MC-NRLF UNIVERSITY OF CALIFORNIA MEDICAL CENTER LIBRARY SAN FRANCISCO A TEXT-BOOK OF PHYSIOLOGY. BY M. (FOSTER, M.A., M.D., LL.D., F.R.S., PROFESSOR OF PHYSIOLOGY IN THE UNIVERSITY OF CAMBRIDGE, AND FELLOW OF TRINITY COLLEGE, CAMBRIDGE. SIXTH AMERICAN EDITION, THOROUGHLY REVISED, WITH NOTES, ADDITIONS, AND TWO HUNDRED AND FIFTY-SEVEN ILLUSTRATIONS. PHILADELPHIA: LEA BROTHERS & CO 1895. Entered according to Act of Congress in the year 1895, by LEA BROTHERS & CO., in the Office of the Librarian of Congress, at Washington. All rights reserved. ELECTROTYPED BY WESTCOTT A THOMSON, PHILADA. AMERICAN PUBLISHER'S NOTICE TO THE SIXTH EDITION. IN the preparation of the Sixth American Edition every page has been subjected to careful scrutiny and considerable liberty taken with the text. Useless verbiage has been omitted, obscure sentences have been revised or entirely rewritten, a large number of typographical errors have been cor- rected, histological details (except of the nervous system) have been mate- rially abridged, much that was too theoretical has been omitted, and such other alterations and additions have been made as to bring the book up to date and render it in a more advantageous form for the student. The his- tology of the nervous system has been retained in full, as has also the valuable Chemical Appendix — features that will be appreciated by both student and teacher. The more important additions have been dis- tinguished by enclosure in brackets [ ]. PHILADELPHIA, September, 1895. r CONTENTS PAGE INTRODUCTION 17 BOOK I. BLOOD. THE TISSUES OF MOVEMENT. THE VASCULAR MECHANISM. CHAPTER I. BLOOD. The Clotting of Blood 24 The Corpuscles of the Blood : The Ked Corpuscles 37 The White or Colorless Corpuscles 43 Blood Platelets 49 The Chemical Composition of Blood 50 The Quantity of Blood, and its Distribution in the Body 53 CHAPTER II. THE CONTRACTILE TISSUES. The Phenomena of Muscle and Nerve : Muscular and Nervous Irritability ... 55 The Phenomena of a Simple Muscular Contraction : 65 Tetanic Contractions 73 On the Changes which Take Place in a Muscle during a Contraction : The Change in Form '. . 77 The Chemistry of Muscle 83 Thermal Changes 90 Electrical Changes ..'.* 92 The Changes in a Nerve during the Passage of a Nervous Impulse 97 The Nature of the Changes through which an Electric Current is Able to Generate a Nervous Impulse: Action of the Constant Current 100 The Muscle-nerve Preparation as a Machine 107 The Circumstances which Determine the Degree of Irritability of Muscles and Nerves * . Ill The Energy of Muscle and Nerve, and the Nature of Muscular and Nervous Action 115 On Some Other Forms of Contractile Tissue : Plain, Smooth or Unstriated Mus- cular Tissue . . . 116 Ciliary Movement 119 Amoeboid Movements 121 10 CONTENTS. CHAPTER III. PAGE GENEEAL FEATUKES OF NERVOUS TISSUES 122 CHAPTER IV. THE VASCULAR MECHANISM. The Structure and Main Features of the Vascular Apparatus . . 133 The Structure of Arteries, Capillaries, and Veins 134 The Main Features of the Apparatus . . . 134 The Main Facts of the Circulation 136 Hydraulic Principles of the Circulation 144 Circumstances Determining the Kate of the Flow 150 The Heart 157 The Phenomena of the Normal Beat 157 Endocardiac Pressure 164 Summary 174 The Work Done 175 The Pulse ... 176 The Regulation and Adaptation of the Vascular Mechanism : The Regulation of the Beat of the Heart 191 The Development of the Normal Beat 192 The Government of Heart-beat by the Nervous System 199 Other Influences Regulating or Modifying the Beat of the Heart 209 Changes in the Calibre of the Minute Arteries. Vasomotor' Actions 211 The Course of Vaso-constrictor and Vaso-dilator Fibres 219 The Effects of Vasomotor Actions 221 Vasomotor Functions of the Central Nervous System 222 The Capillary Circulation 231 Changes in the Quantity of Blood 236 A Review of Some of the Features of the Circulation . 238 BOOK II. THE TISSUES OF CHEMICAL ACTION WITH THEIR RESPECTIVE MECHANISMS. NUTRITION. CHAPTER I. THE TISSUES AND MECHANISMS OF DIGESTION. The Characters and Properties of Saliva and Gastric Juice : Saliva 246 Gastric Juice 251 The Act of Secretion of Saliva and Gastric Juice and the Nervous Mechanisms which Regulate It • . • • ... 260 The Changes in a Gland Constituting the Act of Secretion The Properties and Characters of Bile, Pancreatic Juice, and Succus Entericus . . 278 Bile. 278 CONTENTS. 11 PAGE Pancreatic Juice 281 Succus Entericus 285 The Secretion of Pancreatic Juice and of Bile . . 286 The Structure of the Intestines : The Small Intestine 292 The Muscular Mechanisms of Digestion 293 The Changes which the Food Undergoes in the Alimentary Canal 306 The Changes in the Stomach 306 In the Small Intestine 308 In the Large Intestine 312 The Feces 313 The Lacteals and the Lymphatic System 313 The Nature and Movements of Lymph (including Chyle) 314 The Characters of Lymph 315 The Movements of Lymph 317 Absorption from the Alimentary Canal 325 The Course Taken by the Several Products of Digestion 325 The Mechanism of Absorption . . 329 CHAPTER II. RESPIRATION. The Mechanics of Pulmonary Respiration 333 The Respiratory Movements 339 Changes of the Air in Respiration 344 The Respiratory Changes in the Blood 346 The Relations of Oxygen in the Blood 350 Products of the Decomposition of Haemoglobin 358 The Relations of the Carbonic Acid in the Blood 360 The Relations of the Nitrogen in the Blood 361 The Respiratory Changes in the Lungs : The Entrance of Oxygen 361 The Exit of Carbonic Acid 364 The Respiratory Changes in the Tissues 365 The Nervous Mechanism of Respiration 369 The Effects of Changes in the Composition and Pressure of the Air Breathed . . 386 The Relations of the Respiratory System to the Vascular and Other Systems . . 390 Modified Respiratory Movements 403 CHAPTER III. THE ELIMINATION OF WASTE PRODUCTS. The Composition and Characters of Urine 404 Amounts of the Several Urinary Constituents Passed in Twenty-four Hours. (After Parkes.) 409 The Secretion of Urine . . 410 Secretion of the Renal Epithelium 417 The Discharge of Urine 426 Micturition 427 The Nature and Amount of Perspiration 431 Cutaneous Respiration 432 The Mechanism of the Secretion of Sweat 434 12 CONTENTS. CHAPTER IV. THE METABOLIC PROCESSES OF THE BODY. PAGE The History of Glycogen 437 Diabetes '. 448 The Formation of the Constituents of Bile 453 On Urea and on Nitrogenous Metabolism in General 457 On Some Structures and Processes of Obscure Nature 465 The History of Fat. Adipose Tissue 470 The Mammary Gland 477 Average Composition of Milk in Different Animals 480 CHAPTER V. NUTRITION. Statistics of Nutrition 482 Comparison of Income and Output of Material 485 The Energy of the Body : The Income of Energy 492 The Expenditure 493 Animal Heat 496 On Nutrition in General 506 On Diet . . 513 BOOK III. THE CENTRAL NERVOUS SYSTEM AND ITS INSTRUMENTS. CHAPTER I. THE SPINAL CORD. On Some Features of the Spinal Nerves 525 The Structure of the Spinal Cord 529 The Reflex Actions of the Spinal Cord 564 The Automatic Actions of the Spinal Cord 578 CHAPTER II. THE BRAIN. On Some General Features of the Structure of the Brain 584 The Bulb 589 The Disposition and Connections of the Gray and White Matter of the Brain : The Gray Matter 601 The Central Gray Matter and the Nuclei of the Cranial Nerves 601 CONTENTS. 13 PAGE The Superficial Gray Matter 615 The Intermediate Gray Matter of the Crural System 615 Other Collections of Gray Matter 625 The Arrangement of the Fibres of the Brain 627 Longitudinal Fibres of the Pedal System 628 Longitudinal Fibres of the Tegmental System 631 Transverse or so-called Commissural Fibres ... 634 Summary . 635 On the Phenomena Exhibited by an Animal Deprived of its Cerebral Hemispheres . 637 The Machinery of Coordinated Movements . 643 On Some Histological Features of the Brain 652 The Superficial Gray Matter of the Cerebellum 653 The Cerebral Cortex 655 On Voluntary Movements ....... 661 On the Development within the Central Nervous System of Visual and of some Other Sensations : Visual Sensations 689 Sensations of Smell 700 Sensations of Taste 701 Sensations of Hearing 701 On the Development of Cutaneous and Some Other Sensations 703 Some Other Aspects of the Functions of the Brain 716 On the Time Taken up by Cerebral Operations 724 The Lymphatic Arrangements of the Brain and Spinal Cord 728 The Vascular Arrangements of the Brain and Spinal Cord 732 CHAPTER III. SIGHT. The Eye 738 Dioptric Mechanisms: The Formation of the Image . . 744 Accommodation 745 Imperfections of the Dioptric Apparatus 757 Visual Sensations 759 The Origin of Visual Impulses 760 Simple Sensations 766 Color Sensations 769 Visual Perceptions Modified Perceptions Binocular Vision : Corresponding or Identical Points 781 Movements of the Eyeballs 782 The Horopter 786 Visual Judgments 786 The Protected Mechanisms of the Eye 789 CHAPTER IV. HEARING, SMELL, AND TASTE. Hearing : The Ear 790 The Acoustic Apparatus 798 1 4 CONTENTS. PAGE Auditory Sensations 800 Auditory Judgments •. 805 Smell : The Nasal Fossae 806 Taste: The Gustatory Mucous Membrane 80S CHAPTEK V. FEELING AND TOUCH. General Sensibility and Tactile Perceptions 812 Tactile Sensations : Sensations of Pressure 814 Sensations of Temperature 814 Tactile Perceptions and Judgments 816 The Muscular Sense 818 CHAPTER VI. SPECIAL MUSCULAR MECHANISMS. The Voice: The Larynx 819 Speech : Vowels 826 Consonants 827 Locomotor Mechanisms 829 BOOK IV. THE TISSUES AND MECHANISMS OF REPRODUCTION. CHAPTER I. ORGANS OF REPRODUCTION ,833 CHAPTER II. MENSTRUATION 038 CHAPTER III. IMPREGNATION 841 CHAPTER IV. THE NUTRITION OF THE EMBRYO 847 CHAPTER V. PARTURITION . 853 CONTENTS. 15 CHAPTER VI. PAGE THE PHASES OF LIFE 855 CHAPTER VII. DEATH . 863 APPENDIX. THE CHEMICAL BASIS OF THE ANIMAL BODY , . 865 A TEXT-BOOK OF PHYSIOLOGY. INTRODUCTION. § 1. DISSECTION, aided by microscopical examination, teaches us that the body of man is made up of certain kinds of material, so differing from each other in optical and other physical characters and so built up together as to give the body certain structural features. Chemical examination further teaches us that these kinds of material are composed of various chemical substances, a large number of which have this characteristic, that they possess a considerable amount of potential energy capable of being set free, rendered actual, by oxidation or some other chemical change. Thus the body, as a whole, may, from a chemical point of view, be considered as a mass of various chemical substances, representing altogether a considera- ble capital of potential energy. § 2. This body may exist either as a living body or (for a certain time at least) as a dead body, and the living body may at any time become a dead body. At what is generally called the moment of death (but arti- ficially so, for as we shall see the processes of death are numerous and gradual) the dead body so far as structure and chemical composition are concerned is exceedingly like the living body ; indeed the differences be- tween the two are such as can be determined only by very careful examina- tion, and are still to a large extent estimated by drawing inferences rather than actually observed. At any rate the dead body at the moment of death resembles the living body in so far as it represents a capital of potential energy. From that moment onward, however, the capital is expended ; by processes which are largely those of oxidation, the energy is gradually dis- sipated, leaving the body chiefly in the form of heat. While these chemical processes are going on the structural features disappear, and the body, with the loss of nearly all its energy, is at last resolved into " dust and ashes." The characteristic of the dead body then is that, being a mass of sub- stances of considerable potential energy, it is always more or less slowly losing energy, never gaining energy ; the capital of energy present at the moment of death is more or less slowly diminished, is never increased or replaced. § 3. When on the other hand we study a living body we are struck with the following salient facts : 1. The living body moves of itself, either moving one part of the body on another or moving the whole body from place to place. These move- ments are active ; the body is not simply pulled or pushed by external forces, but the motive power is in the body itself, the energy of each move- ment is supplied by the body itself. 2. These movements are determined and influenced, indeed often seem to be started, by changes in the surroundings of the body. Sudden contact between the surface of the body and some foreign object will often call 18 INTRODUCTION. forth a movement. The body is sensitive to changes in its surroundings, and this sensitiveness is manifested not only by movements but by other changes in the body. 3. It is continually generating heat and giving out heat to surrounding things, the production and loss of heat, in the case of man and certain other animals, being so adjusted that the whole body is warm, that is, of a temperature higher than that of surrounding things. 4. From time to time it eats, that is to say takes into itself supplies of certain substances known as food, these substances being in the main similar to those which compose the body, and being like them chemical bodies of considerable potential energy, capable through oxidation or other chemical changes of setting free a considerable quantity of energy. 5. It is continually breathing; that is, taking in from the surrounding air supplies of oxygen. 6. It is continually, or from time to time, discharging from itself into its surroundings so-called waste matters, which waste matters may be broadly described as products of oxidation of the substances taken in as food, or of the substances composing the body. Hence the living body may be said to be distinguished from the dead body by three main features. The living body like the dead is continually losing energy (and losing it more rapidly than the dead body, the special breathing arrangements per- mitting a more rapid oxidation of its substance), but unlike the dead body is by means of food continually restoring its substance and replenishing its store of energy. The energy set free in the dead body by the oxidation and other chem- ical changes of its substance leaves the body almost exclusively in the form of heat, whereas a great deal of energy leaves the living body as mechanical work, the result of various movements of the body, and as we shall see a great deal of the energy which ultimately leaves the body as heat, exists for a while within the living body in other forms than heat, though eventually transformed into heat. The changes in the surroundings affect the dead body at a slow rate and in a general way only, simply lessening or increasing the amount or rate of chemical change and the quantity of heat thereby set free, but never diverting the energy into some other form such as that of movement ; whereas changes in the surroundings may in the case of the living body rapidly, profoundly, and in special ways affect not only the amount but also the kind of energy set free. The dead body left to itself slowly falls to pieces, slowly dissipates its store of energy, and slowly gives out heat ; a higher or lower temperature, more or less moisture, a free or scanty supply of oxygen, the advent of many or few putrefactive organisms, these may quicken or slacken the rate at which energy is being dissipated but do not divert that energy from heat into motion ; whereas in the living body so slight a change of surroundings as the mere touch by a hair of some par- ticular surface, may so affect the setting free of energy as to lead to such a discharge of energy in the form of movement that the previously appar- ently quiescent body may be suddenly thrown into the most violent con- vulsions. The differences, therefore, between living substance and dead substance though recondite are very great, and the ultimate object of physiology is to ascertain how it is that living substance can do what dead substance cannot — that is, can renew its substance and replenish the energy which it is continually losing, and can, according to the nature of its surroundings, vary not only the amount but also the kind of energy which it sets free. INTRODUCTION. 19 Thus there are two great divisions of physiology : one having to do with the renewal of substance and the replenishment of energy, the other having to do with the setting free of energy. § 4. Now the body of man (or one of the higher animals) is a very com- plicated structure, consisting of different kinds of material, which we call tissues, such as muscular, nervous, connective, and the like, variously arranged in organs such as heart, lungs, muscles, skin, etc., all built up to form the body according to certain morphological laws. But all this com- plication, though advantageous and indeed necessary for the fuller life of man, is not essential to the existence of life. The amoeba [Fig. 1] is a [FIG. 1. Amoeba princeps, sho\Vn in different forms (A, B, C) assumed by the same animal.] living being ; it renews its substance, replenishes its store of energy, and sets free energy now in one form, now in another ; and yet the amoeba may be said to have no tissues and no organs ; at all events this is true of closely allied but not so well known simple beings. Using the more familiar amoeba as a type, and, therefore, leaving on one side the nucleus, and any distinction between endosarc and ectosarc, we may say that its body is homogeneous in the sense that if we divided it into small pieces, each piece would be like all the others. In another sense it is not homogeneous. For we know that the amoeba receives into its substance material as food, and that this food or part of it remains lodged in the body, until it is made use of and built up into the living substance of the body, and each piece of the living substance of the body must have in or near it some of the material which it is about to build up into itself. Further, we know that the amoeba gives out waste matters such as carbonic acid and other substances, and each piece of the amoeba must contain some of these waste matters about to be, but not yet, discharged from the piece. Each piece of the amoeba will, therefore, contain these three things, the actual living substance, the food about to become living substance, and the waste matters which have ceased to be living substance. Moreover, we have reasons to think that the living substance does not break down into the waste matters which leave the body at a single bound, but there are stages in the downward progress between the one and the other. Similarly, though our knowledge on this point is less sure, we have reason to think that the food is not incorporated into the living substance at a single step, but that there are stages in the upper progress from the dead food to the living substance. Each piece of the body of the amoeba 20 INTRODUCTION. will, therefore, contain substances representing various stages of becoming living, and of ceasing to be living, as well as the living substance itself. And we may safely make this statement though we are quite unable to draw the line where the dead food on its way up becomes living, or the living substance on its way down becomes dead. § 5. Nor is it necessary for our present purpose to be able to point out under the microscope, or to describe from a histological point of view, the parts which are living and the parts which are dead food or dead waste. The body of the amoeba is frequently spoken of as consisting of " proto- plasm." The name was originally given to the matter forming the primor- dial utricle of the vegetable cell as distinguished from the cell wall on the one hand, and from the fluid contents of the cell or cell sap on the other, and also we may add from the nucleus. It has since been applied very generally to such parts of animal bodies as resemble, in their general fea- tures, the primordial utricle. Thus the body of a white blood-corpuscle, or of a gland cell, or of a nerve cell, is said to consist of protoplasm. Such parts of animal bodies as do not in their general features resemble the matter of the primordial utricle are not called protoplasm, or, if they at some earlier stage did bear such resemblance, but no longer do so, are some- times, as in the case of the substance of a muscular fibre, called " differen- tiated protoplasm." Protoplasm in this sense sometimes appears, as in the outer part of most amoebae, as a mass of glassy-looking material, either con- tinuous or interrupted by more or less spherical spaces or vacuoles filled with fluid, sometimes as in a gland cell as a more refractive, cloudy-looking, or finely granular material arranged in a more or less irregular network, or spongework, the interstices of which are occupied either by fluid or by some material different from itself. We shall return, however, to the features of this " protoplasm " when we come to treat of white blood-corpuscles and other " protoplasmic" structures. Meanwhile it is sufficient for our present purpose to note that lodged in the protoplasm, discontinuous with it, and forming no part of it, are in the first place collections of fluid, of watery solutions of various substances, occupying the more regular vacuoles or the more irregular spaces of the network, and in the second place discrete granules of one kind or another, also forming no part of the protoplasm itself, but lodged either in the bars or substance of the protoplasm or in the vacuoles or meshes. Now, there can be little doubt that the fluids and the discrete granules are dead food or dead waste, but the present state of our knowledge will not permit us to make any very definite statement about the protoplasm itself. We may probably conclude, indeed we may be almost sure, that protoplasm in the above sense is not all living substance, that it is made up partly of the real living substance, and partly of material which is becoming living or has ceased to be living; and in the case where protoplasm is described as forming a network, it is possible that some of the material occupying the meshes of the network may be, like part of the network itself, really alive. " Protoplasm " in fact, as in the sense in which we are now using it, and shall continue to use it, is a morphological term ; but it must be borne in mind that the same word " protoplasm " is also frequently used to denote what we have just now called " the real living substance." The word then embodies & phy- siological idea ; so used it may be applied to the living substance of all living structures, whatever the microscopical features of those structures ; in this sense it cannot at present, and possibly never will be recognized by the microscope, and our knowledge of its nature must be based on inferences. Keeping then to the phrase " living substance " we may say that each piece of the body of the amoeba consists of living subs-tan ce, in which are INTRODUCTION. 21 lodged, or with which are built up in some way or other, food and waste in various stages. Now, an amoeba may divide itself into two, each half exhibiting all the phenomena of the whole ; and we can easily imagine the process to be repeated, until the amoeba was divided into a multitude of exceedingly minute amoebae, each having all the properties of the original. But it is obvious, as in the like division of a mass of a chemical substance, that the division could not be repeated indefinitely. Just as in division of the chem- ical mass we come to the chemical molecule, further division of which changes the properties of the substance, so in the continued division of the amoeba we should come to a stage in which further division interfered with the physiological actions, we should come to a physiological unit correspond- ing to but greatly more complex than the chemical molecule. This unit to remain a physiological unit and to continue to live must contain not only a portion of the living substance but also the food for that living substance, in several at least of the stages, from the initial raw food up to the final " living " stages, and must similarly contain various stages of waste. § 6. Now, the great characteristic of the typical amoeba (leaving out the nucleus) is that, as far as we can ascertain, all the physiological units are alike; they all do the same things. Each and every part of the body receives food more or less raw and builds it up into its own living substance ; each and every part of the body may be at one time quiescent and at another in motion ; each and every part is sensitive and responds by movement or otherwise to various changes in its surroundings. The body of man, in its first stage, while it is yet an ovum, if we leave aside the nucleus and neglect differences caused by the unequal distribution of food material or yolk, may also be said to be composed of like parts or like physiological units. By the act of segmentation, however, the ovum is divided into parts or cells which early show differences from each other ; and these differences rapidly increase as development proceeds. Some cells put on certain char- acters and others other characters — that is to say, the cells undergo histologi- cal differentiation. And this takes place in such a way that a number of cells lying together in a group become eventually converted into a tissue, and the whole body becomes a collection of such tissues arranged together according to morphological laws, each tissue having a definite structure, its cellular nature being sometimes preserved, sometimes obscured or even lost. This histological differentiation is accompanied by a physiological division of labor. Each tissue may be supposed to be composed of physiological units, the units of the same tissue being alike but differing from the units of other tissues ; and corresponding to this difference of structure, the units of different tissues behave or act differently. Instead of all the units, as in the amoeba, doing the same things equally well, the units of one tissue are told off, as it were, to do one thing especially well, or especially fully, and thus the whole labor of the body is divided among the several tissues. § 7. The several tissues may thus be classified according to the work which they have to do ; and the first great distinction is into (1) the tissues which are concerned in the setting free of energy in special ways, and (2) the tissues which are concerned in replenishing the substance and so renew- ing the energy of the body. Each physiological unit of the amoeba while it is engaged in setting free energy so as to move itself, and by reason of its sensitiveness so directing that energy as to produce a movement suitable to the conditions of its sur- roundings, has at the same time to bear the labor of taking in raw food, of selecting that part of the raw food which is useful and rejecting that which 22 INTRODUCTION. is useless, and of working up the accepted part through a variety of stages into its own living substance— that is to say, it has at the same time that it is feeling and moving to carry on the work of digesting and assimilating. It has, moreover, at the same time to throw out the waste matters arising from the changes taking place in its own substance, having first brought these waste matters into a condition suitable for being thrown out. § 8. In the body of man, movements, as we shall see, are, broadly speak- ing, carried out by means of muscular tissue, and the changes in muscular tissue which lead to the setting free of energy in the form of movement are directed, governed, and adapted to the surroundings of man, by means of nervous tissue. Rays of light fall on the nervous substance of the eye called the retina, and set up in the retina changes which induce in the optic nerve other changes, which in turn are propagated to the brain as nervous impulses, both the excitation and the propagation involving an expenditure of energy. These nervous impulses reaching the brain may induce other nervous im- pulses which, travelling down certain nerves to certain muscles, may lead to changes in those muscles by which they suddenly grow short and pull upon the bones or other structures to which they are attached, in which case we say the man starts ; or the nervous impulses reaching the brain may produce some other effects. Similarly sound falling on the ear, or contact between the skin and some foreign body, or some change in the air or other surround- ings of the body, or some change within the body itself may so affect the nervous tissue of the body that nervous impulses are started and travel to this point or that, to the brain or elsewhere, and eventually may either reach some muscular tissue and so give rise to movements, or may reach other tissues and produce some other effect. The muscular tissue then may be considered as given up to the produc- tion of movement, and the nervous tissue as given up to the generation, transformation, and propagation of nervous impulses. In each case there is an expenditure of energy, which in the case of the muscle, as we shall see, leaves the body partly as heat and partly as work done, but in the case of nervous tissue is wholly or almost wholly transformed into heat before it leaves the body ; and this expenditure necessitates a replenishment of energy and a renewal of substance. § 9. In order that these master tissues, the nervous and muscular tissues, may carry on their important works to the best advantage, they are relieved of much of the labor that falls upon each physiological unit of the amoeba. They are not presented with raw food, they are not required to carry out the necessary transformations of their immediate waste matters. The whole of the rest of the body is engaged (1) in so preparing the raw food, and so bringing it to the nervous and muscular tissues that these may build it up into their own substance with the least trouble, and (2) in receiving the waste matters which arise in muscular and nervous tissues, and preparing them for rapid and easy ejection from the body. Thus to certain tissues, which we may speak of broadly as " tissues of digestion," is allotted the duty of acting on the food and preparing it for the use of the muscular and nervous tissues ; and to other tissues, which we may speak of as "tissues of excretion," is allotted the duty of clearing the body from the waste matters generated by the muscular and nervous tissues. § 10. These tissues are for the most part arranged in machines or mech- anisms called organs, and the workings of these organs involves movement. The movements of these organs are carried out, like the other movements of the body, chiefly by means of muscular tissue governed by nervous tissue. Hence we may make a distinction between the muscles which are concerned in producing an effect on the world outside man's body, the muscles by which INTRODUCTION. 23 man does his work in the world, and the muscles which are concerned in carrying out the movements of the internal organs. And we may similarly make a distinction between the nervous tissue concerned in carrying out the external work of the body and that concerned in regulating the movements and, as we shall see, the general conduct of the internal organs. But these two classes of muscular and nervous tissue, though distinct in work and, as we shall see, often different in structure, are not separated or isolated. On the contrary, while it is the main duty of the nervous tissue as a whole, the nervous system as we may call it, to carry out, by means of nervous impulses passing hither and thither, what may be spoken of as the work of man, and in this sense it is the master tissue, it also serves as a bond of union between itself and the muscles doing external work on the one hand, and the organs of digestion or excretion on the other, so that the activity and conduct of the latter may be adequately adapted to the needs of the former. §11. Lastly, the food prepared and elaborated by the digestive organs is carried and presented to the muscular and nervous tissues in the form of a complex fluid known as blood, which, driven by means of a complicated mechanism known as the vascular system, circulates all over the body, visit- ing in turn all the tissues of the body, and by a special arrangement known as the respiratory mechanism, carrying in itself to the several tissues a sup- ply of oxygen as well as of food more properly so called. The motive power of this vascular system is supplied, as in the case of the digestive system, by means of muscular tissue, the activity of which is similarly governed by the nervous system, and hence the flow of blood to this part or that part is regulated according to the needs of the part. § 12. The above slight sketch will perhaps suffice to show not only how numerous but how varied are the problems with which physiology has to deal. In the first place, there are what may be called general problems, such as, How the food after its preparation and elaboration into blood is built up into the living substance of the several tissues ? How the living substance breaks down into the dead waste ? How the building up and breaking down differ in the different tissues in such a way that energy is set free in different modes, the muscular tissue contracting, the nervous tissue thrilling with a nervous impulse, the secreting tissue doing chemical work, and the like? To these general questions the answers which we can at present give can hardly be called answers at all. In the second place, there are what maybe called special problems, such as, What are the various steps by which the blood is kept replenished with food and oxygen, and kept free from an accumulation of waste, and how is the activity of the digestive, respiratory, and excretory organs, which effect this, regulated and adapted to the stress of circumstances? What are the details of the working of the vascular mechanism by which each and every tissue is forever bathed with fresh blood, and how is that working delicately adapted to all the various changes of the body ? And, compared with which all other special problems are insignificant and preparatory only, How do nervous impulses so flit to and fro within the nervous system as to issue in the movements which make up what we sometimes call the life of man ? It is to these special problems that we must chiefly confine our attention, and we may fitly begin with a study of the blood. BOOK I. BLOOD, THE TISSUES OF MOVEMENT, THE VASCULAR MECHANISM, CHAPTER I. BLOOD. § 13. THE several tissues are traversed by minute tubes, the capillary bloodvessels, to which blood is brought by the arteries, and from which blood is carried away by the veins. These capillaries form networks the meshes of which, differing in form and size in the different tissues, are occu- pied by the elements of the tissue, which consequently lie outside the capil- laries. The blood flowing through the capillaries consists, under normal condi- tions, of an almost colorless fluid, the plasma, in which are carried a num- ber of bodies, the red and the white corpuscles. Outside the capillary walls, filling up such spaces as exist between the capillary walls and the cells or fibres of the tissue, or between the elements of the tissue themselves, is found a colorless fluid resembling in many respects the plasma of blood, and called lymph. Thus all the elements of the tissue and the outsides of all the capil- laries are bathed with lymph, which, as we shall see hereafter, is continually flowing away from the tissue along special channels to pass into lymphatic vessels and thence into the blood. As the blood flows through the capillaries certain constituents of the plasma (together with, at times, white, corpuscles, and under exceptional circumstances red corpuscles) pass through the capillary wall into the lymph, and certain constituents of the lymph pass through the capillary wall into the blood within the capillary. There is thus an interchange of material between the blood within the capillary and the lymph outside. A similar interchange of material is at the same time going on between the lymph and the tissue itself. Hence, by means of the lymph acting as mid- dleman, a double interchange of material takes place between the blood within the capillary and the tissue outside the capillary. In every tissue, so long as life lasts and the blood flows through the bloodvessels, a double stream, now rapid, now slow, is passing from the blood to the tissue and from the tissue to the blood. The stream from the blood to the tissue car- ries to the tissue the material which the tissue needs for building itself up and for doing its work, including the all-important oxygen. The stream from the tissue to the blood carries into the blood certain of the products of the chemical changes which have been taking place in the tissue, products which may be simple waste, to be cast out of the body as soon as possible, or which may be bodies capable of being made use of by some other tissue. A third stream, that from the lymph lying in the chinks and crannies of the tissue along the lymph channels to the larger lymph vessels, carries away from the tissue such parts of the material coming from the blood as 25 26 BLOOD. are not taken up by the tissue itself and such parts of the material coming from the tissue as do not find their way into the bloodvessel. In most tissues, as in muscle for instance, the capillary network is so close set and the muscular fibre lies so near to the bloodvessel that the lymph between the two exists only as a very thin sheet; but in some tis- sues, as in cartilage, the bloodvessels lie on the outside of a large mass of tissue, the interchange between the central parts of which and the nearest capillary bloodvessel is carried on through a long stretch of lymph passages. But in each case the principle is the same ; the tissue, by the help of lymph, lives on the blood; and when in succeeding pages we speak of changes between the blood and the tissues, it will be understood, whether expressly stated so or not, that the changes are effected by means of the lymph. The blood may thus be regarded as an internal medium bearing the same rela- tions to the constituent tissues that the external medium, the world, does to the whole individual. Just as the whole organism lives on the things around it, its air and its food, so the several tissues live on the complex fluid by which they are all bathed, and which is to them their immediate air and food. All the tissues take up oxygen from the blood and give up carbonic acid to the blood, but not always at the same rate or at the same time. More- over, the several tissues take up from the blood and give up to the blood either different things or the same things at different rates or at different times. From this it follows, on the one hand, that the composition and charac- ters of the blood must be forever varying in different parts of the body and at different times ; and on the other hand, that the united action of all the tissues must tend to establish and maintain an average uniform composition of the whole mass of blood. The special changes which blood is known to undergo while it passes through the several tissues will best be dealt with when the individual tissues and organs come under our consideration. At present it will be sufficient to study the main features which are presented by blood brought, so to speak, into a state of equilibrium by the common action of all the tissues. Of all these main features of blood the most striking, if not the most important, is the property it possesses of clotting when shed. THE CLOTTING OF BLOOD. § 14. Blood, when shed from the bloodvessels of a living body, is per- fectly fluid. In a short time it becomes viscid, this viscidity increasing rap- idly until the whole mass of blood under observation becomes a complete jelly. The vessel into which it has been shed can at this stage be inverted without a drop of the blood being spilt. The jelly is of the same bulk as the previously fluid blood, and if carefully shaken out will present a com- plete mould of the interior of the vessel. [Fig. 2.] If the blood in this jelly stage be left untouched in a glass vessel, a few drops of an almost colorless fluid soon make their appearance on the surface of the jelly. Increasing in number, and running together, the drops after a while form a superficial layer of pale, straw-colored fluid. Later on, similar layers of the same fluid are seen at the sides and finally at the bottom of the jelly, which, shrunk to a smaller size and of firmer consistency, now forms a clot or crassamentum, floating in a perfectly fluid serum. [Fig. 3.] The shrinking and condensation of the clot, and the corresponding increase of the serum, continue for some time. The upper surface of the clot is generally slightly concave. A portion of the clot examined under the microscope is seen to THE CLOTTING OF BLOOD. 27 consist of a feltwork of fine granular fibrils, in the meshes of which are entangled the red and white corpuscles of the blood. In the serum nothing [FIG. 2. [FIG. 3. Bowl of recently coagulated blood, showing the whole mass uniformly solidified. After Daltou.] Bowl of coagulated blood, after twelve hours, showing the clot contracted and float- ing in the fluid serum. After Dalton.] [FIG. 4. can be seen but a few stray corpuscles, chiefly white. The fibrils are com- posed of a substance called fibrin. [Fig. 4.] Hence we may speak of the clot as consisting of fibrin and cor- puscles ; and the act of clotting is obviously a substitution for the plasma of fibrin and serum, fol- lowed by a separation of the fibrin and corpuscles from the serum. In man, blood when shed becomes viscid in about two or three minutes, and enters the jelly stage in about five or ten minutes. After the lapse of another few minutes the first drops of serum are seen, and clotting is generally complete in from one to several hours. The time, however, will be found to vary according to circumstances. Among animals the rapidity of clotting varies exceed- ingly in different species. The blood of the horse clots with re- markable slowness ; so slowly, in- deed, that many of the red and also some of the white corpuscles (both these being specifically heavier than the plasma) have time to sink before viscidity sets in. In consequence there appears on the surface of the blood an upper layer of colorless plasma containing in its deeper portions many colorless corpuscles (which are lighter than the red). This layer clots like the other parts of the blood, forming the so-called " buffy coat." A similar buffy coat is sometimes seen in the blood of man in certain abnormal conditions of the body. If a portion of horse's blood be surrounded by a cooling mixture of ice and salt, and thus kept about 0° C., clotting may be almost indefinitely postponed. Under these circumstances a more complete descent of the cor- puscles takes place, and a considerable quantity of colorless transparent plasma free from blood corpuscles may be obtained. A portion of this plasma removed from the freezing mixture clots in the same manner as does the entire blood. It first becomes vascid and then forms a jelly, which sub- sequently separates into a colorless shrunken clot and serum. This shows that the corpuscles are not an essential part of the clot. Coagulated fibrin, showing its fibrillated con- dition. After Dalton.] 28 BLOOD. If a few cubic centimetres of this colorless plasma, or of a similar plasma which may be obtained from almost any blood by means which we will presently describe, be diluted with many times its bulk of a 0.6 per cent, solution of sodium chloride1 clotting is much retarded, and the various stages may be more easily watched. As the fluid is becoming viscid, fine fibrils of fibrin will be seen to be developed in it, especially at the sides of the con- taining vessel. As these fibrils multiply in number, the fluid becomes more and more of the consistence of a jelly and at the same time somewhat opaque. Stirred or pulled about with a needle, the fibrils shrink up into a small opaque stringy mass ; and a very considerable bulk of the jelly may by agitation be resolved into a minute fragment of shrunken fibrin floating in a quantity of what is really diluted serum. If a specimen of such diluted plasma be stirred from time to time, as soon as clotting begins, with a needle or glass rod, the fibrin may be removed piecemeal as it forms, and the jelly stage may be altogether done away with. When fresh blood which has not yet had time to clot is stirred or whipped with a bundle of rods (or anything presenting a large amount of rough surface), no jelly-like clotting takes place, but the rods become covered with a mass of shrunken fibrin. Blood thus whipped until fibrin ceases to be deposited, is found to have entirely lost its power of clotting. Putting these facts together, it is very clear that the phenomena of the clotting of blood are caused by the appearance in the plasma of fine fibrils of fibrin. So long as these are scanty, the blood is simply viscid. When they become sufficiently numerous, they give the blood the firmness of a jelly. Soon after their formation they begin to shrink, and while shrinking enclose in their meshes the corpuscles, but squeeze out the fluid parts of the blood. Hence the appearance of the shrunken colored clot and the colorless serum. § 15. Fibrin, whether obtained by whipping freshly shed blood, or by washing either a normal clot, or a clot obtained from colorless plasma, exhibits the same general characters. It belongs to that class of complex unstable nitrogenous bodies called proteids, which form a large portion of all living bodies and an essential part of all living structures. Our knowledge of proteids is at present too imperfect, and probably none of them have yet been prepared in adequate purity to justify us in attempt- ing to assign to them any definite formula ; but it is important to remember their general composition. 100 parts of a proteid contain rather more than 50 parts of carbon, rather more than 15 of nitrogen, about 7 of hydrogen, and rather more than 20 of oxygen ; that is to say, they contain about half their weight of carbon, and only about i their weight of nitrogen ; and yet, as we shall see, they are eminently the nitrogenous substances of the body. They usually contain a small quantity (1 or 2 per cent.) of sulphur, and many also have some phosphorus attached to them in some way or other. When burnt they leave a variable quantity of ash, consisting of inorganic salts of which the bases are chiefly sodium and potassium, and the acids chiefly hydrochloric, sulphuric, phosphoric, and carbonic. They all give certain reactions, by which their presence may be recog- nized; of these the most characteristic are the following: Boiled with nitric acid they give a yellow color, which deepens into orange upon the addition of ammonia. This is called the xanthoproteie test ; the color is due to a product of decomposition. Boiled with the mixture of mercuric and mercurous nitrates known as Millon's reagent, they give a pink color. Mixed with a strong solution of sodic hydrate they give, on the addition of a drop or two of 1 A solution of sodium chloride of this strength will hereafter be spoken of as " normal saline solution." THE CLOTTING OF BLOOD. 29 a very weak solution of cupric sulphate, a violet or pink color which deepens on heating. These are artificial reactions, not throwing much if any light on the constitution of proteids ; but they are useful as practical tests enabling us to detect their presence. ' The several members of the proteid group are at present distinguished from each other chiefly by their respective solubilities, especially in various saline solutions. Fibrin is one of the least soluble ; it is insoluble in water, almost insoluble in dilute neutral saline solutions, and very sparingly soluble in more concentrated neutral saline solutions and in dilute acids and alkalies. In strong acids and alkalies it dissolves, but in the process becomes com- pletely changed into something which is no longer fibrin. In dilute acids it swells up and becomes transparent, but when the acid is neutralized returns to its previous condition. When suspended in water and heated to 100° C., or even to 75° C., it becomes changed, and still less soluble than before ; it is said in this case to be coagulated by the heat, and, as we shall see, nearly all proteids have the property of being changed in nature, of undergoing coagulation and so becoming less soluble than before, by being exposed to a certain high temperature. Fibrin, then, is a proteid distinguished from other proteids by its smaller solubility ; it is further distinguished .by its peculiar filamentous structure, the other proteids when obtained in a solid form appearing either in amor- phous granules or, at most, in viscid masses. § 16. We may now return to the serum. This is perfectly fluid, and remains fluid until it decomposes. It is of a faint straw-color, due to the presence of a special pigment substance, differing from the red matter which gives redness to the red corpuscles. Tested by the xanthoproteic and other tests it obviously contains a large quantity of proteid matter, and upon examination we find that at least two distinct proteid substances are present in it. If crystals of magnesium sulphate be added to serum and gently stirred until they dissolve, it will be seen that the serum as it approaches saturation with the salt becomes turbid instead of remaining clear, and eventually a white amorphous granular or flocculent precipitate makes its appearance. This precipitate may be separated by decantation or filtration, washed with saturated solutions of magnesium sulphate, in which it is insoluble, until it is freed from all other constituents of the serum, and thus obtained fairly pure. It is then found to be a proteid body, distinguished by the following characters among others : 1. It is (when freed from any adherent magnesium sulphate) insoluble in distilled water ; it is insoluble in concentrated solutions of neutral saline bodies, such as magnesium sulphate, sodium chloride, etc., but readily soluble in dilute (e. g., 1 per cent.) solutions of the same neutral saline bodies. Hence from its solutions in the latter it maybe precipitated either by adding more neutral saline substance or by removing by dialysis the small quantity of saline substance present. When obtained in a precipitated form, and suspended in distilled water, it readily dissolves into a clear solution upon the addition of a small quantity of some neutral saline body. By these various solutions and precipitations it is not really changed in nature. 2. It readily dissolves in very dilute acids (e. g., in hydrochloric acid even when diluted to far less than 1 per cent.), and it is similarly soluble in dilute alkalies, but in being thus dissolved it is wholly changed in nature, and the solutions of it in dilute acid and dilute alkalies gives reactions quite different from those of the solution of the substance in dilute neutral saline solutions. By the acid it is converted into what is called acid-albumin, by the alkali into alkali-albumin, both of which bodies we shall have to study later on. 30 BLOOD. 3. When it is suspended in water and heated it becomes altered in char- acter, coagulated, and all its reactions are changed. It is no longer soluble in dilute neutral saline solutions, not even in dilute acids and alkalies ; it has become coagulated proteid, and is now even less soluble than fresh fibrin. When a solution of it in dilute neutral saline solution is similarly heated, a similar change takes place, a precipitate falls down which on examination is found to be coagulated proteid. The temperature at which this change takes place is somewhere about 75° C., though shifting slightly according to the quantity of saline substance present in the solution. One of the proteids present in blood-serum is paraglobulin, characterized by its solubility in dilute neutral saline solutions, its insolubility in distilled water and concentrated saline solutions, its ready solubility, and at the same time conversion into other bodies, in dilute acids and alkalies, and in its becoming converted into coagulated proteid, and so being precipitated from its solutions at 75° C. These reactions are given by a number of proteid bodies forming a group called globulins, the particular globulin present in blood-serum being para- globulin. The amount of it present in blood-serum varies in various animals, and apparently in the same animal at different times. In 100 parts by weight of serum there are generally present about 8 or 9 parts of proteids altogether, and of these some 3 our 4, more or less, may be taken as paraglobulin. § 17. If the serum from which the paraglobulin has been precipitated by the addition of neutral salt, and removed by filtration, be subjected to di- alysis, the salt added may be removed, and a clear, somewhat diluted serum free from paraglobulin may be obtained. This still gives abundant proteid reactions, so that the serum still contains a proteid, or some proteids still more soluble than the globulins, since they will remain in solution, and are not precipitated, even when dialysis is con- tinued until the serum is practically freed from both the neutral salt added to it and the diffusible salts previously present in the natural serum. When this serum is heated to 75° C. a precipitate makes its appearance ; the proteids still present are coagulated at this temperature. We have some reasons for thinking that more than one proteid is present, but they are all closely allied to each other, and we may for the present speak of them as if they were one, and call the proteid left in serum, after removal of the paraglobulin, by the name of albumin, or, to distinguish it from other albumins found elsewhere, serum-albumin. Serum-albumin is distinguished by being more soluble than the globulins, since it is soluble in distilled water, even in the absence of all neutral salts. Like the glubulins, though with much less ease, it is converted by dilute acids and dilute alkalies into acid- or into alkali-albumin. The percentage amount of serum-albumin in serum may be put down as 4 or 5, more or less, but it varies and some- times is less abundant than paraglobulin. In some animals (snakes) it is said to disappear during starvation. The more important characters of the three proteids which we have just studied may be stated as follows : Soluble in distilled water and in saline solutions of all strengths . . serum-albumin. Insoluble in distilled water, readily soluble in dilute saline solutions, insoluble in concentrated saline solutions paraglobulin. Insoluble in distilled water, bardly soluble at all in dilute saline solutions, and very little soluble in more concentrated saline solu- tions fibrin. Besides paraglobulin and serum-albumin, serum contains a very large number of substances, generally in small quantity, which, since they have THE CLOTTING OF BLOOD. 31 to be extracted by special methods, are called extractives ; of these some are nitrogenous, some non-nitrogenous. Serum contains besides important inor- ganic saline substances ; but to these we shall return. § 18. With the knowledge which we have gained of the proteids of clotted blood we may go back to the question : Clotting being due to the appearance in blood plasma of a proteid substance, fibrin, which previously did not exist in it as such, what are the causes which led to the appearance of fibrin ? We learn something by studying circumstances which affect the rapidity with which the blood of the same individual clots when shed. These are as follows : A temperature of 40° C., which is about or slightly above the tempera- ture of the blood of warm-blooded animals, is perhaps the most favorable to clotting. A further rise of a few degrees is apparently also beneficial, or at least not injurious ; but upon a still further rise the effect changes, and when blood is rapidly heated to 56° C. no clotting at all may take place. At this temperature certain proteids of the blood are coagulated and precipitated before clotting can take place, and with this change the power of the blood to clot is wholly lost. If, however, the heating be not very rapid, the blood may clot before this change has time to come on. When the temperature instead of being raised is lowered below 40° C. the clotting becomes delayed and prolonged ; and at the temperature of 0° or 1° C. the blood will remain fluid, and yet capable of clotting when withdrawn from the adverse circum- stances, for a very long, it might almost be said, for an indefinite time. A small quantity of blood shed into a small vessel clots sooner than a large quantity shed into a larger one ; and in general the greater the amount of foreign surface with which the blood comes in contact the more rapid the clotting. When shed blood is stirred or " whipped " the fibrin makes its appearance sooner than when the blood is left to clot in the ordinary way ; so that here, too, the accelerating influence of contact with foreign bodies makes itself felt. Similarly, movement of shed blood hastens clotting, since it increases the amount of contact with foreign bodies. So also the addition of spongy platinum or of powdered charcoal, or of other inert powders, to tardily clotting blood will, by influence of surface, hasten clotting. Con- versely, blood brought into contact with pure oil does not clot so rapidly as when in contact with glass or metal ; and blood will continue to flow for a longer time without clotting through a tube smeared inside with oil than through a tube not so smeared. The influence of the oil in such cases is a physical not a chemical one ; any pure neutral inert oil will do. As far as we know these influences affect only the rapidity with which the clotting takes place — that is, the rapidity with which the fibrin makes its appear- ance, not the amount of clot, not the quantity of fibrin formed, though when clotting is very much retarded by cold changes may ensue whereby the amount of clotting which eventually takes place is indirectly affected. Mere exposure to air exerts apparently little influence on the process of clotting. Blood collected direct from a bloodvessel over mercury so as wholly to exclude the air, clots as readily as blood freely exposed to the air. It is only when blood is much laden with carbonic acid, the presence of which is antagonistic to clotting, that exclusion of air, by hindering the escape of the excess of carbonic acid, delays clotting. These facts teach us that fibrin does not, as was once thought, make its appearance in shed blood because the blood when shed ceases to share in the movement of the circulation, or because the blood is cooled on leaving the warm body, or because the blood is then more freely exposed to the air ; they further suggest the view that the fibrin is the result of some chemical change, the conversion into fibrin of something which is not fibrin, the change like 32 BLOOD. other chemical changes being most active at an optimum temperature, and like so many other chemical changes, being assisted by the influences exerted by the presence of inert bodies. And we have direct experimental evidence that plasma does contain an antecedent of fibrin which, by chemical change, is converted into fibrin. § 19. If blood be received direct from the bloodvessels into one-third its bulk of a saturated solution of some neutral salt such as magnesium sulphate, and the two gently but thoroughly mixed, clotting, especially at a moder- ately low temperature, will be deferred for a very long time. If the mixture be allowed to stand, the corpuscles will sink, and a colorless plasma will be obtained similar to the plasma gained from horse's blood by cold, except that it contains an excess of the neutral salt. The presence of the neutral salt has acted in the same direction as cold ; it has prevented the occurrence of clotting. It has not destroyed the fibrin ; for if some of the plasma be diluted with from five to ten times its bulk of water, it will clot speedily in quite a normal fashion, with the production of quite normal fibrin. The separation of the fluid plasma from the corpuscles and from other bodies heavier than the plasma is much facilitated by the use of the centrifugal machine. This consists essentially of a tireless \yheel with several spokes, placed in a hori- zontal position and made to revolve with great velocity (1000 revolutions per min- ute for instance) around its axis. Tubes of metal or of very strong glass are sus- pended at the ends of the spokes by carefully adjusted joints. As the wheel rotates with increasing velocity, each tube gradually assumes a horizontal posi- tion, bottom outward, without spilling any of its contents. As the rapid rotation continues the corpuscles and heavier particles are driven to the bottom of the tube, and if a very rapid movement he continued for a long time will form a compact cake at the bottom of the tube. When the rotation is stopped the tubes gradually return to their upright position again without anything being spilt, and the clear plasma in each tube can then be decanted off. If some of the colorless transparent plasma, obtained either by the action of neutral salts from any blood, or by the help of cold from horse's blood, be treated with some solid neutral salt, such as sodium chloride, to saturation, a white flaky, somewhat sticky precipitate will make its appearance. If this precipitate be removed, the fluid no longer possesses the power of clotting (or very slightly so), even though the neutral salt present be removed by dialysis, or its influence lessened by dilution. With the removal of the sub- stance precipitated, the plasma has lost its power of clotting. If the precipitate itself, after being washed with a saturated solution of the neutral salt (in which it is insoluble) so as to get rid of all serum and other constituents of the plasma, be treated with a small quantity of water, it readily dissolves,1 and the solution rapidly filtered gives a clear, colorless filtrate, which is at first perfectly fluid. Soon, however, the fluidity gives way to viscidity, and this in turn to a jelly condition, and finally the jelly shrinks into a clot floating in a clear field ; in other words, the filtrate clots like plasma. Thus there is present in cooled plasma, and in plasma kept from clotting by the presence of neutral salts, a something precipitable by saturation with neutral salts — a something which, since it is soluble in very dilute saline solutions, cannot be fibrin itself, but which in solution speedily gives rise to the appearance of fibrin. To this substance its discoverer, Denis, gave the name of plasmine. The substance thus precipitated is not however a single body, but a mix- turo of at least two bodies. If sodium chloride be carefully added to plasma to an extent of about 13 per cent, a white flaky viscid precipitate is thrown 1 The substance itself is not soluble in distilled water, but a quantity of the neutral •salt always clings to the precipitate, and thus the addition of water virtually gives rise to dilute saline solution, in which the substance is readily soluble. THE CLOTTING OF THE BLOOD. 33 down very much like plasmine. If after the removal of the first precipitate more sodium chloride, and especially if magnesium sulphate be added, a second precipitate is thrown down, less viscid and more granular than the first. The second precipitate when examined is found to be identical with the paraglobulin, coagulating at 75° C., which we have already seen to be a constituent of serum. The first precipitate is also a proteid belonging to the globulin group, but differs from paraglobulin, not only in being more readily precipitated by sodium chloride, and in being when precipitated more viscid, but also in other respects, and especially in being coagulated at a far lower temperature than paraglobulin, viz., at 56° C. Now, while isolated paraglobulin cannot by any means known to us be converted into fibrin, and as its presence in the so-called plasmine does not seem to be essential to the formation of fibrin out of plasmine, the presence in plasmine of the body coagulating at 56° C. does seem essential to the conversion of plasmine into fibrin, and we have reason for thinking that it is itself converted, in part at least, into fibrin. Hence it has received the name of fibrinogen. § 20. The reasons for this view are as follows : Besides blood, which clots naturally when shed, there are certain fluids in the body which do not clot naturally, either in the body or when shed, but which by certain artificial means may be made to clot, and in clotting to yield quite normal fibrin. Thus the so-called serous fluid taken some hours after death1 from the pericardial, pleural, or peritoneal cavities, the fluid found in the enlarged serous sac of the testis, known as hydrocele fluid, and other similar fluids, will in the majority of cases, when obtained free from blood or other admix- tures, remain fluid almost indefinitely, showing no disposition whatever to clot.2 Yet, in most cases at all events, these fluids, when a little blood, or a piece of blood clot, or a little serum is added to them, will clot rapidly and firmly,3 giving rise to an unmistakable clot of normal fibrin, differing only from the clot of blood in that, when serum is used, it is colorless, being free from red corpuscles. Now blood (or blood clot, or serum) contains many things, to any one of which the clotting power thus seen might be attributed. But it is found that in many cases clotting may be induced in the fluids of which we are speaking by the mere addition, and that even in exceedingly small quantity, of a substance which can be extracted from blood, or from serum, or from blood clot, or even from washed fibrin, or indeed from other sources, a sub- stance whose exact nature is uncertain, it being doubtful whether it is a proteid at all, and whose action is peculiar. If serum, or whipped blood or a broken-up clot be mixed with a large quantity of alcohol and allowed to stand some days, the proteids present are in time so changed by the alcohol as to become insoluble in water. Hence if the copious precipitate caused by the alcohol, after longstanding, be sepa- rated by filtration from the alcohol, dried at a low temperature, not exceed- ing 40° C., and extracted with distilled water, the aqueous extract contains very little proteid matter, indeed very little organic matter at all. Never- theless, even a small quantity of this aqueous extract added alone to certain specimens of hydrocele fluid or other of the fluids spoken of above, will bring about a speedy clotting. The same aqueous extract has also a remarkable 1 If it be removed immediately after death it generally clots readily and firmly, giving a colorless clot consisting of fibrin and white corpuscles. 2 In some specimens, however, a spontaneous coagulation, generally slight, but in ex- ceptional cases massive, may be observed. 3 In a few cases no coagulation can thus be induced. 3 34 BLOOD. effect in hastening the clotting of fluids which, though they will eventually clot, do so very slowly. Thus plasma may, by the careful addition of a cer- tain quantity of neutral salt and water, be reduced to such a condition that it clots very slowly indeed, taking perhaps days to complete the process. The addition of a small quantity of the aqueous extract we are describing will, however, bring about a clotting which is at once rapid and complete. The active substance, whatever it be, in this aqueous extract exists in small quantity only, and its clotting virtues are at once and forever lost when the solution is boiled. Further, there is no reason to think that the active substance actually enters into the formation of the fibrin to which it. gives rise. It appears to belong to a class of bodies playing an important part in physiological processes, and called ferments, of which we shall have more to say hereafter. We may, therefore, speak of it as the fibrin ferment, the name given to it by its discoverer, Alexander Schmidt. This fibrin ferment is present in and may be extracted from clotted or whipped blood, and from both the clot1 and the serum of clotted blood ; and since in most, if not all, cases where blood or blood clot or serum produces clotting in hydrocele or pericardial fluid, an exactly similar clotting may be induced by the mere addition of fibrin ferment, we seem justified in con- cluding that the clotting virtues of the former are due to the ferment which they contain. Now, when fibrinogen is precipitated from plasma, as above described, by sodium chloride, redissolved, and reprecipitated, more than once, it may be obtained in solution, by help of a dilute neutral saline solution, in an ap- proximately pure condition, at all events free from other proteids. Such a solution will not clot spontaneously ; it may remain fluid indefinitely ; and yet on the addition of a little fibrin ferment it will clot readily and firmly, yielding quite normal fibrin. This body fibrinogen is also present and may be separated out from the specimens of hydrocele, pericardial, and other fluids which clot on the addition of fibrin ferment, and when the fibrinogen has been wholly removed from these fluids they refuse to clot on the addition of fibrin ferment. Paraglobulin, on the other hand, whether prepared from plasmine by separation of the fibrinogen, or from serum, or from other fluids in which it is found, cannot be converted by fibrin ferment, or indeed by any other means, into fibrin. And fibrinogen isolated, as described above, or serous fluids which contain fibrinogen, can be made, by means of fibrin ferment, to yield quite normal fibrin in the complete absence of paraglobulin. A solu- tion of paraglobulin obtained from serum or blood clot will, it is true, clot pericardial or hydrocele fluids containing fibrinogen, or indeed a solution of fibrinogen, but this is apparently due to the fact that the paraglobulin has in these cases some fibrin ferment mixed with it ; it is also possible that, under certain conditions, the presence of paraglobulin may be favorable to the action of the ferment. When the so-called plasmine is precipitated, as directed in § 19, fibrin ferment is carried down with the fibrinogen and paraglobulin, and when the plasmine is re-dissolved the ferment is present in the solution and ready to act on the fibrinogen. Hence the re-dissolved plasmine clots spontaneously. When fibrinogeu is isolated from plasma by repeated precipitation and solution, the ferment is washed away from it, and the pure ferment-free fibrinogen, ultimately obtained, does not clot spontaneously. So far it seems clear that there does exist a proteid body, fibrinogen, which may by the action of fibrin ferment be directly, without the interven- 1 A powerful solution of fibrin ferment may be readily prepared by simply extracting a washed blood clot with a 10 per cent, solution of sodium chloride. THE CLOTTING OF BLOOD. 35 tion of other proteids, converted into the less soluble fibrin. Our knowledge of the constitution of proteid bodies is too imperfect to enable us to make any very definite statement as to the exact nature of the change thus effected ; but we may say this much. Fibrinogen and fibrin have about the same elementary composition, fibrin containing a trifle more nitrogen. When fibrinogen is converted into fibrin by means of fibrin ferment, the weight of the fibrin produced is always less than that of the fibrinogen which is consumed, and there is always produced at the same time a certain quantity of another proteid, belonging to the globulin family. There are reasons, however, why we cannot speak of the ferment as splitting up fibrinogen into fibrin and a globulin ; it seems more probable that the fer- ment converts the fibrinogen first into a body which we might call soluble fibrin, and then turns this body into a veritable fibrin ; but further inquiries on the subject are needed. It may be added that among the conditions necessary for the due action of fibrin ferment on fibrinogen, the presence of a certain quantity of some neutral salt seems to be one. In the total absence of all neutral salts the ferment cannot convert the fibrinogen into fibrin. There are some reasons also for thinking that the presence of a lime salt, such as calcium sulphate, though it may be in minute quantity only, is essential. If the calcium salts are taken out of fibrinogen, the fibrinogen no longer coagulates upon the addition of fibrin ferment free from lime salts. Oxalate of potassium added to freshly drawn blood also prevents coagulation, apparently because of the precipitation of the lime salts ; the addition now of calcium salts is promptly followed by coagulation. § 21. We may conclude, then, that the plasma of blood when shed, or, at all events, soon after it has been shed, contains fibrinogen ; and it also seems probable that the clotting comes about because the fibrinogen is con- verted into fibrin by the action of fibrin ferment ; but we are still far from a definite answer to the question, why blood remains fluid in the body and yet clots when shed ? We have already said that blood, or blood plasma, brought up to a tem- perature of 56° C. as soon as possible after its removal from the living bloodvessels, gives a proteid precipitate and loses its power of clotting. This may be taken to show that blood, as it circulates in the living blood- vessels, contains fibrinogen as such, and that when the blood is heated to 56° C., which is the coagulating point of fibrinogen, the fibrinogen present is coagulated and precipitated, and consequently no fibrin can be formed. Further, while clotted blood undoubtedly contains an abundance of fibrin ferment, no ferment, or a minimal quantity only, is present in blood as it leaves the bloodvessels. If the blood be received directly from the bloodvessels into alcohol, the aqueous extract prepared as directed above contains no ferment, or merely a trace. Apparently the ferment makes its appearance in the blood as the result of changes taking place in the blood after it has been shed. We might from this be inclined to conclude that blood clots when shed, but not before, because, fibrinogen being always present, the shedding brings about changes which produce fibrin ferment, not previously existing, and this acting on the fibrinogen gives rise to fibrin. But we meet with the fol- lowing difficulty : A very considerable quantity of very active ferment may be injected into the blood-current of a living animal without necessarily producing any clotting at all. Obviously either blood within the blood- vessels does not contain fibrinogen as such, and the fibrinogen detected by heating the blood to 56° C. is the result of changes which have already ensued before the temperature is reached ; or in the living circulation there 36 BLOOD. are agencies at work which prevent any ferment which may be introduced into the' circulation from producing its usual effect on fibrinogeii ; or there are agencies at work which destroy, or do away with the fibrin, little by little, as it is formed. § 22. And indeed, when we reflect how complex blood is and the many and great changes of which it is susceptible, we shall not wonder that the question we are putting cannot be offered off hand. The corpuscles with which blood is crowded are living structures, and consequently are continually acting upon and being acted upon by the plasma. The red corpuscles it is true are, as we shall see, peculiar bodies, with a restricted life and a very specialized work, and possibly their influ- ence on the plasma is not very great ; but we have reason to think that the relations between the white corpuscles and the plasma are close and im- portant. Then again the blood is not only acting upon and being acted upon by the several tissues as it flows through the various capillaries, but along the whole of its course through the heart, arteries, capillaries, and veins, is acting upon and being acted upon by the vascular walls, which like the rest of the body are alive, and being alive are continually undergoing and pro- moting change. That relations of some kind, having a direct influence on the clotting of blood, do exist between the blood and the vascular walls is shown by the following facts : After death, when all motion of the blood has ceased, the blood remains for a long time fluid. It is not until some time afterward, at an epoch when post-mortem changes in the blood and in the bloodvessels have had time to develop themselves, that clotting begins. Thus some hours after death the blood in the great veins may be found still perfectly fluid. Yet such blood has not lost its power of clotting ; it still clots when removed from the body, and clots too when received over mercury without exposure to air, showing that, though the blood, being highly venous, is rich in car- bonic acid and contains little or no oxygen, its fluidity is not due to any excess of carbonic acid or absence of oxygen. Eventually it does clot even within the vessels, but perhaps never so firmly and completely as when shed. It clots first in the larger vessels, but remains fluid in the smaller vessels for a very long time, for many hours in fact, since in these the same bulk of blood is exposed to the influence of, and reciprocally exerts an influence on, a larger surface of the vascular walls than in the larger ves- sels. And if it be urged that the result is here due to influences exerted by the body at large, by the tissues as well as by the vascular walls, this objection will not hold good against the following experiment. If the jugular vein of a large animal, such as an ox or horse, be carefully ligatured when full of blood, and the ligatured portion excised, the blood in many cases remains perfectly fluid, along the greater part of the length of the piece, for twenty-four or even forty-eight hours. The piece so liga- tured may be suspended in a framework and opened at the top so as to imi- tate a living test-tube, and yet the blood will often remain long fluid, though a portion removed at any time into a glass or other vessel will clot in a few minutes. If two such living test-tubes be prepared, the blood may be poured from one to the other without clotting taking place. A similar relation of the fluid to its containing living wall is seen in the case of those serous fluids which clot spontaneously. If, as soon after death as the body is cold and the fat is solidified, the pericardium be carefully re- moved from a sheep by an incision round the base of the heart, the peri- cardia! fluid (which, as we have already seen, during life and some little THE CLOTTING OF BLOOD. 