interrupted by at least two relays, one in the ganglion on the posterior root, another in the medulla ; and on some of the routes perhaps another, or even more than one, between the medulla and the cortex. Numerous as are the nervous ties of the cerebral cortex, those of the grey matter of the cerebellum are, in proportion to its mass, still more extensive, and perhaps not less im- portant. But since our knowledge of the cerebellum is even less complete than our knowledge of the cerebrum, it will be sufficient to indicate in the form of a summary the chief paths by which impulses may enter and leave it. THE CENTRAL NERVOUS SYSTEM. 607 Connections of the Grey Matter of the Cerebellum with the Periphery and other parts of the Central Nervous System. — (i) The dentate nucleus and the grey matter of the worm are connected with the periphery through the restiform body : {a) By an afferent path mostly uncrossed — through the restiform body and the direct cerebellar tract — with two relays on it : one in Clarke's column, the other in the spinal ganglion, {b) By an afferent path — restiform body and the posterior column of both sides ot the cord — through the relays of the gracile and cuneate nuclei and the posterior root ganglion, {c) By a com- missural path — restiform body, inferior olive of opposite side, and formatio reticularis of bulb, pons and crus — with the cerebral cortex. (2) The grey matter of the worm is connected with the periphery by an afferent path — superior peduncle of the cerebellum, formatio reticularis of the pons and medulla, antero-lateral ascending tract of the spinal cord (?). (3) When we add that the dentate nucleus is linked through the superior peduncle of the cerebellum with the red nucleus of the tegmentum of the crus cerebri on the opposite side, and thus with the cortex of the opposite cerebral hemisphere, it will be seen that the path by the restiform body, dentate nucleus, and superior peduncle, may form an alternative route for afferent impressions passing from the periphery to the great brain — a path broken by at least four relays of nerve-cells. (4) Further, a broad tract runs from the cerebellar to the cerebral cortex of the opposite side through the middle peduncle and the relay of the pontine grey matter. (5) An uncrossed connection also exists between the cerebellum and the vestibular branch of the auditory nerve, through one of its nuclei of origin, and possibly between it and other cranial nerves, such as the optic and trigeminal. (6) The cerebellar cortex may be connected by an efferent path through the restiform body and the descending antero-lateral tract with the motor roots of the same side. The Internal Capsule. — We must now learn that the in- ternal capsule embraces other fibres than those which pass down into the spinal cord as the pyramidal tracts, and up from it as the afferent tegmental path. In the first place, it contains numerous fibres running from the Rolandic area, and destined to make connection with the motor nuclei of the cranial nerves in the grey matter underlying the aqueduct of Sylvius and the fourth ventricle. The cranial and spinal fibres, indeed, form but one com- pact bundle (pyramidal tract) in their passage through the corona radiata and internal capsule, the knee of which is occupied by the former, the posterior limb by the latter, and may be followed as a distinct strand throus:h the middle 6o8 A MANUAL OF PHYSIOLOGY. of the crusta into the pons. Here the fibres for the nuclei of the cranial nerves decussate. But we have not yet exhausted the constituents of the internal capsule. Two great cones of fibres sweep down into it, one from the frontal, the other from the occipital and temporal portions of the cerebral cortex. The first passes through its anterior limb, the second behind the sensory path in its posterior limb. Running on through the Fig. 204. -Diagrammatic Horizontal Section of Left Half of Brain to SHOW Internal Capsule. crusta of the cerebral peduncle (Fig. 203), the frontal tract internal, the occipito-temporal external, they end in the grey matter of the pons, and probably serve as one segment of an extensive commissural connection between the cerebral and the cerebellar cortex of the opposite side, the other segment being formed by fibres which reach the pons through the middle cerebellar peduncle. Although their further con- nections are unknown, it is evident that the junction of the cerebral cortex with this pontine grey matter, through and into which so many nerve-tracts pass, multiplies the number THE CENTRAL NERVOUS SYSTEM. 609 of possible routes by which impulses may travel between one part of the brain and another. The pons itself is to a large extent a great transverse commissure between the two halves of the cerebellum, as the corpus callosum is between the two cerebral hemispheres. And intertwined in the corona radiata with the callosal fibres are other commissural systems, of which it is especially necessary to mention the fibres which link nearly every part of the cerebral cortex with the optic thalamus. These fibres pass from the frontal and parietal regions through the anterior, and from the occipital region through the posterior border of the internal capsule, those from the occipital cortex forming what is called the optic radiation. The thalamus is also connected with the cortex of the temporal lobe, with the cerebellum, and through the fillet with the posterior part of the tegmental system, the medulla oblongata and the spinal cord. We have purposely omitted to enumerate many other paths by which the various tracts of grey matter in the brain are brought into communication with each other, and our knowledge of such connections is constantly augmenting. When we add that not only are the cerebral hemispheres united by many ties to the subordinate portions of the cerebro-spinal axis and to each other, but that cortical areas of one and the same hemisphere are in communication by short connecting loops of ' association ' fibres, it will be seen that the linkage of the various parts of the central nervous system is extremely complex ; that an excitation, blocked out from one path, may have the choice of many alternative routes ; and that the apparent simplicity and isolation of the pyramidal tracts must not be allowed too far to govern our views of the possibilities open to a nervous impulse once it has been set going in the labyrinth of the nervous network. Nor is it only by the white fibres that nervous impulses can be conducted. There is the clearest evidence that they can also spread along continuous sheets of grey matter ; and the actual route taken by a given impulse is, in all probability, determined, under certain cir- cumstances at least, as much by molecular conditions as by anatomical relations ; so that a road open at one moment 39 6io A MANUAL OF PHYSIOLOGY. may be closed at another. We may suppose that the greater the number of connections between the cells of the central nervous system, the greater is the complexity of the processes which may be carried on within it. And, indeed, comparison of the brains of different animals shows us that it is not so much by excess in the quantity of grey matter as by the increased complexity of linkage, that a highly developed brain differs from a brain of lower type ; the higher the brain, the smaller is the proportion of grey to white substance. II. Functions of the Central Nervous System. Much of our knowledge of the functions of the central nervous system and of its divisions has been gained by the removal or destruction of more or less extensive tracts of nervous substance, or the cutting off of connection between one part and another. But it is well to warn the reader at the very outset that in no other part of physiology is such caution required in making deductions as to the working of the intact mechanism from the phenomena which mani- fest themselves after such lesions. In the first place, every operation of any magnitude on the brain or cord is imme- diately followed by a depression of the functional power of the nervous tissue, a depression which may extend far from the actual seat of injury and manifest itself by various phenomena, which are grouped together under the name of * shock.' Thus, when the spinal cord of a dog is divided, e.g., in the dorsal region, all power, all vitality one might almost say, seems to be for ever gone from the portion of the body below the level of the section. The legs hang limp and useless. Pinching or tickling them calls forth no reflex movements. The vaso-motor tone is destroyed, and the vessels gorged with blood. The urine accumulates, overfills the paralyzed bladder, and continually dribbles away from it. The sphincter of the anus has lost its tone, and the faeces escape involuntarily. And if we were to continue our observations only for a short time, a few hours or days, we should be apt to appraise at a very low value the functions THE CENTRAL NERVOUS SYSTEM. 6ii of that part of the cord which still remains in connection with the paralyzed extremities. But these symptoms are essentially temporary. They are the results of shock ; they are not true 'deficiency' phenomena. And if we wait for a time, we shall find that this torpor of the lower dorsal and lumbar cord is far from giving a true picture of its normal state ; that, cut off as it is from the influence of the brain, it is still endowed with marvellous powders. If we wait long enough, we shall see that, although voluntary motion never returns, reflex movements of the hind-limbs, complex and co-ordinated to a high degree, are readily induced. Vaso- motor tone comes back. The functions of defaecation and micturition are normally performed. Erection of the penis and ejaculation of the semen take place in a dog. Pregnancy carried on to labour at full term has been observed in a bitch whose cord was completely divided above the lumbar en- largement. Secondly, we must not run into the opposite error, and assume, without proof, that all the powers which the brain or cord is capable of manifesting under abnormal circum- stances are actually exercised by either when, under ordinary conditions, it is working along with and guiding, or being guided by, the other. For example, the reflex powers of the cord are certainly, if not increased, at all events more freely exercised when the controlling influence of the higher centres has been cut off than when the central nervous system is intact. Thirdly, there is another class of phenomena which we must make allowance for, and perhaps more frequently in the case of pathological lesions in man than in experimental lesions in the lower animals. This is the class of ' irrita- tive ' phenomena. The irritation set up by a blood-clot or a collection of pus, or in any other way, in a wound of the grey or white matter, may cause a stimulation of nervous tracts by which, for a time, the ' deficiency ' effects of the lesion may be masked. In the fourth place, we must not hastily conclude that when no obvious deficiency seems to follow the removal of a portion of the central nervous system, the function of 6i2 A MANUAL OF PHYSIOLOGY. that portion must necessarily be of such a nature as to give rise to no objective signs. For we have reason to believe that, to a certain extent, the function of one part may, in its absence, be vicariously performed by another. Bearing in mind the cautions we have just been empha- sizing, we may broadly distinguish between the functions of the cord (including the bulb) and those of the brain proper by saying that the cord is essentially the seat of reflex actions, the brain the seat of automatic actions and con- scious processes. But neither of these conceptions is entirely correct. Both err by defect and by excess. The brain, it is true, is pre-eminently automatic. The move- ments which are started in the grey matter of the cerebral cortex are pre-eminently voluntary (p. 654), but we cannot deny to the brain the possession of reflex powers as well. The movements in which the only nerve centres con- cerned are those of the spinal cord are above all reflex (p. 622). But some of its centres, and especially those lying in the medulla — for example, the respiratory centre — are perhaps, much as they are influenced by afferent im- pulses, capable of discharging automatic impulses too. And while consciousness is certainly bound up with the integrity of the brain, and in all the higher mammals is probably associated with cerebral activity alone, it has been plausibly maintained that the spinal cord, even of such an animal as the frog, is also endowed with something which might be called a kind of hushed consciousness. If this is so for the frog, with its distinct though relatively ill- developed cerebral hemispheres, it must be still more likely in the case of fishes and animals below them, which are practically devoid of a cerebral cortex altogether. Functions of the Spmal Cord (including the Medulla Ob- longata).— The functions of the spinal cord may be classi- fied thus : 1. The conduction of impulses set up elsewhere — either in the brain or at the periphery. 2. The modification of impulses set up elsewhere (reflex action). 3. The origination of impulses (?). THE CENTRAL NERVOUS SYSTEM. 613 I. Conduction of Nervous Impulses by the Cord, —The old controversy as to whether the white fibres of the spinal cord are directly excitable may be considered as definitely settled in the affirmative. Long strands of white matter have been isolated, and laid on electrodes, and contractions of distant muscles have been seen to follow stimulation, even when every precaution has been taken to avoid escape of current on to the anterior roots. And indeed, apart from direct experimental evidence, the fact that the white fibres of the brain are universally admitted to be excitable by artificial means would be of itself almost sufficient to decide the question, for we know of no essential difference between the cerebral and the spinal fibres. But the conditions must rarely occur under which direct stim.ulation of white fibres in their course is possible in the intact body ; and the only impulses with which we need concern ourselves here are those that reach the conducting paths from grey matter in the cord itself or in the brain, or from the peripheral organs. What sort of impulses, then, do the various tracts of the spinal cord conduct ? For the posterior roots this question was first fully answered by Magendie ; for the anterior roots by Sir Charles Bell. Bell observed that, when he cut the motor roots in an animal just killed, and stimulated the peripheral ends, muscular contractions were obtained. He concluded from this that the anterior roots are motor ; but although he is often credited with the discovery of the functions of the posterior roots as well, he never made the decisive experiment necessary to show that they are the conductors of sensory impulses, which indeed, although in language not altogether free from ambiguity, he sometimes appears to assign along with the motor impressions to the anterior roots. When the posterior roots are divided, loss of sensation occurs in the region to which they are distributed. If only one root is cut, the loss of sensation is never complete in any part of the skin ; and Sherrington has found that the areas of distribution of consecutive nerve-roots are not sharply marked off from each other, but to some extent 6i4 A MANUAL OF PHYSIOLOGY. ■overlap (Fig. 205). Stimulation of the peripheral end of the divided posterior root has no effect. Stimulation of the central end gives rise, if the animal be conscious, to •evidences of pain, and other signs of the passage of afferent impulses, e.g., a rise in blood-pressure. The latter may also be observed when the animal is anaesthetized. Head has shown that there is no overlapping in the sensory supply of the viscera from neighbouring spinal segments. He finds that in disease of internal organs the pain is referred to definite regions of the skin for each organ. In these regions the excitability for im- pressions of touch or temperature is increased, and the reflexes elicited by stimulation are exaggerated. There is reason to believe that the bond of connection is a common anatomical origin or a physiological correlation, somewhere or other in the central nervous Fig. 205.— Diagram to illustrate the Overlapping of the Sensory Nerve-supply ok the Skin from Consecutive Segments of the Cord. After section of one posterior root, its area of distribution is still supplied by fibres (represented by the interrupted lines) from the nerve above and the nerve helow it. system, between the sympathetic fibres of any viscus and the sensory supply of the corresponding cutaneous area. On the assumption that any given viscus is supplied with sensory fibres from the same spinal segment or segments as the cutaneous area mapped out in these ways (an assumption which the close correspondence of Head's results with the distribution of the large medullated fibres found in the visceral nerves, and believed to be sensory in function, would in itself render justifiable), he has determined the sources of the visceral sensory supply as follows : THE CENTRAL NERVOUS SYSTEM. 615 Nerve-roots. Dorsal. Lunibar. Sacral. Heart - - 1—3 Lungs - - 1—5 Stomach - 6-9 Intestines 9 — 12 Rectum 12 — 2—4 Liver and gall-bladder - 7 — 10 Kidney and ureter 10 — 12 Bladder 1 1, 12 I 2—4 Prostate TO 12 5 1—3 Epididymis I I, 12 I Testis and ovary 10 Uterus - - - 10 12 I 2—4 The skin of the head and neck has been similarly mapped out into seventeen zones corresponding to the 'viscera' of this region. For example, a lower laryngeal zone extends from the middle line to the median border of the sterno-cleido-mastoid, and downwards to the sterno-clavicular articulation. In diseases of the larynx hyper- algesia (increased sensibility to pain) is present in this area, and stimulation of the skin often causes reflex coughing. The hyper- algetic zones do not correspond to the distribution of the posterior roots of the cervical plexus and the sensory portion of the tri- geminus ; the segmentation in virtue of which the viscera and skin are correlated as regards their sensory supply must, therefore, be higher up in the central nervous system. Recurrent Sensibility. — Although muscular contraction is the most conspicuous event that follows stimulation of the peripheral end of an anterior nerve-root, it is by no means the only one. It is frequently observed, though not in all kinds of animals, that here, too, pain is caused. That this pain is not due to the muscular contraction is proved by the fact that it can still be elicited when the nerve-trunk is divided between the junction of the roots and the periphery. The real explanation of the phenomenon seems to be that certain fibres from the posterior roots bend up for some distance into the anterior roots, and then turn around again and pursue their course to their peripheral distribution in the mixed nerve, or run on in the motor roots to supply the sheath surrounding them (nervi nervorum), and even the membranes of the spinal cord. The afferent impulses that enter the cord along the pos- terior roots have the choice of many paths by which they may reach the brain (Fig. 206). 6i6 A MANUAL OF PHYSIOLOGY. (i) They may pass directly up through the postero-median column. If they take this route, their course will be first interrupted by nerve-cells in the gracile or cuneate nuclei in the medulla oblongata. Thence they may find their way across the middle line Fibr^ connecting CerebeJ 'n/:Jied nucleus &;:thus tir. cerelral cortex Cerehellu rn^\ Fiires connecting \Jh gracile ^ cuneate vS^ nuclei, tir. CereleJlunt \^ throughresti- ~^'"~ fnrnt body f/i .Py ram idal Cell /!.- -B Axis-cylinder- 1 '\^ \;'prccess of I •^■'\SmallNerve-cell \ ,-\p/ cetel'vol corttx\ "".WjRig/X . I \JCercbntl\ fiCorlex^ ...ri, JFihre ofPyrutn. trtscl (ctitshor/r) 1/^e.rve Cells-'"" of gracile &; cuneate nuclei . Fil>re of Direct Cerebellar Tract. Filre of QoU's CoU ''MeduU(y^' OlJg^^ata -Filre- cf Gourers'Tract X— -Nerve-cell cfPo stHcm (?) w \. ^cit.Rootcf&anghonCcU Nertre-Cellof --h^ Ant.HornJ^^ Gan gtion -Cell onFostRoct--(M Post.Root Fiires ^J^h^^e-CellofAnt. Horn ~Ne rve - Ce II of Clarke 's Col. \Middte line. PossilJe Affe rent Pattis. Fig. 206.— Possible Paths ok Afferent Impulses in the Central Nervous System (Schematic). by the arcuate fibres of the upper or sensory decussation, and sweeping along the fillet and the longitudinal fibres of the reticular formation of medulla, pons and crus, and the sensory path in the hinder third of the posterior limb of the internal capsule, finally arrive at the cerebral cortex. THE CENTRAL NERVOUS SYSTEM. 617 (2) They may pass up by the direct cerebellar tract and restiform body. If they take this route, their course will be interrupted by nerve-cells very soon after their entrance into the cord, presumab'y in Clarke's column, and again in the dentate nucleus of the cere- Ce-r e braJ Co rte oc J^ilr'e for- Head Po\n s "ife c ussa tion _ vf Pyramids. Ft I re of I>irect_ Pij rami da I tract. of Ant. Born. J^ , Term tnal Arborisation 1 (faPijramidal Fibre J around Cell of — ^^ Ant Horn Medulla Ohlonqata a yRicrrsscdFiirn^ -. — .'j -. Uncn ssefi Fiir e . ^, Ccrd Anter icr ^Root- Fibres • A > Effi-rent Paths Fig. 207.- -PossiBLE Paths of Efferent Impulses in the Central Nervous System (Schematic). bellum. The impulses may then cross the middle line by the superior peduncle to the tegmental region of the crus cerebri, where they may again make junction with cells in the red nucleus. From the red nucleus they may find their way by the tegmental sensory path to the cerebral cortex. 6i8 A A/AA'UAL OF PHYSIOLOGY. (3) They may reach the cerebellum by the anterolateral ascend- ing tract, passing first through nerve-cells in the lateral nucleus of the medulla (?), then by the formatio reticularis of the medulla and pons to the superior peduncle of the cerebellum, and thence to the grey matter of the worm on the same side. (4) They may cross the middle line through collaterals (p. 626) which run in the posterior grey commissure, enter one of the ascend- ing tracts on the other side, and continue without further decussation up to their central destination. (5) They may spread in the tangle of the grey matter itself and pass out again at a different level into one of the white tracts on the same or on the opposite side of the cord. Efferent impulses, originating in the brain, may travel : (i) Through the direct or crossed pyramidal tract. If they do so their course will not be interrupted by nerve-cells anywhere between the cerebral cortex and the motor cells of the anterior horn. (2) From one side of the cerebral cortex to the other, and then down the pyramidal tracts corresponding to that side(?). (3) From the pre-frontal part of the cerebral cortex, through the anterior limb of the internal capsule to the grey matter in the pons, and thence to the cerebellum by its middle peduncle. (4) From the occipital or temporal cortex in the hinder rim of the internal capsule to the pontine grey matter and through the middle peduncle to the cerebellum. From the cerebellum they may possibly be reflected down the antero-lateral descending tract to the cord, and indirectly, if not directly, to the periphery. All the paths enumerated, as well as others to which it would be tedious to formally refer, and which the ingenuity of the reader may be profitably employed in constructing for himself, from the data already given, are to be looked upon 2iS possible channels for the passage of impulses between the brain and the periphery. But what is certain is in this case much more limited than what is possible. It is certain that the pyramidal tracts are the conductors of voluntary motor impulses, and that in most individuals the great majority of such impulses decussate in the medulla oblongata, only a small minority in the cord. For a lesion involving the pyramidal tract above the decussation of the pyramids causes paralysis of the opposite side of the body, a lesion below the decussation paralysis of the same side- But it is possible that when one pyramidal tract has been destroyed, in certain animals at least, the motor cortex from which it leads may to a certain extent place itself again in THE CENTRAL NERVOUS SYSTEM. 619 communication with the paralyzed muscles through its com- missural connections with the opposite hemisphere. On the other hand, it is certain that pathological or traumatic lesions, involving the destruction of one lateral half of the cord in man and experimental hemisections in animals, are usually followed by symptoms which suggest that the sensory impulses decussate chiefly in the spinal cord — viz., increase of sensibility (hyperaesthesia) below and on the same side as the injury, and diminution of sensibility on the opposite side. This was first pointed out by Brown- Sequard, although long after he saw cause to retract this interpretation of his experiments. It is, however, equally certain that no ascending degeneration is to be found on the opposite side of the cord either after hemisection or after division of posterior roots (Mott). But while this latter fact shows that none of the afferent jihres cross the middle line before being interrupted by nerve-cells, it by no means proves that afferent impulses do not decussate in the cord. And, indeed, we know that some afferent impulses do decussate far below the level of the medulla. For, (i) A part of the negative variation (p. 556) crosses the middle line and ascends in the opposite half of the cord when the central end of one sciatic is stimulated (Gotch and Horsley). (2) Crossed reflex movements are possible ; and when excitation of the central end of the sciatic is followed by contraction of the muscles of the opposite fore-limb, the afferent impulses must either decussate in the lumbar cord, and then run up on the opposite side to the level of the brachial plexus, or must ascend on the same side and cross over somewhere between the plane of the sciatic and the brachial nerve-roots. The only other hypothesis on which crossed reflex action can be explained — but a hypothesis for which there is not a tittle of evidence — is that the afferent impulse always acts on motor cells whose axis-cylinder processes pass over to the opposite side, and there enter anterior nerve-roots. But while, for these reasons, it cannot be denied that some afferent impulses decussate in the cord, it would be a great error to argue from this that all, or even the majority, do so. And, indeed, there is good evidence 620 A MANUAL OF PHYSIOLOGY. that at least the greater part of the impulses concerned in sensation do in reality remain on the side of the cord which they first enter, right up to the medulla oblongata. To sum up, we may say that while it is certain that most of the motor, and many of the sensory, impulses decussate in the medulla, unanimity has not as yet been reached with reference to the place of decussation of the whole of the sensory impressions, and it is possible that some of them decussate in the cord, others in the bulb. And when it is remembered how difficult it sometimes is to interpret the account which a man gives of his sensations and to recognise precisely the degree and nature of sensory defects produced by disease in the human subject, it will not be thought surprising that experiments on animals, from the time of Galen onwards, should have yielded evidence which, although perhaps now at length tending to a definite result, is still unfinished and in part conflicting. If this is true where the problem is merely to determine the crossing- place of afferent impulses which are certainly known to cross, it is only to be expected that we should be still more in the dark as regards the routes by which different kinds of afferent impulses thread their way through the maze of conducting paths in the neural axis to reach their planes of decussation and gain the ' sensory crossway ' in the internal capsule. Some authors have indeed cut the Gordian knot by assuming that any kind of sensory impression may travel up any afferent path. Direct stimulation of a naked nerve- trunk, it has been argued in favour of this view, gives rise to a sensation of pain ; stimulation of the skin in which the end-organs of the nerve lie gives rise to a sensation of touch or a sensation of temperature, according as the stimulus is a mild mechanical or a thermal one, the contact of a feather or of a hot test-tube. Why, it has been asked, should we imagine that the difference in the result of stimulation depends on a difference in the nerve-fibres excited, and not on a difference in the kind of impulses set up in the same nerve-fibres ? This is a question which we shall have again to discuss (p. 671). But apropos of our present problem, we may say that there is very clear evidence from the patho- logical side that a limited lesion in the conducting paths of THE CENTRAL NERVOUS SYSTEM. 621 the central nervous system may be associated with defect or total loss of one kind of sensation, while all the other kinds remain intact. And there seems no other tenable hypo- thesis than that in such cases the pathological change has picked out a particular group of fibres, either collected into a single strand or scattered among unaltered fibres of different function. For example, in locomotor ataxia, a disease in which inco-ordination of movement and derange- ment of the mechanism of equilibration are prominent symptoms, degeneration in the posterior column of the cord is a most constant lesion ; and there is strong evidence that afferent impulses from muscles and tendons, which give rise to impressions belonging to the group of tactile sensations, and which, according to the most widely accepted doctrine, serve as the basis of the muscular sense, and play an im- portant part in the maintenance of equilibrium (p. 644), pass up in the posterior column. A case has been observed where a man received a stab which divided the whole of one side of the cord and the posterior column of the other side. Sensibility to touch was lost on both sides of the body below the level of the injury, sensibility to pain only on the side opposite to the main lesion. This, how- ever, is the only tract which has been associated, on evidence at all sufficient, with the passage of sensory impressions of a particular kind. Definite paths for temperature sensations have, indeed, been described in the lateral column. And Schiff has credited the grey matter of the cord with the power of conducting the impulses that give rise to pain, and has asserted that such impulses can be propagated along a cord in which hardly a vestige of white substance remains uncut. But these statements cannot be considered as resting on adequate proof, although it is certain that im- pressions of pain and of temperature do pass up somewhere or other in the antero-lateral column, and Gowers has brought forward some facts which he interprets as indicating that the antero-lateral ascending tract is the path for sensi- bility to pain. The impulses which descend the cord give token of their arrival at the periphery by causing either contraction of 622 A MANUAL OF PHYSIOLOGY. voluntary muscles, or contraction of the smooth muscles of arteries, or secretion in glands. They all pass down in the antero-lateral column, but the path of the voluntary impulses in the pyramidal tracts is the best known and most sharply defined. 2. Modification of Impulses set up elsewhere (Reflex Action). — The spinal cord, although it is a conductor of nervous impulses originating elsewhere, is by no means a mere con- ductor. Many of the impulses which fall into the cord are interrupted in its grey matter. Some of the efferent impulses proceeding from the brain are perhaps modified in the cord, and then transmitted to the muscles. Some of the afferent impulses are modified, and then transmitted to the brain ; some are modified, and deflected altogether into an efferent path. These last are the impulses which give rise to reflex effects. Strictly speaking, a reflex action is an action carried out in the absence of consciousness ; not necessarily, how- ever, in the absence of general consciousness, but in the absence of consciousness of the particular act itself. But the term is often used so as to embrace all kinds of actions which are not directly voluntary, whether the individual is conscious of them or not. For example, when the sole of the foot is tickled, the leg is irresistibly and involuntarily drawn up by reflex contraction of its muscles ; yet the person is perfectly cognisant both of the movement and of the sensation which accompanies the afferent impulse. Then there is a class of reflex actions in which consciousness is entirely in abeyance ; during sleep most of the ordinary reflexes can be elicited. Normally, it is believed that reflex movements are governed by impulses descending from the higher centres, for {a) it is a matter of common experience that a reflex movement may be to a certain extent controlled, or prevented alto- gether by an effort of the will, and it is worthy of remark that only movements which can be voluntarily produced can be voluntarily inhibited ; (6) an animal responds to stimuli by reflex movements more readily after the medulla oblongata has been divided from the spinal cord ; (c) by stimulation of certain of the higher centres reflex movements which would THE CENTRAL NERVOUS SYSTEM. 523 otherwise be elicited may be suppressed or greatly delayed. If the cerebral hemispheres be removed from a frog, and one leg of the animal be dipped in dilute acetic acid, a certain interval, the (uncorrected) reflex time, will elapse before the foot is drawn up (Tiirck's method, p. 680). If now a cr3'Stal of common salt be applied to the optic lobes or the upper part of the spinal cord, and the experiment be repeated, it will be found that either the interval is much lengthened, or that the reflex disappears altogether. Strong stimulation of any afferent nerve will also abolish or delay a reflex movement. In order that a reflex action may take place, the reflex arc — afferent nerve, central mechanism, and efferent nerve — must be complete; and in fact a whole series of simple reflex movements exists, the suppression, diminution, or exaggera- tion of which can be used as tests of the condition of the reflex arc in diagnosis. Such are the plantar reflex (the drawing-up of the foot v/hen the sole is tickled), the cremasteric reflex (retraction of the testicle when the skin on the inside of the thigh just belov/ Poupart's ligament is stroked, espe- cially in boys), the knee-jerk (a sudden extension of the leg by the rectus femoris muscle when the ligamentum patellae is sharply struck), the gluteal, abdominal, epigastric, and inter- scapular reflexes (contraction of the muscles in those regions when the skin covering them is tickled). The jaw-jerk (a movement of the lower jaw when, with the mouth open, the chin is smartly tapped) and ankle-clonus (a series of spasmodic movements of the foot, brought about by flexing it sharply on the leg) are phenomena of the same class, which can be elicited only in disease. Any condition which impairs the conducting power of the afferent or efferent fibres of the reflex arc necessarily diminishes or abolishes the reflex move- ment, even if the centre is intact. E.g., in locomotor ataxia the disappearance of the knee-jerk is one of the most im- portant and significant diagnostic signs. This disease involves the posterior roots and the fibres that continue them in the posterior column. The anterior nerve-roots are perfectly healthy. The grey matter of the cord — at least, in the earlier stages of the disease — is unaffected. The weak link in the 624 A MANUAL OF PHYSIOLOGY. chain is the afferent path. In anterior poliomyelitis (p. 605) the afferent Hnk is intact, but the other two are broken, and the reflexes also disappear. Any lesion which cuts off the spinal cord from the control of the higher centres without affectingtheintegrity of the reflex arcs increases the strength of reflex movements and the facility with which they are called forth. In paraplegia, e.g. (paralysis of the legs and the lower portion of the body), caused suddenly by accident to the cord, or more slowly by acute or chronic transverse myelitis, or in hemiplegia (par- alysis of one side of the body), caused by disease in the brain, the knee-jerk can usually be elicited with startling promp- titude and exaggeration, and ankle - clonus may also be obtained. In spastic spinal paralysis, which is associated with degenerative changes in the lateral columns, a similar increase in the true and pseudo- reflexes may be seen, due generally to the cutting off of inhibitory impulses, but some- times perhaps to an actual increase of excitability in the grey matter of the cord. The position of the centres in the cord for the various simple reflex movements is shown in Fig. 208. Myotatic Irritability (Muscle Reflex). — Although for con- venience of treatment we have included the knee-jerk (with the jaw-jerk and ankle-clonus) among reflex movements, it might more properly be termed a pseudo-reflex, for there is evidence that the mechanism by which it is produced is V J c D L 5 J ^ 2 3 ■ 4- S.../: ... 7. .8... i... .2 3 ... -4... ,. J S. 1... 6.. J7.. a .9- .1.0. U. 12. /. .....j .3. I .4. 51 / l/esicctl { 2"Rec£di'\ z...9.er!ii.»h.\... ynierscajtuJa r 'Eftiifastric T..'..'.'.'.'.'..' Knee-jerk hnkle-CJonus Fig. 208. — Diagram ok Kefle.x Centres in Cord (after Hill). THE CENTRAL NERVOUS SYSTEM. 625 different from that concerned in the reflex Winking of the eyelid, or the reflex retraction of the testicle, or the drawing- up of the foot when the sole is tickled. The strongest part of this evidence is the fact that the interval which elapses between the tap and the jerk (yfo to ^^ second) is distinctly shorter than the reflex time of the extremely rapid lid-reflex, and is not much greater than the latent period of the quadri- ceps muscle for direct electrical stimulation, as measured under the ordinary conditions of its contraction. The knee- jerk is obtained in undiminished strength when the nerves of the ligamentum patellae have been divided. It is therefore not a reflex movement caused by stimulation of afferent nerves coming from the tendon, and the name ' tendon- reflex' is clearly a misnomer. But that it is related in some way or other to afferent impulses is certain, for division of the posterior roots that enter into the sciatic nerve abolishes the knee-jerk. The phenomenon probably comes under the head of what by som^e authors is called myotatic irritability — that is, it depends on mechanical stimulation of the slightly- stretched muscle by the pull of the tendon when it is struck. It seems to be necessary for this stimulation that the muscle should be to a certain extent tonically contracted. So that when the afferent fibres are interrupted, or the grey matter of the cord disorganized, and the reflex tone abolished, the knee-jerk disappears. Anatomical Basis of Reflex Action. — Since the essence of reflex action is that the arrival of afferent impulses in the spinal cord causes the discharge of efferent impulses, there must be some connection between the incoming and the outgoing nerve-fibres. Moderate stimulation of an afferent nerve causes contraction of muscles con- nected with the same segment of the cord on its own side. Stronger excitation, particularly of the end-organs of a nerve, as in stimula- tion of the skin, will be followed by more extensive movements involving higher or lower segments of the cord, or crossing over to the opposite side. Sometimes the reflex movements are co-ordinated to a high degree, and even ' purposive ' in their action. This also is less true of movements caused by stimulation of naked nerve-trunks than of movements caused by stimulation of sensory surfaces. Let a piece of skin in a brainless frog be severed from the rest, but left in connection vvith its nerves. Excitation of the latter will produce simple and comparatively aimless contractions, while pinching of the skin or painting it with dilute acid may cause extensive movements, 40 626 A MANUAL OF PHYSIOLOGY. evidently aimed at the removal of the irritation. If a drop of dilute acid be applied to the flank of a ' reflex ' frog, it will attempt to wipe it off" with the foot which is situated most conveniently for the pur- pose. If this foot be held, it will use the other. It is evident that the connections between the fibres of the posterior and anterior roots must be very extensive. Indeed, the phenomena of strychnia poisoning seem to show that every afferent fibre is potentially connected with the motor mechanisms of the whole cord. For in a frog under the influence of this drug, stimulation of the smallest portion of the skin will cause violent and general convulsions, which are unaffected by destruction of the brain, but cease at once on destruction of the cord (p. 680). Our problem, then, is to find connections — first, between the afferent fibres of each spinal segment and its efferent fibres, and, secondly, between the central mechanisms of all the segments of the cord. When the nervous system is still only a process of an epithelial (sensory) cell joining hands with a muscular cell, the distinction between afferent and efferent fibre does not exist. When development ,/.'i5N. -■■^^■'s has gone a step further, and the neuro-muscular process is interrupted by a second epi- thelial cell transformed into a nerve-cell, the afferent fibre enters one pole and the effer- ent fibre leaves the other pole of the same cell. With in- creasing complexity of organi- zation the nervous impulse passing up the afferent fibre is offered a choice of many routes when it reaches the nerve-cell. This is effected by means of the plexus formed by its branching pro- cesses with the processes of other cells. It may be seen in preparations of the cord stained by Golgi's method that the fibres of the posterior roots, soon after their entrance into the cord, divide into two processes, one of which runs up and the other down in the posterior column or in the adjoining portion of the posterior horn. From these are given off" at intervals slender side-branches (collaterals), some of which pass into the grey matter, and there break up into a terminal brush of fibrils. These fibrils interlace with the ramifications of the scattered cells of the posterior horn and the cells of Clarke's column, and through them a physio- logical, if not an anatomical, connection is established between the fibres of the posterior root and the cells of the grey matter. Other collaterals from the posterior root-fibres and many of the root-fibres themselves run into the anterior horn. Some cross the middle line in the posterior commissure, and end in the grey matter of the opposite side. There is thus formed an ample connection between the posterior roots and the efferent nerves of the same segment on both sides of the cord, and also between any one posterior root and Fig. 209. — Diagram ok a Simple Reflex Akc. The arrows indicate the direction of the afferent and efferent impulses. THE CENTRAL NERVOUS SYSTEM. 627 the spinal grey matter at different levels. The grey matter of adjoining segments is further united by the commissural fibres of the anterior ground bundle already spoken of (p. 598), and doubtless also by the numerous fibres and fibrils that interlace in its own substance. Under ordinary conditions we must suppose that the resistance to the passage of impulses is greater for certain paths than for others, that it is easier, e.g., for an impulse travelling up a given posterior root to reach the anterior root-fibres of its own segment on its own side than to cross the middle line and tap the opposite efferent tract, or to extend longitudinally along the cord and flow over into efferent tracts coming off at a higher or lower level. The action of strychnia must be to diminish the resistance in the whole of the spinal cord, so that an impulse, instead of being confined to a fairly definite path, spreads indiscriminately over the grey matter. The transition from the afferent to the efferent fibres of a reflex arc, so far as we know, never takes place in highly organized animals except through a nervous plexus. In the peripheral ganglia the nerve- cells appear to give off no branches that form a plexus around them. They seem to be trophic cells interpolated in the course of the fibres whose nutrition they govern, or stations at which nerve-fibres break up for their peripheral distribution, not junctions through which impulses may be shunted from one kind of fibre to another. Thus, the cells of a spinal ganglion represent the original neuroblasts from which the posterior root-fibres grew out as processes towards the cord on the one side and the periphery on the other. A sensory fibre passing into the ganglion makes connection with a cell by a T-shaped junction (which may be considered as a stalk formed by the coalescence of a portion of the entering and outgoing fibres), and passes on its course again. Here it is evident that there is no possibility of a complete reflex arc, and accordingly no reflex function has ever been associated with the spinal ganglia. The sympathetic ganglion-cell may, indeed, have several processes, but one of them is the axis-cylinder of a meduUated fibre that comes to it from a higher centre, and the others the axis-cylinders of, it may be, five or six non- medullated fibres passing away from it to their destination. Here, again, there is no anatomical foundation for a reflex arc, and the most careful physiological experiments have failed to demonstrate any reflex function in the sympathetic ganglia. Sokownin, indeed, observed that stimulation of the central end of the hypogastric nerve caused con- tractions of the bladder, and he considered these movements to be reflex, the centre being the inferior mesenteric ganglion. Langley and Anderson have also recently found that when all the nervous connections of the inferior mesenteric ganglion, except the hypogastric nerves, are cut, stimulation of the central end of one hypogastric causes contraction of the bladder, the efferent path being the other hypogastric. In addition, they have observed an apparent reflex excitation of the nerves which supply the erector muscles of the hairs (pilo-motor nerves) through other sympathetic ganglia. But they believe it likely that in neither case is the action truly reflex, but that it is caused by stimulation of the central ' ends of spinal motor 628 A MANUAL OF PHYSIOLOGY. fibres ' connected with the ganglia. These motor fibres, in the case of the inferior mesenteric ganghon, send a branch to ' the nerve-cells of the opposite hypogastric' Reflex Time. — When a reflex movement is called forth, a measurable period elapses between the application of the stimulus and the commencement of the movement. This interval may be called the uncorrected reflex time. A part of the interval is taken up in the transmission of the afferent impulse to the reflex centre, a part in the transmission of the efferent impulse to the muscles, a part represents the latent period of muscular contraction, and the remainder is the time spent in the centre, or the true reflex time. When the conjunctiva or eyelid is stimulated on one side both eyelids blink. This is a typical reflex action reduced to its simplest expression, and the true reflex time is correspond- ingly short — only about oV second. An additional y^ second is consumed in the passage of the afferent impulse along the fifth nerve to the medulla oblongata, of the efferent impulse from the medulla to the orbicularis palpebrarum along the seventh nerve, and in the latent period of the muscle. When a naked nerve, like the sciatic, is stimulated, the true reflex time is reduced to y^o to -V second. As estimated by Tiirck's method (p. 680), the uncorrected reflex time is greatly lengthened, it may be to several, or even many, seconds. For here it is evident that the time taken by the acid to soak through the skin and reach the nerve-endings in strength sufficient to stimulate them is included. But even when the peripheral factors remain constant, the central factor may vary. With strong stimulation, e.g., the reflex time is shorter than with weak stimulation. Fatigue of the nerve centres delays the passage of impulses through them ; and strychnia, while it increases the excitability of the cord, also lengthens the reflex time. 3. The Origination of Impulses in the Spinal Cord. Automatism. — A physiological action is termed automatic when it depends upon a nervous outburst which seems to be spontaneous, in the sense that it is not brought about by any evident reflex mechanism, or, in other words, is not THE CENTRAL NERVOUS SYSTEM. 