37 time after death, possesses the power of clotting) may be kept in the peri- cardial bag as in a living cup for many hours without clotting, and yet a small portion removed with a pipette clots at once. This relation between the blood and the vascular wall may be disturbed or overridden : clotting may take place or may be induced within the living bloodvessel. When the living membrane is injured, as when an artery or vein is sharply ligatured, or when it is diseased, as for instance in aneurism, a clot is apt to be formed at the injured or diseased spot ; and in certain morbid conditions of the body clots are formed in various vascular tracts. Absence of motion, which in shed blood as we have seen is unfavorable to clotting, is apt within the body to lead to clotting. Thus, when an artery is ligatured, the blood in the tract of the artery on the cardiac side of the ligature, between the ligature and the branch last given off by the artery, ceasing to share in the circulation, remains motionless or nearly so, and along this tract a clot forms, firmest next to the ligature and ending near where the branch is given off; this perhaps may be explained by the fact that the walls of the tract suffer in their nutrition by the stagnation of the blood, and that consequently the normal relation between them and the contained blood is disturbed. That the blood within the living bloodvessels, though not actually clot- ting under normal circumstances, may easily be made to clot, that the blood is always on the point of clotting, is shown by the fact that a foreign body such as a needle thrust into the interior of a bloodvessel or a thread drawn through and left in a bloodvessel, is apt to become covered with fibrin. Some influence exerted by the needle or thread, whatever may be the cha- racter of that influence, is sufficient to determine a clotting, which other- wise would not have taken place. The same instability of the blood, as regards clotting, is strikingly shown, in the case of the rabbit, by the result of injecting into the bloodvessels a small quantity of a solution of a peculiar proteid, prepared from certain structures such as the thymus body. Massive clotting of the blood in almost all the bloodvessels, small and large, takes place with great rapid- ity, leading to the sudden death of the animal. In contrast to this effect may be mentioned the result of injecting into the bloodvessels of a dog a quantity of a solution of a body called albumose, of which we shall here- after have to treat as a product of the digestion of proteid substances, to the extent of 0.3 gramme per kilo of body weight. So far from producing clotting, the injected albumose has such an effect on the blood that for several hours after the injection shed blood will refuse to clot of itself and remain quite fluid, though it can be made to clot by special treatment. § 23. All the foregoing facts tend to show that the blood as it is flow- ing through the healthy bloodvessels is, as far as clotting is concerned, in a state of unstable equilibrium, which may at any moment be upset, even within the bloodvessels, and which is upset directly the blood is shed, with clotting as a result. Our present knowledge does not permit us to make an authoritative statement as to the exact nature of this equilib- rium. There are reasons, however, for thinking that the white corpuscles play an important part in the matter. Wherever clotting occurs natu- rally, white corpuscles are present; and this is true not only of blood but also of such specimens of pericardial or other serous fluids as clot natu- rally. And many arguments which we cannot enter upon here, may be adduced all pointing to the same conclusion, that the white corpuscles play nn important part in the process of clotting. But it would lead us too far into controversial matters to attempt to define what that part is, or to explain the exact nature of the equilibrium of which we have spoken. 38 BLOOD. What we do know is that in blood soon after it has been shed the body which we have called fibrinogen is present, as also the body which we have called fibrin ferment, that the latter acting on the former will produce fibrin, and that the appearance of fibrin is undoubtedly the cause of what is called clotting. We seem justified in concluding that the clotting of shed blood is due to the conversion by ferment of fibrinogen into fibrin. The further inference that clotting within the body is the same thing as clotting outside the body, and similarly due to the transformation of fibrinogen by ferment into fibrin, though probable, is not proved. We do not yet know the exact nature and condition of the blood within the living bloodvessels, and until we know that we cannot satisfactorily explain why blood in the living bloodvessels is usually fluid but can at times clot. THE CORPUSCLES OF THE BLOOD. The Red Corpuscles. § 24. The redness of blood is due exclusively to the red corpuscles. The plasma as seen in thin layers within the living bloodvessels appears colorless, as does also a thin layer of serum ; but a thick layer of serum (and probably of plasma) has a faint yellowish tinge due, as we have said, to the presence of a small quantity of a special pigment. The corpuscles appear under the microscope as fairly homogeneous, im- perfectly translucent biconcave discs with a diameter of 7 to 8 (i. and a [FIG. 5. FIG. 6. FIG. 5.— Human Blood as seen on the Warm Stage (magnified about 1200 diameters) : r, r, single red corpuscles seen lying flat; r', r', red corpuscles on their edge and viewed in profile ; r", red corpuscles arranged in rouleaux ; c, c, crenate red corpuscles; p, a finely granular pale cor- puscle; <7, a coarsely granular pale corpuscle. Both have two or three distinct vacuoles, and were undergoing changes of shape at the moment of observation ; in g a nucleus also was visible. FIG. 6.— Human Red Corpuscles Lying Singly and Collected into Rolls. (As seen under an ordinary high power of the microscope.)] thickness of 1 to 2 //. Being discs they are circular in outline when seen on the flat, but rod-shaped when seen in profile. [Fig. 5.] Being bicon- cave, with a thicker rounded rim surrounding a thinner centre, the rays of THE COKPUSCLES OF THE BLOOD. 39 light in passing through them, when they are examined by transmitted light, are more refracted at the rim than in the centre. The effect of this is that, when viewed at what may be considered the proper focus, the centre of a corpuscle appears clear, while a slight opacity marks out indistinctly the inner margin of the thicker rim, whereas, when the focus is shifted either up or down, the centre becomes dark and the rest of the corpuscle clear. Any body of the same shape, and composed of substances of the same refractive power, would produce the same optical effects. Otherwise the corpuscle appears homogeneous, without distinction of parts and without a nucleus. A single corpuscle seen by itself has a very faint color, look- ing yellow rather than red, but when several corpuscles lie one upon the top of the other the mass is distinctly red. The red corpuscle is elastic, in the sense that it may be deformed by pressure or traction, but when the pressure or traction is removed regains its previous form. Its shape is also much influenced by the physical conditions of the plasma, serum, or fluid in which for the time being it is. If the plasma or serum be diluted with water, the disc, absorbing water, swells up into a sphere [Fig. 7], becoming a disc again on the removal of the dilution. If the serum be concentrated, the disc, giving out water, shrinks irregularly and assumes [FIG. 7. various forms ; one of these forms is that of a a 6 c d e number of blunted protuberances projecting all • ©k tfk JF?| f^\ over the surface of the corpuscle, which is then J |p Jp *"* ^^ said to be crenate ; in a drop of blood examined under the microscope, crenate corpuscles are ^ ^W often seen at the edge of the cover-slip where "%if 9 C& evaporation is^ leading to concentration of the a_e> successive effects of water plasma, or, as it should then perhaps rather be upon a red corpuscle; /, effect of called, serum. In blood just shed the red cor- solution of salt, crenated; g, effect puscles are apt to adhere to each other by their of tannic acid.] flat surfaces, much more than to the glass or other surface with which the blood is in contact, and hence arrange them- selves in rolls. This tendency, however, to form rolls very soon diminishes after the blood is shed. Though a single corpuscle is somewhat translucent, a comparatively thin layer of blood is opaque ; type, for instance, cannot be read through even a thin layer of blood. When a quantity of whipped blood (or blood otherwise deprived of fibrin) is frozen and thawed several times it changes color, becoming -of a darker hue, and is then found to be much more transparent, so that type can now be easily read through a moderately thin layer. It is then spoken of as laky blood. The same change may be effected by shaking the blood with ether, or by adding a small quantity of bile salts, and in other ways. Upon examination of laky blood it is found that the red corpuscles are " broken up" or at least altered, and that the redness which previously was confined to them is now diffused through the serum. Normal blood is opaque because each corpuscle, while permitting some rays of light (chiefly red) to pass through, reflects many others, and the brightness of the hue of normal blood is due to this reflection of light from the surfaces of the several corpuscles. Laky blood is transparent because there are no longer intact corpuscles to present surfaces for the reflection of light, and the darker hue of laky blood is similarly due to the absence of reflection from the several corpuscles. When laky blood is allowed to stand a sediment is formed (and may be separated by the centrifugal machine) which on examination is found^ to consist of discs, or fragments of discs, of a colorless substance exhibiting 40 BLOOD. under high powers an obscurely spongy or reticular structure. These color- less, thin discs seen flatwise often appear as mere rings. The substance composing them stains with various reagents and may thus be made more evident. The red corpuscle, then, consists obviously of a colorless framework, with which in normal conditions a red coloring matter is associated ; but by various means the coloring matter may be driven from the framework and dissolved in the serum. The framework is spoken of as stroma; it is a modified or differentiated protoplasm, and upon chemical analysis yields proteid substances, some of them at least belonging to the globulin group, and other matters, among which is a peculiar complex fat called lecithin, of which we shall have to speak in treating of nervous tissue. The red coloring matter which in normal conditions is associated with this stroma is called haemoglobin, and may by proper methods be split up into a proteid belonging to the globulin group, and into a colored pigment, containing iron, called hcematin. Haemoglobin is, therefore, a very complex body. It is found to have remarkable relations to oxygen, and indeed, as we shall see, the red corpuscles by virtue of their haemoglobin have a special work in respiration ; they carry oxygen from the lungs to the several tissues. We shall therefore defer the further study of haemoglobin until we have to deal with respiration. The red corpuscle, then, consists of a disc of colorless stroma with which is associated in a peculiar way the complex colored body haemoglobin. Though the haemoglobin, as is seen in laky blood, is readily soluble in serum (and it is also soluble in plasma), in the intact normal blood it remains con- fined to the corpuscle; obviously there is some special connection between the stroma and the haemoglobin ; it is not until the stroma is altered, we may perhaps say killed (as by repeated freezing and thawing), that it loses its hold on the haemoglobin, which thus set free passes into solution in the serum. The disc of stroma when separated from the haemoglobin has, as we have just said, an obscurely spongy texture ; but we do not know accurately the exact condition of the stroma in the intact corpuscle or how it holds the haemo- globin. There is certainly no definite membrane or envelope to the corpuscle, for by exposing blood to a high temperature, 60° C., the corpuscle will break up into more or less spherical pieces, each still consisting of stroma and haemoglobin. The quantity of stroma necessary to hold a quantity of haemoglobin is exceedingly small. Of the total solid matter of a corpuscle more than 90 per cent, is haemoglobin. A red corpuscle in fact is a quantity of haemo- globin held together in the form of a disc by a minimal amount of stroma. Hence whatever effect the stroma per se may have upon the plasma, this, in the case of mammals at all events, must be insignificant ; the red corpuscle is practically simply a carrier of haemoglobin. § 25. The average number of red corpuscles in human blood may be probably put down at about 5 millions in a cubic millimetre (the range in different mammals is said to be from 3 to 18 millions), but the relation of corpuscle to plasma varies a great deal even in health, and very much in disease. Obviously the relation may be affected (1) by an increase or de- crease of the plasma, (2) by an actual decrease or increase of red corpus- cles. Now, the former must frequently take place. The blood, as we have already urged, is always being acted upon by changes in the tissues and, indeed, is an index of those changes ; hence the plasma must be continu- ally changing, though always striving to return to the normal condition. Thus when a large quantity of water is discharged by the kidney, the THE CORPUSCLES OF THE BLOOD. 41 skin or the bowels, that water comes really from the blood, and the drain of water must tend to diminish the bulk of the plasma, and so to increase the relative number of red corpuscles, though the effect is probably soon remedied by the passage of water from the tissues into the blood. So again when a large quantity of water is drunk, this passes into the blood and tends temporarily to dilute the plasma (and so to diminish the relative number of red corpuscles), though this condition is in turn soon remedied by the passage of the superfluous fluid to the tissues and excretory organs. The greater or less number of red corpuscles, then, in a given bulk of blood may be simply due to less or more plasma, but we have reason to think that the actual number of the corpuscles in the blood does vary from time to time. This is especially seen in certain forms of disease which may be spoken of under the general term of anaemia (there being several kinds of anaemia), in which the number of red corpuscles is distinctly diminished. The redness of blood may, however, be influenced not only by the number of red corpuscles in each cubic millimetre of blood, but also by the amount of haemoglobin in each corpuscle, and to a less degree by the size of the corpuscles. If we compare, with a common standard, the redness of two specimens of blood unequally red, and then determine the relative number of corpuscles in each, we may find that the less red specimen has as many corpuscles as the redder one, or at least the deficiency in redness is greater than can be accounted for by the paucity of red corpuscles. Obviously, in such a case, the red corpuscles have too little haemoglobin. In some cases of anaemia the deficiency of haemoglobin in each corpuscle is more striking than the scantiness of red corpuscles. The number of corpuscles in a specimen of blood is determined by mixing a small but carefully measured quantity of the blood with a large quantity of some [FIG. 8. Hsemacytometer of Gowers : A, pipette for measuring the diluting solution ; E, capillary tube for measuring blood ; C, cell with divisions on slide, cover-glass and springs ; D, vessel to mix solutions ; E, mixer ; F, guarded spear-pointed needle for sticking finger.] indifferent fluid, e. g., a 5 per cent, solution of sodium sulphate, and then actually counting the corpuscles in a known minimal bulk of the mixture. 42 BLOOD. This, perhaps, may be most conveniently done by the method generally known as that of Growers (Hsemacytometer) [Fig. 8 j, improved by Malassez. A glass slide, in a metal frame, is ruled into minute rectangles, e. g. \ mm. by i mm., so as to give a convenient area of ^V of a square mm. Three small screws in the frame permit a coverslip to be brought to a fixed distance, e. g. \ mm., from the surface of the slide. The blood having been diluted, e. g. to 100 times its volume, a small quantity of the diluted (and thoroughly mixed) blood, sufficient to occupy fully the space between the coverslip and the glass slide when the former is brought to its proper position, is placed on the slide, and the coverslip brought down. The volume of diluted blood now lying over each of the rectangles will be T^o (?\yX£) of a cubic mm.; and if, when the corpuscles have subsided, the number of cor- puscles lying within a rectangle be counted, the result will give the number of corpuscles previously distributed through y^ of a cubic mm. of the diluted blood. This multiplied by 100 will give the number of corpuscles in 1 cubic mm. of the diluted blood, and again multiplied by 100 the number in 1 cubic mm. of the entire blood. It is advisable to count the number of corpuscles in several of the rectangles, and to take the average. For the convenience of count- ing, each rectangle is subdivided into a number of very small squares, e. g. into 20, each with a side of -£$ mm., and so an area of ^^ of a square mm. Since the actual number of red corpuscles in a specimen of blood (which may be taken as a sample of the whole blood) is sometimes more, sometimes less, it is obvious that either red corpuscles may be temporarily withdrawn from and returned to the general blood current, or that certain red corpuscles are, after a while, made away with, and that new ones take their place. We have no satisfactory evidence of the former being the case in normal condi- tions, whereas we have evidence that old corpuscles do die and that new ones are born. § 26. The red corpuscles, we have already said, are continually engaged in carrying oxygen, by means of their haemoglobin, from the lungs to the tissues ; they load themselves with oxygen at the lungs and unload at the tissues. It is extremely unlikely that this act should be repeated indefinitely without leading to changes which may be familiarly described as wear and tear, and which would ultimately lead to the death of the corpuscles. We shall have to state later on that the liver discharges into the alimen- tary canal, as a constituent of bile, a considerable quantity of a pigment known as bilirubin, and that this substance has remarkable relations with, and, indeed, may be regarded as a derivative of hcematin, which, as we have seen (§ 24), is a product of the decomposition of haemoglobin. It appears probable, in fact, that the bilirubin of bile (and this as we shall see is the chief biliary pigment, and the source of the other biliary pigments) is not formed wholly anew in the body, but is manufactured in some way or other out of haematin derived from haemoglobin. This must entail a daily con- sumption of a considerable quantity of haemoglobin, and since we know no other source of haemoglobin besides the red corpuscles, and have no evidence of red corpuscles continuing to exist after having lost their haemoglobin, must, therefore, entail a daily destruction of many red corpuscles. Even in health, then, a number of red corpuscles must be continually disappearing ; and in disease the rapid and great diminution which may take place in the number of red corpuscles shows that large destruction may occur. We cannot at present accurately trace out the steps of this disappearance of red corpuscles. In the spleen pulp, red corpuscles have been seen in various stages of disorganization, some of them lying within the substance of large colorless corpuscles, and as it were being eaten by them. There is also evidence that destruction takes place in the liver itself, and, indeed, elsewhere. But the subject has not yet been adequately worked out. § 27. This destruction of red corpuscles necessitates the birth of new THE CORPUSCLES OF THE BLOOD. 43 corpuscles, to keep up the normal supply of haemoglobin ; and, indeed, the cases in which after even great loss of blood by hemorrhage a healthy ruddiness returns, and that often rapidly, showing that the lost corpuscles have been replaced, as well as the cases of recovery from the disease anaemia, prove that red corpuscles are, even in adult life, born somewhere in the body. In the adult, as in the embryo, the red corpuscles appear to be formed out of preceding colored nucleated cells. In the interior of bones is a peculiar tissue called marrow, which, in most parts being very full of bloodvessels, is called red marrow. In this red marrow the capillaries and minute veins form an intricate labyrinth of rel- atively wide passages with very thin walls, and through this labyrinth the flow of blood is comparatively slow. In the passages of this labyrinth are found colored nucleated cells, that is to say, cells the cell substance of which has undergone more or less differentiation into haemoglobin and stroma. And there seems to be going on in red marrow a multiplication of such colored nucleated cells, which become transformed into red non-nucleated discs, that is, into ordinary red corpuscles, and pass into the general blood current. In other words, a formation of red corpuscles, not wholly unlike that which takes place in the embryo, is in the adult continually going on in the red marrow of the bones. A similar formation of red corpuscles has also been described, though with less evidence, as taking place in the spleen, especially under particular circumstances, such as after great loss of blood. The formation of red corpuscles is, therefore, a special process, taking place in special regions ; we have no satisfactory evidence that the ordinary white corpuscles of the blood are, as they travel in the current of the circu- lation, transformed into red corpuscles. The red corpuscles, then, to sum up, are useful to the body on account of the haemoglobin, which constitutes so nearly the whole of their solid matter. What functions the stroma may have besides the mere, so to speak, mechan- ical one of holding the haemoglobin in the form of a corpuscle we do not know. The primary use of the haemoglobin is to carry oxygen from the lungs to the tissues, and it would appear that it is advantageous to the econ- omy that the haemoglobin should be as it were bottled up in corpuscles rather than simply diffused through the plasma. How long a corpuscle may live carrying oxygen we do not exactly know ; the red corpuscles of one animal, e. g., a bird, injected into the vessels of another, e. g., a mammal, disappear within a few days ; but this affords no measure of the life of a corpuscle in its own home. Eventually, however, the red corpuscle dies, its place being supplied by a new one. The haemoglobin set free from the dead corpuscles appears to have a secondary use in forming the pigment of the bile and possibly other pigments. The White or Colorless Corpuscles. § 28. The white corpuscles are far less numerous than the red ; a speci- men of ordinary healthy blood will contain several hundred red corpuscles to each white corpuscle, though the proportion, even in health, varies consid- erably under different circumstances, ranging from 1 in 300 to 1 in 700. But though less numerous, the white corpuscles are probably of greater importance to the blood itself than are the red corpuscles ; the latter are chiefly limited to the special work of carrying oxygen from the lungs to the tissues, while the former probably exert a considerable influence on the blood plasma itself, and help to maintain it in a proper condition. 44 BLOOD. When seen in a normal condition, and " at rest," the white corpuscle is a small, spherical, colorless mass, varying in size, but with an average diameter of about 10 v, and presenting generally a finely but sometimes a coarsely granular appearance. [Fig. 9.] The surface, even when the corpuscle is [FIG. 9. a, white corpuscles of human blood; d, red corpuscles (high power).] perfectly at rest, is not absolutely smooth and even, but somewhat irregular, thereby contributing to the granular appearance ; and at times these irreg- ularities are exaggerated into protuberances or "pseudopodia" of varying size or form, the corpuscle in this way assuming various forms without changing its bulk, and by the assumption of a series of forms shifting its place. Of these " amoeboid movements," as they are called, we shall have to speak later on. In carrying on these amoeboid movements the corpuscle may transform itself from a spherical mass into a thin, flat, irregular plate ; and when this occurs there may be seen at times in the midst of the extended finely gran- ular mass or cell body, a smaller body of different aspect and refractive power, the nucleus. The normal presence of a nucleus in the white corpuscles may also be shown by treating the corpuscle with dilute acetic acid,, which swells up and renders more transparent the cell body but makes the nucleus more refractive and more sharply defined, and so more conspicuous, or by the use of staining reagents, the majority of which stain the nucleus more readily and more deeply than the cell body. In what perhaps may be considered a typical white corpuscle, the nucleus is a spherical mass about 2-3 // in diameter, but it varies in size in different corpuscles, and not unfrequently is irregular in form, at least after the action of reagents. It occasionally appears as if about to divide into fragments, and sometimes a corpuscle may contain two or even more (then generally small) nuclei. Though staining readily with staining reagents, the nucleus of an ordinary white corpuscle does not show the nuclear network which is so characteristic, as we shall see, of the nuclei of many cells, and which in these is the part of the nucleus which especially stains; in the closely allied lymph corpuscles, to which we shall have immediately to refer, a nuclear network is present. The cell body of the white corpuscle may be taken as a good example of what we have called undiffereritiated protoplasm. Optically, it consists of a uniformly transparent but somewhat refractive material or basis, in which are imbedded minute particles, generally spherical in form, and in which sometimes occur minute vacuoles filled with fluid; it is rarely, if ever, that any distinct network, like that which is sometimes observed in other cells, can be seen in the cell body of a white corpuscle whether stained or not. The imbedded particles are generally very small, and for the most part distributed uniformly over the cell body, giving it a finely granular aspect ; sometimes, however, the particles are relatively large, making the corpuscles coarsely granular, the coarse granules being frequently confined to one or another THE CORPUSCLES OF THE BLOOD. 45 part of the cell body. These particles or granules, whether coarse or fine, vary in nature; some of them, as shown by their greater refractive power, their staining with osmic acid, and their solution by solvents of fat, are fatty in nature; others may similarly be shown by their reactions to be proteid in nature. The material in which these granules are imbedded, and which forms the greater part of the cell body, has no special optical features ; so far as can be ascertained, it appears under the microscope to be homogeneous ; no definite structure can be detected in it. It must be borne in mind that the whole corpuscle consists largely of water, the total solid matter amounting to not much more than 10 per cent. The transparent material of the cell body must, therefore, be in a condition which we may call semifluid, or semi- solid, without being called upon to define what we exactly mean by these terms. This approach to fluidity appears to be connected with the great mobility of the cell body, as shown in its amoeboid movements. § 29. When we submit to chemical examination a sufficient mass of white corpuscles, separated out from the blood by special means and obtained tolerably free from red corpuscles and plasma (or apply to the white blood- corpuscles the chemical results obtained from the more easily procured lymph- corpuscles, which, as we shall see, are very similar to, and, indeed, in many ways related to the white corpuscles of the blood), we find that this small solid matter of the corpuscle consists largely of certain proteids. One of these proteids is a body either identical with, or closely allied to, the proteid called myosin, which we shall have to study more fully in con- nection with muscular tissue. At present we may simply say that myosin is a body intermediate between fibrin and globulin, being less soluble than the latter and more soluble than the former ; thus while it is hardly at all soluble in a 1 per cent, solution of sodium chloride or other neutral salt, it is, unlike fibrin, speedily and wholly dissolved by a 10 per cent, solution. Myosin is further interesting because, as we shall see, just as fibrin is formed in the clotting of blood from fibrinogen, so myosin is formed out of a preceding myosinogen, during a kind of clotting which takes place in muscular fibre and which is spoken of as rigor mortis. And we have reasons for thinking that in the living white blood-corpuscle there does exist a body identical with or allied to myosinogen, which we may speak of as being in a fluid con- dition; and which on the death of the corpuscle is converted, by a kind of clotting, into myosin, or into an allied body which, being solid, gives the body of the corpuscle a stiffness and rigidity which it did not possess during life. Besides this myosin or myosin-like proteid, the white corpuscles also contain either paraglobulin itself or some other member of the globulin group, as well as a body or bodies like or identical with serum-albumin. In addition, there is present, in somewhat considerable quantity, a sub- stance of a peculiar nature, which since it is confined to the nuclei of the corpuscles, and further seems to be present in all nuclei, has been called nudein. This nuclein, which though a complex nitrogenous body is very different in composition and nature from proteids, is remarkable on the one hand for being a very stable inert body, and on the other for containing a large quantity (according to some observers nearly 10 per cent.) of phos- phorus, which appears to enter more closely into the structure of the molecule than it does in the case of proteids. Next in importance to the proteids, as constant constituents of the white corpuscles, come certain fats. Among these the most conspicuous is the complex fatty body lecithin. In the case of many corpuscles at all events we have evidence of the 46 BLOOD. presence of a member of the large group of carbohydrates, comprising starches and sugar, viz., the starch-like body glycogen, which we shall have to study more fully hereafter. This glycogen may exist in the living cor- puscle as glycogen, but it is very apt, after the death of the corpuscles, to become changed by hydration into some form of sugar, such as maltose or dextrose. Lastly, the ash of the white corpuscles is characterized by containing a relatively large quantity of potassium and of phosphates and by being rela- tive poor in chlorides and in sodium. But in this respect the "corpuscle is merely an example of what seems to be a general rule (to which, however, there may be exceptions) that while the elements of the tissues themselves are rich in potassium and phosphates, the blood plasma or lymph on which they live abounds in chlorides and sodium salts. § 30. In the broad features above mentioned, the white blood-corpuscle may be taken as a picture and example of all living tissues. If we examine the histological elements of any tissue, whether we take an epithelium cell, or a nerve cell, or a cartilage cell, or a muscular fibre, we meet with very similar features. Studying the element morphologically, we find a nucleus1 and a cell body, the nucleus having the general characters described above with frequently other characters introduced, and the cell body consisting of at least more than one kind of material, the materials being sometimes so disposed as to produce the optical effect simply of a transparent mass in which granules are imbedded, in which case we speak of the cell body as protoplasmic, but at other times so arranged that the cell body possesses dif- ferentiated structure. Studying the element from a chemical point of view, we find proteids always present, and among these bodies identical with or more or less closely allied to myosin, we generally have evidence of the presence also of fat of some kind and of some member or members of the carbohydrate group, and the ash always contains potassium and phosphates, with sulphates, chlorides, sodium, and calcium, to which may be added mag- nesium and iron. We stated in the Introduction that living matter is always undergoing chemical change ; this continued chemical change we may denote by the term metabolism. We further urged that as long as living matter is alive, the chemical change or metabolism is of a double kind. On the one hand, the living substance is continually breaking down into simpler bodies, with a setting free of energy ; this part of the metabolism we may speak of as made up of katabolic changes. On the other hand, the living substance is continually building itself up, embodying energy into itself and so replen- ishing its store of energy ; this part of the metabolism we may speak of as made up of anabolic changes. We also urged that in every piece of living tissue there might be (1) the actual living substance itself, (2) material which is present for the purpose of becoming, and is on the way to become living substance — that is to say, food undergoing or about to undergo anabolic changes, and (3) material which has resulted from, or is resulting from, the breaking down of the living substance — that is to say, material which has undergone or is undergoing katabolic changes, and which we speak of as waste. In using the word " living substance,'' however, we must remember that in reality it is not a substance in the chemical sense of the word, but material undergoing a series of changes. If, now, we ask the question, which part of the body of the white cor- puscle (or of a similar element of another tissue) is the real living substance, and which part is food or waste, we ask a question which we cannot as yet definitely answer. We have at present no adequate morphological criteria 1 The existence of multinuclear structures does not affect the present argument. THE CORPUSCLES OF THE BLOOD. 47 to enable us to judge, by optical characters, what is really living and what is not. The material which appears in the cell body in the form of distinct granules, merely lodged in the more transparent material, cannot be part of the real living substance ; it must be either food or waste. Many of these granules are fat, and we have at times an opportunity of observing that they have been introduced into the corpuscle from the surrounding plasma. The white corpuscle, as we have said, has the power of executing amoeboid movements ; it can creep around objects, envelope them with its own substance, and so put them inside itself. The granules of fat thus in- troduced may be subsequently extruded or may disappear within the cor- puscle ; in the latter case they are obviously changed, and apparently made use of by the corpuscle. In other words, these fatty granules are apparently food material on their way to be worked up in the living substance of the corpuscle. But we have also evidence that similar granules of fat may make their appearance wholly within the corpuscle ; they are products of the activity of the corpuscle. We have further reason to think that in some cases, at all events, they arise from the breaking down of the living substance of the corpuscle, that they are what we have called waste products. But all the granules visible in a corpuscle are not necessarily fatty in nature ; some of them may undoubtedly be proteid granules, and it is possi- ble that some of them may at times be of carbohydrate or other nature. In all cases, however, they are either food material or waste products. And what is true of the easily distinguished granules is also true of other sub- stances, in solution or in a solid form, but so disposed as not to be optically recognized. Hence a part, and it may be no inconsiderable part, of the white corpus- cle, may be not living substance at all, but either food or waste. Further, it does not necessarily follow that the whole of any quantity of material, fatty or otherwise, introduced into the corpuscle from without, should actually be built up into and so become part of the living substance; the changes from raw food to living substance are, as we have already said, probably many, and it may be that after a certain number of changes, few or many, part only of the material is accepted as worthy of being made alive, and the rest, being rejected, becomes at once waste matter ; or the material may, even after it has undergone this or that change, never actually enter into the living substance, but all become waste matter. We say waste matter, but this does not mean useless matter. The matter so formed may without entering into the living substance be of some subsidiary use to the corpuscle, or, as probably more often happens, being discharged from the corpuscle, may be of use to some other part of the body. We do not know how the living substance builds itself up, but we seem compelled to admit that, in certain cases at all events, it is able in some way or other to produce changes on material while that material is still outside the living substance as it were, before it enters into and indeed without its ever actually entering into the composition of the living substance. On the other hand, we must equally admit that some of the waste substances are the direct products of the katabolic changes of the living substance itself — were actually once part of the living substance. Hence we ought, perhaps, to distinguish the products of the activity of living matter into waste products proper, the direct results of katabolic changes, and into by-products which are the results of changes effected by the living matter outside itself, and which cannot, therefore, be considered as necessarily either anabolic or katabolic. Concerning the chemical characters of the living matter itself we cannot 48 BLOOD. at present make any very definite statement. We may say that the proteid myosin, or rather the proteid antecedent or antecedents of myosin, enter in some way into its structure, but we are not justified in saying that the living substance consists only of proteid matter in a peculiar condition. And, indeed, the persistency with which some representative of fatty bodies and some representative of carbohydrates always appear in living tissue would, perhaps, rather lead us to suppose that these equally with proteid material were essential to its structure. Again, though the behavior of the nucleus, as contrasted with that of the cell body, leads us to suppose that the living substance of the former is a different kind from that of the latter, we do not know exactly in what the difference consists. The nucleus, as we have seen, contains nuclein which, perhaps, we may regard as a largely modified proteid ; but being a body which is remarkable for its stability, for the difficulty with which it is changed by chemical reagents, cannot be regarded as an integral part of the essentially mobile living substance of the nucleus. In this connection it may be worth while to again call attention to the fact that the corpuscle contains a very large quantity of water, viz., about 90 per cent. Part of this, we do not know how much, probably exists in a more or less definite combination with the protoplasm, somewhat after the manner of, to use what is a mere illustration, the water of crystallization of salts. If we imagine a whole group of different complex salts continually occupied in turn in being crystallized and being decrystallized, the water thus engaged by the salts will give us a rough image of the water which passes in and out of the substance of the corpuscle as the result of its meta- bolic activity. We might call this " water of metabolism." Another part of the water, carrying in this case substances in solution, probably exists in spaces or interstices too small to be seen with even the highest powers of the microscope. Still another part of the water similarly holding substances in solution exists at times in definite spaces visible under the microscope, more or less regularly spherical, and called vacuoles. We have dwelt thus at length on the white corpuscle in the first place, because, as we have already said, what takes place in it is in a sense a picture of what takes place in all living structures, and in the second place because the facts which we have mentioned help us to understand how the white corpuscle may carry on in the blood a work of no important kind ; for from what has been said it is obvious that the white corpuscle is continually acting upon and being acted upon by the plasma. § 31. To understand, however, the work of these white corpuscles, we must learn what is known of their history. In successive drops of blood taken at different times from the same individual, the number of colorless corpuscles will be found to vary very much, not only relatively to the red corpuscles, but also absolutely. They must, therefore, " come and go." In treating of the lymphatic system we shall have to point out that a very large quantity of fluid called lymph, containing a very considerable number of bodies, very similar in their general characters to the white cor- puscles of the blood, is being continually poured into the vascular system at the point where the thoracic duct joins the great veins on the left side of the neck, and to a less extent where the other large lymphatics join the venous system on the right side of the neck. These corpuscles of lymph, which, as we have just said, closely resemble, and, indeed, are with difficulty distinguished from the white corpuscles of the blood, but of which, when they exist outside the vascular system, it will be convenient to speak of as leucocytes, are found along the whole length of the lymphatic system, but THE CORPUSCLES OF THE BLOOD. 49 are more numerous in the lymphatic vessels after these have passed through the lymphatic glands. These lymphatic glands are partly composed of what is known as adenoid tissue, a special kind of connective tissue arranged as a delicate network. The meshes of this are crowded with colorless nucle- ated cells, which, though varying in size, are, for the most part, small, the nucleus being surrounded by a relatively small quantity of cell substance. Many of these cells show signs that they are undergoing cell-division, and we have reason to think that cells so formed, acquiring a larger amount of cell substance, become veritable leucocytes. In other words, leucocytes multiply in the lymphatic glands, and leaving the glands by the lymphatic vessels, make their way to the blood. Patches and tracts of similar adenoid tissue, not arranged, however, as distinct glands, but similarly occupied by developing leucocytes and similarly connected with lymphatic vessels, are found in various parts of the body, especially in the mucous membranes. Hence we may conclude that from various parts of the body, the lymph- atics are continually bringing to the blood an abundant supply of leuco- cytes, and that these in the blood become ordinary white corpuscles. This is probably the chief source of the white corpuscles, for though the white corpuscles have been seen dividing in the blood itself, no large increase takes place in that way. § 32. It follows that since white corpuscles are thus continually being added to the blood, white corpuscles must as continually either be destroyed, or be transformed, or escape from the interior of the bloodvessels ; otherwise the blood would soon be blocked with white corpuscles. Some do leave the bloodvessels. In treating of the circulation we shall have to point out that white corpuscles are able to pierce the walls of the capillaries and minute veins, and thus to make their way from the interior of the bloodvessels into spaces filled with lymph, the " lymph spaces," as- they are called, of the tissue lying outside the bloodvessels. This is spoken of as the " migration of the white corpuscles." In an "inflamed area" large numbers of white corpuscles are thus drained away from the blood into the lymph spaces of the tissue ; and it is probable that a similar loss takes place, more or less, under normal conditions. These migrating cor- puscles may, by following the devious tracks of the lymph, find their way back into the blood ; some of them, however, may remain, and undergo various changes. Thus, in inflamed areas, when suppuration follows in- flammation, the white corpuscles which have migrated may become " pus corpuscles," or, where thickening and growth follow upon inflammation, may, according to many authorities, become transformed into temporary or permanent tissue, especially connective tissue ; but this transformation into tissue is disputed. When an inflammation subsides without leaving any effect a few corpuscles only will be found in the tissue; those which had previously migrated must, therefore, have been disposed of in some way or another. In speaking of the formation of red corpuscles (§ 27) we saw that not only it is not proved that the nucleated corpuscles which give rise to red corpuscles are ordinary white corpuscles, but that in all probability the real hsematoblasts, the parents of red corpuscles, are special corpuscles developed in the situations where the manufacture of red corpuscles takes place. So far, therefore, from assuming, as is sometimes done, that the white corpuscles of the blood are all of them on their way to become red corpuscles, it may be doubted whether any of them are. In any case, however, even making allowance for those which migrate, a very considerable number of the white corpuscles must " disappear " in some way or other from the blood stream, and we may, perhaps, speak of their disappearance as being a " destruction " 50 BLOOD. or " dissolution." We have, as yet, no exact knowledge to guide us in the matter, but we can readily imagine, that upon the death of the corpuscle, the substances composing it, after undergoing changes, are dissolved by and become part of the plasma. If so, the corpuscles, as they die, must repeat- edly influence the composition and nature of the plasma. But if they thus affect the plasma in their death, it is even more probable that they influence it during their life. Being alive, they must be continually taking in and giving out. As we have already said, they are known to ingest, after the fashion of an amoeba, solid particles of various kinds, such as fat or carmine, present in the plasma, and probably digest such of these particles as are nutritious. But if they ingest these solid matters they probably also carry out the easier task of ingesting dissolved matters. If, however, they thus take in, they must also give out; and thus by the removal on the one hand of various substances from the plasma, and by the addition on the other hand of others, they must be .continually influencing the plasma. We have already said that the white corpuscles in shed blood as they die are supposed to play an important part in the clotting of blood ; similarly they may dur- ing their whole life be engaged in carrying out changes in the proteids of the plasma which do not lead to clotting, but which prepare them for their various uses in the body. Pathological facts aflbrd support to this view. The disease called leuco- cythsemia (or leukaemia) is characterized by an increase of the white cor- puscles, both absolute and relative to the red corpuscles, the increase, due to an augmented production or possibly to a retarded destruction, being at times so great as to give the blood a pinkish-gray appearance, like that of blood mixed with pus. We accordingly find that in this disease the plasma is in many ways profoundly affected and fails to nourish the tissues. As a further illustration of the possible action of the white corpuscles we may state that, according to some observers in certain diseases in which minute organisms, such as bacteria, make their appearance in the blood, the white corpuscles " take up " these bacteria into their substance, and thus probably, by exerting an influence on them, modify the course of the disease of which these organisms are the essential cause. If the white corpuscles are thus engaged during their life in carrying on important labors, we may expect them to differ in appearance according to their condition. Some of the corpuscles are spoken of as " faintly " or " finely " granular. Other corpuscles are spoken of as " coarsely " granular, their cell substance being loaded with conspicuously discrete granules. It may be, of course, that there are two distinct kinds of corpuscles, having different functions and possibly different origins and histories ; but since intermediate forms are met with containing a few coarse granules only, it is more probable that the one form is a phase of the other ; that a faintly granular corpuscle, by taking in granules from without or by producing granules within itself as products of its metabolism, may become a coarsely granular corpuscle. Whether, however, the white corpuscles are really all of one kind, or whether they are different kinds performing different functions, must at present be left an open question. Blood Platelets. § 33. In a drop of blood examined with care immediately after removal may be seen a number of exceedingly small bodies (2// to 3/Jt in diameter), frequently disc-shaped, but sometimes of a rounded or irregular form, homo- geneous in appearance when quite fresh, but apt to assume a faintly gran- THE CHEMICAL COMPOSITION OF BLOOD. 51 [FiG. 10. ular aspect. They are called blood platelets, or blood plaques. They have been supposed by some to become developed into, and, indeed, to be early stages of, the red corpuscles, arid hence have been called ha3inatoblasts ; but this view has not been confirmed ; indeed, as we have seen (§ 27), the real hsematoblasts, or developing red corpuscles, are of quite a different nature. They speedily undergo change after removal from the body, apparently dissolving in the plasma ; they break up, part of their substance disappearing, while the rest becomes granular. Their granular remains are apt to run together, forming in the plasma the shapeless masses which have long been known and described as <4 lumps of protoplasm." By appropriate re- agents, however, these platelets may be fixed and stained in the condition in which they appear after leaving the body. The substance composing them is peculiar, and, though we may perhaps speak of them as consisting of living material, their nature is at present obscure. They may be seen within the living bloodvessels [Fig. 10], and therefore must be regarded as real parts of the blood, and not as products of the changes taking vem-3 place in blood after it has been shed. When a needle or thread or other foreign body is introduced into the interior of a bloodvessel, they are apt to collect upon, and, indeed, are the precursors of the clot which in most cases forms around the needle or thread. They are also found in the thrombi or plugs which sometimes form in the bloodvessels as the result of disease or injury. Indeed, it has been main- tained that what are called white thrombi (to distinguish them from red thrombi, which are plugs of corpuscles and fibrin) are in reality aggrega- tions of blood platelets ; and for various reasons blood platelets have been supposed to play an important part in the clotting of blood, carrying out the work which, in this respect, is by others attributed to the white corpus- cles. But no very definite statement can at present be made about this ; and, indeed, the origin and whole nature of these blood platelets is at pre- sent obscure. Fibrin Filaments and Blood Platelets: A, network of fibrin, shown after washing away the corpuscles from a preparation of blood that has been allowed to clot ; many of the filaments radiate from small clumps of blood plate- lets. B (from Osier), blood cor- puscles and elementary particles or blood platelets within a small THE CHEMICAL COMPOSITION OF BLOOD. § 34. We may now pass briefly in review the chief chemical characters of blood, remembering always that, as we have already urged, the chief chemical interests of blood are attached to the changes which it undergoes in the several tissues; these will be considered in connection with each tissue at the appropriate place. The average specific gravity of human blood is 1055, varying from 1045 to 1075 within the limits of health. The reaction of blood as it flows from the bloodvessels is found to be distinctly though feebly alkaline. If a drop be placed on a piece of faintly red, highly glazed litmus paper, and then wiped off", a blue stain will be left. The whole blood contains, in a certain quantity, gases — viz., oxygen, car- bonic acid, and nitrogen, which are held in the blood in a peculiar way — which vary in different kinds of blood, and so serve especially to distin- 52 BLOOD. guish arterial from venous blood, and which may be given off from blood when exposed to an atmosphere, according to the composition of that atmosphere. These gases of blood we shall study in connection with res- piration. The normal blood consists of corpuscles and plasma. If the corpuscles be supposed to retain the amount of water proper to them, blood may, in general terms, be considered as consisting by weight of from about one-third to somewhat less than one-half of corpuscles, the rest being plasma. As we have already seen, the number of corpuscles in a specimen of blood is found to vary considerably, not only in different ani- mals and in different individuals, but in the same individual at different times. The plasma is resolved by the clotting of the blood into serum and fibrin. § 35. The serum contains in 100 parts : Proteid substances , . about 8 or 9 parts. Fats, various extractives, and saline matters " 2 or 1 part. Water ...,,.. 90 parts. The proteids are paraglobulin and serum-albumin (there being probably more than one kind of serum-albumin) in varying proportion. We may, perhaps, roughly speaking, say that they occur in about equal quantities. Conspicuous and striking as are the results of clotting, massive as appears to be the clot which is formed, it must be remembered that by far the greater part of the clot consists of corpuscles. The amount by weight of fibrin re- quired to bind together a number of corpuscles, in order to form even a large, firm clot, is exceedingly small. Thus, the average quantity by weight of fibrin in human blood is said to be 0.2 per cent. ; the amount, however, which can be obtained from a given quantity of plasma varies extremely, the variation being due not only to circumstances affecting the blood, but to the method employed. The fats, which are scanty, except after a meal or in certain pathological conditions, consist of the neutral fats — stearin, palmitin, and olein — with a certain quantity of their respective alkaline soaps. The peculiar complex fat lecithin occurs in very small quantities only ; the amount present of the peculiar alcohol cholesterin, which had so fatty an appearance is also small. Among the extractives present in serum may be put down nearly all the nitrogenous and other substances which form the extractives of the body and of food, such as urea, kreatin, sugar, lactic acid, etc. A very large number of these have been discovered in the blood under various circum- stances, the consideration of which must be left for the present. The pecu- liar odor of blood or of serum is probably due to the presence of volatile bodies of the fatty acid series. The faint yellow color of serum is due to a special yellow pigment. The most characteristic and important chemical feature of the saline constitution of the serum is the preponderance, at least in man and most animals, of sodium salts over those of potassium. In this respect the serum offers a marked contrast to the corpuscles. Less marked, but still striking, is the abundance of chlorides and the poverty of phosphates in the serum, as compared with the corpuscles. The salts may in fact briefly be described as consisting chiefly of sodium chloride, with some amount of sodium carbonate, or more correctly sodium bicar- bonate, and potassium chloride with small quantities of sodium sulphate, sodium phosphate,, calcium phosphate, and magnesium phosphate. And of even the small quantity of phosphates found in the ash, part of the phosphorus exists in the serum itself, not as a phosphate, but as phos- phorus in some organic body. QUANTITY OF BLOOD, AND ITS DISTKIBUTION IN THE BODY. 53 § 36. The red corpuscles contain lees water than the serum, the amount of solid matter being variously estimated at from 30 to 40 or more per cent. The solids are almost entirely organic matter, the inorganic salts amounting to less than 1 per cent. Of the organic matter again by far the larger part consists of haemoglobin. In 100 parts of the dried organic matter of the corpuscles of human blood, about 90 parts are haemoglobin, about 8 parts are proteid substances, and about 2 parts are other substances. Of the last, one of the most important, forming about a quarter of them and apparently being always present, is lecithin. Cholesterin appears also to be normally present. The proteids which form the stroma of the red cor- puscles appear to belong chiefly to th^ globulin family. As regards the inorganic constituents, the corpuscles are distinguished by the relative abundance of the salts of potassium and of phosphates. This at least is the case in man ; the relative quantities of sodium and potassium in the corpuscles and serum respectively appear, however, to vary in different animals ; in some the sodium salts are in excess even in the corpuscles. § 37. The proteid matrix of the white corpuscles we have stated to be composed of myosin (or an allied body), paraglobulin and possibly other proteids. The nuclei contain nuclein. The white corpuscles are found to contain, in addition to proteid material, lecithin and other fats, glycogen, extractives and inorganic salts, there being in the ash, as in that of the red corpuscles, a preponderance of potassium salts and of phosphates. The main facts of interest then in the chemical composition of the blood are as follows : The red corpuscles consist chiefly of haemoglobin. The or- ganic solids of serum consist partly of serum-albumin, and partly of para- globulin. The serum or plasma contrasts, in man at least, with the corpus- cles, inasmuch as the former contains chiefly chlorides and sodium salts, while the latter are richer in phosphates and potassium salts. The extrac- tives of the blood are remarkable rather for their number and variability than for their abundance, the most constant and important being perhaps urea, kreatin, sugar, and lactic acid. THE QUANTITY OF BLOOD, AND ITS DISTRIBUTION IN THE BODY. § 38. The quantity of blood contained in the whole vascular system is a balance struck between the tissues which give to, and those which take away from, the blood. Thus the tissues of the alimentary canal largely add to the blood water and the material derived from food, while the excretory organs largely take away water and the other substances constituting the excretions. Other tissues both give and take, and the considerable drain from the blood to the lymph spaces which takes place in the capillaries is met by the flow of lymph into the great veins. From the result of a few observations on executed criminals it has been concluded that the total quantity of blood in the human body is about T^th of the body weight. But in various animals, the proportion of the weight of the blood to that of the body has been found to vary very considerably in different individuals ; and probably this holds good for nian also, at all events within certain limits. In the same individual the quantity probably does not vary largely. A sudden drain upon the water of the blood by great activity of the excretory organs, as by profuse sweating, or a sudden addition to the water of the blood, as by drinking large quantities of water or by injecting fluid into the blood- vessels, is rapidly compensated for by the passage of water from the tissues to the blood, or from the blood to the tissues. As we have already said, the tissues are continually striving to keep up an average composition of the 54 THE CONTRACTILE TISSUES. blood, and in so doing keep up an average quantity. In starvation the quantity (and -quality) of the blood is maintained for a long time at the expense of the tissues, so that after some days' privation of food and drink, while the fat, the muscles, and other tissues have been largely diminished, the quantity of blood remains nearly the same. The total quantity of blood present in an animal body is estimated in the fol- lowing way : As much blood as possible is allowed to escape from the vessels ; this is measured directly. The vessels are then washed out with water or normal saline solution, and the washings carefully collected, mixed, and measured. A known quantity of blood is diluted with water or normal saline solution until it possesses the same tint as a measured specimen of the washings. This gives the amount of blood (or rather of haemoglobin) in the measured specimen, from which the total quantity in the whole washings is calculated. Lastly, the whole body is carefully minced and washed free from blood. The washings are collected and filtered, and the amount of blood in them is estimated, as before, by comparison with a specimen of diluted blood. The quantity of blood, as calculated from the two washings, together with the escaped and directly measured blood, gives the total quantity of blood in the body. The method is not free from objections, but other methods are even more imperfect. The blood is in round numbers distributed as follows : About one-fourth in the heart, lungs, large arteries and veins. About one-fourth in the liver. About one-fourth in the skeletal muscles. About one-fourth in the other organs. Since in the heart and great bloodvessels the blood is simply in transit, without undergoing any great changes (and in the lungs, as far as we know, being limited to respiratory changes), it follows that the alterations which take place in the blood passing through the liver and skeletal muscles far exceed those which occur in the rest of the body. CHAPTER II. THE CONTRACTILE TISSUES. § 39. IN order that the blood may nourish the several tissues it is carried to and from them by the vascular mechanism ; and this carriage entails active movements. In order that the blood may adequately nourish the tis- sues, it must be replenished by food from the alimentary canal, and purified from waste by the excretory organs ; and both these processes entail move- ments. Hence before we proceed further we must study some of the general characters of the movements of the body. Most of the movements of the body are carried out by means of the mus- cles of the trunk and limbs, which being connected with the skeleton are frequently called skeletal muscles. A skeletal muscle when subjected to certain influences suddenly shortens, bringing its two ends nearer together; and it is the shortening, acting upon various bony levers or by help of other mechanical arrangements, which produces the movement. Such a temporary shortening, called forth by certain influences, and due as we shall see to changes taking place in the muscular tissue forming the chief part of the THE PHENOMENA OF MUSCLE AND NERVE. 55 muscle, is technically called a contraction of the muscle ; and the muscular tissue is spoken of as a contractile tissue. The heart is chiefly composed of muscular tissue, differing in certain minor features from the muscular tissue of the skeletal muscles, and the beat of the heart is essentially a contraction of the muscular tissue composing it, a shortening of the peculiar muscular fibres of which the heart is chiefly made up. The movements of the ali- mentary canal and of many other organs are similarly the results of the contraction of the muscular tissue entering into the composition of those organs, of the shortening of certain muscular fibres built up into those organs. In fact, almost all the movements of the body are the result of the contraction of muscular fibres, of various nature and variously disposed. Some few movements, however, are carried out by structures which can- not be called muscular. Thus, in the pulmonary passages and elsewhere, movement is effected by means of cilia attached to epithelium cells ; and elsewhere, as in the case of the migrating white corpuscles of the blood, transference from place to place in the body is brought about by amoeboid movements. But as we shall see the changes in the epithelium cell or white corpuscle which are at the bottom of ciliary or amoeboid movements are, in all probability, fundamentally the same as those which take place in a mus- cular fibre when it contracts : they are of the nature of a contraction, and hence we may speak of all these as different forms of contractile tissue. Of all these various forms of contractile tissue, the skeletal muscles, on account of the more complete development of their functions, will be better studied first ; the others, on account of their very simplicity, are in many respects less satisfactorily understood. All the ordinary skeletal muscles are connected with nerves. We have no reason for thinking that they are thrown into contraction, under normal conditions, otherwise than by the agency of nerves. Muscles and nerves being thus so closely allied, and having besides so many properties in common, it will conduce* to clearness and brevity if we treat them together. THE PHENOMENA OF MUSCLE AND NERVE. Muscular and Nervous Irritability. § 40. The skeletal muscles of a frog, the brain and spinal cord of which have been destroyed, do not exhibit any spontaneous movements or contrac- tions, even though the nerves be otherwise quite intact. Left undisturbed, the whole body may decompose without any contraction of any of the skele- tal muscles having been witnessed. Neither the skeletal muscles nor the nerves distributed to them possess any power of automatic action. If, however, a muscle be laid bare and be more or less violently disturbed — if, for instance, it be pinched, or touched with a hot wire, or brought into contact with certain chemical substances, or subjected to the action of gal- vanic currents — it will move, that is, contract, whenever it is thus disturbed. Though not exhibiting any spontaneous activity, the muscle is (and con- tinues for some time after the general death of the animal to be) irritable. Though it remains quite quiescent when left untouched, its powers are then dormant only — not absent. These require to be roused or " stimulated " by some change or disturbance in order that they may manifest themselves. The substances or agents which are thus able to evoke the activity of an irritable muscle are spoken of as stimuli. But to produce a contraction in a muscle the stimulus need not be ap- plied directly to the muscle ; it may be applied indirectly by means of the 56 THE CONTRACTILE TISSUES. nerve. Thus, if the trunk of a nerve be pinched, or subjected to sudden heat, or dipped in certain chemical substances, or acted upon by various galvanic currents, contractions are seen in the muscles to which branches of the nerves are distributed. The nerve, like the muscle, is irritable; it is thrown into a state of activity by a stimulus : but, unlike the muscle, it does not itself contract. The stimulus does not give rise in the nerve to any visible change of form ; but that changes of some kind or other are set up and propagated along the nerve down to the muscle is shown by the fact that the muscle contracts when a part of the nerve at some distance from itself is stimulated. Both nerve and muscle are irritable, but only the muscle is contractile — L e., mani- fests its irritability by contraction. The nerve manifests its irritability by transmitting along itself, without any visible alteration of form, certain molecular changes set up by the stimulus. We shall call these changes thus propagated along a nerve " nervous impulses." § 41. We have stated above that the muscle may be thrown into con- traction by stimuli applied directly to itself. But it might fairly be urged that the contractions so produced are in reality due to the fact that the stimulus, although apparently applied directly to the muscle, is, after all, brought to bear on some of the many fine nerve-branches, which, as we shall see, are abundant in the muscle, passing along and between the muscular fibres, in which they finally end. The following facts, however, go far to prove that the muscular fibres themselves are capable of being directly stimulated without the intervention of any nerves : When a frog (or other animal) is poisoned with urari, the nerves may be subjected to the strongest stimuli without causing any contractions in the muscles to which they are distributed ; yet even ordinary stimuli, applied directly to the muscle, readily cause contractions. If, before introducing the urari into the system, a ligature be passed underneath the sciatic nerve in one leg — for instance, the right — and drawn tightly round the whole leg to the exclusion of the nerve, it is evident that the urari, when injected into the back of the animal, will gain access to the right sciatic nerve above the ligature, but not below, while it will have free access to the rest of the body, including the whole left sciatic. If, as soon as the urari has taken effect, the two sciatic nerves be stimulated, no movement of the left leg will be produced by stimulating the left sciatic, whereas strong contractions of the muscles of the right leg below the ligature will follow stimulation of the right sciatic, whether the nerve be stimulated above or below the ligature. Now, since the upper parts of both sciatics are equally exposed to the action of the poison, it is clear that the failure of the left nerve to cause contraction is not attributable to any change having taken place in the upper portion of the nerve, else why should not the right, which has in its upper portion been equally exposed to the action of the poison, also fail? Evidently the poison acts on some parts of the nerve lower down. If a single muscle be removed from the circulation (by ligaturing its bloodvessels), previous to the poisoning with urari, that muscle will contract when any part of the nerve going to it is stimulated, though no other muscle in the body will contract when its nerve is stimulated. Here the whole nerve right down to the muscle has been exposed to the action of the poison, and yet it has lost none of its power over the muscle. On the other hand, if the muscle be allowed to remain in the body, and so be exposed to the action of the poison, but the nerve be divided high up and the part connected with the muscle gently lifted up before the urari is introduced into the system, so that no blood flows to it. and so that it is protected from tl & influence of the poison, stimulation of the nerve will be found to produce no contractions in THE PHENOMENA OF MUSCLE AND NERVE. 57 the muscle, though stimuli applied directly to the muscle at once causes it to contract. From these facts it is clear that urari poisons the ends of the nerve within the muscle long before it affects the trunk ; and it is exceedingly probable that it is the very extreme ends of the nerves (possibly the end- plates or peculiar structures in which the nerve fibres end in the muscular fibres, for urari poisoning, at least when profound, causes a slight, but yet distinctly recognizable effect in the microscopic appearance of these struc- tures) which are affected. The phenomena of urari poisoning go far to prove that muscles are capable of being made to contract by stimuli ap- plied directly to the muscular fibres themselves ; and there are other facts which support this view. § 42. When, in a recently killed frog, we stimulate by various means and in various ways the muscles and nerves, it will be observed that the movements thus produced, though very various, may be distinguished to be of two kinds. On the one hand, the result may be a mere twitch, as it were, of this or that muscle ; on the other hand, one or more muscles may remain shortened or contracted for a considerable time — a limb, for instance, being raised up or stretched out, and kept raised up or stretched out for many seconds. And we find, upon examination, that a stimulus may be applied either in such a way as to produce a mere twitch, a passing rapid contraction which is over and gone in a fraction of a second, or in such a way as to keep the muscle shortened or contracted for as long a time as, up to certain limits, we may choose. The mere twitch is called a single or simple muscular contraction; the sustained contraction, which, as we shall see, is really the result of rapidly repeated simple contractions, is called a tetanic contraction. §43. In order to study these contractions adequately, we must have recourse to the " graphic method," as it is called, and obtains a tracing or other record of the change of form of the muscle. To do this conveniently, it is best to operate with a muscle isolated from the rest of the body of a recently killed animal, and carefully prepared in such a way as to remain irritable for some time. The muscles of cold-blooded animals remain irri- table after removal from the body far longer than those of warm-blooded animals, and hence those of the frog are generally made use of. We shall study presently the conditions which determine this maintenance of the irri- tability of muscles arid nerves after removed from the body. A muscle thus isolated, with its nerve left attached to it, is called a muscle-nerve preparation. The most convenient muscle for this purpose in the frog is, perhaps, the gastrocnemius, which should be dissected out so as to leave carefully preserved the attachment to the femur above, some portion of the tendon (tendo Achillis) below, and a considerable length of the sciatic nerve with its branches going to the muscle. (Fig. 11.) § 44. We may apply to such a muscle-nerve preparation the various kinds of stimuli (mechanical, such as pricking or pinching ; thermal, such as sudden heating ; chemical, such as acids or other active chemical sub- stances ; or electrical) and these we may apply either to the muscle directly or to the nerve, thus affecting the muscle indirectly. Of all these stimuli by far the most convenient for general purposes are electrical stimuli of various kinds ; and these, except for special purposes, are best applied to the nerve, and not directly to the muscle. Of electrical stimuli, again, the currents, as they are called, generated by a voltaic cell, are most convenient, though the electricity generated by a rotating magnet, or that produced by friction may be employed. Making use of a cell or battery of cells — Daniell's, Grove's, Leclanche, or any other — we must distinguish between the current produced by the cell itself, the 58 THE CONTRACTILE TISSUES. constant current, as we shall call it, and the induced current obtained from the constant current by means of an induction coil, as it is called ; for FIG. 11. A Muscle-nerve Preparation : TO, the muscle, gastrocnemius of frog; n, the sciatic nerve, all the branches being cut away except that supplying the muscle ; /, femur; cl., clamp ; t. a., tendo Achillis ; sp. c., end of spinal canal. the physiological effects of the two kinds of current are in many ways different. It may, perhaps, be worth while to remind the reader of the following facts : In a galvanic battery, the substance (plate of zinc, for instance) which is acted upon and used by the liquid is called the positive element, and the substance which is not so acted upon and used up (plate, etc., of copper, platinum, or carbon, etc. ) is called the negative element. A galvanic action is set up when the positive (zinc) and the negative (copper) elements are connected outside the battery by some conducting material, such as a wire, and the current is said to flow in a cir- cuit or circle from the zinc or positive element to the copper or negative element inside the battery, and then from the copper or negative element back to the zinc or positive element through the wire outside the battery. If the conducting wire be cut through, the current ceases to flow ; but if the cut ends be brought into contact, the current is re-established and continues to flow so long as the contact is good. The ends of the wires are called " poles," or when used for physiological purposes, in which case they may be fashioned in various ways, are spoken of as electrodes. When the poles are brought into contact or are connected by some conducting material, galvanic action is set up, and the current flows through the battery and wires; this is spoken of as "making the current" or "completing or closing the circuit." When the. poles are drawn apart from each other, or when some non-conducting material is interposed between them, the galvanic action is arrested; this is spoken of as "breaking the current" or "opening the circuit." The current passes from the wire connected with the negative (copper) element in the battery to the wire connected with the positive (zinc) element in the battery ; hence, the pole connected with the copper (negative) element is called the positive pole, and that connected with the zinc (positive) element is called the negative pole. When used for physiological purposes the positive pole becomes the positive elec- THE PHENOMENA OF MUSCLE AND NERVE. 59 trode, and the negative pole the negative electrode. The positive electrode is often spoken of as the anode (ana, up), and the negative electrode as the kathode (kata, down). A piece of nerve of ordinary length, though not a good conductor, is still a conductor, and when placed on the electrodes completes the circuit, permitting the current to pass through it ; in order to remove the nerve from the influence of the current it must be lifted off from the electrodes. This is obviously incon- venient ; and hence it is usual to arrange a means of opening or closing the cir- cuit at some point along one of the two wires. This may be done in various ways — by fastening one part of the wire into a cup of mercury, and so by dipping the other part of the wire into the cup to close the circuit and make the current, and by lifting it out of the mercury to open the circuit and break the current ; or by arranging between the two parts of the wires a movable bridge of good con- ducting material, such as brass, which can be put down to close the circuit or raised up to open the circuit ; or in other ways. Such a means of closing and opening a circuit, and so of making or breaking a current, is called a key. A key which is frequently used by physiologists goes by the name of Du Bois- Reymond's key. Though undesirable in many respects, it has the advantage that it can be used in two different ways ; when arranged as in A, Fig. 12, the brass bridge FIG. 12. Kat Diagram of Du Bois-Reymond Key used, A, for making and breaking ; B, for short-circuiting. of K, the key, being down, and forming a means of good conduction between the brass plates to which the wires are screwed, the circuit is closed and the current passes from the positive pole (end of the negative (copper) element) to the posi- tive electrode, or anode, An., through the nerve, to the negative electrode, or kathode, Kat., and thenc^ back to the negative pole (end of the positive (zinc) element) in the battery ; on raising the brass bridge, the circuit is opened, the current is broken, and no current passes through the electrodes. When arranged as in B, if the brass bridge be " down," the resistance offered by it is so small, compared with the resistance offered by the nerve between the electrodes, that the whole current from the battery passes through the bridge back to the battery, and none, or only an infinitesimal portion, passes into the nerve. When, on the other hand, the bridge is raised, and so the conduction between the two sides suspended, the current is not able to pass directly from one side to the other, but can and does pass along the wire through the nerve back to the battery. Hence, in arrange- ment A, "putting down the key," as it is called, makes a current in the nerve, and "raising" or "opening the key" breaks the current. In arrangement B. however, putting down the key diverts the current from the nerve by sending it through the bridge, and so back to the battery ; the current, instead of making the longer circuit through the electrodes, makes the shorter circuit through the 60 THE CONTRACTILE TISSUES. key ; hence, this is called "short-circuiting." When the bridge is raised the cur- rent passes through the nerve on the electrodes. Thus, " ' putting down ' ' and "raising " or " opening " the key have contrary effects in A and B. In B, it will be observed, the battery is always at work, the current is always flowing either through the electrodes (key up) or through the key (key down) ; in A, the battery is not at work until the circuit is made by putting down the key. And in many cases it is desirable to take, so to speak, a sample of the current while the battery is in full swing, rather than just as it begins to work. Moreover, in B the elec- trodes are, when the key is down, wholly shut off from the current ; whereas, in A, when the key is up, one electrode is still in direct connection with the battery, and this connection leading to what is known as unipolar action, may give rise to stimulation of the nerve. Hence the use of the key in the form B. Other forms of key may be used. Thus, in the Morse key (F, Fig. 1 3) contact is made by pressing down a lever handle (ha) ; when the pressure is removed, the handle, driven up by a spring, breaks contact. In the arrangement shown in the figure, one wire from the battery being brought to the binding screw 6, while the binding screw a is connected with the other wire, putting down the handle makes connection between a and &, and thus makes a current. By arranging the wires in the several binding screws in a different way, the making contact by depressing the handle may be used to short circuit. In an " induction coil," Figs. 13 and 14, the wire connecting the two elements of a battery is twisted at some part of its course into a close spiral, called the jtriiiHinj coil. Thus, in Fig. 13, the wire cc//x, connected with the copper or nega- tive plate c. p. of the battery, E, joins the primary coil, pr. c. , and then passes on as ?/x/, through the "key" F, to the positive (zinc) plate, z.p., of the battery. Over this primary coil, but quite unconnected with it, slides another coil, the secoiidart/ coil ,s\ c. ; the ends of the wire forming this coil, T/X/ and xx/, are con- tinued on in the arrangement illustrated in the figure as y' and ?/, and as x/ and .-c, and terminate in electrodes. If these electrodes are in contact or connected with conducting material, the circuit of the secondary coil is said to be closed ; otherwise it is open. In such an arrangement it is found that at the moment when the primary cir- cuit is closed, i. e., when the primary current is " made," a secondary "induced" current is, for an exceedingly brief period of time, set up in the secondary coil. Thus, in Fig. 13, when, by moving the "key" f] y/// and xx//, previously not in connection with each other, are put into connection, and the primary current thus made, at that instant a current appears in the wires, ?/", x", etc., but almost imme- diately disappears. A similar almost instantaneous current is also developed when the primary current is "broken," but not till then. So long as the primary cur- rent flows with uniform intensity, no current is induced in the secondary coil. It is only when the primary current is either made or broken, or suddenly varies in intensity, that a current appears in the secondary coil. In each case the cur- rent is of very brief duration, gone in an instant almost, and may therefore be spoken of as "a shock," an induction shock; being called a "making shock," when it is caused by the making, and a "breaking shock," when it is caused by the breaking of the primary circuit. The direction of the current in the making shock is opposed to that of the primary current ; thus, in the figure, while, the primary current flows from x/// to y'" , the induced making shock flows from y to x. The current of the breaking shock, on the other hand, flows in the same direction as the primary current from x to ?/, and is therefore in direction the reverse of the making shock. Compare Fig. 14, where arrangement is shown in a diagrammatic manner. The current from the battery, upon its first entrance into the primary coil, as it passes along each twist of that coil, gives rise in the neighboring twists of the same coil to a momentary induced current having a direction opposite to its own, and therefore tending to weaken itself. It is not until this "self-induction" has passed off that the current in the primary coil is established in its full strength. Owing to this delay in the full establishment of the current in the primary coil, the induced current in the secondary coil is developed more slowly than it would be were no such " self-induction " present. On the other hand, when the current from the battery is "broken " or "shut off" from the primary coil, no such delay is offered to its disappearance, and consequently the induced current in the second- THE PHENOMENA OF MUSCLE AND NEKVE. FIG. 13. 61 Diagram illustrating Apparatus arranged for Experiments with Muscle and Nerve: A. The moist chamber containing the muscle-nerve preparation. The muscle m, supported by the clamp cl., which firmly grasps the end of the femur/, is connected by means of the S-hooks and a thread with the lever /, placed below the moist chamber. The nerve n, with a portion of the spinal col- umn ri still attached to it, is placed on the electrode-holder el, in contact with the wires x, y. The whole of the interior of the glass case gl, is kept saturated with moisture, and the electrode-holder is so constructed that a piece of moistened blotting-paper may be placed on it without coming into contact with the nerve. - B. The revolving cylinder bearing the smoked paper on which the lever writes. C. Du Bois-Reymond's key arranged for short-circuiting. The wires x and y of the electrode- 62 THE CONTRACTILE TISSUES. ary coil is developed with unimpeded rapidity. We shall see later on that a rapidly developed current is more effective as a stimulus than is a more slowly. FIG. 14. Diagram of an Induction Coil : + positive pole, end of negative element ; — negative pole, end of positive element of battery ; K, Du Bois-Reymond's key ; pr. c. primary coil, current shown by feathered arrow ; sc. c. secondary coil, current shown by unfeathered arrow. developed current. Hence the making shock, where rapidity of production is interfered with by the self-induction of the primary coil, is less effective as a stimulus than the breaking shock whose development is not thus interfered with. The strength of the induced current depends, on the one hand, on the strength of the current passing through the primary coil — that is, on the strength of the battery. It also depends on the relative position of the two coils. Thus a second- ary coil is brought nearer and nearer to the primary coil and made to overlap it more and more ; the induced current becomes stronger and stronger, though the current from the battery remains the same. With an ordinary battery, the sec- ondary coil may be pushed to some distance away from the primary coil, and yet shocks sufficient to stimulate a muscle will be obtained. For this purpose, how- ever, the two coils should be in the same line ; when the secondary coil is placed crosswise, at right angles to the primary, no induced current is developed, and at intermediate angles the induced current has intermediate strengths. When the primary current is repeatedly and rapidly made and broken, the secondary current being developed with each make and with each break, a rapidly recurring series of alternating currents is developed in the secondary coil and holder are connected through binding screws in the floor of the moist chamber with the wires x', y', and these are secured in the key, one on either side. To the same key are attached the wires x", y", coming from the secondary coils s. c. of the induction coil D. This secondary coil can be made to slide up and down over the primary coilpr. c., with which are connected the two wires x'" and y'"; x'"is connected directly with one pole— for instance, the copper pole c. p. of the battery E; y'" is carried to a binding screw, a, of the Morse key F, and is continued as y'^ from another binding screw, b, of the key to the zinc pole z. p. of the battery. Supposing everything to be arranged, and the battery charged ; on depressing the handle ha, of the Morse key F, a current will be made in the primary coil pr. c., passing from c. p. through x"' to pr. c., and thence through y" to a, thence to 6, and so through y"~ to z. p. On removing the finger from the handle of F, a spring thrusts up the handle, and the primary circuit is in conse- quence immediately broken. At the instant that the primary current is either made or broken, an induced current is for the instant developed in the secondary coil s. c. If the cross-bar h in the Du Bois-Reymond's key be raised (as shown in the thick line in the figure), the wires x", x', x, the nerve between the elec- trodes and the wires y, y', y", form the complete secondary circuit, and the nerve consequently experiences a making or breaking induction-shock whenever the primary current is made or broken. If the cross-bar of the Du Bois-Reymond key be shut down, as in the dotted line h' in the figure, the resistance of the cross-bar is so slight compared with that of the nerve and of the wires going from the key to the nerve, that the whole secondary (induced) current passes from x" to y" (or from y"io x") along the cross-bar, and practically none passes into the nerve. The nerve, being thus " short-circuited," is not affected by any changes in the current. The figure is intended merely to illustrate the general method of studying muscular contraction ; it is not to be supposed that the details here given are universally adopted, or, indeed, the best for all purposes. THP: PHENOMENA OF MUSCLE AND NERVE. 63 passes through its electrodes. We shall frequently speak of this as the interrupted induction current, or more briefly the interrupted current ; it is sometimes spoken of as thefaradic current, and the application of it to any tissue is spoken of as faradization. Such a repeated breaking and making of the primary current may be effected in many various ways. In the instruments commonly used for the purpose, the primary current is made and broken by means of a vibrating steel slip working against a magnet : hence the instrument is called a magnetic interrupter. See Fig. 15. The two wires x and y from the battery are connected with the two brass pillars a and d bv means of screws. Directly contact is thus made current, indicated FIG The Magnetic Interrupter. in the figure by the thick interrupted line, passes in the direction of the arrows, up the pillar a, along the steel spring ft, as far as the screw c, the point of which, armed with platinum, is in contact with a small platinum plate on b. The cur- rent passes from b through c and a connecting wire into the primary coil p. Upon its entering into the primary coil, an induced (making) current is for the instant developed in the secondary coil (not shown in the figure). From the primary coil p the current passes, by a connecting wire, through the double spiral w, and. did nothing happen, would continue to pass from m by a connecting wire to the pillar c?, and so by the wire y to the battery. The whole of this course is indicated by the thick interrupted line with its arrows. As the current, however, passes through the spirals m, the iron cores of these are made magnetic. They, in consequence, draw down the iron bar e, fixed at the end of the spring ft, the flexibility of the spring allowing this. But when e is drawn down, the platinum plate on the upper surface of b is also drawn away from the screw c, and thus the current is " broken " at b. (Sometimes the. screw / is so arranged that when e is drawn down a platinum plate on the wider surface of b is brought into contact with the platinum-armed point of the screw / The cur- rent then passes from b. not to c, but to /, and so down the pillar d, in the direction indicated by the thin interrupted line, and out of the battery by the wire y, and is thus cut off from the primary coil. But this arrangement is unnecessary.) At the instant that the current is thus broken and so cut off from the primary coil, an induced (breaking) current is for the moment developed in the secondary coil. But the current is cut off not only from the primary coil, but also from the spirals m ; in consequence, their cores cease to be magnetized, the bar e ceases to be attracted by them, and the spring ft, by virtue of its elasticity, resumes its former position 64 THE CONTRACTILE TISSUES. in contact with the screw c. This return of the spring, however, re-establishes the current in the primary coil and in the spirals, and the spring is drawn down, to be released once more in the same manner as before. Thus, as long as the current is passing along jc, the contact of b with c is alternately being made and broken, and the current is constantly passing into and being shut off from p, the periods of alternation being determined by the periods of vibration of the spring b. With each passage of the current into or withdrawal from the pri- mary coil, an induced (making and, respectively, breaking) current is developed in" a secondary coil. As thus used, each " making shock," as explained above, is less powerful than the corresponding "breaking shock;" and, indeed, it sometimes happens that instead of each make, as well as each break, acting as a stimulus, giving rise to a contraction, the "breaks" only are effective, the several "makes" giving rise to no contraction. But what is known as Helmholtz's arrangement (Fig. 16), however, the making and breaking shocks may be equalized. For this purpose the screw c is raised out The Magnetic Interrupter with Helmholtz's Arrangement for Equalizing the Make and Break Shock. of reach of the excursions of the spring 6, and a moderately thick wire w, offering a certain amount only of resistance, is interposed between the upper binding screw of on the pillar rr, and the binding screw c' leading to the primary coil. Under these arrangements the current from the battery passes through a', along the inter- posed wire to c', through the primary coil, and thus, as before, to m. As before, by the magnetism of m, e is drawn down and b brought in contact with /. As the result of this contact, the current from the battery can now pass by a, /, and d (shown by the thin interrupted line), back to the battery; but not the whole of the current, some of it can still pass along the wire w to the primary coil, the rela- tive amount being determined by the relative resistance offered by the two courses. Hence at each successive magnetization of m, the current in the primary coil does not entirely disappear when b is brought in contact with /; it is only so far dimin- ished that m ceases to attract e, and hence by the release of b from / the whole current once more passes along w. Since, at what corresponds to the " break " the current in the primary coil is diminished only, not absolutely done away with, self-induction makes its appearance at the "break" as well as at the "make;" thus the " breaking " and "making " induced currents or shocks in the secondary coil are equalized. They are both reduced to the lower efficiency of the "mak- ing ' ' shock in the old arrangement ; hence to produce the same strength of THE PHENOMENA OF MUSCLE AND NERVE. 65 stimulus with this arrangement a stronger current must be applied or the sec- ondary coil pushed over the primary coil to a greater extent than with the other arrangement. The Phenomena of a Simple Muscular Contraction. § 45. If the far end of the nerve of a muscle-nerve preparation (Figs. 11 and 13) be laid on electrodes connected with the secondary coil of an induction-machine, the passage of a single induction-shock, which may be taken as a convenient form of an almost momentary stimulus, will produce no visible change in the nerve, but the muscle will give a twitch, a short, sharp contraction, i. e., will for an instant shorten itself, becoming thicker the while, and then return to its previous condition. If one end of the mus- cle be attached to a lever, while the other is fixed, the lever will by its move- ments indicate the extent and duration of the shortening. If the point of the lever be brought to bear on some rapidly travelling surface, on which it leaves a mark (being for this purpose armed with a pen and ink if the sur- face be plain paper, or with a bristle or finely pointed piece of platinum foil if the surface be smoked glass or paper), so long as the muscle remains at rest the lever will describe an even line, which we may call the base line. If, however, the muscle shortens the lever will rise above the base line and thus describe some sort of curve above the base line. Now it is found that when a single induction-shock is sent through the nerve the twitch which the muscle gives causes the lever to describe some such curve as that shown in Fig. 17 ; the lever (after a brief interval immediately succeeding the open- ing or shutting the key, of which we shall speak presently) rises at first rap- idly but afterward more slowly, showing that the muscle is correspondingly shortening ; then ceases to rise, showing that the muscle is ceasing to grow shorter ; then descends, showing that the muscle is lengthening again, and finally, sooner or later, reaches and joins the base line, showing that the muscle after the shortening has regained its previous natural growth. Such a curve described by a muscle during a twitch or simple muscular contrac- tion, caused by a single induction-shock or by any other stimulus producing the same effect, is called a curve of a simple muscular contraction, or more shortly, a " muscle-curve." It is obvious that the exact form of the curve described by identical contractions of a muscle will depend on the rapidity with which the recording surface is travelling. Thus if the surface be travel- ling slowly the up-stroke corresponding to the shortening will be very abrupt FIG. 17. FIG. 18. A Muscle-curve from the Gastrocnemius of the Frog : This curve, like all succeeding ones, unless otherwise indicated, is to be read from left to right— that is to say, while the lever and tuning-fork were stationary the recording surface was travelling from right to left. a indicates the moment at which the induction-shock is sent into the nerve, b the com- mencement, c the maximum, and d the close of the contraction. Below the muscle-curve is the curve drawn by a tuning-fork making 100 double vibrations a second, each complete curve representing therefore one-hundredth of a second. and the down stroke also very steep, as in Fig. 18, which is a curve from a gastrocnemius muscle of a frog, taken with a slowly moving drum, the 66 THE CONTRACTILE TISSUES. FIG. 19. "tuning-fork being the same as that used in Fig. 17; indeed, with a very slow movement, the two may be hardly separable from each other. On the other hand, if the surface travel very rapidly the curve may be immediately long drawn out, as in* Fig. 19, which is a curve from a gastrocnemius muscle of a frog, taken with a very rapidly moving pendulum myograph, the tuning-fork making about 500 vibra- tions a second. On examination, however, it will be found that both these extreme curves are fundamen- tally the same as the medium one, when account is taken of the different rapidities of the travelling sur- face in the several cases. In order to make the " muscle-curve " complete, it is necessary to mark on the recording surface the exact time at which the induction shock is sent into the nerve, and also to note the speed at which the recording surface is travelling. In the pendulum myograph the rate of movement can be calculated from the length of the pendulum ; but even in this it is convenient, and in the case of the spring myograph and revolving cylinder is neces- sary, to measure the rate of movement directly by means of a vibrating tuning-fork, or of some body vibrating regularly. Indeed it is best to make such a direct measurement with each curve that is taken. A tuning-fork, as is known, vibrates so many times a second according to its pitch. If a tuning-fork, armed with a light marker on one of its prongs and vibrating say 100 a second — i. e., executing a double vibration, moving forward and backward, 100 times a second — be brought while vibrating to make a trac- ing on the recording surface immediately below the lever belonging to the muscle, we can use the curve or rather curves described by the tuning-fork to measure the duration of any part or of the whole of the muscle-curve. It is essential that at starting the point of the marker of the tuning-fork should be ex- actly underneath the marker of the lever, or rather, since the point of the lever as it moves up and down describes not a straight line but an arc of a circle of which its fulcrum is the centre and itself (from the fulcrum to the tip of the marker) the radius, that the point of the marker of the tuning-fork should be exactly on the arc described by the marker of the lever, either above or below it, as may prove most convenient. If, then, at starting the tuning-fork marker be thus on the arc of the lever marker, and we note on the curve of the tuning fork the place where the arc of the lever cuts it at the beginning and at the end of the muscle-curve, as at Fig. 17, we can count the number of vibrations of the tuning- fork which have taken place between the two marks, and so ascertain the whole time of the muscle-curve ; if, for instance, there have been 10 double vibrations, each occupying T^Q- second, the whole curve has taken y1^ second to make. In the same way we THE PHENOMENA OF MUSCLE AND NERVE. 67 can measure the duration of the rise of the curve or of the fall, or of any part of it. Though the tuning-fork may, by simply striking it, be set going long enough for the purposes of an observation, it is convenient to keep it going by means of an electric current and a magnet, very much as the spring in the magnetic interrupter (Fig. 15) is kept going. It is not necessary to use an actual tuning-fork ; any rod, armed with a marker, which can be made to vibrate regularly, and whose time of vibra- tion is known, may be used for the purpose : thus a reed, made to vibrate by a blast of air, is sometimes employed. The exact moment at which the induction shock is thrown into the nerve may be recorded on the muscle-curve by means of a " signal," which may be applied in various ways. A large steel lever armed with a marker is arranged over a small coil by means of a light spring in such a way that when the coil by the passage of a current through it becomes a magnet it pulls the lever down to itself; on the current being broken, and the magnetization of the coil ceasing, the lever by help of the spring Hies up. The marker of such a lever is placed immediately under — i. c. , at some point on the arc described by — the marker of the muscle (or other) lever. Hence by making a current in the coil and putting the signal lever down, or by breaking an already existing current, and letting the signal lever fly up, we can make at pleasure a mark corresponding to any part we please of the muscle (or other) curve. If, in order to magnetize the coil of the signal, we use, as we may do, the pri- mary current which generates the induction-shock, the breaking or making of the primary current, whichever we use to produce the induction-shock, will make the signal lever fly up or come down. Hence we shall have on the recording surface, under the muscle, a mark indicating the exact moment at which the primary cur- rent was broken or made. Now the time taken up by the generation of the induced current and its passage into the nerve between the electrodes is so infinitesimally small, that we may, without appreciable error, take the moment of the breaking or making of the primary current as the moment of the entrance of the induction- shock into the nerve. Thus we can mark below the muscle-curve, or by describing the arc of the muscle lever, on the muscle-curve itself, the exact moment at which the induction-shock falls into the nerve between the electrodes, as is done at a in Figs. 17, 18, 19. In the pendulum myograph a separate signal is not needed. If, having placed the muscle lever in the position in which we intend to make it record, we allow the glass plate to descend until the tooth a' just touches the rod c (so that the rod is just about to be knocked down, and so break the primary circuit) and make on the base line, which is meanwhile being described by the lever marker, a mark to indicate where the point of the marker is under these circumstances, and then bring back the plate to its proper position, the mark which we have made will mark the moment of the breaking of the primary circuit, and so of the entrance of the induction-shock into the nerve. For it is just when, as the glass plate swings down, the marker of the lever comes to the mark which we have made that the rod c is knocked back and the primary current is broken. A ''signal" like the above, in an improved form known as Desprez's, may be used also to record time, and thus the awkwardness of bringing a large tuning- fork up to the recording surface obviated. For this purpose the signal is intro- duced into a circuit the current of which is continually being made and broken by a tuning-fork (Fig. 21 ). The tuning-fork once set vibrating continues to make and break the current at each of its vibrations, and as stated above is kept vibrating by the current. But each make or break caused by the tuning-fork affects also the small coil of the signal, causing the lever of the signal to fall down or fly up. Thus the signal describes vibration-curves synchronous with those of the tuning-fork driving it. The signal may similarly be worked by means of vibrating agents other than a tuning-fork. Various recording surfaces may be used. The form most generally useful is a cylinder covered with smoked paper and made to revolve by clockwork or other- wise; such a cylinder driven by clockwork is shown in Fig. 13, B. By using a 68 THE CONTRACTILE TISSUES. FIG. 20. The Pendulum Myograph : The figure is diagrammatic, the essentials only of the instrument being shown. The smoked glass plate A swings with the pendulum B on carefully adjusted bearings at C. The contrivances by which the glass plate can be removed and replaced at pleasure are not shown. A second glass plate so arranged that the first glass plate may be moved up and down without altering the swing of the pendulum is also omitted. Before com- mencing an experiment the pendulum is raised up (in the figure to the right), and is kept in that position by the tooth a catching on the spring-catch b. On depressing the catch b the glass plate is set free, swings into the new position indicated by the dotted lines, and is held in that posi- tion by the tooth a' catching on the catch b'. In the course of its swing the tooth a' coming in contact with the projecting steel rod c, knocks it on one side into the position indicated by the THE PHENOMENA OF MUSCLE AND NERVE. 69 cylinder of large radius with adequate gear, a high speed for instance, in a second, can be obtained. In the spring myograph a smoked glass plate is thrust rapidly FIG. 21. ! p Diagram of an Arrangement of a Vibrating Tuning-fork with a Desprez Signal : The current flows along the wire / connected with the positive ( + ) pole or end of the negative plate (N) of the battery, through the tuning-fork, down the pin connected with the end of the lower prong, to the mercury in the cup Hg, and so by a wire (shown in figure) to the binding screw e. From this binding screw part of the current flows through the coil d between the prongs of the tuning- fork, and thence by the wire c to the binding screw a, while another part flows through the wire g, through the coil of the Desprez signal back by the wire b, to the binding screw a. From the binding screw a the current passes back to the negative (— ) pole or end of the positive element (P) of the battery. As the current flows through the coil of the Desprez signal from g to b, the core of coil becoming magnetized draws down the marker of the signal. As the current flows through the coil d.the core of that coil, also becoming magnetized, draws up the lower prong of the fork. But the pin is so adjusted that the drawing up of the prong lifts the point of the pin out of the mercury. In consequence, the current, being thus broken at Hg, flows neither through d nor through the Desprez signal. The core of the Desprez thus ceasing to be magnetized, the marker flies back, being usually assisted by a spring (not shown in the figure). But since the current ceases to flow through d, the core of d ceases to lift up the prong, and the pin, in the descent of the prong, makes contact once more with the mercury. The re-establishment of the current, however, once more acting on the two coils, again pulls down the marker of the signal, and again by magnetizing the core of d pulls up the prong and once more breaks the current. Thus the current is continually made and broken, the rapidity of the interruptions being determined by the vibration periods of the tuning-fork, and the lever of the signal rising and falling synchronously with the movements of the tuning-fork. s forward along a groove by means of a spring suddenly thrown into action. In the pendulum myograpli, Fig. 20, a smoked glass plate attached to the lower end of a long frame swinging like a pendulum, is suddenly let go at a certain height, and so swings rapidly through an arc of a circle. The disadvantage of the last two methods is that the surface travels at a continually changing rate, whereas, in the revolving cylinder, careful construction and adjustment will secure a very uniform rate. § 46. Having thus obtained a time record, and an indication of the exact moment at which the induction-shock falls into the nerve, we may for present purposes consider the muscle-curve complete. The study of such a curve, as, for instance, that shown in Fig. 17, taken from the gastrocnemius of a frog, teaches us the following facts : 1. That although the passage of the induced current from electrode to electrode is practically instantaneous, its effect, measured from the entrance of the shock into the 'nerve to the return of the muscle to its natural length dotted line c'. The rod c is in electric continuity with the wire x of the primary coil of an induction-machine. The screw d is similarly in electric continuity with the wire y of the same primary coil. The screw d and the rod c are armed with platinum at the points at which they are in contact, and both are insulated by means of the ebonite block e. As long as c and d are in contact the circuit of the primary coil to which x and y belong is closed. When in its swing the tooth a' knocks c away from d, at that instant the circuit is broken, and a " breaking " shock is sent through the electrodes connected with the secondary coil of the machine, and so through the nerve. The lever I, the end only of which is shown in the figure, is brought to bear on the glass plate, and when at rest describes a straight line, or more exactly an arc of a circle of large radius. The tuning-fork /, the ends only of the two limbs of which are shown in the figure placed immediately below the lever, serves to mark the time. 70 THE CONTRACTILE TISSUES. after the shortening, takes an appreciable time. In the figure, the whole curve from a to d takes up about the same time as eleven double vibrations of the tuning-fork. Since each double vibration here represents T^7 second, the duration of the whole curve is rather more than y1^ second. 2. In the first portion of this period, from a to 6, there is no visible change, no raising of the lever, no shortening of the muscle. 3. It is not until b, that is to say, after the lapse of about T^ second, that the shortening begins. The shortening, as shown by the curve is at first slow, but soon becomes more rapid, and then slackens again until it reaches a maximum at c; the whole shortening occupying rather more than •rfo second. 4. Arrived at the maximum of shortening, the muscle at once begins to relax, the lever descending at first slowly, then more rapidly, and at last more slowly again, until at d the muscle has regained its natural length ; the whole return from the maximum of contraction to the natural length occupying rather more than T-§Q second. Thus a simple muscular contraction, a simple spasm or twitch, produced by a momentary stimulus, such as a single induction-shock, consists of three main phases : 1. A phase antecedent to any visible alteration in the muscle. This phase, during which invisible preparatory changes are taking place in the nerve and muscle, is called the " latent period." 2. A phase of shortening or, in the more strict meaning of the word, contraction. 3. A phase of relaxation or return to the original length. In the case we are considering, the electrodes are supposed to be applied to the nerve at some distance from the muscle. Consequently the latent period of the curve comprises not only the preparatory actions going on in the muscle itself, but also the changes necessary to conduct the immediate effect of the induction-shock from the part of the nerve between the elec- trodes along a considerable length of nerve down to the muscle. It is obvi- ous that these latter changes might be eliminated by placing the electrodes on the muscle itself or on the nerve close to the muscle. If this were done, the muscle and lever being exactly as before, and care were taken that the induction-shock entered into the nerve at the new spot, at the moment when the point of the lever had reached exactly the same point of the travelling surface as before, two curves would be gained having the relations shown in Fig. 22. The two curves resemble each other in almost all points, except that in the curve taken with the shorter piece of nerve, the latent period, the distance a to b as compared with the distance a to bf is shortened ; the contraction begins rather earlier. A study of the two curves teaches us the following two facts : 1. Shifting the electrodes from a point of the nerve at some distance from the muscle to a point of the nerve close to the muscle has only short- ened the latent period a very little. Even when a very long piece of nerve is taken the difference in the two curves is very small, and, indeed, in order that it may be clearly recognized or measured, the travelling surface must be made to travel very rapidly. It is obvious, therefore, that by far the greater part of the latent period is taken up by changes in the muscle itself, changes preparatory to the actual visible shortening. Of course, even when the electrodes are placed close to the muscle, the latent period includes the changes going on in the short piece of nerve still lying between the elec- trodes and the muscular fibres. To eliminate this with a view of determin- ing the latent period in the muscle itself, the electrodes might be placed directly on the muscle poisoned with urari. If this were done, it would be THE PHENOMENA OF MUSCLE AND NEKVE. 71 found that the latent period remained about the same, that is to say, that in all cases the latent period is chiefly taken up by changes in the muscular as distinguished from the nervous elements. 2. Such difference as does exist between the two curves in the figure indicates the time taken up by the propagation, along the piece of nerve, of FIG. 22. Curves Illustrating the Measurement of the Velocity of a Nervous Impulse : The same muscle- nerve preparation is stimulated (1) as" far as possible from the muscle, (2) as near as possible to the muscle ; both contractions are registered in exactly the same way. In (1) the stimulus enters the nerve at the time indicated by the line a, the contraction begins at b'; the whole latent period, therefore, is indicated by the distance from a to b'. In (2) the stimulus enters the nerve at exactly the same time a ; the contraction begins at b ; the latent period, therefore, is indicated by the distance between a and b. The time taken up by the nervous impulse in passing along the length of nerve between 1 and 2 is, therefore, indicated by the distance between 6 and b', which may be measured by the tuning- fork curve below ; each double vibration of the tuning-fork corresponds to 1-120 or 0.0083 second. the changes set up at the far end of the nerve by the induction-shock. These changes we have already spoken of as constituting a nervous impulse ; and the above experiment shows that it takes a small but yet distinctly appreciable time for a nervous impulse to travel along a nerve. In the figure the difference between the two latent periods, the distance between b and 6', seems almost too small to measure accurately ; but if a long piece of nerve be used for the experiment, and the recording surface be made to travel very fast, the difference between the duration of the latent period when the induction-shock is sent in at a point close to the muscle, and that when it is sent in at a point as far away as possible from the muscle, may be satisfactorily measured in fractions of a second. If the length of nerve between the two points be accurately measured, the rate at which a nervous impulse travels along the nerve to a muscle can thus be easily calculated. This has been found to be in the frog about 28, and in man about 33 metres per second, but varies considerably, especially in warm-blooded animals. Thus when a momentary stimulus, such as a single induction-shock, is sent into a nerve connected with a muscle, the following events take place : a nervous impulse is started in the nerve and this travelling down to the muscle produces in the muscle, first the invisible changes which constitute the latent period, secondly the changes which bring about the shortening or contraction proper, and thirdly the changes which bring about the relaxation and return to the original length. The changes taking place in each of these three phases are changes of living matter ; they vary with the condition of the living sub- stance of the muscle, and only take place so long as the muscle is alive. Though the relaxation which brings back the muscle to its original length is assisted by the muscle being loaded with a weight or otherwise stretched, this is not essential to the actual relaxation, and with the same load the return will vary according to the condition of the muscle ; the relaxation must be considered as an essential part of the whole contraction no less than the shortening itself. § 47. Not only, as we shall see later on, does the whole contraction vary 72 THE CONTRACTILE TISSUES. in extent and character according to the condition of the muscle, the strength of the induction-shock, the load which the muscle is bearing, and various attendant circumstances, but the three phases may vary independently. The latent period may be longer or shorter, the shortening may take a longer or shorter time to reach the same height, and especially the relaxation may be slow or rapid, complete or imperfect. Even when the same strength of induction-shock is used the contraction may be short and sharp or very long drawn out, so that the curves described on a recording surface travelling at the same rate in the two cases appear very different ; and under certain cir- cumstances, as when a muscle is fatigued, the relaxation, more particularly the last part of it, may be so slow, that it may be several seconds before the muscle really regains its original length. Hence, if we say that the duration of a simple muscular contraction of the gastrocnemius of a frog under ordinary circumstances is about y1-^ second, of which y^ is taken up by the latent period, Tf ¥ by the contraction, and y^ by the relaxation, these must be taken as " round numbers," stated so as to be easily remembered. The duration of each phase as well as of the whole contraction varies in different animals, in different muscles of the same animal, and in the same muscle under different conditions. The muscle-curve which we have been discussing is a curve of changes in the length only of the muscle ; but if the muscle, instead of being suspended, were laid flat on a glass plate and a lever laid over its belly, we should find, upon sending an induction-shock into the nerve, that the lever was raised, showing that the muscle during the contraction became thicker. And, if we took a graphic record of the movements of the lever, we should obtain a curve very similar to the one just discussed ; after a latent period the lever would rise, showing that the muscle was getting thicker, and afterward would fall, showing that the muscle was becoming thin again. In other words, in contraction the lessening of the muscle lengthwise is accompanied by an increase crosswise ; indeed, as we shall see later on, the muscle in contracting is not diminished in bulk at all (or only to an exceedingly small extent, about y^TTir °f its total bulk), but makes up for its diminution in length by increasing in its other diameters. § 48. A single induction shock is, as we have said, the most convenient form of stimulus for producing a simple muscular contraction, but this may also be obtained by other stimuli, provided that these are sufficiently sudden and short in their action, as, for instance, by a prick of, or a sharp blow on, the nerve or muscle. For the production of a single simple muscular con- traction the changes in the nerve leading to the muscle must be of such a kind as to constitute what may be called a single nervous impulse, and any stimulus which will evoke a single nervous impulse only may be used to produce a simple muscular contraction. As a rule, however, most stimuli, other than single induction-shocks, tend to produce in a nerve several nervous impulses, and, as we shall see, the nervous impulses which issue from the central nervous system, and so pass along nerves to muscles, are, as a rule, not single and simple, but complex. Hence, as a matter of fact, a simple muscular contraction is within the living body a comparatively rare event (at least as far -as the skeletal muscles are concerned), and cannot easily be produced outside the body otherwise than by a single induction-shock. " The ordinary form of muscular contraction is not a simple muscular contraction, but the more complex form known as a tetanic contraction, to the study of which we must now turn. THE PHENOMENA OF MUSCLE AND NERVE. 73 Tetanic Contraction. § 49. If a single induction-shock be followed at a certain interval by a second shock of the same strength, the first simple contraction will be fol- lowed by a second simple contraction, both contractions being separate and distinct ; and if the shocks be repeated a series of rhythmically recurring separate simple contractions may be obtained. If, however, the interval between two shocks be made short, for instance, only just long enough to allow the first contraction to have passed its maximum before the latent period of the second is over, the curves of the two contractions will bear some such relation to each other as that shown in Fig. 23. It will be FIG. 23. Tracing of a Double Muscle-curve. While the muscle (gastrocnemius of frog) was engaged in the first contraction (whose complete course, had nothing intervened, is indicated by the dotted line), a second induction-shock was thrown in, at such a time that the second contraction began just as the first was beginning to decline. The second curve is seen to start from the first, as does the first from the base-line. observed that the second curve is almost in all respects like the first except that it starts, so to speak, from the first curve instead of from the base-line. The second nervous impulse has acted on the already contracted muscle, and made it contract again just as it would have done if there had been no first impulse and the muscle had been at rest. The two contractions are added together and the lever is raised nearly double the height it would have been by either alone. If in the same way a third shock follows the second at a sufficiently short interval, a third curve is piled on top of the second ; the same with a fourth, and so on. A more or less similar result would occur if the second contraction began at another phase of the first. The combined effect is, of course, greatest when the second contraction begins at the maximum of the first, being less both before and afterward. Hence, the result of a repetition of shocks will depend largely on the rate of repetition. If, as in Fig. 24, the shocks follow each other so slowly FIG. 24. Muscle-curve. Single Induction-shock Repeated Slowly. that one contraction is over, or almost over, before the next begins, each t contraction will be distinct, or nearly distinct, and there will be little or no combined effect. If, however, the shocks be repeated more rapidly, as in Fig. 25, each sue- 74 THE CONTRACTILE TISSUES. ceeding contraction will start from some part of the preceding one, and the lever will be raised to a greater height at each contraction. FIG. 25. Muscle-curve. Single Induction-shock Repeated More Rapidly. If the frequency of the shocks be still further increased, as in Fig. 26, the rise due to the combination of contraction will be still more rapid, and a smaller part of each contraction will be visible on the curve. In each of these three curves it will be noticed that the character of the curve changes somewhat during its development. The change is the result FIG. 26. Muscle-curve. Single Induction-shock Still More Rapidly. of commencing fatigue, caused by the repetition of the contractions, the fatigue manifesting itself by an increasing prolongation of each contrac- tion, shown especially in a delay of relaxation, and by an increasing dimi- nution in the height of the contraction. Thus, in Fig. 24, the contractions, quite distinct at first, become fused later ; the fifth contraction, for instance, is prolonged so that the sixth begins before the lever has reached the base line ; yet the summit of the sixth is hardly higher than the summit of the fifth, since the sixth, though starting at a higher level, is a somewhat weaker contraction. See also, in Fig. 25, the lever rises rapidly at first but more slowly afterward, owing to an increasing diminution in the height of the single contractions. In Fig. 26 the increment of rise of the curve due to each contraction diminishes very rapidly, and though the lever does con- tinue to rise during the whole series, the ascent after about the sixth con- traction is very gradual indeed, and the indications of the individual con- tractions are much less marked than at first. Hence, when shocks are repeated with sufficient rapidity, it results that after a certain number of shocks, the succeeding impulses do not cause any further shortening of the muscle, any further raising of the lever, but merely keep up the contraction already existing. The curve thus reaches a maximum, which it maintains, subject to the depressing effects of exhaus- tion, so long as the shocks are repeated. When these cease to be given, the muscle returns to its natural length. THE PHENOMENA OF MUSCLE AND NERVE. 75 When the shocks succeed each other still more rapidly than in Fig. 26, the individual contractions, visible at first, may become fused together and wholly lost to view in the latter part of the curve. When the shocks succeed each other still more rapidly (the second contraction beginning in the ascending portion of the first) it becomes difficult or impossible to trace out any of the single contractions.1 The curve then described by the lever is of the kind shown in Fig. 27, where the primary current of an induction- Tetanus Produced with the Ordinary Magnetic Interrupter of an Induction-machine. (Recording surface travelling slowly.) The interrupted current is thrown in at a. machine was rapidly made and broken by the magnetic interruptor, Fig. 15. The lever, it will be observed, rises at a (the recording surface is travelling too slowly to allow the latent period to be distinguished), at first very rapidly, in fact in an unbroken and almost a vertical line, and so very speedily reaches the maximum, which is maintained so long as the shocks continue to be given ; when these cease to be given, the curve descends at first very rapidly and then more and more gradually toward the base-line, which it reaches just at the end of the figure. This condition of muscle, brought about by rapidly repeated shocks, this fusion of a number of simple twitches into an apparently smooth continuous effort, is known as tetanus or tetanic contraction. The above facts are most clearly shown when induction-shocks, or at least galvanic currents in some form or other, are employed. They are seen, however, whatever be the form of stimulus employed. Thus, in the case of mechanical stimuli, while a single quick blow may cause a single twitch, a pronounced tetanus may be obtained by rapidly striking successively fresh portions of a nerve. With chemical stimulation, as when a nerve is dipped in acid, it is impossible to secure a momentary application ; hence tetanus, generally irregular in cha- racter, is the normal result of this mode of stimulation. In the living body, the contractions of the skeletal muscles, brought about either by the will or otherwise, are generally tetanic in character. Even very short sharp move- ments, such as a sudden jerk of a limb or a wink of the eyelid, are in reality examples of tetanus of short duration. If the lever, instead of being fastened to the tendon of a muscle hung vertically, be laid across the belly of a muscle placed in a horizontal position and the muscle be thrown into tetanus by a repetition of induction-shocks, it will be seen that each shortening of the muscle is accompanied by a corre- sponding thickening, and that the total shortening of the tetanus is accom- panied by a corresponding total thickening. And, indeed, in tetanus we can observe more easily than in a single contraction that the muscle in contract- 1 The ease with which the individual contractions can be made out depends in part, it need hardly be said, on the rapidity with which the recording surface travels. 76 THE CONTRACTILE TISSUES. ing changes in form only — not in bulk. If a living muscle or group of muscles be placed in a glass jar or chamber, the closed top of which is pro- longed into a narrow glass tube, and the chamber be filled with water (or preferably with a solution of sodium chloride, 0.6 per cent, in strength, usually called " normal saline solution," which is less injurious to the tissue than simple water) until the water rises into the narrow tube, it is obvious that any change in the bulk of the muscle will be easily shown by a rising or falling of the column of fluid in the narrow tube. It is found that when the muscle is made to contract, even in the most forcible manner, the change of level in the height of the column which can be observed is practically insignificant ; there appears to be a fall indicating a diminution of bulk to the extent of about one ten-thousandth of the total bulk of the muscle. So that we may fairly say that in a tetanus, and hence in a simple "contraction, the lessening of the length of the muscle causes a corresponding increase in the other directions ; the substance of the muscle is displaced, not diminished. § 50. So far we have spoken simply of an induction-shock or of induction- shocks without any reference to their strength, and of a living or irritable muscle without any reference to the degree or extent of its irritability. But induction-shocks may vary in strength, and the irritability of the muscle may vary. If we slide the secondary coil a long way from the primary coil, and thus make use of extremely feeble induction-shocks, we shall probably find that these shocks, applied even to a quite fresh muscle-nerve preparation, produce no contraction. If we then gradually slide the secondary coil nearer and nearer the primary coil, and keep on trying the effects of the shocks, we shall find that after a while, in a certain position of the coils, a very feeble con- traction makes its appearance. As the secondary coil comes still nearer to the primary coil, the contractions grow greater and greater. After a while, however — and that, indeed, in ordinary circumstances, very speedily increas- ing— the strength of the shock no longer increases the height of the contrac- tion ; the maximum contraction of which the muscle is capable with such shocks, however strong, has been reached. If we use a tetanizing or interrupted current, we shall obtain the same general results ; we may, according to the strength of the current, get no contraction at all, or contractions of various extent up to a maximum, which cannot be exceeded. Under favorable conditions the maximum contraction may be very considerable ; the shortening in tetanus may amount to three- fifths of the total length of the muscle. The amount of contraction, then, depends on the strength of the stimulus, whatever be the stimulus ; but this holds good within certain limits only ; to this point, however, we shall return later on. § 51. If, having ascertained in a perfectly fresh muscle-nerve prepara- tion the amount of contraction produced by this and that strength of stim- ulus, we leave the preparation by itself for some time — say for a few hours — and then repeat the observations, we shall find that stronger stimuli- stronger shocks, for instance — are required to produce the same amount of contraction as before; that is to say. the irritability of the preparation, the power to respond to stimuli, has in the meanwhile diminished. After a further interval we should find the irritability still further diminished ; even very strong shocks would be unable to evoke contractions as large as those previously caused by weak shocks. At last we should find that no shocks, no stimuli, however strong, were able to produce any visible contraction what- ever. The amount of contraction, in fact, evoked by a stimulus depends not only on the strength of the stimulus, but also on the degree of irritability of the muscle-nerve preparation. CHANGES IN A MUSCLE DURING CONTRACTION. 77 Immediately upon removal from the body, the preparation possesses a certain amount of irritability, not differing very materially from that which the muscle and nerve possess while within and forming an integral part of the body ; but after removal from the body the preparation loses irritability, the rate of loss being dependent on a variety of circumstances ; and this goes on until, since no stimulus which we can apply will give rise to a contrac- tion, we say the irritability has wholly disappeared. We might take this disappearance of irritability as marking the death of the preparation, but it is followed sooner or later by a curious change in the muscle, which is called rigor mortis, and which we shall study presently ; and it is convenient to regard this rigor mortis as marking the death of the muscle. The irritable muscle, then, when stimulated either directly, the stimulus being applied to itself, or indirectly, the stimulus being applied to its nerve, responds to the stimulus by a change of form which is essentially a shorten- ing and thickening. By the shortening (and thickening) the muscle in con- tracting is able to do work, to move the parts to which it is attached ; it thus sets free energy. We have now to study more in detail how this energy is set free, and the laws which regulate its expenditure. ON THE CHANGES WHICH TAKE PLACE IN A MUSCLE DURING A CONTRACTION. The Change in Form. § 52. An ordinary skeletal muscle consists of elementary muscle fibres, bound together in variously arranged bundles by connective tissue which carries bloodvessels, nerves, and lymphatics. The contraction of a muscle is the contraction of all or some of its ele- mentary fibres, the connective tissue being passive ; hence while those fibres of muscle which end directly in the tendon, in contracting pull directly on the tendon, those which do not so end pull indirectly on the tendon by means of the connective tissue between the bundles, which connective tissue is continuous with the tendon. Each muscle is supplied by one or more branches of nerves composed of medullated fibres, with a certain proportion of non-medullated fibres. These branches running in the connective tissue divide into smaller branches and t\vigs between the bundles and fibres. Some of the nerve fibres are dis- tributed to the bloodvessels, and others end in a manner of which we shall speak later on in treating of muscular sensations ; but by far the greater part of the medullated fibres and in the muscular fibres, the arrangement being such that every muscular fibre is supplied with at least one medullated nerve fibre, which joins the muscular fibre somewhere about the middle between its two ends or sometimes nearer one end, in a special nerve ending, of which we shall presently have to speak, called an end- plate. The nerve fibres thus destined to end in the muscular fibres divide as they enter the muscle, so that what, as it enters the muscle, is a single nerve 'fibre, may, by dividing, end as several nerve fibres in several muscu- lar fibres. Sometimes two nerve fibres join one muscular fibre, but in this case the end-plate of each nerve fibre is still at some distance from the end of the muscular fibre. It follows that when a muscular fibre is stimulated by means of a nerve fibre, the nervous impulse travelling down the nerve fibre falls into the muscular fibre not at one end but at about its middle ; it is the middle of the fibre which is affected first by the nervous impulse, and the changes in the muscular substance started in the middle of the muscu- lar fibre travel thence to the two ends of the fibre. In an ordinary skele- 78 THE CONTRACTILE TISSUES. tal muscle, however, as we have said, the fibres and bundles of fibres begin and end at different distances from the ends of the muscle, and the nerve or nerves going to the muscle divide and spread out in the muscle in such a way that the end-plates, in which the individual fibres of the nerve end, are distributed widely over the muscle at very different distances from the ends of the muscle. Hence, if we suppose a single nervous impulse, such as that generated by a single induction-shock, or a series of such impulses to be started at the same time at some part of the trunk of the nerve in each of the fibres of the nerve going to the muscle, these impulses will reach very different parts of the muscle at about the same time and the contractions which they set going will begin, so to speak, nearly all over the whole mus- cle at the same time, and will not all start in any particular zone or area of the muscle. § 53. The wave of contraction. We have seen, however, that under the influence of urari the nerve fibre is unable to excite contractions in a mus- cular fibre, although the irritability of the muscular fibre itself is retained. Hence in a muscle poisoned by urari the contraction begins at that part of the muscular substance which is first affected by the stimulus, and we may start a contraction in what part of the muscle we please by properly placing the electrodes. Some muscles, such, for instance, as the sartorius of the frog, though of some length, are composed of fibres which run parallel to each other from one end of the muscle to the other. If such a muscle be poisoned with urari so as to eliminate the action of the nerves and stimulated at one end (an induction-shock sent through a pair of electrodes placed at some little distance apart from each other at the end of the muscle may be employed, but better results are obtained if a mode of stimulation, of which we shall have to speak presently, viz. the application of the " constant current," be adopted), the contraction which ensues starts from the end stimulated, and travels thence along the muscle. If two levers be made to rest on, or be suspended from, two parts of such a muscle placed horizontally, the parts being at a known distance from each other and from the part stimulated, the progress of the contraction may be studied. The movements of the levers indicate in this case the thickening of the fibres which is taking place at the parts on which the levers rest or to which they are attached ; and if we take a graphic record of these movements, bringing the two levers to mark one immediately below the other, we shall find that the lever nearer the part stimulated begins to move earlier, reaches its maximum earlier, and returns to rest earlier than does the further lever. The contraction, started by the stimulus, in travelling along the muscle from the part stimulated reaches the nearer lever some little time before it reaches the further lever, and has passed by the nearer lever some little time before it has passed by the further lever ; and the further apart the two levers are the greater will be the difference in time between their movements. In other words, the contraction travels along the muscle in the form of a wave, each part of the muscle in succession from the end stimulated swelling out and shortening as the contraction reaches it, and then returning to its original state. And what is true of the collection of parallel fibres which we call the muscle is also true of each fibre, for the swelling at any part of the muscle is only the sum of the swelling of the individual fibres ; and if we were able to take a single long fibre and stimulate it at one end, we should be able, under the microscope, to see a swelling or bulging accom- panied by a corresponding shortening, i. e., to see a contraction, sweep along the fibre from end to end. If, in the graphic record of the two levers just mentioned, we count the CHANGES IN A MUSCLE DURING CONTRACTION. 