629 discharged by afferent impulses falling into the centre where it arises. An action known to be caused or conditioned by such afferent impulses is called a reflex action. Automatic actions being thus defined in a negative manner by the defect of a quality, there is always a possibility that some day or other it may be demonstrated that any given action which at present seems automatic in its origin depends on afferent impulses hitherto unnoticed. As a matter of fact, the supposed proofs of spinal automatism have in more than one case vanished with the advance of knowledge, and as the domain of purely automatic action has been narrowed, that of reflex action has extended, until the controversy as to the boundaries between the two seems not unlikely to be ended by the absorption of the automatic in the reflex. And as we seem almost driven to conclude that from the anatomical standpoint the nervous system is essentially a vast collection of looped conducting paths, each with an afferent portion, an efferent portion, and connections be- tween them formed by cells and cell networks, so it may be that no true physiological automatism really exists either in cord or brain, that every form of physiological activity — muscular movement, secretion, intellectual labour, conscious- ness itself — would cease if all afferent impulses were cut off from the nervous centres. But there are certain groups of actions so widely separated from the most typical reflex actions that, provisionally at least, they may be distin- guished as automatic. Such are the voluntary movements, and certain involuntary movements, like the beat of the heart. And we may proceed to inquire whether the spinal cord has any power of originating movements or other actions of this high degree of automatism. Muscular Tone. — So long as a muscle is connected with the spinal segment from which its nerves arise, it is never com- pletely relaxed ; its fibres are in a condition of slight tonic contraction, and retract when cut. If a frog whose brain has been destroyed is suspended so that the legs hang down, and one sciatic nerve is cut, the corresponding limb may be observed to elongate a little as compared with the other. At one time this tone of the muscles was supposed 630 A MANUAL OF PHYSIOLOGY. to be due to the continual automatic discharge of feeble impulses from the grey matter of the cord along the motor nerves. But it has been proved that if the posterior roots be cut, or the skin removed from the leg, its tone is com- pletely lost although the anterior roots are intact. So that the tone of the skeletal muscles depends on the passage of afferent impulses to the cord, and must be removed from the group of automatic actions and included in the re- flexes. The ' rigidity ' of the muscles, often observed in paralysis from lesions of the central nervous system, and denominated * early ' or * late ' according as it comes on within a few days or a few weeks after the occurrence of the lesion, is also probably in part a reflex phenomenon, although possessing some of the characters of a tonic contraction due to auto- matic discharge from the spinal centres. For in such cases myotatic irritability is increased; the knee-jerk is exaggerated; a finger-jerk may be elicited by tapping the wrist, an arm- jerk by striking the skin over the insertion of the biceps or triceps, ankle-clonus by flexing the foot (Gowers). Now, myotatic irritability depends on reflex muscular tone (p. 624). It is probable that the tone of such visceral muscles as the sphincters of the anus and bladder have also a reflex element, and possible that the same is true of the tone of the smooth muscular fibres of the bloodvessels on which the maintenance of the mean blood -pressure so largely depends. And it may be that if all afferent impulses could be cut off from the vaso-motor centre, as by section of the whole of the posterior spinal roots and other centripetal paths to the medulla, general dilatation of the arterioles would take place, and the blood - pressure be greatly diminished. Trophic Tone. — The degenerative changes that occur in muscles, nerves, and other tissues when their connection with the central nervous system is interrupted have been already referred to (p. 536). It is possible to explain these changes in some cases without the assumption that tonic impulses are constantly passing out from the brain and cord to THE CENTRAL NERVOUS SYSTEM. 631 control the nutrition of the peripheral organs ; and we have seen that there is no real evidence of the existence of specific trophic fibres. But the degeneration of muscles after section of their motor nerves is inexplicable except on the hypothesis that impulses descending from the cells of the anterior horn influence their nutrition. The only ques- tion is whether these are the impulses to which muscular tone is due, and therefore reflex, or different in nature and automatically discharged. Now the nutrition of a muscle is not affected, or at least not for a long time, by interrup- tion of its afferent nerve-fibres, as in locomotor ataxia, or after section of the posterior nerve-roots (Mott and Sherring- ton). We can hardly suppose that in any case the trophic influence of the cells of the spinal or sympathetic ganglia, to which all other reflex powers have been denied, is of reflex nature. And there is, indeed, more evidence in favour of trophic tone being an automatic action of the cord than for any of the other tonic functions hitherto considered. Respiratory Automatism. — But the evidence upon which the spinal cord has been credited with true automatic action is chiefly connected with the central respiratory mechanism. It is known (p. 177) that a section above a certain level in the medulla oblongata does not abolish the respiratory movements. The respiratory centre, then, must be continually sending out impulses which are not originated by impulses reaching it from the brain. But this is far from being a proof of definite automatic action by the spinal cord, for although afferent impulses do not, under the conditions of that experiment, reach the respiratory centre from the brain, they may and do reach it from the periphery; and the only true test of automatic activity would be to sever the whole of the afferent paths leading to the centre, and then to observe whether or no the respira- tory movements continued. This is an experiment which it is difficult, if not almost impossible, to carry out. But to say this is merely to confess that, in the present state of ex- perimental physiology, it is difficult or impossible to apply a crucial test to the doctrine of respiratory automatism. The ' Centres ' of the Cord and Bulb. — We have frequently used 632 A MANUAL OF PHYSIOLOGY. the word ' centre ' in describing the functions of the spinal cord, but the term, although a convenient one, is apt to convey the idea that our knowledge is far more minute and precise than it really is. When we say that a centre for a given physiological action exists in a definite portion of the spinal cord, all that is meant is that the action can be called out experimentally, or can normally go on, so long as this portion of the cord and the nerves coming to it and leaving it are intact, and that destruction of the ' centre ' abolishes the action. For example, a part of the medulla oblongata on each side of the middle line in the floor of the fourth ventricle above the calamus scriptorium is so related to the function of respiration that when it is destroyed the animal ceases to breathe. But this respiratory centre, the ' nceud vital ' of Flourens, does not correspond in position with any definite collection of grey matter, although it includes the nuclei of origin of several cranial nerves, and forms an important point of departure for efferent, and of arrival for afferent, fibres con- nected with the respiratory act. Its destruction involves the cutting off of the impulses constantly travelling up the vagus to modify the respiratory rhythm, and of the impulses constantly passing down the cord to the phrenics and the intercostal nerves. And just as the traffic of a wide region can be paralyzed at a single blow by severing the lines in the neighbourhood of a great railway junction, or more laboriously, though not less effectually, by separate section of the same tracks at a radius of a hundred miles, so destruction of the respiratory centre accomplishes by a single puncture what can be also performed by section of all the respiratory nerves at a distance from the medulla oblongata. But while nobody speaks of the destruction of a ' centre ' when a reflex action is abolished by division of the peripheral nerves concerned in it, there is a tendency, when the same effect is brought about by a lesion in the brain or cord, to invoke that mysterious name, and to forget that the cerebro- spinal axis is at least as much a stretch of conducting paths as a col- lection of discharging nervous mechanisms. It is, perhaps, a profitless task to enumerate all the so-called centres in the bulb and cord with which the perverse ingenuity of investigators and systematic writers has encumbered the archives and text-books of physiology. In addition to the great vaso-motor, respiratory, cardio-inhibitory and cardio-augmentor centres in the bulb, which, perhaps, have more right than the rest to be regarded as distinct physiological mechanisms, if not as definitely bounded anatomical areas, there have been distinguished ano-spinal, vesico- spinal, and genito-spinal centres in the lumbar cord, a cilio-spinal centre for dilatation of the pupil in the cervical cord, and in the medulla centres for sneezing, for coughing, for sweating, for sucking, for masticating, for swallowing, for salivating, for vomiting, for the production of general convulsions, for closure of the eyes. It would be just as correct, and more practically useful (for it would perhaps encourage the student who has lost his way amidst these intermin- able distinctions), to say that the cerebral cortex contains a centre for learning sense, and another for forgetting nonsense, and that in a THE CENTRAL NERVOUS SYSTEM. 633 healthy brain it is the latter which is generally thrown into activity in the study of this portion of modern physiology. The Cranial Nerves. Unlike the spinal nerves, which arise at not very unequal intervals from the cord, the nuclei of origin of the cranial nerves, with the exception of the olfactory and optic, are crowded together in the inch or two of grey matter of the primitive neural axis in the Fig. 210.— Schematic Transparent Section of Medulla Oblongata. The numerals V to XII refer to the nuclei of origin of the respective cranial nerves. V is the motor nucleus ; RV, the roots of the fifth nerve ; V', sensory nucleus ; V'', sensory nucleus and ascending root; RVI, root of si.xth nerve; RVII, root of seventh nerve; Py. pyramid; Py. kr. , decussation of the pyramids; O.s., superior olive; O, olive ; G.f., genu of the facial. immediate neighbourhood of the fourth ventricle and the Sylvian aqueduct. Of these nuclei some are sensory — sensory nucleus of fifth, both nuclei of eighth, and probably the common nucleus of ninth, tenth, and eleventh. The motor nuclei lie, upon the whole, in two longitudinal rows — a median row, which consists of the nuclei of the third and fourth nerves in the floor of the aqueduct, and those 634 A MANUAL OF PHYSIOLOGY. of the sixth and twelfth nerves in the floor of the fourth ventricle ; and a lateral row comprising the motor nuclei of the fifth, tenth, and eleventh nerves, and the nucleus of the seventh. The clumps of grey matter which make up these nuclei may be considered as homo- logous with the grey matter of the anterior (including the lateral) horn of the spinal cord ; and the motor fibres of the nerves them- selves as homologous with the anterior spinal roots, although it does not follow that each cranial motor nerve represents one anterior root and one only. Tlie first or olfactory nerve of anatomists is really a lobe of the brain, and is better termed the olfactory tract or bulb, the real olfactory nerves being the short terminal twigs that pierce the cribri- form plate of the ethmoid bone to reach the upper part of the nasal mucous membrane. The olfactory tract can be traced to the uncinate gyrus of the same side. It seems, however, to be also related in some indirect way to the opposite side of the brain, for an injury to the posterior part of the internal capsule has been found associated with impairment of smell in the opposite nostril. Exces- sive stimulation of the olfactory nerve by exposure to a strong odour has been known to cause complete and permanent loss of smell. The second or optic nerve is connected centrally with the lateral geniculate body and pulvinar (or posterior portion) of the optic thalamus, the anterior corpus quadrigeminum, and both directly and indirectly with the occipital cortex (Fig. 219). Peripherally it expands into Its end-organ, the retina. At the chiasma the fibres of the optic nerve decussate partially in man and some mammals, as the dog, cat, rabbit, and monkey, completely in animals whose visual field is entirely independent for the two eyes, as in fishes and in many mammals (horse, sheep, deer). In man the fibres for the nasal halves of both retinae cross the middle line at the chiasma, those for the temporal halves do not. Since the field of vision of the nasal side of the retina is more extensive than that of the temporal side, more than half of the fibres decussate. A lesion involving the whole of the upper part of the occipital cortex, or the posterior portion of the optic thalamus, or the optic tract, causes hemi- anopia* (blindness of the corresponding halves of the two retinae) on the side of the lesion. Thus, a lesion equivalent to complete section of the right optic tract would cause blindness of the nasal half of the left, and of the temporal half of the right eye, and the left half of the field of vision would be blotted out— the patient would be unable, with his eyes directed forwards, to see an object at his left. A lesion, e.g.^ a tumour of the pituitary body, involving the whole of the optic nerve in front of the chiasma, would cause complete blindness of the corresponding eye. Sometimes in disease of the optic nerve vision is not totally destroyed in the eye to which it belongs, but the field is narrowed by a circumference of blindness. * The terms ' hemiopia,' ' hemianopia,' ' hemianopsia,' are sometimes used with reference to the blind side of the retinje, sometimes to the dark half of the visual field. We shall always use the word 'hemianopia' with reference to the retina. THE CENTRAL NERVOUS SYSTEM. 635 In this case the pathological change involves the circumferential fibres of the nerve. When the chiasma is affected by disease, a very frequent symptom is nasal hemianopia, blindness of the nasal halves of the retinse, with loss of the outer or temporal half of each field of vision. It may be added that not only does a central lesion lead to peripheral atrophy, but a peripheral lesion may cause central atrophy. Extirpation of the eyeball in young animals is followed by atrophy of the anterior corpus quadrigeminum, optic thalamus, and occipital cortex. The third nerve, or oculo-motor, arises from a series of nuclei in the floor of the Sylvian aqueduct below the anterior corpora quadri- gemina. The root-bundles coming off from the most anterior of the nuclei carry fibres that have to do with the mechanism of accommodation. The nuclei behind these are connected with fibres that cause contraction of the pupil when light falls on the retina ; while, in dogs at least, the posterior portion of the series gives off fibres for the muscles of the eye in the following order from before backwards : internal rectus, superior rectus, levator palpebrEe superioris, inferior rectus, inferior oblique. Complete paralysis of the third nerve causes loss of the power of accommodation of the corresponding eye, dilatation of the pupil by the unopposed action of the sympathetic fibres, diminution of the power of moving the eyeball, ptosis, or drooping of the upper lid, external squint, and consequent diplopia, or double vision. The fourth or trochlear nerve arises from the posterior part of the same tract of grey matter which gives origin to the third nerve. It supplies the superior oblique muscle. Paralysis of the nerve causes internal and upward squint owing to the unopposed action of the inferior rectus. There is diplopia on looking down. Unlike the other cranial nerves, the two trochlear nerves decussate after they emerge from their nuclei of origin. The fifth or trigeminus nerve appears on the surface of the pons as a large sensory root and a smaller motor root. Its deep origin is more extensive than that of any of the other cerebral nerves, stretch- ing as it does from the level of the anterior corpus quadrigeminum above to the upper part of the spinal cord below. Its sensory root, in fact, seems to include the sensory divisions of all the motor cranial nerves. The motor root arises partly from a nucleus in the floor of the fourth ventricle below the pons, partly as the so-called descending root from large nerve-cells scattered in the grey matter around the aqueduct of Sylvius all the way from the anterior quadrigeminate body to the point at which the motor root is given off. The sensory root has likewise two deep origins : a nucleus in the neighbourhood of the motor nucleus in the floor of the fourth ventricle, and a long ascending root running up from the level of the second cervical nerve through the medulla oblongata and the tegmentum of the pons, where it lies external to the descending root. 636 A MANUAL OF PHYSIOLOGY. The motor fibres of the fifth nerve supply the muscles of mastica- tion and the tensor tympani. The sensory fibres confer common sensation on the face, conjunctiva, the mucous membranes of the mouth and nose, and the structures contained in them, and special sensation, through branches given off to the facial and glosso- pharyngeal nerves, on the organs of taste. Complete paralysis of the nerve causes loss of movement in the muscles of mastication, some- times impaired hearing, and loss of common sensation in the area supplied by it. Loss or impairment of taste in the corresponding half of the tongue is also often seen in disease involving the sensory root, although not in affections of the trunk of the nerve, since the taste-fibres leave it near its origin. Vaso-motor changes are occasionally, and ' trophic ' changes frequently, observed in disease of the fifth nerve. The trophic disturbance is most conspicuous in the eyeball (ulceration of the cornea, going on, it may be, to complete disorganization of the eye). These effects seem to be partly due to the loss of sensation in the eye, and the consequent risk of damage from without, and the un- regarded presence of foreign bodies and accumulation of secretion within the lids. But this is not a complete explanation, since the eye may remain perfectly normal for many years after total paralysis of the fifth nerve. The sixth or ahducens nerve takes origin from a nucleus in the floor of the fourth ventricle at the level of the posterior portion of the pons. It supplies the external rectus muscle of the eyeball. Paralysis of it causes internal squint. The seventh or facial nerve arises from a nucleus in the reticular formation of the medulla oblongata, and running up some distance into the pons. It supplies the muscles of the face ; and when these are greatly developed, as in the trunk of the elephant, the nerve reaches very large proportions. Since the fibres which connect the nucleus with the cerebral cortex decussate about the middle of the pons, a lesion above this level which causes hemiplegia paralyzes the face on the same side as the rest of the body, i.e , on the side opposite the lesion. But the paralysis is confined to the muscles of the lower portion of the face, and affects especially the muscles about the mouth. Sometimes the pyramidal tract and the facial nerve, or nucleus, are involved in a common lesion. In this case paralysis of the face is on the side of the lesion, and is total, while the rest of the body is paralyzed on the opposite side. Complete facial paralysis is often caused by an inflammatory process in the nerve itself (neuritis). The symptoms of complete facial paralysis are very characteristic. The face and forehead on the paralyzed side are smooth, motionless, and devoid of expression. The eye remains open even in sleep, owing to paralysis of the orbicularis palpebrarum. A smile becomes a grimace. An attempt to wink with both eyes results in a grotesque contortion. The mouth appears like a diagonal slit in the face, its angle being drawn up on the sound side, and the patient cannot bring the lips sufficiently close together to be able to blow out a candle or to whistle. Liquids escape from the mouth, THE CENTRAL NERVOUS SYSTEM. 637 and food collects between the paralyzed buccinator and the teeth. The labial consonants are not properly pronounced. Taste is lost in the anterior two-thirds of the tongue when the nerve is injured between the entrance of the gustatory fibres from the trigeminus and their exit by the chorda tympani, Imt not when the lesion is in the nucleus of origin, or anywhere above it. Hearing is sometimes impaired because the auditory and facial nerves, lying close together for part of their course, are apt to suffer together, but perhaps also because the stapedius muscle is supplied by the seventh nerve. The eighth or auditory nerve arises from the medulla oblongata by two roots, one of which passes in on each side of the restiform body. The auditory nucleus in the floor of the fourth ventricle con- sists of two parts, a lateral and a mesial nucleus, the first of which is connected with the fibres of the ventral, and the second with those of the dorsal root. The accessory nucleus on the ventral surface of the restiform body forms an additional nucleus for the dorsal root. It is believed that the two roots of the auditory nerve are physiologi- cally as well as anatomically distinct, for the dorsal root seems to carry the fibres which are distributed in the cochlear division of the auditory nerve to the cochlea, the ventral root those which pass to the semicircular canals and the vestibule of the internal ear. And, as we shall see (p. 646), it is extremely probable that the cochlea subserves the function of hearing, the semicircular canals and vestibule the function of equilibration. It is important also to note that many of the fibres of the ventral root, after making junction with nerve-cells in the lateral division of the auditory nucleus, are continued up in the restiform body to the cerebellum. We must assume, from clinical and experimental data, that the dorsal root is connected through its nuclei with the first or first and second temporo- sphenoidal convolutions on the opposite side, but the exact path and the place of decussation are unknown. Two prominent symptoms may be associated with disease of the auditory nerve — {a) disturbance or loss of hearing ; {b) loss or impairment of equilibration. The ninth or glosso-pharyngeal nerve arises from the upper portion of an elongated nucleus in the medulla oblongata, the lower portion of which gives origin to the accessory division of the spinal accessory, and the middle to the vagus. An additional origin is formed by a bundle of fibres, the ascending root of the glosso-pharyngeal, which arises from the grey matter of the lateral horn of the cord and the formatio reticularis of the medulla, and commences as far down as the fourth cervical nerve. The glosso-pharyngeal has both sensory and motor fibres — sensory for the posterior third of the tongue and the mucous membrane of the back of the mouth, motor for the middle constrictor of the pharynx and the stylo-pharyngeus. It also contains the nerves of taste for the posterior third of the tongue, but these reach it from the fifth nerve. The tenth or vagus or pneumogastric nerve is joined near its origin by the accessory portion of the spinal accessory, that is, the portion which arises from the medulla oblongata, and we shall describe them together. The mixed nerve contains both sensory and 638 A MANUAL OF PHYSIOLOGY. motor fibres, the latter chiefly derived from the accessory, the former entirely from the vagus. The distribution of the nerve is more extensive than that of any other in the body. The oesophagus receives both motor and sensory branches from the oesophageal plexus. The pharyngeal branch of the vagus is the chief motor nerve of the pharynx and soft palate (including the tensor palati). The superior laryngeal branch is the nerve of common sensation for the larynx above the vocal cords, and the motor nerve of the crico- thyroid muscle. The inferior or recurrent laryngeal supplies the rest of the laryngeal muscles, and is sensory for the mucous membrane of the trachea and the larynx below the glottis. The superior laryngeal contains afferent fibres, stimulation of which gives rise to coughing, slows respiration, or stops it in expiration. Reflex movements of deglutition are also caused. The vagus supplies the lung both with motor and sensory filaments through the pulmonary plexus. The motor fibres when stimulated cause constriction of the bronchi ; the afferent fibres cause increase in the rate of respiration or reflex stoppage of the diaphragm in inspiratory spasm. The cardiac branches contain inhibitory fibres derived from the spinal-accessory, and depressor fibres which pass up in the vagus trunk (dog), or as a separate nerve to join the vagus or its superior laryngeal branch or both (rabbit). The gastric and intestinal branches contain both motor and sensory nerves for the stomach and intestines. The latter are probably large medullated fibres (7 /a to 9 /x). The afferent vagus fibres from the stomach carry up impulses which excite the action of vomiting. Lesions of the vagus, its nuclei of origin, or its branches, are associated with many interesting forms of paralysis and other symptoms. Paralysis of the pharynx is generally caused by disease of the nucleus in the medulla. From its anatomical relation to the nuclei of the glosso-pharyngeal and hypoglossal, it will be easily understood that these nerves are often involved in localized central lesions along with the vagus. But the fact that in glosso-labio- laryngeal palsy — a condition characterized by progressive paralysis and atrophy of the muscles of the tongue, lips, larynx, and pharynx — the orbicularis oris is paralyzed, while the other muscles supplied by the facial remain intact, would seem to show that in system diseases it is not so much anatomical groups of nerve-cells which are liable to simultaneous degeneration and failure, as physiological groups normally associated in particular functions. Such functional groups of cells, occupied with the same kinds of labour at the same times and under the same conditions, may be supposed to take on a similar bias or tendency to degeneration, a tendency not indicated, it may be, by any structural peculiarity, but traced deep in the mole- ular activity of the cells. Difficulty in swallowing is the chief symptom of pharyngeal paralysis. The symptoms of laryngeal paralysis have been already described under 'Voice' (p. 229). Tachycardia, or a permanent increase in the rate of the heart, has been stated to occur in certain cases of paralysis of the vagus, caused by disease or accidental interference ; and a persistent slowing of the respiration has been occasionally attributed to the same cause. But it is difficult THE CENTRAL NERVOUS SYSTEM. 639 to reconcile many of these cases with experimental results, for in most of them the lesion only involved one vagus ; and in animals section of one vagus has little effect on the rate of the heart or of the respiratory movements. Destruction of the nerve near its origin has been sometimes found associated with disappearance of the food-appetites, hunger and thirst, and it has been assumed that this was due to loss of afferent impulses from the stomach. But clinical testimony is by no means unanimous on this point, and experiments on animals show that other factors are involved in these sensations. The eleventli or spinal-accessory nerve consists of two parts : the accessory or internal branch, which arises from the medulla oblongata, and which we have just considered in conjunction with the vagus ; and the external or spinal branch, which, arising from the lateral rim of the anterior horn of the cord from the sixth or seventh cervical nerve upwards, passes out to supply the trapezius and sterno-mastoid muscles with motor fibres. The twelfth or hypoglossal nerve contains the motor supply of the intrinsic and extrinsic muscles of the tongue and of the thyro- and genio-hyoid. Paralysis of it causes deficient movement of the corre- sponding half of the tongue. When the tongue is put out, it deviates towards the paralyzed side, pushed over by the unparalyzed genio-hyo- glossus of the opposite side, which is thrown into action in protruding the tongue. The Functions of the Brain. The paths by which the various parts of the central nervous system are connected with each other and with the periphery have been already described, and we have completed the examination of the functions of the spinal cord and medulla oblongata. The events that take place in the upper part of the central nervous stem and in the cortex of the cerebellum and cerebrum now claim our attention. From very early times the brain has been popularly believed to be the seat of all that we mean by consciousness — sensation, ideation, emotion, volition. And he who loves to trace the roots of things back into the past may see, if he choose, running through the whole texture of the older speculations a belief that the brain does not act as a whole, but is divided into mechanisms, each with its special work — a foreshadowing, often in grotesque outlines, of the doctrine of localization so widely held to-day. But until comparatively recent times, cerebral physiology remained a kind of scientific terra incognita ; and no notable additions were made for a thousand years to the doctrines of Galen. Even to day the utmost limit of our knowledge is reached when in certain cases we have connected a particular movement or sensation with a more or less sharply defined anatomical 640 .1 MANUAL OF PHYSIOLOGY. area. How the cerebral processes that lead to sensations and move- ments, to emotions and intellectual acts, arise and die out ; what molecular changes are associated with them ; above all, how the molecular changes are translated into consciousness — how, for example, it is that a series of nerve-impulses flickering across the labyrinth of the occipital cortex should light up there a visual sensation — these are questions to which we can as yet give no answer, and the answers to some of which must for ever remain hidden from us. Functions of the Upper Part of the Central Stem and Basal Ganglia. — Some of the transverse fibres of the pons form a commissure between the hemispheres of the cerebellum, but many of them are the cerebellar portions of commissural arcs interrupted by pontine grey matter, and continued by fibres of the corona radiata to the pre-frontal, temporal and occi- pital portions of the cerebral cortex (p. 5o8). The posterior corpora quadrigemina (testes) and internal geniculate bodies are connected with the cochlear division of the auditory nerves, and therefore have some relation to the sense of hearing. Stimulation of the testes causes a pecuhar cry, and the pupils dilate. The anterior corpora quadrigemina (nates) and the lateral corpora geniculata are connected with the optic tracts. Their development is arrested after extirpation of the eyeball in young animals, and they may therefore be assumed to be concerned in vision, although the size of their homologues, the optic lobes or corpora bigemina, in animals below the rank of mammals (birds, reptiles, amphibians), does not seem to be related to the development of the organs of sight. The Proteus and the Hag-fish, e.g., have large optic lobes, rudimentary eyes and optic tracts. The optic nerve, the nuclei of the oculo-motor nerve in the wall of the Sylvian aqueduct, and the fibres which it carries to the iris, form reflex arcs for the contraction of the pupil to Hght and during accommodation. The functions of the optic thalami have not been satisfactorily defined either by experiment or pathological observation. Lying as they do in the isthmus of the brain, begirt by the great motor and sensory paths, it is to be expected that lesions of the thalami should affect also the internal capsule, and give rise to the symptoms of motor and sensory paralysis. THE CENTRAL NERVOUS SYSTEM. 641 But no definite defect of motor power or common sensation has ever been unequivocally connected with a lesion restricted to the thalami. The posterior portion of the thalamus, or pulvinar, however, seems to form part of the central visual apparatus ; for (a) it is found to be undeveloped in animals from which the eyeballs have been removed soon after birth ; (6) a portion of the optic tract is certainly connected with it ; (c) in some cases of atrophy of the occipital cortex, which, as we shall see, is undoubtedly a central area for visual sensations, atrophy of the pulvinar has also been jV-- Corpus striatum \ \ % Anterior pillar of the ^\ i * fornix Optic thalamus Third ventricle Fig. 211.— Horizontal Section through Brain to show the Basal Ganglia and Third Ventricle (Human). noticed ; ((i)a lesion of the pulvinar may apparently give rise to hemianopia (p. 634). Haemorrhage into the caudate or lenticular nucleus of the corpus striatum often causes hemiplegia, but this is always due to implication of the internal capsule. Experimental lesions in dogs and rabbits are followed by disturbances of the heat-regulating mechanism and rise of temperature. Certain structures, belonging to the primary fore-brain, which have now no functional importance, may nevertheless be mentioned as milestones in the march of development. The pineal body is made up of the vestiges of the single mesial eye of the ancient amphibians, which resembled the eye of invertebrates in having the retinal rods directed towards the cavity instead of towards the circumference of 41 642 A MANUAL OF PHYSIOLOGY. the eyeball. The ganglia haboiuke seem to represent the optic ganglia of this cyclopean eye. The itifu7idibiilum is probably what remains of the gullet of the ancestors of the vertebrates. The pituitary body consists of two portions, the anterior being derived from the buccal cavity, the posterior from the primary fore-brain. It has been stated that after excision of the thyroid glands, the anterior division, the tissue of which has a resemblance to thyroid tissue, has sometimes been found atrophied (but see p. 417). Functions of the Cerebellum. — The elaborate pattern of the arbor vitse, the appearance given by the branched laminge in Fig. 212.— LoNGiTL'DixAL Section of the Gkky Matter of a Lamella OF the Cerebellum (Diagrammatic, after Kolliker). gi", a ' granule ' cell, with its nervous process, ii ; 71' , bifurcation of 71, in the molecular layer, into tuo fine longitudinal branches ; m, a Pui kmje's cell ; m' , antler process (Golgi's method). a section of the cerebellum, excited the speculation of the old anatomists. A structure so marvellous must be matched, they thought, with functions no less unique. At a time when the discoveries of Galvani and Volta were fresh, and the world ran mad on electricity, the hypothesis of Rolando, that ' nerve-force ' was generated by the lamellse of the cerebellum as electrical energy is generated by the plates of the voltaic pile, ridiculous as it now appears, was not unnatural. The speculation of Gall, who connected the cerebellum with the development of sexual emotions and the action of the generative mechanisms, was based on no THE CENTRAL NERVOUS SYSTEM. 643 fact. It has been definitely disproved by the observations of Luciani, who found that a bitch deprived of its cerebellum showed all the phenomena of heat or ' rut,' was impregnated, whelped at full term in an entirely normal manner, and manifested the maternal instincts in their full intensity. Flourens put forward the doctrine that the cerebellum is an organ especially concerned in the co-ordination of move- ments and the maintenance of equilibrium, supporting his conclusions by an elaborate series of experiments. Notwith- standing the very large amount of experimental and clinical study which has been devoted to the cerebellum since the time of Flourens, our know- ledge of its functions has hardly advanced beyond the point then reached. Indeed, it may be said that the tendency has been rather to abridge than to extend the field of current physiological doctrine on this subject. For while it has been shown that the integrity of the cerebellum is essential to equilibration, it is by no means certain that it is essential for the co-ordination of move- ments other than those con- cerned in the maintenance of equilibrium. Animals entirely deprived of the cerebellum have shown, after the primary effects of the operation have passed away, no impairment in general co-ordinative power ; and cases are on record in which the human cerebellum has been found at death to be utterly disorganized, and yet in which many classes of movements have been well co- ordinated during life. But what has been noticed in such cases is a marked inability to maintain the upright posture, a staggering gait, twitching movements of the eyes (nystag- mus)— in a word, a general disorder of the mechanism of equilibration. In cases of congenital defect of the cerebellum, Fig. 213. — A Purkin'je's Cell from THE Cerebellum of a Cat (after Cajal (Golgi's Method). 644 A MANUAL OF PHYSIOLOGY. the power of walking, and even of standing, is late in being acquired, and usually imperfect. The connections of the cerebellum with other parts of the central nervous system and with the periphery corroborate the direct results of experiment. For the most important afferent impulses concerned in equilibration are those from the muscles, the skin, the semicircular canals and vestibule of the internal ear, and the eyes. And the cerebellum, as we have seen (p. 607), is linked with all of these, and has besides an extensive crossed connection through the middle and superior peduncles with the opposite cerebral hemisphere. Further, the superficial grey matter of the two cerebellar hemispheres is united by a massive commissure, the fibres of which pass partly through the pons, partly through the middle lobe or worm. We do not as yet know the full significance of this extra- ordinarily free communication of the grey matter of the cerebellum with every part of the central nervous system. But it is evident that by the broad highway of the restiform body, or the cross-country routes from cerebral cortex to cerebellum impulses may pass into it from every quarter ; and it is an organ so connected that is suited to take cog- nizance of the multitudes of impressions concerned in the maintenance of equilibrium. This is a convenient place to consider a little more in detail the nature and peripheral sources of the most important of these impressions. (i) Afferent Impressions from the Muscles. — Muscles are richly supplied with afferent fibres, for about half of the fibres in the nerves of skeletal muscles degenerate after section of the posterior roots beyond the ganglia (Sherring- ton). Various kinds of impressions may pass up these muscular nerves : (a) Impressions giving rise to pain, as in muscular cramp and in experimental excitation of even the finest muscular nerve-filament; {b) impulses causing a rise of blood-pressure ; (c) impulses which are not associated with a distinct impression in consciousness, but enable us to localize the position of the limbs, head, eyes, and other parts of the body ; {d) impulses which inform us as to the extent and force of muscular contraction, and seem to THE CENTRAL NERVOUS SYSTEM. 645 underlie the so-called muscular sense. It is the last two kinds — if, indeed, they are distinct — which must be con- cerned in equilibration. In locomotor ataxia such impres- sions are blocked by degeneration in a part of the afferent path (p. 623), and disorders of equilibrium are the result. (2) Afferent Impressions from the Skin. — Of the various kinds of nerve-impulses that arise in the nerve-endings of the skin, only those of touch and pressure seem to be con- cerned in the maintenance of equilibrium. When the soles of the feet are anaesthetized by chloroform or by cold, and the person is directed to close his eyes, he staggers and sways from side to side. The dis- turbance of equilibrium in loco- motor ataxia must be partly attri- buted to the loss of these tactile sensations, for numbness of the feet is a frequent symptom, and the patient asserts that he does not feel the ground. An interest- ing illustration of the importance of afferent impulses from the skin in the maintenance of equilibrium is afforded by the behaviour of a frog deprived of its cerebral hemi- spheres. Such a frog will balance itself on the edge of a board like a normal animal, but if the skin be removed from the hind-legs, it will fall like a log. (3) Afferent Impulses from the Semicircular Canals. — The semicircular canals are three in number, and lie nearly in three mutually rectangular planes : the external canal in the horizontal plane, the superior canal in a vertical longi- tudinal plane, and the posterior canal in a vertical transverse plane. Each canal bulges out at one end into a swelling, or ampulla, which opens into the utricular division of the vestibule (Fig. 271). The other extremities of the superior and posterior canals join together, and have a common aperture into the utricle, but the undilated end of the external or horizontal canal opens separately. The utricle and the semicircular canals are thus connected by five distinct Fig. 214. — The Semicircular Canals (Diagrammatic). H, horizontal or external ; S, superior ; P, posterior. 646 A MANUAL OF PHYSIOLOGY. orifices. The greater part of the internal surface of the membranous canals, utricle and saccule, is lined by a single layer of flattened epithelium. But at one part of each ampulla projects a transverse ridge, the crista acustica, covered not with squamous, but with long columnar epithe- lium. Hair-like processes (auditory hairs), borne either by the columnar cells or by spindle-shaped cells scattered among them, project into the endolymph, which fills all the membranous labyrinth, and are covered by a thin mem- brana tectoria. The utricle and saccule have each a some- what similar but broader elevation, the macula acustica, covered with epithelium and hair-cells of the same character, and the hairs project into an otolith, or small mass of carbonate of lime. The vestibular branch of the auditory nerve breaks up into five twigs : one for each ampulla, one for the utricle, and one for the saccule. The nerve-fibres, on which lie ganglion-cells, lose their medulla as they approach the layer of hair-cells in which they terminate. There is very strong evidence that the semicircular canals are concerned, not in hearing, but in equilibration. A pigeon from which the membranous canals have been re- moved still hears perfectly well so long as the cochlea is intact, but exhibits the most profound and remarkable dis- turbances of equilibrium. If the horizontal canal is destroyed or divided, the pigeon moves its head continually from side to side around a vertical axis ; if the superior canal is divided, the head moves up and down around a horizontal axis. The power of co-ordination of movements is diminished, but not to the same extent in all kinds of animals. Thrown into the air, the pigeon is helpless ; it cannot fly ; but a goose with divided semicircular canals can still swim. The condition is only temporary, even when the injury involves the three canals on one side ; but if the canals on both sides are destroyed, recovery is tardy, and often incomplete. In mammals the loss of co-ordination is much less than in birds ; and movements of the eyes, the direction of which depends on the canal destroyed, take to a large extent the place of movements of the head. The effects of destructive lesions have their counterpart in the phenomena caused by THE CENTRAL NERVOUS SYSTEM. 647 stimulation; excitation of a posterior canal, for example, in the pigeon causes movements of the head from side to side. Lee's results in fishes are, on the whole, of similar tenor. Mechanical stimulation of the ampullae in the dogfish, by pressing on them with a blunt needle, calls forth characteristic movements of the eyes and fins, and electrical stimulation of the auditory nerve causes move- ments compounded of the separate movements obtained by stimula- tion of the ampullce one by one. Lee concludes that the semicircular canals are the sense-organs for dynamical equilibrium {i.e., equilibrium of an animal in motion), and the utricle and saccule for statical equilibrium {i.e., equilibrium of an animal at rest). Each canal has a principal function, the appreciation of movements of rotation of the body in its own plane and towards its own side, and a subordinate function, the appreciation of similar movements to the opposite side. The canals can be arranged in functionally opposite pairs, thus : Left. Right. Anterior (superior). Posterior. Posterior. Anterior. External. External. Loss of one canal does not affect dynamical equilibrium much. Destruction of a functional pair of canals causes displacement of the eyes and fins, and may be followed by forced movements. Loss of the three canals of one side may cause forced rolling or circus move- ments towards that side. Loss of all six canals is equivalent to complete abolition of dynamical equilibrium, with forced movements. The evidence from all sources points strongly to the con- clusion that afferent impulses are actually set up in the fibres of the auditor}^ nerve, through the hair-cells, by alterations of pressure or by streaming movements of the endolymph when the position of the head is changed. Rotation of the head to the right may be supposed to cause the endolymph in the right external canal, in virtue of its inertia, to lag behind the movement, and to press upon the anterior surface of the ampulla. The disorders of movement after lesions of the canals may be explained as the result of the withdrawal of certain of these afferent impulses, and the consequent overthrow of that equipoise of excitation necessary for the maintenance of equilibrium. Even in man there is evidence of the existence of some mechanism not depending on the muscular sense or on impressions passing up the channels of ordinary or special sensation, by which orientation (the determination of the position of the body in space) is rendered possible. For a 648 A MANUAL OF PHYSIOLOGY. man lying perfectly still, with eyes shut, on a horizontal table which is made to rotate uniformly, can not only judge whether, but also in what direction, and approximately through what angle, he is moved (Crum Brown). The phenomena of pathology afford weighty additional testimony in favour of the equilibratory function of the semicircular canals. For many cases of vertigo are associated with changes in the internal ear (Meniere's disease). And while nearly every normal individual becomes dizzy when rapidly rotated, 35 per cent, of deaf-mutes are entirely unaffected (James), and the proportion seems to be much higher among congenital deaf-mutes. Kreidl and Bruck, too, have found that abnormalities of locomotion and equilibration are much more common in deaf and dumb children than in others. Now, in these cases the defect is usually in the internal ear. We must conclude, then, that the co-ordination of muscular movements necessary for equilibrium is achieved in some centre, to which afferent impulses pass from the internal ear by the vestibular branch of the auditory nerve, and from which efferent impulses pass out to the muscles. If, as there is strong reason to believe, this centre is situated in the cere- bellum, the efferent path is in all probability an indirect one (perhaps by commissural fibres to the Rolandic area, and then out along the pyramidal tract) ; for, as we have seen, the cerebellum is either not connected directly with the anterior roots at all, or only by a few fibres. It is the middle lobe of the cerebellum which seems to be concerned in the co-ordination of movements and mainten- ance of equilibrium. In birds and lower vertebrates the worm is alone present. The cerebellar hemispheres become more prominent the higher we ascend, and it cannot be doubted that they have important functions, but what these are is entirely unknown. The fact that they are connected chiefly with those parts of the cerebral cortex which are supposed to be concerned in psychical and sensory processes suggests that, at any rate, the superficial grey matter of the cerebellum is not motor, and no movements can be obtained on stimulating it ; while stimulation of the worm may cause movements of the eye. THE CENTRAL NERVOUS SYSTEM. 