79 number of vibrations of the tuning-fork which intervene between the mark on the record which indicates the beginning of the rise of the near lever (that is, the arrival of the contraction wave at this lever) and the mark which indicates the beginning of the rise of the far lever, this will give us the time which it has taken the contraction wave to travel from the near to the far lever. Let us suppose this to be 0.005 second. Let us suppose the distance between the two levers to be 15 mm. The contraction wave, then, has taken 0.005 second to travel 15 mm., that is to say it has travelled at the rate of 3 metres per second. And, indeed, we find by this, or by other methods, that in the frog's muscles the contraction wave does travel at a rate which may be put down as from 3 to 4 metres a second, though it varies under different conditions. In the warm-blooded mammal the rate is somewhat greater, and may probably be put down at 5 metres a second in the excised muscle, rising possibly to 10 metres in a muscle within the living body. If, again, in the graphic record of the two levers we count, in the case of either lever, the number of vibrations of the tuning-fork which intervene between the mark where the lever begins to rise and the mark where it has finished its fall and returned to the base-line, we can measure the time inter- vening between the contraction wave reaching the lever and leaving the lever on its way on ward, that is to say we can measure the time which it has taken the contraction wave to pass over the part of the muscle on which the lever is resting. Let us suppose this time to be, say, 0.1 second. But a wave which is travelling at the rate of 3 metres a second, and takes 0.1 second to pass over any point must be 300 mm. long. And, indeed, we find that in the frog the length of the contraction wave may be put down as varying from 200 to 400 mm., and in the mammal it is not very different. Now, as we have said, the very longest muscular fibre is stated to be at most only about 40 mm. in length ; hence, in an ordinary contraction, dur- ing the greater part of the duration of the contraction the whole length of the fibre will be occupied by the contraction wave. Just at the beginning of the contraction there will be a time when the front of the contraction wave has reached, for instance, only half way down the fibre (supposing the stimulus to be applied, as in the case we have been discussing, at one end only), and just at the end of contraction there will be a time, for instance, when the contraction has left the half of the fibre next to the stimulus, but has not yet cleared away from the other half. But nearly all the rest of the time every part of the fibre will be in some phase or other of contraction, though the parts nearer the stimulus will be in more advanced phases than the parts further from the stimulus. This is true when a muscle of parallel fibres is stimulated artificially at one end of the muscles, and when, therefore, each fibre is stimulated at one end. It is, of course, all the more true when a muscle of ordinary construc- tion is stimulated by means of its nerve. The stimulus of the nervous impulse impinges in this case on the muscle fibre at the end-plate which, as we have said, is placed toward the middle of the fibre, and the contrac- tion wave travels from the end-plate in opposite directions toward each end, and has accordingly only about half the length of the fibre to run in. All the more, therefore, must the whole fibre be in a state of contraction at the same time. It will be observed that the contraction wave includes not only the con- traction proper and the thickening and shortening, but the relaxation and return to the natural form ; the first part of the wave up to the summit of the crest corresponds to the shortening and thickening ; the decline from the summit onward corresponds to the relaxation. But we have already 80 THE CONTRACTILE TISSUES. insisted that the relaxation is an essential part of the whole act ; indeed, in a certain sense, as essential as the shortening itself. § 54. Optical changes in a muscular fibre during contraction. So far we have been dealing with the muscle as a whole and as observed with the naked eye, though we have incidentally spoken of fibres. We have now, confining our attention exclusively to skeletal muscles, to consider what mi- croscopic changes take place during a contraction, what are the relations of the histological features of the muscle fibre to the act of contraction. Un- fortunately, our knowledge of the minute structure of the fibre is as yet so limited that any statements must of necessity be but speculative. When muscle contracts there is a translocatiou of molecules whereby there occurs not only a change of form, but other optical (polariscopical and microscopi- cal) alterations which are due to the movement of refractive particles. The long cylindrical sheath of sarcolemma is occupied by muscle sub- stance. After death the muscle substance may separate from the sarco- lemma, leaving the latter as a distinct sheath, but during life the muscle substance is adherent to the sarcolemma, so that no line of separation between the two can be made out ; the movements of the one follow exactly all the movements of the other. Scattered in the muscle substance, but, in the mammal, lying for the most part close under the sarcolemma, are a number of nuclei, oval in shape, with their long axes parallel to the length of the fibre. Around each nucleus is a thin layer of granular-looking substance very similar in appearance to that forming the body of a white blood-corpuscle, and like that often spoken of as undifferentiated protoplasm. A small quantity of the same granular substance is prolonged for some distance, as a narrow conical streak from each end of the nucleus, along the length of the fibre. With the exception of these nuclei with their granular-looking bed and the end-plate or end-plates, to be presently described, all the rest of the space enclosed by the sarcolemma from one end of the fibre to the other appears to be occupied by a peculiar material, striated muscle substance. It is called striated because it is marked out, and that along the whole length of the fibre, by transverse bands [Fig. 28], stretching right across the fibre, of substance which is very transparent, bright [FIG. 28. substance, alternating with similar bands of substance which has a dim cloudy appearance, dim substance ; that is to say, the fibre is marked out along its whole length by alternate bright bands and dim bands. The ^ t bright bands are on an average about 1 p. or 1.5 >j. and Diagrammatic Repre- the dim bands about 2.5 // or 3 /JL thick. By careful sentation of a Muscle- focusing, both bright bands and dim bands may be ^Tri-ht'bSsr^85 traced through the whole thickness of the fibre, so' that the whole fibre appears to be composed of bright discs and dim discs placed alternately one upon the other along the whole length of the fibre, the arrangement being broken by the end-plate and here and there by the nuclei. § 55. We may now return to the question, What happens when a con- traction wave sweeps over the fibre ? Muscular fibres may be examined even under high powers of the micro- scope while they are yet living and contractile ; the contraction itself may be seen, but the rate at which the wave travels is too rapid to permit satis- factory observations to be made as to the minute changes which accompany the contraction. It frequently happens however that when living muscle has been treated with certain reagents, as for instance with osmic acid vapor, and subsequently prepared for examination, fibres are found in which a CHANGES IN A MUSCLE DURING CONTRACTION. 81 bulging, a thickening and shortening, over a greater or less part of the length of the fibre, has been fixed by the osmic acid or other reagent. Such a bulging obviously differs from a normal contraction in being confined to a part of the length of the fibre, whereas, as we have said, a normal wave of contraction, being very much longer than any fibre, occupies the whole length of the fibre at once. We may however regard this bulging as a very short, a very abbreviated wave of contraction, and assume that the changes visible in such a short bulging also take place in a normal contraction. Admitting this assumption, we learn from such preparations that in the contracting region of the fibre, while both dim and bright bands become broader across the fibre, and correspondingly thinner along the length of the fibre, a remarkable change takes place between the dim bands, bright bands, and granular lines. We have seen that in the fibre at rest the intermediate line in the bright band is in most cases inconspicuous ; in the contracting fibre, on the contrary, a dark line in the middle of the bright band in the position of the intermediate line becomes very distinct. As we pass along the fibre from the beginning of the contraction wave to the summit of the wave, where the thickening is greatest, this line becomes more and more striking, until at the height of the contraction it becomes a very marked dark line or thin dark band. Pari passu with this change, the distinction between the dim and the bright bands become less and less marked ; these appear to become confused together, until at the height of the contraction, the whole space between each two now conspicuous dark lines is occupied by a substance which can be called neither dim nor bright, but which in con- trast to the dark line appears more or less bright and transparent. So that in the contracting part there is, at the height of the contraction, a reversal of the state of things proper to the part at rest. The place occupied by the bright band, in the state of rest, is now largely filled by a conspicuous 'dark line which previously was represented by the inconspicuous intermediate line, and the place occupied by the conspicuous dim band of the fibre at rest now seems by comparison with the dark line the brighter part of the fibre. The contracting fibre is, like the fibre at rest, striated, but its striation is dif- ferent in its nature from the natural striation of the resting fibre ; and it is held by some that in the earlier phases of the contraction, while the old nat- ural striation is being replaced by the new1 striation, there is a stage in which all striation is lost. We may add that the outline of the sarcolemma, which in the fibre at rest is quite even, becomes during the contraction indented opposite the intermediate line, and bulges out in the interval between each two interme- diate lines, the bulging and indentation becoming more marked the greater the contraction. § 56. We can learn something further about this remarkable change by examining the fibre under polarized light. When ordinary light is sent through a Nicol prism (which is a rhomb of Ice- land spar divided into two in a certain direction, the halves being subsequently cemented together in a special way) it undergoes a change in passing through the prism arid is said to be polarized. One effect of this polarization is that a ray of light which has passed through one Nicol prism will or will not pass through a second Nicol according to the relative position of the two prisms. Thus, if the second Nicol be so placed that what is called its "optic axis " be in a line with or parallel to the optic axis of the first Nicol the light passing through the first Nicol will also^pass through the second. But if the second Nicol be rotated until its optic axis is at right angles with the optic axis of the first Nicol none of the light- passing through the former will pass through the latter; the prisms in this position are said to be "crossed." In intermediate positions more or less light passes through the second Nicol according to the angle between the two optic axes. 6 82 THE CONTRACTILE TISSUES. Hence when one Nicol is placed beneath the stage of a microscope so that the light from the mirror is sent through it, and another Nicol is placed in the eye- piece, the field of the microscope will appear dark when the eye-piece Nicol is rotated so that its optic axis is at right angles to the optic axis of the lower Nicol, and consequently the light passing through the lower Nicol is stopped by it. If, however, the optic axis of the eye-piece Nicol is parallel to that of the lower Nicol, the light from the latter will pass through the former and the field will be bright ; and as the eye-piece is gradually rotated from one position to the other the bright- ness of the field will diminish or increase. Both the Nicols are composed of doubly refractive material. If now a third doubly refractive material be placed on the stage, and therefore between the two Nicols, the light passing through the lower Nicol will (in a certain position of the doubly refractive material on the stage, that is to say, when its optic axes have a certain position) pass through it. and also through the crossed Nicol in the eye- piece. Hence the doubly refractive material on the stage (or such parts of it as are in the proper position in respect to their optic axes) will, when the eye-piece Nicol is crossed, appear illuminated and bright on a dark field. In this way the existence of doubly refractive material in a preparation may be detected. When muscle prepared arid mounted in Canada balsam is examined in the microscope between Nicol prisms, one on the stage below the object, and the other in the eye-piece, the fibres stand out as bright objects on the dark ground of the field when the axes of the prisms are crossed. On closer examination it is seen that the parts which are bright are chiefly the dim bands. This indicates that it is the dim bands which are doubly refractive, anisotropic, or are chiefly made up of anisotropic substance; there seems, however, to be some slight amount of anisotropic substance in the bright bands, though these as a whole appear singly refractive or isotropic. The fibre accordingly appears banded or striated with alternate bands of aniso- tropic and isotropic material. According to most authors such an .alterna- tion of anisotropic and (chiefly) isotropic bands which is obvious in a dead and prepared fibre.exists also in the living fibre ; but some maintain that the living fibre is uniformly anisotropic. Now, when a fibre contracts, in spite of the confusion previously men- tioned between dim and bright bands, there is no confusion between the anisotropic and isotropic material. The anisotropic, doubly refractive bands, bright under crossed Nicols, occupying the position of the dim bands in the resting fibre, remain doubly refractive, bright under crossed Nicols, even at the very height of the contraction. The isotropic, singly refractive bands, dark under crossed Nicols, occupying the position of the bright bands in the fibre at rest, remain isotropic and dark under crossed Nicols at the very height of the contraction. All that can be seen is that the singly refractive isotropic bands become very thin indeed during the contraction, while the anistropic bands, though of course becoming thinner and broader in the contraction, do not become so thin as do the isotropic bands ; in other words, while both bands become thinner and broader, the doubly refractive aniso- tropic band seems to increase at the expense of the singly refractive isotropic band. § 57. The mere broadening and shortening of each section of the fibre is at bottom a translocation of the molecules of the muscle substance. If we imagine a company of 100 soldiers, ten ranks deep, with ten men in each rank, rapidly, but by a series of gradations, to extend out into a double line with 50 men in each line, we shall have a rough image of the movement of the molecules during a muscular contraction. But, from what has been said, it is obvious that the movement, in striated muscle at least, is a very com- plicated one ; in other forms of contractile tissue it may be, as we shall see, more simple. Why the movement is so complicated in striated muscle, what purposes it serves, why the skeletal muscles are striated, we do not at present CHANGES IN A MUSCLE DURING CONTRACTION. 83 know. Apparently where swift and rapid contraction is required the con- tractile tissue is striated muscle ; but how the striation helps, so to speak, the contraction we do not know. We cannot say what share in the act of con- traction is to be allotted to the several parts. Since, during a contraction, the fibre bulges out more opposite to each dim disc, and is indented opposite to each bright disc, since the dim disc is more largely composed of aniso- tropic material than the rest of the fibre, and since the anisotropic material in the position of the dim disc increases during a contraction, we might per- haps infer that the dim disc rather than the bright disc is the essentially active part. Assuming that the fibrillar substance is more abundant in the dim discs, while the intern" brillar substance is more abundant in the bright discs, and that the fibrillar substance is anisotropic (and hence the dim discs largely anisotropic), while the interfibrillar substance is isotropic, we might also be inclined to infer it is the fibrillar and not the interfibrillar substance which really carries out the contraction ; but even this much is not yet definitely proved. One thing must be remembered. The muscle substance, though it pos- sesses the complicated structure, and goes through the remarkable changes which we have described, is while it is living and intact in a condition which we are driven to speak of as semi-fluid. The whole of it is essentially mobile. The very act of contraction indeed shows this ; but it is mobile in the sense that no part of it, except of course the nuclei and sarcolemma, neither dim nor bright substance, neither fibrillar nor interfibrillar substance, can be regarded as a hard and fast structure. A minute nematoid worm has been seen wandering in the midst of the substance of a living contractile fibre ; as it moved along, the muscle substance gave way before it, and closed up again behind it, dim bands and bright bands all falling back into their proper places. We may suppose that in this case the worm threaded its way in a fluid interfibrillar substance between and among highly extensible and elastic fibrilke. But even on such a view, and still more on the view that the fibrillar substance also was broken and closed up again, the maintenance of such definite histological features as those which we have described in material so mobile can only be effected, even in the fibre at rest, at some con- siderable expenditure of energy, which energy it may be expected has a chemical source. During the contraction there is a still further expenditure of energy, some of which, as we have seen, may leave the muscle as " work done ; " this energy, likewise, may be expected to have a chemical source. We must, therefore, now turn to the chemistry of muscle. The Chemistry of Muscle. § 58. We said in the Introduction that it was difficult to make out with certainty the exact chemical differences between dead and living substance. Muscle, however, in dying undergoes a remarkable chemical change, which may be studied with comparative ease. All muscles, within a certain time after "general " death of the body, lose their irritability, which is succeeded by an event somewhat more sudden, viz., the entrance into the condition known as rigor mortis. The occurrence of rigor mortis, or cadaveric rigidity, as it is sometimes called, which may be considered as a token of the death of the muscle, is marked by the following features: The living muscle possesses a certain translucency, the rigid muscle is distinctly more opaque. The living muscle is very extensible and elastic, it stretches readily and to a considerable extent when a weight is hung upon it, or when any traction is applied to it, but speedily and, under normal circumstances, completely returns to its original length when the weight of traction is removed ; as we 84 THE CONTRACTILE TISSUES. shall see, however, the rapidity and completeness of the return depends on the condition of the muscle, a well-nourished active muscle regaining its normal length much more rapidly and completely than a tired and exhausted muscle. A dead rigid muscle is much less extensible, and at the same time much less elastic ; the muscle now requires considerable force to stretch it, and when the force is removed, does riot, as before, return to its former length. To the touch the rigid muscle has lost much of its former softness, and has become firmer and more resistant. The entrance into rigor mortis is, moreover, accompanied by a shortening or contraction, which may, under certain circumstances, be considerable. The energy of this contraction is not great, so that any actual shortening is easily prevented by the presence of even a slight opposing force. Now the chemical features of the dead rigid muscle are also strikingly different from those of the living muscle. § 59. If a dead muscle, from which all fat, tendon, fascia, and connec- tive tissue have been as much as possible removed, and which has been freed from blood by the injection of "normal " saline solution, be minced and repeatedly washed with water, the washings will contain certain forms of albumin and certain extractive bodies of which we shall speak directly. When the washing has been continued until the wash-water gives no proteid reaction, a large portion of muscle will still remain undissolved. If this- be treated with a 10 per cent, solution of a neutral salt, ammonium chloride being the best, a large portion of it will become dissolved ; the solution, however, is more or less imperfect and filters with difficulty. If the filtrate be allowed to fall drop by drop into a large quantity of dis- tilled water, a white flocculent matter will be precipitated. This flocculent precipitate is myosin. Myosin is a proteid, giving the ordinary proteid reactions, and having the same general elementary composition as other proteids. It is soluble in dilute saline solutions, especially those of ammo- nium chloride, and may be classed in the globulin family, though it is not so soluble as paraglobulin, requiring a stronger solutio"n of a neutral salt to dissolve it ; thus, while soluble in a 5 or 10 per cent, solution of such a salt, it is far less soluble in a 1 per cent, solution, which, as we have seen, readily dissolves paraglobulin. From its solutions in neutral saline solu- tion it is precipitated by saturation with a neutral salt, preferably sodium chloride, and may be purified by being washed with a saturated solution, dissolved again in a weaker solution, and reprecipitated by satu- ration. Dissolved in saline solutions it readily coagulates when heated — i. e.y is converted into coagulated proteid — and it is worthy of notice that it coagulates at a comparatively low temperature, viz., about 56° C. ; this, it will be remembered, is the temperature at which fibrinogen is coagulated, whereas paraglobulin, serum-albumin, and many other proteids, do not coagulate until a higher temperature (75° C.) is reached. Solutions of myosin are precipitated by alcohol, and the precipitate, as in the case of other proteids, becomes, by continued action of the alcohol, altered into coagulated insoluble proteid. We have seen that paraglobulin, and, indeed, any member of the globulin group, is very readily changed by the action of dilute acids into a body called acid-albumin, characterized by not being soluble either in water or in dilute saline solutions, but readily soluble in dilute acids and alkalies, from its solutions in either of which it is precipitated by neutralization, and by the fact that the solutions in dilute acids and alkalies are not coagu- lated by heat. When, therefore, a globulin is dissolved in dilute acid, what takes place is not a mere solution, but a chemical change ; the globulin cannot be got back from the solution, it has been changed into acid-albu- CHANGES IN A MUSCLE DURING CONTRACTION. 85 min. Similarly when globulin is dissolved in dilute alkalies it is changed into alkali-albumin ; and, broadly speaking, alkali-albumin precipitated by neutralization can be changed by solution with dilute acids into acid-albu- min, and acid-albumin by dilute alkalies into alkali-albumin. Now myosin is similarly, and even more readily than is globulin, con- verted into acid-albumin, and by treating a muscle, either washed or not, directly with dilute hydrochloric acid, the myosin may be converted into acid-albumin and dissolved out. Acid-albumin obtained by dissolving muscle in dilute acid used to be called syntonin, and it used to be said that a muscle contained syntonin ; the muscle, however, contains myosin, not syntonin, but it may be useful to retain the word syntonin to denote acid- albumin obtained by the action of dilute acid on myosin. By the action of dilute alkalies, myosin may similarly be converted into alkali-albumin. From what has been above stated it is obvious that myosin has many analogies with fibrin, and we have yet to mention some striking analogies ; it is, however, much more soluble than fibrin, and, speaking generally, it may be said to be intermediate in its character between fibrin and globulin. On keeping, and especially on drying, its solubility is much diminished. Of the substances which are left in washed muscle, from which all the myosin has been extracted by ammonium chloride solution, little is known. If washed muscle be treated directly with dilute hydrochloric acid, a large part of the material of the muscle passes, as we have said, at once into syntonin. The quantity of syntonin thus obtained may be taken as roughly representing the quantity of myosin previously existing in the muscle. A more prolonged action of the acid may dissolve out other proteids, besides myosin, left after the washing. The portion insoluble in dilute hydrochloric acid consists in part of the gelatin-yielding and other substances of the sarcolemma and of the connective and other tissues between the bundles, of the nuclei of these tissues and of the fibres them- selves, and in part, possibly, of some portions of the muscle substance itself. We are not, however, at present in a position to make any very definite statement as to the relation of the myosin to the structural features of muscle. Since the dim bands are rendered very indistinct by the action of a 10 per cent, sodium chloride solution, we may, perhaps, infer that myosin enters largely into the composition of the dim bands, and, therefore, of the fibrillse ; but it would be hazardous to say much more than this. § 60. Living muscle may be frozen, and yet, after certain precautions, will, on being thawed, regain its irritability, or, at all events, will for a time be found to be still living in the sense that it has not yet passed into rigor mortis. We may, therefore, take living muscle which has been frozen as still living. If living contractile muscle, freed as much as possible from blood, be frozen, and while frozen minced and rubbed up in a mortar with four times its weight of snow containing 1 per cent, of sodium chloride, a mixture is obtained which, at a temperature just below 0° C., is sufficiently fluid to be filtered, though with difficulty. The slightly opalescent filtrate, or muscle- plasma, as it is called, is at first quite fluid, but will, when exposed to the ordinary temperature, become a solid jelly, and afterward separate into a clot and serum. It will, in fact, coagulate like blood-plasma, with this dif- ference, that the clot is not firm and fibrillar, but loose, granular, and floc- culent. During the coagulation the fluid, which before was neutral or slightly alkaline, becomes distinctly acid. The clot is myosin. It gives all the reactions of myosin obtained from dead muscle. The serum contains an albumin very similar to, if not identical with 86 THE CONTRACTILE TISSUES. serum-albumin, a globulin differing somewhat from and coagulating at a lower temperature than paraglobulin, and whic,h to distinguish it from the globulin of blood has been called myoglobulm, some other proteids which need not be described here, and various " extractives " of which we shall speak directly. Such muscles as are red also contain a small quantity of haemoglobin, and of another allied pigment called kistohcematin, to which pigments, indeed, their redness is due. Thus, while dead muscle contains myosin, albumin, and other proteids, extractives, and certain insoluble matters, together with gelatinous and other substances not referable to the muscle substance itself, living muscle contains no myosin, but some substance or substances which bear somewhat the same relation to myosin that the antecedents of fibrin do to fibrin, and which give rise to myosin upon the death of the muscle. There are, indeed, reasons for thinking that the myosin arises from the conversion of a previously existing body which may be called myosinogen, and that the conversion takes place, or may take place, by the action of a special ferment, the conversion of myosinogen into myosin being very analogous to the conversion of fibrinogen into fibrin. We may, in fact, speak of rigor mortis as characterized by a coagulation of the muscle-plasma, comparable to the coagulation of blood-plasma, but differing from it inasmuch as the product is not fibrin, but myosin. The rigidity, the loss of suppleness, and the diminished translucency appear to be at all events largely, though probably not wholly, due to the change from the fluid plasma to the solid myosin. We might compare a living muscle to a number of fine transparent membranous tubes containing blood-plasma. When this blood-plasma entered into the "jelly" stage of coagulation, the system of tubes would present many of the phenomena of rigor mortis. They would lose much of their suppleness and translucency, and acquire a certain amount of rigidity. § 61. There is, however, one very marked and important difference be- tween the rigor mortis of muscle and the coagulation of blood. Blood during its coagulation undergoes a slight change only in its reaction ; but muscle during the onset of rigor mortis becomes distinctly acid. A living muscle at rest is in reaction neutral, or, possibly from some remains of lymph adhering to it, faintly alkaline. If, on the other hand, the reaction of a thoroughly rigid muscle be tested, it will be found to be most distinctly acid. This development of an acid reaction is witnessed not only in the solid untouched fibre but also in expressed muscle-plasma ; it seems to be associated in some way with the appearance of the myosin. The exact causation of this acid reaction has not at present been clearly worked out. Since the coloration of the litmus produced is permanent, carbonic acid, which, as we shall immediately state, is set free at the same time, cannot be regarded as the active acid, for the reddening of litmus produced by carbonic acid speedily disappears on exposure. On the other hand, it is possible to extract from rigid muscle a certain quantity of lactic acid, or rather of a variety of lactic acid known as sarcolactic acid;1 and it has been thought that the appearance of the acid reaction of rigid muscle is due to a new formation or to an increased formation of this sarcolactic acid. There is much to be said in favor of this view, but it cannot at present be regarded as established beyond dispute. Coincident with the appearance of this acid reaction, though, as we have said, not the direct cause of it, a large development of carbonic acid takes 1 There are many varieties of lactic acid, which are isomeric, having the same compo- sition, CsHeOs, but differ in their reactions and especially in the solubility of their zine salts. The variety present in muscle is distinguished as sarcolactic acid. CHANGES IN A MUSCLE DURING CONTRACTION. 87 place when muscle becomes rigid. Irritable living muscular substance, like nil living substance, is continually respiring, that is to say, is continually consuming oxygen and giving out carbonic acid. In the body, the arterial blood going to the muscle gives up some of its oxygen, and gains a quantity of carbonic acid, thus becoming venous as it passes through the muscle capillaries. Even after removal from the body, the living muscle continues to take up from the surrounding atmosphere a certain quantity of .oxygen and to give out a certain quantity of carbonic acid. At the onset of rigor mortis there is a very large and sudden increase in this production of carbonic acid, in fact an outburst, as it were, of that gas. This is a phenomena deserving special attention. Knowing that the car- bonic acid which is the outcome of the respiration of the whole body is the result of the oxidation of carbon-holding substances, we might very natu- rally suppose that the increased production of carbonic acid attendant on the development of rigor mortis is due to the fact that during that event a certain quantity of the carbon-holding constituents of the muscle are sud- denly oxidized. But such a view is negatived by the following facts : In the first place, the increased production of carbonic acid during rigor mortis is not accompanied by a corresponding increase in the consumption of oxygen. In the second place, a muscle (of a frog, for instance) contains in itself no free or loosely attached oxygen ; when subjected to the action of a mercurial air-pump it gives off no oxygen to a vacuum, offering in this respect a marked contrast to blood ; and yet, when placed in an atmosphere free from oxygen, it will not only continue to give off carbonic acid while it remains alive, but will also exhibit at the onset of rigor mortis the same increased production of carbonic acid that is shown by a muscle placed in an atmosphere containing oxygen. It is obvious that in such a case the carbonic acid does not arise from the direct oxidation of the muscle sub- stance, for there is no oxygen present at the time to carry on that oxidation. We are driven to suppose that during rigor mortis, some complex body, con- taining in itself ready-formed carbonic acid, so to speak, is split up, and thus carbonic acid is set free, the process of oxidation by which that car- bonic acid was formed out of the carbon-holding constituents of the muscle having taken place at some anterior date. Living resting muscle, then, is alkaline or neutral in reaction, and the substance of its fibres contains a coagulable plasma. Dead rigid muscle, on the other hand, is acid in reaction, and no longer contains a coagulable plasma, but is laden with the solid myosin. Further, the change from the living irritable condition to that of rigor mortis is accompanied by a large and sudden development of carbonic acid. It is found, moreover, that there is a certain amount or parallelism between the intensity of the rigor mortis, the degree of acid reaction and the quantity of carbonic acid given ont. If we suppose, as we fairly may do, that the intensity of the rigidity is dependent on the quantity of myosin deposited in the fibres, and the acid reaction to the development, if not of lactic acid, at least of some other substance, the parallelism between the three products, myosin, acid-producing substance, and carbonic acid, would suggest the idea that all three are the results of the splitting-up of the same highly complex substance. No one has at present, however, succeeded in isolating or in otherwise definitely proving the existence of such a body, and though the idea seems tempting, it' may in the end prove totally erroneous. § 62. As to the other proteids of muscle, such as the albumin and the globulin, we know as yet nothing concerning the parts which they play and the changes which they undergo in the living muscle or in rigor mortis. Besides the fat which is found, and that riot infrequently in abundance, 88 THE CONTRACTILE TISSUES. in the connective tissue between the fibres, there is also present in the muscular substance within the sarcolemma, always some and at times a great deal of fat, chiefly ordinary fat, viz., stearin, palmitiri, and olein in variable proportion, but also the more complex fat lecithin. As to the function of these several fats in the life of the muscle we know little or nothing Carbohydrates, the third of the three great classes in which we may group the energy-holding substances of which the animal body and its food are alike composed, viz., proteids, fat, and carbohydrates, are represented in muscle by a peculiar body, glycogen, which we shall have to study in detail later on. We must here merely say that glycogen is a body closely allied to starch, having a formula, which may be included under the general formula for starches, x (C6H,0O5), and may like it be converted by the action of acids, or by the action of particular ferments known as amylolytic fer- ments, into some form of sugar, dextrose (C6H,2O6), or some allied sugar. Many, if not all, living muscles contain a certain amount, and some, under certain circumstances, a considerable amount, of glycogen. During or after rigor mortis this glycogen is very apt to be converted into dextrose, or an allied sugar. The muscles of the embryo at an early stage contain a rela- tively enormous quantity of glycogen, a fact which suggests that the glyco- gen of muscle is carbohydrate food of the muscle about to be wrought up into the living muscular substance. The bodies which we have called extractives are numerous and varied. They are especially interesting, since it seems probable that they are waste products of the metabolism of the muscular substance, and the study of them may be expected to throw light on the chemical change which mus- cular substance undergoes during life. Since, as we shall see, muscular substance forms by far the greater part of the nitrogenous, that is, proteid, portion of the body, the nitrogenous extractives of muscle demand peculiar attention. Now the body urea, which we shall have to study in detail later on, far exceeds in importance all the other nitrogenous extractives of the body as a whole, since it is practically the one form in which nitrogenous wastes leave the body ; if we include with urea the closely allied uric acid (which for present purposes may simply be regarded as a variety of urea), we may say that all the nitrogen taken in as food sooner or later leaves the body as urea ; compared with this all other nitrogenous waste thrown out from the body is insignificant. Of the urea which thus leaves the body, a considerable portion must at some time or other have existed, or to speak more exactly, its nitrogen must have existed as the nitrogen of the proteids of muscular substance. Nevertheless, no urea at all is, in normal condi- tions, present in muscular substance either living and irritable or dead and rigid ; urea does not arise in muscular substance itself as one of the imme- diate waste products of muscular substance. There is, however, always present in relatively considerable amount, on an average about 0.25 per cent, of wet muscle, a remarkable body, kreatin. This is, in one sense, a compound of urea ; it may be split up into urea and sarcosin. This latter body is a methyl glycin, that is to say, a glycin in which methyl has been substituted for hydrogen, and glycin itself is amido- acetic acid, a compound of amidogen, that is a representative of ammonia and acetic acid. Hence kreatin contains urea, which has close relations with ammonia, together with another representative of ammonia, and a sur- plus of carbon and hydrogen arranged as a body belonging to the fatty acid series. We shall have to return to this kreatin and consider its relation to urea and to muscle when we come to deal with urine. The other nitrogenous extractives, such as karnin, hypoxanthin (or CHANGES IN A MUSCLE DURING CONTRACTION, 89 sarkin), xanthiu, taurin, etc., occur in small quantity, and need not be dwelt on here. Among non-nitrogenous extractives the most important is the sarcolactic acid, of which we have already spoken ; to this may be added sugar in some form or other, either coming from glycogen or from some other source. The ash of muscle, like the ash of the blood corpuscles, and, indeed the ash of the tissues in general, as distinguished from the blood, or plasma, or lymph on which the tissues live, is characterized by the preponderance of potassium salts and of phosphates ; these form, in fact, nearly 80 per cent, of the whole ash. § 63. We may now pass on to the question, What are the chemical changes which take place when a living resting muscle enters into a con- traction ? These changes are most evident after the muscle has been sub- jected to a prolonged tetanus ; but there can be no doubt that the chemical events of a tetanus are, like the physical events, simply the sum of the results of the constituent single contractions. In the first place the muscle becomes acid, not so acid as in rigor mortis, but still sufficiently so after a vigorous tetanus to turn blue litmus distinctly red. The cause of the acid reaction, like that of rigor mortis, is doubtful, but is in all probability the same in both cases. In the second place, a considerable quantity of carbonic acid is set free ; and the production of carbonic acid in muscular contraction is altogether similar to the production of carbonic acid during rigor mortis ; it is not accompanied by any corresponding increase in the consumption of oxygen. This is evident even in a muscle through which the circulation of blood is still going on ; for though the blood passing through a contracting muscle gives up more oxygen than the blood passing through a resting muscle, the increase in the amount of oxygen taken up falls below the increase in the carbonic acid given out. But it is still more markedly shown in a muscle removed from the body ; for in such a muscle both the contraction and the increase in the production of carbonic acid will go on in the absence of oxy- gen. A frog's muscle suspended in an atmosphere of nitrogen will remain irritable for some considerable time, and at each vigorous tetanus an increase in the production of carbonic acid may be readily ascertained. Moreover, there seems to be a correspondence between the energy of the contraction and the amount of carbonic acid and the degree of acid reaction produced, so that, though we are now treading on somewhat uncertain ground, we are naturally led to the view that the essential chemical process lying at the bottom of a muscular contraction as of rigor mortis is the split- ting up of some highly complex substance. But here the resemblance between rigor mortis and contraction ends. We have no satisfactory evi- dence of the formation during a contraction of any body like myosin. And this difference in chemical results tallies with an important difference between rigid muscle and contracting muscle. The rigid muscle, as we have seen, becomes less extensible, less elastic, less translucent ; the contracting muscle remains no less translucent, elastic, and extensible than the resting muscle, indeed, there are reasons for thinking that the muscle in contracting becomes actually more extensible for the time being. But if during a contraction myosin is not formed, what changes of proteid or nitrogenous matter do take place? We do not know. We have no evi- dence that kreatin, or any other nitrogenous extractive, is increased by the contraction of muscle ; we have no evidence of any nitrogen waste at all as the result of a contraction ; and, indeed, as we shall see later on, the study of the waste products of the body as a whole lead us to believe that the energy of the work done by the muscles of the body comes from the poten- 90 THE CONTRACTILE TISSUES. tial energy of carbon compounds, and not of nitrogen compounds at all. But to this point we shall have to return. § 64. We may sum up the chemistry of muscle somewhat as follows : During life the muscular substance is continually taking up from the blood, that is, from the lymph, proteid, fatty and carbohydrate material, saline matters and oxygen ; these it builds up into itself, how we do not know, and so forms the peculiar complex living muscular substance. The exact nature of this living substance is unknown to us. What we do know is that it is largely composed of proteid material, and that such bodies as myosinogen, myoglobulin, and albumin have something to do with the build- ing of it up. During rest this muscular substance, while taking in and building itself up out of or by means of the above-mentioned materials is continually giving off carbonic acid and continually forming nitrogenous waste such as kreatin. It also probably gives off some amount of sarcolactic acid, and possibly other non-nitrogenous waste matters. During a contraction there is a great increase in the quantity of carbonic acid given off, of lactic acid and some other substance formed giving an acid reaction, a greater consumption of oxygen, though the increase is not equal to the increase of carbonic acid, but as far as we can learn, no increase of nitrogenous waste. During rigor mortis there is a similar increased production of carbonic acid and of some other acid-producing substance, accompanied by remark- able conversion of myosinogen into myosin, by which the rigidity of the dead fibre is brought about. Thermal Changes. § 65. The chemical changes during a contraction set free a quantity of energy, but only a portion of this energy appears in the " work done," a con- siderable portion takes on the form of heat. Though we shall have hereafter to treat this subject more fully, the leading facts may be given here. Whenever a muscle contracts its temperature rises, indicating that heat is given out. When a mercury thermometer is plunged into a mass of mus- cles, such as those of the thigh of the dog, a rise of the mercury is observed upon the muscles being thrown into a prolonged contraction. More exact results, however, are obtained by means of a thermopile, by the help of which the rise of temperature caused by a few repeated single contractions, or indeed by a single contraction, may be observed, and the amount of heat given out approximately measured. The thermopile may consist either of a single junction in the form of a needle plunged into the substance of the muscle, or of several junctions, either in the shape of a flat surface carefully opposed to the surface of muscle (the pile being balanced so as to move with the contracting muscle, and thus to keep the contact exact), or in the shape of a thin wedge, the edge of which comprising the actual junctions, is thrust into a mass of muscles and held in position by them. In all cases the fellow-junction or junctions must be kept at a constant temperature. Another delicate method of determining' the changes of temperature of a tissue is based upon the measurement of alterations in electric resistance which a fine wire, in contact with or plunged into the tissue, undergoes as the temperature of the tissue changes. It has been calculated that the heat given out by the muscles of the thigh of a frog in a single contraction amounts to 3.1 micro-units of heat1 for each gramme of muscle, the result being obtained by dividing by five the total amount of heat given out in five successive single contractions. It 1 The micro-unit being a milligramme of water raised one degree Centigrade. CHANGES IN A MUSCLE DURING CONTRACTION. 91 will, however, be safer to regard these figures as illustrative of the fact that the heat given out is considerable, rather than as data for elaborate calcula- tions. Moreover, we have no satisfactory quantitative determinations of the heat given out by the muscles of warm-blooded animals, though there can be no doubt that it is much greater, than that given out by the muscles of the frog. There can hardly be any doubt that the heat thus set free is the product of chemical changes within the muscle — changes which, though they cannot for the reasons given above (§ 63) be regarded as simple and direct oxida- tions, yet, since they are processes dependent on the antecedent entrance of oxygen into the muscle, may be spoken of in general terms as a combustion ; so that the muscle may be likened to a steam-engine, in which the combustion of a certain amount of material gives rise to the development of energy in two forms, as heat and as movement, there being certain quantitative rela- tions between the amount of energy set free as heat and that giving rise to movement. We must, however, carefully guard ourselves against pressing this analogy too closely. In the steam-engine we can distinguish clearly between the fuel which, through its combustion, is the sole source of energy, and the machinery, which is not consumed to provide energy, and only suffers wear and tear. In the muscle we cannot with certainty at present make such a distinction. It may be that the chemical changes at the bottom of a con- traction do not involve the real living material of the fibre, but only some substance manufactured by the living material and lodged in some way, we do not know how, in the living material. It may be that when a fibre con- tracts it is this substance within the fibre which explodes, and not the fibre itself. If we further suppose that this substance is some complex compound of carbon and hydrogen, into which no nitrogen enters, we shall have an explanation of the difficulty referred to above (§ 63), namely, that nitro- genous waste is not increased by a contraction. The special contractile carbon-hydrogen substance, may then be compared to the charge of a gun, the products of its explosion being carbonic and sarcolactic acids, while the real living material of the fibre may be compared to the gun itself, but to a gun which itself is continually undergoing change far beyond mere wear and tear, among the products of which change nitrogenous bodies like kreatin are conspicuous. This view will certainly explain why kreatin is not increased during the contraction, while the carbonic and lactic acids are. But it must be remembered that such a view is not yet proved ; it may be the living material of the fibre, as a whole, which is continually breaking down in an explosive decomposition, and as continually building itself up again out of the material supplied by the blood. In a steam-engine only a certain amount of the total potential energy of the fuel issues as work, the rest being lost as heat, the proportion varying, but the work rarely, if ever, exceeding one-tenth of the total energy, and generally being less. In the case of the muscle we are not at present in a position to draw up an exact equation between the latent energy on the one hand, and the two forms of actual energy on the other. We have reason to think that the proportion between heat and work varies considerably under different circumstances, the work sometimes rising as high as one-fifth, some- times possibly sinking as low as one-twenty-fourth of the total energy ; and observations seem to show that the greater the resistance which the muscle has to overcome, the larger the proportion of the total energy expended which goes out as work done. The muscle, in fact, seems to be so far self- regulating that the more work it has to do the greater, within certain limits, is the economy with which it works. Lastly, it must be remembered that the giving out of heat by the muscle 92 THE CONTRACTILE TISSUES. is not confined to the occasions when it is actually contracting. When, at a later period, we treat of the heat of the body generally, evidence will be brought forward that the muscles, even when at rest, are giving rise to heat, so that the heat given out at a contraction is not some wholly new phenomenon, but a temporary exaggeration of what is continually going on at a more feeble rate. Electrical Changes. § 66. Besides chemical and thermal changes, a remarkable electric change takes place whenever a muscle contracts. Muscle-currents.— If a muscle be removed in an ordinary manner from the body, and two non-polarizable electrodes,1 connected with a delicate galvanometer and many convolutions and high resistance, be placed on two FIG. 29. ch.c Non-polarizable Electrodes : a, the glass tube ; z, the amalgamated zinc slips connected with their respective wires ; 2. s., the zinc sulphate solution ; ch. c. , the plug of china-clay ; c', the por- tion of the china-clay plug projecting from the end of the tube ; this can be moulded into any required form. points of the surface of the muscle, a deflection of the galvanometer will take place, indicating the existence of a current passing through the gal- vanometer from the one point of the muscle to the other, the direction and amount of the deflection varying according to the position of the points. The "muscle-currents" thus revealed are seen to the best advantage when the muscle chosen is a cylindrical or prismatic one with parallel fibres, and when the two tendinous ends are cut off by clean incisions at right angles to the long axis of the muscle. The muscle then presents a transverse section (artificial) at each end and a longitudinal surface. We may speak of the latter as being divided into two equal parts by an imaginary transverse line on its surface called the " equator," containing all the points of the surface midway between the two ends. Fig. 30 is a diagrammatic representation of such a muscle, the line ab being the equator. In such a muscle the develop- ment of the muscle-currents is found to be as follows : The greatest deflection is observed when one electrode is placed at the 1 These (Fig. 29) consist essentially of a slip of thoroughly amalgamated zinc, dipping into a saturated solution of zinc sulphate, which in turn is brought into connection with the nerve or muscle by means of a plug or bridge of china-clay moistened with normal sodium chloride solution ; it is important that the zinc should be thoroughly amalga- mated. This form of electrode gives rise to less polarization than do simple platinum or copper electrodes. The clay affords a connection between the zinc and the tissue, which neither acts on the tissue nor is acted on by the tissue. Contact of any tissue with copper or platinum is in itself sufficient to develop a current. CHANGES IN A MUSCLE DURING CONTRACTION. 93 mid-point or equator of the muscle, and the other at either cut end ; and the deflection is of such a kind as to show that positive currents are con- tinually passing from the equator through the galvanometer to the cut end ; that is to say, the cut end is negative, relatively to the equator. The cur- rents outside the muscle may be considered as completed by currents in the muscle from the cut end to the equator. In the diagram, Fig. 30, the arrows FIG. 30. Diagram illustrating the Electric Currents of Nerve and Muscle: Being purely diagrammatic, it may serve for a piece either of nerve or of muscle, except that the currents at the transverse section cannot be shown in a nerve. The arrows show the direction of the current through the galvanometer. ab, the equator. The strongest currents are those shown by the dark lines, as from a, at equator, to x or to y at the cut ends. The current from a to c is weaker than from a to y, though both, as shown by the arrows, have the same direction. A current is shown from e, which is near the equator, to /, which is further from the equator. The current (in muscle) from a point in the cir- cumference to a point nearer the centre of the transverse section is shown at gh. From a to b, or from x to y, there is no current, as indicated by the dotted lines. indicate the direction of the currents. If one electrode be placed at the equator ab, the effect is the same at whichever of the two cut ends, x or y, the other is placed. If, one electrode remaining at the equator, the other be shifted from the cut end to a spot (c) nearer to the equator, the current con- tinues to have the same direction, but is of less intensity in proportion to the nearness of the electrodes to each other. If the two electrodes be placed at unequal distances (c and /), one on either side of the equator, there will be a feeble current from the one nearer the equator to the one further off, and the current will be the feebler the more nearly they are equidistant from the equator. If they are quite equidistant — as, for instance, when one is placed on one cut end (x) and the other on the other cut end (y) — there will be no current at all. If one electrode be placed at the circumference of the transverse section and the other at the centre of the transverse section, there will be a current through the galvanometer from the former to the latter ; there will be a cur- rent of similar direction, but of less intensity, when one electrode is at the circumference ( caplllaries> and corresponding to the diastole of the ventricle. 5. These oscillations, which we may speak of as the pulse, are largest and most conspicuous in the large arteries near the heart, diminish from the heart toward the capillaries, and are, under ordinary circumstances, wholly absent from the veins along the whole extent from the capillaries to the heart. Obviously a great change takes place in that portion of the circulation which comprises the capillaries, the minute arteries leading to and the minute veins leading away from the capillaries, and which we may speak of as the " peripheral region." It is here that a great drop of pressure takes place ; it is here also that the pulse disappears. § 106. If the web of a frog's foot be examined with a microscope, the blood, as judged of by the movements of the corpuscles, is seen to be passing in a continuous stream from the small arteries through the capillaries to the veins. The velocity is greater in the arteries than in the veins, and greater in both than in the capillaries. In the arteries faint pulsations, synchronous with the heart's beat, are frequently visible ; but these disappear in the capillaries, in which the flow is even, 'that is, not broken by pulsations, and THE MAIN FACTS OF THE CIRCULATION. 143 this evenness of flow is continued on along the veins as far as we can trace them. Not infrequently variations in velocity and in the distribution of the blood, due to causes which will be hereafter discussed, are witnessed from time to time. The character of the flow through the smaller capillaries is very variable. Sometimes the corpuscles are seen passing through the chan- nel in single file with great regularity ; • at other times they may be few and far between. Some of the capillaries are wide enough to permit two or more corpuscles abreast. In all cases the blood as it passes through the capillary stretches and expands the walls. Sometimes a corpuscle may remain stationary at the entrance into a capillary, the channel itself being for some little distance entirely free from corpuscles. Sometimes many corpuscles will appear to remain stationary in one or more capillaries for a brief period and then to move on again. Any one of these conditions readily passes into another ; and, especially with a somewhat feeble circu- lation, instances of all of them may be seen in the same field of the micro- scope. It is only when the vessels of the web are unusually full of blood that all the capillaries can be seen equally filled with corpuscles. The long, oval red corpuscle moves with its long axis parallel to the stream, occasionally rotating on its long axis, and sometimes, in the larger chan- nels, on its short axis. The flexibility and elasticity of a corpuscle are well seen when it is being driven into a capillary narrower than itself, or when it becomes temporarily lodged at the angle between two diverging channels. These and other phenomena, on which we shall dwell later on, may be readily seen in the web of the frog's foot or in the stretched-out tongue or in the mesentery of the frog ; and essentially similar phenomena may be observed in the mesentery or other transparent tissues of a mammal. All over the body, wherever capillaries are present, the corpuscles and the plasma are being driven in a continuous and though somewhat irregular yet on the whole steady flow through channels so minute that the passage is manifestly attended with considerable difficulties. It is obvious that the peculiar characters of the flow through the minute arteries, capillaries, and veins affords an explanation of the great change taking place in the peripheral region between the arterial flow and the venous flow. The united sectional area of the capillaries is, as we have seen, some hundreds of times greater than the sectional area of the aorta ; but this united sectional area is made up of thousands of minute passages, varying in man from 5 to 20 //, some of them, therefore, being in an undis- tended condition, smaller than the diameter of a red corpuscle. Even were the blood a simple liquid free from all corpuscles, these extremely minute passages would occasion an enormous amount of friction, and thus present a considerable obstacle or resistance to the flow of blood through them. Still greater must be the friction and resistance occasioned by the actual blood with its red and white corpuscles. The blood in fact meets with great dif- ficulties in its passage through the peripheral region, and sometimes, as we shall see, the friction and resistance are so great in the peripheral vessels of this or that area that no blood passes through them at all, and an arrest of the flow takes place in the area. The resistance to the flow of blood thus caused by the friction generated in so many minute passages is one of the most important physical facts in the circulation. In the large arteries the friction is small ; it increases gradually as they divide, but receives its chief and most important addition in the minute arteries and capillaries; it is relatively greater in the minute arteries than in the capillaries on account of the flow being more rapid in the former, 144 THE VASCULAR MECHANISM. for friction diminishes rapidly with a diminution in the rate of flow. We may speak of it as the " peripheral friction," and the resistance which it offers as the " peripheral resistance." It need perhaps hardly be said that this peripheral resistance not only opposes the flow of blood through the capillaries and minute arteries themselves where it is generated, but, working backward along the whole arterial system, has to be overcome by the heart at each systole of the ventricle. Hydraulic Principles of the Circulation. § 107. In the circulation, then, the following three facts of fundamental importance are met with : 1. The systole of the ventricle, driving at intervals a certain quantity of blood, with a certain force, into the aorta. 2. The peripheral resistance just described. 3. A long stretch of elastic tubing (the arteries), reaching from the ventricle to the region of peripheral resistance. From these facts we may explain the main phenomena of the circula- tion, which we have previously sketched, on purely physical principles without any appeal to the special properties of living tissues, beyond the provision that the ventricle remains capable of good rhythmical contrac- tions, that the arterial walls retain their elasticity, and that the friction be- tween the blood and the lining of the peripheral vessels remains the same ; we may thus explain the high pressure and pulsatile flow in the arteries, the steady stream through the capillaries, the low pressure and the uniform pulseless flow in the veins, and finally the continued flow of the blood from the aorta to the mouths of the venae cavse. All the above phenomena in fact are the simple results of an intermit- tent force (like that of the systole of the ventricle) working in a closed circuit of branching tubes, so arranged that while the individual tubes first diminish in calibre (from the heart to the capillaries) and then increase (from the capillaries to the heart), the area of the bed first increases and then diminishes, the tubes together thus forming two cones placed base to base at the capillaries, with their apices converging at the heart, and pre- senting at their conjoined bases a conspicuous peripheral resistance, the tubing on one side, the arterial, being eminently elastic, and, on the other, the venous, affording a free and easy passage for the blood. It is the peripheral resistance (for the resistance offered by the friction in the larger vessels may, when compared with this, be practically neglected), reacting through the elastic walls of the arteries upon the intermittent force of the heart, which gives the circulation of the blood its peculiar features. § 108. Circumstances determining the character of the flow. When fluid is driven by an intermittent force, as by a pump, through a perfectly rigid tube, such as a glass one (or a system of such tubes), there escapes at each stroke of the pump from the distal end of the tube (or system of tubes) just as much fluid as enters it at the proximal end. What happens is very like what would happen if, with a wide glass tube completely filled with billiard balls lying in a row, an additional ball were pushed in at one end : each ball would be pushed on in turn a stage further and the last ball at the further end would tumble out. The escape, moreover, takes place at the same time as the entrance. This result remains the same when any resistance to the flow is intro- duced into the tube, as for instance when the end of the tube is narrowed. The force of the pump remaining the same, the introduction of the resist- ance undoubtedly lessens the quantity of fluid issuing at the distal end at THE MAIN FACTS OF THE CIRCULATION. 145 each stroke, but it at the same time lessens the quantity entering at the proximal end ; the inflow and outflow remain equal to each other, and still occur at the same time. In an elastic tube, such as an India-rubber one (or in a system of such tubes), whose sectional area is sufficiently great to offer but little resistance to the progress of the fluid, the flow caused by an intermittent force is also intermittent. The outflow being nearly as easy as the inflow, the elasticity of the walls of the tube is scarcely at all called into play. The tube be- haves practically like a rigid tube. When, however, sufficient resistance is introduced into any part of the course, the fluid being unable to pass by the resistance as rapidly as it enters the tube from the pump, tends to accu- mulate on the proximal side of the resistance. This it is able to do by ex- panding the elastic walls of the tube. At each stroke of the pump a cer- tain quantity of fluid enters the tube at the proximal end. Of this only a fraction can pass through the resistance during the stroke. At the moment when the stroke ceases, the rest still remains on the proximal side of the resistance, the elastic tube having expanded to receive it. During the interval between this and the next stroke, the distended elastic tube, striving to return to its natural undistended condition, presses on this extra quantity of fluid which it contains and tends to drive it past the resistance. Thus, in the rigid tube (and in the elastic tube without the resistance) there issues, from the distal end of the tube at each stroke, just as much fluid as enters it at the proximal end, while between the strokes there is perfect quiet. In the elastic tube with resistance, on the contrary, the quan- tity which passes the resistance is only a fraction of that which enters the tube from the pump at any one stroke, the remainder or a portion of the- remainder continuing to pass during the interval between the strokes. In the former case the tube is no fuller at the end of the stroke than at the beginning ; in the latter case there is an accumulation of fluid between the pump and the resistance, and a corresponding distention of that part of the tube at the close of each stroke — an accumulation and distention, however, which go on diminishing during the interval between that stroke and the next. The amount of fluid thus remaining after the stroke will depend on the amount of resistance in relation to the force of the stroke and on the distensibility of the tube ; and the amount which passes the resistance before the next stroke will depend on the degree of elastic reaction of which the tube is capable. Thus, if the resistance be very considerable in relation to the force of the stroke, and the tube very distensible, only a small portion of the fluid will pass the resistance, the greater part remaining lodged be- tween the pump and the resistance. If the elastic reaction be great, a large portion of this will be passed on through the resistance before the next stroke comes. In other words, the greater the resistance (in relation to the force of the stroke), and the more the elastic force is brought into play, the less intermittent, the more nearly continuous, will be the flow on the far side of the resistance. If the first stroke be succeeded by a second stroke before its quantity of fluid has all passed by the resistance, there will be an additional accumula- tion of fluid on the near side of the resistance, an additional distention of the tube, an additional strain on its elastic powers, and, in consequence, the flow between this second stroke and the third will be even more marked than that between the first and second, though all three strokes were of the same force, the addition being due to the extra amount of elastic force called into play. In fact, it is evident that, if there be a sufficient store of elastic power to fall back upon, by continually repeating the stroke a state of things will be at last arrived at in which the elastic force, called into play by the con- 10 146 THE VASCULAK MECHANISM. tinually increasing distention of the tube on the near side of the resistance, will be sufficient to drive through the resistance, between each two strokes, just as much fluid as enters the near end of the system as each stroke. In other words, the elastic reaction of the walls of the tube will have converted the intermittent into a continuous flow. The flow on the far side of the resistance is in this case not the direct result of the strokes of the pump. All the force of the pump is spent, first in getting up, and afterward in keeping up, the distention of the tube on the near side of the resistance ; the imme- diate cause of the continuous flow lies in the distention of the tube which leads it to empty itself into the far side of the resistance at such a rate that it discharges through the resistance during a stroke and in the succeeding interval just as much as it receives from the pump by the stroke itself. This is exactly what takes place in the vascular system. The friction in the minute arteries and capillaries presents a considerable resistance to the flow of blood through them into the small veins. In consequence of this resistance the force of the heart's beat is spent in maintaining the whole of the arterial system in a state of great distention ; the arterial walls are put greatly on the stretch by the pressure of the blood thrust into them by the repeated strokes of the heart ; this is the pressure which we spoke of above as blood-pressure. The greatly distended arterial system is, by the elastic reaction of its elastic walls, continually tending to empty itself by overflow- ing through the capillaries into the venous system ; and it overflows at such a rate that just as much blood passes from the arteries to the veins during each systole and its succeeding diastole as enters the aorta at each systole. § 109. Indeed, the important facts of the circulation which we have not as yet studied may be roughly but successfully imitated on an artificial model, Fig. 42, in which an elastic syringe represents the heart, a long piece of elastic India-rubber tubing the arteries, another piece of tubing the veins, and a number of smaller connecting pieces the minute arteries and capil- laries. If these connecting pieces be made at first somewhat wide, so as to offer no great resistance to the flow from the artificial arteries to the artificial veins, but be so arranged that they may be made narrow by the screwing-up of clamps or otherwise, it is possible to illustrate the behavior of the vascular mechanism when the peripheral resistance is less than usual (and as we shall see later on it is possible in the living organism either to reduce or to increase what may be considered as the normal peripheral resistance), and to compare that behavior with the behavior of the mechanism when the peripheral resistance is increased. The whole apparatus being placed flat on a table, so as to avoid differences in level in different parts of it, and filled with water, but so as not to distend the tubing, the two manometers attached, one (A) to the arterial side of the tubing and the other (V) to the venous side, ought to show the mercury standing at equal heights in both limbs of both instruments, since nothing but the pressure of the atmosphere is bearing on the fluid in the tubes, and that equally all over. If, now, the connecting pieces being freely open, that is to say, the periph- eral resistance being very little, we imitate a ventricular beat by the stroke of the pump, we shall observe the following : Almost immediately after the stroke the mercury in the arterial manometer will rise, but will at once fall again, and very shortly afterward the mercury in the venous tube will in a similar manner rise and fall. If we repeat the strokes with a not too rapid rhythm, each stroke having the same force, and make, as may by a simple contrivance be effected, the two manometers write on the same recording surface, We shall obtain curves like those of Fig. 43, A and V. At each stroke of the pump the mercury in the arterial manometers rises, but forthwith falls again to or THE MAIN FACTS OF THE CIRCULATION. 147 nearly to the base line ; no mean arterial pressure, or very little, is established. The contents of the ventricle (syringe) thrown into the arterial system dis- FIG. 42. Arterial Scheme : P, unshaded, is an elastic tube to represent the arterial system, branching at .AT and Y, and ending in the region of peripheral resistance, including the capillaries, which are imitated by filling loosely with small pieces of sponge the parts shown as dilated in the figure. The capillaries are gathered up into the venous system, shaded, which terminates at 0. Water is d riven into the arterial system at P by means of an elastic bag syringe or any other form of pump. Clamps are placed on the undilated tubes, c, c', c". When these clamps are tightened, the only access for the water from the arterial to the venous side is through the dilated parts filled with sponge, which offers a considerable resistance to the flow of fluid through them. When the clamps are unloosed the fluid passes, with much less resistance, through the undilated tubes. Thus, by tightening or loosening the clamps the "peripheral" resistance may be increased or diminished at pleasure. At A, on the arterial side, and at V, on the venous side, manometers can be attached. At a and v (and also at x and y), by means of clamps, the flow of fluid from an artery and from a vein, under various conditions, may be observed. At Sa, S'a, and Sv, sphygmographs may be applied. tend it, but the passage through the peripheral region is so free that an equal quantity of fluid passes through to the veins immediately, and hence the FIG. 43. Tracings taken from an Artificial Scheme, with the Peripheral Resistance Slight : A, arterial ; V, venous manometer. This figure, to save space, is on a smaller scale than the corresponding Fig. 44. mercury at once falls. But the fluid thus passing easily into the veins dis- tends these too, and the mercury in their manometer rises too, but only to 148 THE VASCULAR MECHANISM. fall again, as a corresponding quantity issues from the ends of the veins into the basin, which serves as an artificial auricle. Now introduce " peripheral resistance " by screwing up the clamps on the connecting tubes, and set the pump to work again as before. With the first stroke the mercury in the arterial manometer (Fig. 44, A1) rises as before, but instead of falling rapidly it falls slowly, because it now takes a longer time for a quantity of fluid equal to that which has been thrust into the arterial system by the ventricu- lar stroke to pass through the narrowed peripheral region. Before the curve has fallen to the base line, before the arterial system has had time to dis- charge through the narrowed peripheral region as much fluid as it received from the ventricle, a second stroke drives more fluid into the arteries, dis- tending them this time more than it did before, and raising the mercury to FIG. 44. Tracings taken from an Artificial Scheme, with the Peripheral Resistance Considerable: Alt arterial ; V1, venous manometer. a still higher level. A third, a fourth, and succeeding strokes produce the same effect, except that the additional height to which the mercury is raised at each stroke becomes at each stroke less and less, until a state of things is reached in which the mercury, being on the fall when the stroke takes place, is by the stroke raised just as high as it was before, and then beginning to fall again is again raised just as high, and so on. With each succeeding stroke the arterial system has become more and more distended ; but the more distended it is the greater is the elastic reaction brought into play ; this greater elastic reaction more and more overcomes the obstacle presented by the peripheral resistance and drives the fluid more and more rapidly through the peripheral region. At last the arterial system is so distended, and the force of the elastic reaction so great, that during the stroke and the succeed- ing interval just as much fluid passes through the peripheral region as enters the arteries at the stroke. In other words, the repeated strokes have estab- lished a mean arterial pressure which, at the point where the manometer THE MAIN FACTS OF THE CIRCULATION. 