649 Forced Movements. — We have incidentally mentioned that in fishes injuries to the semicircular canals may give rise to movements which seem to be beyond the control of the animal, and which have consequently received the name of * forced movements.' It may be added that when the in- ternal ear of a Menobranchus (one of the tailed amphibia) is destroyed on one side, rapid movements of rotation around a longitudinal axis are observed. The animal spins round and round apparently without voluntary control, purpose, or fatigue. After a time it becomes quiescent ; but the forced movements can be again produced by pinching or exciting it in other ways. In man, too, during the passage of a gal- vanic current between the two mastoid processes, a tendency to move the head towards the anode is experienced. The person may resist the tendency, but if the current be strong enough his resistance will be overcome ; he will execute a forced movement. Complex as such an experiment is, involving as it does stimulation of so many structures within the cranium, there is very clear evidence that it is the excitation of the semicircular canals that is responsible for this forced movement. For when the experiment is per- formed on a pigeon, forced movements are caused so long as the membranous canals are intact, but not after they have been destroyed (Ewald). But forced movements may also follow injuries (especially unilateral) to many portions of the brain — e.g., the pons, crus cerebri, posterior corpora quadrigemina, corpus striatum, cerebellum, and even the cerebral cortex. The movements are of the most various kinds. The animal may run round and round in a circle (circus movements) ; or, with the tip of its tail as centre and the length of its body as radius, it may describe a circle with its head, as the hand of a clock does (clock-hand movement) ; or it may rush forward, turning endless somersaults as it goes. Intervals of rest alternate with paroxysms of excitement, and the latter may be brought on by stimulation. In man forced movements associated with vertigo have been sometimes seen in cases of tumour of the cerebellum — e.g., involuntary rotation of the body in tumour of the middle peduncle. No entirely satisfactory 650 A MA NUA L OF PH YSIOL OGY. explanation of these forced movements has been given. They are evidently connected with disturbance of the mechanism of co-ordination, leading to a loss of proportion in the amount of the motor discharge to muscles or groups of muscles accustomed to act together in executing definite movements. For instance, in circus movements the muscles of the outer side of the body contract more powerfully than those of the inner side, and the animal is therefore con- strained to trace a circle instead of a straight line, the excess of contraction on the outer side being analogous to the acceleration along the radius in the case of a point moving in a circle. Co-ordination of Movements, — The capacity of executing some co-ordinated movements, occasionally of considerable complexity, seems to be inborn in man, and to a still greater extent in many of the lower animals. The new-born child brings with it into the world a certain endowment of co- ordinative powers ; it has inherited, for example, from a long line of mammalian ancestors the power of performing those movements of the cheeks, lips, and tongue, on which sucking depends ; perhaps from a long, though somewhat shadowy, race of arboreal ancestors the power of clinging with hands and feet, and thus suspending itself in the air. Many movements, such as walking and the co-ordinated muscular contractions involved in standing, and even in sitting, which, once acquired, appear so natural and spon- taneous, have to be learnt by painful effort in the hard school of (infantile) experience. Most people learn, and are willing to confess that they have learnt, to execute a con- siderable number of co-ordinated movements with the arms, and especially with the fingers ; but few have considered that the extreme dexterity of jaws, tongue, and teeth dis- played by a hungry mouse or schoolboy is the result of the much practice which maketh perfect. The exquisite and highly-developed co-ordination of the muscles of the eye- ball, which we shall afterwards have to speak of, and the no less wonderful balance of effort and resistance, of power put forth and work to be done, of which we have already had glimpses in studying the mechanism of voice and speech, THE CENTRAL NERVOUS SYSTEM. 651 become to a great extent the common property of all fully- developed persons. But the technique of the finished singer or musician, of the swordsman or acrobat, and even the operative skill of the surgeon, are in large part the outcome of a special and acquired agility of mind or body, in virtue of which highly-complicated co-ordinated movements are promptly determined on and immediately executed. With such special and elaborate movements it is impos- sible to occupy ourselves in a book like this. Their number may be almost indefinitely extended, and their nature almost infinitely varied, by the needs and training of special trades and professions. It will be sufficient for our purpose to sketch in a few words the mechanism of one or two of the most common and fundamental co-ordinations of muscular effort, passing over the rest with the general statement that the more refined and complex movements are in general brought about not by the abrupt contraction of crude anatomical groups of muscles, but by the contraction of portions of muscles, perhaps even single fibres or small bundles of fibres, while the rest remain relaxed. The excitation may gradually wax and wane as the different stages of the movement require. Antagonistic muscles may be called into play to balance and tone down a con- traction which might otherwise be too abrupt. A most interesting illustration of this process of ' give and take ' between opposing muscles has been recently reported by Sherrington. In the cortex cerebri, as we shall see (pp. 658, 662], there is an area in the frontal region, and another in the occipital region, stimulation of which gives rise to conjugate deviation of the eyes— that is, rotation of both eyes — to the opposite side. Sherrington divided the third and fourth cranial nerves in monkeys — say on the left side. The ex- ternal recti, which are supplied by the sixth nerve, caused now by their unopposed contraction external squint of the left eye. When either of the cortical areas referred to, or even the subjacent portion of the corona radiata, was stimulated on the left side, both eyes moved towards the right, the left eye, however, only reaching the middle line— that is, the position in which it looked straight forward. The same thing was observed when the animal, after complete re- covery from the operation, was caused to voluntarily turn its eyes to the right by the sight of food. Here an inhibitory influence must have descended the fibres of the abducens, the only nervous path connected with the extrinsic muscles of the left eye, and the relaxation of the left 652 A MANUAL OF PHYSIOLOGY. external rectus must have kept accurate step with the contraction of the internal rectus. Standing. — In the upright posture the body is supported chiefly by non-muscular structures, the bones and ligaments. But muscles also play an essential part, for it is only peculiarly-gifted individuals like some of the fishermen of the North Sea who can go to sleep on their feet, and a dead body cannot be made to stand erect. The condition of equilibrium is that the perpendicular dropped from the centre of gravity to the ground should fall within the base of support — that is, within the area enclosed by the outer borders of the feet and lines joining the toes and heels respectively. The centre of gravity alters its position with the position of the body, which tends to fall whenever the perpendicular cuts the ground beyond the base of support. The centre of gravity of the head is a little in front of the vertical plane passing through the occipital condyles. A slight degree of contraction of the muscles of the nape of the neck is required to balance it. When these muscles are relaxed, as in sleep, the head must fall forward, and this is the reason why Homer or any lesser individual nods. In animals which go upon all fours, none of the weight of the head bears directly upon the occipito-atloid articulation ; its support by muscular action alone would be an intolerable fatigue, and the ligamentum nuchse is specially strengthened to hold it up. The vertebral column is kept erect by the ligaments and muscles of the back. The centre of gravity of the trunk lies between the ensiform cartilage and the eighth or tenth dorsal vertebra. The perpendicular dropped from it passes a little behind the horizontal line joining the two acetabula ; but the body is prevented from falling backward by the tension of the ileo-femoral ligament and the fascia lata, and perhaps by slight contraction of some of the muscles on the front of the thigh. The perpendicular let fall from the centre of gravity of the whole of the body above the knee passes very slightly behind the axis of rotation of that joint, so that but little muscular action is required to keep the knee- joints rigid. The whole weight of the body is finally trans- THE CENTRAL NERVOUS SYSTEM. 653 ferred to the astragalus on each side, the perpendicular from the centre of gravity of the whole, which is situated near the sacral promontory, falling a little in front of these bones. By means of the muscular sense, and the tactile sensations set up by the pressure of the soles on the ground, alterations in the position of the centre of gravity, and consequent deviations of the perpendicular passing through it, are detected, and equilibrium is maintained by adjustment of the amount of contraction of this or the other muscular group. In standing at ' attention,' the heels are close together, the legs and back straightened to the utmost, and the head erect ; the weight falls equally upon both legs, but the advantage is much more than counterbalanced by the con- siderable muscular exertion required to maintain this more ornamental than useful position. In ' standing at ease,' practically the whole weight is supported by one leg, the perpendicular from the centre of gravity passing through the knee and ankle-joints. The centre of gravity is brought over the supporting leg by flexure of the body to the cor- responding side, and comparatively little muscular effort is required. The other foot rests lightly on the ground, the weight of the leg itself being almost balanced by the atmo- spheric pressure acting upon the air-tight and air-free cavity of the hip-joint. The light touch of this foot varies slightly from time to time, so as to maintain equilibrium. When the arms or head are moved, or the body swayed, the centre of gravity is correspondingly displaced, and it is by such movements that tight-rope dancers continue to keep the perpendicular passing through it always within the narrow base of support. In sitting, the base of support is larger than in standing, and the equilibrium therefore more stable. The easiest posture in sitting without support to the back or feet is that in which the perpendicular from the centre of gravity passes through the horizontal line joining the two tubera ischii. Locomotion. — In walking, the legs are alternately swung forward and rested on the ground. In military marching, it is directed that toe and heel be simultaneously set down. But with most persons the swinging foot first strikes the 654 A MANUAL OF PHYSIOLOGY. ground by the heel; then the sole comes down, the heel rises, the leg is extended, and, with a parting push from the toe, the leg again swings free. By this manceuvre the body is raised vertically, tilted to the opposite side, and also pushed in advance. The forward swing of the leg is only slightly, if at all, due to muscular action ; it is more like the oscillation of a pendulum displaced behind its position of equilibrium, and swinging through that position, and in front of it, under the influence of gravity. For this reason the natural pace of a tall man is longer and slower than that of a short man ; but it may be modified by voluntary effort, as when a rank of soldiers of different height keeps step. The lateral swing of the body is illustrated by the every- day experience that two persons knock against each other when they try to walk close together without keeping step. In step, both swing their bodies to the same side at the same moment, and there is no jarring. Even in the fastest walking there is a short time during which both feet are on the ground together, the one leg not beginning its swing until the other foot has been set down. In running, on the other hand, there is an interval during which the body is completely in the air. Functions of the Cerebral Cortex. — When an animal, like a frog, is deprived of its cerebral hemispheres, the power of automatic voluntary movement appears to be definitively and entirely lost. The animal, as soon as the effects of the ansesthetic and the shock of the operation have passed away, draws up its legs, erects its head, and assumes the charac- teristic position of a normal frog at rest. So close may be the resemblance, that if all external signs of the operation have been concealed, it may not be possible to tell merely by inspection which is the intact and which the ' brainless * frog. The latter will jump if it be touched or otherwise stimulated. It will croak if its flanks be stroked or gently squeezed together. It will swim if thrown into water. If placed on its back, it will promptly recover its normal position. But it will do all these things as a machine would do them, without purpose, without regard to its environ- THE CENTRAL NERVOUS SYSTEM. 655 ment, with a kind of ' fatal ' regularity. Every time it is stimulated it will jump, every time its flanks are squeezed it will croak, and, in the absence of all stimulation, it will sit still till it withers to a mummy, even by the side of the water that might for a time preserve it. A Menobranchus, without its cerebral hemispheres, will, Hke the frog — immediately after the operation, at any rate — refuse to lie on its back. On stimulation it moves its feet or tail, or its whole body; but if not interfered with, it lies for an indefinite time in the same position. Its gills are seen to execute rhythmic movements, which never stop, and rarely slacken, except for an instant, when some part of the skin, particularly in the region of the head, is mechanically or electrically stimulated. The normal Meno- branchus, on the other hand, lies for long periods with its gills at perfect rest, and when stimulated moves for a con- siderable distance. After a time, two months or more, it is true the brainless frog, if it be kept alive, as may be done by careful attention, will recover a certain portion of the powers which it has lost by removal of the cerebral hemispheres ; and, indeed, the longer it lives, the nearer it approximates to the condition of a normal frog. Even in the pigeon the loss of the hemispheres, which at first induces a state of profound and seemingly permanent and hopeless lethargy, is to a great extent compensated for, as time passes on, by the unfolding in the lower centres of capabilities previously dormant, undeveloped, or suppressed. In the dog, as might be expected from its greater intellectual development, recovery is more imperfect than in the bird, much more imperfect than in the frog. But even in the dog wonderful resources lie hidden in the grey matter of the central neural axis, and are called forth by degrees to replace the lost powers of the cerebral cortex. It is true that a ' brainless ' dog is a less efficient animal than a brainless fish, or even than a brain- less frog ; but in favourable cases even in the dog, the move- ments of walking may still be carried out with tolerable precision in the absence of the cerebral hemispheres. The animal can swallow food pushed well back into the mouth, although it cannot feed itself Stupid and listless as it is 656 A MANUAL OF PHYSIOLOGY. compared with the normal dog, it seems to be by no means devoid of the power of experiencing sensations as the result of impressions from without, nor of carrying on many mental operations of a low intellectual grade. (loltz had a dog which lived more than a year and a half without its cerebral hemispheres, and another which lived thirteen weeks. He believes that they had lost understanding, reflection, and memory, but not sensation, special or general, nor emotions and voluntary power. Their condition may be best described as one of general imbecility. Hunger and thirst are present. They experience satis- faction when fed, become angry when attacked, see a very bright light, avoid obstacles, hear loud sounds, such as those produced by a fog-horn, and can be awakened by them. They are not completely deprived of sensations of taste and touch. But it ought to be re- membered that the interpretation of the objective signs of sensation in animals is beset with difficulties ; and although everybody admits the accuracy of Goltz's description of what is to be seen, his inter- pretation of the facts has been severely criticised, particularly by H. Munk. To the monkey it is probable that the loss of the cerebral hemispheres is a heavier and more irremediable blow than to the dog. We see, then, that homologous organs are not necessarily, nor indeed usually, of the same physiological value in different kinds of animals. A loss which perhaps hardly narrows the range of the psychical, and certainly restricts onl}^ to a slight extent the physical powers of a fish, cuts off from the dog a great part, from the monkey almost all, of its intellectual life, and is in man incompatible with life altogether. The results of the removal of the entire cerebral hemi- spheres help us to fix their position as a whole in the physiological hierarchy. A more minute analysis shows us that the cerebral cortex itself is not homogeneous in function, that certain regions of it have been set aside for special labours. Our knowledge of this localization of function in the cerebral cortex has been derived partly from clinical, coupled with pathological observations on man, and partly from the results of the removal or stimulation of definite areas in animals. And so varied and extensive have been the contributions from both of these sources, that it is difficult to decide to which we owe most. THE CENTRAL NERVOUS SYSTEM. 657 It is a fact which might appear strange and almost inexplicable did the history of science not constantly present us with the like, that a ([uarter of a century ago the universal opinion among physiologists, pathologists, and physicians was that the cerebral cortex is inexcitable to artificial stimuli, that no visible response can be obtained from it. The great names of Flourens and Magendie stood sponsors for this error, and repressed research. In 1870, however, Hitzig had occasion to pass a voltaic current through the brain of a soldier wounded in the war with France, and observed that movements of the eyes were produced, and, along with Fritsch, he entered on a series of experiments. These observers were rewarded by finding that not only was it possible to elicit muscular contractions by stimu- lation of the cortex of the brain in the dog with vol- taic currents, but that the excitable area occupied a definite region in the neigh- bourhood of the crucial sulcus, which lies over the convexity of the hemi- spheres nearly at right angles to the longitudinal fissure. In this region they were further able to isolate several distinct areas, stim- ulation of which was fol- lowed by movements re- spectively of the head, face, neck, hind-leg, and fore- leg. This was the starting- point of a long series of re- searches by Ferrier, Munk, Horsley, Schiifer, Heiden- hain, and many others, on the brains of monkeys as well as dogs — researches which have formed the basis of an exact cortical localization in the brain of man, and have enriched surgery with a new province. In these later experi- ments the interrupted current from an induction machine has been found the most suitable form of stimulus (see 'Practical Exercises,' p. 681). Fig. 215. — Motor Areas of Dog's Brain. //, neck ;/./., fore-limb ; //./., hind-limb ; t, tail ; /", face; <:.5., crucial sulcus; e.??i.,eye movements. All the areas are marked in the figure only on the left side except the eye areas, whose position, to avoid confusion, is indicated on the right hemi- sphere. Motor Areas, — Lying around the fissure of Rolando, and lapping over on the mesial surface of the hemisphere in this region, are the so-called motor areas (Figs. 216, 217, 218). They occupy the whole of the ascending frontal and parietal convolutions, running forward a little into the horizontal frontal 42 658 A MANUAL OF PHYSIOLOGY. convolutions, backward a little into the superior parietal con- volution, and turning over on the mesial surface into the marginal convolution. Highest of all on the convexity of the hemisphere lies the area of the leg ; below this, in order, the areas for the face, mouth, pharynx, and larynx. In SYLVIA IM FISSURE Fig. 216. — Lateral View of Left Hemisphere (Man ), with Motor and Sensory Areas. The front of the brain is towards the left. front of the leg and arm areas lies the area of the head, neck, and eyes, passing out into the posterior portions of the first and second frontal convolutions. On the mesial surface in the marginal convolution lie areas for the head, arm, trunk, and leg in order from before backwards. It is to be particularly noted (i) that within the larger THE CENTRAL NERVOUS SYSTEM. 659 areas, such as those of the arm and leg, smaller foci can be mapped off which are related to movements of the separate joints — thus, in the leg area, the hip, knee, and ankle Fig. 217.— Cerebral Cortex (Man) seen from above. The front of the brain is towards the right. The dotted line shows the position of the fissure of Rolando, as fixed by Thane's rule (p. 661). joints, and the great toe, are represented by separate and special centres; (2) that stimulation of any one of these areas leads, not to contraction of individual muscles, but to Fig. 218.— Motor and Sensory Areas of Mesial Surface of Human Brain. The front of the brain is towards the left. contraction of muscular groups which have to do with the execution of definite movements. Removal of the whole of the motor cortex of one hemi- 66o A MANUAL OF PHYSIOLOGY. sphere causes paralysis of movement on the opposite side of the body. The paralysis is less marked in the case of bilateral muscles that habitually act together than in the case of those which ordinarily act alone. Thus the muscles of respiration and the muscles of the trunk in general are, although perhaps weakened, never completely paralyzed. This is an indication that each member of such functional pairs of muscles is innervated from both hemispheres ; and this physiological deduction is supported by the anatomical fact already referred to, that after removal of the motor cortex, or injury to the pyramidal tracts in the internal capsule or crus, some degeneration is found in the crossed pyramidal tract on the side of the lesion, as well as in the anterior pyramidal tract on that side and the opposite crossed pyramidal tract (p. 604). It was supposed by some that these fibres are really rccrossed, i.e., have decussated twice — once, perhaps in the medulla oblongata, and again at a lov/er level in the cord ; but this view has since been modified (p. 606). Removal of a single motor region leads to paralysis only of the corresponding limb, or part of a limb, on the opposite side. In the dog after a time the paralysis may more or less completely disappear, the loss of the cortical centres on one side being perhaps compensated by increased activity of those that are left. In the monkey restoration is much less complete ; in man it probably never occurs. The movements with which the motor areas are con- cerned are essentially skilled movements, and we may sup- pose that it is more difficult for a monkey to educate again a centre for such complex and elaborate manoeuvres as are performed by its hand than for a dog to regain cortical control of the comparatively simple movements of its paw. It is in the light of the results obtained in monkeys, and by the aid of clinical and pathological observations, that the motor areas in man have to a great extent been mapped out. An extensive haemorrhage involving the cerebral cortex on both sides of the fissure of Rolando, or an embolus blocking the middle cerebral artery, causes paralysis of the opposite side of the body. An embolus of a branch of the middle cerebral artery causes paralysis of the muscles, or rather movements, represented in the area supplied by it. A THE CENTRAL NERVOUS SYSTEM. 66 1 tumour causes symptoms of irritation, motor or sensory — con- vulsions beginning in, or an aura referred to, the parts represented in the regions on which it presses. In connection with the localiza- tion of lesions in the motor area of the cortex, and operative inter- ference for their cure, the exact position of the fissure of Rolando becomes important ; and Thane has given the following simple method for fixing it : The distance from the root of the nose to the occipital protuberance is measured with a tape. The upper end of the fissure of Rolando lies half an inch behind its middle point. The fissure makes an angle of 67^ with the longitudinal fissure (Fig. 217). When we have deducted from the cortex of the hemi- sphere the whole Rolandic area, there still remains a large portion unaccounted for. The greater part of the frontal lobe anterior to the ascending frontal convolution responds to stimulation by neither motor nor sensor}' sign ; and by a process of exclusion it has been supposed that it is the seat of intellectual processes. Extensive destruction and loss of substance of this pre-frontal region may occur without any marked symptoms, except some restriction of mental power or loss of moral restraint. Thus in the famous 'American crowbar case,' an iron bar completely transfixed the left frontal lobe of a man engaged in blasting. Although stunned for the moment, he was able in an hour to climb a long flight of stairs, and to answer the inquiries of the surgeon. Finally, he recovered, and lived for nearly thirteen years without either sensory or motor deficiency, except that he suffered occasionally from epileptic convulsions. But his intellect was impaired ; he became fitful and vacillating, profane in his language, and inefficient in his work, although previously decent in conversation and a diligent and capable workman. Sensory Areas — Visual Centres. — In the occipital lobe an area of considerable extent has been found, destruction of which causes hemianopia, i.e., loss of vision in the correspond- ing halves of the retinas. Thus, if the right occipital cortex is destroyed, the right halves of the two retinae are paralyzed, and the left half of the field of vision is a blank. Destruc- tion of this region on both sides causes, according to Munk, complete blindness. Ferrier believes that for this it is necessary that the angular gyrus should also be destroyed- 6^2 A MANUAL OF PHYSIOLOGY. When the same region is stimulated, the eyes and head are turned to the left — that is, to the opposite side. The move- ments differ from those produced by stimulation of the Rolandic area. They are not so certain, their latent period is longer, and they are considered to be not direct, but reflex movements. It can- not be doubted that the occipital region is concerned in vision, and it is a very natural suggestion that the movements are the result of visual sensations in the ex- cited occipital cortex. The right occipital lobe is concerned with vision in the right halves of the two re- tinae. NoWjUnder nor- mal conditions a vm or^ Ti,,^,. ^„ ,^,- o , r^ vlsual 1 m agB would bc rIG. 2IQ. — Diagram of Relations ok Drri- o " 219.— Diagram ok Relations of Occi- pital Cortex to the Retin.^-;. RO, LO, right and left occipital cortex ; RE, LE, right and left retina ; C, optic chiasma ; RF, right and left visnal fields. The continuous LF lines passing back from the retinas to the occipital cortex represent the crossed, the broken lines the uncrossed, fibres of the optic nerves and tracts. cast on the two right retinal halves by an object placed towards the left of the field. The movements of the head and eyes to the left may therefore be plausibly explained as an attempt to look at, and a rotation towards, the supposed object. The pathological evidence is very clear that disease of the occipital lobe, especially of the cuneus, causes hemianopia in man. A limited lesion may even be associated with an incomplete hemianopia, and cases have been recorded in which colour hemianopia (blindness of the corresponding halves of the two retinje for coloured objects) existed with normal vision for white light. Sometimes dimness of vision in the opposite eye (crossed amblyopia), and not hemianopia, is caused by a lesion of the occipital cortex. It seems impossible to THE CENTRAL NERVOUS SYSTEM. 663 explain this and other facts without postulating the existence of more than one visual centre in the occipital lobe ; and it has been supposed that in the angular gyrus a higher visual centre exists which is con- nected with the lower occipital centres for the two halves of the opposite eye. Thus, the right angular gyrus would be in connection with the part of the right occipital cortex which has to do with vision in the nasal half of the left eye, and with the part of the left occipital cortex which has to do with vision in the temporal half of that eye. Auditory Centre. — On the outer surface of the temporo- sphenoidal lobe, in the first and second temporal convolu- tions, lies an area supposed to be associated with the sense of hearing. Stimulation in the region of the first temporal convolution may cause the animal to prick up its ear on the opposite side. Destruction of this area is followed, accord- ing to some observers, by complete and irremediable loss of hearing. According to others it has no such effect. In deaf- mutes the first temporal convolution may be atrophied. There is some evidence that the posterior corpora quadri- gemina and the mesial geniculate body form an inferior relay on the route between the fibres of the auditory nerve and the temporal cortex. Centre for Smell. — As to the position of the centre for smell, direct experiment on animals cannot teach us much, for if the outward tokens of visual and auditory sensations are dubious and fluctuating, still more is this the case with the signs of sensations of smell. A further source of fallacy is the fact that other sensations than those of smell are caused by stimulation of the mucous membrane of the nose. Sub- stances like ammonia, for example, affect entirely the endings of the trigeminus, which is the nerve of common sensation for the nostrils. Pathological and clinical evidence would be of great value, but it is as yet scanty, and of itself indecisive. So far as it goes, however, it undoubtedly supports the view derived from the anatomical connections of the olfactory tracts, that the centre for smell is situated in the uncinate gyrus on the mesial aspect of the temporal lobe, for the olfactory tract may be traced into this region. In animals with a very acute sense of smell, this gyrus is magnified into a veritable lobe, called from its shape the pyriform lobe ; from its supposed function, the rhinencephalon. 664 A MANUAL OF PHYSIOLOGY. Ordinary sensation and in part tactile sensation are located on the mesial surfaces of the hemispheres — by Ferrier in the hippocampal convolution, by Schafer and Horsley in the gyrus fornicatus. But whatever may be the truth in this matter, it would appear that this is not the only region where ordinary sensation is represented. For example, it is practically certain that the Rolandic area has sensory as well as motor functions. We have seen that pathological evidence in man agrees, upon the whole, with wonderful precision with the results of experiments on animals ; and, indeed, before any experi- mental evidence of the minute and elaborate subdivision of the cortex had been obtained, Broca had already, from the phenomena of the sick-bed and the post-mortem room, located a centre for speech in the left inferior frontal convo- lution, and Hughlings Jackson had associated pathological lesions of the Rolandic area with certain cases of epilepti- form convulsions. Aphasia. — In most persons the inferior frontal convolution on the left side is concerned in the expression of ideas in spoken or written language. It is even said that oratorical powers have been found associated with marked development of this convolution (as in the case of Gambetta, the French statesman). Words are, at bottom, arbitrary signs by which certain ideas are expressed. The power of intelligent com- munication by spoken or written language may be lost : (i) by paralysis of the muscles of articulation or the muscles which guide the pen ; (2) by inability to hear or see the spoken or written word, i.e., by deafness or blind- ness ; (3) by inability to comprehend the meaning of spoken or written language, although sensations of hearing and sight may not be abolished — that is to say, by inability to interpret the auditory or visual symbols by which ideas are conveyed ; (4) by inability to clothe ideas in words, although the ideas conveyed by speech or writing may be perfectly comprehended. Neither (i) nor (2) is considered to con- stitute the condition of aphasia ; (3) represents what is called amnesia, or sensory aphasia ; (4) is aphasia in the ordinary restricted sense, or motor apJuisia. In motor aphasia THE CENTRAL NERVOUS SYSTEM. 665 the patient understands quite well what is said to him, and also knows quite well what to reply, but the words necessary to express his meaning do not come to him. He makes no answer whatever, or strings together a series of words each correctly articulated but having no meaning, or utters a jargon not composed of known words at all. The failure does not lie in the articulator}^ mechanism. The patient uses the same muscles of articulation, without any sign of impairment of function, for chewing and swallowing his food. He may sometimes sing a song without a single slip in words or measure, and yet be unable to speak or write it. In certain cases the change is confined to loss of the power of spontaneous speech, and the patient may be able to read intelligently. Sometimes he can express his ideas in speech but not in writing (agraphia). Sometimes the loss is restricted to certain sets of ideas. For example, a boy was injured by falling on his head. Typical symptoms of motor aphasia developed, but the power of dealing with ideas of number was not interfered with, and the boy continued to learn arithmetic as if nothing had happened. Proper names and nouns are more easily lost than adjec- tives and verbs. Motor aphasia is generally accompanied by paralysis, frequently transient, of voluntary movement on the right side, sometimes amounting to complete hemi- plegia, but more often involving the arm or the head and face alone. This association is explained by the proximity of the inferior frontal convolution to the motor areas of the arm and head, and their common blood-supply. Why, now, is it that motor aphasia is commonly due to a lesion in the left hemisphere alone ? The answer to this question is partly supplied by the important and curious observation that in left-handed individuals damage to the right inferior frontal convolution may cause aphasia. In the right-handed man the motor areas of the left hemi- sphere may be supposed to be more highly educated than those of the right hemisphere. The movements of the right side which they initiate or control are stronger and more delicate and precise than those of the left side. It is only necessary to assume that this process of specialization, 666 A MANUAL OF PHYSIOLOGY. of selective training, has been carried on to a still greater extent in the left frontal convolution, that in most men the speech-centre there has taken upon itself the whole of the labour of clothing ideas in words, leaving to the right centre only its primitive but undeveloped powers. In left-handed persons the speech-centre on the right side may be supposed to share in the general functional development of the right hemisphere. That great capabilities are lying dormant in the right speech-centre of the ordinary right-handed individual, is strongly indicated by the fact that after complete de- struction of the left inferior frontal convolution the power of speech may be to a considerable extent, though slowly and laboriously, regained ; but the proof is still wanting that this second accumulation may be swept away, and without remedy, by a second lesion in the right inferior frontal convolution. Temporary aphasia may occur without any structural change in the speech-centre, for example during an attack of migraine. In children it may even be caused by some comparatively slight irritation in the digestive tract, such as that due to the presence of a tape- worm. Sensory Aphasia. — In typical motor aphasia the person understands quite well what is said to him. Spoken and written words have to him their ordinary meaning, and they call up in his mind the usual sequence of ideas, but the chain is broken at the speech-centre, and the outgoing ideas cannot be clothed in words. In another class of cases the patient may be perfectly capable of rational speech ; he may talk to himself or on a set topic with fluency and sense, but he may be unable to respond to a question or read a single line of print. Damage to two regions of the brain has been found associated with this strange condition, (i) the occipital, (2) the temporal cortex. When the lesion is confined to the occipital region spoken language is perfectly understood, written language not at all. When the temporal region is alone affected it is the spoken word that is missed, the written that is understood. Sensory, like motor aphasia, may exist in any degree of completeness, from absolute word-deafness or word-blindness, in which no spoken or THE CENTRAL NERVOUS SYSTEM. 667 printed word calls up any mental image, to a condition not amounting to much more than a marked absence of mind or unusual obtuseness. Sometimes both motor and sensory aphasia may be present together. Cortical Epilepsy, — While it was still believed that the cortex was inexcitable, epilepsy was supposed to be ex- clusively due to morbid conditions, structural or functional, of the medulla oblongata (Kussmaul and Tenner). Some more recent writers have put forward precisely the opposite opinion, that the disease is always cortical in origin (Unver- richt, etc.). What we know for certain is that some cases, but only a minority, are associated with lesions in the Rolandic area (cortical or Jacksonian epilepsy), and it has even been found possible to localize the position of the lesion from the part of the body in which the fit, or the aura (the sensation or group of sensations peculiar to each case, which precedes and announces it), begins. For example, if the convulsions commence with a twitching of the right thumb and extend over the arm, or if the aura consists of sensations beginning in the thumb, there is a strong presumption that the seat of the lesion is the part of the arm-area known as the ' thumb-centre ' in the left cerebral hemisphere. It is the seat of the convulsion at its commencement, not the regions to which it may afterwards spread, that is important in diagnosing the position of the lesion. For just as strong or long-continued stimulation of a given ' centre' of the motor cortex may give rise to contractions of muscles associated with other ' centres,' so the excitation set up by localized disease may spread far and wide from its original focus, involving area after area of the Rolandic region first in the one hemisphere and then in the other. The part of the body to which a sensory aura is referred is as significant an indication of the seat of the discharging lesion as is the part of the body which first begins to twitch. And this is one of the proofs that the Rolandic region is not a purely motor, but a sensori-motor area. From the field of ex- periment further evidence is forthcoming. (i) It has been found that if the posterior roots of the nerves supplying one of the limbs be cut in a monkey, all 668 A MANUAL OF PHYSIOLOGY. the most delicate and skilled movements of the limb are either greatly impaired or totally abolished (Mott and Sherrington). The limb is not used for progression or for climbing, but hangs limp, and apparently helpless, by the side of the animal. That this condition is not due to any loss of functional power by the peripheral portion of the motor path may be assumed, since the anterior roots remain intact. That it is not due to any want of capacity on the part of the motor centres to discharge impulses when stimu- lated may be shown by exciting the cortical area of the limb — either electrically or by inducing epileptic convulsions by intravenous injection of absinthe — when movements of the affected limb take place just as readily as movements of the sound limbs. The cause of the impairment of voluntary motion, then, can only be the loss of the afferent impulses which normally pass up to the brain, and presumably to the motor cortex. When only one sensory nerve-root is cut, no defect of movement can be seen ; and this is evidently in accordance with the fact already mentioned (p. 613), that complete anaesthesia of even the smallest patch of skin is never caused by section of a single posterior root. And that it is the loss of impulses from the skin which plays the chief part is shown by the fact that after division of the posterior roots supplying the muscles of the hand or foot, which only partially interferes with the sensory supply of the skin, joints, sheaths of tendons, etc., movement is unimpaired ; while section of the nerve-roots supplying the skin, those of the muscles being left intact, causes extreme loss of motor power. (2) If a strength of stimulus be sought which will just fail to cause contraction of the muscular group related to a given motor area, and a sensory nerve, or, better, a sensory surface (best of all, the skin over the corresponding muscles), be now stimulated, contraction will occur — that is to say, the excitability of the motor centres will be increased. This shows that the motor region is en rapport not only with efferent, but also with afferent fibres, that it receives im- pulses as well as discharges them. The same experiment is a proof that the results of excitation of THE CENTRAL NERVOUS SYSTEM. 