149 is affixed, is raised slightly at each ventricular stroke, and falls slightly between the strokes. Turning now to the venous manometer, Fig. 44, V1, we observe that each stroke of the pump produces on this much less effect than it did before the introduction of the increased peripheral resistance. The mercury, instead of distinctly rising and falling at each stroke, now shows nothing more than very gentle undulations ; it feels to a very slight degree only the direct effect of the ventricular stroke ; it is simply raised slightly above the base line, and remains fairly steady at this level. The slight rise marks the mean pressure exerted by the fluid at the place of attachment of the manom- eter. This mean " venous " pressure is a continuation of the mean arterial pressure so obvious in the arterial manometer, but is much less than that be- cause a large part of the arterial mean pressure has been expended in driv- ing the fluid past the peripheral resistance. What remains is, however, sufficient to drive the fluid along the wide venous tubing right to the open end. Thus this artificial model may be made to illustrate how it comes about that the blood flows in the arteries at a relatively high pressure, which at each ventricular systole is raised slightly above and at each diastole falls slightly below a certain mean level, and flows in the veins at a much lower pressure, which does not show the immediate effects of each heart-beat. If two manometers, instead of one, were attached to the arterial system, one near the pump and the other further off, close to the peripheral resist- ance, the pressure shown by the near manometer would be found to be greater than that shown by the far one. The pressure at the far point is less because some of the pressure exerted at the near point has been used to drive the fluid from the near point to the far one. Similarly on the venous side, a manometer placed close to the peripheral region would show a higher pres- sure than that shown by one further off, because it is the pressure still remain- ing in the veins near the capillaries which, assisted, as we shall see, by other events, drives the blood onward to the larger veins. The blood-pressure is at its highest at the root of the aorta and at its lowest at the mouths of the vena3 cavse, and is falling all the way from one point to the other, because all the way it is being used up to move the blood from one point to the other. The great drop of pressure is, as we have said, in the peripheral region, because more work has to be done in driving the blood through this region than in driving the blood from the heart to this region, or from this region to the heart. The 'manometer on the arterial side of the model shows, as we have seen, an oscillation of pressure, a pulse due to each heart-beat, and the same pulse may be felt by placing a finger, or rendered visible by placing a light lever, on the arterial tube. It may further be seen that this pulse is most marked nearest the pump, and becomes fainter as we pass to the periphery ; but we must reserve the features of the pulse for a special study. On the venous side of the model no pulse can be detected by the manometer or by the finger, provided that the peripheral resistance be adequate. If the periph- eral resistance be diminished, as by unscrewing the clamps, then, as neces- sarily follows from what has gone before, the pulse passes over on to the venous side ; and, as we shall have occasion to point out later on, in the living organism the peripheral resistance in particular areas may be at times so much lessened that a distinct pulsation appears in the veins. If in the model, when the pump is in full swing, and arterial pressure well established, the arterial tube be pricked or cut, or the small side tube a be opened, the water will gush out in jets, as does blood from a cut artery in the living body ; whereas, if the venous tube be similarly pricked or cut, or 150 THE VASCULAR MECHANISM. the small tube v be opened, the water will simply ooze out or well up, as does blood from a vein in the living body. If the arterial tube be ligatured, it will swell on the pump side and shrink on the peripheral side; if the venous tube be ligatured, it will swell on the side nearest the capillaries and shrink on the other side. In short, the dead model will show all the main facts of the circulation which we have as yet described. § 110. In the living body, however, there are certain helps to the circu- lation which cannot be imitated by such a model without introducing great and undesirable complications ; but these chiefly affect the flow along the veins. The veins are in many places provided with valves so constructed as to offer little or no resistance to the flow from the capillaries to the heart, but effectually to block a return toward the capillaries. Hence any external pressure brought to bear upon a vein tends to help the blood to move for- ward toward the heart. In the various movements carried out by the skeletal muscles, such an external pressure is brought to bear on many of the veins, and hence these movements assist the circulation. Even passive movements of the limbs have a similar effect. So, also, the movements of the alimentary canal, carried out by means of plain muscular tissue, promote the flow along the veins coming from that canal, and when we come to deal with the spleen we shall see that the plain muscular fibres which are so abundant in that organ in some animals, serve by rhythmical contractions to pump the blood regularly away from the spleen along the splenic veins. When we come to deal with respiration, we shall see that each enlarge- ment of the chest constituting an inspiration tends to draw the blood toward the chest, and each return or retraction of the chest walls in expiration tends to drive the blood away from the chest. The arrangement of the valves of the heart causes this action of the respiratory pump to promote the flow of blood in the direction of the normal circulation ; and, indeed, were the heart perfectly motionless, the working of this respiratory pump alone would tend to drive the blood from the vense cavse through the heart into the aorta, and so to keep up the circulation ; the force so exerted, however, would, without the aid of the heart, be able to overcome a very small part only of the resistance in the capillaries and small vessels of the lungs, and so would prove actually ineffectual. There are, then, several helps to the flow along the veins, but it must be remembered that, however useful, they are helps only, and not the real cause of the circulation. The real cause of the flow is the ventricular str.oke, and this is sufficient to drive the blood from the left ventricle to the right auricle, even when every muscle of the body is at rest and breathing is for a while stopped, when, therefore, all the helps we are speaking of are wanting. Circumstances Determining the Rate of the Flow. § 111. We may now pass on to consider briefly the rate at which the blood flows through the vessels, and first the rate of flow in the arteries. When even a small artery is severed, a considerable quantity of blood escapes from the proximal cut end in a very short space of time. That is to say, the blood moves in the arteries from the heart to the capillaries with a very considerable velocity. By various methods, this velocity of the blood- current has been measured at different parts of the arterial system ; the results, owing to imperfections in the methods employed, cannot be regarded as satisfactorily exact, but may be accepted as approximately true. They show that the velocity of the arterial stream is greatest in the largest arteries near the heart, and diminishes from the heart toward the capillaries. Thus, THE MAIN FACTS OF THE CIRCULATION. 151 in a large artery of a large animal, such as the carotid of a dog or horse, and probably in the carotid of a man, the blood flows at the rate of 300 or 500 mm. a second. In the very small arteries the rate is probably only a few mm. a second. Methods. The haemadromometer of Volkmann. [Fig. 45.] An artery— e.g., a carotid— is clamped in two places, and divided between the clamps. Two canulse, [FiG. 45. Volkmann's Hsemadromometer: The conical portions of the instrument are inserted in the cut ends of a vein or artery. By a simple arrangement of a double stopcock the blood-current can be made to pass immediately through the transverse arm, as in A, or to pass through the graduated U-shaped tube, as in B.] of a bore as nearly equal as possible to that of the artery, or of a known bore, are inserted in the two ends. The two canulse are connected by means of two stop- cocks, which work together, with the two ends of a long glass tube, bent in the shape of a U, and filled with normal saline solution, or with a colored innocuous fluid. The clamps on the artery being released, a turn of the stopcocks permits the blood to enter the proximal end of the long U-tube, along which it courses, driving the fluid out into the artery through the distal end. Attached to the tube is a graduated scale, by means of which the velocity with which the blood flows along the tube may be read off. Even supposing the canulse to be of the same bore as the artery, it is evident that the conditions of the flow through the tube are such as will only admit of the resu]t thus gained being considered as an approxi- mative estimation of the real velocity in the artery itself. The rheometer (StronnihrT of Ludwig. This consists of two glass bulbs, A and B, Fig. 46, communicating above with each other and with the common tube C, by which they can be filled. Their lower ends are fixed in the metal disc />, which can be made to rotate, through two right angles, round the lower disc E. In the upper disc are two holes, a and b, continuous with A and B respectively, and in the lower disc are two similar holes a' and &', similarly continuous with the tubes G and H. Hence, in the position of the discs shown in the figure, the tube G is continuous through the two discs with the bulb A, and the tube H with the bulb B. On turning the disc D through two right angles, the tube G 152 THE VASCULAK MECHANISM. becomes continuous with B instead of A. and the tube H with A instead of B. There is a further arrangement, omitted from the figure for the sake of simplicity, by which when the disc D is turned through one instead of two right angles from either of the above positions, G becomes directly continuous with H, both being complete!}7 shut off from the bulbs. The ends of the tubes Hand G are made to fit exactly into two canulse inserted into the two cut ends of the artery about to be experimented upon, and having a bore as nearly equal as possible to that of the artery. The method of experimenting is as follows : The disc /), being placed in the intermediate position, so that a and b are both cut off from a' and b', the bulb A is filled with pure olive oil up to the mark x, and the bulb B, the rest of A, and the junction C, with defibrinated blood ; and C is then clamped. The tubes H and G are also filled with defibrinated blood, and G is inserted into the canula of the central, H into that of the peripheral, end of the artery. On removing FIG. 46. Ludwig's Stromuhr and a Diagrammatic Representation of the Same. the clamps from the artery the blood flows through G to H, and so back into the artery. The observation now begins by turning the disc D into the position shown in the figure , the blood then flows into A, driving the oil there contained out before it into the bulb B, in the direction of the arrow, the defibrinated blood previously present in B passing by H into the artery, and so into the system. At the moment that the blood is seen to rise to the mark x, the disc D is with all possible rapidity turned through two right angles ; and thus the bulb J5, now largely filled with oil, placed in communication with G. The blood-stream now drives the oil back into A, and the new blood in A through H into the artery. As soon as the oil has wholly returned to its original position, the disc is again turned round, and A once more placed in communication with £, and the oil once more driven from A to B. And this is repeated several times, indeed generally until the clotting of the blood or the admixture of the oil with the blood puts an end to the experiment. Thus the flow of blood is used to fill alternately with blood or oil the space of the bulb A, whose cavity as far as the mark x has been exactly measured ; hence if the number of times in any given time the disc D has to be turned round be known, the number of times A has been filled is also known, and thus the quantity of blood which has passed in that time through the canula connected with the tube G is directly measured. For instance, sup- THE MAIN FACTS OF THE CIRCULATION. 153 [FiG. 47. posing that the quantity held by the bulb A when filled up to the mark x is 5 c.c., and supposing that from the moment of allowing the first 5 c.c. of blood to begin to enter the tube to the moment when the escape of the last 5 c.c. from the artery into the tube was complete, 100 seconds had elapsed, during which time 5 c.c. has been received ten times into the tube from the artery (all but the last 5 c.c. being returned into the distal portion of the artery), obviously 0.5 c.c. of blood had flowed from the proximal section of the artery in one second. Hence, sup- posing that the diameter of the canula (arid of the artery, they being the same) were 2 mm., with area therefore of 3.14 square mm., an outflow through the sec- tion of 0.5 c.c. or 500 mm. in a second would give (-|~) a velocity of about 159 mm. in a second. The hgematachometer of Vierordt [Fig. 47] is constructed on the principle of measuring the velocity of the current by observing the amount of deviation under- gone by a pendulum, the free end of which hangs loosely in the stream. A square or rectangular chamber, one side of which is of glass and marked with a graduated scale in the form of an arc of a circle, is connected by means of two short tubes with the two cut ends of an artery ; the blood consequently flows from the proximal (central) por- tion of the artery through the chamber into the distal portion of the artery. Within the chamber and sus- pended from its roof is a short pendulum, which when the blood-stream is cut off from the chamber hangs motionless in a vertical position, but when the blood is allowed to flow through the chamber, is driven by the force of the current out of its position of rest. The pendulum is so placed that a marker attached to its free end travels close to the inner surface of the glass side along the arc of the graduated side. Hence the amount of deviation from a vertical position may easily be read off on the scale from the outside. The graduation of the scale having been carried out by experi- menting with streams of known velocity, the velocity can at once be calculated from the amount of deviation. An instrument based on the same principle has been invented by Chauveau and improved by Lortet, Fig. 48. In this the part which corresponds to the pendulum FIG. 48. Hsematachometer of Vierordt • a, b, mouthpieces.] Hsematachometer of Chauveau and Lortet. in Vierordt' s instrument is prolonged outside the chamber, and thus the portion within the chamber is made to form the short arm of a lever, the fulcrum of which is at the point where the wall of the chamber is traversed, and the long arm of which projects outside. A somewhat wide tube, the wall of which is at one point 154 THE VASCULAR MECHANISM. composed of an India-rubber membrane, is introduced between the two cut ends of an artery. A long light lever pierces the India-rubber membrane. The short expanded arm of this lever projecting within the tube is moved on its fulcrum in the India-rubber ring by tne current of blood passing through the tube, the greater the velocity of the current the larger being the excursion of the lever. The movements of the short arm give rise to corresponding movements in the oppo- site direction of the long arm outside the tube, and these, by means of a marker attached to the end of the long arm, may be directly inscribed on a recording sur- face. This instrument is very well adapted for observing changes in the velocity of the flow. In determining actual velocities, for which purpose it has to be experimentally graduated, it is not so useful. In the capillaries, the rate is slowest of all. In the web of the frog the flow as judged by the movement of the red corpuscles may be directly measured under the microscope by means of a micrometer, and is found to be about half a millimeter in a second ; but this is probably a low estimate, since it is only when the circulation is somewhat slow, slower perhaps than what ought to be considered the normal rate, that the red corpuscles can be distinctly seen. In the mammal the rate has been estimated at about 0.75 millimetres a second, but is probably quicker than even this. As regards the veins, the flow is very slow in the small veins emerging from the capillaries, but increases as these join into larger trunks, until in a large vein, such as the jugular of the dog, the rate is about 200 mm. a second. § 112. It will be seen, then, that the velocity of the flow is in inverse proportion to the width of the bed, to the united sectional areas of the vessels. It is greatest at the aorta, it diminishes along the arterial system to the capillaries, to the united bases of the cones spoken of in § 101, where it is least, and from thence increases again along the venous system. And, indeed, it is this width of the bed, and this alone, which determines the general velocity of the flow at various parts of the system. The slowness of the flow in the capillaries is not due to there being so much more friction in their narrow channels than in the wider canals of the larger arteries. For the peripheral resistance caused by the friction in the capillaries and small arteries is an obstacle not only to the flow of blood through these small vessels where the resistance is actually generated, but also to the escape of the blood from the large into the small arteries, and indeed from the heart into the large arteries. It exerts its influence along the whole arterial tract. And it is obvious that if it were this peripheral resistance which checked the flow in the capillaries, there could be no recovery of velocity along the venous tract. The blood is flowing through a closed system of tubes, the bloodvessels, under the influence of one propelling force, the systole of the ventricle, for this is the force which drives the blood from ventricle to auricle, though, as we have seen, its action is modified in the several parts of the system. In such a system the same quantity of fluid must pass each section of the sys- tem at the same time, otherwise there would be a block at one place and a deficiency at another. If, for instance, a fluid FIG. 49. is made to flow by some one force, pressure or gravity, through a tube A (Fig. 49) with an enlargement B, it is obvious that the same quantity of fluid must pass through the sec- tion b as passes through the section a in the same time — for instance, a second. Other- a I c wise, if less passes through b than a, the fluid would accumulate in B, or if more, B would be emptied. In the same way just as much must pass in the THE MAIN FACTS OF THE CIRCULATION. 155 same time through the section c as passes through a or b. But if just as many particles of water have to get through the narrow section a in the same time as they have to get through the broader section c, they must move quicker through a than through c, or more slowly through c than through a. For the same reason water flowing along a river impelled bv one force — viz., that of gravity — rushes rapidly through a " narrow " and flows sluggishly when the river widens out into a " broad." The flow through B will be similarly slackened if B, instead of being simply a single en- largement of the tube A, consists of a number of small tubes branching out from A, with a united sectional area greater than the sectional area of A. In each of such small tubes, at the line c, for instance, the flow will be slower than at a, where the small tubes branch out from A, or at b, where they join again to form a single tube. Hence it is that the blood rushes swiftly through the arteries, tarries slowly through the capillaries, but quickens its pace again in the veins. An apparent contradiction to this principle that the rate of flow is de- pendent on the width of the bed is seen in the case where, the fluid having alternative routes, one of the routes is temporarily widened. Suppose a tube A dividing into two branches of equal length x and y which unite again to form the tube V. Suppose, to start with, x and y are of equal diameter ; then the resistance offered by each being equal, the flow will be equally rapid through the two, being just so rapid that as much fluid passes in a given time through x and y together as passes through A or through V- But now suppose y to be widened ; the widening will diminish the resistance offered by y, and in consequence, supposing that no material change takes place in the pressure or force which is driving the fluid along, more fluid will now pass along y in a given time than did before ; that is to say, the rapidity of the flow in y will be increased. It will be increased at the ex- pense of the flow through x, since it will still hold good that the flow through x and y together is equal to the flow through A and through V. We shall have occasion later on to point out that a small artery, or a set of small arteries, may be more or less suddenly widened without materially affecting the general blood-pressure which is driving the blood through the artery or set of arteries. In such cases the flow of blood through the widened artery or arteries is for the time being increased in rapidity, not only in spite of, but actually in consequence of, the artery being widened. It must be understood in fact that this dependence of the rapidity of the flow on the width of the bed applies to the general rate of flow of the whole circulation, and that, besides the above instance, other special and temporary variations occur due to particular circumstances. Thus changes of pressure may alter the rapidity of flow. The cause of the flow through the whole system is the pressure of the ventricular systole manifested as what we have called blood-pressure. At each point along the system nearer the left ven- ;ricle, and therefore further from the right auricle, the pressure is greater lan at a point further from the left ventricle and so nearer the right auricle ; it is this difference of pressure which is the real cause of the flow from the one point to the other ; and other things being equal the rapidity of the flow will depend on the amount of the difference of pressure. Hence, temporary or local variations in rapidity of flow may be caused by the establishment of temporary or local differences of pressure. For example, at any point ilong the arterial system the flow is increased in rapidity during the tem- porary increase of pressure due to the ventricular systole, i. e., the pulse, and diminished during the subsequent temporary decrease, the increase and decrease being the more marked the nearer the point to the heart. And we shall probably meet later on with other instances. 156 THE VASCULAR MECHANISM. § 113. Time of the entire circuit. It is obvious from the foregoing that a red corpuscle in performing the whole circuit, iii travelling from the left ventricle back to the left ventricle, would spend a large portion of its time in the capillaries, minute arteries, and veins. The entire time taken up in the whole circuit has been approximately estimated by measuring the time it takes for an easily recognized chemical substance after injection into the jugular vein of one side to appear in the blood of the jugular vein of the other side. While small quantities of blood are being drawn at frequently repeated intervals from the jugular vein of one side, or while the blood from the vein is being allowed to fall in a minute stream on an absorbent paper covering some travelling surface, an iron salt such as potassium ferrocyanide (or preferably sodium ferrocyanide as being more innocuous) is injected into the jugular vein of the other side. If the time of the injection be noted, and the time after the injection into one side at which evidence of the presence of the iron salt can be detected in the sample of blood from the vein of the other side be noted, this gives the time it has taken the salt to perform the circuit ; and on the supposition that mere diffusion does not materially affect the result, the time which it takes the blood to perform the same circuit is thereby given. In the horse this time has been experimentally determined at about 30 seconds and in the dog at about 15 seconds. In man it is probably from 20 to 25 seconds. Taking the rate of flow through the capillaries at about 1 mm. a second it would take a corpuscle as long a time to get through about 20 mm. of capil- laries as to perform the whole circuit. Hence, if any corpuscle had in its circuit to pass through 10 mm. of capillaries, half the whole time of its journey would be spent in the narrow channels of the capillaries. Inasmuch as the purposes served by the blood are chiefly carried out in the capillaries, it is obviously of advantage that its stay in them should be prolonged. Since, however, the average length of a capillary is about 0.5 mm., about half a second is spent in the capillaries of the tissues and another half sec- ond in the capillaries of the lungs. § 114. We may now briefly summarize the broad features of the circu- lation, which we have seen may be explained on purely physical principles, it being assumed that the ventricle delivers a certain quantity of blood with a certain force into the aorta at regular intervals, and that the physical properties of the bloodvessels remain the same. We have seen that owing to the peripheral resistance offered by the capillaries and small vessels the direct effect of the ventricular stroke is to establish in the arteries a mean arterial pressure which is greatest at the root of the aorta and diminishes toward the small arteries, some of it being used up to drive the blood from the aorta to the small arteries, but which retains at the region of the small arteries sufficient power to drive through the small arteries, capillaries, and veins just as much blood as is being thrown into the aorta by the ventricular stroke. We have seen, further, that in the large arteries at each stroke the pressure rises and falls a little above and below the mean, thus constituting the pulse, but that this extra distention with its subsequent recoil diminishes along the arterial tract and finally vanishes ; it diminishes and vanishes because it too, like the whole force of the ventricular stroke, of a fraction of which it is the expression, is used up in establishing the mean pressure ; we shall, however, consider again later on the special features of this pulse. We have seen, further, that the task of driving the blood through the peripheral resistance of the small arteries and capillaries consumes much of this mean pressure, which consequently is much less in the small veins than in the corresponding small arteries, but THE HEART. 157 that sufficient remains to drive the blood, even without the help of the aux- iliary agents which are generally in action, from the small veins right back to the auricle. Lastly we have seen that while the above is the cause of the flow from ventricle to auricle, the changing rate of the flow, the diminish- ing swiftness in the arteries, the sluggish crawl through the capillaries, the increasing quickness through the veins are determined by the changing width of the vascular " bed." Before we proceed to consider any further details as to the phenomena of the flow through the vessels, we must turn aside to study the heart. THE HEART. § 115, The heart is a valvular pump which works on mechanical princi- ples, but the motive power of which is supplied by the contraction of its muscular fibres. Its action consequently presents problems which are partly mechanical and partly vital. Regarded as a pump, its effects are determined by the frequency of the beats, by the force of each beat, by the character of each beat — whether, for instance, slow and lingering, or sudden and sharp — and by the quantity of fluid ejected at each beat. Hence, with a given frequency, force, and character of beat, and a given quantity ejected at each beat, the problems which have to be dealt with are for the most part mechanical. The vital problems are chiefly connected with the causes which determine the frequency, force, and character of the beat. The quantity ejected at each beat is governed more by the state of the rest of the body than by that of the heart itself. The Phenomena of the Normal Beat. The visible movements. When the chest of a mammal is opened and arti- ficial respiration kept up the heart may be watched beating. Owing to the removal of the chest-wall, what is seen is not absolutely identical with what takes place within the intact chest, but the main events are the same in both cases. A complete beat of the whole heart or cardiac cycle may be observed to take place as follows : The great veins, inferior and superior vense cavse, and pulmonary veins are seen, while full of blood, to contract in the neighborhood of the heart ; the contraction runs in a peristaltic wave toward the auricles, increasing in intensity as it goes. Arrived at the auricles, which are then full of blood, the wave suddenly spreads, at a rate too rapid to be fairly judged by the eye, over the whole of those organs, which accordingly contract with a sudden sharp systole. In the systole, the walls of the auricles press toward the auriculo-ventricular orifices, and the auricular appendages are drawn inward, becoming smaller and paler. During the auricular systole, the ventricles may be seen to become turgid. Then follows, as it were immediately, the ventricular systole, during which the ventricles become more conical. Held between the fingers they are felt to become tense and hard. As the systole progresses, the aorta and pulmonary arteries expand and elongate, the apex is tilted slightly upward, and the heart twists somewhat on its long axis, moving from the left and behind toward the front and right so that more of the left ventricle becomes displayed. As the systole gives way to the suc- ceeding diastole, the ventricles resume their previous form and position, the aorta and pulmonary artery shrink and shorten, the heart turns back toward the left, and thus the cycle is completed. In the normal beat, the two ventricles are perfectly synchronous in ac- tion, they contract at the same time and relax at the same time, and the 158 THE VASCULAK MECHANISM. two auricles are similarly synchronous in action. It has been maintained, however, that the synchronism may at times not be perfect. Before we attempt to study in detail the several parts of this compli- cated series of events, it will be convenient to take a rapid survey of what is taking place within the heart during such a cycle. § 116. The cardiac cycle. We may take as the end of the cycle the moment at which the ventricles having emptied their contents have relaxed and returned to the diastolic or resting position and form. At this moment the blood is flowing freely with a fair rapidity, but as we have seen at a very low pressure, through the venae cavse into the right auricle (we may confine ourselves at first to the right side), and since there is now nothing to keep the tricuspid valve shut, some of this blood probably finds its way into the ventricle also. This goes on for some little time, and then comes the sharp, short systole of the auricle, which, since it begins, as we have seen, as a wave of contraction running forward along the ends of the venae cavse, drives the blood not backward into the veins but forward into the ventricle ; this end is further secured by the fact that the systole has behind it on the venous side the pressure of the blood in the veins, increasing, as we have seen, back- ward toward the capillaries, and before it the relatively empty cavity of the ventricle, in which the pressure is at first very low. By the complete con- traction of the auricular walls the complete or nearly complete emptying of the cavity is insured. No valves are present in the mouth of the superior vena cava, for they are not needed ; and the imperfect Eustachian valve at the mouth of the inferior vena cava cannot be of any great use in the adult, though in its more developed state in the foetus it had an important function in directing the blood of the inferior vena cava through the foramen ovale into the left auricle. The valves in the coronary vein are, however, probably of some use in preventing a reflux into that vessel. As the blood is being driven by the auricular systole into the ventricle, a reflux current is probably set up, by which the blood, passing along the sides of the ventricle, gets between them and the flaps of the tricuspid valve and so tends to float these up. [Figs. 50, 51.] It is further probable that [Fio. 50. FIG. 51. Diagrams of Valves of the Heart. After Dalton.] the same reflux current, continuing somewhat later than the flow into the ventricle, is sufficient to bring the flaps into apposition, without any regurgi- tation into the auricle, at the close of the auricular systole, before the ven- THE HEART. 159 tricular systole has begun. According to some authors, however, the closure of the valve is effected, at the very beginning of the ventricular systole, by the contraction of the papillary muscles ; the chordae tendineae of a papillary muscle are attached to the adjacent edges of two flaps, so that the shorten- ing of the muscle tends to bring these edges into apposition. The auricular systole is, as we have said, immediately followed by that of the ventricle. Whether the contraction of the ventricular walls (which as we shall see is a simple though prolonged contraction and not a tetanus) begins at one point and swiftly travels over the rest of the fibres, or begins all over the ventricle at once, is a question not at present definitely settled ; but in any case the walls exert on the contents a pressure which is soon brought to bear on the whole contents and very rapidly rises to a maximum. The only effect upon the valve of this increasing intra-ventricular pressure is to render the valve more and more tense, and in consequence more secure, the chordae tendinese (the slackening of which through the change of form of the ventricle is probably obviated by a regulative contraction of the papillary muscles) at the same time preventing the valve from being inverted or even bulging largely into the auricle, and indeed, according to some observers, keeping the valvular sheet actually convex to the ventricular cavity, by which means the complete emptying of the ventricle is more fully effected. [Figs. 50, 51.] The connection, to which we have just referred, of the chordae of the same papillary muscle with the adjacent edges of two flaps, also assists in keeping the flaps in more complete apposition. Morever the extreme borders of the valves, outside the attachments of the chordae, are excessively thin, so that when the valve is closed, these thin portions are pressed flat together back to back ; hence, while the tougher central parts of the valves bear the force of the ventricular systole, the opposed thin membranous edges, pressed together by the blood, more completely secure the closure of the orifice. At the commencement of the ventricular systole the semilunar valves of the pulmonary artery are closed, and are kept closed by the high pressure of the blood in the artery. As, however, the ventricle continues to press with greater and greater force on its contents, making the ventricle hard and tense to the touch, the pressure within the ventricle becomes greater than that in the pulmonary artery, and this greater pressure forces open the semi- lunar valves and allows the escape of the contents into the artery. The ventricular systole may be seen and felt in the exposed heart to be of some duration ; it is strong enough and long enough to empty the ventricle com- pletely ; indeed, as we shall see, it probably lasts longer than the discharge of blood, so that there is a brief period during which the ventricle is empty but yet contracted. During the ventricular systole the semilunar valves are pressed outward toward but not close to the arterial walls, reflux currents probably keeping them in an intermediate position, so that their orifice forms an equilateral triangle with curved sides ; thus they offer little obstacle to the escape of blood from the cavity of the ventricle. The ventricle, as we have seen, pro- pels the blood with great force and rapidity into the pulmonary artery, and the whole contents are speedily ejected. Now, when a force which is driving a fluid with great rapidity along a closed channel suddenly ceases to act, the fluid, by its momentum, continues to move onward after the force has ceased ; in consequence of this a negative pressure makes its appearance in the rear of the fluid, and, sucking the fluid back again, sets up a reflux cur- rent. So when the last portions of blood leave the ventricle a negative pressure makes its appearance behind them, and leads to a reflux current from the artery toward the ventricle. This alone would be sufficient to bring 160 THE VASCULAR MECHANISM. the valves together ; and, in the opinion of some, is the real cause of the closure of the valves ; others, however, as we shall see later on, maintain that subsequent to this reflux due to mere negative pressure a somewhat later reflux, in which the elastic reaction of the arterial walls is concerned, more completely fills and renders tense the pockets, causing their free margins to come into close and firm contact, and thus entirely blocks the way. The corpora Arantii meet in the centre, and the thin membranous festoons or lunulse are brought into exact apposition. As in the tricuspid valves, so here, while the pressure of the blood is borne by the tougher bodies of the several valves, each two thin adjacent lunulse, pressed together by the blood acting on both sides of them, are kept in complete contact, without any strain being put upon fhem ; in this way the orifice is closed in a most efficient manner. The ventricular systole now passes off, the muscular walls relax, the ventricle returns to its previous form and position, and the cycle is once more ended. What thus takes place in the right side takes place in the left side also. There is the same sudden sharp auricular systole beginning at the roots of the pulmonary veins, the same systole of the ventricle, but, as we shall see, one much more powerful and exerting much more force ; the mitral valve with its two flaps acts exactly like the tricuspid valve, and the action of the semilunar valves of the aorta simply repeats that of the valves of the pulmonary artery. We may now proceed to study some of the cardiac events in detail. § 117. The change of form. The exact determination of the changes in form and position of the heart, especially of the ventricles, during a cardiac cycle is attended with difficulties The ventricles, for instance, are continually changing their form : they change while their cavities are being filled from the auricles, they change while the contraction of their walls is getting up the pressure on their con- tents, they change while under the influence of that pressure, their contents being discharged into the arteries, and they change when, their cavities having been emptied, their muscular walls relax. We may take it for granted that the internal cavities are obliterated by the systole, for it is probable that practically the whole contents are driven out at. each stroke, and probably also each cavity is emptied from its apex toward the mouth of the artery. With regard to changes in external form, there seems no doubt that the side-to-side diameter is much lessened. It seems also clear that the front-to back diameter is greater during the whole time of the systole than during the diastole, the increase taking place during the first part of the systole. If a light lever be placed on the surface of the heart of a mammal, the chest having been opened and artificial respiration being kept up, some such curve as that represented in Fig. 52 is obtained. The rise of the lever in describing such a curve is due to the elevation of the part of the front surface of the heart on which the lever is resting. Such an elevation might be caused, especially if the lever were placed near the apex, by the heart being " tilted " upward during the systole, but only a small portion at most of the rise can be attributed to this 'cause; the rise is perhaps best seen when the lever is placed in the middle portion of the ventricle, and must be chiefly due to an increase in the front-to-back diameter of the ventricle during the beat. We shall discuss this curve later on in connection with other curves and may here simply say that the part of the curve from b' to d probably corresponds to the actual systole of the ventricle, that is, to the time during which the fibres of the ventricle are undergoing contraction, the sudden fall from d THE HEAET. 161 onward representing the relaxation which forms the first part of the diastole. If this interpretation of the curve he correct, it is obvious that the front-to- FIG. 52. Tracing from Heart of Cat, obtained by placing a Light Lever on the Ventricle, the Chest having been Opened. The tuning-fork curve marks 50 vibrations per second. back diameter is greater during the whole of the systole than it is during diastole, since the lever is raised up all this time. This increase of the front-to-back diameter combined with a decrease of the side-to-side diameter has for a result a change in the form of the section of the base of the ventricles. During the diastole this has somewhat the form of an ellipse with the long axis from side to side, but with the front part of the ellipse much more convex than the back, since the back surface of the ventricle is somewhat flattened. During the systole this ellipse is by the shortening of the side-to-side diameter and the increase of the front-to- back diameter converted into a figure much more nearly resembling a circle. It is urged, moreover, that the whole of the base is constricted, and that the greater efficiency of the auriculo-ventricular valves is thereby secured. As to the behavior of the long diameter from base to apex observers are not agreed. Some maintain that it is shortened, and others that it is prac- tically unchanged. If any shortening does take place, it must be largely compensated by the elongation of the great vessels, which, as stated above, 1 The vertical or rather curved lines (segments of circles) introduced into this and many other curves are of use for the purpose of measuring parts of the curve. A complete curve should exhibit an "abscissa" line. This may be drawn by allowing the lever, ar- ranged for the experiment but remaining at rest, to mark with its point on the recording surface set in motion ; a straight line, the abscissa line, is thus described, and may be drawn before or after the curve itself is made, and may be placed above or preferably be- low the curve. When a tuning-fork or other time-marker is used, the line of the time- marker or a line drawn through the curves of the tuning-fork will serve as an abscissa line. After a tracing has been made, the recording surface should be brought back to such a position that the point of the lever coincides with some point of the curve which it is desired to mark ; if the lever be then gently moved up and down, the point of the lever will describe a segment of a circle (the centre of which lies at the axis of the lever), which segment should be made long enough to cut both the curve and the abscissa line (the tuning-fork curves or other time-marking line) where this is drawn. By moving the recording surface backward and forward similar segments of circles may be drawn through other points of the curve. The lines a, b, c in Fig. 52 were thus drawn. The distance between any two of these points may thus be measured on the tuning-fork curve or other time curve, or on the abscissa line. Similar lines may be drawn on the tracing after its removal from the recording instrument in the following way: Take a pair of compasses, the two points of which are fixed just as far apart as the length of the lever used in the experiment, ^measured from its axis to its writing point. By means of the compasses find the position on the tracing of the centre of the circle of which any one of the previously drawn curved lines forms a segment. Through this centre draw a line parallel to the abscissa. By keeping one point of the compass on this line but moving it along the line backward or forward a segment of a circle may be drawn so as to cut any point of the curve that may be desired, and also the abscissa line or the time line. Such a segment of a circle may be used for the same purposes as the original one, and any number of such segments may be drawn. ' 162 THE VASCULAR MECHANISM. may be seen in an inspection of the beating heart. For there is evidence that the apex, though, as we have seen, it is during the systole somewhat twisted round and at the same time brought closer to the chest-wall, does not change its position up or down — i. e., in the long axis of the body. If in a rabbit or dog a needle be thrust through the chest-wall so that its point plunges into the apex of the heart, though the needle quivers its head moves neither up nor down, as it would do if its point in the apex moved down or up. § 118. Cardiac impulse. If the hand be placed on the chest, a shock or impulse will be felt at each beat, and on examination this impulse, " cardiac impulse," will be found to be synchronous with the systole of the ventricle. In man, the cardiac impulse may be most distinctly felt in the fifth costal interspace, about an inch below and a little to the median side of the left nipple. In an animal the same impulse may also be felt in another way — viz., by making an incision through the diaphragm from the abdomen, and placing the finger between the chest-wall and the apex. It then can be dis- tinctly recognized as the result of the hardening of the ventricle during the systole. And the impulse which is felt on the outside of the chest is chiefly the effect of the same hardening of the stationary portion of the ventricle in contact with the chest-wall, transmitted through the chest-wall to the finger. In its flaccid state, during diastole, the apex is (in a standing position, at least) at this point in contact with the chest-wall, lying between it and the tolerably resistant diaphragm. During the systole, while being brought even closer to the chest-wall by the tilting of the ventricle and by the move- ment to the front and to the right, of which we have already spoken, it suddenly grows tense and hard. The ventricles, in executing their systole, have to contract against resistance. They have to produce within their cavities pressures greater than those in the aorta and pulmonary arteries, respectively. This is, in fact, the object of the systole. Hence, during the swift systole, the ventricular portion of the heart becomes suddenly tense, somewhat in the same way as a bladder full of fluid would become tense and hard when forcibly squeezed. The sudden pressure exerted by the ventricle, thus become suddenly tense and hard, aided by the closer contact of the apex with the chest-wall (which, however, by itself without the hardening of contraction would be insufficient to produce the effect), gives an impulse of shock both to the chest-wall and to the diaphragm, which may be felt readily both on the chest-wall, and also through the diaphragm when the abdomen is opened and the finger inserted. If the modification of the sphygmograph (of which we shall speak in dealing, later on, with the pulse), called the cardiograph, be placed on the spot where the impulse is felt most strongly, the lever is seen to be raised during the systole of the ventricles, and to fall again as the systole passes away, very much as if it were placed on the heart directly. A tracing may thus be obtained (see Fig. 58), of which we shall have to speak more fully immediately (see § 122). If the button of the lever be placed, not on the exact spot of the impulse, but at a little distance from it, the lever will be depressed during the sys- tole. While at the spot of impulse itself the contact of the ventricle is increased during systole, away from the spot the ventricle retires from the chest-wall (by the diminution of its right-to-left diameter), and hence, by the mediastinal attachments of the pericardium, draws the chest-wall after it. § 119. The sounds of the heart. When the ear is applied to the chest, either directly or by means of a stethoscope, two sounds are heard, the first a comparatively long, dull, booming sound, the second a short, sharp, sudden one. Between the first and second sounds the interval of time 'is very THE HEART. 163 short — too short to be measurable — but between the second and the suc- ceeding first sound there is a distinct pause. The sounds have been likened to the pronunciation of the syllables lubb, dup, so that the cardiac cycle, as far as the sounds are concerned, might be represented by : liibb, dup, pause. The second sound, which is short and sharp, presents no difficulties. It is coincident in point of time with the closure of the semilunar valves, and is heard to the best advantage over the second right costal cartilage close to its junction with the sternum — i. e., at the point where the aortic arch comes nearest to the surface, and to which sounds generated at the aortic orifice would be best conducted. Its characters are such as would belong to a sound generated by membranes like the semilunar valves being suddenly made tense and so thrown into vibrations. It is obscured and altered or replaced by a " murmur " when the semilunar valves are affected by disease, and may be artificially obliterated, a murmur taking its place, by passing a wire down the arteries and hooking up the aortic valves. There can be no doubt, in fact, that the second sound is due to the semilunar valves being thrown into vibrations at their sudden closure. The sound heard at the second right costal cartilage is chiefly that generated by the aortic valves, and murmurs or other alterations in the sound caused by changes in the aortic valves are heard most clearly at this spot. But even here the sound is not exclusively of aortic origin, for in certain cases in which the semi- lunar valves on the two sides of the heart are not wholly synchronous in action the sound heard here is double (" reduplicated second sound "), one being due to the aorta and one to the pulmonary artery. While the sound is listened to on the left side of the sternum at the same level, the pulmonary artery is supposed to have the chief share in pro- ducing what is heard, and changes in the sound heard more clearly here than on the right side are taken as indications of mischief in the pulmo- nary valves. The first sound, longer, duller, and of a more " booming " character than the second, heard with greatest distinctness at the spot where the cardiac impulse is felt, presents many difficulties in the way of a complete explana- tion. It is heard distinctly when the chest-walls are removed. The cardiac impulse, therefore, can have little or nothing to do with it. In point of time it is coincident with the systole of the ventricles, and may be heard to the greatest advantage at the spot of the cardiac impulse — that is to say, at the place where the ventricles corne nearest to the surface, and to which sounds generated in the ventricle would be best conducted. It is more closely coincident with the closure and consequent vibrations of the auriculo-ventricular valves than with the entire systole ; for, on the one hand, it dies away before the second sound begins, whereas, as we shall see, the actual systole lasts up to, if not beyond, the closure of the semilunar valves ; and, on the other hand, the auriculo-ventricular valve ceases to be tense and to vibrate as soon as the contents of the ventricle are driven out. This suggests that the sound is caused by the sudden tension of the auriculo-ventricular valves, and this view is supported by the facts that the sound is obscured, altered, or replaced by murmurs when the tricuspid or mitral valves are dis- eased, and that the sound is also altered, or, according to some observers, wholly done away with, when blood is prevented from entering the ven- tricles by ligature of the venae cavse. On the other hand, the sound has not the sharp character which one would expect in a sound generated by the vibration of membranes such as the valves in question, but in its booming qualities rather suggests a muscular sound. Further, according to some observers, the sound, though somewhat modified, may still be heard when 164 THE VASCULAR MECHANISM. the large veins are clamped so that no blood enters the ventricle, and, indeed, may be recognized in the few beats given by a mammalian ventricle rapidly cut out of the living body by an incision carried below the auriculo-ven- tricular ring. Hence the view has been adopted that this first sound is a muscular sound. In discussing the muscular sound of skeletal muscle (see § 78), we saw reasons to distrust the view that this sound was generated by the repeated individual simple contractions which made up the tetanus, and hence correspond in tone to the number of those simple contractions re- peated in a second, and to adopt the view that the sound was really due to a repetition of unequal tensions occurring in a muscle during the contraction. Now, the ventricular systole is undoubtedly a simple contraction, a prolonged simple contraction, not a tetanus, and therefore under the old view of the nature of a muscular sound, could not produce such a sound ; but, accepting the other view, and reflecting how complex must be the course of the systolic wave of contraction over the twisted fibres of the ventricle, we shall not find great difficulty in supposing that that wave is capable in its progress of pro- ducing such repetitions of unequal tensions as might give rise to a " muscular sound," and consequently in regarding the first sound as mainly so caused. Accepting such a view of the origin of the sound, we should expect to find the tension of the muscular fibres, and so the nature of sound dependent on the quantity of fluid present in the ventricular cavities, and hence modified by ligature of the great veins, and still more by the total removal of the auricles with the auriculo-ventricular valves. We may add that we should expect to find it modified by the escape of blood from the ventricles into the arteries during the systole itself, and might regard this as explaining why it dies away before the ventricle has ceased to contract. Moreover, seeing that the auriculo-ventricular valves must be thrown into sudden tension at the onset of the ventricular systole, which, as we have seen, is developed with considerable rapidity, not far removed at all events from the rapidity with which the semilunar valves are closed, a rapidity, there- fore, capable of giving rise to vibrations of the valves adequate to produce a sound, it is difficult to escape the conclusion that the closure of these valves must also generate a sound which in a normally beating heart is mingled in some way with the sound of muscular origin, although the ear cannot detect the mixture. If we accept this view, that the sound is of double origin, partly " muscu- lar," partly " valvular," both causes being dependent on the tension of the ventricular cavities, we can perhaps more easily understand how it is that the normal first sound is at times so largely, indeed we may say so com- pletely, altered and obscured in diseases of the auriculo-ventricular valves. Since the left ventricle forms the entire left apex of the heart, the mur- murs or other changes of the first sound heard most distinctly at the spot of cardiac impulse belong to the mitral valve of the left ventricle. Murmurs generated in the tricuspid valve of the right ventricle are heard more dis- tinctly in the median line below the end of the sternum. Endocardiae Pressure. § 120. Since the heart exists for the purpose of exerting pressure on the blood within its cavities, by which pressure the circulation of the blood is effected, the study of the characters of this endocardiac pressure possesses great interest. ITn fortunately, the observation of this pressure is attended with great difficulties. The ordinary mercury manometer which is so useful in studying the pressure in the arteries fails us when applied to the heart. It is true that a long canula, or tube open at the end, filled with sodium THE HEART. 165 carbonate solution, may be introduced into the jugular vein and so slipped down into either the right auricle or the right ventricle, or may be similarly introduced into the carotid artery and with care slipped down through the aorta, past the semilunar valves, into the left ventricle, and having been thus introduced may, like the ordinary canula used in studying arterial pressure (§ 104), be brought into connection with a mercury manometer. In this way, as in the case of an artery, a graphic record may be obtained of the changes of pressure taking place in either of the above three cavities. But the changes in the ventricular cavities are so great and rapid, that the inertia of the mercury, an evil in the case of an artery, comes so largely into play that the curve described by the float on the mercury is far from being an accurate record of the changes of pressure in the cavity. The mercury manometer may, however, be made to yield valuable results by adopting the ingenious contrivance of converting the ordinary manometer into a maximum or a minimum instrument. The principle of the maximum manometer, Fig. 53, consists in the introduction into the tube leading from the heart to the mercury column of a (modified cup- [FiG. 53. The Maximum Manometer of Goltz and Gaule. At e a connection is made with the tube lead- ing to the heart. When the screw-clamp k is closed, the valve v comes into action, and the in- strument, in the position of the valve shown in the figure, is a maximum manometer. By revers- ing the direction of v it is converted into a minimum manometer. When k is opened, the varia- tions of pressure are conveyed along a, and the instrument then acts like an ordinary manometer. and-ball) valve, opening, like the aortic semilunar valves, easily from the heart, but closing firmly when fluid attempts to return to the heart. The highest pres- sure is that which drives the longest column of fluid past the valve, raising the mercury column to a corresponding height. Since this column, once past the valve, cannot return, the mercury remains at the height to which it was raised by it and thus records the maximum pressure. By reversing the direction of the valve, the manometer is converted from a maximum into a minimum instrument. The maximum manometer applied to the cavity of either ventricle or of the right auricle, gives a record of the highest pressure reached within that cavity, and the minimum manometer similarly shows the lowest pressure reached, during the time that the instrument is applied. The maximum manometer thus employed shows that the maximum pres- 166 THE VASCULAR MECHANISM. sure in the left ventricle is distinctly greater than the mean pressure in the aorta (the ordinary mercury manometer having previously given the para- doxical result, due" to the inertia of the mercury, that the mean pressure in the left ventricle might be less than in the aorta), that the maximum pres- sure in the right ventricle is less than in the left, and in the right auricle is still less. In the dog, for example, the pressure in the left ventricle reaches a maximum of about 140 mm. (mercury), in the right ventricle of about 60 mm., and in the right auricle of about 20 mm. But the chief interest attaches to the minimum pressure observed ; for the minimum manometer records a negative pressure in the cavities of the heart— i. , notch preceding this. D, succeeding secondary wave. The curve above is that of a tuning-fork with ten double vibrations in a second. and in many of the other tracings given, these secondary elevations are marked, as B, C, D. When one such secondary elevation only is conspicu- ous, so that the pulse-curve presents two notable crests only, the primary crest and a secondary one, the pulse is said to be " dicrotic " ; when two secondary crests are prominent, the pulse is often called "tricrotic"; where several, " polycrotic." As a general rule, the secondary elevations appear only on the descending limb of the primary wave, as in most of the curves given, and the curve is then spoken of as " katacrotic." Sometimes, however, the first elevation or crest is not the highest, but ap- pears on the ascending portion of the main curve; such a curve is spoken of as " anacrotic," Fig. 69. Of these secondary elevations the most frequent, conspicuous, and impor- tant is the one which appears some way down on the descending limb, and is marked C on Fig. 68 and on most of the curves here given. It is more or less distinctly visible on all sphygmograms, and may be seen in those of the aorta as well as of other arteries. Sometimes it is so slight as to be hardly discernible ; at other times it may be so marked as to give rise to a really double pulse (Fig. 70), i. e., a pulse which can be felt as double by the FIG. 70. n Anacrotic Sphygmograph- tracing from the Ascending Aorta. (Aneurism.) Two Grades of Marked Dicrotism in Radial Pulse of Man. (Typhoid fever.) finger ; hence it has been called the dierotic elevation or the dicrotic wave, the notch preceding the elevation being spoken of as the " dicrotic notch." Neither it nor any other secondary elevations can be recognized in the tracings of blood-pressure taken with a manometer. This may be explained, 186 THE VASCULAR MECHANISM. as we have said (§ 128) by the fact that the movements of the mercury column are too sluggish to reproduce these finer variations ; but dicrotism is also conspicuous by its absence in the tracings given by more delicately responsive instruments. Moreover, when the normal pulse is felt by the finger, most persons find themselves unable to detect any dicrotism. But that it does really exist in the normal pulse is shown by the fact that it appears in a most unmistakable manner in the tracing obtained by allow- ing the blood to spurt directly from an opened small artery, such as the dorsalis pedis, upon a recording surface. Less constant and conspicuous than the dicrotic wave, but yet appearing in most sphygmograms, is an elevation which appears higher up on the descending limb of the main wave ; it is marked B in Fig. 68, and on several of the other curves, and is frequently called the pre-dicrotie wave ; it may become very prominent. Sometimes other secondary waves, often called " post-dicrotic," are seen following the dicrotic wave, as at D in Fig. 68, and some other curves ; but these are not often present, and usually, even when present, inconspicuous. When tracings are taken from several arteries, or from the same artery under different conditions of the body, these secondary waves are found to vary very considerably, giving rise to many characteristic forms of pulse- curve. Were we able with certainty to trace back the several features of the curves to their respective causes, an adequate examination of sphygmo- graphic tracings would undoubtedly disclose much valuable information concerning the condition of the body presenting them. Unfortunately, the problem of the origin of these secondary waves is a most difficult and com- plex one; so much so, that the detailed interpretation of a sphygmographic tracing is still in most cases extremely uncertain. § 135. The chief interest attaches to the nature and meaning of the di- crotic wave. In general, the main conditions favoring dicrotism are (1) a highly extensible and elastic arterial wall, (2) a comparatively low mean pressure, leaving the extensible and elastic reaction of the arterial wall free scope to act, and (3) a sufficiently vigorous and sufficiently rapid stroke of the ventricle, and the discharge of a large quantity of blood into the aorta. The development of the dicrotic wave may probably be explained as follows : At each beat the time during which the contents of the left ventricle are injected into the aorta is, as we have seen (§ 125), very brief. The expan- sion of the aorta is very sudden, and the cessation of that expansion is also very sudden. Now, when fluid is being driven with even a steady pressure through an elastic tube or a system of elastic tubes, levers placed on the tube wall describe curves indicating variations in the diameter of the tube, if the inflow into the tube be suddenly stopped, as by sharply turning a stop-cock ; and a comparison of levers placed at different distances from the stop-cock will show that these variations of diameter travel down the tube from the stop- cock in the form of waves. The lever near the stop-cock will first of all fall, but speedily begin to rise again, and this subsequent rise will be followed by another fall, after which there may be one or more succeeding rises and falls — that is, oscillations — with decreasing amplitudes, until the fluid comes to rest. The levers further from the stop-cock will describe curves similar to the above in form but of less amplitude, and it will be found that these occur somewhat later in time, the more so the further the lever is from the stop- cock. Obviously these waves are generated at or near the stop-cock, and travel thence along the tubing. We may infer that at each beat of the heart similar waves would be generated at the foot of the aorta upon the sudden cessation of the flow from THE PULSE. 187 the ventricle, and would travel thence along the elastic arteries. The facts that each beat is rapidly succeeded by another, and that the flow which sud- denly ceases is also, by the nature of the ventricular stroke, suddenly gen- erated, may render the waves more complicated, but will not change their essential nature. The exact interpretation of the generation of these waves is perhaps not without difficulty, but two factors seem of especial importance. In the first place, as we have already more than once said, when a rapid flow is suddenly stopped a negative pressure makes its appearance behind the column of fluid. In a rigid tube this simply tends to a reflux of fluid. In an elastic tube its effects are complicated by the second factor, the elastic action and inertia of the walls of the tube. Upon the sudden cessation of the flow, the expansion of the tube, or as we may at once say, of the aorta, ceases, the vessel begins to shrink, and the lever placed on its walls falls, as from A onward in the pulse- curve. This shrinking is in part due to the elastic reaction of the walls of the aorta, but is increased by the " suction " action of the negative pressure spoken of above. In thus shrinking, however, under these combined causes, the aorta, through the inertia of its walls, overshoots the mark, it is carried beyond its natural calibre — i. e., the diameter it would possess if left to itself with the pressure inside and outside equal ; it shrinks too much and conse- quently begins again to expand. This secondary expansion (taking for simplicity sake a pulse-curve in which the so-called pre-dicrotic wave, B, is absent or inconspicuous) causes the secondary rise of the lever up to C — that is, the dicrotic rise. In thus expanding again the aorta tends to draw back toward the heart the column of blood which by loss of momentum had come to rest, or, indeed, under the influence of the negative pressure spoken of above, was already undergoing a reflux. In this secondary expansion, more- over, the aorta is by the inertia of its walls, aided by that of the blood, again carried, so to speak, beyond its mark, so that no sooner has it become ex- panded and filled with fluid to a certain extent than it again begins to shrink as from C onward. And this shrinking may in a similar manner to the first be followed by a further expansion and shrinking, giving rise to a post- dicrotic wave, or it may be to post-dicrotic waves. And the successive changes thus inaugurated at the root of the aorta travel as so many waves along the arterial system, diminishing as they go. It will be observed that for the development of these waves a certain quality in the walls of the tubing is necessary. The tube must be such as possesses when at rest an open lumen ; the walls must be of such a kind that the tube remains open when empty — " e.y when the atmospheric pressure is equal inside and outside— so that when it shrinks too much it expands again in striving to retain its natural calibre. This we have seen to be a characteristic of the arteries. A collapsible ube of thin membrane will not show the phenomena ; such a tube when the stop-cock is turned collapses and empties itself, continuing to be collapsed without any effort to expand again. In the above explanation no mention has been made of the closing of the semiluuar valves ; we shall have to speak of these a little later on in refer- •ing to the pre-dicrotic wave, and shall see that, under the view we have just given, the closing of the semilunar valves is to be regarded rather as the effect than the cause of the dicrotic wave. Many authors, however, give in interpretation of the dicrotic wave different from that detailed above, "'hus, it is held that the primary shrinking from A onward, being brought bear on the column of blood already come to rest, in face of the great >ressure in front, drives the blood back against the semilunar valves, thus closing them, and that the impact of the column of blood against the valves irts a new wave of expansion, which reinforcing the natural tendency of 188 THE VASCULAR MECHANISM. the elastic walls to expand again after their primary shrinking, produces tho dicrotic wave C. On this view, it is the blood driven back from the valves which expands the artery ; on the view given above, it is the ex- panding artery which draws the blood back toward the valves. Moreover, quite other views have been or are held concerning this dicrotic wave. According to many authors, it is what is called a " re- flected " wave. Thus, when the tube of the artificial model bearing two levers is blocked just beyond the far lever, the primary wave is seen to be accompanied by a second wave, which at the far lever is seen close to, and often fused into, the primary wave (Fig. 64, VI. af), but at the near lever is at some distance from it (Fig. 64, I. a'), being the further from it the longer the interval between the lever and the block in the tube. The second wave is evidently the primary wave reflected at the block and travel- ling backward toward the pump. It thus, of course, passes the far lever be- fore the near one. And it has been argued that the dicrotic wave of the pulse is really such a reflected wave, started either at the minute arteries and capillaries, or at the points of bifurcation of the larger arteries, and travelling backward to the aorta. But if this were the case, the distance between the primary crest and the dicrotic crest ought to be less in arteries more distant from than in those nearer to the heart, just as in the artificial scheme the reflected wave is fused with a primary wave near the block (Fig. 64, VI. 6 a. a'), but becomes more and more separated from it the further back toward the pump we trace it (Fig. 64, I. 1 a. a'}. Now this is not the case with the dicrotic wave. Careful measurements show that the distance between the primary and dicrotic crests is either greater, or certainly not less, in the smaller "or more distant arteries than in the larger or nearer ones. This feature indeed proves that the dicrotic wave cannot be due to reflection at the periphery, or, indeed, in any way a retrograde wave. Be- sides, the multitudinous peripheral division would render one large periph- erally reflected wave impossible. Again, the more rapidly the primary wave, is obliterated, or at least diminished, on its way to the periphery, the less conspicuous should be the dicrotic wave. Hence increased extensibility and increased elastic reaction of the arterial walls which tend to use up rapidly the primary wave, should also lessen the dicrotic wave. But as a matter of fact these conditions, as we have said, are favorable to the promi- nence of the dicrotic wave. On the other hand, these and the other conditions- which favor dicrotism in the pulse are exactly those which would favor such a development of secondary waves as has been described above, and their absence would be unfavorable to the occurrence of such waves. Thus dicrotism is less marked in rigid arteries (such as those of old people) than in healthy elastic ones ; the rigid wall neither expands so readily nor shrinks so readily, and hence does not so readily give rise to such secondary waves. Again, dicrotism is more marked when the mean arterial pressure is low than when it is high ; indeed, dicrotism may be induced when absent, or increased when slightly marked by diminishing, in one way or another, the mean pressure. Now, when the pressure is high, the arteries are kept continually much expanded, and are therefore the less capable of further expansion ; that is to say, are, so far, more rigid. Hence the additional expansion due to the systole is not very great ; there is a less tendency for the arterial walls to swing backward and forward, so to speak, and hence a less tendency to the development of secondary waves. When the mean pressure is low, the opposite state of things exists ; supposing, of course, that the ventricular stroke is adequately vigorous (the low pressure being due, not to diminished cardiac force, but to diminished peripheral resistance), the relatively empty but highly distensible THE PULSE. 189 artery is rapidly expanded, and, falling rapidly back, enters upon a second- ary (dicrotic) expansion, and even a third. Moreover, the same principles may be applied to explain why sometimes dicrotisrn will appear marked in a particular artery while it remains little marked in the rest of the system. In experimenting with an artificial tubing such as the arterial model, the physical characters of which remain the same throughout, both the primary and the secondary waves retain the same characters as they travel along the tubing, save only that both gradually diminish toward the periphery ; and in the natural circulation, when the vascular conditions are fairly uniform throughout, the pulse-curve, as a rule, possesses the same general characters throughout, save that it is gradually " damped off." But suppose we were to substitute for the first section of the tubing a piece of perfectly rigid tubing ; this at the stroke of the pump, on account of its being rigid, would show neither primary nor secondary ex- pansion, but the expanding force of the pump's stroke would be transmitted through it to the second elastic section, and here the primary and secondary waves would at once become evident. This is an extreme case, but the same thing would be seen to a less degree in passing from a more rigid, that is, less extensible and elastic section, to a less rigid, more extensible and elastic section ; the primary and secondary expansions, in spite of the general damp- ing effect, would suddenly increase. Similarly in the living body a pulse- curve which, so long as it is travelling along arteries in which the mean pressure is high, and which are therefore practically somewhat rigid, is not markedly dicrotic, may become very markedly dicrotic when it comes to a particular artery in which the mean pressure is low (and we shall see pres- ently that such a case may occur), and the walls of which are therefore for the time being relatively more distensible than the rest. Lastly, we may recall the observation made above (§ 130), that the curve of expansion of an elastic tube is modified by the pressure exerted by the lever employed to record it, and that hence, in the same artery and with the same instrument, the size, form, and even the special features of the curve vary according to the amount of pressure with which the lever is pressed upon the artery. Accordingly the amount of dicrotism apparent in a pulse may be modified by the pressure exerted by the lever. In Fig. 64, for instance, the dicrotic wave is more evident in the middle than in the upper tracing. § 136. The pre-dicrotic wave (marked B on Fig. 68, and on several other of the pulse-curves), which precedes the dicrotic wave and is still more variable than that wave, being sometimes slight or even invisible and sometimes conspicuous, has given rise to much controversy. In the inter- pretation of the dicrotic wave given in the preceding paragraph it was stated that the negative pressure developed on the cessation of the flow in the rear of the column of blood, led by itself to a reflux toward the ventricle ; and it has been suggested that this reflux meeting and closing the semi- lunar valves starts a small wave of expansion before the larger dicrotic wave has had time to develop itself. On this view the semilunar valves would be actually closed before the occurrence of the secondary dicrotic expansion of the arterial walls, though the larger, more powerful reflux of this later event must render the closure more complete, and in doing so possibly gives rise to the second sound. According, however, to the second view given in the same paragraph, which regards the reflux due to the shrinking of the artery in face of the great pressure in front as firmly closing the semilunar valves, and as thus starting the secondary dicrotic wave of expansion, the firm closing of the semilunar valves must take place before the beginning, riot during the development of the dicrotic wave ; it 190 THE VASCULAR MECHANISM. is still possible, however, even on this view, as on the other, to suppose that an antecedent reflux, due to the negative pressure succeeding the cessation of flow from the ventricle, closes the valves and starts the pre-dicrotic wave. But the matter is one not yet beyond the stage of controversy. § 137. In an anacrotic pulse the first rise is not the highest, but a second rise (B, Fig. 69) which follows and is separated from it by a notch is higher than, or at least as high as, itself. Such an anacrotic wave, though it may sometimes be produced temporarily in healthy persons, is generally associated with diseased conditions, usually such in which the arteries are abnormally rigid. In describing the ventricular systole, we spoke of the pressure within the ventricle as reaching its maximum just before the opening of the semilunar valves ; and this is apparently the normal event ; but there are curves which seem to show that after the first sudden rise of pressure which opens the valves, followed by a brief lessening of pressure, which appears on the curve as a notch, the pressure may again rise, and that to a point higher than before. And a similar curve is sometimes de- scribed by the front-to-back diameter of the ventricle. The systole opens the valve as it were with a burst ; this is followed by a slight relapse, and then the systole, strengthening again, discharges the whole of the ven- tricular contents into the aorta and so brings about a tardy maximum ex- pansion. And what is thus started in the aorta travels onward over the arterial system. It is difficult to see how these anacrotic events can be pro- duced, except by a certain irregularity in the ventricular systole ; and, indeed, the anacrotic pulse is frequently associated with some disease or defect of the ventricle. §138. Venous pulse. Under certain circumstances the pulse may be carried on from the arteries through the capillaries into the veins. Thus, as we shall see later on, when the salivary gland is actively secreting, the blood may issue from the gland through the veins in a rapid pulsating stream. The nervous events which give rise to the secretion of saliva, lead at the same time, by the agency of vasomotor nerves, of which we will pre- sently speak, to a dilatation of the small arteries of the gland. When the gland is at rest the minute arteries are, as we shall see, somewhat con- stricted and narrowed, and thus contribute largely to the peripheral resist- ance in the part ; this peripheral resistance throws into action the elastic properties of the small arteries leading to the gland, and the remnant of the pulse reaching these arteries is, as we before explained, finally de- stroyed. When the minute arteries are dilated, their widened channels allow the blood to flow more easily through them and with less friction ; the peripheral resistance which they normally offer is thus lessened. In conse- quence of this the elasticity of the walls of the small arteries is brought into play to a less extent than before, and these small arteries cease to do their share in destroying the pulse which comes down to them from the larger arteries. As in the case of the artificial model, where the " periph- eral " tubing is kept open, not enough elasticity is brought into play to convert the intermittent arterial flow into a continuous one, and the pulse which reaches the arteries of the gland passes on through them and through the capillaries, arid is continued on into the veins. A similar venous pulse is also sometimes seen in other organs. Careful tracings of the great veins in the neighborhood of the heart show elevations and depressions, which appear due to the variations of intra- cardiac (auricular) pressure, and which may, perhaps, be spoken of as constituting a " venous pulse," though they have a quite different origin from the venous pulse just described in the salivary gland ; but at present they need further elucidation. In cases, however', of insufficiency of the THE VASCULAE MECHANISM. 191 tricuspid valves, the systole of the ventricle makes itself distinctly felt in the great veins ; and a distention travelling backward from the heart becomes very visible in the veins of the neck. This is sometimes spoken of as a venous pulse. Variations of pressure in the great veins, due to the respiratory move- ments, are also sometimes spoken of as a venous pulse ; the nature of these variations will be explained in treating of respiration. THE REGULATION AND ADAPTATION OF THE VASCULAR MECHANISM. The Regulation of the Beat of the Heart. § 139. So far the facts with which we have had to deal, with the excep- tion of the heart's beat itself, have been simply physical facts. All the essential phenomena which we have studied may be reproduced on a dead model. Such an unvarying mechanical vascular system would, however, be useless to a living body whose actions were at all complicated. The prominent feature of a living mechanism is the power of adapting itself to changes in its internal and external circumstances. The vascular mechanism in all animals in which it is present is capable of local and general modifications, adapting it to local and general changes of circumstance. These modifications fall into two great classes : 1. Changes in the heart's beat. These, being central, have, of course, a general effect; they influence or may influence the whole body. 2. Changes in the peripheral resistance, due to variations in the calibre of the minute arteries, brought about by the agency of their contractile mus- cular coats. These changes may be either local, affecting a particular vas- cular area only, or general, affecting all or nearly all the bloodvessels of the body. These two classes of events are chiefly governed by the nervous system. It is by means of the nervous system that the heart's beat and the calibre of the minute arteries are brought into relation with each other, and with almost every part of the body. It is by means of the nervous system acting either on the heart or on the small arteries, or on both, that a change of cir- cumstances affecting either the whole or a part of the body is met by com- pensating or regulative changes in the flow of blood. It is by means of the nervous system that an organ has a more full supply of blood when at work than when at rest, that the tide of blood through the skin rises and ebbs with the rise and fall of the temperature of the air, that the work of the heart is tempered to meet the strain of overfull arteries, and that the arterial gates open and shut as the force of the central pump waxes and wanes. The study of these changes becomes, therefore, to a large extent a study of nervous actions. The circulation may also be modified by events not belonging to either of the above two classes. Thus, in this or that peripheral area, changes in the capillary walls and the walls of the minute arteries and veins may lead to an increase of the tendency of the blood corpuscles to adhere to the vascular walls, and so, quite apart from any change in the calibre of the bloodvessels, may lead to increase of the peripheral resistance. This is seen in an extreme case in inflammation, but may possibly intervene to a less extent in the ordinary condition of the circulation, and may also be under the influence of the nervous system. Further, any decided change in the quantity of blood actually in circulation must also influence the working of the vascular mechanism. But both these changes are unimportant compared with the other two kinds of changes. Hence, the two most important problems for us to study are, 1, how the nervous system regulates the beat of the heart, 192 THE VASCULAR MECHANISM. and 2, how the nervous system regulates the calibre of the bloodvessels. We will first consider the former problem. The Development of the Normal Seat. | 140. The heart of a mammal, or of a warm-blooded animal, generally ceases to beat within a few minutes after being removed from the body in the ordinary way, the hearts of newly-born animals continuing, however, to beat for a longer time than those of adults. Hence, though by special pre- caution and by means of an artificial circulation of blood, an isolated mammalian heart may be preserved in a pulsating condition for a much longer time, our knowledge of the exact nature and of the causes of the cardiac beat is as yet very largely based on the study of the hearts of cold- blooded animals, which will continue to beat for hours, or under favorable circumstances even for days, after they have been removed from the body with only ordinary care. * We have reason to think that the mechanism by which the beat is carried on varies in some of its secondary features in differ- ent kinds of animals ; that the heart, for instance, of the eel, the snake, the tortoise, and the frog, differ in some minor details of behavior, both from each other and from the bird and the mammal ; but we may, at first at all events, take the heart of the frog as illustrating the main and important truths concerning the causes and mechanism of the beat. In studying closely the phenomena of the beat of the heart it becomes necessary to obtain a graphic record of various movements. 1. In the frog or other cold-blooded animal, a light lever may be placed directly on the ventricle (or on an auricle, etc.), and changes of form, due either to disten- tion by the influx of blood or to the systole, will cause movements of the lever, which may be recorded on a travelling surface. The same methods, as we have seen, may be applied to the mammalian heart. 2. Or, as in Gaskell's method, the heart may be fixed by a clamp carefully ad- justed around the auriculo- ventricular groove, while the apex of the ventricle and some portion of one auricle are attached by threads to horizontal levers placed respectively above and below the heart. The auricle and the ventricle each in its systole pulls at the lever attached to it, and the times and extent of the contrac- tions may thus be recorded. 3. A record of endocardiac pressure may he taken in the frog or tortoise, as in the mammal, by means of an appropriate manometer. And in these animals, at all events, it is easy to keep up an artificial circulation. A canula is introduced into the sinus venosus, and another into the ventricle through the aorta. Serum or dilute blood (or any other fluid which it may be desire.d to employ) is driven by moderate pressure through the former ; to the latter is attached a tube connected by means of a side piece with a small mercury manometer. So long as the exit-tube is open at the end fluid flows freely through the heart and apparatus. Upon closing the exit-tube at its far end the force of the ventricular systole is brought to bear on the manometer, the index of which registers in the usual way the movements of the mercury column. Newell Martin has succeeded in applying a modification of this method to the mammalian heart. 4. The movements of the ventricle may be registered by introducing into it through the auricnlo-ventricular orifice a so-called " perfusion " canula. Figs. 71 and 72, 1., with a double tube, one inside the other, and tying the ventricle on to the canula at the auricnlo-ventricular groove, or at any level below that which may be desired. The blood or other fluid is driven at an adequate pressure through the tube a. enters the ventricle, and returns by the tube b. If b be connected with a manometer as in method 3, the movements of the ventricle may be registered. 5. In the apparatus of Roy, Fig. 72, II., the exit-tube is free, but the ventricle (the same method may be adopted for the whole heart) is placed in an air-tight chamber filled with oil, or partly with normal saline solution and partly with oil. By means of the tube b the interior of the chamber a is continuous with that of a small cylinder c in which a piston <7, secured by a thin flexible animal membrane THE VASCULAR MECHANISM. 193 FIG. 71. works up and down. The piston again bears on a lever e by means of which its movements may be registered. When the ventricle con- tracts, and by contracting diminishes in volume, there is a lessening of pressure in the interior of the chamber ; this is transmitted to the cylinder, and the piston correspondingly rises, carrying with it the lever. As the ventricle subsequently becomes distended the pressure in the chamber is increased, and the piston and lever sink. In this way variations in the volume of the ventricle may be recorded, without any great interference with the flow of blood or fluid through it. The heart of the frog, as we have just said, will con- tinue to beat for hours after removal from the body, even after the cavities have been cleared of blood, and, indeed, when they are almost empty of all fluid. The beats thus carried out are in all important respects identical with the beats executed by the heart in its normal condition within the living body. Hence we may infer that the A perfusion Camiia. beat of the heart is an automatic action ; the muscular contractions which constitute the beat are due to causes which arise spon- taneously in the heart itself. In the frog's heart, as in that of the mammal, §115, there is a distinct sequence of events which is the same whether the heart be removed from, or Purely Diagrammatic Figures of— I. Perfusion canula tied into frog's ventricle : a, entrance : b, exit-tube ; A, wall of ventricle ; B, ligature. II. Roy's apparatus modified by Gaskill , a, chamber filled with saline solution and oil, con- taining the ventricle A tied on to perfusion canula /; 6, tube leading to cylinder c, in which moves piston d, working the lever e. be still in its normal condition within, the body. First comes the beat of the sinus venosus, preceded by a more or less peristaltic contraction of the large veins leading into it, next follows the sharp beat of the two auricles together, then comes the longer beat of the ventricle, and lastly, the cycle is completed by the beat of the bulbus arteriosus, which does not, like the mammalian aorta, simply recoil by elastic reaction after distention by the ventricular stroke, but carries out a distinct muscular contraction passing in a wave from the ventricle outward. When the heart in dying ceases to beat, the several movements cease, as a rule, in an order the inverse of the above. Omitting the bulbus arte- 194 THE VASCULAR MECHANISM. riosus, which sometimes exhibits great rhythmical power, we may say that first the ventricle fails, then the auricles "fail, and lastly the sinus venosus fails. The heart after it has ceased to beat spontaneously remains for some time irritable — that is, capable of executing a beat, or a short series of beats, when stimulated either mechanically, as by touching it with a blunt needle or electrically by an induction shock or in other ways. The artificial beat so called forth may be in its main features identical with the natural beat, all the divisions of the heart taking part in the beat, and the sequence of events being the same as in the natural beat. Thus when the sinus is pricked the beat of the sinus may be followed by a beat of the auricles and of the ventricle ; and even when the ventricle is stimulated, the directly following beat of the ventricle may be succeeded by a complete beat of the whole heart. Under certain circumstances, however, the division directly stimulated is the only one to beat; when the ventricle is pricked for instance it alone beats, or when the sinus is pricked it alone beats. The results of stimulation, moreover, may differ according to the condition of the heart and according to the particular spot to which the stimulus is applied. With an increasing loss of irritability, the response to stimulation ceases in the several divisions in the same order as that of the failure of the natural beat — the ventricle ceases to respond first, then the auricles, and lastly the sinus venosus, which frequently responds to stimulation long after the other divisions have ceased to make any sign. It would appear as if the sinus venosus, auricles, and ventricle formed a descending series in respect to their irritability and to the power they possess of carrying on spontaneous rhythmic beats, the sinus being the most potent. This is also seen in the following experiments : In order that the frog's heart may beat after removal from the body with the nearest approach in rapidity, regularity, and endurance to the normal condition, the removal must be carried out so that the excised heart still retains the sinus venosus intact. When the incision is carried through the auricles so as to leave the sinus venosus behind in the body, the sinus venosus beats forcibly and regularly, having suffered hardly any interruption from the operation. The excised heart, however, remains in the majority of cases for some time motionless. Stimulated by a prick or an induction-shock, it will perhaps give one, two, or several beats, and then come to rest. In the majority of cases, however, the animal having previously been in a vigorous condition, it will after a while recommence its spontaneous beating, the systole of the ventricle following that of the auricles ; but the rhythm of beat will not be the same as that of the sinus venosus left in the body, but will be slower, and the beats will not continue to go on for so long a time as will those of a heart still re- taining the sinus venosus. When the incision is carried through the auriculo-ventricular groove, so as to leave the auricles and sinus venosus within the body, and to isolate the ventricle only, the results are similar but more marked. The sinus and auricles beat regularly and vigorously, with their proper sequence, but the ventricle, after a few rapid contractions due to the incision acting as a stimu- lus, generally remains for a long time quiescent. When stimulated, how- ever, the ventricle will give one, two, or several beats, and after a while, in many cases at least, will eventually set up a spontaneous pulsation with an independent rhythm ; and this may last for some considerable time, but the beats are not so regular and will not go on for so long a time as will those of a ventricle to which the auricles are still attached. THE VASCULAR MECHANISM. 195 If a transverse incision be carried through the ventricle at about its upper third, leaving the base of the ventricle still attached to the auricles, the por- tion of the heart left in the body will go on pulsating regularly, with the ordinary sequence of sinus, auricles, ventricle, but the isolated lower two- thirds of the ventricle will not beat spontaneously at all, however long it be left. Moreover, in response to a single stimulus such as an induction-shock or a gentle prick it gives, not, as in the case of the entire ventricle when stimulated at the base or of the ventricle to which the auricles are attached, a series of beats, but a single beat. Lastly, to complete the story, we may add that when the heart is bisected longitudinally, each half continues to beat spontaneously, with an indepen- dent rhythm, so that the beats of the two halves are not necessarily syn- chronous, and this continuance of spontaneous pulsations after longitudinal bisection may be seen in the conjoined auricle and ventricle, or in the iso- lated auricles, or in the isolated but entire ventricle. Moreover, the auricles may be divided in many ways and yet many of the segments will continue beating; small pieces even may be seen under the microscope pulsating, feebly, it is true, but distinctly and rhythmically. In these experiments, then, the various parts of the frog's heart also form, as regards the power of spontaneous pulsation, a descending series : sinus venosus, auricles, entire ventricle, lower portions of ventricle, the last -exhibiting under ordinary circumstances no spontaneous pulsations at all. § 141. Now we have seen (§ 139) that these parts form to a certain •extent a similar descending series as regards the presence of ganglia ; at least so far that the ganglia are very numerous in the sinus venosus, that they occur in the auricles, and that while Bidder's ganglia are present at the junction of the ventricle with the auricles, ganglia are wholly absent from the rest of the ventricle. Hence, on the assumption (which we have already, § 96, seen reason to doubt) that the nerve cells of ganglia are sim- iilar in general functions to the nerve cells of the central nervous system, the view very naturally presents itself that the rhythmic spontaneous beat of the heart of the frog is due to the spontaneous generation in the ganglionic nerve cells of rhythmic motor impulses, which, passing down to the muscular fibres of the several parts, cause rhythmic contractions of these fibres, the sequence and coordination of the beating of the several divisions of the heart being the result of a coordination between the several ganglia in re- gard to the generation of impulses. Under this view the cardiac muscular fibre simply responds to the motor impulses reaching it along its motor nerve iibre in the same way as the skeletal muscular fibre responds to the motor impulses reaching it along its motor nerve fibre ; in both cases the muscular iibre is, as it were, a passive instrument in the hands of the motor nerve, or rather of the nervous centre (ganglion or spinal cord) from which the motor nerve proceeds. And the view, thus based on the fact of the frog's heart, has been extended to the hearts of (vertebrate) animals generally. There are reasons, however, which show that this view is not tenable. For instance, the lower two-thirds, or lower third, or even the mere tip of the frog's ventricle — that is to say, parts which are admitted not to con- tain nerve cells — may, by special means, be induced to carry on for a con- siderable time a rhythmic beat, which in its main features is identical with the spontaneous beat of the ventricle of the intact heart. If such a part of the frog's ventricle be tied on to the end of a perfusion canula (Fig. 71), the portion of the ventricular cavity belonging to the part may be ade- quately distended and at the same time be " fed " with a suitable fluid, such as blood, made to flow through the canula ; it will then be found that the portion of ventricle so treated will, after a preliminary period of qui- 196 THE VASCULAR MECHANISM. escence, commence to beat, apparently spontaneously, and will continue so beating for a long period of time. It may be said that in this case the dis- tention of the cavity and the supply of blood or other fluid acts as a stim- ulus ; but if so the stimulus is a continuous one, or at least not a rhythmic one, and yet the beat is most regularly rhythmic. Then, again, the reluctance of the ventricle to execute spontaneous rhythmic beats is to a certain extent peculiar to the frog. The ventricle of the tortoise, for instance, the greater part of the substance of which is as free from nerve cells as is that of the i'rog, will beat spontaneously when isolated from the auricles with great ease and for a long time. Further, a mere strip of this ventricular muscle tissue, if kept gently extended and continually moistened with blood or other suitable fluid, will continue to beat spontaneously with very great regularity for hours, or even days, especially if the series be started by the preliminary application of induc- tion-shocks rhythmically repeated. In connection with this question we may call attention to the fact that the cardiac muscular fibre is not wholly like the skeletal muscular fibre ; in many respects the contraction or beat of the former is in its very nature different from the contraction of the latter ; the former cannot be considered, like the latter, a mere instrument in the hands of the motor nerve fibre. The features of the beat or contraction of cardiac muscle maybe studied on the isolated and quiescent ventricle, or part of the ventricle, of the frog. When such a ventricle is stimulated by a single stimulus, such as a single induction-shock or a single touch with a blunt needle, a beat may or may not result. If it follows it resembles, in all its general features at least, a spontaneous beat. Between the application of the stimulus and the first appearance of any contraction is a very long latent period, varying accord- ing to circumstances, but in a vigorous fresh frog's ventricle being about 0.3 second. The beat itself lasts a variable but considerable time, rising slowly to a maximum and declining slowly again. Of course, when the beat is recorded by means of a light lever placed on the ventricle, what the tracing shows is really the increase in the front-to-back diameter of the ventricle during the beat — that is to say, one of the results of the contrac- tion of the cardiac fibres — and gives, in an indirect manner only, the extent of the contraction of the fibres themselves ; and the same is the case with the other methods of recording the movements of the whole ventricle. We may, however, study in a more direct way the contraction of a few fibres by taking a slip of the ventricle (and for this purpose the tortoise is prefer- able to the frog) and suspending it to a lever after the fashion of a muscle- nerve preparation. We then get a curve of contraction, characterized by a long latent period, a slow long-continued rise, and a slow long-con- tinued fall — a contraction, in fact, more like that of a plain muscular fibre than of a skeletal muscular fibre. In the tortoise the contraction is partic- ularly long, the contraction of even the skeletal muscles being long in that animal ; it is less long, but still long, in the frog ; shorter still, but yet long as compared with the skeletal muscles, in the mammal. The beat of the ventricle, then, is a single but relatively slow, prolonged contraction wave sweeping over the peculiar cardiac muscle-cell, passing through the cement substance from cell to cell along the fibre, from fibre to fibre along the bundle, and from bundle to bundle over the labyrinth of the ventricular walls. Like the case of the skeletal muscle, this single contraction is accom- panied by an electric change, a current of action. The intact ventricle at rest is, as we have already said (§ 66), isoelectric, but each part just as it is about to enter into a state of contraction becomes negative toward the rest. THE VASCULAR MECHANISM. 197 Hence, when the electrodes of a galvanometer are placed on two points, A, B, of the surface of the ventricle, a diphasic variation of the galvanom- eter needle is seen just as a beat, natural or excited, is about to occur. Sup- posing that the wave of contraction reaches A first, this will become nega- tive toward the rest of the ventricle, including B, but when the wave some time afterward reaches B, B will become negative toward the rest of the ventricle, including A. Compare § 67. The beat of the auricles, that of the sinus venosus, and that of thebulbus arteriosus are similar in their main features to that of the ventricle, so that the whole beat may be considered to be a wave of contraction sweeping through the heart from sinus to bulbus ; but the arrangement of fibres is such that this beat is cut up into sections in such a way that the sinus, the auricles, the ventricle, and thebulbus have each a beat, so to speak, to them- selves. In a normal state of things these several parts of the whole beat follow each other in the sequence we have described, but under abnormal conditions the sequence may be reversed, or one section may beat while the others are at rest, or the several sections may beat out of time with each other. So far the description of the contraction which is the foundation of the beat differs from that of a skeletal muscle in degree only ; but now comes an important difference. When we stimulate a skeletal muscle with a strong stimulus we get a large contraction ; when we apply a weak stimulus we get a small contraction ; within certain limits (see § 77) the contraction is pro- portional to the stimulus. This is not the case with the quiescent ventricle or heart. When we apply a strong induction-shock we get a beat of a cer- tain strength ; if we now apply a weak shock, we get either no beat at all or quite as strong a beat as with the stronger stimulus. That is to say, the magnitude of the beat depends on the condition of the ventricle (or heart), and not on the magnitude of the stimulus. If the stimulus can stir the ven- tricle up to beat at all, the beat is the best which the ventricle at the time can accomplish ; the stimulus either produces its maximum effect or none at all. It would seem as if the stimulus does not produce a contraction in the same way that it does when it is brought to bear on a skeletal muscle, but rather stirs up the heart in such a way as to enable it to execute a spon- taneous beat, which, without the extra stimulus, it could not bring about. And this is further illustrated by the fact that when a ventricle is beating rhythmically, either spontaneously or as the result of rhythmic stimulation, the kind of effect produced by a new stimulus thrown in will depend upon the exact phase of the cycle of the beat at which it is thrown in. If it is thrown in just as a relaxation is taking place, a beat follows prematurely, before the next beat would naturally follow, this premature beat being obvi- ously produced by the stimulus. But if it be thrown in just as a contraction is beginning, no premature beat follows ; the ventricle does not seem to feel the stimulus at all. There is a period during which the ventricle is insen- sible to stimuli, and that however strong ; this period is called the " refrac- tory " period. (There is, it may be mentioned, a similar refractory period in skeletal muscle, but it is of exceedingly short duration.) From this it results that, when a succession of stimuli repeated at a certain rate are sent into the ventricle, the number of beats does not correspond to the number of stimuli; some of the stimuli falling in refractory periods are ineffective and produce no beat. Hence, also, it is difficult if not impossible to produce a real tetanus of the ventricle, to fuse a number of beats into one. And there are other facts tending to show that the contraction of a cardiac muscular fibre, even when induced by artificial stimulation, is of a peculiar nature, and that the analogy with the contraction of a skeletal muscular fibre, 198 THE VASCULAR MECHANISM. induced by motor impulses reaching it along its nerve, does not hold good. These and other considerations, taken together with the facts already mentioned, that portions of cardiac muscular tissue in which ganglionic cells are certainly not present, can in various animals be induced, either easily or with difficulty, to execute rhythmic beats which have all the appearance of being spontaneous in nature, lead us to conclude that the beat of the heart is not the result of rhythmic impulses proceeding from the cells of the ganglia to passive muscular fibres, but is mainly the result of changes taking place in the muscular tissue itself. And here we may call attention to the peculiar histological features of cardiac muscular tissue ; though so far differentiated as to be striated, its cellular constitution and its " protoplasmic " features, including the obscurity of the striation, show that the differentiation is in- complete. Now, one attribute of undifferentiated primordial protoplasm is the power of spontaneous movement. § 142. We have, moreover, evidence that it is the muscular tissue, and not the arrangement of ganglia and nerves, which is primarily concerned in maintaining the remarkable sequence of sinus beat, auricle beat, and ven- tricle beat. This is perhaps better seen in the heart of the tortoise than in that of the frog. In this animal the nerves passing from the sinus to the ventricle may be divided, or the several ganglia may be respectively removed, and yet the normal sequence is maintained. On the other hand, we find that interference with the muscular substance of the auricle, when carried to a certain extent, prevents the beat of the auricle passing over to the ventricle, so that the sequence is broken after the auricle beat. If, for instance, the auricle be cut through until only a narrow bridge of muscle be left connecting the part of the auricle adjoining the sinus with the part adjoining the auriculo-ventric- ular ring, or if this part be compressed with a clamp, a state of things may be brought about in which every second beat only, or every third beat only, of the sinus and auricle is followed by a beat of the ventricle ; and then, if the bridge be still further narrowed or the clamp screwed tighter, the ven- tricle does not at all follow in its beat the sequence of sinus and auricle, though it may after a while set up an independent rhythm of its own. This experiment suggests, and other facts support, the view that the normal sequence is maintained as follows: The beat begins in the sinus (including the ends of the veins) ; the contraction wave, beginning at the ends of the veins, travels over the muscular tissue of the sinus, and reaching the auricle starts a contraction in that segment of the heart ; similarly the contraction wave of the auricular beat reaching the ventricle starts a ventricular beat, which in turn in like fashion starts the beat of the bulbus. And in hearts in a certain condition it is possible by stimulation to reverse this sequence, or to produce, by alternate stimulation, an alternation of a normal and a reversed sequence ; thus in the heart of the skate, in a certain condition, mechanical stimulation of the bulbus by indicating a beat of the bulbus will start a sequence of the bulbus. ventricle, auricle, and sinus, and similar stimulation of the sinus will produce a normal sequence of sinus, auricle, ventricle, and bulbus. It would, perhaps, be premature to insist that the nervous elements do- not intervene in any way in the maintenance of this sequence ; but the evi- dence shows that they are not the main factors, and we have at present no satisfactory indications of the way in which they do or may intervene. Two questions naturally suggest themselves here. The first is, Why does the cardiac cycle begin with the sinus beat? We have previously (§ 141) given the evidence that the sinus has a greater potentiality of beating than THE VASCULAR MECHANISM. 199 the other parts ; in and by itself it beats more readily and with a quicker rhythm than the other parts. When we ask the further question, Why has it this greater potentiality ? the only answer we can at present give is that it is inborn in the substance of the sinus. The problem is somewhat of the same kind as why the heart of one animal beats so much quicker than that of another. All we can say at present is that the rate is the outcome of the molecular constitution of tissue, without being able to define that molecular constitution. The second question is, Why does not the contraction wave starting at the sinus spread as a continuous wave over the whole heart? why is it broken up into sinus beat, auricle beat, ventricle beat ? We may here call to mind the fact mentioned in § 140 of the existence, more or less marked in all hearts and well seen in the heart of the tortoise, of a muscular ring or collar between the sinus and the auricle, and of a similar ring between the auricle and ventricle. The muscular tissue in these rings seems to be of a somewhat different nature from the muscular tissue forming the body of the sinus, or of the auricle, or of the ventricle. If we suppose that this tissue has a low conducting power, it may offer sufficient resistance to the progress of the contraction to permit the sinus, for example, to carry out or to be far on in the development of its beat before the auricle begins its beat (and thus bisect, so to speak, the beat which would otherwise be common to the two), and yet not offer so much resistance as to prevent the contraction wave passing ulti- mately on from the sinus to the auricle. We may in the tortoise by careful clamping or section of the auricle in its middle, by which an obstacle to the contraction wave is introduced, bisect the single auricular beat into two beats, one of the part between the sinus and the obstacle and another between the obstacle and the ventricular. We may thus consider the breaking up the primitive unbroken peristaltic wave of contraction from sinus to bulbus to be due to the introduction of tissue of lower conducting power at the junctions of the several parts. We do not say that this is the complete solution of the problem, but it at least offers an approximate solution ; and here as elsewhere we have no satisfactory evidence of nervous elements being main factors in the matter. In the above we have dealt chiefly with the heart of the cold-blooded animal, but as far as we know the same conclusions hold good for the mammalian heart also. The question now arises, If the ganglia are not the prime cause of the heart's rhythmic beat, or of the maintenance of the normal sequence, what purposes do they serve ? But before we even attempt to answer this question we must deal with the nervous mechanisms by which the beat of the heart, thus arising spontaneously within the tissues of the heart itself, is modified and regulated to meet the requirements of the rest of the body. The Government of the Heart-beat by the Nervous System. § 143. It will be convenient to begin with the heart of the frog, which, as we have seen, is connected with the central nervous system through and therefore governed by the two vagi nerves, each of which though apparently a single nerve contains, as we shall see, fibres of different origin and nature. If while the beats of the heart of a frog are being carefully registered an interrupted current of moderate strength be sent through one of the vagi, the heart is seen to stop beating. It remains for a time in diastole, perfectly 200 THE VASCULAR MECHANISM. motionless and flaccid ; all the muscular fibres of the several chambers are for the time being in a state of relaxation. The heart has been inhibited by the impulses descending down the vagus from the part of the nerve stimulated. If the duration of the stimulation be short and the strength of the current great, the standstill may continue after the current has been shut off; the beats when they reappear are generally at first feeble and infrequent, but soon reach or even go beyond their previous vigor and frequency. If the duration of the current be very long, the heart may recommence beating while the stimulation is still going on, but the beats are feeble and infrequent though gradually increasing in strength and frequency. The effect of the stimulation is at its maximum at or soon after the commencement of the application of the stimulus, gradually declining afterward ; but even at the end of a very prolonged stimulation the beats may still be less in force or in frequency, or in both, than they were before the nerve was stimulated, and on the removal of the current may show signs of recovery by an increase in force and frequency. The effect is not produced instantaneously ; if on the curve the point be exactly marked when the current is thrown in, as at on, Fig. 73, it will frequently be found that one beat at least occurs after the FIG 73. A/\M) Inhibition of Frog's Heart by Stimulation of Vagus Nerve: on marks the time at which the interrupted current was thrown into the vagus, off when it was shut off. The time-marker below marks seconds. The beats were registered by suspending the ventricle from a clamp attached to the aorta and attaching a light lever to the tip of the ventricle. current has passed into the nerve; the development of that beat has taken place before the impulses descending the vagus have had time to affect the heart. The stimulus need not necessarily be the interrupted current ; mechanical, chemical, or thermal stimulation of the vagus will also produce inhibition ; but in order to get a marked effect it is desirable to make use of not a single nervous impulse but a series of nervous impulses ; thus it is difficult to obtain any recognizable result by employing a single induction-shock of moderate intensity only. As we shall see later on, "natural" nervous impulses descending the vagus from the central nervous system, and started there, by afferent impulses or otherwise, as parts of a reflex act, may produce inhibition. The stimulus maybe applied to any part of the course of the vagus from high up in the neck right down to the sinus ; indeed, very marked results are obtained by applying the electrodes directly to the sinus, where, as we have seen, the two nerves plunge into the substance of the heart. The stimulus may also be applied to either vagus, though in the frog and some other animals, one vagus is sometimes more powerful than the other. Thus, it not infrequently happens that even strong stimulation of the vagus on one THE VASCULAR MECHANISM. 201 side produces no change of the rhythm, while even moderate stimulation of the nerve on the other side of the neck brings the heart to a stand- still at once. If during the inhibition the ventricle or other part of the heart be stimu- lated directly — for instance, mechanically by the prick of a needle — a beat may follow ; that is to say, the impulses descending the vagus, while inhibit- in n the spontaneous beats, have not wholly abolished the actual irritability of the cardiac tissues. With a current of even moderate intensity, such a current, for instance, as would produce a marked tetanus of a muscle-nerve preparation, the stand- still is complete, that is to say, a certain number of beats are entirely dropped ; but with a weak current the inhibition is partial only, the heart does not stand absolutely still but the beats are slowed, the intervals between them being prolonged, or weakened only without much slowing, or both slowed and weakened. Sometimes the slowing and sometimes the weaken- ing is the more conspicuous result. It sometimes happens that, when in the frog the vagus is stimulated in the neck, the effect is very different from that just described ; for the beats are increased in frequency, though they may be at first diminished in force. And, occasionally, the beats are increased both in force and in frequency ; the result is augmentation, not inhibition. But this is due to the fact that in the frog the vagus along the greater part of its course is a mixed nerve and contains fibres other than those of the vagus proper. § 144. If we examine the vagus nerve closely, tracing it up to the brain, we find that just as the nerve has pierced the cranium, just where it passes through the ganglion ( G. V., Fig. 74), certain fibres pass into it from the sympathetic nerve of the neck, Sy., of the further connections of which we shall speak presently. This being the case, we may expect that we should get different results according as we stimulated (1) the vagus in the cranium before it was joined by the sympathetic, (2) the sympathetic fibres before they join the vagus, and (3) the vagus trunk containing the real vagus and the sympathetic fibres added. What we have previously described «re the ordinary results of stimulating the mixed trunk, and these, as we have said, are not wholly constant, though usually and in the main most distinct inhibitory results follow. If we stimulate the sympathetic in the neck, as at Sy., Fig. 74, cutting the nerve below, so as to block all impulses from passing downward, and only allow impulses to pass up to the vagus and thence down the mixed vagus trunk to the heart, we get very remarkable results. The beat of the heart, instead of being inhibited, is augmented ; the beats are increased either in frequency or in force, or most generally both in frequency and in force. The effect is, perhaps, best seen when the heart before stimulation is beating slowly and feebly ; upon stimulation of the cervical sympathetic the beats at once improve in vigor and frequency ; indeed, a heart which, for one reason or another, has almost ceased to beat may, by proper stimulation of the sympathetic, be called back into vigorous activity. If, on the other hand, we stimulate the vagus before it has been joined by the sympathetic fibres (and to insure the result not being marred by any escape of the stimulating current on to the sympathetic fibres it is necessary to stimulate the vagus within the cranium), we get pure and constant inhib- itory results — the beats are for a time wholly abolished, or are slowed, or are weakened, or are both slowed and weakened. Obviously, then, the heart of the frog is supplied through the vagus by two sets of fibres coming from the central nervous system, the one by the 202 THE VASCULAR MECHANISM. vagus proper and the other by the cervical sympathetic nerve, and these two sets have opposite and antagonistic effects upon the heart. We find upon examination that we can make the following statements concerning them : The one set, those belonging to the vagus proper, are inhibitory ; they weaken the systole and prolong the diastole, the effect with a strong stimula- FIG. 74. IX s. v, a in Diagrammatic Representation of the Course of Cardiac Augmentor Fibres in the Frog: V.r., roots of vagus (and ixth) nerve. G. V., ganglion of same. Cr., line of cranial wall. Vg.. vagus trunk, ix., ninth, glosso-pharyngeal nerve. S. V. C., superior vena cava. Sy., sympathetic nerve in neck. G. c., junction of sympathetic ganglion with vagus ganglion sending i. c. intra-cranial fibres passing to Gasserian ganglion. The rest of the fibres pass along the vagus trunk. G1, splanchnic ganglion connected with the first spinal nerve. (?n, splanchnic ganglion of the sec- ond spinal nerve. An. V., annulus of Vieussens. A.sb., subclavian artery. G111, splanchnic gan- glion of the third spinal nerve. ///., third spinal nerve, r.c., ramus communicans. The course of the augmentor fibres is shown by the thick black line. They may be traced from the spinal cord by the anterior root of the third spinal nerve, through the ramus communicans to the corresponding splanchnic ganglion Gm and thence by the second ganglion Gn the annulus of Vieussens, and the first ganglion G1 to the cervical sympathetic Sy. and so by the vagus trunk to the superior vena cava 5. V. C. tion being complete, so that the heart is for a time brought to a standstill. Sometimes the slowing, sometimes the weakening, is the more prominent. When the nerve and the heart are in good condition it needs only a slight stimulus, a weak current, to produce a marked effect ; and it may be men- tioned that the more vigorous the heart, the more rapidly it is beating, the easier it is to bring about inhibition. Although, as we have said, the effect THE VASCULAR MECHANISM. 203 is at its maximum soon after the beginning of stimulation, a very prolonged inhibition may be produced by prolonged stimulation ; indeed by rhythmi- cal stimulation of the vagus the heart may be kept perfectly quiescent for a very long time and yet beat vigorously upon the cessation of the stimulus. In other words, the mechanism of inhibition — that is, the fibres of the vagus and the part or substance of the heart upon which these act to produce in- hibition, whatever that part or substance may be — is not readily exhausted. Further, the inhibition when it ceases is, frequently at all events, followed by a period of reaction, during which the heart for a while beats more vig- orously and rapidly than before. Indeed, the total effect of stimulating the vagus fibres is not to exhaust the heart, but rather to strengthen it ; and by repeated inhibitions carefully administered, a feebly beating heart may be nursed into vigorous activity. The other set, those joining the vagus from the sympathetic, are "aug- mentor " or " accelerating " fibres ; the latter name is the more common, but the former is more accurate, since the effect of stimulating these fibres is to increase not only the rapidity but the force of the beat ; not only is the diastole shortened, but the systole is strengthened, sometimes the one result and sometimes the other being the more prominent. In contrast with the case of the vagus fibres, a somewhat strong stimulation is required to produce an effect ; the time required for the maximum effect to be produced is also remarkably long. Moreover, at all events, in the case of a heart in which the circulation is not maintained, and which is therefore cut off from its normal nutritive supply, the augmentor fibres are far less easily exhausted than are the inhibitory fibres. Hence, when in such a heart both sets of fibres are stimulated together, as when the vagus trunk in the neck is stimu- lated, the first effects produced are those of inhibition ; but these on con- tinued stimulation may become mixed with those of augmentation, and finally the latter alone remain. Lastly, the contrast is completed by the fact that the augmentation resulting from the stimulation of the sympathetic is followed by a period of reaction in which the beats are feebler ; in other words, augmentation is followed by exhaustion ; and, indeed, by repeated stimulation of these sympathetic fibres a fairly vigorous bloodless heart may be reduced to a very feeble condition. By watching the effects of stimulating the sympathetic nerve at various points of its course we may trace these augmentor fibres from their junction with the vagus down the short sympathetic of the neck through the first splanchnic or sympathetic ganglion connected with the first spinal nerve, 6rl (Fig. 74), through one or both the loops of the annulus of Vieussens, An. V, through the second ganglion connected with the second spinal nerve, 6rn, to the third ganglion connected with the third spinal nerve, 6rni, and thence through the ramus communicans or visceral branch of that ganglion, r. c., to the third spinal nerve, ///., by the anterior root of which they reach the spinal cord. § 145. Both sets of fibres may then be traced to the central nervous system ; and we find accordingly that the heart may be inhibited or aug- mented by nervous impulses which are started in the nervous system either by afferent impulses as part of a reflex act or otherwise, and which pass to the heart by the inhibitory or by the augmenting tract. Thus, if the medulla oblongata, or a particular part of the medulla oblon- gata which is specially connected with the vagus nerve, be stimulated, the heart is inhibited ; if, for instance, a needle be thrust into this part, the heart stands still. This region in question may be stirred into action in a " reflex " manner by afferent impulses reaching it from various parts of the body. Thus, if the abdomen of a frog be laid bare, and the intestines be struck sharply 204 THE VASCULAK MECHANISM. with the handle of a scalpel, the heart will stand still in diastole with all the phenomena of vagus inhibition. If the nervi mesenteriei, or the connec- tions of these nerves with the spinal cord, be stimulated with the interrupted current, cardiac inhibition is similarly produced. If in these two experiments both vagi are divided, or the medulla oblongata is destroyed, inhibition is not produced, however much either the intestine or the mesenteric nerves be stimulated. This shows that the phenomena are caused by impulses ascend- ing along the mesenteric nerves to the medulla, and so affecting a portion of that organ as to give rise by reflex action to impulses which descend the vagi as inhibitory impulses. The portion of the medulla thus mediating between the afferent and efferent impulses may be spoken of as the cardio- inhibitory centre. Reflex inhibition through one vagus may be brought about by stimula- tion of the central end of the other. In general the alimentary tract seems in closer connection with the cardio-inhibitory centre than other parts of the body ; and if the peritoneal surface of the intestine be inflamed, very gentle stimulation of the inflamed surface will produce marked inhibition. But apparently stimuli, if sufficiently powerful, will through reflex action pro- duce inhibition, whatever be the part of the body to which they are applied. Thus, crushing a frog's foot will stop the heart, and adequate stimulation of most afferent nerves will produce some amount of inhibition. The details of the reflex chain and the portion of the centre concerned in the development of augmenting impulses have not been worked out so fully as in the case of inhibitory impulses, but there can be little doubt that the former, like the latter, are governed by the central nervous system. § 146. So far we have been dealing with the heart of the frog, but the main facts which we have stated regarding inhibition and augmentation of the heart beat apply also to other vertebrate animals, including mammals ; and, indeed, we meet similar phenomena in the hearts of invertebrate animals. If in a mammal the heart be exposed to view by opening the thorax, and the vagus nerve be stimulated in the neck, the heart may be seen to stand still in diastole, with all the parts flaccid and at rest. If the current em- ployed be too weak, the result as in the frog is not an actual arrest, but a slowing or weakening of the beats. If a light lever be placed on the heart a graphic record of the standstill or of the slowing, of the complete or incom- plete inhibition, may be obtained The result of stimulating the vagus is also well shown on the blood-pressure curve, the effect of complete cardiac inhibition on blood-pressure being most striking. If, while a tracing of arterial pressure is being taken, the beat of the heart be suddenly arrested, some such curve as that represented in Fig. 75 will be obtained. It will be observed that two beats follow the application of the current marked by the point a, which corresponds to the signal x on the line below. Then for a space of time no beats at all are seen, the next beat b taking place almost immediately after the shutting off the current at y. Immediately after the last beat following a there is a sudden fall of the blood-pressure. At the pulse due to the last systole the arterial system is at its maximum of disten- tion ; forthwith the elastic reaction of the arterial walls propels the blood for- ward into the veins, and, there being no fresh fluid injected from the heart, the fall of the mercury is unbroken, being rapid at first, but slower afterward, as the elastic force of the arterial walls is more and more used up. With the returning beats the pressure correspondingly rises in successive leaps until the normal mean pressure is regained. The size of these returning leaps of the mercury may seem disproportionately large, but it must be remembered that by far the greater part of the force of the first few strokes of the heart THE VASCULAR MECHANISM. 205 is expended in distending the arterial system, a small portion only of the blood which is ejected into the arteries passing on into the veins. As the arterial pressure rises, more and more blood passes at each beat through the capillaries, and the rise of the pressure at each beat becomes less and less, until at last the whole contents of the ventricle pass at each stroke into the veins, and the mean arterial pressure is established. To this it may be added that, as we have seen, the force of the individual beats may be some- what greater after than before inhibition. Besides, when the mercury Tracing showing the Influence of Cardiac Inhibition on Blood-pressure. From a Rabbit, x, the marks on the signal line when the current is thrown into, and y, shut off from the vagus. The time-marker below marks seconds, the heart, as is frequently the case in the rabbit, beating very rapidly. monometer is used, the inertia of the mercury tends to magnify the effects of the initial beats. In the mammal inhibition may be brought about by impulses passing along fibres which, starting in the medulla oblongata, run down over the vagus nerve and reach the heart by the cardiac nerves. It would appear, however, that the inhibitory fibres do not belong to the vagus proper, but leave the central nervous system by the spinal accessory nerve. Thus if the roots of the spinal accessory be divided, those of the vagus proper being left intact, the spinal accessory fibres in the vagus trunk degenerate, and when this takes place stimulation of the vagus trunk fails to produce the ordinary inhibitory effects. In the mammal, as in the frog, inhibition may be brought about not only by artificial stimulation of the vagus trunk, but by stimula- tion in a reflex manner or otherwise of the cardio-inhibitory centre. Thus the fainting which often follows upon a blow on the stomach is a repetition of the result just mentioned as obtained on the frog by striking the stomach or stimulating the nervi mesenterici. So also the fainting, complete or partial, which accompanies severe pain or mental emotion, is an illustration of cardiac inhibition by the vagus. In fact, cardiac inhibition so far from being a mere laboratory experiment enters repeatedly into the every-day working of our own organism as well as that of other living beings. Indeed there is some reason for thinking that the central nervous system by means of the cardiac inhibitory fibres keeps as it were a continual rein on the heart, for, in the dog at least, section of both vagi causes a quickening of the heart's beat. In the dog the augmentor fibres (Fig. 76) leave the spinal cord by the anterior roots of the second and third dorsal nerves, possibly also to some extent by the fourth and fifth, pass along the rami communicantes of those nerves to the ganglion stellatum, first thoracic ganglion, or respectively to one or other of the ganglia forming part of the thoracic, splanchnic, or sympathetic chain immediately below, and thence upward through the 206 THE VASCULAR MECHANISM. O.Tr.Vg.- Vg _ annulus of Vieussens, passing along one or other or both loops, to the inferior cervical ganglion. Their further course to the heart is along the nerves springing either from the inferior cer- FIG. 76. vical ganglion or from the loop of Vieussens directly. Their exact path from the ganglia in fact seems to vary in different individuals. The path of the augmentor fibres has not been worked out so fully in other mammals as in the dog, but it \ r.Sp.Ac.'ls most probable that in all cases they leave the spinal cord by the anterior roots of the second and third dorsal nerves (possibly also by the fourth and fifth) and, passing up the sympa- thetic chain to the ganglion stellatum and annulus of Vieussens, proceed to the heart by nerves branching off from some part or other of the annu- lus or from the lower and middla cervical ganglia. Diagrammatic Representation of the Cardial Inhibitory and Augmentor Fibres in the Dog. The upper portion of the figure represents the inhibitory, the lower the augmentor fibres. r.Vg., roots of the vagus; r.Sp.Ac., roots of the spinal accessory ; both drawn very diagram- matically. G.J., ganglion jugulare ; G.Tr.Vg., ganglion trunci vagi; Sp.Ac., spinal accessory trunk; ext.Sp.Ac., external spinal accessory; i.Sp.Ac , internal spinal accessory ; V(j., trunk of vagus nerve; n.c., branches going to heart; C.Sy., cervical sympathetic; O.C., lower cervi- cal ganglion: A.sb., subclavian artery; An. V., annulus of Vieussens; G.St.(Th.1), ganglion stellatum or first thoracic ganglion; G.Th.*, G.Th3, G.Th*, second, third, and fourth tho- racic ganglia ; D.IL, D.III., D.IV., D.V., second third, fourth, and fifth thoracic spinal nerves ; r.c., ramus communicans ; n.c., nerves (car- diac) passing to heart (superior vena cava) from cervical ganglion and from the annulus of Vieussens. The inhibitory fibres, shown by black line, run in the upper (medullary roots) of the spinal accessory, by the internal branch of the spinal accessory, past the ganglion trunci vagi, along the trunk of the vagus, and so by branches to the superior vena cava and the heart. The augmentor fibres, also shown by black line, pass from the spinal cord by the anterior roots of the second and third thoracic nerves (possibly also from fourth and fifth as indicated by broken black line), pass the second and first (stellate) thoracic ganglia by the annulus of Vieussens to the lower cervical ganglion, from whence, as also from the annulus itself, they pass along the cardiac nerves to the superior vena cava. The effects of stimulating these augmentor fibres in the mammal are, in general, the same as those witnessed in the frog. In the mammal, as in the frog, impulses along these augmentor fibres may be originated in the central THE VASCULAR MECHANISM. 207 nervous system, and that probably in various ways. That palpitation of the heart which is so conspicuous an effect of certain emotions is probably due to the sudden positive action of augmenting impulses, though it may possibly be due, in part at least, to sudden withdrawal of normal, continuous, tonic, and inhibitory impulses. In the mammal, then, as in the frog, the heart is governed by two sets of nerves, the one antagonistic to the other. In the dog the roots of the spinal accessory nerve, by which inhibitory fibres leave the central nervous system, consists entirely of inedullated fibres. Among these are fibres of fine calibre, 2/J.-&/J. in diameter, which may be traced down the trunk of the vagus, along the branches going to the heart, right down to the heart itself. There can be little doubt that these medullated fibres of fine calibre are the inhibitory fibres of the vagus, and indeed there is evidence which renders it probable that the inhibitory fibres of the heart are always medul- lated fibres of fine calibre, which continue as medullated fibres right dow?n to the heart, but eventually lose their medulla in the heart itself. The anterior roots of the second and third dorsal nerves, and the (white) rami communicantes belonging to them, which, as we have just seen, con- tain in the dog augmentor fibres, also consist exclusively of medullated fibres. But the nerves which convey the augmenting impulses from the lower cervical ganglion, or from the annulus of Vieussens to the heart, consist of non-medullated fibres. Hence, the augmentor fibres must have lost their medulla, and become continuous with non-medullated fibres some- where in their course along the sympathetic chain. It is probable that the change occurs in the ganglion stellatum and lower cervical ganglion, and it is further probable that the change is effected by the medullated fibre passing into one of the ganglion cells, and so losing its medulla, the im- pulses which it conveys passing out of the nerve cell by one or more of the other processes of the cell which are continued on as non-medullated fibres. Cf. § 94. In the dog then these two sets of nerve fibres, antagonistic to each other in function, differ in structure, the augmentor fibres early losing their medulla, and hence being over a large part of their course non-medullated fibres, whereas the inhibitory fibres are medullated fibres which, though they may pass by or through ganglia (as the ganglion jugulare and ganglion trunci vagi), do not lose their medulla in these ganglia, but remain as medullated fibres right down to the heart. And this difference in structure appears to hold good for all mammals, and is possibly true for vertebrates generally. § 147. The question, What is the exact nature of the change brought about by the inhibitory and augmenting impulses respectively on their arrival at the heart? or, in other words, by virtue of what events produced in the heart itself do the impulses of one kind bring about inhibition, of the other kind augmentation ? is a very difficult one, which we can- not attempt to discuss fully here. We may, if we please, speak of an " inhibitory mechanism " placed in the heart itself, but we have no exact knowledge of the nature of such a mechanism. Still less do we possess any satisfactory information as to an augmenting mechanism. It has been suggested that some of the ganglia in the heart serve as such an inhibi- tory (or augmenting) mechanism ; but there is evidence that the inhibitory impulses produce their effect by acting directly on the muscular fibres, or at all events do not produce their effect by acting exclusively on any gan- glia. One evidence of this kind is supplied by the action of the drug atropine. If, either in a frog Or a mammal, or other animal, after the vagus fibres 208 THE VASCULAR MECHANISM. have been proved by trial to produce upon stimulation the usual inhibitory effects, a small quantity of atropine be introduced into the circulation (when the experiment is conducted on a living animal, or be applied in a weak solution to the heart itself when the experiment is conducted, as in the case of a frog, on an excised heart, or after the circulation has ceased), it will after a short time be found not only that the stimulation, the application of a current, for instance, which previously when applied to the vagus pro- duced marked inhibition, now produces no inhibition, but even that the strongest stimulus, the strongest current applied to the vagus will wholly fail to affect the heart, provided that there be no escape of current on to the cardiac tissues themselves ; under the influence of even a small dose of atropine, the strongest stimulation of the vagus will not produce standstill or appreciable slowing or weakening of the beat. Now it might be supposed that the atropine produces this remarkable effect by acting on some ganglionic or other mechanism intervening between the vagus fibres and the cardiac muscular tissue ; but we have evidence that the atropine acts either on the muscular tissue itself or on the very endings of the nerves in the muscular fibres. We have said (§ 140) that a properly prepared strip of the ventricle of the tortoise will execute for a long time spontaneous rhythmic contractions, it will go on "beating" for a long time. A strip of the auricle will exhibit the same phenomena even still more readily. If now, while such a strip from the auricle is satisfac- torily beating, a gentle interrupted current be passed through it, it will stop beating ; the current inhibits the spontaneous beats ; a very gentle interrupted current must be used, otherwise the effect is obscured by the more direct stimulating action of the current. If now the strip be gently bathed with a weak solution of atropine no such inhibitory effect is pro- duced by the interrupted current ; the beats go on regardless of the action of the current. The interruption of this experiment is that in the first case the interrupted current stimulated the fine termination of the inhibitory fibres in the muscular strip, and that in the second case the atropine pro- duced some effect either on these fine fibres, or on their connections with the muscular substance or on the actual muscular substance itself, by virtue of which they ceased to act. But if this be so, if the same inhibitory effects are produced alike by stimulating the vagus trunk and stimulating the very endings of the nerves in the muscles of the heart, if not the actual muscular tissue itself, then there is no need to suppose the existence of any special inhibitory mechanism placed between the fibres in the vagus branches and the cardiac muscular tissue. The action of atropine on the heart is, so to speak, complemented by the action of muscarine, the active principle of many poisonous mushrooms. If a small quantity of muscarine be introduced into the circulation, or applied directly to the heart, the beats become slow and feeble, and if the dose be adequate the heart is brought to a complete standstill. The effect is in some respects like that of powerful stimulation of the vagus, but the standstill is much more complete, the effect is much more profound. Now if, in a frog, the heart be brought to a standstill by a dose of muscarine. the application of an adequate quantity of atropine will bring back the beats to quite their normal strength. The one drug is, as far as the heart is con- cerned (and, indeed, in many other respects), the antidote of the other. And, as in the case of atropine, so in the case of muscarine, there is evi- dence that the drug acts not on any ganglionic mechanisms, but on the car- diac tissue itself. The conclusion that inhibition is the result of changes in the cardiac tis- sue itself may serve to explain why in inhibition sometimes the slowing, THE VASCULAR MECHANISM. 209 sometimes the weakening is the more prominent. When the inhibitory impulses, by reason of particular fibres being affected or otherwise, are brought to bear chiefly on those parts of the heart, such as the sinus, which possessing higher rhythmic potentiality (see § 142) determine the sequence and set the rate of rhythm, it is the rate which is most markedly affected. When, on the other hand, the inhibitory impulses fall chiefly on the parts possessing lower rhythmic potentiality, the most marked effect is a diminu- tion in the force of the contractions. There is no adequate evidence then that the cardiac ganglia act as an inhibitory mechanism in the sense that they produce important changes in the nature of the impulses reaching them along vagus inhibitory fibres before those impulses pass on to the muscular tissue. We may add that there is similarly no adequate evidence that any of the ganglia act as an " aug- menting " mechanism. We have previously seen (§§ 141, 142) reasons for thinking the ganglia are not centres for the origination or regula- tion of the spontaneous beats. The question then arises, What are their functions? To this question we cannot at present give a wholly satisfac- tory answer. The inhibitory fibres remain, as we have seen, medullated fibres until they reach the heart, but it would appear that they lose their medulla somewhere in the heart before they actually reach the muscular tissue, and it is probable that the loss takes place in connection with some of the cardiac ganglia much in the same way that the augmenting fibres lose their medulla in the ganglia of the sympathetic chain ; but we do not know what is the physi- ological effect or the purpose of this loss of the medulla, and we cannot suppose that this is the sole or even chief use of the ganglia. Coincident with the loss of the medulla an increase of fibres frequently takes place, more than one non-medullated fibre leaving a nerve cell into which one medullated fibre enters ; and we may suppose that this mode of branching has purposes not fulfilled by the mere division of a fibre. Then again, bearing in mind the nutritive or "trophic" function of the spinal gan- glia alluded to in § 96, we may suppose that the cardiac ganglia are in some way concerned in the nutrition of the cardiac nerve fibres. But our knowledge is not yet sufficiently ripe to allow exact statements to be made. Other Influences Regulating or Modifying the Beat of the Heart. § 148. Important as is the regulation of the heart by the nervous system, it must be borne in mind that other influences are or may be at work. The beat of the heart may, for instance, be modified by influences bearing directly on the nutrition of the heart. The tissues of the heart, like all other tissues, need an adequate supply of blood of a proper quality ; if the blood vary in quality or quantity the beat of the heart is correspondingly affected. The excised frog's heart, as we have seen, continues to beat for some considerable time, though apparently empty of blood. After a while, however, the beats diminish and disappear ; and their disappearance is greatly hastened by washing out the heart with a normal saline solution, which when allowed to flow through the cavities of the heart readily permeates the tissues on account of the peculiar construction of the ventricular walls. If such a " washed out " quiescent heart be fed with a perfusion canula, in the manner described (§ 141), with diluted blood (of the rabbit, sheep, etc.), it may be restored to functional activity. A similar but less complete restoration may be witnessed if serum be used instead of blood ; and a heart fed regularly with fresh supplies of blood or even of serum may be kept beating for a 14 210 THE VASCULAR MECHANISM. very great length of time. In treating of the skeletal muscles we saw that in their case the exhaustion following upon withdrawal of the blood-stream might be attributed either to an inadequate supply of new nutritive mate- rial and oxygen, or to an accumulation in the muscular substance of the products of muscular metabolism, or to both causes combined. And the same considerations hold good for the nervous and muscular structures of the heart, though the subject has not yet been sufficiently well worked out to permit any very definite statements to be made. It seems prob- able, however, that an important factor in the matter is the accumulation in the muscular fibres and in the surrounding lymph of carbonic acid, and especially of the substances which give rise to the acid reaction. When the frog's heart is thus " fed " with various substances the interest- ing fact is brought to light that some substances, such, for instance, as very dilute lactic acid, lead to increased expansion, and others, such, for instance, as very dilute solutions of sodium hydrate, to diminished expansion, that is to continued contraction, of the quiescent ventricle. It would appear that the muscular fibres of the ventricle over and above their rhythmic contrac- tions are capable of varying in length, so that at one time they are longer, and the ventricle when pressure is applied to it internally dilates beyond the normal, while at another time they are shorter, and the ventricle, with the same internal pressure, is contracted beyond the normal. Further, in the frog at least, when the pause between two beats is lengthened the relaxa- tion of the ventricle goes on increasing, so that apparently the ventricle when beating normally is already somewhat contracted when a new beat begins. In other words, the ventricle possesses what we shall speak of in reference to arteries as tonicity or tonic contraction, and the amount of this tonic contraction, and in consequence the capacity of the ventricle, varies according to circumstances. We have, moreover, evidence that inhibitory impulses diminish and augmenting impulses increase this tonic contraction. When the frog's ventricle is thus artificially fed with serum or even with blood, the beats, whether spontaneous or provoked by stimulation, are apt to become intermittent and to arrange themselves into groups. This intermit- tence is possibly due to the serum or blood being unable to carry on nutrition in a completely normal manner, and to the consequent production of abnor- mal chemical substances ; and it is probable that cardiac intermittences seen during life have often a similar causation. Various chemical substances in the blood, natural or morbid, may thus affect the heart's beat by acting on its muscular fibres or its nervous elements, or both, and that probably in various ways, modifying in different directions the rhythm or the individual contractions, or both. The physical or mechanical circumstances of the heart also affect its beat ; of these perhaps the most important is the amount of the distention of its cavities. The contractions of cardiac muscle, like those of ordinary muscle (see § 79), are increased up to a certain limit by the resistance which they have to overcome ; a full ventricle will, other things being equal, contract more vigorously than one less full ; though, as in ordinary muscle, the limit at which resistance is beneficial maybe passed, and an overfull ventricle will fail to beat at all. Under normal conditions the ventricle probably empties itself completely at each systole. Hence an increase in the quantity of blood in the ventricle would augment the work done in two ways : the quantity thrown out would be greater, and the increased quantity would be ejected with greater force. Further, since the distention of the ventricle is (at the commencement of the systole at all events) dependent on the auricular systole, the work of the VASOMOTOR ACTIONS. 