669 the motor cortex are due to stimulation of tiie grey matter, and not, as has been asserted, of the white fibres of the corona radiata. It is undoubtedly possible to excite these fibres by electrodes directly apphed to the motor cortex, but in the latter case the current has to be made stronger than is sufficient to excite the grey matter alone. Further evidence is afforded by the following facts : ( i ) The ' period of delay,' that is, the period which elapses between stimula- tion and contraction, is greater by nearly 50 per cent, when the cortex is stimulated than when the white fibres are directly excited. (2) Morphia greatly increases the period of delay for stimulation of the cortex, and at the same time renders the resulting contractions more prolonged than normal, while the results of direct stimulation of the white fibres are much less, if at all, affected. (3) Mechanical stimulation of the motor areas also causes appropriate movements. (4) Stimulation of the grey matter, when separated from the sub- jacent white matter by the knife but left in position, is without effect unless the strength of stimulus be increased, although twigs of the current ought, of course, to pass into the corona radiata as easily as before. Evidence that the phenomena are not due to accidental excitation of the corona radiata is a fortiori evidence that they are not caused by escape of current to the basal ganglia, for the distance of the basal ganglia from the larger part of the motor cortex is much greater than the thickness of the grey matter ; and, indeed, that portion of the grey matter at the bottom of the Sylvian fissure which lies nearest to the basal ganglia does not respond to stimulation by motor effects. Localization of Function in the Central Nervous System. — Let us now consider a little more closely the real meaning of this localization of function. Scattered all over the grey matter of the primitive neural axis, and, as we have seen, over the grey mantle of the brain as well, are numerous ' centres ' which seem to be related in a special way to special mechanisms, sensory, secretory or motor. The question may fitly be asked whether those centres are really dis- tinct from each other in quality of structure or action, or whether they owe their peculiar properties solely to differences in situation and anatomical connection. It is clear at the outset that the nature of the work in which a centre is engaged must be largely determined by its connections. The kind of activity which goes on in the vaso- motor centre in the bulb, for example, may in no essential respect differ from that which goes on in the respiratory centre. I'he calibre of the bloodvessels will alter in response to a change of activity in the one because it is anatomically connected with the muscular coat of the bloodvessels. The rate or depth of the respiratory movements will alter in response to a change of activity in the other because it is connected with muscles which can act upon the chest-walls. The localization of function in the cerebral cortex has been likened to the localization of industries in the multiplex commercial life of the modern world. The barbarian household in which cloth is woven and worked into garments, sandals or moccasins cobbled 670 A MANUAL OF PHYSIOLOGY. together, rough pottery baked in the kitchen fire, and all the rude furniture of the lodge fashioned by the hands which built it, and which rest beneath it at night — this state of things where centraliza- tion has not yet begun, it has been said, is a picture of what goes on in the undeveloped brains of the frog, the pigeon, or the rabbit. The ' diffusion ' of industries which is characteristic of a primitive state has given place among the most highly civilized men to extreme centralization and concentration. Manchester spins cotton and Liverpool ships it. Chicago handles wheat and pork that have been produced on the prairies of Minnesota and Illinois. Amsterdam cuts diamonds. Munich brews beer. Lyons weaves silk. New York and London are centres of finance. This, it is said, is the picture of the highly specialized brain of a monkey or a man. But ingenious and alluring though such analogies are, they do not rest upon a sufficient basis of fact. It has never been shown, either by experimental evidence or by general reasoning, that there is any difference whatever in the physical, chemical or psychical processes which go on in the various centres of the Rolandic cortex. It may be supposed, indeed, that the so- called sensory areas of the cortex differ more widely in their internal activity from the motor areas than the latter do among themselves, and that the activity of the anterior portion of the brain, the portion which has been credited par excelletice with psychical functions, differs in kind, not merely in degree, from that of all the rest. But, as we have just seen, even the motor areas have sensory functions ; and although a cast-iron physiology may explain this by the assumption of ' sensory ' as well as ' motor ' cells in the Rolandic area, there is absolutely nothing to contradict the supposition that the discharge of energy from the most circumscribed motor area or element (be it cell, or nervous network, or both) may be accompanied not only with consciousness, but with a high degree of psychical activity. And, indeed, some writers have supposed that such a consciousness of, or even conscious measurement of, the discharge from the motor areas is the basis of the muscular sense (Bain, Wundt). So far, at least, as the Rolandic region and the grey matter imme- diately around the neural canal is concerned, the analogy of an electrical switch-board connected with machines of various kinds might be more correct. Touch one key or another, and an engine is set in motion to grind corn, or to saw wood, or to light a town. The difference in result lies not in any difference of material or workman- ship in the switches, but solely in the difference in their connections. Grey matter in the upper part of the Rolandic cortex is excited, and the muscles of the leg contract. Grey matter around the lower part of the fissure is excited, and there are movements of the head, neck, and mouth. Grey matter in the medulla oblongata is excited, and the salivary glands pour forth a thin, watery fluid, poor in proteids, and containing an amylolytic ferment. Another portion of grey (?) matter in the medulla is thrown into activity, and the pan- creatic ducts become flushed with a thick secretion, rich in proteids and in ferments which act on proteids, starch, and fat. Here, too, THE CENTRAL NERVOUS SYSTEM. 671 there is a variety in result according as one or another nervous switch is closed ; here, too, the variety is due, not to essential differences in the structure or the activity of the nervous centres, but to their connection, by nervous paths, with peripheral organs of different kinds. There is, indeed, a specialization, a localization, of function, but the localization is at the periphery, the specialization is in the peripheral organs. It may be asked whether, if this is the case for the peripheral organs of efferent nerves, the converse does not hold true for the afferent nerves, in other words, whether the localization here is not at the centre. And that there is in some degree a central localization of sensation, may be considered proved by the well-known clinical fact, already referred to, that sensations of various kinds may be pro- duced by pathological changes in the cortex. For example, a tumour involving the upper part of the temporal lobe may give rise to epileptiform convulsions preceded by an auditory aura, a sound, it may be, resembling the ringing of bells ; a tumour involving the occipital region may cause a visual aura, and so on. Central sensory localization is, indeed, inevitable if we accept the old doctrine of ' specific energy.' If the impulses set up in the auditory nerve when sound impinges on the tympanic membrane do not differ essentially from those set up in the optic nerve when a ray of light falls upon the retina, or from those set up in the trigeminal nerve by the irritation of a carious tooth, or from those set up in certain fibres of all cutaneous nerves when a warm body comes in contact with the skin ; then, since the results in consciousness are very different, we must assume that somewhere or other in the central nervous system there exist organs that are differently affected by the same kinds of afferent impulses ; in other words, that sensory localization is at the centre. On this view, the visual areas in the cortex respond to all kinds of stimuli by visual sensations ; the auditory areas by sensations of sound ; and possibly the whole or part of the limbic lobe (the convolutions lying around the corpus callosum on the mesial surface of the hemisphere) by sensations of touch and pain. But while it cannot be doubted that special sensory regions exist in the grey matter of the brain, there is no reason to suppose that the nerve-impulses which travel up the optic and up the auditory nerve are absolutely similar until they have reached the visual and auditory centres, and that there they suddenly become, or produce, sensations absolutely different. And it would seem that the tendency of research is at present to increase the evidence in favour of a certain amount of sensory specialization at the periphery, and, therefore, to diminish the scope, if not the necessity, of such a specialization in the brain. For example, when an ordinary nerve-trunk is touched, the resultant sensation is not one of touch. If there is any sensation at all, it is one of pain. Heating or cooling a naked nerve-trunk gives rise to no sensations of temperature. When the ulnar nerve is artificially cooled at the elbow, the first effect is severe pain in the parts of the hand supplied by the nerve. The pain disappears somewhat abruptly as cooling goes on, and is succeeded by gradual loss of all sensation, 672 A MANUAL OF PHYSIOLOGY. touch pain and the temperature sense disappearing in the uhiar area of the hand in the order named ; but the cooUng of the nerve-trunk does not give rise to any sensation of cold (Weir Mitchell). Stimu- lation of the end organs is essential in order that sensations of touch and temperature should be experienced. The tradition which has come down from the older surgery before the days of anaesthetics, that when the optic nerve was cut in removing the eyeball the patient experienced the sensation of a flash of light, was long looked upon as the strongest prop of the law of specific energy. But neither the evidence of the alleged fact nor the consequences deduced from it have escaped modern criticism. And it is possible that in some cases, at least, the retina was excited — directly by mechanical stimu- lation, or by means of fibres carrying impulses peripherally (?) in the optic nerve — at the moment when the knife entered it, and that sufficient time elapsed before the section was completed for the ex- citation to pass up across an isthmus of uncut fibres. Ewald has stated too, that even after extirpation of the end organs of the auditory nerve in the pigeon, sounds are still heard so long as the nerve-trunk itself is intact. This would go to show either that the impulses set up in this nerve by the mechanical stimulation of aerial waves sutificiently large to excite ordinary cutaneous nerves are of a special kind, and therefore result in a special sensation, or that, the impulses being alike in the auditory and other nerves, the former is peculiarly susceptible to sound-waves. In the first case a certain amount of specialization in the afferent impulses would be proved to be accomplished before they reach their centres. One reason, then, why excitation of the temporal cortex by impulses falling into it along the auditory nerve-fibres causes a sensation different from that caused by impulses reaching the occipital cortex through the fibres of the optic nerve may be a difference in the nature of the impulses. If this were the only reason it would follow that were it possible to physiologically connect the fibres of the optic radiation with the temporal cortex, and those of the temporal radiation with the occipital cortex, sights and sounds would still be perceived and dis- criminated in a normal manner, although now the integrity of the occipital lobe would be bound up with the perception of sound, the integrity of the temporal lobe with visual sensation. This state of affairs would correspond to complete specialization for sensation in the peripheral organs, complete absence of specialization in the centres. On the other hand, it is conceivable that, after such an ideal experiment, soundwaves falling on the auditory ajiparatus might cause visual sensations, and luminous impressions falling on the retina sensations of sound. This would correspond to complete specialization of sensation in the centres, complete absence of specialization at the periphery. A third possibility would be that the ' transposed ' centres, responding at first feebly or not at all to the new impulses, might, by slow degrees, become more and more excitable to them. This would correspond to a peripheral specializa- tion, combined with a tendency to development of central specializa- tion. And, indeed, it is not easy to conceive in what way, except THE CENTRAL NERVOUS SYSTEM. 673 as the result of differences in the nature of impulses coming from the periphery, specialization of sensory areas in the central nervous system could have at first arisen. Reaction Time. — Just as in a reflex act a certain measure- able time {reflex time) is taken up by the changes that occur in the lower nervous centres, so we may assume that in all psychical processes the element of time is involved. And, indeed, when the interval that elapses between the applica- tion of a stimulus and the signal which announces that it has been felt {reaction time) is measured, it is found that the cerebral processes associated with the perception of even the simplest sensation and the production of even the simplest voluntary contraction is longer than the time which the spinal centres require for the elaboration of even com- plex and co-ordinated reflex movements. Suppose, e.g., that the stimulus is an induction shock applied to a given point of the skin, and that the signal is the closing of the circuit of an electro-magnet, then, if both events are automatically recorded on a revolving drum, the interval can be readily determined. It is evident that this includes, not only the time actually consumed in the central pro- cesses, but also the time required for the afferent impulse to reach the brain, and the efferent impulse the hand, along with the latent period of the muscles. The time taken up in these three events can be approximately cal- culated, and when it is subtracted, the remainder repre- sents the reduced or corrected reaction time ; that is, the interval actually spent in the centres themselves. This is by no means a constant. It is influenced not only by the degree of complexity of the psychical acts involved, and the mental attitude of the person (whether hs expects the stimulus or is taken by surprise, whether he has to choose between several possible kinds of stimuli and respond to only one, etc.), but it varies also for different kinds of sensa- tion, for the same sensation at different times, and, as is recognised in the j!)^rsona/ ^(/zm^/o;; of astronomers, in different individuals. For sensations of touch and pain it may be taken as one-ninth to one-fifth, for hearing one-eighth to one-sixth, and for sight one-eighth to one-fifth of a second. 43 674 A MANUAL OF PHYSIOLOGY. So that the proverbial quickness of thought is by no means great, even in comparison with that of such a gross process as the contraction of a muscle (one-tenth of a second). Nor is it the case that the man 'of quick apprehension' has always a short reaction time, or the dullard always a long one, although in all kinds of persons practice will reduce it. Sleep. — Certain gland-cells, certain muscular fibres, and the epithelial cells of ciliated membranes, never rest, and perhaps hardly ever even slacken their activity. But in most organs periods of action alternate at more or less frequent intervals with periods of relative repose. In all the higher animals the central nervous system enters once at least in the twenty-four hours into the condition of rest which we call sleep. What the cause of this regular periodicity is we do not know. Some have suggested that sleep is in- duced by the action of the waste products of the tissues, and especially lactic acid, when they accumulate beyond a certain amount in the blood, or in the nervous elements themselves. Others have looked for an explanation to vascular changes in the bram, but so far are the possible causes of such changes from being understood, that it is even yet a question whether in sleep the brain is congested or anaemic. In coma, a pathological condition which in some respects has analogies to profound and long-continued sleep, the brain is congested, and the proper elements of the nervous tissue presumably compressed. And artificial pressure (applied by means of a distensible bag introduced through a trephine hole into the cranial cavity) may cause not only unconscious- ness, but absolute anaesthesia. But it is possible that this artificial increase of intracranial pressure may produce its effects by rendering the brain anaemic, and it has been actually observed that the retinal vessels, as seen with the ophthalmoscope, and the vessels of the pia mater exposed to direct observation in man by disease of the bones of the skull, or in animals by operation, shrink during sleep. Further, a condition closely resembling, if not identical with, natural sleep can be induced by tying the cerebral arteries ; so that the balance of evidence is decidedly in favour of the view that sleep is associated with anaemia, although it is not THE CENTRAL NERVOUS SYSTEM. 675 a good argument to say. as some writers have done, that when the brain rests the quantity of blood in it must be supposed, as in other resting organs, to be diminished. For when the whole body rests, as it does in sleep, it has as much blood in it as when it works ; in sleep, therefore, if some resting organs have less blood than in waking life, other resting organs must have more ; and it is the province of experiment to decide which are congested and which anaemic. In general, the depth of sleep, as measured by the intensity of sound needed to awaken the sleeper, increases rapidly in the first hour, falls abruptly in the second, and then slowly creeps down to its minimum, which it reaches just before the person awakens. As to the amount of sleep required, no precise rules can be laid down. It varies with age, occupation, and perhaps climate. An infant, whose main business is to grow, spends, or ought to spend, if mothers were wise and feeding-bottles clean, the greater part of its time in sleep. The man, whose main business it is to work with his hands or brain, requires his full tale of eight hours' sleep, but not usually more. The dry and exhilarating air of some of the inland portions of North America, and perhaps the plains of Victoria and New South Wales, incite, and possibly enable, a new-comer to live for a considerable period with less than his ordinary amount of sleep. Idiosyncrasy, and perhaps to a still greater extent habit, have also a marked influence. The great Napoleon, in his heyday, never slept more than four or five hours in the twenty-four. Five or six hours or less was the usual allowance of Frederick of Prussia throughout his long and active life. Hypnosis is a condition in some respects allied to natural slumber ; but instead of the activity of the whole brain — or perhaps we should rather say, the whole activity of the brain — being in abeyance, the susceptibility to external impressions remains as great as in waking life, or may be even increased, while the critical faculty, which normally sits in judgment on them, is lulled to sleep. The condi- tion can be induced in many ways — by asking the subject to look fixedly at a bright object, by closing his eyes, by occupying his atten- tion, by a sudden loud sound or a flash of light, etc. The essential condition is that the person should have the idea of going to sleep, and that he should surrender his will to the operator. In the hypnotic condition the subject is extremely open to suggestions made by the operator with whom he is en lapport. He adopts and acts upon them without criticism. If, for example, the hypnotizer raises the subject's arm above his head, and suggests that he cannot bring it down again, it stays fixed in that position for a long time without any appearance of fatigue ; or the whole body may be thrown, on a mere hint, into some unnatural pose in which it remains rigid as a statue. Suggested hemiplegia or hemian^esthesia, or paralysis of motion 676 A MANUAL OF PHYSIOLOGY. and sensation together or apart in limited areas, can also be realized ; and surgical operations have been actually performed on hypnotized persons without any appearance of suffering. If, on the other hand, the operator suggests that the subject is undergoing intense pain, he will instantly take his cue, writhing his body, pressing his hands upon his head or breast, and in all respects behaving as if the suggestion were in accord with the facts. If he is told that he is blind or deaf, he will act as if this were the case. If it is sug- gested that a person actually present is in Timbuctoo the subject will entirely ignore him, will leave him out if told to count the persons in the room, or try to walk through him if asked to move in that direction. What is even more curious is that the organic functions of the body are also liable to be influenced by suggestion. A postage-stamp was placed on the skin of a hypnotized person, and it was suggested that it would raise a blister. Next day a blister was actually found beneath it. The letter K, embroidered on a piece of cloth, was suggested to be red-hot. The left shoulder was then ' branded ' with it, and on the right shoulder appeared a facsimile of the K as if burnt with a hot iron. The secretions can be increased or diminished, subcutaneous haemorrhages, veritable stigmata, can be caused, and many of the ' miracles ' of Lourdes and other shrines, ancient and modern, repeated or surpassed by the aid of hypnotic suggestion. Hypnotism has also been practically employed in the treatment of various diseases, and particularly in functional derange- ments of the nervous system. But care and judgment are necessary on the part of the operator, and although as a rule there is no diffi- culty in putting an end to the condition by a suitable suggestion, it is said that in rare instances grave mischances have occurred. There seems to be no ground for the opinion that women are more easily hypnotized than men. Out of more than a thousand persons Lie- bault found only i 7 absolutely refractory. Relation of Size of Brain to Intelligence. — While it is the case that some men of great ability have had remarkably heavy and richly convoluted brains, it would seem that in general neither great size nor any other anatomical peculiarity of the cerebrum is constantly associated with exceptional intellectual power. In the animal kingdom as a whole, there is undoubtedly some relation between the status of a group and the average brain development within the group. But that this is a relation which is complicated by other circumstances than the mere degree of intelligence is sufficiently shown by the fact that a mouse has more brain, in proportion to its size, than a man, and thirteen times more than a horse ; while both in the rabbit and sheep the ratio of brain-weight to body- weight is nearly twice as great as in the horse, in the dog only half as great as in the cat and not very much more than in the donkey. The following tables, too, which illustrate the weight of the brain in man at different ages, show that, although we might give ' the infant phenomenon ' an anatomical basis, we should greatly overrate the intellectual acuteness of the average baby if we were to measure it by the ratio of brain to body-weight alone. THE CENTRAL NERVOUS SYSTEM. 677 Age. Brain- weight. Age. Brain-weight I year. 885 grm. 8 years. 1045 grm. 2 years. 909 )) 10 „ 1315 » 3 „ 1071 )) II ,, 1 168 „ 4 ,. 1099 M 12 ,, 1286 „ 5 M ^OZZ )) 13 » 1505 >, 6 » 1 147 )> 14 » ^?>2>^ n 7 „ 1201 )> 15 M I414 „ Age. Men. Women. 10 — 19 141 1 grm. 1219 grm. 20 — 29 1419 ,, 1260 „ 30—39 1424 „ 1272 „ 40—49 1406 „ 1272 „ (Bischoff.) Age. Men. Women. 50—59 1389 g™- 1239 grm. 60 — 69 1292 ,, 1219 „ 70—79 1254 „ 1129 „ 80—90 1303 „ 898 ,, (Huschke.) In some small birds the ratio is as high as i : 12, in large birds as low as I : 1,200 ; in certain fishes a gramme of brain has to serve for over 5 kilos of body. As a rule, especially within a given species, the brain is proportionally of greater size in small than in large animals. The Circulation in the Central Nervous System. — The arrange- ment of the cerebral bloodvessels has certain peculiarities which it is of great importance to remember in connection with the study of the diseases of the brain, many of which are caused by lesions in the vascular system — haemorrhage or embolism. Four great arterial trunks carry blood to the brain, two internal carotids and two verte- brals (Plate V., 4). The vertebrals unite at the base of the skull to form the single mesial basilar artery, which, running forward in a groove in the occipital bone, splits into the two posterior cerebral arteries. Each carotid, passing in through the carotid foramen, divides into a middle and an anterior cerebral artery ; the latter runs forward in the great longitudinal fissure, the former lies in the fissure of Sylvius. A communicating branch joins the middle and posterior cerebrals on each side, and a short loop connects the two anterior cerebrals in front. In this way a hexagon is formed at the base of the brain, the so-called circle of Willis. While the anas- tomosis between the large arteries is thus very free, the opposite is true of their branches. All the arteries in the substance of the brain and cord are ' end-arteries,' that is to say, each terminates within its area of distribution without sending any communicating branches to make junction with its neighbours. The consequence of these two anatomical facts is: (i) that interference with the blood- supply of the brain between the heart and the circle of Willis does not produce symptoms of cerebral ansemia — e.g., both common carotids may be tied without any harmful effect ; (2) that the block- ing of any of the arteries which arise from the circle or any of their branches leads to destruction of the area supplied by it. The basal ganglia are fed by twigs from the circle of Willis and the beginning of the posterior, middle, and anterior cerebral arteries. 6/8 A MANUAL OF PHYSIOLOGY. Of these the most important are the lenticulo-striate and lenticulo- optic branches of the middle cerebral, which are given off near its origin, and run through the lenticular nucleus into the internal capsule, and thence to the caudate nucleus and optic thalamus respectively. The chief part of the blood from the circle of Willis is carried by the three great cerebral arteries over the cortex of the brain. The white matter, with the exception of that in the immediate neighbourhood of the basal ganglia, is nourished by straight arteries which penetrate the cortex. The middle cerebral supplies the whole of the parietal as well as that portion of the frontal lobe which lies immediately in front of the fissure of Rolando and the upper part of the temporal lobe. The rest of the frontal lobe is supplied by the anterior cerebral, and the occipital lobe, with the lower part of the temporal lobe, by the posterior cerebral. The medulla oblongata, cerebellum, and pons are fed from the vertebrals and the basilar artery before the circle of Willis has been formed. PRACTICAL EXERCISES ON CHAPTER XII. I. Hemisection of the Spinal Cord.* — Put a small dog under morphia (p. 150), and fasten it on a holder in the prone position. Clip and shave the skin over the three lower dorsal vertebra. Wash with soap and water, then with corrosive sublimate solution. Then, giving ether if necessary, make a longitudinal incision under anti- septic precautions down to the spines of the vertebra. Dissect the muscles away from the spines and vertebral laminae ; with bone forceps or strong scissors cut through the laminae on each side of one of the lower dorsal vertebrae, and remove the posterior portion of the arch with the spinous process. The spinal cord will now come into view, covered by the dura mater. Seize the dura with fine-pointed forceps, and divide it freely in the mesial line. Then with a narrow- bladed, sharp knife (a cataract-knife, e.g.) divide one half of the cord. If there is not room enough to work satisfactorily in the spinal canal, remove another vertebral arch. Sponge the wound with iodoform gauze wrung out of normal saline solution previously boiled and still as hot as the hand can bear ; then put in a row of deep sutures, bring the skin together by stitches, and paint the surface with collodion. Place the dog in its cage, and study the loss of motion and sensation in the two hind-legs during 'the stage of shock' (first few days), and then later on when a certain degree of recovery has taken place. Test the sensibility for pain by pinching the legs or toes ; for temperature by placing them in hot or cold water, and comparing the promptitude with which they are withdrawn with what happens in the case of the fore-limbs; for slight tactile sensation by blowing through a tube on the legs. Note the rectal temperature from day to day, and observe whether the freces and urine are * Experiments i and 3 are difficult, and are only to be attempted by advanced students selected by the demonstrator. PRACTICAL EXERCISES. 679 normally under control. After five or six weeks, or a longer or shorter time according to whether the symptoms are stationary or not, kill the animal by chloroform. Take out the brain and cord, noting particularly the state of matters at the site of the hemi- section. Harden first in Miiller's fluid (essentially potassium bichro- mate, with a little sodic sulphate) for ten days, then put portions into Marchi's fluid (a mixture of one part of a i per cent, solution of osmic acid with two parts of Miiller's fluid), cut in celloidin, and examine the degenerated tracts (p. 597). 2. Section and Stimulation of the Spinal Nerve-roots in the Frog. —Select a large frog (a bull-frog if possible). Pith the brain. Fasten the frog, belly down, on a plate of cork. Make an incision in the middle line over the spinous processes of the lowest three or four vertebrae, separate the muscles from the vertebral arches, and with strong scissors open the spinal canal, taking care not to injure the cord by passing the blade of the scissors too deeply, f^xtend the open- ing upwards till two or three posterior roots come into view. Pass fine silk ligatures under two of them, tie, and divide one root central to the ligature, the other peripheral to it. Stimulate the central end, and reflex movements will occur. Stimulate the peripheral end : no effect is produced. Now cut away the exposed posterior roots and isolate and ligature two of the anterior roots, which are smaller than the posterior. Stimulate the central end of one: there is no effect. Stimulation of the peripheral end of the other causes contractions of the corresponding muscles. 3. Perform the same experiment with antiseptic precautions on a rabbit which has received \ gramme chloral hydrate in the rectum, and is etherized for the operation if necessary. Similar phenomena may be observed, but when the peripheral end of an anterior root is stimulated, reflex movements may be produced in muscles other than those supplied by the motor fibres of the root. When this is the case, we may conclude that the animal would have showed signs of pain on stimulation of the anterior root if it were not narcotized. The recurrent fibres are the afferent channels. Divide all the posterior roots which can be seen in the wound, cleanse the latter thoroughly, first with cotton-wool wrung out of corrosive sublimate solution, then with iodoform gauze wrung out of hot water. Dust with iodoform, close with a double row of sutures, and paint with collodion. _ If the animal recovers, study the defects of sensation and motion. The muscles supplied by the divided anterior roots, with the roots themselves and the motor-fibres of the nerves, will degenerate, and the reaction of degeneration may possibly be obtained from the muscles. The sensory fibres of the mixed nerves will not degenerate if the posterior roots have been divided above the ganglia, as would be the case in this e.xperiment. After a month kill the animal by chloroform, harden the cord, medulla oblongata, and the divided nerve-roots, with portions of the nerves to which they belong and the muscles supplied by them, in Miiller's and Marchi's fluids, and make sections. But if, as is probable, the wound becomes septic, the rabbit must be at once killed. 68o A MANUAL OF PHYSIOLOGY. 4. Reflex Action : Inhibition of the Reflexes. — Pith a frog (brain only). Pass a hook through the jaws. Holding the frog by the hook, dip one leg into a dilute solution of sulphuric acid ("2 to '5 percent), and note with the stop-watch the interval which elapses before the frog draws up its leg (Tiirck's method of determining the reflex time). Wash the acid off with water. Now touch the skin of one thigh with blotting-paper soaked in strong acetic acid. The leg is drawn up, and the foot moved as if to get rid of the irritant. If the leg is held, the other is brought into action. Immerse the frog in water to wash away the acid. Again dip one leg into the dilute acetic acid, and estimate the reflex time. Then apply a crystal of common salt to the upper part of the spinal cord. If the opening made for pithing the frog is not large enough to enable the cord to be clearly seen, enlarge it. Again dip the leg in the dilute acid. It will either not be drawn up at all, or the interval will be distinctly longer than before. 5. Action of Strychnia. — Pith a frog (brain only). Inject into one of the lymph-sacs 3 or 4 drops of a o"i per cent, solution of strychnia. In a few minutes general spasms come on, which have intermissions, but are excited by the slightest stimulus. The extensor muscles of the trunk and limbs overcome the flexors. Destroy the spinal cord ; the spasms at once cease, and cannot again be excited. 6. Excision of Cerebral Hemispheres in the Frog. — Put a frog under a bell-jar with a small piece of cotton-wool soaked in ether. In a few minutes it will be anaesthetized. Then, holding it in a cloth, make an incision through the skin over the skull in the mesial line. With scissors open the cranium about the position of a line drawn at a tangent to the posterior borders of the two tympanic membranes. Remove the roof of the skull in front of this line with forceps, scoop out the cerebral hemispheres, and sew up the wound. As soon as the animal has recovered from the ether, the phenomena described at p. 654 should be verified. Let the frog live for a day, keeping it in a moist atmosphere ; then expose the brain again, determine the reflex time by Tiirck's method ; apply a crystal of common salt to the optic lobes, and repeat the observation. The reflex move- ments will be completely inhibited or delayed. Remove the salt, wash with normal saline, and excise the optic lobes. The frog will still swim when thrown into water, and will refuse to lie on its back, but it will fall if the board on which it lies be gradually slanted. 7. Excision of the Cerebral Hemispheres in a Pigeon. — Feed a pigeon for two or three days on dry food, etherize it by holding a piece of cotton-wool sprinkled with ether over its beak, or inject into the rectum \ gramme chloral hydrate. The pigeon being wrapped up in a cloth, and the head held steady by an assistant, the feathers are clipped off the head, an incision made in the middle line through the skin, and the flaps reflected so as to expose the skull. Cut through the bones with scissors, and make a sufficiently large opening to bring the cerebral hemispheres into view. They are rapidly divided from the corpora bigemina and lifted out with the handle of a scalpel. The bleeding is very free, but may be partially controlled by stuffing the cavity with pengawahr yambi, which should be re- PRACTICAL EXERCISES. 68 1 moved in a few minutes, the wound cleansed with iodoform gauze wrung out of normal salt solution at 50° C, and sewed up. Study the phenomena described on p. 654. 8. Stimulation of the Motor Areas in the Dog. — {a) Study a hardened brain of a dog, noting especially the crucial sulcus (Fig. 215), the convolutions in relation to it, and the areas mapped out around it by Hitzig and Fritsch and others, {b) Inject morphia under the skin of a dog. Set up an induction-coil arranged for tetanus, with a single Daniell in the primary circuit. Connect a pair of fine but not sharp- pointed electrodes through a short-circuiting key with the secondary. Fasten the dog on the holder, belly down, and put a large pad under the neck to support the head. Clip the hair over the scalp. Feel for the condyles of the lower jaw, and join them by a string across the top of the head. Connect the outer canthi of the eyes by another thread. The crucial sulcus lies a little behind the mid-point between these two lines. Now give the dog ether if necessary, make a mesial incision through the skin down to the bone, and reflect the flaps on either side. Detach as much of the temporal muscle from the bone as is necessary to get room for two trephine holes, the internal borders of which must be not less than \ inch from the middle line, so as to avoid wounding the longitudinal sinus. Care- fully work the trephine through the skull, taking care not to press heavily on it at the last. Raise up the two pieces of bone with forceps, connect the holes with bone forceps, and enlarge the opening as much as may be necessary to reach all the motor areas. At this stage only enough ether should be given to prevent suffering. Now unbind the hind and fore limbs on the side opposite to that on which the brain has been exposed, apply blunt electrodes successively to the arm and leg areas, and stimulate. Contraction of the corresponding groups of muscles will be seen if the narcosis is not too deep. Move- ments of the head, neck, and eyelids may also be called forth by stimulating the motor areas for these regions. Stimulation in front of the crucial sulcus may also cause great dilatation of the pupil, the iris almost disappearing. Repeat the experiment on the opposite side of the brain. In the course of his observations the student will almost certainly have the opportunity of seeing general epileptiform convulsions set up by a localized excitation. They begin in the group of muscles represented in the portion of the cortex directly stimulated. After the phenomena of such convulsions have been sufficiently studied, they should be again induced, and the stimulated motor area rapidly excised during their course. In some cases this will be followed by immediate cessation of the spasms. 9. Removal of the Motor Areas on One Side in the Dog. — Proceed as in 8, but use antiseptic precautions, and instead of stimulating, destroy with the actual cautery or remove with the knife all the grey matter around the crucial sulcus on one side. Stop bleeding by iodoform gauze wrung out of hot normal saline solution. Sew up the muscles by one set of sutures, the skin by another, and cover the wound with collodion. When the dog has recovered from the operation, study the deficiency of motor and sensory power on the opposite side (p. 660). CHAPTER XIII. THE SENSES. Hitherto we have been considering from a purely objective stand- point the organs that compose the body, and their work. The student has been assumed to be in the Httle world — ' the micro- cosmos ' — of organization which he has been studying, but not of it. He has listened to the sounds of the heart, seen its contraction, felt it hardening under his fingers ; but we have not inquired as to the meaning or the mechanism of this hearing, seeing, and feeling. We have now to recognise that all our knowledge of external things comes to us by the channels of the senses, and, like the light that falls through coloured windows on the floor of a church, is tinged, and perhaps distorted, in the act of reaching us. The Senses in General. — The old and orthodox enumeration of ' the five senses ' of sight, hearing, touch, taste, and smell must be augmented by at least two more, the senses of pressure and temperature. The power of appreciating the amount of a muscular effort ; the power of localizing the various portions of the body in space ; the sensations of pain, tickling, itching, hunger, and thirst ; the sensations accompanying the generative act, etc., have also been looked upon by some as separate senses subserved by special nerves and connected with definite centres. In the development of a simple sensation we may distinguish three stages : the stimulation of a peripheral end-organ, the propagation of the impulses thus set up along an afferent nerve, and their reception and elaboration in a central organ. We do not know in what manner a series of transverse vibrations in the ether when it falls upon the eye, or a series of longitudinal vibrations in the air when it strikes the ear, excites a sensation of light or sound. We can trace the ray of light through the refractive THE SENSES. 683 media of the eyeball, see it focussed on the retina, lead off the current of action set up in that membrane, which, doubtless, gives token of the passage of nervous impulses into and up the optic nerve. We can even follow the nervous impulses to a definite portion of the cortex of the occipital lobes, and determine that if this is removed no sensation of sight will result from any excitation of retina or optic nerve. And it is fair to conclude that in some manner this part of the cerebral cortex is essential to the production of visual sensations. But in what way the chemical or physical processes in the axis cylinders or nerve-cells are related to the psychical change, the inter- ruption of the smooth and unregarded flow of consciousness which we call a sensation of light, we do not know. To our reasoning, and even to our imagination, there is a great gulf fixed between the physical stimulus and its psychical consequence : they seem incom- mensurable quantities ; the transition from light to sensation of light is certain, but unthinkable. Each kind of peripheral end-organ is peculiarly suited to respond to a certain kind of stimulus. The law of ' adequate ' or ' homologous ' stimuli is an expression of this fact. The ' adequate ' stimuli of the organs of special sense may be divided into: (i) vibrations set up at a distance without the actual contact of the object, e.g., light, sound, radiant heat ; (2) changes produced by the contact of the object, e.g., in the production of sensations of taste, touch, pressure, altera- tion of temperature (by conduction). Midway between (i) and (2) lies the adequate stimulus of the olfactory end-organs, which are excited by material particles given off from the odoriferous body and borne by the air into the upper part of the nostrils. The end-organs of the special senses all agree in consisting essen- tially of modified epiblastic cells, but they occupy areas by no means proportioned to their importance and to the amount of information we acquire through them. The extent of surface which can be affected by light in an adult man is not more than 20 sq. cm. ; the endings of both nerves of hearing taken together do not at most expand to more than 5 sq. cm. ; the olfactory portion of the mucous membrane of the nose has an area of not more than 10 sq. cm. ; the sensations of taste are ministered to by an area of less than 50 sq. cm. ; the end-organs of the senses of pressure, touch, and temperature are distributed over a surface reckoned by square metres. As the physiological status of the sensory end-organs rises, their anatomical distribution tends to shrink. The organs of comparatively coarse and common sensations are widely spread, intermingled with each other, and seated in tissues whose primary function may not be sensory at all. Even the nerve-endings of the sense of taste are not confined to one definite and circumscribed 684 A MANUAL OF PHYSIOLOGY. patch, but scattered over the tongue and palate ; and both tongue and palate are at least as much concerned in mastication and deglutition as in taste. The olfactory portion of the nasal mucous membrane, although a continuous area with fairly distinct boun- daries, is still a part of the general lining of the nostril. The epithelial surfaces which minister to the supreme sensations of sight and sound — the retina and the sensitive structures of the cochlea — are the most sequestered of all the sensory areas, as the organs of which they form a part are, of all the organs of sense, the most highly specialized in function, and anatomically the most limited. But although hidden in protected hollows, they are endowed, either in virtue of their own movements or of those of the head, with the power of receiving impressions from every side, and their actual size is thus indefinitely multiplied. VISION. Physical Introduction. — Physically a ray of light is a series of disturbances or vibrations in the luminiferous ether, which radiates out from a luminous body in what is practically a straight line. The ether is supposed to fill all space, including the interstices between the molecules of matter and the atoms of which those molecules are composed. Suppose a bar of iron to be gradually heated in a dark room. In the cold iron the molecules are moving on the average at a relatively slow rate, and the waves set up in the ether by their vibrations are comparatively long. Now the long ethereal vibrations do not excite the retina, because it is only fitted to respond to the impact of the shorter waves ; and, indeed, the long waves are absorbed by the watery media of the eye. As the temperature of the iron bar is increased, the molecules begin to move more quickly, and waves of smaller and smaller length, of greater and greater frequency, are set up, until at last some of them are just able to stimulate the retina, and the iron begins to glow a dull red. As the heating goes on the molecules move more quickly still, and, in addition to waves which cause the sensation of red, shorter waves that give the sensation of yellow appear. Finally, when a high temperature has been reached, the very shortest vibrations which can affect the eye at all mingle with the medium and long waves, and the sensation is one of intense white light. We have said that a ray of light travels in a straight line, and the direction of the straight line does not change so long as the medium is homogeneous. But when a ray reaches the boundary of the medium through which it is passing, a part of it is in general turned back or reflected. If the second medium is transparent (water or glass, e.g. ), the greater part of the ray passes on through it, a smaller portion is reflected. If the second medium is opaque, the ray does not penetrate it for any great distance ; if it is a piece of polished metal, e.g.., nearly the whole of the light is reflected; if it is a layer of lampblack, very little of the light is reflected, most of it is absorbed. Reflection. — The first law of reflection is that the reflected ray, the THE SENSES. 685 ray which falls tipon the reflecting surface {incide?it ray), and the normal to the surface, are in one plane. The second law is that the reflected ray makes, with the perpendicular (normal) to the reflecting surface, the same angle as the incident ray. A corollary to this is that a ray perpendicular to the surface is reflected along its own path. -Reflection from a Plane Mirror. — Let a ray of light coming from the point P meet the surface L)E at B, making an angle PBA with the normal to the surface. The retlected ray BC will make an equal angle ABC with the normal ; and the eye at C will see the image of P as if it were placed at P', the point where the prolongation of BC cuts the straight line drawn from P perpendicular to DE. This is the position of an ordinary looking-glass image. -Reflection from a Concave Spherical Mirror. — A spherical surface may be supposed to be made up of an infinite number of infinitely small plane surfaces. The normal to each of these plane surfaces is the radius of the si)here, and the reflected ray makes with the radius at the point of incidence the same angle as the incident ray. Let D (Fig. 221) be the middle point of the mirror, and C its centre of curvature, i.e., the centre of the sphere of which it is a segment. Then CD is the principal axis, and any other line through C which Fig. 220. — Reflection fku.m .\ Pl.we Mirror. Fig. 221. — Reflection from a Concave Spherical Mirror. Fig. 222. — luRM.ATiON of Real Inverted Im.vge by a Concave Spherical Mirror. cuts the mirror is a secondary axis. When the mirror is a small portion of a sphere, rays parallel to the principal a.xis are focussed at the principal focus F midway between C and D ; rays parallel to any secondary axis are focussed in a point lying on that axis ; and rays diverging from a point on any axis are focussed in a point on the same axis. These facts afford a simple construction for finding the position of the image of an object formed by a concave mirror. Let AB be the 686 A MA NUA L OF PH\ ^SIOL OGY. object (Fig. 222). Then the image of A is the point in which all rays proceeding from A and falling on the mirror, including rays parallel to the principal axis, are focussed. But the ray AE, parallel to the principal axis, passes after reflection through the principal focus F, therefore the image of A must lie on the straight line EF. If any secondary axis ACD be drawn, the image of A must lie on ACD. It must therefore be the point of intersection, a, of EF and ACD. Similarly, the image of B must be the point of intersection, b, of GF and BCH. The image ab of an object AB farther from the mirror than the principal focus is real and inverted. The Purkinje-Sanson image reflected from the concave anterior surface of the vitreous humour (Fig. 236) is an example. After reflection from a convex mirror, rays of light always diverge, and only erect, virtual images are formed, i.e., images which do not reallyexist in space but which, from the direc- tion of the rays of light, we judge to exist. I'he position of the image of an object AB (Fig. 2 2-^) may be found by a construc- tion similar to that for reflection from a con- cave mirror. The image of a flame reflected from the anterior surface of the cornea or lens is erect and virtual. It diminishes in size with increase in the curvature or convexity of the reflecting surface (Fig. 256). Refraction. — A ray of light passing from one medium into another has its velocity, and consequently its direction, altered. It is said to be refracted. The first law of refraction is that i/ie refracted ray is in the same plane as the incident ray and the normal to the surjace. 