211 ventricle (and so of the heart as a whole) is in a measure governed by the auricle. An interesting combination of direct mechanical effects and indirect ner- vous effects is seen in the relation of the heart's beat to blood-pressure. When the blood -pressure is high, not only is the resistance to the ventricular systole increased, but other things being equal, more blood flows (in the mamma- lian heart) through the coronary artery. Both these events would increase the activity of the heart, and we might expect that the increase would be manifest in the rate of the rhythm as well as in the force of the individual beats. As a matter of fact, however, we do not find this. On the contrary the relation of heart-beat to pressure may be put almost in the form of a law, that the " rate of the beat is in inverse ratio to the arterial pressure," a rise of pressure being accompanied by a diminution, and fall of pressure with an increase, of the pulse-rate. This, however, only holds good if the vagi be intact. If these be previously divided, then in whatever way the blood-pressure be raised — whether by injecting blood or clamping the aorta or increasing the peripheral resistance, through that action of the vasomotor nerves which we shall have to describe directly — or in whatever way it be lowered, no such clear and decided inverse relation between blood-pressure and pulse-rate is observed. It is inferred, therefore, that increased blood- pressure causes a slowing of the pulse, when the vagi are intact, because the cardio-inhibitory centre in the medulla is stimulated by the high pressure, either directly by the pressure obtaining in the bloodvessels of the medulla, or in some indirect manner, and the heart in consequence to a certain extent inhibited. CHANGES IN THE CALIBRE OF THE MINUTE ARTERIES. VASOMOTOR ACTIONS. § 149. All arteries contain plain muscular fibres, for the most part cir- cularly disposed, and most abundant in, or sometimes almost entirely con- iined to, the middle coat. Moreover, as the arteries become smaller the muscular element, as a rule, becomes more and more prominent as compared with the other elements, until, in the minute arteries, the middle coat consists almost entirely of a series of plain muscular fibres wrapped around the in- ternal coat. Nerve fibres, of whose nature and course we shall presently speak, are distributed largely to the arteries and appear to end chiefly in fine plexuses around the muscular fibre, but their exact terminations have not as yet been clearly made out. By mechanical, electrical, or other stimulation, this muscular coat may, in the living artery, be made to con- tract. During this contraction, which has the slow character belonging to the contractions of all plain muscles, the calibre of the vessel is diminished. The veins also, as we have seen, possess muscular elements, but these vary in amount and distribution very much more in the veins than in the arteries. Most veins, however, are contractile, and may vary in calibre according to the condition of their muscular elements. Veins are also supplied with nerves. It will be of advantage, however, to consider separately the little we know concerning the changes in the veins, and to confine ourselves at present to the changes in the arteries. If the web of a frog's foot be watched under the microscope, any indi- vidual small artery will be found to vary considerably in calibre from time to time, being sometimes narrowed and sometimes dilated ; and these changes may take place without any obvious changes either in the heart-beat or in the general circulation ; they are clearly changes of the artery itself. Dur- ing the narrowing, which is obviously due to a contraction of the muscular 212 THE VASCULAR MECHANISM. coat of the artery, the capillaries fed by the artery and the veins into which these lead become less filled with blood and paler. During the widening, which corresponds to the relaxation of the muscular coat, the same parts are fuller of blood and redder. It is obvious that, the pressure at the entrance into any given artery remaining the same, more blood will enter the artery when relaxation takes place, and consequently the resistance offered by the artery is diminished, and less when contraction occurs and the resistance is consequently increased ; the blood flows in the direction of least resistance. The extent and intensity of the narrowing or widening, the constriction or dilatation which may thus be observed in the frog's web, vary very largely. Variations of slight extent, either more or less regular and rhythmic or irregular, occur even when the animal is apparently subjected to no disturb- ing causes, and may be spoken of as spontaneous ; larger changes may follow events occurring in various parts of the body ; while as the result of experi- mental interference the arteries may become either constricted, in some cases almost to obliteration, or dilated until they acquire double or more than double their normal diameter. This constriction or dilation may be brought about not only by treatment applied directly to the web, but also by changes affecting the nerve of the leg or other parts of the body. Thus, section of the sciatic nerve is generally followed by a widening which may be slight or which may be very marked, and which is sometimes preceded by a passing constriction ; while stimulation of the peripheral stump of the divided nerve by an interrupted current of moderate intensity generally gives rise to constriction, often so great as almost to obliterate some of the minute arteries. Obviously, then, the contractile muscular elements of the minute arteries of the web of the frog's foot are capable by contraction or relaxation of causing decrease or increase of the calibre of the arteries ; and this condition of constriction or dilation may be brought about through the agency of the nerves. Indeed, not only in the frog, but also, and still more so, in warm- blooded animals, have we evidence that in the case of nearly all, if not all, the arteries of the body, the condition of the muscular coat, and so the calibre of the artery, is governed by means of nerves ; these nerves have received the general name of vasomotor nerves. §150. If the ear of a rabbit, preferably a light-colored one, be held up before the light, a fairly conspicuous artery will be seen running up the middle line of the ear accompanied by its broader and more obvious veins. If this artery be carefully watched it will be found, in most instances, to be undergoing rhythmic changes of calibre, constriction alternating with dila- tation. At one moment the artery appears as a delicate, hardly visible, pale streak, the whole ear being at the same time pallid. After a while the artery slowly widens out, becomes broad and red, the whole ear blushing, and many small vessels previously invisible coming into view. Again the artery narrows and the blush fades away ; and this may be repeated at somewhat irregular intervals of a minute, more or less. The extent and regularity of the rhythm are usually markedly increased if the rabbit be held up by the ears for a short time previous to the observation. Similarly rhythmic variations in the calibre of the arteries have been observed in several places, e.g., in the vessels of the mesentery and elsewhere; probably they are widely spread. Sometimes no such variations are seen ; the artery remains constant in a condition intermediate between the more extreme widening and extreme narrowing just described. In fact, we may speak of an artery as being at any given time in one of three phases. It may be very constricted, in which case its muscular fibres are very much contracted ; or it may be dilated, in VASOMOTOR ACTIONS. 213 which case its muscular fibres are relaxed ; or it may be moderately con- stricted, the muscular fibres being contracted to a certain extent, and remaining in such a condition that they may, on the one hand, pass into stronger contraction, leading to marked constriction, or, on the other hand, into distinct relaxation, leading to dilatation. We have reason to think, as we shall see, that many arteries of the body are kept habitually, or at least for long periods together, in this intermediate condition, which is frequently spoken of as tonic contraction, or tonus, or arterial tone. § 151. If, now, in a vigorous rabbit, in which the heart is beating with adequate strength and the whole circulation is in a satisfactory condition, the cervical sympathetic nerve be divided on one side of the neck, remark- able changes may be observed in the bloodvessels of the ear of the same side. The arteries and veins widen, they together with the small veins and the capillaries become full of blood, many vessels previously invisible come into view, the whole ear blushes, and if the rhythmic changes described above were previously going on, these now cease ; and, in consequence of the extra supply of warm blood, the whole ear becomes distinctly warmer. Now these changes take place, or may take place, without any alteration in the heart- beat or in the general circulation. Obviously the arteries of the ear have, in consequence of the section of the nerve, lost the tonic contraction which previously existed ; their muscular coats, previously somewhat contracted, have become quite relaxed, and whatever rhythmic contractions were pre- viously going on have ceased. The more marked the previous tonic contraction, and the more vigorous the heart-beats, so that there is an adequate supply of blood to fill the widened channels, the more striking the results. Sometimes, as when the heart is feeble, or the pre-existing tonic contraction is slight, the section of the nerve produces no very obvious change. If, now, the upper segment of the divided cervical sympathetic nerve — that is, the portion of the nerve passing upward to the head and ear— be laid upon the electrodes of an induction machine and a gentle interrupted current be sent through the nerve, new changes take place in the blood- vessels of the ear. A short time after the application of the current, for in this effect there is a latent period of very appreciable duration, the ear grows paler and cooler, many small vessels previously conspicuous become again invisible, the main artery shrinks to the thinnest thread, and the main veins become correspondingly small. When Jhe current is shut off from the nerve these effects still last some time, but eventually pass off; the ear reddens, blushes once more, and indeed may become even redder and hotter, with the vessels more filled with blood than before. Obviously the current has generated in the cervical sympathetic nerve impulses which, passing upward to the ear and finding their way to the muscular coats of the arteries of the ear, have thrown the muscles of those coats into forcible contractions, and have thus brought about a forcible narrowing of the calibre of the arteries — a forcible constriction. Through the narrowed constricted arteries less blood finds its way, and hence the paleness and coldness of the ear. If the impulses thus generated be very strong, the constriction of the arteries may be so great that the smallest quantity only of blood can make its way through them, and the ear may become almost bloodless. If the impulses be weak, the constriction induced may be slight only; and, indeed, by careful manipu- lation the nerve may be induced to send up to the ear impulses only just sufficiently strong to restore the moderate tonic constriction which existed before the nerve was divided. We infer from these experiments that among the various nerve fibres making up the cervical sympathetic, there are certain fibres which, passing 214 THE VASCULAR MECHANISM. FIG. 77. V.M.C.. Sp.C. upward to the head, become connected with the arteries of the ear, and that these fibres are of such a kind that impulses generated in them and passing upward to the ear lead to marked contraction of the muscular fibres of the arteries, and thus produce constriction. These fibres are vasomotor fibres for the bloodvessels of the ear. From the loss of tone, so frequently follow- ing section of the cervical sympathetic, we may further infer that, normally during life, impulses of a gentle kind are continually passing along these fibres upward through the cervical sympathetic, which impulses, reaching the arteries of the ear, maintain the normal tone of those arteries. But, as we said, the existence of this tone is not so constant, and these tonic impulses are not so conspicuous as the artificial constrictor impulses generated by stimulation of the nerve. § 151. The above results are obtained what- ever be the region of the cervical sympathetic which we divide or stimulate from the upper cervi- cal ganglion to the lower. We may, therefore, de- scribe these vasomotor impulses as passing upward from the lower cervical ganglion along the cervical sympathetic to the upper cervical ganglion, from which they issue by branches which ultimately find their way to the ear. But these impulses do not start from the lower cervical ganglion ; on the contrary, by repeating the experiments of di- vision and stimulation in a series of animals, we may trace the path of these impulses from the lower cervical ganglion (Fig. 77) through the annulus of Vieussens to the ganglion stellatum or first thoracic ganglion, and thence either along the ramus communicans (visceral branch) to the an- terior root of the second dorsal nerve, and thus to the spinal cord, or lower down along the thoracic sympathetic chain, and thence by other rami com- municantes to some other of the upper dorsal nerves, and thus to the spinal cord. The path taken by these vasomotor impulses for the ear is in fact very similar to that of the augmentor fibres for the heart (cf. Fig. 76), from the spinal cord up to the annulus of Vieussens and to the lower cervical ganglion ; but there they part company. We can thus trace these impulses along the cer- vical sympathetic to the anterior roots of certain dorsal nerves, and through these to a particular part of the spinal cord, where we will for the pres- ent leave them. We may accordingly speak of vasomotor fibres for the ear as passing from the dorsal spinal cord to the ear along the track just marked out ; stimulation of these fibres at their origin in the spinal cord or at any part of their course (along the anterior roots of the second, third, or other upper dorsal nerves, visceral branches of those nerves, ganglion stellatum or upper part of thoracic sympathetic chain, annulus of Vieussens, etc.) leads to constriction in the bloodvessels of the ear of that side ; and section of these fibres at any part of the same course tends to abolish any previously Diagram illustrating the Paths of Vasoconstrictor Fi- bres along the Cervical Sym- pathetic and (part of) the Ab- dominal Splanchnic : Aur., artery of ear ; G. C.s., superior cervical ganglion ; Abd. Spl., upper roots of and part of ab- dominal splanchnic nerve ; V. M. 0., vasomotor centre in me- dulla. The other references are the same as in Fig. 76, 1 146. The paths of the constric- tor fibres are shown by the arrows. The dotted line in the spinal cord, Sp. C., is to in- dicate the passage of constric- tor impulses down the cord from the vasomotor centre in the medulla. VASOMOTOR ACTIONS. 215 existing tonic constriction of the bloodvessels of the ear, though this effect is not so constant or striking as that of stimulation. § 153. We must now turn to another case. In dealing with digestion we shall have to study the submaxillary salivary gland. We may for the present simply say that this is a glandular mass well supplied with blood- vessels, and possessing a double nervous supply. On the one hand it receives fibres from the cervical sympathetic, Fig. 78, v. sym. (in the dog, in which the effects which we are about to describe are best seen, the vagus and cervical FIG. 78. v.sym. fsn.sym.f. n.sym.sm. Diagrammatic Representation of the Submaxillary Gland of the Dog, with its Nerves and Bloodvessels. The dissection has been on an animal lying on its back, but since all the parts shown in the figure cannot be seen from any one point of view, the figure does not give the exact anatomical relations of the several structures. sm. gld. Thesnbmaxillary gland, into the duct (sin. d.) of which a canula has been tied. The sublingual gland and duct are not shown. n.l., n.l'. The lingual branch of the fifth nerve, the part n.l. is going to the tongue, ch.t., ch.t'., ch.t". The chorda tympani. The part ch.t". is pro- ceeding from the facial nerve ; at ch. V. it becomes conjoined with the lingual n.l'., and afterward diverging passes as ch. t. to the gland along the duct; the continuation of the nerve in company with the lingual n.l. is not shown, sm. gl. The submaxillary ganglion with its several roots. a. car. The carotid artery, two small branches of which, a. sm. a. and r. sm. p., pass to the anterior and posterior parts of the gland, v. sm. The anterior and posterior veins from the gland, falling into v.j., the jugular vein. v. sym. The conjoined vagus and sympathetic trunks, g. cer. s. The upper cervical ganglion, two branches of which, forming a plexus (a./.) over the facial artery, are distributed (n. sym. sm.) along the two glandular arteries to the anterior and posterior portions of the gland. The arrows indicate the direction taken by the nervous impulses during reflex stimulation of the gland. They ascend to the brain by the lingual and descend by the chorda tympani. sympathetic are enclosed in a common sheath so as to form what appears to be a single trunk), which reach the gland in company with the arteries sup- plying the gland (n. sym. sm.}. On the other hand, it receives fibres from a small nerve called the chorda tympani (ch. t.), which, springing from the seventh cranial (facial) nerve, crosses the tympanum of the ear (hence the name) and, joining the lingual branch of the fifth nerve, runs for some dis- tance in company with that nerve, and then ends partly on the tongue, and partly in a small nerve which, leaving the lingual nerve before reach- ing the tongue, runs along the duct of the submaxillary gland, and is lost in the substance of the gland ; a small branch is also given off to the sub- lingual gland. 216 THE VASCULAR MECHANISM. Now when the chorda tympani is simply divided no very remarkable changes take place in the bloodvessels of the gland, but if the peripheral segment of the divided nerve, that still in connection with the gland, be stimulated, very marked results follow. The small arteries of the gland become very much dilated and the whole gland becomes flushed. (As we shall see later on, the gland at the same time secretes saliva copiously, but this does not concern us just now.) Changes in the calibre of the blood- vessels are of course not so readily seen in a compact gland as in a thin, extended ear; but if a fine tube be placed in one of the small veins by which the blood returns from the gland, the effects on the bloodvessels of stimulating the chorda tympani become very obvious. Before stimulation the blood trickles out in a thin slow stream of a dark venous color ; during stimulation the blood rushes out in a rapid full stream, often with a distinct pulsation and frequently of a color which is still scarlet and arte- rial in spite of the blood having traversed the capillaries of the gland ; the blood rushes so rapidly through the widened bloodvessels that it has not time to undergo completely that change from arterial to venous which nor- mally occurs while the blood is traversing the capillaries of the gland. This state of things may continue for some time after the stimulation has ceased, but before long the flow from the veins slackens, the issuing blood becomes darker and venous, and eventually the circulation becomes normal. Obviously the chorda tympani contains fibres which we may speak of as " vasomotor," since stimulation of them produces a change in, and brings about a movement in the bloodvessels ; but the change produced is of a character the very opposite to that produced in the bloodvessels of the ear by stimulation of the cervical sympathetic. There stimulation of the nerve caused contraction of the muscular fibres, constriction of the small arteries ; here stimulation of the nerve causes a widening of the arteries, which widening is undoubtedly due to relaxation of the muscular fibres. Hence we must distinguish between two kinds of vasomotor fibres, fibres the stim- ulation of which produces constriction, vaso-constrictor fibres, and fibres the stimulation of which causes the arteries to dilate, vaso-dilator fibres, the one kind being the antagonist of the other. The reader can hardly fail to be struck with the analogy between these two kinds of vasomotor fibres on the one hand, and the inhibitory and aug- mentor fibres of the heart on the other hand. The augmentor cardiac fibres increase the rhythm and the force of the heart-beats ; the vaso-constrictor fibres increase the contractions of the muscular fibres of the arteries ; the one works upon a rhythmically active tissue, the other upon a tissue whose work is more or less continuous, but the effect is in each case similar — an increase of the work. The inhibitory cardiac fibres slacken or stop the rhythm of the heart and diminish the beats ; the vaso-dilator fibres di- minish the previously existing contraction of the muscular fibres of the arteries so that these expand under the pressure of the blood. § 154. But we must return to the vasomotor nerves. The cervical sympa- thetic contains vaso-constrictor fibres for the ear, and we may now add for other regions, also of the head and face. Thus the branches of the cervical sympathetic, going to the submaxillary gland of which we just spoke (Fig. 78, n. sym. sm.\ contain vaso-constrictor fibres for the vessels of the gland ; stimulation of these fibres produces on the vessels of the gland an effect exactly the opposite of that produced by stimulation of the chorda tympani. But to this particular point we shall have to return when we deal with the gland in connection with digestion. A more important fact for our present purpose is that the cervical sympathetic appears to contain only vaso-con- VASOMOTOR ACTIONS. 217 stricter fibres ; if we put aside as exceptional and doubtful the result of certain observers who obtained vaso-dilator effects in the mouth and face, we may say that in no region to which the fibres of the cervical sympathetic are distributed can any vaso-dilator action be observed as the result of stimulation of the nerve at any part of its course. In the chorda tympani, on the other hand, the vasomotbr fibres are exclusively vaso-dilator fibres, and this is true both of the part of the nerve ending in the submaxillary and sublingual glands and the rest of the ending of the nerve in the tongue. Stimulation of the chorda tympani (as far as the vasomotor functions of the nerve are concerned, for it has, as we shall see, other functions) at any part of its course, from its leaving the facial nerve to its endings in the tongue or gland, produces only vaso-dilator effects, never vaso- constrictor effects. With many other nerves of the body the case is different. In the frog, division of the sciatic nerve leads to a widening of the arteries of the web of the foot of the same side, and stimulation of the peripheral end of the nerve causes a constriction of the vessels, which, if the stimulation be strong, may be so great that the web appears for the time being to be devoid of blood. Also, in a mammal, division of the sciatic nerve causes a similar widening of the small arteries of the skin of the leg. Where the condition of the circulation can be readily examined, as, for instance, in the hairless balls of the toes, especially when these are not pigmented, the vessels are seen to be dilated and injected, and a thermometer placed between the toes shows a rise of temperature amounting, it may be, to several degrees. If, moreover, the peripheral end of the divided nerve be stimulated, the vessels of the skin become constricted, the skin grows pale, and the temper- ature of the foot falls. And very similar results are obtained in the fore- limb by division and subsequent stimulation of the nerves of the brachial plexus. The quantity of blood present in the bloodvessels of the mammal, though it may sometimes be observed directly, has frequently to be determined indirectly. The temperature of passive structures subject to cooling influences, such as the skin, is largely dependent on the supply of blood ; the more abundant the supply the warmer the part. Hence, in these parts variations in the quantity of blood may be inferred from variations of temperature ; but in dealing with more active structures there are obviously sources of error in the possibility of the treatment adopted, such as the stimulation of a nerve giving rise to an increase of temper- ature due to increased metabolism, independent of variations in blood-supply. The quantity of blood may also be determined by the pkthy smog raph. In this instrument a part of the body, such as the arm, is introduced into a closed chamber filled with fluid, ex. gr., a large glass tube, the opening by which the arm is intro- duced being secured with a stout caoutchouc membrane. An increase or decrease of blood sent into the arm will lead to an increase or decrease of the volume of the arm, and this will make itself felt by an increase or diminution of pressure in the fluid of the closed chamber, which may be registered and measured in the usual way. We shall have to speak again of a modification of this instrument when we are dealing with the kidney. So far the results are quite like those obtained by division and stimulation of the cervical sympathetic, and we might infer that the sciatic nerve and brachial plexus contain vaso-constrictor fibres for the vessels of the skin of the hind-limb and fore-limb, vaso-dilator fibres being absent. But some- times a different result is obtained : on stimulating the divided sciatic nerve the vessels of the foot are not constricted, but dilated — perhaps widely dilated. And this vaso-dilator action is almost sure to be manifested when the nerve is divided, and the peripheral stump stimulated some days after division, by which time commencing degeneration has begun to interfere with the irrita- 218 THE VASCULAR MECHANISM. bility of the nerve. For example, if the sciatic be divided, and some days afterward, by which time the flushing and increased temperature of the foot following upon the section has wholly or largely passed away, the peripheral stump be stimulated with an interrupted current, a renewed flushing and rise of temperature is the result. We are led to conclude that the sciatic nerve (and the same holds good for the brachial plexus) contains both vaso- constrictor and vaso-dilator fibres, and to interpret the varying results as due to variations in the relative irritability of the two sets of fibres. The con- strictor fibres appear to predominate in these nerves, and hence constriction is the more common result of stimulation ; the constrictor fibres also appear to be more readily affected by a tetanizing current than the dilator fibres. When the nerve after division commences to degenerate, the constrictor fibres lose their irritability earlier than the dilator fibres, so that at a certain stage a stimulus, such as the interrupted current, while it fails to affect the constrictor fibres, readily throws into action the dilator fibres. The latter, indeed, in contrast to ordinary motor nerves (§ 81), retain their irritability after section of the nerve for very many days. The result is, perhaps, even still more striking if a mechanical stimulus, such as that of " crimping " the nerve by repeated snips with the scissors, be employed. Exposure to a low temperature again seems to depress the constrictors more than the dilators ; hence, when the leg is placed in ice-cold water stimulation of the sciatic, even when the nerve has been but recently divided, throws the dilator only into action and produces flushing of the skin with blood. Rhythmical stimula- tion, moreover, of even a freshly divided nerve produces dilatation. And there are other facts which support the same view that the sciatic nerve (and brachial plexus) contains both vaso-constrictor and vaso-dilator fibres which are differently affected by different circumstances. We may point out that the case of the vagus of the frog is a very analogous one ; in it are both cardiac inhibitory (true vagus) and cardiac augmentor (sympathetic) fibres, but the former, like the vaso-constrictor fibres in the sciatic, are predominant, and special means are required to show the presence of the latter. In the splanchnic nerve (abdominal splanchnic), which supplies fibres to the bloodvessels of so large a part of the abdominal viscera, there is abun- dant evidence of the presence of vaso-constrictor fibres, but the presence of vaso-dilator fibres has not clearly been shown. Division of this nerve leads to a widening of the bloodvessels of the abdominal viscera, stimulation of the nerve to a constriction ; and, as we shall see, since the amount of blood- vessels thus governed by this nerve is very large indeed, interference either in the one direction or the other with its vasomotor functions produces very marked results, not only on the circulation in the abdomen, but on the whole vascular system. In nerves going to muscles vaso-dilator fibres predominate ; indeed, in these the presence of any vaso-constrictor fibres at all has not at present been satisfactorily established. When a muscle contracts there is always an increased flow of blood through the muscle; this may be in part a mere mechanical result of the change of form, the shortening and thickening of the fibres opening out the minute bloodvessels, but is not wholly, and prob- ably not even largely, thus produced. A notable feature of vasomotor fibres is that, in very many cases at all events, their action is not affected by small or moderate doses of urari such as render the motor nerves of striated muscle powerless. Thus, in a frog placed under the influence of a moderate amount of urari, stimulation of a nerve going to a muscle will produce vasomotor effects unaccompanied and unobscured by any contraction of the striated fibres. By placing a thin muscle of a frog, such as the mylo-hyoid, VASOMOTOR ACTIONS. 219 under the microscope, and watching the calibre of the small arteries and the circulation of the blood through them while the nerve is being stimulated, the widening of the bloodvessels as the result of the stimulation may be ac- tually observed. This experiment appears not to succeed in a mammal ; and it has been suggested that when a muscle contracts some of the chemical products of the metabolism of the muscle may, by direct action on the mi- nute bloodvessels apart from any nervous agency, lead to a widening of those bloodvessels ; this, however, is doubtful. With regard to the vaso-constrictor fibres, the only evidence that they exist in muscles is that when the nerve of a muscle is divided the bloodvessels of the muscle widen, somewhat like bloodvessels of the ear after division of the cervical sympathetic. This sug- gests the presence of vaso-constrictor fibres carrying the kind of influence which we called tonic, leading to an habitual moderate constriction ; it can- not, however, be regarded by itself as conclusive evidence ; but we must not discuss the matter here. Speaking generally, then, most if not all the arteries of the body are sup- plied with vasomotor fibres running in this or that nerve, the fibres being either vaso-constrictor or vaso-dilator, and some nerves containing one kind of fibres only, some both in varying proportion. Almost every nerve in the body, therefore, may be looked upon as influencing a certain set of blood- vessels, as governing a vascular area, the area being large or small, and the government being exclusively constrictor or exclusively dilator, or mixed. The Course of Vaso-constrictor and Vaso-dilator Fibres. § 155. Both the vaso-constrictor and the vaso-dilator fibres have their origin in the central nervous system, the spinal cord, or the brain, but the course of the two sets appears to be very different. In the mammal, as far as we know at present, all the vaso-constrictor fibres for the whole body take their origin in the middle region of the spinal cord, or rather leave the spinal cord by the nerves belonging to this middle region. Thus in the dog the vaso-constrictor fibres, not only for the trunk but for the limbs, head, face, and tail, leave the spinal cord by the anterior roots of the spinal nerves reaching from about the second dorsal to the fourth lumbar nerve, both inclusive. Running in the case of each nerve root to the mixed nerve trunk they pass along the visceral branch, white ramus communicans, to the chain of splanchnic ganglia lying in the thorax and abdomen — the so-called thoracic and abdominal sympathetic chain (Fig. 77). From these ganglia they reach their destination in various ways. Thus those going to the head and neck pass chiefly through the second and third dorsal and partly through the fourth, fifth and first dorsal nerves, thence upward through the annulus of Vieussens to the lower cervical ganglion, and thence, as we have seen, up the cervical sympathetic. Those for the abdominal viscera pass off in a similar way to the abdominal splanchnic nerves (Fig. 77, abd. spl.). Those destined for the fore limbs pass along in the fourth to the ninth dorsal nerves, both inclusive, chiefly in the seventh, and sometimes a few in the tenth, and so reach the brachial plexus ; while those for the leg pass through the eleventh dorsal to the third lumbar, both inclusive, a few passing through the tenth dorsal and the fourth lumbar, and finally to the sciatic plexus. Those for the tail pass through in the first to third lumbar inclusive. The constrictor fibres of the skin of the trunk probably reach the spinal nerves in which they ultimately run in a similar manner. All the vaso-constrictor fibres, whatever their destination, leave the spinal cord by the anterior roots of spinal nerves, and then, passing through the appropriate visceral branches, join the thoracic or abdominal 220 THE VASCULAK MECHANISM. chain of splanchnic ganglia. In these ganglia the fibres undergo a remark- able change. Along the anterior root and along the visceral branch they are medullated fibres, but long before they reach the bloodvessels for which they are destined they become non-medullated fibres ; they appear to lose their medulla in the system of splanchnic ganglia. We may add that in the anterior roots and along the visceral branches, white rarni communicantes, these fibres are invariably of small diameter, not more than 1.8/x to 3.6 //. § 156. The course of the vaso-dilator fibres appears to be a somewhat different one, some apparently accompanying the vaso-constrictor fibres, and others running an independent course, though the details have as yet been fully worked out in the case of only a few of the fibres. It is chiefly in the nerves belonging to the cranial and sacral regions of the central nervous system, whence, as we have seen, no vaso-constrictor fibres are known to issue, that the course of the vaso-dilator fibres has been successfully traced. Thus the vaso-dilator fibres for the submaxillary gland running in the chorda tympani may be traced, as we have seen, back to the facial or seventh nerve ; and the continuation of the chorda tympani along the lingual nerve to the tongue contains vaso-dilator fibres for that organ ; when the lingual is stim- ulated, the bloodvessels of the tongue dilate owing to the stimulation of the conjoined corda tympani fibres. The ramus tympanicus of the glosso-pharyn- geal nerve contains vaso-dilator fibres for the parotid gland, and it appears probable that the trigeminal nerve contains vaso-dilator fibres for the eye and nose and possibly for other parts. In the anterior roots of the sacral nerves run vaso-dilator fibres which pass into the so-called nervi erigentes, the nerves stimulation of which by leading to a widening of the arteries of the penis, brings about the erection of that organ, the effect being assisted by a simultaneous hindrance to the venous outflow. Though vaso-dilator fibres are, as we have seen, present in the nerves of the limbs, and probably also in those of the trunk, the investigation of their several paths is rendered very difficult by the concomitant presence of vaso-constrictor fibres. There are some reasons for thinking that the vaso-dilator fibres in these nerves pur- sue a direct course from the spinal cord through the anterior spinal roots, and thus afford a contrast with the constrictor fibres of the same nerves, which, as we have seen, take a roundabout course, passing into the splanch- nic system before they join the nerve trunk. Our information, however, is too imperfect to allow any very positive statement to be made. Accept- ing this view, however, we may say that while all the vaso-constrictor fibres, as far as we know, come from a particular, though considerable, part of the spinal cord and pass into the splanchnic system on their way to their sev- eral destinations, the vaso-dilator fibres arise from all parts of the spinal cord as well as from the medulla oblongata, and pursue a more or less direct course to their destination. Further, while the vaso-dilator fibres, as they leave the central nervous system, are, like the vaso-constrictor fibres, fine medullated fibres, unlike the vaso-constrictors they retain their medulla for the greater part of their course, and only lose it near their termination in the tissue whose blood- vessels they supply. Lastly, while the vaso-constrictor fibres, as in the case of the cervical sympathetic, of the abdominal splanchnic, and of the nerves of the skin, and probably in all cases, are normally in a state of moderate activity (so long as they remain in connection with the central nervous system), the moderate activity maintaining that moderate constriction which we spoke of above as " tone," the vaso-dilators appear to possess no such continued activity. Section of vaso-constrictor fibres leads to loss of tone, diminution of constriction, lasting, as we shall see, for some considerable time; but VASOMOTOR ACTIONS. 221 section of vaso-dilators, according, at all events, to most observers, does not lead to analogous constriction or diminution of dilatation ; all that is observed is a transient increase of dilatation due probably to the section acting as a transient stimulus to the nerve at the place of section. But before we study the use made by the central nervous system of vasomotor nerves, it will be best to consider briefly some features of The Effects of Vasomotor Actions. § 157. A very little consideration will show that vasomotor action is a most important factor in the circulation. In the first place the whole flow of blood in the body is adapted to and governed by what we may call the general tone of the arteries of the body at large. In a normal condition of the body a very large number of the minute arteries of the body are in a state of tonic, i. e., of moderate, contraction, and it is the narrowing due to this contraction which forms a large item of that peripheral resistance which we have seen to be one of the great factors of blood-pressure. The normal general blood-pressure, and, therefore, the normal flow of blood, is in fact dependent on the " general tone " of the minute arteries. In the second place local vasomotor changes in the condition of the minute arteries changes — i. e., of any particular vascular area — have very decided effects on the circulation. The changes, though local themselves, may have effects which are both local and general, as the following con- siderations will show : Let us suppose that the artery A is in a condition of normal tone, is mid- way between extreme constriction and dilatation. The flow through A is determined by the resistance in A, and in the vascular tract which it sup- plies in relation to the mean arterial pressure, which is again dependent on the way in which the heart is beating and on the peripheral resistance of all the small arteries and capillaries, A included. If, while the heart and the rest of the arteries remain unchanged, A be constricted, the peripheral resistance in A will increase, and this increase of resistance will lead to an increase of the general arterial pressure. Since, as we have seen (§ 108), it is arterial pressure which is the immediate cause of the flow from the arteries to the veins, this increase of arterial pressure will tend to drive more blood from the arteries into the veins. The constriction of A, however, by in- creasing the resistance, opposes any increase of the flow through A itself, in fact will make the flow through A less than before. The whole increase of discharge from the arterial into the venous system will take place through the arteries in which the resistance remains unchanged, that is, through channels other than A. Thus, as the result of the constriction of an artery there occur (1) diminished flow through the artery itself, (2) increased gen- eral arterial pressure, leading to (3) increased flow through the other arteries. If, on the other hand, A be dilated, while the heart and other arteries remain unchanged, the peripheral resistance in A is diminished. This leads to a lowering of the general arterial pressure, which in turn tends to drive less blood from the arteries into the veins. The dilatation of A, however, by diminishing the resistance, permits, even with the lowered pressure, more blood to pass through A itself than before. Hence the diminished flow tells all the more on the rest of the arteries in which the resistance remains unchanged. Thus, as the result of the dilatation of any artery, there occur (1) increased flow of blood through the artery itself, (2) diminished general pressure, and (3) diminished flow through the other arteries. Where the artery thus constricted or dilated is small, the local effect, the diminution or increase of flow through itself, is much more marked than the general effects, 222 THE VASCULAR MECHANISM. the change in blood-pressure and the flow through other arteries. When, however, the area, the arteries of which are affected, is large, the general effects are very striking. Thus if while a tracing of the blood- pressure is being taken by means of a manometer connected with the carotid artery, the abdominanl splanchnic nerves be divided, a conspicuous but steady fall of pressure is observed, very similar to but more marked than that which is seen in Fig. 99. The section of the abdominal splanchnic nerves causes the mesenteric and other abdominal arteries to dilate, and these being very numerous, a large amount of peripheral resistance is taken away, and the blood-pressure falls accordingly ; a large increase of flow into the portal veins takes place, and the supply of blood to the face, arms, and legs is pro- portionately diminished. It will be observed that the dilatation of the arteries is not instantaneous but somewhat gradual, as shown by the pressure sinking not abruptly but with a gentle curve. The general effects on blood-pressure by vasomotor changes are so marked that the manometer may be used to detect vasomotor actions. Thus, if the stimulation of a particular nerve or any other operation leads to a marked rise of the mean blood-pressure, unaccompanied by any changes in the heart-beat, we may infer that constriction has taken place in the arteries of some considerable vascular area ; and similarly, if the effect be a fall of blood-pressure, we may infer that constriction has given way to dilatation. Vasomotor Functions of the Central Nervous System. § 158. The central nervous system, to which we have traced the vaso- motor nerves, makes use of these nerves to regulate the flow of blood through the various organs and parts of the body ; by the local effects thus produced it assists or otherwise influences the functional activity of this or that tissue; by the general effects it secures the well-being of the body. The use of the vaso-dilator nerves, which is more simple than that of the vaso-constrictors since it appears not to be complicated by the presence of habitual tonic influences, is frequently conspicuous as part of a reflex act. Thus, when food is placed in the mouth, afferent impulses, generated in the nerves of taste, give rise in the central nervous system to efferent impulses, which descend the chorda tympani and other nerves to the salivary glands, and, by dilating the bloodvessels, secure a copious flow of blood through the glands, while, as we shall see later on, they excite them to secrete. The centre of this reflex action appears to lie in the medulla oblongata, and may be thrown into activity not only by impulses reaching it along the specific nerves of taste, but also by impulses passing along other channels ; thus, emotions started in the brain by the sight of food or otherwise may give rise to impulses passing down along the central nervous system itself to the medulla oblongata, or even in the stomach may send impulses up the vagus nerve, or stimulation of one kind or another may send impulses up almost any sentient nerve, and these various impulses reaching the medulla may, by reflex action, throw into activity the vaso-dilator fibres of the chorda tym- pani and other analogous nerves, and bring about a flushing of the salivary glands, while at the same time they cause the glands to secrete. The vaso-dilator fibres of the nervi erigentes may be thrown into activity in a similar reflex way, the centre in this case being placed in the sacral or lumbar portion of the spinal cord, though it is easily thrown into activity by impulses descending down the spinal cord from the brain that such a centre does exist, is shown by the fact that when in a dog the spinal cord is completely divided in the dorsal region, erection of the penis may readily be VASOMOTOR ACTIONS. 223 brought about by stimulation of the sentient surfaces. And other instances might be quoted in which vaso-dilator fibres appear to be connected with a " centre " soon after their entrance into the nervous system. If, as seems probable (§ 153), the bloodvessels of a'muscle dilate by vaso- motor action whenever the muscle is thrown into contraction, either in a reflex or voluntary movement, the vaso-dilator fibres of the muscle would seem to be thrown into action by impulses arising in the spinal cord not far from the origin of the ordinary motor impulses and accompanying those motor impulses along the motor nerve. § 159. The case of the vaso-constrictor fibres is somewhat more com- plicated on account of the existence of tonic influences ; since the same fibres may, on the one hand, by an increase in the impulses passing along them, be the means of constriction, and, on the other hand, by the removal or diminution of the tonic influences passing along them, be the means of dila- tation. We have already traced all the vaso-constrictor fibres from the middle region of the spinal cord to the splanchnic system in the thorax and abdomen, from whence they pass (1) by the abdominal splanchnic and by the hypogastric nerves to the viscera of the abdomen and pelvis (concerning the vasomotor nerves of the thoracic viscera we know at present very little) ; (2) by the cervical sympathetic or cervical splanchnic, as it might be called, to the skin of the head and neck, the salivary glands and mouth, the eyes and other parts, and probably the brain, including its membranes ; (3) by the brachial and sciatic plexuses to the skin of the fore and hind limbs, and by various other nerves to the skin of the trunk. The chief parts of the body supplied by vaso-constrictor fibres appear to be the skin, with its ap- pendages, and the alimentary canal, with its appendages, glandular and other ; the great mass of skeletal muscles appears to receive an insignificant supply of vaso-constrictor fibres. If, now, in an animal, the spinal cord be divided in the lower dorsal region, the skin of the legs becomes flushed, their temperature frequently rises, and there is a certain amount of fall in the general blood-pressure as measured, for instance, in the carotid ; and this state of things may last for some considerable time. Obviously, the section of the spinal cord has cut off the usual tonic influences descending to the lower limbs ; in consequence the bloodvessels have become dilated, thus causing the general peripheral resistance to become proportionately diminished, and the general blood- pressure to fall. The tonic vaso-constrictor impulses for the lower limbs, therefore, have their origin in the central nervous system higher up than the lower dorsal region of the spinal cord. If the spinal cord be divided between the roots of the fifth and sixth dorsal nerves (that is to say, at the level where the path of the splanchnic fibres from the cord seems to divide (see Fig. 77) those issuing above pass- ing upward to the fore limbs and head, and those issuing below passing to the abdomen and lower limbs), the cutaneous bloodvessels of the lower limbs dilate, as in the former case, and on examination it will be found that the bloodvessels of the abdomen are also largely dilated ; at the same time the blood-pressure undergoes a very marked fall ; it may, indeed, be reduced to a very few millimetres of mercury. Obviously, the tonic vaso-constrictor impulses passing to the abdomen and to the lower limbs take origin in the central nervous system higher up than the level of the fifth dorsal nerve. If the section of the spinal cord be made above the level of the second dorsal nerve, in addition to the above-mentioned results the vessels of the head and face also become dilated ; but, in consequence of the fall of general blood-pressure just mentioned, these vessels never become so full of blood, the loss of tone is not so obvious in them as after simple division of the 224 THE VASCULAR MECHANISM. cervical sympathetic, since the latter operation produces little or no effect on the general blood-pressure. Obviously, then, the tonic vaso-constrictor impulses, which passing to the skin and viscera of the body maintain that tonic narrowing of so many small arteries by which the general peripheral resistance, and so the general blood- pressure, is maintained, proceed from some part of the central nervous system higher up than the upper dorsal region of the spinal cord. And, since exactly the same results follow upon section of the spinal cord in the cervical region right up to the lower limit of the medulla oblongata, we infer that these tonic impulses proceed from the medulla oblongata. On the other hand, we may remove the whole of the brain right down to the upper parts of the medulla, and yet produce no flushing, or only a slight transient flushing, of any part of the body, and no fall at all, or only a slight transient fall, of the general blood-pressure. We, therefore, seem justified in assuming the existence in the medulla oblongata of a nervous centre, which we may speak of as a vasomotor centre, or the medullary vasomotor centre, from which proceed tonic vaso-constrictor impulses, or which regu- lates the emission and distribution of such tonic vaso-constrictor impulses or influences over various parts of the body. § 160. The existence of this vasomotor centre may, moreover, be shown in another way. The extent or amount of the tonic constrictor impulses proceeding from it may be increased or diminished, the activity of the centre may be augmented or inhibited by impulses reaching it along various afferent nerves ; and provided no marked changes in the heart-beat take place at the same time, a rise or fall of general blood-pressure may be taken as a token of an increase or decrease of the activity of the centre. In the rabbit there is found in the neck, lying side by side with the cervical sympathetic nerve and running for some distance in company with it, a slender nerve which may be ultimately traced down to the heart, and which if traced upward is found to come off somewhat high up from the vagus, by two or more roots, one of which is generally a branch of the superior laryngeal nerve. This nerve (the fibres constituting which are, in the dog, bound up with the vagus, and do not form an independent nerve) appears to be exclusively an afferent nerve ; when, after division of the nerve the peripheral end, the end still in connection with the heart, is stimulated, no marked results follow. The beginnings of the nerve in the heart are therefore quite different from the endings of the inhibitory fibres of the vagus, or of the augmentor fibres of the splanchnic (sympathetic) system ; the nerve has nothing to do with the nervous regulation of the heart (see §§ 139 et seq.*). If, now, while the pressure in an artery such as the carotid is being registered, the central end of the nerve — i. e., the one connected with the brain — be stimulated with the interrupted current, a gradual but marked fall of pressure (Fig. 79) in the carotid is observed, lasting, when the period of stimulation is short, some time after the removal of the stimulus. Since the beat of the heart is not markedly changed, the fall of pressure must be due to the diminution of peripheral resistance occasioned by the dilatation of some arteries. And it is probable that the arteries thus dilated are chiefly, if not exclusively, those arteries of the abdominal viscera which are governed by the abdominal splanchnic nerves ; for if these nerves are divided on both sides previous to the experiment, the fall of pressure when the nerve is stimulated is very small — in fact, almost insignificant. The inference we draw is as follows : The afferent impulses, passing upward along the nerve in question, have so affected some part of the central nervous system that the influences which, in a normal condition of things, passing along the abdominal splanchnic nerves keep the minute arteries of the VASOMOTOK ACTIONS. 225 abdominal viscera in a state of moderate tonic constriction, fail altogether, and those arteries in consequence dilate just as they do when the abdominal FIG. 79. Tracing showing the Effect on Blood-pressure of Stimulating the Central End of the Depressor Nerve in the Rabbit. On the time-marker below the intervals correspond to seconds. At x an interrupted current was thrown into the nerve. splanchnic nerves are divided, the effect being possibly increased by the similar dilatation of other vascular areas. Since stimulation of the nerve of which we are speaking always produces a fall, never a rise, of blood-pres- sure— the amount of fall, of course, being dependent on circumstances, such as the condition of the nervous system, state of blood-pressure, etc. — the nerve is known by the name of the depressor nerve. As we shall point out later on, by means of this afferent nerve from the heart the peripheral resist- ance is, in the living body, lowered to suit the weakened powers of a laboring heart. This gradual lowering of blood-pressure by diminution of peripheral resistance affords a marked contrast to the sudden lowering of blood-pres- sure by cardiac inhibition. (Compare Fig. 79 with Fig. 75.) § 161. But the general blood-pressure may be modified by afferent im- pulses passing along other nerves than the depressor, the modification taking on, according to circumstances, the form either of decrease or of increase. Thus, if, in an animal placed under the influence of urari (some anaes- thetic other than chloral, etc., being used), the central stump of the divided sciatic nerve be stimulated, an increase of blood-pressure (Fig. 80) almost FIG. 80. Effect on Blood-pressure Curve of Stimulating Sciatic Nerve under Urari. (Cat.) x marks the moment in which the current was thrown into the nerve. Artificial respiration was car- ried on, and the usual respiratory undulations are absent. exactly the reverse of the decrease brought about by stimulating the de- pressor, is observed. The curve of the blood-pressure, after a latent period during which no changes are visible, rises, steadily without any corre- sponding change in the heart's beat, reaches a maximum, and after a 15 226 THE VASCULAR MECHANISM. while slowly falls again, the fall sometimes beginning to appear before the stimulus has been removed. There can be no doubt that the rise of pres- sure is due to the constriction of certain arteries ; the arteries in question being those of the abdominal splanchnic area certainly, and possibly those of other vascular areas as well. The effect is not confined to the sciatic ; stimulation of any nerve containing afferent fibres may produce the same rise of pressure, and so constant is the result that the experiment has been made use of as a method of determining the existence of afferent fibres in any given nerve and even the paths of centripetal impulses through the spinal cord. If, on the other hand, the animal be under the influence not, of urari,' but of a large dose of chloral, instead of a rise of blood-pressure, a fall quite similar to that caused by stimulating the depressor is observed when an afferent nerve is stimulated. The condition of the central nervous system seems to determine whether the effect of afferent impulses on the central nervous system is one leading to an augmentation of vaso-constrictor impulses and so to a rise, or one leading to a diminution of vaso-constrictor impulses and so to a fall of blood-pressure. § 162. We have used the words " central nervous system " in speaking of the above ; we have evidence, however, that the part of the central nervous system acted on by the afferent impulses is the vasomotor centre in the medulla oblongata, and that the effects in the way of diminution (depressor) or of augmentation (pressor) are the results of afferent impulses inhibiting or augmenting the tonic activity of this centre or of a part of this centre especially connected with abdominal splanchnic nerves. The whole brain may be removed right down to the medulla oblongata, and yet the effects of stimu- lation in the direction either of diminution or of augmentation may still be brought about. If the medulla oblongata be removed, these effects vanish too, though all the rest of the nervous system be left intact. Nay, more, by partially interfering with the medulla oblongata, we may partially diminish these effects and thus mark out, so to speak, the limits of the centre in ques- tion within the medulla itself. Thus, in an intact animal under urari, stimu- lation of the sciatic nerve with a stimulus of a certain strength will produce a rise of blood-pressure up to a certain extent. After removal of the whole brain right down to the medulla oblongata, the same stimulation will produce the same rise as before ; the vasomotor centre has not been interfered with. Directly, however, in proceeding downward, the region of the centre in ques- tion is reached, stimulation of the sciatic produces less and less rise, until at last when the lower limit of the centre is arrived at no effect at all on blood- pressure can be produced by even strong stimulation of the sciatic or other afferent nerve. In this way the lower limit of the medullary vasomotor centre has been determined in the rabbit at a horizontal line drawn about 4 or 5 mm. above the point of the calamus scriptorius, and the upper limit at about 4 mm. higher up — i. e., about 1 or 2 mm. below the corpora quadri- gemina. When transverse sections of the brain are carried successively lower and lower down, an effect on blood-pressure in the way of lowering it and also of diminishing the rise of blood-pressure resulting from stimulation of the sciatic, is first observed when the upper limit is reached. On carrying the sections still lower, the effects of stimulating the sciatic become less and less, until when the lower limit is reached no effects at all are observed. The centre appears to be bilateral, the halves being placed not in the middle line, but more sideways and rather nearer the anterior than the posterior surface. It may perhaps be more closely defined as a small prismatic space in the forward prolongation of the lateral columns after they have given off their fibres to the decussating pyramids. This space is largely occupied by a mass VASOMOTOR ACTIONS. 227 of gray matter, called by Clarke the antero-lateral nucleus, and containing large multipolar cells ; but it is by no means certain that this group of nerve cells really acts as the centre in question. § 163. The above experiments appear to afford adequate evidence that, in a normal state of the body, the integrity of the medullary vasomotor centre is essential to the production and distribution of those continued constrictor impulses by which the general arterial tone of the body is maintained, and that an increase or decrease of vaso-constrictor action in particular arteries, or in the arteries generally, is brought about by means of the same medullary vasomotor centre. But we must not, therefore, conclude that this small por- tion of the medulla oblongata is the only part of the central nervous system which can act as a centre for vaso-constrictor fibres ; and, as we have seen, there is no evidence at present that the vaso-dilator fibres are connected with either this or any other one centre. In the frog reflex vasomotor effects may be obtained by stimulating various afferent nerves after the whole medulla has been removed, and, indeed, even when only a comparatively small portion of the spinal cord has been left intact and connected, on the one hand, with the afferent nerve which is being stimulated, and, on the other, with the efferent nerves in which run the vasomotor fibres whose action is being studied. In the mammal such effects do not so readily appear, but may with care and under special conditions be obtained. Thus in the dog, when the spinal cord is divided in the dorsal region, the arteries of the hind limbs and hinder part of the body, as we have already said (§ 158), become dilated. This one would naturally expect as the result of their severance from the medullary vasomotor centre. But if the animal be kept in good condition for some time, a normal or nearly normal arterial tone is after a while re-established ; and the tone thus regained may, by afferent impulses reaching the cord below the section, be modified in the direction certainly of diminution — i. e., dilatation — and possibly, but this is by no means so cer- tain, of increase — i. e., constriction. Dilatation of various cutaneous vessels of the limbs may be readily produced by stimulation of the central stump of one or another nerve. These remarkable results, which, though they are most striking in connec- tion with the lower part of the spinal cord, hold good apparently for other parts also of the spinal core, naturally suggest a doubt whether the explana- tion just given above of the effects of section of the medulla oblongata is a valid one. When we come to study the central nervous system, we shall again and again see that the immediate effect of operative interference with these delicate structures is a temporary suspension of nearly all their func- tions. This is often spoken of as "shock" and may be regarded as an extreme form of inhibition. An example of it occurs in the above experi- ment of section of the dorsal cord. For some time after the operation the vaso-dilator nervi erigentes (which, as far as we know, have no special connec- tion with the medullary vasomotor centre) cannot be thrown into activity as part of a reflex action ; their centre remains for some time inactive. After a while, however, it recovers, and erection of the penis through the nervi erigentes may then still be brought about by suitable stimulation of sensory surfaces. Hence the question may fairly be put whether the effects of cut- ting and injuring the structures which we have spoken of as the medullary vasomotor centre, are not in reality simply those of shock, whether the vas- cular dilatation which follows upon sections of the so-called medullary vaso- motor centre, does not come about because section of or injury to this^ region exercises a strong inhibitory influence on all the vasomotor centres situated in the spinal cord below. Owing to the special function of the medulla oblongata in carrying on the all-important work of respiration, a mammal 228 THE VASCULAR MECHANISM. whose medulla has been divided cannot be kept alive for any length of time. We cannot, therefore, put the matter to the simple experimental test of extir- pating the supposed medullary vasomotor centre and seeing what happens when the animal has completely recovered from the effects of the operation ; we have to be guided in our decision by more or less indirect arguments. And against the argument that the effects are those of shock, we may put the argument, evidence for which we shall meet with in dealing with the central nervous system, that when one part of the central nervous system is removed or in any way placed hors de combat, another part may vicariously take on its function ; in the absence of the medullary vasomotor centre, its function may be performed by other parts of the spinal cord which in its presence do no such work. And we may, in connection with this, call attention to the fact that the dilatation or loss of tone which follows upon section of the cervical sympathetic (and the same is true of the abdominal splanchnic) is not always, though it may be sometimes, permanent ; in a certain number of cases "it has been found that after a while, it may not be until after several days, the dilatation disappears and the arteries regain their usual calibre ; on the other hand, in some cases no such return has been observed after months or even years. This recovery, when it occurs, cannot always be attributed to any regenera- tion of vasomotor fibres in the sympathetic, for it is stated to have been observed when the whole length of the nerve including the superior cervical ganglion has been removed. When recovery of tone has thus taken place, dilatation or increased constriction may be occasioned by local treatment ; the ear may be made to blush or pale by the application of heat or cold, by gentle stroking or rough handling and the like ; but neither the one nor the other condition can be brought about by the intervention of the central nervous system. So also the spontaneous rhythmic variations in the calibre of the arteries of the ear of which we speak, though they cease for a time after division of the cervical sympathetic, may in some cases eventually reap- pear and that even if the superior cervical ganglion be removed ; in other cases they do not. And the analogous rhythmic variations of the veins of the bat's wing have been proved experimentally to go on vigorously when all connection with the central nervous system has been severed ; they may continue, in fact, in isolated pieces of the wing provided that the vessels are adequately filled and distended with blood or fluid. From these and other facts, even after making allowance for the negative cases, we may conclude that what we have spoken of as the tone of the vessels of the face, though influenced by and in a measure dependent on the central nervous system, is not simply the result of an effort of that system. The muscular walls of the arteries are not mere passive instruments worked by the central nervous system through the vasomotor fibres ; they appear to have an intrinsic tone of their own, and it seems natural to suppose that when the central nervous system causes dilatation or constriction of the vessels of the face, it makes use, in so doing, of this intrinsic local tone. It has been supposed that this intrinsic tone is dependent on some local nervous mechanism ; in the ear at least no such mechanism has yet been found ; and, indeed, as we have said above (§ 176), no such peripheral nervous mechanism is really necessary. In the case both of a vessel governed by vaso-dilator fibres and one governed by vaso-constrictor fibres, we may suppose a certain natural condition of the muscular fibres which we may call a condition of equilibrium. In a vessel governed only by vaso-dilator fibres, if there be such, this condition of equilibrium is the permanent condition of the muscular fibre, from which it is disturbed by vaso-dilator impulses, but to which it speedily returns. In a vessel governed by vaso-constrictor fibres, and subject to tone, the muscu- VASOMOTOR ACTIONS. 