'Ihe second law is that the sitie of the angle of incidence has a cojistant ratio (for any given pair of media) to the situ of the ang/e of refraction. The angle of incidence is the angle which the ray makes with the normal to the surface, separating the two media ; the angle of refraction is the angle made with the normal in the second medium. This ratio is called the index of refraction between the two media. For purposes ■of comparison, the refractive index of a substance is usually taken as the ratio of the sine of the angle of incidence to the sine of the angle •of refraction of a ray passing from air into the substance. When a ray strikes a surface at right angles, it passes through without suffering refraction. When a ray passes from a less dense to a denser medium {e.g., from air to water), it is bent towards the perpendicular. When it passes from a more dense to a less dense medium (as from water to air), it is bent away from the perpendicular Fig. 223.- -FOKMATION OF IMAGE BY .^ CONVEX MlKKOK. THE SENSES. 687 When a ray passes across a medium bounded by parallel planes, it issues parallel to itself; in other words, it undergoes no refraction (Fig. 225). Refraction and Dispersion by a Prism. — The beam of light is bent towards the normal N as it passes across BA and away from the normal N' as it passes across BC (Fig. 226); at both surfaces it is c P B p' /h Fig. 224.— Rekkactujn at a Plane Surface. AB is the incident ; BD, the refracted ray; CB, the normal to the surface. When the ray passes from air into another medium, the refractive index of the latter is the fraction sin .1 sin p Fig. 225. — y^EFRACTION BY A MEDIU.M BOUNDED BY PARALLEL PLANES. P AND P'. The ray ABDE issues parallel to its original direction ; CB, FD, normals to P and P' ; ", angle of incidence ; ti, t, angles of refraction. bent towards the base of the prism A C. At the same time the light suffers dispersion ; that is, the rays of shorter wave-length are more refracted than those of greater wave-length. The deviation of any given ray is measured by the angle which the refracted ray makes Fig. 226.— Rekkaction and Dispersion by a Prism. with its original direction. The amount of dispersion produced by a prism is measured by the difference in the deviation of the extreme rays of the spectrum. The dispersion produced by any given sub- stance is proportional to the difference of its refractive index for the extreme visible rays. A MANUAL OF PHYSIOLOGY. Refraction by a Biconvex Lens.— A straight line ACB passing through the centres of curvature of the two surfaces of the lens is called the principal axis. A point C lying on the principal axis between the two centres of curvature, and possessing the property that rays passing through it do not suffer refraction, is called the optical centre of the lens. Any straight line, DCE, passing through Fig. 227. — Refraction by a Biconvex Lens. the optical centre is a secondary axis. Rays of light proceeding from a point in the principal axis are focussed in a point on that axis. When the rays proceed from an infinitely distant point in the principal axis, i.e., when they are parallel to it, they are focussed in F, the principal focus. Similarly, rays parallel to, or proceedmg from, a point in a secondary axis are focussed in a point on that axis ; but if Fig. 228.— Formation of Image bv Biconvex Lens. the focus is to be sharp, the angle between the secondary and the principal axis must not be so large as is indicated in Fig. 227. Formation of Image by Biconvex Lens (Fig. 228).— Let AB be the object; then if AHD be the path of a ray from A parallel to the principal axis, the image of A will be the intersection of the straight line D F and the secondary axis passing through A. Similarly, the THE SENSES. Fig. 229 — Refkaction by a Biconcave Lens. image of B will be the intersection of GF and the secondary axis BC. Where AB is farther from the lens than the principal focus, the image ab is real and inverted. This is the case with the image of an external object formed on the retina. When the object is nearer than the principal focus, the image is virtual and erect. The image formed by the objective of a microscope when the object is in focus is real and inverted ; the ocular forms a virtual erect image of this real image. Refraction by a Bi- concave Lens (Fig. 229). — Parallel rays are rendered diver- gent by the lens ; there is no real focus ; but if the rays are prolonged backwards they meet in the virtual focus F, from which they appear to come when received by the eye through the lens. Formation of Image by Biconcave Lens (Fig. 230).— Let AB be the object. Let AHDI be the path of a ray from any point A of the object parallel to the principal axis. Produce DI back- wards (dotted line) ; it will pass through the principal focus F. Through A draw the secondary axis AC The image of A must lie both on AC and on IDF; i.e., it must be the intersection, a, of these straight lines. Similarly, the image of B is b, the intersection of KGF and BC. The image is virtual and erect. Absorption. — No substance is perfectly transparent ; in addition to what is reflected, some light is always absorbed. In other words, in passing through a body some of the light is transformed into heat, a portion of the energy of the short, luminous waves going to in- crease the vibrations of the molecules of the medium, just as a wave passing under a row of barges or fishing-boats sets them swinging and pitching, and so imparts to them a certain amount of energy^ which is ultimately changed into heat by friction against the water, and against each other, and by the straining and rubbing of the chains at their points of attachment. Some bodies absorb all the rays in the proportion in which they occur in white light ; whether looked at or looked through, they appear colourless or white. Other substances absorb certain rays by preference, and the amount of absorption is proportional to the thickness of the layer. The colours 44 Fuj. 230. -Formation of Image by Biconcave Lens. 690 A MANUAL OF PHYSIOLOGY. of most natural bodies are due to this selective absorption. Even when looked at in reflected light, they are seen by rays that have penetrated a certain way into the substance and have then been reflected ; and, of course, a smaller number of the rays which the body specially absorbs are reflected than of the rays which it readily transmits, for more of the latter than of the former reach any given depth. This is called ^ body colour \; and such substances have the same colour when seen by reflected and by transmitted light. The colour of haemoglobin is due to the absorption of the violet and many of the yellow and green rays, as is shown by the position of the absorptioji bauds in its spectrum (p. 35). In Fig. 231 the violet rays are represented as being totally absorbed before passing through the substance. Some of the green rays are re- flected, some trans- mitted, some ab- sorbed. The red rays are supposed to be mostly reflected and transmitted, only to a slight extent ab- sorbed. The colour of such a substance, both when looked at and when looked through, would there- fore be that due to a mixture of red light with a smaller quantity of green. Then there is another class of substances which owe their colour to selective reflection. Certain rays only are reflected from their surface, and the light transmitted through a thin layer is complementary to the reflected light ; that is, the reflected and transmitted rays together would make up white light. These bodies have what is called ^ surf ace colour,' dir\6. include metals, various aniline dyes, and other substances. Comparative. — Many invertebrate animals possess rudimentary sense-organs, by means of which they may receive certain luminous impressions. It is true that the mere sensation of light is not in itself sufficient for the exact appreciation of the form and situation of surrounding objects. But even the closure of the eyelids does not prevent a person of normal eyesight from distinguishing differences in the intensity of illumination. And it is possible that many of the humbler animals may, through the pigment spots which are often called eyes, or perhaps, as in the earthworm, by means of end-organs more generally diffused in the skin, attain to some such dim con- sciousness of light and shadow as will enable them to avoid an obstacle or an enemy, to seek the sunny side of a boulder or the Fig. 231. — Diagram to show Connection of Body Colour with Selective Absorption. THE SENSES. 691 obscurity of an overhanging ledge of rock. But the indispensable condition of distinct vision is that an image of each part of an object should be formed upon a separate portion of the receiving or sensitive surface. This condition is, to a certain extent, fulfilled by the com- pound eyes of some of the higher invertebrates (insects, e.g.). Here rays from one point of the object pass through one of the funnel- shaped elements of the compound eye, and rays from another point through another. Rays striking obliquely on the facets are stopped by the opaque partitions between them. In the Cephalopods we find that this compound type of eye has already been abandoned ; the single system of curved refracting surfaces so characteristic of the Fig. 232.— Diagrammatic Horizontal .Section of the Left Eye. vertebrate eye has made its appearance ; and the formation of a clean-cut image of the object on the retina, with the excitation of a sharply-bounded area of that membrane, follows as a geometrical consequence from the theory of lenses. We have to consider (i) the mechanism by which an image is formed on the retina, and (2) the events that follow the formation of such an image and their relations to the stimulus that calls them forth. Structure of the Eye. — The eye may be described with sufficient 692 A MANUAL OF PHYSIOLOGY. accuracy as a spherical shell, transparent in front, but opaque over the posterior five-sixths of its surface, and filled up with a series of trans- parent liquids and solids. The shell consists of three layers concen- trically arranged, like the coats of an onion : (i) An external tough, fibrous coat, the sclerotic, the anterior portion of which appears as the white of the eye. In front this external layer is completed by the transparent cornea. (2) A vascular and pigmented layer, the choroid., which, in the restricted sense of the term, ends in front in a series of folds or plaits, the ciliary processes. These abut on the outer boundary of the iris, which may be looked upon as an an- terior continuation of the choroidal or middle coat of the eyeball. Between the corneo-sclerotic junction and the anterior portion of the choroid is inter- posed a ring of unstriped muscular fibres, the ciliary muscle. (3) The inner or sensitive coat, termed the retina (Fig. 233). This covers the choroid as a delicate membrane, extending nearly to the anterior termination of the ciliary processes, where it ends in a toothed margin, the ora serrata. The optic nerve forms a kind of stalk to which the eyeball is attached. Its point of entrance at the optic disc is a little nearer the median line than the antero- posterior axis, which nearly passes through the centre of a small depres- sion, the fovea centralis, situated in the middle of the macula lutea, or yellow spot. From the optic disc (sometimes called the optic papilla, but inappropri- ately, since it does not project beyond the general surface), the optic nerve spreads over the retina as a layer of non-medullated fibres, 2, separated from the interior of the eyeball only by the internal limiting membrane, i. This so- called membrane is formed by the ex- panded feet of the fibres of Miiller, which run like a scaffolding or framework through nearly the whole thickness of the retina, terminating at the outer limiting membrane. External to the layer of nerve-fibres is the stratum of large ganglion cells, with which they are connected, 3 ; next to this the inner molecular layer, made up largely of the branching processes of these cells, 4. The fifth layer is the inner granular or nuclear layer, containing many fusiform nucleated cells which throw out dendrites into the fourth and sixth, or outer molecular layer, and Fig. 233. — The Retina (after Helmholtz). THE SENSES. 693 are thus brought into physiological, if not "into anatomical, con- nection with the ganglion cells of the third layer on the one hand, and with the seventh or outer nuclear layer on the other. This stratum receives its name from the large number of nuclei which it contains. These seem to be connected with the rods and cones of the ninth layer, which is divided from the seventh by the external limiting membrane, 8. At the fovea cejitralis the rods are entirely absent, and the other layers of the retina greatly thinned; over the optic disc neither rods nor cones are present. External to the rods and cones is a sheet of pigmented epithelial cells of hexagonal shape, belonging to the choroid, but remaining attached to the retina when the latter is separated, and therefore often reckoned as its most external layer, 10. A little behind the cornea and anterior to the retina is the lens^ enclosed in a capsule, and attached to the choroid by the suspensory ligament, or zonule of Zinn. The iris hangs down in front of the lens like a diaphragm, with a central hole, the pupil. Between the iris and the posterior surface of the cornea is the anterior chamber of the eye, filled with the aqueous humour. Between the iris and the anterior surface of the lens lies the posterior chamber, which is rather a potential, than an actual, cavity. The space between the lens and the retina is accurately occupied by an almost structureless semi fluid mass, the vitreous humour, enclosed by the delicate hyaloid membrane, which in front is reflected over the folds of the ciliary processes, and blends with the suspensory ligament of the lens. Refraction in the Eye — Formation of the Retinal Image. — The amount of refraction which a ray of light undergoes at a curved surface depends upon two factors, the radius of curvature of the surface, and the difference between the re- fractive indices of the media from which the ray comes and into which it passes. The smaller the radius of curvature, and the greater the difference of refractive index, the more is the ray bent from its original direction. A ray of Hght passing into the eye meets first the approximately spherical anterior surface of the cornea, covered with a thin layer of tears. Since the refractive index of the tears and of the cornea is greater than that of air, refraction must occur here. At the parallel posterior surface of the cornea, how- ever, the ray is but slightly bent, for the refractive indices of aqueous humour and corneal substance are nearly equal. At the anterior and posterior surface of the lens the ray is again refracted, since the refractive index of the aqueous and vitreous humour is less than that of the lens. The following tables show the radii of curvature of the refracting surfaces 694 A MANUAL OF PHYSIOLOGY. and the refractive indices of the dioptric media, as well as some other data which are of use in studying the problems of refraction in the eye : In accommodation for Far Vision. Near Vision. [Cornea - - - 7 '8 mm. 7 '8 mm. Radiusof curvature of-^ Anterior surface of lens- io"o „ 6"o ,, [Posterior surface of lens 6'o „ 5*5 ,, Anterior surface of cornea and an- terior surface of lens - - - 3"6 ,, 3'2 „ Distance] Anterior surface of cornea and pos- betweenj terior surface of lens - - - 7'2 ,, 7"2 „ Anterior and posterior surface of lens 3'6 „ 4'o ,, I Posterior surface of lens and retina - i4'6 ,, i4'6 „ Anteroposterior diameter of eye along the axis 21*8 ,, 218 ,, Refractive Indices — Air ------- i-ooo Cornea- ------ 1*337 Aqueous humour ----- i'3365 Vitreous humour ----- i'3365 Lens (mean for all its layers)- - - i'437 Water - 1-335 It will be seen that the refractive indices of the cornea and the aqueous and vitreous humours are all nearly the same as that of water. That of the lens differs for its various layers, the central core having a higher refractive index than the more superficial portions ; but a mean may be struck, and, although such calculations are open to error, it has been computed that the lens acts as a homogeneous lens of the same curvatures, and with a refractive index of i'437, would do. The optical problems connected with the formation of the retinal image are complicated by the existence in the eye of several media, with different refractive indices, bounded by surfaces of different and, in certain cases, of variable curva- ture. For many purposes, however, the matter can be greatly simplified, and a close enough approximation yet arrived at, b}' considering a single homogeneous medium, of definite refractive index, and bounded in front by a spherical surface of definite curvature, to replace the transparent solids and liquids of the eye. The position of the principal focus and nodal point {i.e., the point through which rays THE SENSES. 695 pass without refraction) of such a ' reduced ' or ' schematic' eye, and other constants are shown in the following table : Reduced Eye — Radius of curvature of the single refracting surface - 5't mm. Index of refraction of the single refracting medium - i"35* ,, Antero-posterior diameter of reduced eye (distance of principal focus from the single refracting surface) - 20'o ,, Distance of the single refracting surface behind the anterior surface of the cornea - - - - i'8 „ Distance of the nodal point of the reduced eye from its anterior surface - - - - - - 5'o n Distance of the nodal point from the principal focus (retina)- --...--- 15-0 „ Knowing the position of the centre of curvature of the single ideal refracting surface, i.e., the nodal point of the re- S, the single spherical refracting surface, i'8 mm. behind the an- terior surface of the cornea ; N, the nodal point, 5 mm. behind S ; F, the principal focus (on the retina), 20 mm. behind S. The cornea and lens are put in in dotted lines in the position which they occupy in the normal eye. Fig. 234. — I'he KEDUctu 1:.ye. duced eye, all that is necessary in order to determine the position of the image of an object on the retina is to draw straight lines from its circumference through the nodal point. Each of these lines cuts the refracting surface at right angles, and therefore passes through without any deviation. The retinal image is accordingly inverted, and its size is proportional to the solid angle contained between the lines drawn from the boundary of the object to the nodal point, or the equal angle contained by the prolonga- tions of the same lines towards the retina. This angle is called the visual angle, and evidently varies directly as the size of the object, and inversely as its distance. Thus the visual angle under which the moon is seen is much larger than that under which we view any of the fixed stars, * Or about the same as that of the aqueous humour. 696 A MANUAL OF PHYSIOLOGY. because the comparative nearness of the earth's satelHte more than makes up for its relatively small size. The dimensions of the retinal image of an object are easily calcu- lated when the size of the object and its distance are known. For let AB in Fig. 235 represent one diameter of an object, A'B' the image of this diameter, and let AB', BA', be straight lines passing through the nodal point. Then AB and A'B' may be considered as parallel lines, and the triangles of which they form the bases, and the nodal point the common apex, as similar triangles. Fiu. 235. Figure to show how the visual angle and size of retinal image varies with the distance of an object of given size. For the distant position of AB the visual angle is u, for the near position (dotted lines) fi. Accordingly, if D is the distance of the nodal point from A, AB A'B' and d its distance from B', we have -^^- = — j- . Now, d may Da approximately be taken as 15 mm. Suppose, then, that the size of the moon's image on the retina is required. Here D = 238,000 miles, and AB (the diameter of the moon) = 2,160 miles. Thus we get 2,160 A'B' , , I A'B' , , . , .,^, , , ,. — o = , or (say) = , from which AB (the diameter 238,000 15 ^ ■" no 15 ^ of the retinal image) = — , or about 1 mm. ° ' I 1 o ' The mast of a ship 120 feet high, seen at a distance of 25 miles, will ,, , . . , , ... 120 feet throw on the retina an image whose height is •, x 15 mm., ° ° 25 miles ^ 120 feet I '•^•> - — 5 7 — 7 X 15 mm., or x i =; mm., equal to '013 mm., 5,280x25 feet -^ ' 1,100 0 ' H o > or 13/X in size. This is not much larger than a red blood-corpuscle, and only four times the diameter of a cone in the fovea centralis, where the cones are most slender. Accommodation. — A lens adjusted to focus upon a screen the rays coming from a luminous point at a given distance will not be in the proper position for focussing rays from a point which is nearer or more remote. Now, it is evident that a normal eye possesses a great range of vision. The THE SENSES. 697 image of a mountain at a distance of 30 miles, and of a printed page at a distance of 30 cm., can be focussed with equal sharpness upon the retina. In an opera-glass or a telescope accommodation is brought about by altering the relative position of the lenses ; in a photographic camera and in the eyes of fishes (Beer), by altering the distance between lens and sensitive surface ; in the eye of man, by altering the curvature, and therefore the refractive power of the lens. That the cornea is not alone concerned in accommodation, as was at one time widely held, is shown by the fact that under water the power of accommodation is not wholly lost. Now, the re- fractive index of the cornea being practically the same as that of water, no changes of curvature in it could affect refraction under these circumstances. That the sole effective change is in the lens, can be most easily and deci- sively shown by studying the behaviour of the mirror images of a luminous object reflected from the bounding surfaces of the various re- fractive media when the degree of accommodation of the eye is altered. Three images are clearly recognised : the brightest, an erect virtual image, from the anterior (convex) surface of the cornea ; an erect virtual image, larger, but less bright, from the anterior (convex) surface of the lens ; and a small in- verted real image from the (concave) posterior boundary of the lens (Purkinje-Sanson images). The second image is intermediate in position between the other two. It is possible with special care to make out a fourth image, and A B (^ m \ 0 \ fa B \ N \n -] ', n E! a i \ 1^ / / \ 1 A • A \ B^ Fig. 236. — Purkinje-Sanson Images. A, in the absence of accommodation ; B, during accommodation for a near object. The upper pair of circles enclose the images as seen when the light falls on the eye through a double slit or a pair of prisms ; the lower pair show the images seen when the slit is single and triangular in shape. 698 A MANUAL OF PHYSIOLOGY. even a fifth ; but since these are reflected from surfaces (the posterior surface of the cornea, e.g.) at which only a sHght change in the refractive index occurs, they are much less bril- liant than the first three. When the eye is accommodated for near vision, as in focussing the ivory point of the phakoscope (Fig. 273), the corneal image is entirely unchanged in size, brightness, and position. The middle image diminishes in size, comes forward, and moves nearer to the corneal image. This shows that the curvature of the anterior surface of the lens has been increased — that is to say, its radius of curvature diminished — for the size of the image of an object reflected from a convex mirror varies directly as the radius of curvature. A slight change takes place in the image from the posterior surface of the lens, indicating a small increase of its curvature too. By means of a method founded on the observation of the changes in these images, and a special instrument called an ophthalmometer which allows of their measurement, Helmholtz has calculated that, during maxi- mum accommodation, the radius of curvature of the anterior surface of the lens is only 6 mm., as compared with 10 mm. when the eye is directed to a distant object and there is no accommodation. When the lens has been removed for cataract, fairly distinct vision may still be obtained by compensating for its loss by convex spectacles of suitable refractive power (10 diopters* for distant vision, and 15 diopters for the distance at which a book is usually held), but no power of accommodation remains. The person does indeed contract the pupil in regarding a near object, just as happens in the intact eye ; the most divergent rays are thus cut off and the image made somewhat sharper, and there may appear to be some faculty of accommodation left. But the loss of the whole iris by operation does not affect accommodation in the least ; the iris, therefore, takes no part in it. That no change in the antero-posterior diameter of * A diopter (i D) is the unit of refractive power generally adopted in measuring the strength of lenses, and corresponds to a lens of i metre focal length. A lens of 2 diopters (2 D) has a focal length of | metre, a lens of 4 diopters (4 D) a focal length of \ metre, and so on. The diverging power of concave lenses is similarly expressed in diopters, with the negative sign prefixed. Thus, a concave lens of i metre focal length has a strength of — i D and will just neutralize a convex lens of i D. THE SENSES. 699 the eyeball, caused by its deformation by the contraction of the extrinsic muscles, can have any share in accommodation, as has been suggested, is clearly proved by the fact that atropia, which does not affect the action of these muscles, paralyzes the mechanism of accommodation. To the con- sideration of that mechanism we now turn. The Mechanism of Accommodation. — While everybody is agreed that the main factor in accommodation is the altera- tion in the curvature of the lens, there is by no means the same unanimity as to the manner in which this is brought about. Helmholtz's explanation, which has long been the most popular, is as follows : In the unaccommodated eye the suspensory ligament and the capsule of the lens are tense and taut, the anterior surface of the lens is flattened by their pressure, and parallel rays (or, what is the same thing, rays from a distant object) are focussed on the retina without any sense of effort. In accommodation for a near object, the meridional or antero-posterior fibres of the ciliary muscle by their contraction pull forward the choroid and relax the suspensory ligament. The elasticity of the lens at once causes it to bulge forwards till it is again checked by the tension of the capsule. The explanation of Helmholtz, although widely adopted in the text- books, is being more and more called in question in the archives. Tscherning, for example, has put forward the view that when the ciliary muscle (which consists of a superficial layer of meridional, and a deep layer of radial, fibres) contracts, the ciliary processes are drawn back, and pull the zonule of Zinn backwards and outwards. The curvature of the lens is thus altered, and, in particular, the region around its anterior pole becomes more convex. At the same time the contraction of the posterior portion of both layers of the ciliary muscle pulls the choroid forward, and so causes the vitreous body to press against the posterior surface of the lens, and prevent its dis- placement backwards by the pull of the anterior portion of the muscle. And Schoen, reviving a theory originated forty years ago by Mannhardt, believes that the contraction of the ciliary muscle causes an alteration in the curvature of the anterior part of the zonule, which change the lens, always keeping accurately in contact with this portion of the zonule, is forced to follow. He likens the increase of curvature to the bulging of an indiarubber ball when it is held in both hands and compressed by the fingers a little behind one of the poles. It has been already mentioned that along with the altera- 7CO A MANUAL OF PHYSIOLOGY. tion in the curvature of the lens a change in the diameter of the pupil takes place in accommodation. When a distant object is looked at, the pupil becomes larger ; when a near object is looked at, it becomes smaller. Narrowing of the pupil is thus associated with contraction of the ciliary muscle, and widening of the pupil with its relaxation. This physiological correlation has its anatomical counterpart; for the third nerve supplies both the iris and the ciliary muscle. Stimu- lation of the nerve within the cranium causes contraction of the pupil, while stimulation of certain portions of its nuclei in the floor of the third ventricle and the Sylvian aqueduct or of the short ciliary nerves coming off from the ophthalmic ganglion, which receives branches from the third nerve, or of the ganglion itself, is followed by that change in the anterior surface of the lens which constitutes ac- commodation (Hensen and Voelckers). This can be observed either through a window in the sclerotic in a dog or by following the move- ments of a needle thrust into the eyeball. By carefully localized stimulation near the junction of the aqueduct with the third ventricle, it is possible to bring about the forward bulging of the lens without any change in the iris ; but the normal and voluntary act of accom- modation cannot be disjoined from the corresponding alterations in the size of the pupil. It is not only by accommodation that the size of the pupil maybe affected. In the dark it dilates; when light falls upon the retina it contracts, and the amount of contraction is roughly proportional to the intensity of the light. Con- traction of the pupil to light is brought about by a reflex mechanism, of which the optic nerve forms the afferent and the oculo-motor the efferent path, while the centre is situated in the floor of the aqueduct of Sylvius. The relation of this centre to that which controls the changes in the pupil during accommodation has not as yet been sufficiently elucidated ; but this we do know, that one of the reflex arcs may be interrupted by disease while the other is intact, for in locomotor ataxia the light-reflex sometimes disappears, the accommodation - reflex remains (Argyll - Robertson pupil). Artificial stimulation of the optic nerve has the same effect on the pupil as the 'adequate' stimulus of light; and in many animals (including man), though not in all {e.g., not in the rabbit), both pupils contract when one retina or optic nerve is excited. This should be remembered in using the pupil-reaction as a test of the condition of the retina. THE SENSES. 701 For although the absence of contraction may show that the retina of the eye on which the hght is allowed to fall is insensible (unless there is some physical hindrance to its passage, such as opacity of the lens or cataract), the occur- rence of contraction does not exclude insensibility of the retina unless the other eye has been protected from the light. But not only is the iris under the control of constrictor nerve-fibres, it is also governed by dilator nerves ; and the size of the pupil at any given moment depends on the pla}- of two nicely-balanced forces. Fig. 237. Ill, third or oculomotor nerve ; IV, fourth or trochlear nerve ; V, ophthalmic branch of fifth nerve ; VI, sixth or abducens ; C, carotid artery with its plexus of sympathetic fibres ; i, ophthalmic ganglion, with its motor root 2, its sympathetic root 3, and its sensory root 4 ; 5, direct ciliary filament ; 6, ciliary muscle ; 7, iris ; 8, cornea ; 9, con- junctiva ; 10, lachrymal gland ; 11, frontal nerve ; 12, nasal nerve ; 13, recurrent branch of ophthalmic division of fifth. The thick while lines represent the motor nerves ; the thin continuous lines the sympathetic fibres ; the dotted lines the sensory nerves. The dilator fibres pass out by the anterior roots of the first three thoracic nerves (dog, cat, rabbit), accompanied apparently by vaso- constrictor fibres for the iris. Reaching the sympathetic chain through the corresponding rami communicantes, they traverse the first thoracic ganglion, the annulus of Vieussens, the inferior cervical ganglion and the cervical sympathetic. After making junction with some of the cells of the superior cervical ganglion (Langley), they eventually arrive at the Gasserian ganglion, and running along the ophthalmic division of the trigeminal to the eye, reach the iris by its ciliary branches. 702 A MANUAL OF PHYSIOLOGY. Stimulation of the cervical sympathetic causes marked dilatation of the pupil (see Practical Exercises), even when the third nerve is excited at the same time. All the evidence at our command goes to show that the pupillo- dilator fibres do not act by constricting the bloodvessels of the iris. For dilatation of the pupil can be caused in a blood- less animal by stimulating the sympathetic, and even when the circulation is going on, a short stimulation of the sympa- thetic causes dilatation of the pupil without vaso-constriction, while with longer excitation the dilatation of the pupil begins before the narrowing of the bloodvessels. Nor does it seem possible to accept the view that the sympathetic fibres are inhibitory for the sphincter muscle of the iris. In all probability they act directly upon dilator muscular fibres. It has, indeed, long been known that in the iris of the otter and of birds a radial dilator muscle exists ; and it has been shown by the recent experiments of Langley and Anderson that in the iris of the rabbit, cat and dog, the presence of radially arranged contractile substance, different it may be in some respects from ordinary smooth muscle, must be assumed. Reflex dilatation of the pupil through the sympathetic fibres is caused in man by painful stimulation of the skin, by dyspnoea, by muscular exertion, and in some individuals even by tickling of the palms. In animals the stimulation of naked sensory nerves has the same effect. The ' starting of the eyeballs from their sockets,' which the records of torture so often note, is probably due to a similar reflex excitation of the sympathetic fibres supplying the smooth muscle of the orbits and eyelids. The statement has been made that in addition to the sympathetic dilators of the pupil, dilating fibres pass out directly from the brain along the fifth nerve ; and it has been said that after section of the cervical sympathetic or excision of the superior cervical ganglion, reflex dilatation can still be caused, presumably through these fibres. There appears, however, to be no real evidence in favour of their existence. The reflex centre for dilatation of the pupil is in the medulla oblongata. The lower cervical and upper thoracic portion of the spinal cord has received the name of the cilio-spinal region from its relation to the pupillo-dilator fibres. It must not be looked upon as a centre in any proper sense of the term, but rather as the pathway by which these fibres pass down from the bulb, and where they may accordingly be tapped by stimulation. THE SENSES. 703 That, in addition to the cerebral centre for the constrictor and the bulbar centre for the dilator fibres, there exists within the eye some local mechanism which controls the muscles of the iris and regulates the size of the pupil is rendered certain by many facts. The excised eye of a frog or an eel constricts its pupil on exposure to light, and dilates it in the dark. It is said that even the isolated iris of the eel contracts to light ; and it is known, although here the explanation is less difficult, that the iris both of cold- and warm-blooded animals contracts in warm, and dilates in cold normal saline solution. The local application oi atropia causes temporary paralysis of accommodation and dilatation of the pupil. When the third nerve is divided, the pupil dilates ; it dilates still more when atropia is administered after the operation. Dropped into one eye in small quantity, atropia only produces a local effect ; the pupil of the other eye remains of normal size, or somewhat con- stricted on account of the greater reflex stimulation of its third nerve by the greater quantity of light now entering the widely-dilated pupil of the atropinised eye. Even in an excised eye the effect of the drug is the same. Introduced into the blood, atropia causes both pupils to dilate. Other mydriatic, or pupil-dilating drugs, are cocaine, datiirine, and hyoscy amine. Eserine, pilocarpine, and morphia are the chief myotics, or pupil-constricting substances. They also cause spasm of the ciliary muscle, and inability to accommodate for distant objects. The work of the mydriatics can be undone by the myotics. Thus the dilatation produced by atropia is removed by pilocarpine. The most plausible explanation of the action of these drugs is that the mydriatics paralyze the third nerve, and stimulate the dilator nerve- fibres of the iris, while the myotics paralyze the dilators and stimulate the third. Nicotine, which ultimately causes con- striction of the pupil, does so by paralyzing the cells on the course of the dilating fibres in the superior cervical ganglion. Inward rotation of the eyes is associated with contraction of the pupil, and the contraction that occurs during sleep is probably to be thus explained. When the pressure in the anterior chamber of the eye is diminished, as by tapping the aqueous humour through the 704 A MANUAL OF PHYSIOLOGY. cornea, contraction of the pupil occurs ; and stimulation of the sympathetic has now a far smaller dilating effect than usual. Removal of the cornea narrows the pupil, partly by occasioning direct stimula- tion of the sphincter pupillse, partly by abolishing the pressure of the aqueous humour. The attached (ciliary) border of the iris then bulges forward, and the pupil becomes smaller. On the other hand, an increased pressure in the anterior chamber forces back the ciliary border of the iris, and causes mechanical dilatation of the pupil. Functions of the Iris, — In vision, the iris performs two chief functions : (i) It regulates the quantity of light allowed to fall upon the retina. The larger the aperture of a lens the greater is its collecting power, the more light does it gather in its focus. In the eye, the area of the pupil determines the breadth of the pencil of light that falls upon the lens ; if this area was invariable, the retina would either be ' dark from excess of light ' in bright sunshine, or dark from defect of light in dull weather or at dusk. In order that the iris may act as an efficient diaphragm it must be pigmented, and it is the pigment in it which gives the colour to the normal eye. The vision of albinos, in whose eyes this pigment is wanting, is often, though not invariably, deficient in sharpness. There is always intolerance of bright light ; and the same is true in the condition known as irideremia, or congenital absence or defect of the iris. (2) Another, and perhaps equally important, function of the iris is to cut off the more divergent rays of a pencil of light falling upon the eye, and thus to increase the sharpness of the image. This leads us to the con- sideration of cer- tain defects in the dioptric arrange- ments of the eye. Defects of the Eye as an Optical Fig. 238.— Spherical Aberration. Instrument, (i) Rays passing through the more peripheral parts of a g-rjlierical Aberia- biconvex lens, L, are brought to a focus, F, nearer the *^ . lens than F', the focus of rays passing through the central tion. — it IS a pro- portions of the lens. perty of a spherical refracting surface that rays of light passing through the peripheral portions are more strongly refracted than rays passing near the prin- cipal axis. Hence a luminous point is not focussed accurately in a THE SENSES. 705 single point by a spherical lens ; the image is surrounded by circles of diffusion. In the eye this spherical aberration is partly corrected by the interposition of the iris, which cuts off the more peripheral rays, especially in accommodation for a near object, when they are most divergent. In addition, the anterior surfaces of the cornea and lens are not segments of spheres, but of ellipsoids, so that the curva- ture diminishes somewhat with the distance from the optic axis, and, therefore, the refracting power as we pass away from the axis does not increase so rapidly as it would do if the surfaces were truly spherical ; Further, the refractive index of the peripheral parts of the lens is less than that of its central portions. (2) Chromatic Aberration. — All the rays of the spectrum do not travel with the same velocity through a lens, and are, therefore, unequally refracted by it, the short violet rays being focussed nearer the lens than the long red rays. It was at one time supposed that this chromatic aberration, as it is called, is compensated in the eye ; and it is said that this mistake gave the first hint that Newton's dictum as to the proportionality between deviation and dispersion Fig. 239. -Chku.matic Ahekkation. The violet r^iys are brought to a focus V nearer the lens than R, the focus of the red rays. !'h;. 240— To show Disper- sion IN Eye. View the figure from a distance too small for accommodation. Ap- jjro^ch the eye towards it ; the wliite rings appear bluish owing to circles of dispersion falling on them. A little closer, and the black rings become white or yellowish white, being covered by circles of dispersion and diffusion. was erroneous, and led to the discovery of achromatic lenses. But in reality the eye is not an achromatic combination ; and the violet rays are focussed about i- mm. in front of the red. Thus, in Fig. 239 the white light passing through the lens is broken up into its con- stituents ; the violet focus is at V, and the red at R, behind it. A screen placed at R would show not a point image, but a central point surrounded by concentric circles of the spectral colours, with violet outside. If the screen was placed at V, the centre would be violet and the red would be external. For this reason it is impossible to focus at the same time and with perfect sharpness objects of different colours : a red light on a railway track appears nearer than a blue light, partly perhaps for the reason that it is necessary to accom- modate more strongly for the red than for the blue, and we associate stronger accommodation with shorter distance of the object, although other data are also involved in such a visual judgment. \\'hen we look at a white gas-flame through a cobalt glass, which allows only red and violet to pass, we see either a red flame surrounded by a 45 job A MANUAL OF PHYSIOLOGY. violet ring, or a violet flame surrounded by a red ring, according as we focus for the red or for the violet rays. The dispersive power of the eye, however, is so small, and the capacity of rapidly altering its accommodation so great, that no practical inconvenience results from the lack of achromatism, which, however, may be easily demonstrated by looking at a pattern such as that in Fig. 240 at a distance too small for exact accommodation. It is also reckoned among the optical imperfections of the eye (3) that the curved surfaces of the cornea and lens do not form a ' centred ' system — that is to say, their apices and their centres of curvature do not all lie in the same straight line ; (4) that the pupil is eccentric, being situated not exactly opposite the middle of the lens and cornea, but nearer the nasal side, and that in consequence the opfk axis, or straight line joining the centres of curvature of the lens and cornea, does not coincide with the visual axis, or straight line joining the fovea centralis with the centre of the pupil, which is also the straight line joining the centre of the pupil and any point to which the eye is directed in vision. The angle between the optic Fig. 241. — Refraction in the (Normal) Emmrtkopic Eye. The image P' of a distant point P falls on the retina when the eye is not accommodated. and visual axis is about 5° (Fig. 232). (5) Muscae volitantes, the curious bead-like or fibrillar forms that so often flit in the visual field when one is looking through a microscope, are the token that the refractive media of the eye are not perfectly transparent at all parts ; they seem to be due to floating opacities in the vitreous humour. (6) Lastly, it may be mentioned that slight irregularities in the curvature of the lens exist in all eyes, so that a point of light, like a star or a distant street lamp, is not seen as a point, but as a point surrounded by rays (irregular astigmatism). In bringing this review of the imper- fections of the dioptric media of the normal eye to a close, it may be well to explain that what are defects from the point of view of the student of pure optics, are not necessarily defects from the freer standpoint of the physiologist, who surveys the mechanism of vision as a whole, the relations of its various parts to one another and to the needs of the organism it has to serve, the long series of develop- mental changes through which it has come to be what it is, and the possibilities, so far as we can limit them, that were open to THE SENSES. 707 evolution in the making of an eye. The optician may perhaps assert, and with justice, that he could easily have made a better lens than nature has furnished, but the physiologist will not readily admit that he could have made as good an eye. While the defects hitherto mentioned are shared in greater or less degree by every normal eye, there are certain other defects which either occur in such a comparatively small number of eyes, or lead to such grave disturbances of vision when they do occur, that they must be reckoned as abnormal conditions. In the normal or emmetropic eye, parallel rays — and for this purpose all raj'S coming from an object at a distance greater than 65 metres may be con- sidered parallel — are brought to a focus on the retina without any effort of accommodation. The distance at Fig. 242.— Myopic Eye. The innge P' of a distant point P falls in front ot the retina even without accommo- dation. By means of a concave lens L the image may be made to fall on the retina {dotted lines). To save space, P is placed much too near the eye in Figs. 241-243. which objects can be distinctly seen is only limited by their size, the clearness of the atmosphere, and the curvature of the earth ; in other words, the punctiim reuioium, or far point of vision, the most distant point at which it is possible to see with distinctness, is practically at an infinite distance. When accommodation is paralyzed by atropia, only remote objects can be clearly seen. On the other hand, the normal eye, or to be more precise, the normal eye of a middle-aged adult, can be adjusted for an object at a dis- tance of not more than 12 cm. (or 5 inches). Nearer than this it is not possible to see distinctly ; this point is accord- ingly called the puiictuin proximiun, or near point. The range 7o8 A MANUAL OF PHYSIOLOGY, of accommodation for distinct vision in the emmetropic eye is from 12 cm. to infinity. Myopia, or short-sightedness, is generally due to the excessive length of the antero-posterior diameter of the eye- ball in relation to the converging power of the cornea and the lens. Even in the absence of accommodation, parallel rays are not focussed on the retina, but in front of it ; and in order that a sharp image may be formed on the retina the object must be so near that the rays proceeding from it to the eye are sensibly divergent, that is to say, it must be at least nearer than 65 metres ; but as a rule an object at a distance of more than 2 to 3 metres cannot be distinctly seen. With the strongest accommodation the near point Frci 243. — Hypermetropic Eye. The image P' of a point P falls behind the retina in the unaccommodated eye. By means of a convex lens it may be focussed on the retina without accommodation (dotted lines). may be as little as 5 cm. from the eye. The range of vision in the myopic eye is therefore very small. The defect may be corrected by concave glasses, which render the rays more divergent. It is to be noted that many cases of internal squint in children are connected with myopia, the eyes neces- sarily rotating inwards as they are made to fix an abnormally near object. The treatment both of the squint and the myopia in these cases is the use of concave spectacles (Fig. 242). In hypermetropia, or long-sightedness, the eye is, as a rule, too short in relation to its converging power ; and with the lens in the position of rest, parallel rays would be focussed behind the retina. Accordingly the hypermetropic eye must accommodate even for distant objects, while even THE SENSES. 709 •with maximum accommodation an object cannot be dis- tinctly seen unless it is farther away than the near point of the emmetropic eye. The far point of distinct vision is at the same distance as in the emmetropic eye, viz., at infinity ; the near point is farther from the eye. The defect is cor- rected by convex glasses (Fig. 243). Presbyopia, or the long-sightedness of old age, is not to be confounded with hypermetropia. It is essentially due to failure in the power of accommodation, chiefly through weakness of the ciliary muscle, but partly owing to increased rigidity and loss of elasticity of the lens. Images of distant objects are still formed on the retina of the unaccommodated eye with perfect sharpness ; i.e., the far point of vision is not affected. But the eye is unable to accommodate sufficiently for the rays divergmg from an object at the ordinary near point ; in other words, the near point is farther away than normal. Convex glasses are again the remedy. The near point of distinct vision can be fixed in various ways — among others, by means of Scheiner's experiment (see Practical Exercises). Two pin-holes are pricked in a card at a distance less than the diameter of the pupil. A needle viewed through the holes appears single when it is accommodated for, double if it is out of J focus. The near point of vision is the nearest point at which the needle can still, by the strongest effort of accommodation, be seen single. Astigmatism. — It has been mentioned that slight differences of curvature along different meridians-' of the refracting surfaces exist in all eyes. But in some cases the difference in two meridians at right angles to each other is so great as to amount to a serious defect of vision. To this condition the name of * astigmatism ' or * regular astigmatism ' has been given. It is usually due to an excess of curvature in the vertical meridians of the cornea, less frequently in the horizontal meridians ; occasionally the defect is in the lens. Rays proceeding from a point are not focussed in a point, but along two lines, a horizontal and a vertical, the horizontal linear focus being in front of the other, when the vertical curvature is too great, behind it when the horizontal curvature is excessive. The two limbs of a cross or the two 710 A MANUAL OF PHYSIOLOGY. hands of a clock when they are at right angles to each other cannot be seen distinctly at the same time, although they can be successively focussed. The condition may be cor- rected by glasses which are segments of cylinders cut parallel to the axis. The Ophthalmoscope. — The pupil of the normal eye is dark, and the interior of the eye invisible, without special means of illuminating it. But this is not because all the light that falls upon the fundus is absorbed by the pigment of the choroid, for even the pupil of an albino appears dark when the eye is covered by a piece of black cloth with a hole in front of the pupil. Let the rays from a luminous point P be focussed by the lens L at P' (Fig. 244). It is plain that rays proceeding from P' will exactly retrace the path of those from P and be focussed at P. Now the eye receives rays from all directions, and, when it is suf- ficiently well illumi- nated, sends rays out ^"-^- ^■++ in all directions. The moment, however, that the observing eye is placed in front of the observed eye, the latter ceases to receive light from the part of the field occupied by the pupil of the former, and therefore ceases to reflect light into it. This difficulty is avoided by the use of an ophthalmo- scopic mirror. The original, and theoretically the most perfect, form of such a mirror is a plate, or several superposed plates, of glass, from which a beam of light from a laterally placed candle or lamp is reflected into the observed eye, and through which the eye of the observer looks (Fig. 245). But the illumination thus obtained is comparatively faint ; and a concave mirror, with a small hole in the centre for the pupil of the observer's eye, is now generally used. In the direct method of examination (Fig. 246), the mirror is held close to the observed eye, and an erect virtual image of the fundus is seen. When the eye of the observer and of the THE SENSES. l\i patient are both emmetropic, and both eyes are unaccommo- dated, the ravs of hght proceeding from a point of the retina Fig. 245.— Figure to illustrate the Principle oe the Ophthalmoscope. Rays of light from a point P are reflected by a glass plate M (several plates together in Helmhohz's original form) into the observed eye E'. Their focus would fall, as shown in the figure at P', a little behind the retina of E'. The portion of the retina AB is there- fore illuminated by diffusion circles; and the ravs from a point of it F will, if E' is emmetropic and unaccommodated, issue parallel from E' and be brought to a focus at F' on the retina of the (emmetropic and unaccommodated) observing eye E. of the latter are rendered parallel by its dioptric media, and are again brought to a focus on the observer's retina. P'lG. 246. — Direct jMethod of using the Uphthalmoscope. Light falling on the perforated concave mirror M passes into the observed eye E', and, both E' and the observing eye E being supposed emmetropic and unaccommodated, an erect virtual image of the illuminated retina of E' is seen by E. If the observed eye is myopic, the rays of light coming from a point of the retina leave the eye, even when it is un- 712 A MANUAL OF PHYSIOLOGY. accommodated, as a convergent pencil ; and the emme- tropic non-accommodated eye of the observer must have a Fig. 247. Use of the Ophthalmoscope (Direct Method) for testing Ekkors of Refraction. Myopic £;'^.— Rays issuing from a point of the retina of E', the observed (myopic and unaccommodated) eye, pass out, not parallel, but convergent. They will therefore be focussed in front of the retina of the observing unaccommodated eye E, if the latter is emmetropic. By introducing a concave lens L of suitable strength, however, a clear view of the retina of E' will be obtained, and the strength of this lens is the measure of the amount of myopia. concave lens placed before it in order that the fundus may be distinctly seen. When the observed eye is hypermetropic, the rays emerg- FiG. 248.— Testing Errors of Refraction in Hypermetropic Eve. Rays from a point of the retina of E', the observed eye, issue divergent, and are focussed beliind the rttina of the observing (unaccommodated and emmetropic) eye £. The strength of the convex lens L, which must be introduced in front of E to give clear vision of the retina of E', measures the degree of hypermetropia. ing from the unaccommodated eye are divergent, and a con- vex lens, the strength of which is proportional to the amount THE SENSES. 713 of hypermetropia, must be placed before the observer's eye if he is to see the fundus distinctly. By this method errors of refraction in the eye may be detected and measured. The observer must always keep his eye unaccommodated, and if it is not emmetropic, he must know the amount of his short- or long-sightedness, i.e., the strength and sign of the lens needed to correct his defect of refraction, and must allow for this in calculating Fig. 249. — l.NDiKECT Method of using the OPHTHALMoiiCui'E. The rays of light issuing from E', the observed eye, are focussed by the biconvex lens L. .iiid a real inverted image of a portion of the retina of E, magnified four or five times, is formed in the air between '.he lens and the observing eye E. This image is viewed by E at the ordinary distance of distinct vision (10 or 12 inches). (The exaggera- tion of the size of the mirror makes it appear as if some of the rays frnni the lamp passed through the lens before being reflected from the mirror. This would not usually be the case in an actual observation.) the defect of his patient. Non-accommodation of the eye of the latter can always be secured by the use of atropia. By the direct method of ophthalmoscopic examination only a small portion of the retina can be seen at a time, and this is highly magnified. A larger, though less magnified, view can be got by the indirect method. The observed eye is illuminated as before, but the mirror and the observer's eye are at a greater distance (Fig. 249). Here the rays from a considerable portion of the retina, emerging in parallel pencils if the observed eye is emmetropic and not accommodated, are brought to a focus by a convex lens held 714 A MANUAL OF PHYSIOLOGY. near the eye of the patient, so as to form a real and inverted aerial image of the retina. This image is viewed by the observer at his ordinary visual distance. Single Vision with Both Eyes — Diplopia. — Scheiner's experi- ment shows that it is possible to have double vision, or diplopia, with a single eye when two separate images of the same object fall upon different parts of the retina. In vision with both eyes, or binocular vision, an image of every object looked at is, of course, formed on each retina, and we have to enquire how it is that as a rule these images are blended m consciousness so as to produce the perception of a single object ; and how it is that under certain conditions this blending does not take place, and diplopia results. Two chief theories have been invoked in the attempt to answer these questions : (i) the theory of identical points, (2) the theory of projection. In regard to the second theory, we shall merely say that it assumes that in some way or other the retina, or, rather, the retino-cerebral apparatus, has the power of appreciating not only the shape and size of an image, but also the direction of the rays of light which form it, and that the position of the object is arrived at by a process of mental projection of the image into space along these directive lines. The first theory we shall examine in some detail. The Theory of Identical Points. — This theory assumes that every point of one retina ' corresponds ' to a definite point of the other retina, and that in virtue of this correspondence, either by an inborn necessity or from experience, the mind refers simultaneous impressions upon two corresponding or identical points to a single point in external space. If we imagine the two retinae in the position which the eyes occupy when fixing an infinitely distant object (that is, with the visual axes parallel) to be superposed, with fovea over fovea, every point of the one retina will be covered by the corresponding point of the other retina, so that identical points could be pricked through with a needle. But since the actual centre of the retina does not correspond with the fovea centralis (Fig. 232), but lies nearer the nasal side, the nasal edge of the left retina will overlap the temporal edge THE SENSES. 715 of the right, and the nasal edge of the right will overlap the temporal edge of the left ; so that a part of each retina has no corresponding points in the other. When the eyes are directed to two distant objects at the same height as themselves — when, in other words, the visual axes are parallel and horizontal — neither the middle vertical meridians nor the middle horizontal meridians of the two retinee, as a rule, exactly correspond, although the correspondence is much nearer for the horizontal than for the vertical meridians. A meridian of the left retina, the upper end of which is slightly inclined towards the left, contains the points corresponding to a meridian of the right eye whose upper end is slightly inclined to the right. When \)\\'i physio- logical ificongnience of the retime is taken into account in determining the points which are to be considered as identical, the adherents of this theory claim, and with justice, that a small object so situated that its image must be formed on corresponding points of the two retinas does, as a rule, appear single, and, what is even more striking, that a phosphene, or luminous circle produced by pressing the blunt end of a pencil or the finger-nail on a point of the globe of one eye, is not doubled by pressure over the corresponding point of the other eye, although two circles are seen when pressure is made upon points which do not correspond. But too much weight must not be allowed to such evi- dence, for it is also a fact that images situated on corre- sponding points may not, and that images not situated on corresponding points may, give rise to a single impression. For example, if one of the closed eyes be held slightly out of its ordinary position by the finger, pressure on identical points of the two eyes gives rise to two separate phosphenes. And some of the phenomena of stereoscopic vision (p. 720) show clearly that images falling on non-corresponding points may give a single impression; while we do not habitually see double, although it is certain that the images of multitudes of objects are constantly falling on points of the retinas not anatomically identical. The Horopter.* — In every fixed position of the eyes, the objects whose images fall on corresponding points will be arranged on certain definite lines or surfaces, which vary with the direction of the visual axis, and to which the name of horopter, or pointhoropter, has been given. Thus, let the eyes be directed to a point A (Fig. 250) at such a distance that the lines of vision are sensibly convergent. Suppose a plane drawn in each eye through the visual axis and the middle * This section may be omitted by the junior student. 7i6 A MANUAL OF PHYSIOLOGY. longitudinal (vertical) section of the retina. These planes will cut each other in a line passing through the fixing-point A, and it is evident that an image of any point situated on that line will be thrown on corresponding meridians of the two retina. Similarly, if we imagine other planes all passing through a straight line perpendicular to the visual axis, and drawn in the first plane through the nodal point, the intersections of these planes with the retina will always be its longitudinal (vertical) meridians. The lines in which the planes passing through corresponding meridians of the retina intersect each other will evidently be lines every point of which will have its image formed on corresponding vertical meridians. The locus of the straight lines in which the planes passing through corresponding meridians cut each other will be a cylindrical surface at right angles to the plane passing through the two visual lines and the fixing-point. Now,[this plane (the visual plane) intersects corresponding trans- verse (horizontal) meridians of the two L retinae, viz., the middle \ transverse meridian of each, and any point in it must, therefore, have its image formed upon corresponding trans- verse meridians. Any point which lies both on the cylindrical sur- face and in the visual J. lane must have its image formed both on corresponding vertical and on corresponding transverse meridians ; i.e., its image must fall on the intersection of such meridians — in other words, on corre- sponding points of the two retinje. But the only points common to the cylindrical surface and the plane which cuts it at right angles are those which lie on the circle of section. This is the famous horopteric circle of Miiller. Every point on it has its image formed on corresponding points of the middle transverse meridians of the two retinae. But this circle does not form the whole hoiopter for the given position of the eyes, for some points on the cylindrical surface may have their images formed on corresponding points of the other transverse meridians. To find whether this is so, we must imagine a perpendicular to each visual axis drawn in their common plane through the nodal points. Now suppose an infinite number of planes passing through this perpen- dicular, one of which intersects each transverse meridian of the retina ; Fig. 2m. THE SENSES. 717 these planes, it is evident, from tlie symmetrical position of the two eyes, will intersect each other in a mesial plane at right angles to the visual plane. Any point on the line of intersection of a pair of planes passing through corresponding transverse meridians of the retinae will have its image formed on corresponding transverse meridians. And the points common to the surface on which all the lines of intersec- tion lie (the median plane) and the cylindrical surface, will have their images formed on corresponding retinal points. Now, such common points evidently lie in the straight line in which the median plane cuts the cylindrical surface — a straight line passing through the point of -fixation and at right angles to the visual plane. This line is also part ot the horopter in the given position of the eye. In the above discussion we have assumed for the sake of simplicity that the true middle longitudinal meridian of the retina is at right angles to the middle transverse meridian. In most eyes this is not the case, and the linear part of the horopter is not at right angles to the visual plane, but cuts it obliquely, the upper end of the straight line being tilted away from the eyes. It can be proved very easily by elementary geometry that the images of any point B lying in Miiller's horopteric circle (Fig. 250) fall on corresponding retinal points. For if C and D are the nodal points of the two eyes, and A', K' , the centres of the foves, the angles DAC, 7i8 A MANUAL OF PHYSIOLOGY. DBC, being angles in the same segment of a circle, are equal ; and in the triangles AEC, BED, the angles AEC, BED, being opposite angles, are also equal. Therefore, the angles ACE and EDB are equal ; i.e., the angles B'CA' and B"DA" are equal. And if the left eye be laid on the right so that CA' corresponds with DA", B" must correspond with B'. For most eyes when directed to the horizon, the horopter is practically the horizontal plane of the ground, so that all objects within the field of vision and resting on the ground fall upon corre- sponding points, and are seen single. The images of a point P outside the horopteric circle (Fig. 251) will not fall on corresponding points. For in the triangles DPE, EAC, Fig. 252. the angles DEP, CEA, are equal, but the angle DPE is less than EAC. Therefore, the angle EDP is greater than ECA, and the angle A'T)P" is greater than A'CP'. Similarly, a point Q(Fig. 252) inside the circle will not have corre- sponding images. For in the triangles QED, AEC, the angles QED, AEC, are equal, and DQE is greater than EAC. Therefore, QDE is less than ACE, i.e., A"DQ" is less than A'CQ'. In both cases when the departure from identity is more than a certain amount (for absolute geometrical correspondence is not necessary for single vision) double vision ensues. And on the theory of identical points, it is easy to explain the directions in which the double images are seen and their relation to the two eyes. For imagine the two eyes to be superposed and placed so as to form a single median eye — a replica, in fact, of that celebrated organ of the THE SENSES. 719 Fig. 253 • 254- Cyclops in which Ulysses twirled the burning brand with such unscientific gusto. Then the direction in space of any object is given by joining the point of the retina on which its image is cast to the nodal point, and producing this straight line. Let the points P', P" in Fig. 251 be pricked out and the eyes then superposed so that A' and A" coincide as in Fig. 253. It is evident that hole P' will lie to the right of hole P", and that the line joining P' to the nodal point will fall to the left of that joining P" to the nodal point. The image p' which is towards the left in the visual field will there fore belong to the left eye^in other words, the images will be un- crossed : and closing either of the eyes will extinguish the image of the corresponding side. When the point which is seen double is within the horopteric circle, as Q in Fig. 252, Q" is farther to the right than Q' when the eyes are superposed as in Fig. 254, therefore the image q' belonging to the left eye will correspond to the rightward of the double images —that is, the images are crossed ; when the left eye is closed the right- hand image q disappears ; when the right eye is closed it is the left- ward image (f which is cut out. Now, as we have said, the images of many objects must in almost every act of vision be formed on points of the retinae which are not identical ; and the question arises, How is it that we do not see these double images ? This is one of the difficulties of the theory of identical points. The following is a partial explanation : (i) The'images of objects in the portion of the field most distinctly seen, that is, the portion in the immediate neighbourhood of the intersection of the visual hnes, or the part to which the gaze is directed, are formed on identical points ; and by rapid movements the eyes fix successively different parts of the field of view. (2) Vision grows less distinct as we pass out from the centre of the retina, and we are accustomed to neglect the blurred peripheral images in comparison with those formed on the fovea. (3) When the image of an object does not fall on 720 A MANUAL OF PHYSIOLOGY. identical points, one of the points on which it does fall may be occupied with the images of other objects, some of which may be so boldly marked as to enter into conflict with the extra image and to suppress it. (4) And lastly, the physio- logical ' identical point ' is not a geometrical point, but an area which increases in size in the more peripheral zones of the retina, so that images which lie wholly or in chief part within two corresponding areas practically coincide. Stereoscopic Vision. — Although the retinal image is a pro- jection of external objects on a surface, we perceive not only the length and breadth, but also the depth or solidity of the things we look at. When we look directly at the front of a building, the impression as to its form is the same whether one or both eyes be used, although with a single eye its distance cannot be judged so accurately. But when we view the building from such a position that one of the corners is visible, we obtain a more correct impression of its depth with the two eyes. This is partly due to the fact that to fix points at different distances from the eyes the visual lines must be made to converge more or less, and of the amount of this convergence we are conscious through the contraction of the muscles which regulate it. But there is another element involved. When the two eyes look at a uniformly-coloured plane surface, the retinal image is pre- cisely the same in both. But when the two eyes are directed to a solid object, say a book lying on a table, the picture formed on the left retina differs slightly from that formed on the right, for the left eye sees more of the left side of the book, and the right eye more of the right side. That there is a close connection between uniformity of retinal images and impression of a plane surface on the one hand, and difference of retinal images and impression of solidity on the other, is proved by the facts of stereoscopy. It is evident that if an exact picture of the solid object as it is seen by each eye can be thrown on the retina, the impression produced will be the same, whether these images are really formed by the object or not. Now, two such pictures can be produced with a near approach to accuracy by photographing the object from the point of view of each eye. It only remains to cast the image of each picture on the corresponding retina, while the eyes are converged to the same extent as would be the case if they were viewing the actual object. This is accomplished by means of a stereoscope (Fig. 255). THE SENSES. 721 It is found that the resultant impression is that of the solid object. It is impossible to reconcile this with the doctrine of strictly identical points. A pair of identical pictures gives with the stereoscope not the impression of a solid, but of a plane surface. If the relative position of any two points differs in the two pictures, the blended picture has a corresponding point in high or low relief. So great is the delicacy of this test that a good and a bad banknote will not blend under the stereoscope to a flat surface, and the method may be actually used for the detection of forgery. When the pictures are inter- changed in the stereoscope so that the image which ought to be formed on the right retina falls on the left, and that which is intended for the left eye falls on the right, what were projections before become hollows, and what were hollows stand out in relief. The pseudo- scope of Wheatstone is an arrange- ment by which each eye sees an object by reflection, so that the images which would be formed on the two retinae, if the object were looked at directly, are interchanged, with the same reversal of our judgments of relief. 255. — Brewster's Stereo- scope. / and n- are prisms, with their re- fracting angles turned towards each other. The prisms refract the rays coming from the points f, •, of the pictures ab and <'/i so that they appear to come from a single point q. Similarly, the points a and a appear to be situated at f, and the points b and /3 at 'i". Visual Judgments. — We say judgments of relief ; for what we call seeing is essentially an act that involves intellectual processes. As the retina is anatomically and developmentally a projection of the cerebrum pushed out to catch the waves of light which beat in upon the organism from every side, so physiologically retina, optic nerve and visual nervous centre are bound together in an indissoluble chain. We cannot say that the retina sees, we cannot say that the optic nerve sees — the optic nerve in itself is blind — we cannot say that the visual centre sees. The ethereal waves falling on the retina set up impulses in it which ascend the optic nerve ; certain portions of the brain are stirred to action, and the resulting sensations of light springing up. we know not where, are elaborated, we 46 722 A MANUAL OF PHYSIOLOGY. know not how (by processes of which we have not the faintest guess), into the perception of what we call external objects — trees, houses, men, parts of our own bodies, and into judgments of the relations of these things among them- selves, of their distance and movements. A child learns to see, as it learns to speak, by a process, often un- conscious or subconscious, of * putting two and two together.' The musical sounds united by noises which make up the spoken word " apple ' are gradually associated in its mind with the visual sensation of a red or green object, the tactile sensation of a smooth and round object, and the gustatory and olfactory sensations which we call the taste or flavour of an apple. And as it is by experience that the child learns to label this bundle of sensations with a spoken, and afterwards with a written name, so it is by experience that it learns to group the single sensations together, and to make the induction that if the hand be stretched out to a certain distance and in a certain direction (i.e.^ if various muscular movements, also associated with sensations, be made), the tactile sensation of grasping a smooth, round body will be felt, and that if the further muscular movements involved in conveying it to the mouth be carried out, a sensation agreeable to the youthful palate will follow. At length the child comes to believe, and, unless he happens to be specially instructed, carries his belief with him to his grave, that when he looks at an apple he sees a round, smooth, tolerably hard body, of definite size and colour; while in reality all that the sense of sight can inform him of is the differ- ence in the intensity and colour of the light falling on his retina when he turns his head in a particular direction. An interesting illustration of the role of experience in shaping our visual judgments is found in the sensations of persons born blind and relieved in after life by operation. A boy between thirteen and four- teen years of age, operated on by Cheselden, thought all the objects he looked at touched his eyes. ' He forgot which was the dog and which the cat, but catching the cat (which he knew by feeling), he looked at her steadfastly and said, "So, Puss, I shall know you another time." Pictures seemed to him only parti-coloured planes; but all at once, two months after the operation, he discovered they represented solids.' Nunnely, perhaps, remembering the dictum of Diderot, true as it is in the main, though tinged with the exaggera- tion of the Encyclopcdie, that ' to prepare and interrogate a person born blind would not have been an occupation unworthy of the united talents of Newton, Des Cartes, Locke and Leibnitz,' made an elaborate investigation in the case of a boy nine years old, on whom he operated for congenital cataract of both eyes, and, what is of special importance, instituted a set of careful experiments and interrogations before the operation so as to gain data for com- parison. Objects (cubes and spheres) which before the operation he could easily recognise by touch were shown him afterwards, but although ' he could at once perceive a difference in their shapes, he THE SENSES. 7^3 could not in the least say which was the cube and which the sphere.' It took several days, and the objects had to be placed many times in his hands before he could tell them by the eye. ' He said every- thing touched his eyes, and walked most carefully about, with his hands held out before him to prevent things hurting his eyes by touching them.' The apparent size and form of an object is intimately related to the size, form, and sharpness of its image on the retina. We are, therefore, able to discriminate with great precision the unstimulated from the excited portions of that In A the opaque body o is in the plane of the pupil. The position of the shadow relatively to the bright field is not altered when the illuminating pencil is focussed at P' instead of P. In B the opaque body is in front of the plane of the pupil. When P is lowered to P', the shadow moves towards the upper edge of the bright field, and appears to move down- wards in the visual field. When P is raised, the shadow moves towards the lower edge of the bright field, and appears to move upwards. In C the opaque body is behind the plane of the pupil. When P is moved downwards to P', the shadow moves towards the lower edge of the bright field, and appears to the person under observation to move upwards, and vict^- versd when P is moved up- wards. The farther the opaque body is from the pupil, the greater is the apparent movement, or parallax, of its shadow for a given movement of the source of light. Fig. 256. membrane, especially in the fovea centralis, and also the degree of excitation of neighbouring excited parts. But instead of localizing the image on the retina as we localize on the skin the pressure of an object in contact with it, we project the retinal image into space, and see everything outside the eye. In vision, in fact, we have no conception of the existence of either retina or retinal image : and even 724 A MANUAL OF PHYSIOLOGY. the shadows of objects within the eye are referred to points outside it. Thus, for instance, an opacity or a foreign body in any of the refractive media — and no eye is entirely free from relatively opaque spots — can be detected, and its position determined b)) the shadow which it casts on the retina when the eye is examined by a pencil of light pro- ceeding from a very small point. Let a diaphragm with a small hole in it be placed in front of the eye at such a distance that a pencil diverging from the hole will pass through the vitreous humour as a parallel beam, equal in cross-section to the pupil (Fig. 256), and let the aperture be illuminated by focussing on it the light of a lamp placed behind a screen. Opaque bodies in the vitreous humour will cast shadows equal in area to themselves. The shadows of opacities in the lens and in front of it will be somewhat larger than the bodies themselves, since the latter intercept rays which are still diverging ; but since the greater part of the refraction of the eye occurs at the anterior surface of the cornea, it is only the shadows of objects on the front of the cornea, such as drops of mucus, which will be much magnified. Fig. 256 shows diagrammatically how the shadows shift their position within the bright field when the direction of the illuminating beam is altered. Generally, opacities in the vitreous humour are movable, in the lens not. The muscae volitantes which flit across the field of vision, and are sometimes troublesome in microscopic work, are due to small movable opacities. Purkinje's Figures. — As was first pointed out by Purkinje, the shadows of the bloodvessels in the retina itself, and even of the corpuscles circulating in them, although neglected in ordinary vision, may be recognised under suitable condi- tions, a conclusive proof that the sensitive layer must lie behind the vessels (p. 726). If a beam of sunlight is concentrated on the sclerotic as far as possible from the margin of the cornea, and the eye directed to a dark ground, the network of retinal bloodvessels will stand out on it. Another method is to look at a dark ground while a lighted candle, held at one side of the eye at a distance from the visual line, is moved slightly to and fro. In the first method, a point of the sclerotic behind the lens is illuminated, and rays passing from it across the THE SENSES. 725 Fig. 257. — Method of rendering the Retinal Bloodvessels visible by concentratikg a Beam of Light on the Sclerotic. C From the brightly illuminated point of the sclerotic, a, rays issue, and a shadow of a vessel, v, is cast at a'. It is referred to an external point a" in the direction of the straight line joining a' with the nodal point. When the light is siiifted so as to be focussed at b, the shadow cast at b' is referred to b" , i.e., it appears to move in the same direction as the illuminated point of the sclerotic. interior of the eyeball in every direction cast shadows of the vessels of the retina on its sensitive layer. In the second method, the image of the flame formed on the retina by rays falling obliquely through the pupil be- comes in the general darkness itself a source of light, by interrupt- ing the rays from which the retinal vessels form shadows. The distance of the sensitive from the vas- cular layer may be approximately calcu- lated by measuring the amount by which the shadows change their position, when the position of the illu- minated point of the sclerotic is altered. The nearer a vessel lies to the sensitive layer, the smaller must be the angle through which the apparent position of its shadow moves for a given movement of the spot of light. In this way it has been calculated that the sensitive layer is about 0*2 to 0*3 mm. behind the stratum which con- tains the bloodvessels. This corresponds sufficiently well with the position of the layer of rods and cones, which all other evidence shows to be the portion of the retina actually stimulated by light. The shadows of the blood- corpuscles in the retinal vessels may be rendered visi- ble by looking at a bright and uniformly illuminated ground, like the milk glass shade of a lamp or the blue sky, and moving the slightly separated fingers or a perforated card rapidly before the eye. From the rate of their apparent movement, Vierordt calculated the velocity of the blood in the retinal capillaries at 0*5 to o'9 mm. per second. One reason why the Fig. 258. — Method of rendering the Bloodvessels of the Retina visible BY Oblique Illumination through the Cornea. Light from a candle at a illuminates a', and rays proceeding from a' cast a shadow of the bloodvessel v at a" , which is referred to a"'. When a is moved to b, the shadow on the retina moves to b" , and the shadow in the visual field of the illuminated eye to b'". 726, A MANUAL OF PHYSIOLOGY. shadows of these intra-retinal structures do not appear in ordinary vision seems to be their small size. The retinal vessels are in reality only vascular threads ; the thickest branch of the central vein is not -}.; mm. in diameter. The apex of the cone of com- plete shadow (umbra) cast by a disc of this size, at a distance of 20 mm. from a pupil 4 mm. wide, would lie only 1 mm. behind the disc — that is to say, the umbra of the retinal vessels would not reach the layer of the rods and cones at all, and only the penumbra, or region of relative darkness, would fall upon it. When the eyes, after being closed for some time, are suddenly opened, the branches of the retinal vessels may be seen for a moment. This is especially the case after sleep ; and a good view of the phenomenon may be obtained by looking at a white pillow or the ceiling immediately on awaking. If the eyes are kept open for a few seconds, the branching pattern fades away ; if they are only allowed to remain open for an instant, it may be seen many times in succession. Relation of the rods and cones to vision. — We have more than once referred to the rods and cones as the sensitive layer of the retina. It is now necessary to develop a little more the evidence in favour of this statement. And at the outset, since the sensitive layer has been shown to lie behind the plane of the retinal bloodvessels, the only com- petitors of the. rods and cones are the external nuclear layer and the pigmented epithelium. The nuclear layer may be at once excluded, because in the fovea centralis, where vision is most distinct, it becomes very thin and in- conspicuous. The layer of pigmented hexagonal cells, or at least their pigment, cannot be essential to vision, for albino rats, rabbits and men, in whose eyes pigment is absent, can see. In man and most mammals there are cones, but no rods in the yellow spot and fovea centralis ; the relative proportion of rods increases as we pass out from the fovea towards the ora serrata. But this does not enable us to analyze the bacillary layer into sensitive cones and non-sensitive rods, for on the rim of the retina, which is still sensitive to light, there are only rods ; in the bat and mole there are no cones in the yellow spot, in the rabbit very few. Reptiles possess only cones over the whole retinal surface, and birds, true to their reptilian affinities, have everywhere more cones than rods, as have also fish. THE SENSES. 727 One of the most serious difficulties in the way of under- standing how a ray of hght can set up an excitation in a rod or cone is the transparency of these structures. An absolutely transparent substance — that is, a substance which would allow light to traverse it without the least absorption — would, after the passage of a ray, remain in precisely the same state as before ; its condition could not be altered by the passage of the light unless some of the energy of the ethereal vibrations was transferred to it. But an absolutely transparent body does not exist in nature ; and it is not necessary to suppose that all the energy required to stimulate the end-organs of the optic nerve comes from the luminous vibrations. These may, and probably do, act by setting free energy stored up in the retina, just as the touch of a child's hand could be made to fire a mine, or launch a ship, or flood a province. Some have looked upon the transverse lamellae into which the outer members of the rods and cones can be made to split as an arrangement for reflecting back the light to the inner members, and have compared them to a pile of plates of glass, which, transparent as it is, is a most efficient reflector. It is even possible, although here we are already treading the thin air of pure speculation, that the light may be polarized in the process of reflection, and that the rods and cones may be less transparent to light polarized in certain planes than to unpolarized light. As to the nature of the transformation undergone by the ethereal vibrations in the rods and cones, various theories have been formed. Some have supposed that the absorbed light-waves are transformed into long heat-waves, and that the endings of the optic nerve are thus excited by thermal stimuli. This hypothesis has so little evidence in its favour that it is perhaps an unjustifiable waste of time even to mention it. It is ruled out of court by the mere fact that the long radiations of the ultra red, filtered from luminous rays by being passed through a solution of iodine, and focussed on the eye by a lens of rock-salt, produce not the slightest sensation of light, although they are by no means all absorbed in their passage through the dioptric media. Again, it has been suggested that the energy of the waves of 728 A MANUAL OF PHYSIOLOGY. light is first transformed into electrical energy, and that the visual stimulus is really electrical. In support of this view it has been urged that light undoubtedly causes (p. 575) an electrical change in the retina and optic nerve. But, as has more than once been pointed out, an electrical change is the token and accompaniment of the activity of the excitable tissues in general ; and all that the currents of action of the retina show is that light excites the retina — a proposition which nobody who can see requires an objective proof of, and which does not carry us very far towards the solution of the problem how that excitation is brought about. Lastly, there is the photo-chemical theory, which owes its origin to the discovery, or rather re-discovery, of the famous visual purple or rhodopsin by Boll, and its present form to the investigations and arguments of Kiihne. Though it has not fulfilled all the hopes excited in sanguine minds, and has not explained, or even lessened, the mystery of vision, the discovery of the visual purple is in itself so interesting and so suggestive as a basis for future work, that a short account of the properties of the substance cannot be omitted here. Visual Piirple. — If the eye of a frog or rabbit, which has been kept in the dark, be cut out in a dimly-lighted chamber or in a chamber illuminated only by yellow light, and the retina removed, it is seen, when viewed in ordinary light, to be of a beautiful red or purple colour. Exposed to bright light, the colour soon fades, passing through red and orange to yellow, and then disappearing altogether. The yellow colour is due to the formation of another pigment, visual yellow ; the preceding stages are due to the intermix- ture of this visual yellow with the unchanged visual purple in different proportions. With the microscope it may be seen that the pig- ment is entirely confined to the outer seg- ment of the rods, where it exists in most • 259.— PTOGRAM. vertebrate animals. It may be extracted Part of retina of rabbit, by a watery solution of bile-salts, and the the eye of which had been ^- r ^u • ^ • i ..• directed to an illuminated Properties of the pigment in solution are plate of glass covered with very much the same as its properties in strips of black paper. ^if^ . Ugj^^ bleaches the solution as it does the retina. Examined with the spectroscope, the solution shows no definite bands, but only a general absorption, which is very slight in the red, and reaches its maximum in the yellowish-green. In accordance with this, it is found that of all kinds of monochromatic THE SENSES. jzc) light the yellowish-green rays bleach the purple most rapidly, the red rays most slowly. If a portion of the retina is kept dark while the rest is exposed to light, only the latter portion is bleached. And when the image of an object possessing well-marked contrasts of light and shadow {e.g., a glass plate with strips of black paper pasted on it at intervals, or a window with dark bars), is allowed to fall on an eye otherwise pro- tected from light, the pattern of the object is picked out on the retina in purple and white. A veritable photograph or ' optogram ' may thus be formed even on the retina of a living rabbit ; and if the eye be rapidly excised, the picture may be ' fixed ' by a solution of alum, and thus rendered permanent. These facts certainly suggest that light falling on the retina may cause in some sensitive substance or substances chemical changes, the products of which stimulate the end- ings of the optic nerve, and set up the impulses that result in visual sensations. The visual purple cannot itself be such a substance, for it is absent from the cones of all animals and the rods of some. Frogs and rabbits can undoubtedly see at a time when, by continued exposure to bright sunlight, the purple must have been completely bleached. And although the absence of the pigment in the eye of the bat might seem to afford a ready explanation of the proverbial ' blindness ' of that animal, such a hasty deduction would be at once corrected by the fact that birds with as sharp vision as the pigeon are equally devoid of visual purple. The pigmented retinal epithelium is undoubtedly sensitive to light, and has im- portant relations to the formation of the visual purple. When the eye is exposed to light the pigmented cells push down processes between the rods. In the dark they draw them back again, so that while it is easy to separate the retina without the pigmented layer from the eye of an animal kept in the dark, the hexagonal epithelium always adheres to a retina which has shortly before death been acted upon by light. The precise meaning of these changes of form in the pigmented cells is unknown. It has been plausibly urged that in bright light the processes that stretch in among the rods serve as insulators to confine the excita- tion by preventing the lateral passage of scattered light from one element to another; but it may be that the movements 730 A MANUAL OF PHYSIOLOGY. are related rather to the formation of photo-chemical substances to act as stimuli to the end-organs of the optic nerve. And the pigmented epithelium is known to be con- cerned in the regeneration of the visual purple. When a frog is curarized, oedema occurs between the retina and the choroid, so that the former membrane is separated from the hexagonal epithelium. If the frog is now exposed to sunlight till the visual purple is bleached, and the retina then taken out and placed in the dark, no regeneration of the pigment takes place. When the same experiment is repeated on a non-curarized frog, the visual purple is restored in the dark, and may be seen under the microscope in the rods. The only difference in the two experiments is that in the latter the pigmented epithelium adheres to the retina, and it must therefore have a hand in the regener- ation of the pigment. Even the visual purple of a retina from which the epithelium has been detached will, after being bleached, be restored if the retina is simply laid again on the epithelial surface. And it does not seem to be the black pigment of the hexagonal cells which is the agent in this restoration, for it takes place in the pigment-free retinae of albino rabbits or rats. Even a retina isolated from the pigmented epithelium, and then bleached, may, to a certain extent, develop new visual purple in the dark. This is even true when it has been kept in the dark in a saturated solution of sodium chloride, and is then, after washing with normal saline, bleached by light. Here the regenera- tion of the pigment cannot be the result of vital processes, but must be due to chemical changes in products formed from the original pigment by the action of light. There is no such regeneration in a retina which, after having been bleached in situ, is removed without the pigmented epithelium and placed in the dark ; and the only probable explanation of the difference is that in this case the photo-chemical sub- stances from which visual purple can be formed have been absorbed into the circulation, and have so escaped. The inner segments of the cones of certain animals (birds, reptiles and some fishes) contain globules of various colours, ranging over almost the whole spectrum, and including, besides, the non-spectral THE SENSES. 731 colour, purple. The globules are composed chiefly of fat with the pigments (chromophanes, as they have been called) dissolved in it. The function of these globules is unknown. They cannot be con- cerned in colour vision, or, at least, they cannot be essential to it, for in the human retina they do not exist. The yellow pigment of the macula lutea does not belong to the layer of rods and cones ; it only exists in the external molecular layer and the layers in front of it ; in the fovea centralis it is absent. The Blind Spot. — The fibres of the optic nerve are insensible to light ; light only stimulates them through their end-organs. This can be proved by directing by means of an ophthalmo- scope a beam of light upon the optic disc, where the true retinal layers do not exist. The person experimented on has no sensation of light w^hen the beam falls entirely upon the disc ; when its direction is shifted so that it impinges upon any other portion of the retina, a sensation of light is at once experienced. The blind spot is not recognised in ordinary vision, for (i) the two optic discs do not corre- spond. The left disc has its corresponding points on a sensitive part of the right retina, and the right disc on a sensitive part of the left retina ; and the consequence is that in binocular vision the objects whose images are formed on the corresponding points fill up the blind spots. (2) The optic disc does not lie in the line of direct, and therefore distinct, vision. The eye is constantly moving so as to bring the surrounding objects successively on the fovea centralis ; and the gap which the blind spot makes in the visual field of a single eye is thus more easily neglected. In any case we ought not to see it as a dark spot, for darkness is only associated with the absence of excitation in parts of the retina capable of being excited by light. There is no more reason why the optic discs should appear dark than there is for our having a sensation of darkness behind us when we are looking straight in front. And since the experience of our other senses, the sense of touch, for example, tells us that the objects we look at do not in general have a gap in the position corresponding to the part of the image that falls on the blind spot, we see, so to speak, across the spot. By Mariotte's experiment, however, the existence of the blind spot can not only be demonstrated, but its size determined and its 732 A MANUAL OF PHYSIOLOGY. boundaries mapped out. Let the left eye be closed, and fix with the right the small cross ; then, if the eye be moved towards or away from the paper, keeping the cross fixed all the time, a position will Fig. 260. — Mariotte's Experiment. be found in which the white disc disappears altogether. In this position its image falls on the blind spot. (See Practical Exercises, Fig- 275-) Time necessary for Excitation of the Retina by light. — Fusion of stimuli. — Whatever the exact nature of retinal excitation may be, it is called forth by exceedingly slight stimuli. A lightning flash, although it may last only th of a •^ 1,000,000 second, lasts long enough to be seen. A beam of hght thrown from a rotating mirror on the eye, stimulates when it only acts for th of a second. The minimum 8,000,000 stimulus in the form of green light corresponds, as we have already seen (p. 521), to a quantity of work equivalent to no more than — x — r^ gramme-degree, i.e. —^ gramme- 4-2 10^^ ^ ^ 10^" ^ millimetre, or — - milligramme-millimetre, which is the work 10*^ -th of a milligramme in falling through done by 10,000,000 a millimetre ; and it cannot be doubted that a portion even of this Lilliputian bombardment is wasted as heat. So quickly, too, is the stimulus followed by the response that no latent period has as yet ever been measured. It cannot be doubted, however, that there is a latent period, as certainly as there is a latent period in the excitation of a naked nerve-trunk, although this also has never been experimentally detected. The analogies, in fact, between a muscular contraction and a retinal excitation, are numerous and close. Like the muscle, the retina seems to possess a store of explosive THE SENSES. 733 material which the stimulus serves only to fire off. The retina, like the muscle, is exhausted by its activity, and recovers during rest. Like the muscle curve, the curve of retinal excitation rises not abruptly, but with a measurable slowness to its height, and when stimulation is stopped, takes a sensible time to fall again. With comparatively slow intermittent stimuli the retinal, like the muscle curve, flickers up and down. When the rate of stimulation is increased, the steady contraction of the tetanized muscle is analogous to the fusion of the individual stimuli by the tetanized retina (or retino-cerebral apparatus) into a con- tinuous sensation of light. But the maximum retinal excita- tion which a stimulus of given strength can call forth depends much more closely upon the time during which the stimulus acts than the maximum contraction does upon the length of the muscular stimulus. As the strength of the light increases in geometrical pro- gression, the time during which it must act in order to pro- duce its maximum effect decreases approximately in arith- metical progression (Exner). For light of moderate intensity this time is about \ second. As soon as the stimulus of light is withdrawn the retinal excitation begins to sink ; while a stimulated muscle need not even com- mence its contraction till the stimulus has ceased to act. The result is, that while a muscle in complete tetanus reaches a degree of contraction as great as, or greater than, that produced by any one of a series of stimuli acting alone, the retinal excitation, as measured by the resultant sensation, is always less when a succession of similar stimuli are fused than when any one of the stimuli is allowed to produce its maximum effect. If the time of each stimulus is equal to the interval during which there is no stimulation, the sensation, when complete fusion has been reached, is the same as would be produced by a constant light of half the strength employed. And, in general, if in be the pro- portion of the time during which the eye is stimulated by a light of intensity ^ and 11 the proportion of the time during which it is not stimulated, the resultant impression is the same as that which would be produced by an uninterrupted light of intensity ( — — )/. This is Talbot's law, which may be expressed without the aid of symbols 734 A MANUAL OF PHYSIOLOGY. thus : When a light of given intensity is allowed to act on the eye at ifitervals so short that the impressions are completely fused, the resultant sensation is independent of the absolute lefigth of each flash, atid is p}'oportional only to the fraction of the whole time which is occupied by flashes and to the intensity of the light. Talbot's law may be readily demonstrated by means of a rotating disc with alternate white and black sectors (Fig. 261), so arranged that the same proportion of the circumference of each of the three concentric zones is black. When the rotation is sufficiently rapid to give complete fusion (say 20 to 30 times a second), the whole disc appears equally bright. However much the rate of rotation is now increased, no further change occurs. It has been shown that even for stimuli as short as the -gTrTj^TRnrth of a second, repeated at intervals of yro^h second, Talbot's law Fig. 261.— Disc for de- holds good. So that not only does a flash so MONSTRATiNG Talbots inconccivably brief affect the retina, but it sets ^^' up changes which last for a measurable time. Colour Vision. — Besides differences in the distance, size, shape, and brightness of objects, the eye recognises differ- ences in their colour ; and we have now to consider the physical and physiological differences on which these depend. Colours may differ from each other — (i) In tone or hue, e.g., red, yellow, green. (2) In degree of saturation or fulness or purity, i.e., in the degree in which they are free from admixture with white light ; e.g., a 'pale' or 'light ' blue is a blue mixed with much white light, a 'deep ' or ' full ' blue with little or none. (3) In brightness or in- tensity, i.e., in the amount of the light coming from unit area of the coloured object. Thus a ' dark ' red cloth sends comparatively little light to the eye, a ' bright ' red cloth sends a great deal. When a beam of sunlight falls into the eye, a sensation of 'white light' results. When a prism is placed before the eye, the sensation is entirely different ; we see a spectrum running up from red through green to violet, with a multitude of intermediate shades. What, then, has happened? Physi- cally, nothing more has taken place than a rearrangement of the rays in the beam of white light. A few of them may have been lost by reflection, but upon the whole the beam is made up of exactly the same constituents as before ; only the rays are now arranged in the precise order of their refrangibility, the more refrangible, which are also those of shortest wave-length, being displaced more towards the base of the prism than the longer and less refrangible rays. THE SENSES. 735 Instead of the long and short rays falling together on the same elements of the retina, as they did in the absence of the prism, they now fall, if proper precautions have been taken to secure a pure spectrum, in regular order from one side to the other of the portion of retina on which the image is formed. The physical condition, then, of our sensations of the prismatic colours is, that rays of approxi- mately the same wave-length should fall unmixed with other rays upon the retinal elements. Rays of a wave-length of y^OytrW to 650j-^j5j(^ give the sensation of red ; from 650^^5"^^^ to 590to1jo. the sensation of orange ; from 430T(j"oir to 400 j-^''^^^, the sensation of violet, and so on. When.rays of all these wave-lengths fall together, in the proportions in which they are present in sunlight, upon the same part of the retina, the resultant physiological effect is very different ; we are no longer able to distinguish red, blue, green, etc. ; we receive the single sensation of white light. The sensation is a simple one ; in consciousness we have no hint that it has a multiple physical cause. But we find further that it is not necessary for the sensation of white light that waves of every length present in the solar spectrum should be mixed. If rays of wave- length 675jy"oo (which acting alone produce the sensation of red) be mixed in certain proportions, i.e., be allowed to fall on the same part of the retina, with rays of wave-length 4g6yy"(jy (which give the sensation of bluish-green), the re- sultant sensation is also that of white light. And an indefi- nite number of sets can be combined, two and two, so as to give the same sensation of white. Such colours are called complementary. The following are pairs of complemen- tary colours : Red and greenish-blue. Yellow and indigo-blue. Orange and cyan-blue. Greenish yellow and violet. The green of the spectrum has no simple complementary colour ; purple, a mixture of red and violet, may be considered complementary to it. Suppose now that one of a pair of complementary colours is added to the other in greater intensity than is required to give white, the resultant sensa- tion is a colour which has a certain amount of resemblance both to white and to the colour present in excess. Thus, if 7Z(> A MANUAL OF PHYSIOLOGY. the two colours are orange and blue, and the blue is present in greater intensity than is necessary to give white, the resultant colour is a whitish or pale blue, or, to use the technical phrase, an unsaturated blue. The more nearly the intensity of the blue rays in a mixed light approaches the proportion necessary to give white, the less saturated is the resultant colour ; the greater the excess of blue the more nearly does the resultant sensation approach that of the saturated blue of the spectrum. But any non-saturated spectral colour produced by the mixture of two comple- mentary colours may be equally well produced by the mixture of the corresponding spectral colour with a certain quantity of ordinary white light. And it is found that when The ' colour triangle ' is a graphic method of re- presenting various facts in colour mixture : (i) On the curve the spectral colours are arranged at such dis- tances that the angle con- tained between straight lines drawn from the point W and intersecting the curve at the positions cor- responding to any two colours is proportional to their difference in tone. (2) The distance of any point on the curve from W IS proportional to the stimu- lation intensity of the colour corresponding to it. (If the stinmlation intensities of all the colours be represented by proportional weights lying at the corresponding points on the curve, W will be the centre of gravity of the system.) (3) The position of a colour produced by the mixture of any pair of spectral colours is found by joining the corresponding points by a straight line. The mi.\ed colour lies on tliis line at distances from the two points inversely proportional to the stimulation intensity of the two colours, i.e., it lies m the centre of gravity of the weights representing the two colours. (4) It is a particular case of (3) that the complementary colours are situated at the points where straight lines drawn through W intersect the curve, since W is the centre of gravity correspond- ing to a pair of colours only when it lies on the straight line joining them. The non- spectral purple is represented by a broken line. two spectral colours which are not complementary are mixed together the resultant is not white, but a colour which may be matched by some spectral colour lying between the two, plus a larger or smaller quantity of ordinary white light. From all this it follows that the retina may be excited by an infinite number of different physical stimuli, and yet the resultant sensation may be the same. This leads straight to the conclusion that somewhere or other in the retino- cerebral apparatus simplification, or synthesis, of impressions Fig. 262.— -Colour Triangle. (In the description the point marked ' White' is re- ferred to as W.) THE SENSES. lyi must take place; and we have to inquire what the simplest assumptions are which will explain all the phenomena. Now it is not possible, from two spectral colours alone, to produce a sensation corresponding to any of the others. By mixing three standard spectral colours, however, in various proportions, we can produce not only the sensation of white light, but that of every colour of the spectrum. The simplest assumption we can make, then, is that there are three standard sensations, and that either the retina itself can respond by no more than three distinct modes of excitation to the multiplex stimuli of the luminous vibra- tions, or that complex impulses set up in the retina are reduced to simplicity because the central apparatus is capable of responding by only three distinct kinds of sensa- tion. Which three sensations we select as fundamental or primary is, to a certain extent, arbitrary. Fick chooses red, Fig. 263. — Diagram of Curves of Excitability of the Three F'ibre-grolps- green, and blue ; most commonly red, green, and violet are accepted as the primary colours. The theory which best explains the facts, and has been most widely accepted, is that of Young, generally called, on account of its adoption and extension by Helmholtz, the Young-Helmholtz theory. It assumes that in the retina, or in the retino-cerebral apparatus, there are three kinds of elements — (i) 'jed fibres,' which are chiefly excited by light of comparatively long wave-length (red), to a less extent by light of medium wave-length (green), and to a still less extent by the shortest visible waves (viokt) ; (2) ' green fibres,' mainly excited by rhedium, but also to a certain extent by long and short waves ; (3) ' violet fibres,' chiefly affected by the short vibra- tions, less by the medium, and still less by the long waves. The curves in Figs. 263 and 264 illustrate these relations. It must be carefully remembered that here the 47 738 . A MANUAL OF PHYSIOLOGY. word ' fibre ' is merely a convenient term to avoid some such cumbrous phrase as ' physiological unit.' There is no ground for believing that an anatomical distinction of three 'fibre ' groups can be made in retina, optic nerve, or brain. This assumption explains the phenomena of colour- mixture to which we have referred above. When all the rays of the spectrum act upon the retina together, the three groups of fibres are about equally excited, and this equal excitation may be supposed to be the condition of the sensa- tion of white light. When the green of the spectrum alone falls on the retina, the green fibres are strongly excited, the other two groups only slightly; this is the relation between Fig. 264.— Curves of Excitabii.itv (jk Primary Sensation^ fki^m Observa- tions ON Colour Mixtures (Konig). The numbers give wave-lengths of the spectrum in millionths of a mm. the amount of excitation in the three groups which is associated with a sensation of spectral green. When two complementary colours, such as red and bluish green, fall together on the same portion of the retina, the three fibre groups are excited in the relative proportions associated with the sensation of white light. It is a point of great theoretical interest and importance that on this theory the pure spectral colours, although physically saturated, ought not to be physiologically saturated, since they all excite the three fibre groups although in different degrees. Now it is found that this is really the case. If, for example, we look first at the bluish-green and then at the red of the spectrum, the sensation of red is fuller or more saturated than if we had looked at the red directly. Similarly, if we look first at a small bluish-green square on a black ground, and then at a red ground, we see a more fully saturated square in the THE SENSES. 739 middle of the latter. The explanation, on the Young-Helmholtz theory, is that the 'green ' fibres being tired before the eye is turned upon the red, the latter colour no longer affects them, or affects them less than it would otherwise do, and therefore the excitation is almost entirely confined to the red fibres in the area fatigued for green. This brings us to the subject of retinal fatigue, and the related phenomena of after-images and contrast. After-images. — We have seen that the retinal excitation always takes time to die away after the stimulus is removed. If a white object is looked at, especially when the eye is fresh, for a time not long enough to cause fatigue, and the eye is then closed, an image of the object remains for a short time, diminishing in brightness at first rapidly, then more slowly. This is a positive after-image, and by careful obser- vation it may, under certain conditions, be seen that the positive after-image of a white object, of a slit illuminated by sunlight, for example, undergoes changes of colour as it fades, passing through greenish-blue, indigo, violet, or rose, to dirty orange. On the Young-Helmholtz theory this is ex- plained b}' the supposition that the excitation does not decline with the same rapidity in the three hypothetical fibre groups. If the object is looked at for a longer time, or if the eye is fatigued, a dark or negative image may be seen upon the faintly-illuminated ground of the closed eyes; but negative after-images may be more easily obtained when the eye, after being made to fix a small white object on a black ground, is suddenly turned upon a white or neutral tint surface. Here the portion of the retina on which the image of the object is formed may be assumed to be more or less fatigued. And this fatigue will extend to all three kinds of fibres ; so that white light of a given intensity will now cause less excitation in this part than in the rest of the retina. It is easy to understand that the negative after-image of a coloured object will be seen, upon a white ground, in the complementary colour, for the fibres chiefly excited by the latter will have been least fatigued. The negative after-images seen when the eye, after receiving the positive impression, is turned upon a coloured ground, vary with the colour of the object and ground in a manner which can be readily explained as due to fatigue of one or other fibre group The phenomena of negative after-images are often included together as examples of successive contrast, the name implying mutual influence of the portions of the retina successively stimu- lated. We have now to consider simultaneous contrast, often spoken of simply as contrast. 740 A MANUAL OF PHYSIOLOGY Contrast. — A small white disc in a black field appears whiter, and a small black disc in a white field darker, than a large surface of exactly the same objective brightness. A disc with alternate sectors of white and black, so arranged that the proportion of white to black increases in each zone from centre to circumference, when set in rotation, ought, by Talbot's law, to show sharply marked and uniform rings, of which each is brighter than that internal to it. But each zone appears brightest at its inner edge, where it borders on a zone darker than itself, and darkest at its outer edge, where it borders on a brighter zone. The most natural explanation of this is that in the neighbourhood of an excited area of the retina, as well as within the area itself, the excitability is diminished ; and the same explanation holds for the contrast phenomena of coloured objects. A small piece of grey paper, e.g., is placed on a green sheet, and the whole covered with translucent tracing-paper. The grey patch appears in the complementary colour of the ground, viz., rose-red (Meyer). Here we may suppose that the fatigue of the group of fibres chiefly excited by the ground colour spreads into the portion of the retina occupied by the image of the gray paper ; the white light coming from the latter, therefore, excites mainly the fibres which give the sensation of the complementary colour. The curious phenomenon of coloured shadows is also an illustra- tion of contrast. They may be produced in various ways. For example, when a lamp is lit in a room in the twilight, before it has yet grown too dark, the shadows cast by opaque objects on a white window blind are coloured blue. The yellow light of the lamp overpowers the feeble daylight which passes through the blind, and the general ground is yellowish : but wherever a shadow is thrown it appears of a bluish tint in contrast to the yellow ground. Here the only illumination the eye receives from the region occupied by the shadow is the feeble daylight. Falling upon an area in which the fibres chiefly excited by yellow rays are more or less fatigued, it causes a sensation of the complementary colour. As darkness comes on, the shadows become black, for now practically no light at all comes from them. Helmholtz looked upon simultaneous contrast as a result of false judgment, and not a change of excitability in parts of the retina bordering on the actually excited parts. For the sake of perspective, it will be worth while to apply this theory, by way of illustrating it, to the explanation of the case of contrast we have just been consider- ing, from the other point of view in Meyer's experiment. Helm- holtz's explanation of this experiment is as follows : When a coloured surface is covered with translucent paper, the latter appears as a coloured covering spread over the field. The mind does not recog- nise that at the gray patch there is any breach of continuity in this covering ; it is therefore assumed that the greenish veil extends over this spot too. Now the gray seen through the translucent white paper is objectively white ; i.e., sends to the eye the vibrations which together would give the sensation of white light. But with a green veil in front of it, this could only happen if the really gray THE SENSES. 741 patch was of the colour complementary to green ; that is, rose- red. The mind, therefore^ judges falsely that the patch is red. Hering has severely criticised this theory of Helmholtz as to false judgments ; and the weight of evidence certainly seems to be in favour of the view that simultaneous, like successive, contrast is due to the influence of one portion of the retina, or reti no-cerebral apparatus, on another. The Young-Helmholtz theory of colour vision has not met with universal acceptance. The most important rival theory is that of Hering, who takes his stand upon the fact that certain sensations of light (red, yellow, green, blue, white, black) do appear to us to be fundamentally distinct from each other, while all the rest are obviously mixtures of these. Accepting these six as primary sensations, he assumes the existence in the- visual nervous apparatus of substances of three different kinds, which may be called the black-white, the green-red, and the blue-yellow. Like all other constituents of the body, these substances are broken down and built up again ; in other words, undergo disassi- milation and assimilation, destructive and constructive metabolism. The sensation of black, of green, and of blue he supposes to be associated with the constructive, and the sensations of white, of red, and of yellow with the destruc- tive, processes in the three substances. The black-white substance is used up under the influence of all the rays of the spectrum, but in different degrees ; the smaller the quantity of light falling on the retina, the more rapidly is it restored, and the more intense is the sensation of black. The green-red substance is built up by green rays, broken down by red. The blue-yellow substance is destroyed by yellow rays, restored by blue. When any of the visual substances are consumed at one part of the retina, they are supposed to be more rapidly built up in the surrounding parts, and in this way many of the phenomena of contrast receive an easy and natural explanation. Sensibility of Different Parts of the Retina. — The perception of colours, like the perception of white light, is not equally distinct over the whole retina. We have repeatedly had occasion to refer to the fovea centralis as the region of most distinct vision ; but it would be a mistake to suppose that it is therefore necessarily more sensitive than the rest of the retina. As a matter of fact, when the 742 A MANUAL OF PHYSIOLOGY minimum intensity of white light which will cause an impression at all is determined for each portion of the retina, it is found that the fovea centralis requires a somewhat stronger stimulus than the zone im- mediately surrounding it. But, with this exception, the sensibility of the retina diminishes steadily from centre to periphery, both for white and for coloured light. Konig has, indeed, upheld the para- do.xical view that the fovea is absolutely blind for blue rays, support- ing this assertion by two main experiments : {a) that when a number of feebly illuminated blue points are looked at, those that fall on the fovea disappear; (b) that when the moon is examined through a blue glass, her image is blotted out as soon as it falls on the fovea: But, as Gad has pointed out, the moon's image is of such dimen- 0.70 : 0.60 1 1 n, jO 5: VX p.-.^o ^ \\ \^ (.'.30 O.-JO i i^?^ n.iO i "^^^---^ mr^--- 0 J 10 \i 20 25 30 40 30 60 70 Degrees vf the field of vrision Fig. 26=;. — Sensibility of the Retina for Coi.olks. The figures along the vertical axis show the distance in metres at which colours of constant intensity can be perceived by different zones of the retina (Charpentier). sions that it would lie well within the fovea, and there ought, there- fore, to be no difficulty in getting it to disappear if Konig's theory were true. Yet Konig himself admits that his second experiment is difficult, and succeeds only under special conditions. Hering, too, seems to have shattered Konig's first argument by showing that the disappearance of the weakly illuminated blue points is only an illus- tration of the phenomenon known as Maxwell's spot, a dark-blue or almost black blot, seen in the visual field when the eye, after being kept closed for a short time, is directed to a surface illuminated by a weak blue light. It is due to the absorption of blue light by the pigment of the yellow spot, and stands out as a rose-coloured THE SENSES. 743 disc when a source of white h'ght is looked at through a sokition of chrome alum, since all the light which the chrome alum permits to pass is absorbed by the macula lutea, except the red rays. Hering; indeed, asserts that the fovea is the most sensitive part of the retina for colours, in opposition to Charpentier, who finds it slightly less sensitive for blue than the zone immediately external to it (Fig. 265). When the eye is fixed and the visual field — that is, the whole space from which light can reach the retina in the given position — or, what comes to the same thing, the projection of the visual field on the retina by straight lines passing through the nodal point, explored by means of a perimeter (Fig. 266), it is found that, under ordinary conditions, a white ob- ject is seen over a wider field than any coloured object, a blue object over a wider field than a red, and a red over a wider field than a green object. The exact shape, as well as size, of the visual field also differs somewhat for different colours. And although it has been shown by Aubert and others that monochromatic light of sufficient intensity can be perceived over the whole retina, yet it may be said that the retinal rim is even then relatively and, under ordinary conditions, absolutely colour-blind. This brings us to the subject of colour-blindness proper, a phenomenon of the greatest interest in its theoretical as well as in its practical bearings. Colour - blindness. — A considerable number of persons (about 4 per cent, of all males, but only one-tenth of this proportion of females) are deficient in the power of distin- guishing between certain colours. They are said to be colour-blind ; but the term must not be taken to signify that they are absolutely devoid of colour-sensations. A very small minority of the colour-bhnd appear to have but one sensation of colour ; a few confuse green with blue ; the ^-,-- / Fig. 260.— Priestley Smith's Perimeter (Jl'ng, Heidelberg). K. rest for chin ; O. posiiioii of eye ; Ob, object, white or coloured, which sUdes on the graduated arc B ; f, point fixed by the eye. 744 A MANUAL OF PHYSIOLOGY. great majority are unable to distinguish between red and green. The condition will be most easily understood by considering some of the extraordinary mistakes which may be made by the colour-blind without necessarily leading them to suspect that there is anything abnormal in their vision. Thus, to quote the words of a distinguished writer on this subject, himself a sufferer from the deficiency : ' A naval officer purchases red breeches to match his blue / / A ^/'' ^m Jy/i V^«AP>'' 90 Fig. 267. — Perimetric Chart. Obtained with the perimeter in Fig. 266. Tlie numbers represent degrees of the visual field measured on the graduated arc of the perimeter. uniform ; a tailor repairs a black article of dress with crimson cloth ; a painter colours trees red, the sky pink, and human cheeks blue.' The shoemaker, Harris, the dis- coverer of colour-blindness, picked up a stocking, and was surprised to hear other people describe it as a red stocking ; it seemed to him only a stocking. The celebrated Dalton was twenty-six years of age before he knew that he was colour-blind. He matched samples of red, pink, orange. THE SENSES. 745 and brown silk with green of different shades ; blue both with pink and with violet ; lilac with gray. When the condition of vision in the great majority of the colour- blind is tested by means of the spectrum, it is found that they fall into two classes : (i) A class (of green-blind) by whom the whole of the spectrum from red to yellow is described as yellow of different degrees of brightness (intensity) ; the green appears as a pale yellow with a grey or white band in its midst ; while the violet end is seen as different shades of blue. (2) A class (of red-blind) whose whole spectrum, from red to green, is seen as green of different intensities, the extreme red being entirely invisible. The violet end is blue, as in (i), and there is a band of white or grey near the blue end of the green. The brightest part of the spectrum to a normal eye, and also to a green-blind eye, is the yellow ; to a red-blind person it is the green. This may perhaps explain the terms which the colour-blind employ in describing their less refrangible spectral colours. 'To the green-blind red and yellow are the same colour, but the yellow being the brighter, he looks on red as degraded or darkened yellow. On the other hand, to the red-blind green is brighter than yellow or orange, and these appear as degraded green.'* Sir John Herschell explained Dalton's peculiarity of vision on the hypothesis that he only possessed two, instead of three, primary sensations. On the Young-Helmholtz theory, the missing sensation is supposed to be either red or green. At the intersection of the curves that represent the violet and green sensations (Figs. 263, 264), the red-blind individual will see what he describes as white ; viz., the sensation produced by the stimulation of the only two fibre-groups he possesses. Similarly, at the intersection of the red and violet curves, the green-blind person will see what is white to him. On Hering's theory the colour-blind possess the blue- yellow, but lack the green-red, visual substance. So that on this theory there should be no difference between red- blindness and green-blindness. It is, however, equally difficult to reconcile some of the phenomena of colour- blindness produced by disease (atrophy of the optic nerve) or by abuse of tobacco with the Young-Helmholtz theory, for in some of these cases the only colour seen in the spec- trum is blue, the rest is white ; and the theory does not * Rep. Roy. Soc. Com. on Colour-Blindness. 746 A MANUAL OF PHYSIOLOGY. provide for the production of the sensation of white by excitation of a single group of fibres. Colour-blindness, in its true sense, is always congenital, often hereditary; the colour-blind are ' born, not made.' And although the con- dition cannot be cured, it is of great importance that it should be recognised in the case of persons occupying positions such as those of engine-drivers, railway guards, and sailors, in which coloured lights have to be distin- guished. For, while it is true that the sensations which red and green lights give the colour-blind are far from being identical (Pole) under favourable conditions, it is precisely when the conditions are unfavourable, as in a fog or a snow-storm, that the capacity of distinguishing them becomes invaluable. Irradiation was first described by Kepler, who gave as an example the appearance known as the ' new moon in the old moon's arms,' where the crescent of the new moon seems to overlap and embrace the unilluminated portion of the lunar disc. The white circle on a black ground in Fig. 268 appears, in a good light, to be larger than the exactly equal black circle on a white ground. The ex- planation seems to be as fol- lows ; Owing to the aberration of the refractive media of the eye, all the rays proceeding from the luminous object are not brought accurately to a focus on the retina, and the image is surrounded by diffu- sion circles which encroach upon the unilluminated boundary. Physically these represent a weaker illumination than that of the image proper, and therefore the latter ought to stand out in its real size as a brighter area surrounded by weaker haloes. That this is not the case, and that the image is projected in its full brightness for a certain distance over its dark boundary, is due to two things: (i) That the eye does not recognise very small differ- ences of brightness, and (2) that not only is the neighbourhood of the directly illuminated field stimulated by the light which falls on it in diffusion circles, but the excitation set up in a given area of the retina is propagated for a short distance into the surrounding parts (Descartes). When the accommodation is not perfect, the diffusion circles are, of course, much wider, and irradiation is better marked when the object is a little out of focus. When it is too much out of focus, however, the diffusion circles are no longer blended with the rest of the image ; and since their formation weakens the illumination at the edge of the true image as much as it strengthens the illumination Fig. 268. THE SENSES. 747 beyond the edge, the effect when the Hght is very weak is a negative irradiation. Under these conditions, a white disc on a black ground seems smaller than a black disc on a white ground (Volkmann). The Movements of the Eyes, — That the eyes may be efficient instruments of vision, it is necessary that they should have the power of moving independently of the head. An eye which could not move, though certainly better than an eye which could not see, would yet be as imperfect after its kind as a ship which could run before the wind, but could not tack. The mere fact that the angle between the visual axes must be adapted to the distance of the object looked at renders this obvious ; and the beauty of the intrinsic mechanism of the eyeball has its fitting complement in the precision, delicacy, and range of movement conferred upon it by its extrinsic muscles. Not only are movements of convergence and divergence of the eyeballs necessary in accommodating for objects at different distances, but without compensatory movements of the eyes it would be impossible to avoid diplopia with every movement of the head ; for the images of an object fixed in one position of the head would not continue to fall on corresponding points of the retinae in another position. All the complicated movements of the eyeball may be looked upon as rotations round axes passing through a single point, which to a near approximation always remains fixed, and is situated about 1*77 mm. behind the centre of the eye. * The position which the eyeballs take up when the gaze is directed to the horizon, or to any distant point at the level of the eyes, is called the primary position. Here the visual axes are parallel, and the plane passing through them horizontal. While the head remains fixed in this position, the eyeballs can rotate up or down around a horizontal axis, or from side to side around a vertical axis ; or upwards and inwards, downwards and outwards, downwards and inwards, and upwards and outwards around oblique axes, which always lie in the same plane as the vertical and horizontal axes of rotation, i.e., in the vertical plane passing through the fixed centre of rotation. These facts, spoken of collectively as Listing's law, and first deduced by him from theoretical considerations, were afterwards proved experi- mentally by Helmholtz and Bonders. It necessarily follows from Listing's law (and this is, indeed, another way of stating it) that in moving from the primary position into any other, there is no * The passage in small printmay be omitted by the junior student. 748 A MANUAL OF PHYSIOLOGY. rotation of the eyeball round the visual axis — ^no wheel-movement, as it is called. This is most easily proved in the following manner : A. band of coloured paper, gceen for example, is gummed on a large sheet of gray paper fastened on a vertical board which is free to rotate round a horizontal axis perpendicular to its plane, say an axle supported from a wall at the height of the eye. The gray ground is ruled with parallel lines crossed at right angles by a single line passing through the centre of rotation, and the coloured strip of paper is arranged with its long axis parallel to these, and cutting the centre of rotation of the board. By appropriate means, which need not be described here, it is possible to ensure that the visual line of one eye shall pass through the axis of rotation of the board, while that of the other eye is parallel to it. Now, suppose the board arranged so that the parallel lines on the gray ground are vertical. The eye is moved along the single horizontal line first to one side and then to the other ; and the red after-image of the green band, moving along with it, always remains parallel to the vertical lines. This could not be the case if there was any rolling or rotation of the eye round the visual axis, for the after-image would then cease to be vertical on the retina, and its projection on the gray ground would, therefore, appear inclined. If the board be now rotated till the green stripe is horizontal, and an after-image developed in the sarne way, it is found that no vertical movement of the eye causes the after-image to alter its horizontal position. Similarly, if the board be fixed so that the green band makes any given angle with the horizontal plane, it may be shown that movement of the eye along the single line never causes the after-image to become inclined to the parallel lines ; it always remains parallel to them. This constitutes an experimental proof of Listing's law. A true rotation of the eye round the visual axis does, however, occur when the eyes are converged as in accommodation for a near object, each eyeball rotating towards the temporal side. This is especially the case when the eyes are at the same time converged and directed downwards ; and the rotation may amount to as much as 5°. When the head is rolled from side to side, while the eyes are kept fixed on an object, a slight compensatory rotation of the eyeballs takes place against the direction of rotation of the head. The amount of rotation of the eyes is relatively greater for small than for large movements of the head (eye 5° for head 20° ; eye 10° for head 80° — Kiister). The Extrinsic Muscles of the Eye. — The eyeball is acted upon by six muscles arranged in three pairs, which may be considered, roughly speaking, as antagonistic sets. These are the internal and external recti, the superior and inferior recti, and the superior and inferior obliqui. Although the movements of the eye have been very fully studied, and are, upon the whole, well understood, our THE SENSES. 749 knowledge of the manner in which any given movement is brought about, and the exact action of the muscles which take part in it, is by no means as copious and precise. And from the nature of the case, the greater part of what we do know has been inferred from the anatomical relations of the muscles as revealed by dissection in the dead body rather than gained from actual observation of the living eye. A plane, called the plane of traction, is supposed to pass through the middle points of the origin and insertion of the muscle whose action is to be investigated, and through the centre of rotation of the eyeball. A straight line drawn at right Fig. 269.— Horizontal Section of Left Eve. Arrows show direction of pull of the muscles. The axis of rotation of the external and internarrecti would pass the intersection of " and /S at right angles to the plane of the paper. angles to this plane through the centre of rotation is evidently the axis round which the muscle when it contracts will cause the eye to rotate, provided that the fibres of the muscle are symmetrically distributed on each side of the plane of traction. The axes of rotation of the antagonistic pairs almost, but not completely, coincide with each other. The common axis of the external and internal recti practically coincides with the vertical axis of the eyeball (Fig. 269) in the primary position. The eye is turned towards the temple when the external rectus alone contracts, towards the nose when the internal rectus alone contracts. The common axis of the superior and inferior recti, /3, lies in the horizontal 750 A MANUAL OF PHYSIOLOGY. visual plane in the primary position, but makes an angle of about 20° with the transverse axis, its inner end being tilted forwards. The consequence is that contraction of the superior rectus turns the eye up, and contraction of the inferior rectus turns it down, but both movements are also combined with a slight inward rotation. The common axis of the oblique muscles, a, makes an angle of 60° with the transverse axis, the outer end of it being the most anterior. The direction of traction of the superior oblique is, of course, given not by the line joining its bony origin and its insertion, but by the direction of the portion reflected over the pulley. When the superior oblique contracts alone, the eyeball is rotated outwards and downwards ; the inferior oblique causes an outward and upward rotation. None of the common axes of rotation of the pairs of muscles, except that of the external and internal recti, lies in Listing's plane. Now as we have seen that every movement which the eye, supposed to be originally in the primary position, can execute may be considered as a rotation round an axis in this plane, it is clear that every movement, except truly transverse rotation, must be brought about by more than one pair of muscles. For vertical rotation, the inward pull of the superior rectus is antagonized by a simultaneous out- ward pull of the inferior oblique ; for downward rotation, the inferior rectus and superior oblique act together. In oblique movements, a muscle of each of the three pairs is concerned. HEARING. The transverse vibrations of the ether fall upon all parts of the surface of the body, but only find nerve-endings capable of giving the sensation of light in the little discs which we call the retinse. So the much longer and slower longitudinal waves of condensation and rarefaction which are being constantly originated in the air or im- parted to it by solid or liquid bodies that have been themselves set vibrating fall upon all parts of the surface, but only produce the sensation of sound when they strike upon the tiny mechanism of the internal ear. But just as the ethereal vibrations, and especially those of greater wave-length, are able to excite certain end-organs in the skin which have to do with the sensation of temperature, so the sound-waves, when sufficiently large, are also capable of stimulating certain THE SENSES. 751 cutaneous nerves and of giving rise to a sensation of intermittent pressure or thrill. This is readily perceived when the finger is immersed in a vessel of water into which dips a tube connected with a source of sound, or when a vibrating bell or tuning-fork is touched. So far as we know, what takes place in the ear is essen- tially similar— that is to say, a mechanical stimulation of the ends of the auditory nerve, but a stimulation which acts through, and is graduated and controlled by, a special intermediate mechanism. As the visual apparatus consists of a sensitive surface, the retina, which contains the end-organs of the optic nerve and of dioptric arrangements which receive and focus the rays of light, the auditory apparatus consists of the sensitive end- organs of the eighth nerve and of a mechanism which receives the sound-waves and communicates them to these. f h h m, external meatus ; /I head of malleus ; h, o, short process of malleus ; i ^i;, handle of malleus : 'g h, incus ; £ /, foot of stapes in oval foramen e, tyiiipanic membrane. Fig. 270. — The E.\r. Physiological Anatomy of the Ear. — At the bottom of the external auditory meatus lies the membrana tympani, a nearly circular mem- brane set like a drum-skin in a ring of bone, and separating the meatus from the tympanum or middle ear. Its external surface looks obliquely downwards, and at the same time somewhat forwards, so that if prolonged the membranes of the two ears would cut each other in front of, and also below, the horizontal line passing through the centre of each (Figs. 270, 271). The tympanum contains a chain of little bones stretching right across it from outer to inner wall. Of these the malleus, or hammer, is the most external. Its manubrium, or handle, is inserted into the membrana tympani, which is not stretched taut within its bony ring, but bulges inwards at the centre, where the handle of the malleus is attached. The stapes, or stirrup, is the most internal of 752 A MANUAL OF PHYSIOLOGY. the chain of ossicles, and is inserted by its foot-plate into a small oval opening — the foramen ovale — on the inner wall of the tympanic cavity. A membranous ring — the orbicular membrane — surrounds the foot of the stapes, helping to fill up the foramen and attaching the bone to its edges. The incus, or anvil, forms a link between the malleus and the stapes. The auditory ossicles, as well as the whole cavity of the tympanum, are covered by pavement epithelium. The tympanum is not an absolutely closed chamber; it has one channel of communication with the external air — the Eustachian tube. By the action of the cilia which line this tube the scanty secretion of the middle ear is moved towards its pharyngeal opening. The loosely- jointed chain of ossicles is steadied and its movements directed by ligaments and by the tension of its terminal membranes. It forms a kind of bent lever, by which the oscillations of the membrana tympani are transferred to the membrane covering the oval foramen, and at the same time reduced in size. Two slender muscles, the tensor tympani and stapedius, contained in the tympanic cavity, are also connected with and may act upon the ossicles. The former lies in a groove above the Eustachian tube, and its tendon, passing round a kind of osseous pulley (processus cochleariformis), is inserted into the handle of the malleus ; the stapedius is lodged in a hollow of the inner bony wall of the tympanum. Its tendon is attached to the neck of the stapes near its articulation with the incus. This inner wall is pierced not only by the oval foramen, but also by a round opening, the fenestra rotunda, which is closed by a membrane to which the nalne of secondary membrana tympani is sometimes given. The internal ear consists of the bony labyrinth, a series of curiously excavated and communicating spaces in the substance of the petrous portion of the temporal bone, filled with a liquid called the peri lymph, in which, anchored by strands of connective tissue, floats a corresponding series of membranous canals (the membranous laby- rinth), filled with a liquid called endolymph. The labyrinth of the internal ear is divided into three well-marked parts : the cochlea, the vestibule, and the semicircular canals (Fig- 271). The cochlea, the most anterior of the three, consists of a convoluted tube which coils round a central pillar or modiolus like a spiral staircase. The lamina spiralis, which, except that it forms a continuous surface, may be taken as representing the steps, projects from the modiolus and divides the tube into an upper compartment, the scala vestibuli, and a lower, the scala tympani (Fig. 272). The part of the lamina next the modiolus is of bone, but it is completed at its outer edge by a membrane, the lamina spiralis membranacea. The scala tympani abuts on the fenestra rotunda, and its perilymph is only separated from the air of the tympanic cavity by the membrane which closes that opening. At the apex of the cochlea the lamina spiralis is incomplete, ending in a crescentic border, so that the scala tympani and the scala vestibuli here communicate by a small opening, the helicotrema. The scala vestibuli communicates with the vestibule, and the vestibule with the semicircular canals, so that the peri- lymph of the entire labyrinth forms a continuous sheet, separated THE SENSES. from the cavity of the middle ear by the structures that fill up the round and oval foramina. In the membranous labyrinth, and in it alone, are contained the end organs of the auditory nerve. The membranous portion of the cochlea is a small canal of triangular section, cut off from the scala vestibuli by Vesti lule iirith Scala Vestibuli ...,. m"k openings cf Senitcircular Canals Cochlea! llncus [Malleus .Stanes Scala': Tymnani ^^^ Ext.Aud.Meoh/s ^.Membrana Tymnani ..Eustachian tube Fig. 271.— Middle and Internal Ear (Uiagram.matic). the membrane of Reissner, which stretches from near the edge of the bony spiral lamina to the outer wall (Fig. 272). It has received the name of the scala media, or canal of the cochlea. Below it ends blindly, but communicates by a side-channel with the portion of the membranous vestibule called the saccule, which in its turn communicates with the utricle by a Y-shaped sac, the saccus endo- FiG. 272. — IKANSVERSE Section of a Tl'rn of the Cochlea (Diagrammatic). lymphaticus. Into the utricle open the three semicircular canals, the endolymph of which has, therefore, free communication with that of the vestibule and cochlea. But although the semicircular canals and vestibule belong anatomically to the internal ear, and are supplied by branches of the auditory nerve, we have no positive 48 754 A MANUAL OF PHYSIOLOGY. proof that in the higher animals, at least, they are in any way con- cerned in hearing ; and since experiment has assigned them, with a great degree of probability, a definite function of another kind (p. 645), we shall not consider them further in this connection. The scala media contains the organ of Corti, which (Fig. 272) consists of a series of modified epithelial cells planted upon the membranous spiral lamina or basilar membrane. The most con- spicuous constituent of the latter is a layer of parallel transparent fibrils. The epithelial cells are of two kinds: (i) the pillars or rods of Corti, sloped against each other like the rafters of a roof, and covering in a vault or tunnel which runs along the whole of the scala media from the base to the apex of the cochlea ; (2) the hair-cells, which are columnar epithelial cells running out below into processes connected with the terminal fibres of the auditory nerve, and surmounted by hairs. They are arranged in several rows, one row lying just internal to the inner line of pillars, and four or five rows external to the outer line of pillars. A thin membrane, the membrana reticularis, covers the pillars and hair-cells of Corti, and is pierced by the hairs ; while a thicker membrane, the membrana tectoria, springing from the edge of the osseous spiral lamina near the attachment of Reissner's membrane, forms a kind of canopy over both pillars and hair-cells. The fact that the hair-cells of Corti's organ are connected with the fibres of the cochlear division of the auditory nerve, and its elaborate structure suggest that it must play a peculiar part in auditory sensation. Comparative anatomy shows us that the cochlea is the most highly-developed portion of the internal ear, the last to appear in its evolution, and the most specialized. It is absent in fishes, which possess only a vestibule and one to three semicircular canals. It first acquires importance in reptiles, but attains its highest development in mammals ; and there is every reason to believe that it is the terminal apparatus of the sense of hearing. Function of the Auditory Ossicles. — The anatomical arrangements of the middle ear suggest that the tympanic membrane and the chain of ossicles have the function of transmitting the sound-waves to the liquids of the labyrinth ; and observation and experiment fully confirm this idea. Tracings of the movements of the ossicles have been obtained by attaching very small levers to them, and their movements have been directly observed with the microscope. Even in man it may be shown, by viewing the membrane through a series of slits in a rapidly-revolving disc (strobo- scope), that it vibrates when sound-waves fall on it. When the handle of the malleus moves inwards, the joint between that bone and the incus is locked, on account of the shape of the articular surfaces, and the stapes is pressed THE SENSES. 755 into the oval foramen. When the tympanic membrane passes outwards, the handle of the malleus and foot of the stapes do the same. But the joint now unlocks, and exces- sive outward movement of the stapes, which might result in its being torn from its orbicular attachment, is prevented. The ossicles vibrate en juasse. It is only to a trifling extent that sound can be conducted through them to the labyrinth as a molecular vibration ; for when they are anchylosed, and the foot of the stapes fixed immovably in the foramen ovale, as sometimes occurs in disease, hearing is greatly impaired. Of course, every vibration of the tympanic membrane must cause a corresponding condensation and rarefaction of the air in the middle ear ; and this may act on the mem- brane closing the fenestra rotunda, and set up oscillations in the perilymph of the scala tympani. That this is a possible method of conduction of sound is shown by the fact that, even after closure of the oval foramen, a slight power of hearing may remain. But under ordinary conditions by far the most important part of the conduction takes place via the ossicles. And when it is remembered that the tympanic membrane is about thirty times larger than that which fills the oval foramen, it will be seen that the force acting on unit area of the foot of the stapes may be much greater than that acting on unit area of the membrana tympani, and that the mode of transmission by the ossicles is a very advantageous method of transforming the feeble but comparatively large excursion of the tympanic membrane into the smaller but more powerful movements of the stapes. Even the so-called cranial conduction of sound which takes place when a tuning- fork is held between the teeth or put in contact with the head, and which was at one time supposed to be due to direct transmission of the vibrations through the bones of the skull to the liquids of the labyrinth or the end-organs of the auditory nerve, has been shown to take place, in great part at least, through the membrana tympani and ossicles ; the vibrations travel through the bones to the tympanic mem- brane, and set it oscillating. So that this test can no longer be regarded as sufficient to distinguish deafness caused by 756 A MANUAL OF PHYSIOLOGY. disease of the middle ear from deafness due to disease of the labyrinth or the central nervous system, although it enables us to say whether the auditory meatus is blocked (by wax, e.g.) beyond the tympanic membrane. When a tuning-fork is held between the teeth, a part of the sound passes out of the ear from the vibrating membrana tympani ; if one ear is closed, the sound is heard better in this than in the open ear. If the tuning-fork is held before the ear till it just ceases to be heard, it will still be heard on placing it between the teeth ; if it be kept there till it again becomes inaudible, it will be heard for a short time if one or both ears be stopped ; and when in this position the sound again becomes inappreciable, it can still be caught if the handle be introduced into the auditory meatus. A membrane, like a drum-head, has a note of its own, which it gives out when struck, and it vibrates more readily to this note than to any other. But the tympanic membrane receives all kinds of vibrations, and responds to all ; so that if it is in reality attuned to any particular note, the effect is weakened in some way or other, and does not obtrude itself The damping of the movements of the membrane by the ossicles and the liquids of the labyrinth may partly account for this ; and it is to be remembered also that it is not stretched, but lies slackly in its bony frame, so that when the handle of the malleus is detached from it, it retains its shape and position. The tensor tympani, when it contracts, pulls inwards the handle of the malleus, and thus increases the tension of the tympanic mem- brane. The precise object of this is obscure. It has been suggested that damping of the movements of the auditory ossicles is thus secured ; but another theory is that the increased tension of the membrane renders it more capable of responding to higher tones, and that the muscle thus acts as a kind of accommodating mechanism. But Hensen has observed that the tensor only contracts at the beginning of a sound, and relaxes again when the sound is continued ; and this is difficult to reconcile with either of these hypotheses. The muscle is normally excited reflexly through the vibrations of the membrana tympani, but some individuals have the power of throwing it into voluntary contraction, which is accompanied by a feeling of pressure in the ear and a harsh sound. The function of the stapedius is unknown. Its contraction would tend to press the posterior end of the foot-plate of the stapes deeper into the foramen ovale, and cause the anterior end to move in the opposite direction ; but it is not easy to see how this would affect the action of the auditory mechanism. A desire to explain everything, so far as the fitting of a phrase to every fact can explain, has led to the suggestion that the role of the stapedius is to damp the oscillations of the stapes and orbicular ligament when very loud sounds are listened to, and thus prevent shocks of too great intensity from being transmitted to the labyrinth. The tensor tympani is supplied by the fifth nerve through a branch from the otic ganglion ; the stapedius is supplied by the seventh. THE SENSES. 757 Paralysis of the fifth nerve may be accompanied with difficulty of hearing, especially for faint sounds. When the seventh nerve is paralyzed, increased sensitiveness to loud sounds has been observed. The Perception of Pitch — Analysis of Complex Sounds. — As the eye, or, rather, the retina plus the brain, can perceive colour, so the labyrinth plus the brain can perceive pitch. The colour-sensation produced by ethereal waves of definite frequency depends on that frequency ; and upon the fre- quency of the aerial vibrations depends also the pitch of a musical note. But there is this difference between the eye and the ear : that while the sensation produced by a mixture of rays of light of different wave-length is always a simple sensation — that is, a sensation which we do not perceive to be built up of a number of sensations, which, in other words, we do not analyze — the ear can perceive at the same time, and distinguish from each other, the components of a com- plex sound. When a number of notes of different pitch are sounded together at the same distance from the ear, the disturbance which reaches the membrana tympani is the physical resultant of all the disturbances produced by the individual notes, and it strikes upon the membrane as a single wave. The ear or brain must, therefore, possess the power of resolving the complex vibrations into their con- stituents, else we should have a mixed or blended sensation, and not a sensation in which it is possible to distinguish the constituents of which it is made up. Two chief hypotheses have been proposed to explain this physiological analysis of sound : (i) the theory that the analysis takes place in the labyrinth ; (2) the theory that it takes place in the brain. (i) Helmholtz attempted to explain the perception of pitch on the assumption that in the internal ear there exists a series of resonators, each of which is fitted to respond by sympathetic vibration to a particular note, while the others are unaffected ; just as when a note is sung before an open piano it is taken up by the string which is attuned to the same pitch and ignored by the rest. Let us suppose that a given fibre of the auditory nerve ends in an organ which is only set vibrating by waves impinging on it at the rate of 100 a second, and that the end-organ of another fibre is 758 A MANUAL OF PHYSIOLOGY. only influenced by waves with a frequency of 200 a second. Then, on the doctrine of ' specific energy ' (according to which the sensation caused by stimulation of a nerve depends not on the particular kind of stimulus but on the anatomical connection of the nerve with certain nerve centres), in whatever way the first fibre is excited, a sensation corresponding to a note with a pitch of 100 a second will be perceived. Whenever the second fibre is excited, the sensation will be that of a note of 200 a second, or the octave of the first. If both fibres are excited at the same time the two notes will be heard together. Now, Hensen actually observed that in the auditory organs of some crustaceans the hair-like processes of certain epithelial cells can be set swinging by waves of sound, and, further, that they do not all vibrate to the same note unless the sound is very loud. In the lobster there are between four and five hundred of these hairs, varying in length from 14 /^ to 720 /x ; and in some insects, such as the locust, similar hairs, also graduated in length, exist. To gain an anatomical basis for his theory, Helmholtz supposed first of all that the pillars of Corti were the vibrating structures, and that, directly or through the hair- cells, their mechanical vibrations were translated into impulses in the auditory nerve-fibres. But apart from the fact that their number is too small (about 3,000) to allow us to assign one rod to each perceptible difference of pitch, and their dimensions too similar to permit of the requisite range of vibration frequency, it was pointed out that birds do not possess pillars of Corti — a fact which was decisive against the assumption of Helmholtz, since nobody denies to singing birds the power of appreciating pitch. Helmholtz accordingly, choosing between the remaining possi- bihties, gave up the pillars of Corti and adopted the radial fibres of the basilar membrane as his hypothetical resonators. But while it is true that these are much more adequate to the task imposed on them, since their range of length is far greater (41 /i at the base to 495 yx at the apex of the cochlea) (Hensen) ; and while the structure of Corti's organ certainly suggests that some one or other of its elements may be THE SENSES. 759 endowed with such a function, the theory of peripheral analysis of pitch tends upon the whole rather to break down than to be strengthened as evidence gathers. When two notes of different frequency are sounded together, they ' interfere ' with each other. If two tuning-forks A and B, making 100 and loi vibrations a second respectively, be started together, at the end of the first vibration of A, B will be y^o^h of a vibration ahead, at the end of the second i^^ths of a vibration, at the end of the fiftieth half a vibration. Here the crest of B's wave will coincide with the trough of A's, and if the forks are vibrating with the same amplitude the resultant for this vibration will be zero, the wave will be blotted out. If the amplitudes are not the same, the wave will still be weakened. At the end of the hundredth vibration of A, IJ will have gained a whole vibration, the tops of the two waves will coincide, and the sound will be strengthened. We recognise the alternate changes in the amplitude of the interfering sound waves by a change in the auditory sensation, which is called a beat : and in the case supposed there will be one beat a second. If the difference in the frequency of the forks is five there will be five beats a second. If the difference is twenty there will be twenty beats a second. As the difference is increased the beats will ultimately follow each other so rapidly that they will themselves be fused into a note — a beat-tone, as it is called, whose pitch will correspond to the frequency of the beats. Now, Hermann has found that the ear may perceive a beat- tone which elicits no response from a resonator attuned to its note and readily set into vibration by the same note when sounded by a tuning- fork. This shows that the process by which pitch is appreciated, whatever it may be, is not entirely explicable on the theory of resonance. (2) The second theory, in accordance with the simile used by Rutherford, to whom we owe it in its present form, may be conveniently labelled the ' telephone theor}'.' He sup- poses that the organ of Corti (or, at any rate, the hair-cells) is set into vibration as a whole by all audible sounds, and that its vibrations are translated into impulses in the auditory nerve, which are the physiological counterpart of the aerial waves and the waves of increased and diminished pressure in the liquids of the labyrinth to which they give rise. Thus, a sound of 100 vibrations a second would start 100 impulses a second in the auditory nerve ; a loud sound would set up impulses more intense than a feeble sound ; and a complex wave, which is the resultant of several sounds of different vibration-frequency, would also in some way or other stamp the impress of its form on the auditory 76o A MANUAL OF PHYSIOLOGY. excitation-wave ; just as in a telephone every wave in the air causes a swing of the vibrating plate, and thus sets up a current of corresponding intensity and duration in the wires. This theory evidently abandons the doctrine of specific energy for the particular case of the analysis of pitch, for it assumes that differences of auditory sensation are related to differences in the nature of the impulses travelling up the auditory nerve, and not merely to differences in the anatomical connections (peripheral and central) of the auditory nerve-fibres. Smell and Taste. Smell was defined by Kant as ' taste at a distance ' ; and it is obvious that these two senses not only form a natural group when the quality of the sensations is considered, but are closely associated in their physiological action, especi- ally in connection with the perception of the flavour of the food. The olfactory end-organs are situated in the mucous membrane of the upper part of the nostrils, the so-called regio olfactoria. They are cells prolonged externally into long narrow rods which terminate at the free surface of the mucous membrane, and prolonged towards their deep ends into processes which become continuous with fine branches of the first nerve. These olfactory cells are scattered among the ordinary cylindrical cells which line the mucous mem- brane. In cases of anosmia, in which the olfactory nerve is absent or paralyzed, smell is abolished ; but substances such as ammonia and acetic acid, which stimulate the ordinary sensory nerves (nasal branch of fifth) of the olfactory mucous membrane, are still perceived though not distinguished from each other. In fact, the so-called pungent odour of these substances is no more a true smell than the sense of smarting they produce when their vapour comes in contact with a sensory surface like the conjunctiva or a piece of skin devoid of epidermis. It was at one time believed that odoriferous particles could not be appreciated unless they were borne by the air into the nostrils ; but this appears not to be the case, for THE SENSES. 761 the smell of substances dissolved in normal saline solution is distinctly perceived when the nostrils are filled with the liquid ; and fish, as every line-fisherman knows, have no difficulty in finding a bait in the dark. Beaunis has classified the substances which can affect the olfactory mucous membrane as follows : 1. Those which act only on the olfactory nerves : a. Pure scents or perfumes, without pungency. b. Odours with a certain pungency, e.g.^ menthol. 2. Substances which act at the same time on olfactory nerves and on nerves of common sensation (tactile nerves), e.g., acetic acid. 3. Substances which act only on the nerves of common sensation (tactile nerves), f.^^., carbonic acid. Electrical excitation of the olfactory mucous membrane causes a sensation like the smell of phosphorus. The sensation is experienced at the kathode on closure and the anode on opening. Taste, — The sense of taste is not so strictly localized as the sense of smell. The tip and sides of the tongue, its root, the neighbouring portions of the soft palate, and a strip in the centre of the dorsum, are certainly endowed with the sense of taste ; but the exact limits of the sensitive areas have not been defined, and, indeed, seem to vary in different individuals. The nerves of taste are the glosso-pharyngeal, which innervates the posterior part of the tongue ; and the lingual, which supplies its tip. The end-organs of the gustatory nerves are the taste-buds or taste-bulbs, which stud the fungiform and circumvallate papillae, and are most characteristically seen in the moats surrounding the latter. They are barrel-like bodies, the staves of the barrel being repre- sented by supporting cells ; each bud encloses a number of gustatory Cells with fine processes at their free ends projecting through the superficial end of the barrel. Their deep ends also terminate in processes which become continuous with the fibres of the gustatory nerves. As to the properties in virtue of which sapid substances are enabled to stimulate the gustatory nerve endings, we know that they must be soluble in the liquids of the mouth, and there our knowledge ends. An attempt has been made by various authors to connect the taste of such bodies with their chemical composition, but researches of this kind have not hitherto yielded much fruit. Sapid substances have 762 A MANUAL OF PHYSIOLOGY. been divided into four classes : i, sweet ; 2, acid ; 3, bitter ; 4, saline. Sweet and acid tastes are best appreciated by the tip, and bitter tastes by the base, of the tongue. Normal lymph, which bathes the gustatory end-organs, does not excite any sensation or taste, bu: when the composition of the blood is altered in disease or by the introduction of foreign substances, tastes of various kinds may be perceived. Sometimes this may be due to the stimulation of substances excreted in the saliva; but in other cases it seems that, without passing beyond the blood and lymph, foreign substances may excite the gustatory nerves. When a constant current is passed through the tongue, an acid taste is experienced at the positive, and an alkaline taste at the nega- tive, pole ; and it is said that this is the case even when the current is conducted to and from the tongue by unpolarizable combinations, which prevent the deposition of electrolytic products on the mucous membrane (p. 471). Flavour is a mixed sensation, in which smell and taste are both concerned, as is shown by the common observation that a person suffering from a cold in the head, which blunts his sense of smell, loses the proper flavour of his food, and that some nauseous medi- cines do not taste so badly when the nostrils are held. In common speech, the two sensations are frequently confounded ; thus the ' bouquet ' of wines, which most people imagine to be a sensation of taste, is in reality a sensation of smell ; the astringent ' taste ' of tannic acid is not a taste at all, but a tactile sensation ; the ' hot ' taste of mustard is no more a true sensation of taste than the sensation produced by the same substance when applied in the form of a mustard poultice to the skin. Tactile Sensations. Under the sense of touch it is usual to include a group of sensations which differ in quality — and that in some instances to as great an extent as any of the sensations which are universally considered as separate and distinct — but agree in this, that the end-organs by which they are perceived are all situated in the skin, the mucous membrane, or the subcutaneous tissue. Such are the common tactile sensations — including pressure — and the sensations of tem- perature, or, more correctly, of change of temperature. The sensation of pain cannot be justly grouped along with these. It is called forth by excessive stimulation of any of the sense- THE SENSES. 7(^3 organs, or by the stimulation of afferent nerve-fibres in their course ; and it may originate, under certain conditions, in internal organs which are devoid of tactile sensibility, and the functional activity of which in their normal state gives rise to no special sensation at all. The peculiar sen- sation associated with voluntary muscular effort, to which the name of the muscular sense has been given, also deserves a separate place ; for although it may in part depend on tactile sensations set up through the medium of end-organs situated in muscle, tendon, or the structures which enter into the formation of the joints, other elements are, in all probability, involved. The simplest form of tactile sensation is that of mere contact, as when the skin is lightly touched with the blunt end of a pencil. This soon deepens into the sensation of pressure if the contact is made closer ; and eventually the sense of pressure merges into a feeling of pain. It is not easy to say whether these various sensa- tions are due to the stimulation of different nervous elements, or to different grades of stimulation of the same elements. But there is some pathological evidence in favour of the former view, e.g., it is said that the sensation of contact is abolished in cicatrices where the true skin has been destroyed, although sensibility to pressure persists. The existence of different forms of sensory end-organs in the skin and other tissues (touch-corpuscles, corpuscles of Pacini, end-bulbs of Krause, etc.) is also, so far as it goes, in favour of tke same view. The minimum pressure necessary to evoke a sensation of contact is not the same for every portion of the skin. The fore- head and palm of the hand are most sensitive. If two points of the skin are touched at the same time there is a double sensation when the distance between the points exceeds a certain minimum, which varies for different parts of the sensitive surface. Distance at which two points can be distinctly felt, in mm. Point of tongue - IT Palmar surface of third phalanx of finger 2*2 Dorsal surface of third phalanx of finger 6-7 Tip of nose 67 Back - - - - II"2 Eyelids II"2 Skin over sacrum 40"5 Upper arm 67-6 764 A MANUAL OF PHYSIOLOGY. Practice increases the acuity of touch. Even in a few hours it may be temporarily quadrupled on some parts of the skin. Since at the same time it is increased in the corresponding part of the opposite side of the body, it is argued that the modification takes place in the central nervous system, not in the end-organs them- selves. Few of the internal organs seem to be supplied with tactile nerves. The movements of a tapeworm in the intes- tines are not recognised as tactile sensations, nor the move- ments of the alimentary canal during digestion, nor the rubbing of one muscle on another during its contraction. It would seem that pressure is only perceived when it affects two neighbouring areas to a different degree. Thus, the atmospheric pressure, bearing uniformly on the whole surface of the body, causes no sensation ; we are so entirely unconscious of it that it needed the inspiration of genius to discover it, and the patience of genius to force the discovery on the world. When the finger is dipped in a trough of mercury at its own temperature, no sensation is perceived except a feeling of constriction at the surface of the liquid. Sensations of Temperature. — When a body colder or hotter than the skin is placed on it, or when heat is in any other way withdrawn from or imparted to the cutaneous tissues with sufficient abruptness, a sensation of cold or heat is experienced. And when two portions of the skin at different temperatures are put in contact, we feel that, relatively to one another, one is warm and the other cold. But it is worthy of remark that it is only difference of temperature, and not absolute height, that we are able to estimate by our sensations. Thus, a hand which has been working in ice-cold water will feel water at io° as warm ; whereas it would appear cold to a warm hand. When the temperature of the skin is raised above or diminished below a certain limit, the sensation of change of temperature gives place to one of pain ; and this may be considered as due either to excessive stimulation of the end-organs of the temperature sense, or as due to stimulation of the ordinary sensory nerves, which are normally insensible to more moderate variations of temperature. The recent researches of Blix, Goldscheider and others have thrown new light upon the anatomical basis of the sensations which have their origin in the skin. They have THE SENSES. 765 found that the whole skin is not endowed with the capacity of distinguishing temperature. The temperature sense is confined to minute areas scattered over the cutaneous surface, some of which are * cold ' points, i.e., respond to variations of temperature only by a sensation of cold, while others are ' warm ' points and respond only by a sensation of heat. ' Cold ' points are present in greater number than 'warm.' It has even been stated that electrical or mechani- cal or thermal stimulation of a nerve-trunk like the radial in its course, may give rise to sensations of temperature. But there is strong evidence on the other side, and even if this were shown to be the case, it might be due merely to excitation of nerves of the temperature sense supplying the sheath (nervi nervorum). When a nerve is compressed, the sensibility of the tract supplied by it disappears for cold sooner than for heat. The simplest explanation of these facts seems to be that the skin is supplied with several kinds of nerve-fibres, anatomically as well as functionally distinct. Some fibres minister to the sensation of cold, others to that of heat, others to that of pressure, others, perhaps, to that of contact, and, possibly, others still to common sensation. And just as stimulation of the optic nerve gives rise to a sensation of light, so stimulation of any one of the cutaneous nerves gives rise to the specific sensation proper to the group to which it belongs. But with the eyes closed a thermal may sometimes be mistaken for a tactile stimulus. It is not only of physiological interest, but of practical importance, that most mucous membranes are in comparison with the skin but slightly sensitive to changes of temperature ; some, as the mucous membrane of the greater portion of the alimentary canal, seem to be entirely devoid of nerves of temperature. Only towards its ends in the mouth, pharynx and rectum, and to some extent in the stomach does a blunted sensibility appear. The uterus, too, is quite insensible to heat ; and hot liquids may be injected into its cavity at a temperature higher than that which can be borne by the hand, without causing inconvenience — a fact which finds its application in the practice of gynaecology and obstetrics. It is, indeed, obvious that in the greater number of the internal organs the conditions necessary for stimulation of temperature nerves, even if such were present, could hardly ever exist. It has already been mentioned that changes of external temperature exert a remarkable influence on the intensity of metabolism (p. 437), and it has been supposed that this is brought about by afferent impulses travelling up the cutaneous nerves. We have also seen that for certain kinds of stimuli the excitability of nerve-fibres is 766 A MANUAL OF PHYSIOLOGY. increased by cooling (p. 522). It is possible that this is the case for the fibres in the skin which are concerned in the regulation of the production of heat, and it has been suggested that this fact may have a bearing on the reflex regulation of temperature (Lorrain Smith). The Muscular Sense. Voluntary muscular movements are accompanied with a peculiar sensation of effort, graduated according to the strength of the contraction, and affording data from which a judgment as to its amount and direction may be formed. To these sensations the name of the muscular sense has been given. Some writers have supposed that the muscular sense does not depend upon afferent impulses at all ; but that the nervous centres from which the voluntary impulses depart, take cognizance, retain a record, so to speak, of the quantity of outgoing nervous force ; that the effort which we feel in lifting a heavy weight is an effort of the cells of the motor centres from which the innervation of the groups of muscles takes origin, and not of the muscles themselves. But although this feeling of central effort or outflow (we can hardly say of central fatigue) may play a part in the muscular sense, it cannot be doubted that the brain is kept in touch with the contracting muscle by impulses of various kinds which reach it by different afferent channels. The corpuscles of Pacini, which exist in considerable numbers in the neighbourhood of joints and ligaments, and in the periosteum of bones, would seem well fitted to play the part of end-organs for the tactile sensations caused by the movements of flexion, extension, or rotation of one bone on another, which form so large a portion of all voluntary muscular movements. And it has been stated that paralysis of these bodies in the limbs of a cat by section of the nerves going to them causes a characteristic uncertainty of move- ment which suggests that something necessary to normal co-ordination has been taken away. We have already seen that the skeletal muscles possess numerous afferent fibres (p. 644). Some of these may be nerves of ordinary sensation. For although, when a muscle is laid bare in man and stimulated electrically, the sensation does not in general amount to actual pain, it is capable, under the influence of strong stimuli, of taking on a painful character. And nobody who has felt the severe and sometimes almost intolerable pain of muscular cramp would be likely to deny the existence of sensory muscular nerves. THE SENSES. 767 But after deducting these, we must assume that a very large proportion of the afferent nerves of muscle have other functions, and among them may be the conveyance of impulses connected with the muscular sense. In the spinal cord, these impulses are probably conducted up through the posterior column ; and, although nothing is known as to the paths they follow in the higher parts of the central nervous system, it is certain that there is some afferent bond of connection between the cortical motor areas and the muscles which they control (p. 667). Tactile sensations set up in the skin or mucous membrane lying over contracting muscles may also help the nervous motor mechanism in appreciating and regulating the amount of contraction ; but the fact that, in anaesthesia of the mucous membrane covering the vocal cords produced by cocaine, the voice is not at all impaired, shows that muscular contractions of extreme nicety can be carried on without any such aid. Pain. Pain has been defined as 'the prayer of a nerve for pure blood.' The idea is not only true as poetry, but, with certain deductions and limitations, true as physiology. That is to say, pain, as a rule, is a sign that something has gone wrong with the bodily machinery ; freedom from pain is the normal state of the healthy body. Physio- logically, pain acts as a danger-signal ; it points out the seat of the mischief, and even, in certain cases, by compelling rest favours the process of repair. Thus, the surgeon has sometimes looked upon pain as 'Nature's splint.' But as a matter of fact, a certain amount of pain occurring at intervals is not incompatible with high health ; and probably nobody, even when accidents and indiscretions of all kinds are avoided, is entirely free from pain for any considerable time. Sometimes, indeed, the mere fixing of the attention on a particular part of the body is sufficient to bring out or to detect a slight sensation of pain in it ; and it is matter of common experience that a dull continuous pain, like that of some forms of toothache, is aggravated by thinking of it, and relieved when the attention is diverted. In general, the skin is far more sensitive to pain than the deeper structures. The most painful part of an operation is generally the stitching of the wound. The cutting of healthy muscle causes no pain. The spasmodic contraction of the intestines and stomach causes the intense pain of colic and gastralgia. Labour is an example of a strictly physiological function which is the occasion of severe pain. Tissues normally insensible to pain may become acutely painful when inflamed. It is not quite settled as yet whether the afferent fibres which minister to painful sensations are anatomically distinct from the fibres of tactile sensation, and of the other sensations included under 768 A MANUAL OF PHYSIOLOGY. the sense of touch ; but, upon the whole, the balance of evidence, physiological and pathological, seems to incline to the view that there is such a distinction. For the conducting paths in the spinal cord appear not to be the same for tactile and for painful impressions. And in certain cases of disease sensibility to pain may be lost, while tactile sensations are still perceived ; or on the other hand pain may be felt in cases where tactile sensibility is abolished. Relation of Stimulus to Sensation. It is impossible to measure sensation in terms of stimulus. All that we can do is to compare differences in the intensity of stimuli and differences in the resultant sensations, or, in other words, to compare stimuli together and to compare sensations together. And when we determine the amount by which a given stimulus must be increased or diminished in order that there may be a just perceptible increase or diminution in the sensation, it is found that (with certain limitations) the two are connected by a simple law : Whatever the absolute strength of a stimulus of given kind may be, it ?nust be increased by the same fraction of its amount in order that a difference in the sensation may be perceived (sometimes called Weber's hnv). Thus a light of the strength of one standard candle must be increased by T^o^h candle, a light of lo candles by yVV^^' ^"^ ^ '^S^^ ^^ ^°° candles by a candle, in order that the eye may perceive that an increase has taken place, just as the weight necessary to turn a balance increases with the amount already in the pans. The frac- tion varies for the different senses. It is about j-^q- for light, \ for sound. But it would appear that Weber's law does not hold for the pressure sense, nor for the other senses above and below certain limits. Fechner, making various assumptions, has thrown Weber's l0£ X law into the form y = k — ^-- , where y is the intensity of sensation, X the intensity of stimulation, and .y^, the smallest mtensity of stimulus which can be perceived (liminal intensity). This so-called psycho-physical law of Fechner states that the sensation varies as the logarithm of the stimulus. But Fechner's law has been subjected to serious criticism, and the subject cannot be further pursued here. PRACTICAL EXERCISES ON CHAPTER XIII. I. Formation of Inverted Image on the Retina. — Fix the eye of an ox or of a dog or rabbit (preferably an albino), after removal of part of the posterior surface of the sclerotic, in a hole cut in a blackened box. Place a candle in front of the eye. Look from behind, and observe the inverted image of the candle formed on the retina. Move the candle until the image is as sharp as possible. Now bring between the candle and the eye a concave spectacle-glass. PRACTICAL EXERCISES. 769 Fig. 273.^Phakoscope. The image becomes blurred, the candle must be put farther away to render it distinct, and perhaps no position of the candle can be found which will give a sharp image. If the glass is convex, the candle must be brought nearer, and a sharp image can always be formed by bringing it near enough. If both a convex and a concave glass be placed in front of the eye, they will partially or wholly neutralize each other. 2. Helmholtz's Phakoscope (Fig. 273). — This instrument is em- ployed in studying the changes that take place in the curvature of the lens during accommodation. It is to be used in a dark room. A candle is placed in front of the two prisms P, P'. The observer looks through the hole B ; the observed eye is placed opposite the hole A. The candle or the observed eye is moved till the observer sees three pairs of images, one pair, the brightest of all, reflected from the an- terior surface of the cornea ; another, the largest of the three, but dim, reflected from the anterior surface of the lens ; and a third pair, the smallest of all, re- flected from the posterior surface of the lens (Fig. 236). The last two pairs can, of course, only be seen within the pupil. The observed eye is now focussed first for a distant object (it is enough that the person should simply leave his eye at rest, or imagine he is looking far away), and then for a near object (an ivory pin at A). During accommodation for a near object no change takes place in the size, brightness, or position of the first or third pair of images ; therefore the cornea and the posterior surface of the lens are not altered. The middle images become smaller, somewhat brighter, approach each other, and also come nearer to the corneal images. This proves {a) that the anterior surface of the lens undergoes a change ; (/-') that the change is increase of curvature (diminution of the radius of cur- vature), for the virtual image reflected from a convex mirror is smaller the smaller is its radius of curvature. (The third pair of images really undergo a slight change, such as would be caused by a small increase in the curvature of the posterior surface of the lens ; but the student need not attempt to make this out.) 3. Scheiner's Experiment. — Two small holes are pricked with a needle in a card, the distance between them being less than the diameter of the pupil. The card is nailed on a wooden holder, and a needle stuck into a piece of wood is looked at with one eye through the holes. When the eye is accomm.odated for the needle, it appears single; when it is accommodated for a more distant object, or not accommodated at all, the needle appears double. The two images approach each other when the needle is moved away from the eye, 49 770 A MANUAL OF PHYSIOLOGY. and separate out from each other when it is moved towards the eye. When the eye is accommodated for a point nearer than the needle, the image is also double ; the images approach each other when the needle is brought closer to the eye, and move away from each other when it is moved away from the eye. If while the needle is in focus one of the holes be stopped by the finger, the image is not affected. When the eye is focussed for a greater distance than that of the needle, stopping one of the holes causes the image on the other side of the field of vision to disappear • if the eye is focussed for a smaller distance, the image on the same side as the blocked hole disappears ,for "or" read "oi." Page 774, line <), for "squares" /' COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special ar- rangement with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE HI C2e(l 140)MIOO M$ i!M>:±, ■i ■i'"M':"r,x -U^'"' ir;''i';-v