229 lar fibre is habitually kept on the constrictor side of this equilibrium, and, as in the cases quoted above, may strive of itself toward some amount of active constriction even when separated from the central nervous system. But to return to the medullary vasomotor centre. Without attempting to discuss the matter fully, we may say that, after all due weight has been attached to the play of inhibitory impulses or " shock " as a result of opera- tive interference, there still remains a balance of evidence in favor of the view that the region of the medulla of which we are speaking does really act as a general vasomotor centre in the manner previously explained, and plays an important part in the vasomotor regulation of the living body. It is not, however, to be regarded as the single vasomotor centre, whence alone can issue tonic-constrictor impulses or whither afferent impulses from all parts of the body must always travel before they can affect the vaso- motor impulses passing along this or that nerve. We are rather to suppose that the spinal cord along its whole length contains, interlaced with the reflex and other mechanisms by which the skeletal muscles are governed, vasomotor centres and mechanisms of varied complexity, the details of whose functions and topography have yet largely to be worked out ; and though, as we have seen, the medullary centre is essentially a centre of im- pulses issuing along vaso-constrictor fibres, it is possible that there are ties between it and vaso-dilator fibres also. As in the absence of the sinus venosus, the auricles and ventricle of the frog's heart may still continue to beat, so in the absence of the medulla oblongata these spinal vasomotor centres provide for the vascular emergencies which arise. As, however, in the normal entire frog's heart, the sinus, so to speak, gives the word and governs the work of the whole organ, so the medullary vasomotor centre rules and co-ordinates the lesser centres of the cord, and through them pre- sides over the chief vascular areas of the body. By means of these vaso- motor central mechanisms, by means of the head centre in the medulla, and the subsidiary centres in the spinal cord, the delicate machinery of the circu- lation which determines the blood-supply, and so the activity of each tissue and organ, is able to respond by narrowing or widening arteries to the ever- varying demands and to meet by compensating changes the shocks and strains of daily life. § 164. We may sum up the history of vasomotor actions somewhat as follows : All, or nearly all — or, as far as we know, all — the arteries of the body are connected with the central nervous system by nerve fibres, called vaso- motor fibres, the action of which varies the amount of contraction of the muscular coats of the arteries, and so leads to changes in calibre. The action of these vasomotor fibres is more manifest and probably more important in the case of small and minute arteries than in the case of larger ones. These vasomotor fibres are of two kinds : the one kind, vaso-constrictor fibres, are of such a nature or have such connections at their central origin or peripheral endings that stimulation of them produces narrowing, con- striction of the arteries ; and during life these fibres appear to be the means by which the central nervous system exerts a continued tonic influence on the arteries and maintains an arterial " tone." The other kind, the vaso- dilator fibres, are of such a kind or have such connections that stimulation of them produces widening, dilation of the arteries. There is no adequate evidence that these vaso-dilator fibres serve as channels for tonic dilating impulses or influences. The vaso-constrictor fibres leave the spinal cord by the anterior roots of the nerves coming from middle regions only of the spinal cord (in the dog, 230 THE VASCULAR MECHANISM. and probably in other mammals from about the first dorsal to the fifth lumbar nerve), pass into the splanchnic ganglia connected with those nerves (thoracic and abdominal chain of sympathetic ganglia), where the fibres lose their medulla, and proceed to their destination as non-medullated fibres, either still in so-called sympathetic nerves, such as splanchnic, cervical sympathetic, hypogastric, etc., or along recurrent branches of the splanchnic system, to join the spinal nerves of the arm, leg, and trunk. In the intact organism the emission and distribution along these vaso- constrictor fibres of tonic-constrictor impulses, by which general and local arterial tone is maintained and regulated, is governed by a limited portion of the medulla oblongata known as the medullary vasomotor centre ; and when some change of conditions or other natural stimulus brings about a change in the activity of the vaso-constrictor fibres of one or more vascular areas, or of all the arteries supplied with vaso-constrictor fibres, this same medullary vasomotor centre appears in such cases to play the part of a centre of reflex action. Nevertheless, in cases where the nervous connections of this medullary vasomotor centre with a vascular area are cut off by an operation, as by section of the cord, other parts of the spinal cord may act as centres for the vaso-constrictor fibres of the area, and possibly these subordinate centres may be to a certain extent in action in the intact organism. The vaso-dilator fibres appear to take origin in various parts of the central nervous system and to proceed in a direct course to their destination along the (anterior) roots and as part of the trunks and branches of various cerebro-spinal nerves ; they do not lose their medulla until they approach their termination. They do not appear to serve as channels of tonic dilating influences ; they are thrown into action generally as part of a reflex action, and their centre in the reflex act appears in each case to lie in the central nervous system not far from the centre of the ordinary motor fibres which they accompany. The effects of the activity of the vaso-dilator fibres appear to be essentially local in nature ; when any set of them come into action the vascular area which these govern is dilated. And the vascular areas so governed are relatively so small that changes in them produce little or no effect on the vascular system in general. The effects of changes in the activity of the vaso-constrictor fibres are both local and general, and may be also double in nature. By an inhibition of tonic-constrictor impulses a certain amount of dilation may be effected ; by an augmentation of constrictor impulses, constriction, it may be of con- siderable extent, may be brought about. When the vascular area so affected is small, the effects are local, more or less blood is distributed through the area ; when the vascular area affected is large, the inhibition of constriction may lead to a marked fall, and an augmentation of constriction to a marked rise of general blood-pressure. § 165. We shall have occasion later on again and again to point out instances of the effects of vasomotor action, both local and general, but we may here quote one or two characteristic ones. " Blushing " is one. Ner- vous impulses started in some parts of the brain by an emotion produce a powerful inhibition of that part of the medullary vasomotor centre which governs the vascular areas of the head supplied by the cervical sympathetic, and hence has an effect on the vasomotor fibres of the cervical sympathetic almost exactly the same as that produced by section of the nerve. In conse- quence the muscular walls of the arteries of the head and face relax, the arteries dilate, and the whole region becomes suffused. Sometimes an emo- tion gives rise not to blushing, but to the opposite effect, viz., to pallor. THE CAPILLARY CIRCULATION. 231 In a great number of cases this has quite a different cause, being due to a sudden diminution or even temporary arrest of the heart's beats ; but in some cases it may occur without any change in the beat of the heart, and is then due to a condition the very converse of that of blushing, that is, to an increased arterial constriction ; and this increased constriction, like the dila- tation of blushing, is effected through the agency of the central nervous system and the cervical sympathetic. The vascular condition of the skin at large affords another instance. When the temperature of the air is low the vessels of the skin are con- stricted and the skin is pale ; when the temperature of the air is high the vessels of the skin are dilated and the skin is red and flushed. In both these cases the effect is mainly a reflex one, it being the central nervous system which brings about augmentation of constriction in the one case and inhibition in the other, though possibly some slight effect is reproduced by the direct action of the cold or heat on the vessels of the skin simply. More- over, the vascular changes in the skin are accompanied by corresponding vascular changes in the viscera (chiefly abdominal) of a reverse kind. When the vessels of the skin are dilated those of the viscera are constricted, and vice versa, so that a considerable portion of the whole blood ebbs and flows, so to spaak, according to circumstances from skin to viscera and from viscera to skin. By these changes, as we shall see later on, the maintenance of the normal temperature of the body is in large measure secured. When food is placed in the mouth the bloodvessels of the salivary glands, as we have seen, are flushed with blood as an adjuvant to the secretion of digestive fluid ; and as the food passes along the alimentary canal, each section in turn, with the glandular appendages belonging to it, welcomes its advent by flushing with blood, the dilatation being sometimes, as in the case of the salivary gland, the result of the activity chiefly of vaso-dilator fibres, but sometimes the result of the cessation of constrictor impulses and some- times the result of the two combined. So also when the kidney secretes urine, its vessels become dilated, and in general, wherever functional activity comes into play, the metabolism of tissue which is the basis of that activity is assisted by a more generous flow of blood through the tissue. § 166. Vasomotor nerves of the veins. Although the veins are provided with muscular fibres and are distinctly contractile, and although rhythmic variations of calibre due to contractions may be seen in the great veins opening into the heart, in the veins of the bat's wing, and elsewhere, and similar rhythmic variations, also possibly due to active rhythmic contrac- tions, but possibly also of an entirely passive nature, have been observed in the portal veins, very little is known of any nervous arrangements govern- ing the veins. When in the frog the brain and spinal cord are destroyed, very little blood comes back to the heart as compared with the normal supply, and the heart in consequence appears almost bloodless and beats feebly. This has been, by some, regarded as more than can be accounted for by mere loss of arterial tone, and accordingly interpreted as indicating the existence of a normal tone in the veins dependent on the central nervous system. When the latter is destroyed, the veins become abnormally distended and a large quantity of blood becomes lodged and hidden, as it were, in them. THE CAPILLARY CIRCULATION. § 167. We have already some time back (§ 106) mentioned some of the salient features of the circulation through the capillaries, viz., the difficult passage of the corpuscles (generally in single file, though sometimes in the larger channels two or more abreast) and plasma through the narrow chan- 232 THE VASCULAR MECHANISM. nels, in a stream which though more or less irregular is steady and even, not broken by pulsations, and slower than that in either the arteries or the veins. We have further seen that the capillaries vary very much in width from time to time ; and there can be no doubt that the changes in their calibre are chiefly of a passive nature. They are expanded when a large supply of blood reaches them through the supplying arteries, and, by virtue of their elasticity, shrink again when the supply is lessened or withdrawn ; they may also become expanded by an obstacle to the venous outflow. On the other hand, as we have also stated, there is a certain amount of evidence that, in young animals at all events, the calibre of a capillary canal may vary, quite independently of the arterial supply or the venous outflow, in consequence of changes in the form of the epithelioid cells, allied to the changes which in a muscle-fibre or muscle-cell constitute a contrac- tion ; and though the matter requires further investigation, it is possible that these active changes play an important part in determining the quantity of blood passing through a capillary area ; but there is as yet no satisfactory evidence that they, like the corresponding changes in the arteries, are governed by the nervous system. Over and above these changes of form, the capillaries and minute vessels are subject to changes and exert influences by virtue of which they play an important part in the work of the circulation. Their condition determines the amount of resistance offered by their channels to the flow of blood through those channels, and determines the amount and character of that interchange between the blood and the tissues which is the main fact of the circulation. If the web of the frog's foot, or, better still, if some transparent tissue of a mammal be watched under the microscope, it will be observed that, while in the small capillaries the corpuscles are pressed through the channel in single file, one after the other, each corpuscle as it passes occupying the whole bore of the capillary, in the larger capillaries (of the mammal), and especially in the small arteries and veins which permit the passage of more than one corpuscle abreast, the red corpuscles run in the middle of the channel, forming a colored core, between which and the sides of the vessels all around is a colorless layer, containing no red corpuscles, called the " plasmatic layer " or " peripheral zone." This division into a peripheral zone and an axial stream is due to the fact that in any stream passing through a closed channel the friction is greatest at the sides, and diminishes toward the axis. The corpuscles pass where the friction is least, in the axis. A quite similar axial core is seen when any fine particles are driven with a sufficient velocity in a stream of fluid through a narrow tube. As the veloc- ity is diminished the axial core becomes less marked and disappears. In the peripheral zone, especially in that of the veins, are frequently seen white corpuscles, sometimes clinging to the sides of the vessel, some- times rolling slowly along, and in general moving irregularly, stopping for a while and then suddenly moving on. The greater the velocity of the flow of blood, the fewer the white corpuscles in the peripheral zone, and with a very rapid flow they, as well as the red corpuscles, may be all confined to the axial stream. The presence of the white corpuscles in the peripheral zone has been attributed to their being specially lighter than the red corpus- cles, since when fine particles of two kinds, one lighter than the other, are driven through a narrow tube, the heavier particles flow in the axis and the lighter in the more peripheral portions of the stream. But, besides this, the white corpuscles have a greater tendency to adhere to surfaces than have the red, as is seen by the manner in which the former become fixed to the glass slide and cover-slip when a drop of blood is mounted for microscopical THE CAPILLAKY CIRCULATION. 233 examination. They probably thus adhere by virtue of the amoeboid move- ments of their protoplasm, so that the adhesion is to be considered not so much a mere physical as a physiological process, and hence may be expected to vary with the varying nutritive conditions of the corpuscles and of the bloodvessels. Thus while the appearance of the white corpuscles in the peripheral zone may be due to their lightness, their temporary attachment to the sides of the vessels and characteristic progression is the result of their power to adhere ; and as we shall presently see, their amoeboid movements may carry them on beyond mere adhesion. § 168. These are the phenomena of the normal circulation, and may be regarded as indicating a state of equilibrium between the blood on the one hand and the bloodvessels with the tissues on the other; but a different state of things sets in when that equilibrium is overthrown by causes leading to what is called inflammation or to allied conditions. If an irritant, such as a drop of chloroform or a little diluted oil of mustard, be applied to a small portion of a frog's web, tongue, mesen- tery, or some other transparent tissue, the following changes may be ob- served under the microscope ; they may also be seen in the mesentery or other transparent tissue of a mammal. The first effect that is noticed is a dilatation of the arteries, accompanied by a quickening of the stream. The irritant, probably by a direct action on the muscular fibres of the arteries, has led to a relaxation of the muscular coat and hence to a widening ; and we have already (§ 112), explained how such a widening in a small artery may lead to a temporary thickening of the stream. In consequence of the greater flow through the 'arteries, the capillaries become filled with corpus- cles, and many passages, previously invisible or nearly so on account of their containing no corpuscles, now come into view. The veins at the same time appear enlarged and full. If the stimulus be very slight, this may all pass away, the arteries gaining their normal constriction and the capillaries and veins returning to their normal condition ; in other words, the effect of the stimulus in such a case is simply a temporary blush. Unless, however, the chloroform or mustard be applied with especial care the effects are much more profound, and a series of remarkable changes sets in. In the normal circulation, as we have just said, white corpuscles may be seen in the peripheral, plasmatic zone, but they are scanty in number, and each one after staying for a little time in one spot suddenly gets free, sometimes almost by a jerk, as it were, and then rolls on for a greater or less distance. In the area now under consideration a large number of white corpuscles soon gather in the peripheral zones, especially of the veins and venous capillaries (that is, of the larger capillaries which are joining to form veins), but also, to a less extent, of the arteries ; and this takes place although the vessels still remain dilated and the stream still continues rapid though not so rapid as at first. Each white corpuscle appears to ex- hibit a greater tendency to stick to the sides of the vessels, and though driven away from the arteries by the stronger arterial stream, becomes lodged, so to speak, in the veins. Since new white corpuscles are continu- ally being brought by the blood-stream on to the scene, the number of them in the peripheral zones of the veins increases more and more, and this may go on until the inner surface of the veins and venous capillaries appears to be lined with a layer of white corpuscles. The small capillaries, too, contain more white corpuscles than usual, and even in the arteries these are abundant, though not forming the distinct layer seen in the veins. The white corpuscles, however, are not the only bodies present in the peripheral zone. Though in the normal circulation blood-platelets (see § 33) cannot 234 THE VASCULAR MECHANISM. be seen in the peripheral zone, and hence must be confined (on the view, which has the greater support, that these bodies are really present in quite normal blood) to the axial stream, they make their appearance in that zone with the changes which we are now describing. Indeed, in many cases they are far more abundant than the white corpuscles, the latter appearing imbedded at intervals in masses of the former. Soon after their appearance the individual platelets lose their outline and run together into formless masses. § 169. This much, the appearance of numerous white corpuscles and platelets in the peripheral zones may take place while the stream, though less rapid than at the very first, still remains rapid ; so rapid at all events that, owing to the increased width of the passages, in spite of the obstruc- tion offered by the adherent white corpuscles, the total quantity of blood flowing in a given time through the inflamed area is greater than normal. But soon, though the vessels still remain dilated, the stream is observed most distinctly to slacken and then a remarkable phenomenon makes its appearance. The white corpuscles lying in contact with the walls of the veins or of the capillaries are seen to thrust processes through the walls ; and, the process of a corpuscle increasing at the expense of the rest of the body of the corpuscle, the whole corpuscle, by what appears to be an ex- ample of amoeboid movement, makes its way through the wall of the ves- sel into the lymph space outside ; the perforation appears to take place in the cement substance joining the epithelioid plates together. This is the migration of the white corpuscles to which we alluded in § 32, and takes place chiefly in the veins and capillaries, not at all or to a very slight ex- tent in the arteries. Through this migration the lymph spaces around the vessels in the inflamed area become crowded with white corpuscles. At the same time the lymph in the same spaces not only increases in amount but changes somewhat in its chemical characters ; it becomes more distinctly and readily coagulable, and is sometimes spoken of as " exudation fluid," or by the older writers as " coagulable lymph." This turgescence of the lymph spaces, together with the dilated, crowded condition of the blood- vessels, gives rise to the swelling which is one of the features of inflam- mation. If the inflammation now passes off the white corpuscles cease to emi- grate, cease to stick for any length of time to the sides of the vessels, the stream of blood through the vessels quickens again, and the vessels them- selves, though they may remain for a long time dilated, eventually regain their calibre, and a normal circulation is re-established. The migrated cor- puscles move away from the region, along the labyrinth of lymph spaces, and the surplus lymph also passes away along the lymph spaces and lym- phatic vessels. § 170. The condition of things, however, instead of passing off may go on to a further stage. More and more white corpuscles, arrested in their passage, crowd the channels and block the way, so that though the vessels remain dilated the stream becomes slower and slower, until at last it stops altogether and " stagnation " or " stasis " sets in. The red corpuscles are driven in, often in masses, among the white corpuscles and platelets, the distinction between axial stream and peripheral zone becoming lost; and arteries, veins, and capillaries, all distended, sometimes enormously so, are filled with a mass of mingled red and white corpuscles and platelets. When actual stagnation occurs the red corpuscles run together so that their outlines are no longer distinguishable ; they appear to become fused into a homogeneous red mass. And it may now be observed that, not only white corpuscles but also red corpuscles make their way through THE CAPILLAKY CIRCULATION. 235 the distended and altered walls of the capillaries, chiefly, at all events, at the junctions of the epithelioid plates, into the lymph spaces beyond. This is spoken of as the diapedesis of the red corpuscles. This latter " stagnation " stage of inflammation may be the prelude to further mischief and indeed to the death of the inflamed tissue, but it, too, like the earlier stages, may pass away. As it passes away the outlines of the corpuscles become once more distinct, those on the venous side of the block gradually drop away into the neighboring currents — little by little the whole obstruction is removed, and the current through the area is re-established. The slowing and final arrest of the blood current described above is not due to any lessening of the heart's beat ; the arterial pulsations, or at least the arterial flow, may be seen to be continued in full force down to the affected area, and there to cease very suddenly. It is not due to any con- striction of the small arteries increasing the peripheral resistance, for these continue dilated, sometimes exceedingly so. It must, therefore, be due to some new and unusual resistance occurring in the area itself, and there can be no doubt that this is to be found in an increased tendency of the corpuscles, especially of the white corpuscles, to stick to the sides of the vessels. The increase of adhesiveness is not caused by any change con- fined to the corpuscles themselves; for if, after a temporary delay, one set of corpuscles has managed to pass away from the affected area, the next set of corpuscles brought to the area in the blood-stream is sub- jected to the same delay and the same apparent fusion. The cause of the increased adhesiveness must, therefore, lie in the walls of the blood- vessels or in the tissue of which these form a part. That the increased adhesion is due to the vascular walls and not primarily to the corpuscles themselves is further shown by the fact that if in the frog, an artificial blood of normal saline solution to which milk has been added be substituted for normal blood, a stasis may by irritants be induced in which oil-globules play the part of corpuscles, and by their aggregation. bring about an arrest of the flow. We are driven to conclude that there exist in health certain relations between the blood, on the one hand, and the walls of the vessel on the other, by which the tendency of the corpuscles to adhere to the bloodvessels is kept within certain limits; these relations consequently determine the normal flow, with its axial stream and peripheral zone, and the normal amount of peripheral resistance ; in inflammations these relations, in a manner we cannot as yet fully explain, are disturbed so that the tendency of the corpuscles to adhere to the sides of the vessel is largely and progressively increased. Hence the tarrying of the corpuscles in spite of the widening of their path, and finally their agglomeration and fusion in the distended channels. We may add that the changes occurring in the vascular walls also at least facilitate the migration of the corpuscles, and modify the passage from the blood to the tissue of the fluid parts of the blood, the lymph of inflamed areas being richer in proteids than normal lymph. We must not, however, pursue this subject of inflammation any further. We have said enough to show that the peripheral resistance (and consequently all that depends on that peripheral resistance) is not wholly determined by the varying width of the minute passages, but is also dependent on the vital condition of the tissue of which the walls of the passage form a part. When the tissue is in health, a certain resistance is offered to the passage of blood through the capillaries and other minute vessels, and the whole vascular mechanism is adapted to overcome this resistance to such an extent that a 236 THE VASCULAR MECHANISM. normal circulation can take place. When the tissue becomes affected, the disturbance of the relations between the tissue and the blood may, as in the later stages of inflammation, so augment the resistance that the passage of the blood becomes at first difficult and ultimately impossible. And it is quite open to us to suppose that under certain circumstances the reverse of the above may occur in this or that area, conditions in which the resist- ance may be lowered below the normal and the circulation in the area quickened. Thus the vital condition of the tissue becomes a factor in the maintenance of the circulation ; and it is possible, though not yet proved, that these vital conditions are directly under the dominion of the nervous system. § 171. Changes in the peripheral resistance may also be brought about by changes in the character of the blood, especially by changes in the relative amount of gases present. When a stream of defibrinated blood is artificially driven through a perfectly fresh excised organ such as the kidney, it is found that the resistance to the flow of blood through the organ, measured for in- stance by the amount of outflow in relation to the pressure exerted, varies considerably owing to changes taking place in the organ, and may be in- creased by increasing the venous character and diminished by increasing the arterial character of the blood. Remarkable changes in the resistance are also brought about by the addition of small quantities of certain drugs such as chloral, atropine, etc., to the blood. These changes have been attributed to the altered blood acting on the walls of the vessels, inducing, for instance, constriction or widening of the small arteries, or it may be affecting the capillaries, for it has been asserted that the epithelioid plates of the capillaries vary in form according to the relative quantities of carbonic acid and oxygen present in the blood. But this is not the whole explanation of the matter, since similar variations in resistance are met with when blood is driven through fine capillary tubes of inert matter. In such experiments it is found that the resistance to the flow increases with a diminution of the oxygen carried by the red corpuscles, and is modified by the addition to the blood of even small quantities of certain drugs. It is obvious then that in the living body the peripheral resistance, being the outcome of complex conditions, may be modified in many ways. Ex- perience teaches us that, even in dealing with non-living inert matter, the flow of fluid through capillary tubes may be modified on the one hand by changes in the substance of which the tubes are composed, and on the other hand by changes in the chemical nature (even independent of the specific gravity) of the fluid which is used. In the living body both the fluid, the blood, and the walls of the minute vessels being both alive, are incessantly subject to change ; the changes in the one, moreover, are capable of reacting upon and inducing changes in the other ; and, lastly, the changes both of the one and of the other may be primarily set going by events taking place in some part of the body far away from the region in which these changes are modifying the resistance to the flow. CHANGES IN THE QUANTITY OF BLOOD. § 172. In an artificial scheme changes in the total quantity of fluid in circulation will have an immediate and direct effect on the arterial pressure, increase of the quantity heightening and decrease diminishing it. This effect will be produced partly by the pump being more or less filled at each stroke, and partly by the peripheral resistance being increased or diminished by the greater or less fulness of the small peripheral channels. The venous CHANGES IN THE QUANTITY OF BLOOD. 237 pressure will under all circumstances be raised with the increase of fluid, but the arterial pressure will be raised in proportion only so long as the elastic walls of the arterial tubes are able to exert their elasticity. In the natural circulation the direct results of change of quantity are modified by compensatory arrangements. Thus experiment shows that when an animal with normal blood-pressure is bled from one carotid, the pressure in the other carotid sinks so long as ihe bleeding is going on,1 and remains depressed for a brief period after the bleeding has ceased. In a short time, however, it regains or nearly regains, the normal height. This recovery of blood-pressure, after hemorrhage, is witnessed so long as the loss of blood does not amount to more than about 3 per cent, of the body- weight. Beyond that a large and frequently a sudden dangerous permanent depression is observed. The restoration of the pressure after the cessation of the bleeding is too rapid to permit us to suppose that the quantity of fluid in the bloodvessels is repaired by the withdrawal of lymph from the extra-vascular elements of the tissues. In all probability the result is gained by an increased action of the vasomotor nerves, increasing the peripheral resistance, the vasomotor centres being thrown into increased action by the diminution of their blood- supply. When the loss of blood has gone beyond a certain limit, this vaso- motor action is insufficient to compensate the diminished quantity (possibly the vasomotor centres in part become exhausted), and a considerable de- pression takes place ; but at this epoch the loss of blood frequently causes anaemic convulsions. Similarly when an additional quantity of blood is injected into the vessels, no marked increase of blood-pressure is observed so long as the vasomotor centre in the medulla oblongata is intact. If, however, the cervical spinal cord be divided previous to the injection, the pressure, which on account of the removal of the medullary vasomotor centre is very low, is permanently raised by the injection of blood. At each injection the pressure rises, falls somewhat afterward, but eventually remains at a higher level than before. This rise is stated to continue until the amount of blood in the vessels above the normal quantity reaches from 2 to 3 per cent, of the body-weight, be- yond which point it is said no further rise of pressure occurs. These facts seem to show, in the first place, that when the volume of the blood is increased, compensation is effected by a lessening of the peripheral resistance by means of a vaso-dilator action of the vasomotor centres, so that the normal blood-pressure remains constant. They further show that a much greater quantity of blood can be lodged in the bloodvessels than is normally present in them. That the additional quantity injected does re- main in the vessels is proved by the absence of extravasations and of any considerable increase of the extra-vascular lymphatic fluids. It has already been insisted that, in health, the veins and capillaries must be regarded as being far from filled, for were they to receive all the blood which they can, even at a low pressure, hold, the whole quantity of blood in the body would be lodged in them alone. In these cases of large addition of blood the extra quantity appears to be lodged in the small veins and capillaries (espe- cially of the internal organs), which are abnormally distended to contain the surplus. We learn from these facts the two practical lessons, first, that blood- pressure cannot be lowered directly by bleeding, unless the quantity removed be dangerously large, and secondly, that there is no necessary connection 1 Chiefly in consequence of the free opening in the vessel from which the bleeding is going on cutting off a great deal of the peripheral resistance and so leading to a general lowering of the blood-pressure. 238 THE VASCULAR MECHANISM. between a high blood-pressure and fulness of blood or plethora, since an enormous quantity of blood may be driven into the vessels without any marked rise of pressure. A REVIEW OF SOME OF THE FEATURES OF THE CIRCULATION. § 173. The facts dwelt on in the foregoing sections have shown us that the factors of the vascular mechanism may be regarded as of two kinds: one constant or approximately constant, the other variable. The constant factors are supplied by the length, natural bore, and distri- bution of the bloodvessels, by the extensibility and elastic reaction of their walls, and by such mechanical contrivances as the valves. By the natural bore of the various bloodvessels is meant the diameter which each would assume if the muscular fibres were wholly at rest, and the pressure of fluid within the vessel were equal to the pressure outside. It is obvious, however, that even these factors are only approximately constant for the life of an individual. The length and distribution of the vessels change with the growth of the whole body or parts of the body, and the physical qualities of the walls, especially of the arterial walls, their extensibility, and elastic reaction change continually with the age of the individual. As the body grows older the once supple and elastic arteries become more and more stiff and rigid, and often in middle life, or it may be earlier, a lessening of arterial resilience which proportionately impairs the value of the vascular mechanism as an agent of nutrition, marks a step toward the grave. The valvular mechanisms, too, also show signs of age as years advance, and more or less marked and increasing imperfections diminish the usefulness of the machine. The chief variable factors are, on the one hand, the beat of the heart, and, on the other, the peripheral resistance, the variations in the latter being chiefly brought about by muscular contraction or relaxation in the minute arteries, but also, though to what extent has not yet been accurately deter- mined, by the condition of the walls of the minute vessels according to which the blood can pass through them with less or with greater ease, as well as by the character of the circulating blood. § 174. These two chief variables, the beat of the heart and the width of the minute arteries, are known to be governed and regulated by the cen- tral nervous system, which adapts each to the circumstance of the moment, and at the same time brings the two into mutual interdependence ; but the central nervous system is not the only means of government ; there are other modes of regulation, and so other safeguards. Thus while undoubtedly the two prominent governors of the heart are the inhibitory fibres of the vagus and the augmentor fibres from the splanch- nic system, the one slowing the rhythm and weakening the stroke, the other quickening the rhythm and strengthening the stroke, other causes may vary the beat in the absence of any action of either of these two nerves. Mere distention of the ventricle, by increasing the tension of the ventricular fibres, and so increasing the force of the contraction of each fibre (see § 148), brings about a more forcible beat. As we shall see in dealing with respiration, a powerful inspiration leads to a larger flow of blood into the heart, and forthwith the ventricle, out of its very fulness, gives stronger beats for the time. So also when by valvular disease or otherwise an un- usual obstacle is presented to the outflow from the ventricle, increased vigor in the strokes of the distended organ strives to compensate the mischief. As, however, in the case of the skeletal muscle, the tension, if too great, may be injurious. In a similar manner the auricle, by a stronger or a weaker con- SOME FEATURES OF THE CIRCULATION. 239 traction, may distend the ventricle to a greater or to a less extent, and so produce a stronger or weaker ventricular systole. § 175. Still more efficient, perhaps, as a direct governor of the heart's beat is the quality and quantity of blood passing in the mammal through the coronary arteries and regulating the nutrition of the cardiac substance. In the absence of all interference by inhibitory and augmentor fibres the heart will continue beating with a certain rhythm and force, determined by the metabolism going on certainly in its muscular, and possibly to a certain extent also in its nervous elements. We have seen that the energy set free in an ordinary skeletal muscle, in response to a stimulus, may vary from nothing to a maximum according to the metabolism going on — according to the nutritive vigor of the muscular fibres. The spontaneous rhythmic beat of the cardiac substance may be regarded as the outcome of a metabolism more highly pitched, more elaborate, of a higher order than that which simply furnishes the ordinary skeletal fibre with mere irritability toward stimuli. All the more, therefore, may the beat be expected to be influenced by any change in the metabolism of the cardiac substance, and so by any change in the blood which furnishes the basis for that metabolism. Hence the beat of the heart, quite apart from extrinsic nervous influences, may vary largely in consequence of changes in its own metabolism, which in turn may result from alterations in the blood-supply, or may have a deeper origin, and be due to the fact that the cardiac substance, owing to failure in its molecular organization (a failure which may be temporary or permanent), is unable to avail itself properly of the nutritive opportunities afforded by a normal quantity of normal blood. § 176. As is well known, the beat of the heart may become temporarily or permanently irregular ; that many hearts go on beating day after day, year after year, without any such irregularity is a striking proof of the com- plete balance which usually obtains between the several factors of which we are speaking. Sometimes such cardiac irregularities, those of a transient nature and brief duration, are the results of extrinsic nervous influences. Some events taking place in the stomach, for instance, give rise to afferent im- pulses which ascending from the mucous membrane of the stomach along cer- tain afferent fibres of the vagus to the medulla oblongata, so augment the action of the cardio-inhibitory centre as to stop the heart for a beat or two, the stoppage being frequently followed by a temporary increase in the rapid- ity and force of the beat. Such a passing failure of the heart-beat, in its sud- den onset, in its brief duration, and in the reaction which follows, very closely resembles the temporary inhibition brought about by artificial stimu- lation of the vagus. But these characters are not essential to cardiac inhibi- tion. For it must be remembered that the central nervous system possesses, in the form of natural nervous impulses of various origin, a means of stimu- lation far finer, more delicate and more varied than anything we can effect by our rough means of induction coils and electrodes. Thus in many cases of fainting, the heart-beats, instead of stopping abruptly, gradually die away or fade away it may be to an absolute brief arrest, but more frequently merely down to a feebleness which is insufficient to supply the brain with a quantity of blood adequate to maintain consciousness, and then in many cases, at all events, are resumed, or recover strength gradually and quietly without any boisterous reaction. In all probability all cases of simple faint- ing from emotion, pain, digestive troubles, etc., as distinguished from the syncope of actual heart disease, are instances of vagus inhibition, and though we cannot accurately reproduce their varied phases by direct stimulation of the vagus trunk, we may approach them more nearly by producing reflex inhibition, as by mechanical irritation of the abdomen. (See § 145.) 240 THE VASCULAK MECHANISM. Whether definite temporary irregularity is ever brought about by means of the augmentor fibres we have at present no clear evidence ; but cases do occur of palpitation without previous stoppage, cases in which a few hurried strong beats come on, pass off, and are followed by feebler beats ; and these may possibly be due to some transient influence of augmentor fibres thrown into activity as part of a reflex act or otherwise. And though we have no direct experimental evidence, it is very probable that the acceleration or augmentation of the beat, or a combination of the two, which so often follows emotion, is carried out by augmentor fibres. In all probability, however, irregularity in the heart-beat is much more frequently the result of intrinsic events, or the product of a disordered nutri- tion of the cardiac substance. The normal nutrition sets the pace of the normal rhythm. We cannot explain how this is affected ; nor can we explain why in one individual the normal pace is set so low as 50 or even 30 beats a minute, and in another as high as 90 a minute or even more, while in most persons it is about 70 a minute. The slower or the quicker the pace, though not normal to the species, must be considered as normal to the individual, for it may be kept up through long years in an organism capable of carry- ing on a normal man's duties and work. So long as we cannot explain these differences we cannot hope to explain how it is that a disordered nutrition brings about an irregular heart-beat, either the more regular irregularity of a " dropping " pulse, that is, a failure of sequence rather than an irregularity, or a more actively irregular rhythm, such as that accompanying a dilated ventricle. We may, however, distinguish two kinds of irregularity : one in which, in spite of all favorable nutritive conditions, the cardiac substance cannot secure, even perhaps for a minute, a steady rhythm ; and another in which the rhythm, though normal under ordinary circumstances, is, so to speak, in a condition of unstable equilibrium, so that a very slight change in conditions, too much or too little blood, or some small alteration in the composition of the blood, or the advent of some, it may be slight, nervous impulse, augmentor or inhibitory, develops a temporary irregularity. § 177. No one thing, perhaps, concerning the heart is more striking than the fact that a heart which has gone on beating for many years, with only temporary irregularities, and those few and far between, a heart which must, therefore, have executed with long-continued regularity, many mill- ions of beats, should suddenly, apparently without warning, after a brief, flickering struggle, cease to beat any more. But we must remember that each beat is an effort — an effort, moreover, which, as we have seen (§ 141), is the best that the heart can make at the moment ; the accom- plishment of each beat is, so to speak, a hurdle which has to be leaped — one of the long series of hurdles which make up the steeple-chase of life. At any one leap failure may occur ; so long as failure does not occur, so long as the beat is made, and a fair proportion of the ventricular contents are discharged into the great vessels, the chief end is gained, and whether the leap is made clumsily or well is, relatively considered, of secondary im- portance. But if the beat be not made, everything almost (provided that the miss be due, not to vagus inhibition, but to intrinsic events) is unfavorable for a succeeding beat ; the mysterious molecular changes, by which the actual occurrence of one beat prepares the way for the next, are missing, the favorable influences of the extra rush of blood through the coronary arteries due to a preceding beat are missing also, and even the dis- tention of the cardiac cavities, at first favorable, speedily passes the limit and becomes unfavorable. And these untoward influences accumulate rapidly as the first miss is followed by a second and by a third. In this way a heart, which has been brought into a state of unstable equilibrium SOME FEATUKES OF THE CIRCULATION. 241 by disordered nutrition (as, for instance, by imperfect coronary circulation, such as seems to accompany diseases of the aortic valves leading to regur- gitation from the aorta into the ventricle, in which cases sudden death i& not uncommon), which is able just to accomplish each beat, but no more, which has but a scanty saving store of energy, under some strain or other untoward influence, misses a leap, falls, and is no more able to rise. Doubt- less in such cases could adequate artificial aid be promptly applied in time, could the fallen heart be stirred even to a single good beat, the favorable reaction of that beat might bring a successor, and so once more start the series ; but such a period of grace, of potential recovery, is a brief one. Even a coarse skeletal muscle, when cut off from the circulation, soon loses its irritability beyond all recovery, and the heart cut off from its own influ- ence on itself runs down so rapidly that the period of possible recovery is measured chiefly by seconds. § 178. Turning now to the minute arteries and the peripheral resist- ance which they regulate, we may call to mind the existence of the two kinds of mechanism, the vaso-constrictor mechanism, which, owing to the maintenance by the central nervous system of a tonic influence, can be worked both in a positive constrictor and in a negative dilator direc- tion, and the vaso-dilator mechanism, which, as far as we know, exerts its influence in one direction only, viz., to dilate the bloodvessels. The latter dilator mechanism seems, as we have seen, to be used in special instances only, as seen in the cases of the chorda tympani and nervi erigentes ; the use of the former constrictor mechanism appears to be more general. Thus the relaxation of the cutaneous arteries of the head and neck, which is the essential feature in blushing, seems due to mere loss of tone, to the removal of constrictor influences previously exerted through the vaso-constrictor fibres of the cervical sympathetic. Though probably dilator fibres pass directly along the roots of the cervical and of certain cranial nerves to the nerves of the head and neck, we have no evidence that these come into play in blushing ; as we have seen, blushing may be imitated by mere sec- tion of the cervical sympathetic. So also the " glow " and redness of the skin of the whole body — i. e., dilatation generally of the cutaneous arteries — which is produced by external warmth, is probably another in- stance of diminished activity of tonic constrictor influences ; though the result, that the dilatation produced by warming an animal in an oven is greater than that produced by section of nerves, seems to point to the dilator fibres for the cutaneous vessels which, as we have seen, probably exist in the sciatic and brachial plexuses and possibly in all the spinal nerves, also taking part in the action. A similar loss of constrictor action in the cutaneous vessels may be the result of certain emotions, whether going so far as actual blushing of the body, or merely producing a " glow." The effect of cold, on the other hand, and of certain emotions, or of emotions under certain conditions, is to increase the constrictor action on the cutane- ous vessels, and the skin grows pale. It may be worth while to point out that in both the above cases, while both the cold and warmth produce their effect chiefly at all events through the central nervous system, and very slightly, if at all, by direct action on the skin, their action on the central nervous system is not simply a general augmentation or inhibition of the whole vasomotor centre. On the contrary, the cold, while it constricts the cutaneous vessels, so acts on the vasomotor centre as to inhibit that portion of the vasomotor centre which governs the abdominal splanchnic area ; while less blood is carried to the colder skin, by the opening up of the splanchnic area more blood is turned on to the warmer regions of the body,, and the rise of blood-pressure which the constriction of the cutaneous vessels 16 242 THE VASCULAR MECHANISM. tended to produce, and which might be undesirable, is thereby prevented. Conversely when warmth dilates the cutaneous vessels, it at the same time constricts the abdominal splanchnic area, and prevents an undesirable fall of pressure. The warm and flushed condition of the skin, which follows the drink- ing of alcoholic fluids, is probably in a similar manner the result of an in- hibition of that part of the vasomotor centre which governs the cutaneous arteries ; and it is probable also that except for the local effect of the fluid on the gastric mucous membrane, whereby some amount of blushing of the gastric bloodvessels takes place as a reflex act, this effect on the vessels of the skin is accompanied by an inverse constrictor action in the splanch- nic area. This last point, however, has not been proved experimentally and may not occur, since the influence of the alcohol is at the same time to increase the heart's action, and thus to obviate the fall of pressure which would certainly occur were the cutaneous and splanchnic vascular areas to be dilated at the same time. This effect of the alcohol on the heart may be a direct action of the alcohol on the cardiac substance, being car- ried thither by the blood ; but the effect, in being an augmentation of the force, and acceleration of the pace of the heart-beat of a temporary character, followed by a reaction in the direction of feebleness and slowness, so strik- ingly resemble the effects of artificially stimulating the cardiac augmentor fibres, that it is at least probable that the alcohol does act upon the cardiac augmentor mechanism. § 179. The influence on the body of exercise illustrates both the manner in which the two vascular factors, the heart-beat and the peripheral resist- ance, are modified by circumstances, and the mutual action of these on each other. When the body passes from a condition of comparative rest and quiet to one of exertion and movement, the metabolism of the skeletal muscles (and of the nervous system) is increased and more heat is generated in them. We know for certain that the increased metabolism throws into the blood of the veins coming from the muscles an increased amount of carbonic acid, and it is probable, but not so certain, that it also loads the blood with lactic acid and other metabolic products ; at the same time, there is an increased consumption of oxygen ; the blood of the body tends to become less arterial and more venous. In dealing with respiration, we shall see that the influ- ence thus exerted on the blood leads to an increase in the respiratory move- ments, and we shall further see that the more vigorous working of the respiratory pump, since it promotes the flow of blood to and through the heart and lungs, quickens and strengthens the heart-beats. Possibly this mere mechanical effect of the more vigorous breathing is sufficient by itself to account for the increase in the frequency and vigor of the heart's action, but it is more than probable that it is the changed condition of the blood, which, while it hurries on the respiratory pump, also stimulates the vascular pump, either by a direct action on the cardiac substance, or through the medium of the central nervous system and the augmentor fibres. If, as experiments seem to show, the increased vigor of the respiratory movements compensates, or even over-compensates, the tendency of the whole blood to become more venous, so that during exercise the blood, which is distributed by the aorta, actually does not contain more carbonic acid and less oxygen than the rest, but even the reverse, then these efforts must be due to some of the products of muscular metabolism other than carbonic acid. The same changed condition of blood, while it thus excites the heart, di- lates the cutaneous vessels, as is clearly shown by the warm flushed skin, and at the same time throws into activity the perspiratory mechanism with which SOME FEATURES OF THE CIRCULATION. 243 we shall hereafter have to deal. There can be no doubt, as we shall see later on, that the perspiration which accompanies muscular exercise is brought about by means of the central nervous system, and we may almost with certainty conclude that the dilatation of the cutaneous arteries is also brought about by means of the central nervous system, and most probably by means of an inhibition of that part of the vasomotor centre which main- tains under ordinary circumstances a greater or less tonic constriction of the cutaneous arteries ; how far this may be assisted by the special action of vaso-dilator fibres we do not know. This widening of the cutaneous arteries diminishes largely the peripheral resistance, and so tends to lower the blood-pressure. Moreover, with each effort of each skeletal muscle the minute arteries of that muscle are dilated, so that during exercise, and especially during vigorous exercise calling into action many skeletal muscles, there must be in the body at large a very con- siderable widening of the minute arteries distributed to the various muscles, and in consequence a very considerable diminution of the peripheral resist- ance. These two diminutions of peripheral resistance, cutaneous and mus- cular, would tend to lower the blood-pressure — a result which would be most injurious, since the increased metabolism of the muscles demands a more rapid circulation in order to get rid of the products of metabolism, and for a rapid circulation a high blood-pressure is in most cases necessary, and in all cases advantageous. The evil is, in part at all events, met by the increased force and frequency of the heart's beats, for, as we have said again and again, the mean blood-pressure is the product of the heart-beat working against the peripheral resistance, and may remain constant when one factor is increased or diminished, provided that the other factor be proportionately diminished or increased. It is possible, then, that the mere increase in the heart's beats are, during exercise, sufficient to neutralize the diminution of peripheral resistance, or even to raise the blood-pressure above the normal ; and, indeed, we find, as a matter of fact, that during exercise there is such an increase of the mean blood-pressure. But it is more than probable that much valuable labor of the heart is economized by neutralizing the imminent fall of blood-pressure in another manner. It would appear that while that part of the vasomotor centre which governs the cutaneous vascular area is being inhibited, that part which governs the abdominal splanchnic area is, on the contrary, being augmented. And in this way a double end is gained. On the one hand, the mean blood-pressure is maintained or increased in a more economical manner than by increasing the heart-beats, and, on the other hand, the blood during the'exercise is turned away from the digestive organs, which at the time are, or ought to be, at rest, and therefore requiring comparatively little blood. These organs certainly, at all events, ought not during exercise to be engaged in the task of digesting and absorbing food, and the old saying, " after dinner sit a while," may serve as an illustration of the working of the vascular mechanism with which we are dealing. The duty which some of the digestive organs have to carry out in the way of excretion of metabolic waste products is during exercise probably taken on by the flushed and perspiring skin. It is true that at the beginning of a period of exercise, before the skin, so to speak, has settled down to its work, an increased flow of urine, dependent on or accompanied by an increased flow of blood through the kidney, may make its appearance ; but in this case, as we shall see later on in dealing with the kidney, the flow of blood through the kidney may be increased in spite of constriction of the rest of the splanchnic area* and, besides, such an initial increase of urine speedily gives way to a decrease. § 180. The effect of food on the vascular mechanism affords a marked 244 THE VASCULAR MECHANISM. contrast to the effect of bodily labor. The most marked result is a widening of the whole abdominal splanchnic area, accompanied by so much constric- tion of the cutaneous vascular area, and so much increase of the heart's beat, as is sufficient to neutralize the tendency of the widening of the splanchnic area to lower the mean pressure, or perhaps even sufficient to raise slightly the mean pressure. Any large widening of the cutaneous area, especially if accompanied by muscular labor and the incident widening of the arteries of the muscles, would tend so to lower the general blood-pressure (unless met by a wasteful use of cardiac energy) as injuriously to lessen the flow through the active digesting viscera. A moderate constriction of the cutaneous vessels, on the other hand, by throwing more blood on the abdominal splanchnic area with- out tasking the heart, is favorable to digestion, and is probably the physio- logical explanation of the old saying, " If you eat till you're cold, you'll live to be old." In fact, during life there seems to be a continual give-and-take between the bloodvessels of the somatic and those of the splanchnic divisions of the body ; to fill the one, the other is proportionately emptied, and vice versa. ^ § 181. We have seen (§ 160) that certain afferent fibres of the vagus forming in the rabbit a separate nerve, the depressor nerve, are associated with the vaso-constrictor nerves and the vasomotor centre in such a way that impulses passing centripetally along them from the heart lower the blood- pressure by diminishing the peripheral resistance, probably inhibiting the tonic constrictor influences exerted along the abdominal splanchnic nerves, and so, as it were, opening the splanchnic flood-gates. We do not possess much exact information about the use of these afferent depressor fibres in the living body, but probably when the heart is laboring against the blood- pressure which is too high for its powers, the condition of the heart starts impulses which, passing along the depressor fibres up to the medulla oblongata, temper down, so to speak, the blood-pressure to suit the cardiac strength. We have, moreover, reason to think that not only does the heart thus regulate the blood-pressure by means of the depressor fibres, but also that the blood-pressure, acting, as it were, in the reverse direction, regulates the heart-beat ; a too high pressure, by acting directly on the cardio-inhibitory centre in the medulla oblongata (either directly — that is, as the result of the vascular condition of the medulla itself — or indirectly, by impulses reaching the medulla along afferent nerves from various parts of the body) may send inhibitory impulses down the vagus, or so slacken or tone down the heart-beats. In the following sections of this work we shall see repeated instances, similar to or even more striking than the above, of the management of the vascular mechanism by means of the nervous system, and we, therefore, need dwell no longer on the subject. We may simply repeat that at the centre lies the cardiac muscular fibrer and at the periphery the plain muscular fibre of the minute artery. On these two elements the central nervous system, directed by this or that impulse reaching it along afferent nerve fibres, or affected directly by this or that influence, is during life continually playing, now augmenting, now inhibiting, now the one, now the other, and so, by help of the elasticity of the arteries and the mechanism of the valves, directing the blood-flow ac- cording to the needs of the body. BOOK II. THE TISSUES OF CHEMICAL ACTION, THEIR RESPECTIVE MECHANISMS, NUTRITION. CHAPTER I. THE TISSUES AND MECHANISMS OF DIGESTION. § 182. THE food in passing along the alimentary canal is subjected to the action of certain juices supplied by the secretory activity of the epithe- lial cells which line the canal itself or which form part of its glandular appendages. These juices, viz., saliva, gastric juice, bile, pancreatic juice, and the secretions of the small and large intestines, poured upon and min- gling with the food produce in it such changes that, from being largely insol- uble, it becomes largely soluble, or otherwise modify it in such a way that the larger part of what is eaten passes into the blood, either directly by means of the capillaries of the alimentary canal, or indirectly by means of the lacteal system, while the smaller part is discharged as excrement. Those parts of the food which are thus digested, absorbed, and made use of by the body, are spoken of as food-stuffs (they have also been called alimentary principles'), and may be conveniently divided into four great classes : 1. Proteids. We have previously (§ 15) spoken of the chief characters of this class, and have dealt with several members in treating of blood and muscle. We may here repeat that in general composition they contain in 100 parts by weight " in round numbers" rather more than 15 parts of nitrogen, rather more than 50 parts of carbon, about 7 parts of hydrogen, and rather more than 20 parts of oxygen ; though essentially the nitro- genous bodies of food and of the body, they are made up of carbon to the extent of more than half their weight. The nitrogenous body gelatin, which occurs largely in animal food, and some other bodies of less importance, while more closely allied to proteid bodies than to any other class of organic substances, differ considerably from proteids in composition and especially in their behavior in the body ; they are not of sufficient importance to form a class by themselves. 2. Fats, frequently but erroneously called hydrocarbons. These vary very widely in chemical composition, ranging from such a comparatively simple fat as butyrin to the highly complex lecithin (§ 69) ; they all possess, in view of the oxidation of both their carbon and their hydrogen, a large amount of potential energy. 3. Carbohydrates, or sugars and starches. These possess, weight for weight, relatively less potential energy than do fats ; they already contain in themselves a large amount of combined oxygen, and when completely oxidized give out, weight for weight, less heat than do fats. 245 246 THE TISSUES AND MECHANISMS OF DIGESTION. 4. Saline or mineral bodies, and water. These salts are for the most part inorganic salts, and this class differs from the three preceding classes inas- much as the usefulness of its members to the body lies not so much in the amount of energy which may be given put by their oxidation as in the various influences which, by their presence, they exercise on the metabolic events of the body. These several food-stuffs are variously acted upon in the several parts of the alimentary canal, and we may distinguish, as the food passes along the digestive tract, three main stages : digestion in the mouth and stomach, digestion in the small intestine, and digestion in the large intestine. In many animals the first stage is, to a large extent, preparatory only to the second, which in all the animals is the stage in which the food undergoes the greatest change ; in the third stage the changes begun in the previous stages are completed, and this stage is especially characterized by the absorp- tion of fluid from the interior of the alimentary canal. It will be convenient to study these stages more or less apart, though not wholly so, and it will also be convenient to consider the whole subject of digestion under the following heads : First, the characters and properties of the various juices and the changes which they bring about in the food eaten. Secondly, the nature of the processes by means of which the epithelium cells of the various glands and various tracts of the canal are able to manu- facture so many various juices out of the common source, the blood, and the manner in which the secretory activity of the cells is regulated and subjected to the needs of the economy. Thirdly, the mechanisms, here as elsewhere, chiefly of a muscular nature, by which the food is passed along the canal and most efficiently brought into contact with the several juices. Fourthly and lastly, the means by which the nutritious digested material is separated from the undigested or excremental material and absorbed into the blood. THE CHARACTERS AND PROPERTIES OF SALIVA AND GASTRIC JUICE. Saliva. § 183. Mixed saliva, as it appears in the mouth, is a thick, glairy, gen- erally frothy and turbid fluid. Under the microscope it is seen to contain, beside the molecular debris of food, bacteria and other organisms (fre- quently cryptogamic spores), epithelium scales, mucous corpuscles and granules, and the so-called salivary corpuscles. Its reaction in a healthy subject is alkaline, especially when the secretion is abundant. When the saliva is scanty, or when the subject suffers from dyspepsia, the reaction of the mouth may be acid. Saliva contains but little solid matter, on an aver- age probably about 5 per cent., the specific gravity varying from 1002 to 1006. Of these solids, rather less than half, about 2 per cent., are salts (including at times a minute quantity of potassium sulphocyanate). The organic bodies which can be recognized in it are globulin and serum albumin (see §§ 16, 17), found in small quantities only — other obscure bodies occur- ring in minute quantity, and mucin ; the latter is by far the most conspicu- ous organic constituent, the glairiness or ropiness of mixed and other kinds of saliva being due to its presence. Mucin. If acetic acid be cautiously added to mixed saliva, the viscidity of the saliva is increased, and on further addition of the acid a semi-opaque ropy mass separates out, leaving the rest of the saliva limpid. This ropy SALIVA AND GASTRIC JUICE. 247 mass, which is mucin, if stirred carefully with a glass rod, shrinks, becoming opaque, clings to the glass rod, and may be thus removed from the fluid. If the quantity of mucin be small and the saliva be violently shaken or stirred while the acid is being added, the mucin is apt to be precipitated in flakes, and may then be separated by filtration. It may be added that the precipi- tation of mucin by acid is greatly influenced by the presence of sodium chloride and other salts ; thus, after the addition of sodium chloride, acetic acid, even in considerable excess, will not cause a precipitate of mucin. Mucin, thus prepared and purified by washing with acetic acid, swells out in water without actually dissolving ; it will, however, dissolve into a viscid fluid readily in dilute (0.1 per cent.) solutions of potassium hydrate, more slowly in solutions of alkaline salts. In order to filter a mucin solu- tion, great dilution with water is necessary. Mucin is precipitated by strong alcohol and by various metallic salts ; it may also be precipitated by dilute mineral acids, but the precipitate is then soluble in excess of the acid. Mucin gives the three proteid reactions mentioned in § 15, but it is a very complex body, more complex even than proteids, for by treatment with dilute mineral acids and in other ways, it may be converted into some form of proteid (acid-albumin when dilute mineral acid is used), while at the same time there is formed a body which appears to be carbohydrate and resembles a sugar in having the power of reducing cupric sulphate solutions. Solutions of mucin, moreover, on mere keeping are apt to lose their viscidity and to become converted into a proteid not unlike the body peptone, which, as we shall see, is the result of gastric digestion, and into a reducing body. Several kinds of mucin appear to exist in various animal bodies, but they seem all to agree in the character that they can by appropriate treatment be split up into a proteid of some kind and into a carbohydrate or allied body. § 184. The chief purpose served by the saliva in digestion is to moisten and soften the food and to assist in mastication and deglutition. In some animals this is its only function. In other animals and in man it has a specific solvent action on some of the food-stuffs. Such minerals as are soluble in slightly alkaline fluids are dissolved by it. On fats it has no effect save that of producing a very feeble emulsion. On proteids it has also no specific action, though pieces of meat, cooked or uncooked, appear greatly altered after they have been masticated for some time ; the chief alteration, however, which thus takes place is a change in the haemoglobin and a general softening of the muscular fibres by aid of the alkalinity of the saliva. Of course, when particles of food are retained for a long time in the mouth, as in the interstices or in cavities of the teeth, the bacteria or other organ- isms which are always present in the mouth may produce much more pro- found changes, but these are not the legitimate products of the action of saliva. The characteristic property of saliva is that of converting starch into some form of sugar. Action of saliva on starch. If to a quantity of boiled starch, which is always more or less viscid and somewhat opaque or turbid, a small quantity of saliva be added, it will be found after a short time that an important change has taken place, inasmuch as the mixture has lost its previous viscidity and become thinner and more transparent. In order to under- stand this change the reader must bear in mind the existence of the follow- ing bodies, all belonging to the class of carbohydrates : 1. Starch, which forms with water not a true solution but a more or less viscid mixture, and gives a characteristic blue color with iodine. The for- mula is C6H10O5, or more correctly (C6H10O5)n since the molecule of starch 248 THE TISSUES AND MECHANISMS OF DIGESTION. is some multiple (n being not less than 5) of the simpler formula. A kind of starch known as soluble starch, while giving a blue color with iodine, forms, unlike ordinary starch, a clear solution. 2. Dextrin*, differing from starch in forming a clear solution. Of these there are at least two ; one, erythrodextrin, often spoken of simply as dextrin, giving a port-wine red color with iodine, and second, achroodextrin, which gives no color at all with iodine. The formula for dextrin is the same as that for starch, but has a smaller molecule and might be represented by (c6H10o5r. 3. Dextrose, also called glucose or grape-sugar, giving no coloration with iodine, but characterized by the power of reducing cupric and other metallic salts ; thus, when dextrose is boiled with a fluid known as Fehling's fluid, which is a solution of hydrated cupric oxide in an excess of caustic alkali and double tartrate of sodium and potassium, the cupric oxide is reduced and a red or yellow deposit of cuprous oxide is thrown down. This reaction serves with others as a convenient test for dextrose. Neither starch nor that commonest form of sugar known as cane-sugar gives the reaction ; whether the dextrins do is doubtful. The formula for dextrose is C6H,2O6 ; it is more simple than that of starch or dextrin and contains an additional H2O for every C6. Unlike starch and dextrin it can be obtained in a crystalline form, either from aqueous solutions (it being readily soluble in water), in which case the crystals contain water of crystallization, or from its solutions in alcohol (in which it is sparingly soluble), in which case the crystals have no water of crystallization. Solutions of dextrose have a marked dextro- rotatory power with rays of light. 4. Maltose, very similar to dextrose, and like it capable of reducing cupric salts. The formula is somewhat different, being C^H^On. Besides this, it differs from dextrose chiefly in its smaller power — i. e., a given weight will not convert so much cupric oxide into cuprous oxide as will the same weight of dextrose — and in having a stronger rotatory action on rays of light. Like dextrose it can be crystallized, the crystals from aqueous solutions con- taining water of crystallization. Now, when a quantity of starch is boiled with water we may recognize in the viscid imperfect solution, on the one hand, the presence of the starch by the blue color which the addition of iodine gives rise to ; and on the other hand, the absence of sugar (maltose, dextrose), by the fact that when boiled with Fehling's fluid no reduction takes place and no cuprous oxide is precipitated. If, however, the boiled starch be submitted for a while to the action of saliva, especially at a somewhat high temperature such as 35° or 40° C., it is found that the subsequent addition of iodine gives no blue color at all or very much less color, showing that the starch has disappeared or diminished ; on the other hand, the mixture readily gives a precipitate of cuprous oxide when boiled with Fehling's fluid, showing that maltose or dextrose is present. That is to say, the saliva has converted the starch into maltose or dextrose. The presence of the previously absent sugar may also be shown by fermentation arid by the other tests for sugar. Moreover, if an adequately large quantity of starch be subjected to the charge, the sugar formed may be isolated, and its characters determined. When this is done it is found that while some dextrose is formed the greater part of the sugar which appears is in the form of maltose. As is well known, starch may, by the action of dilute acid, be converted into dextrin, and by further action into sugar ; but the sugar thus formed is always wholly dextrose, and not maltose at all. The action of saliva in this respect differs from the action of dilute acid. SALIVA AND GASTRIC JUICE. 249 While the conversion of the starch by the saliva is going on the addition of iodine, frequently gives rise to a red or violet color instead of a pure blue, but when the conversion is complete no coloration at all is observed. The appearance of this red color indicates the presence of dextrin (erythrodex- trin) ; the violet color is due to the red being mixed with the blue of still unchanged starch. The appearance of dextrin shows that the action of the saliva on the starch is somewhat complex ; and this is still further proved by the fact that even when the saliva has completed its work the whole of the starch does not reappear as maltose or dextrose. A considerable quantity of the other dextrin (achroodextrin) always appears and remains unchanged to the end ; and there are probably several other bodies also formed out of the starch, the relative proportions varying according to circumstances. The change, therefore, though perhaps we may speak of it in a general way as one of hydration, cannot be exhibited under a simple formula, and we may rest content for the present with the statement that starch when subjected to the action of saliva is converted chiefly into the sugar known as maltose with a comparatively small quantity of dextrose and to some extent into achroodextrin (erythrodextrin appearing temporarily only in the pro- cess), other bodies on which we need not dwell being formed at the same time. Raw unboiled starch undergoes a similar change but at a much slower rate. This is due to the fact that in the curiously formed starch grain the true starch, or granulose, is invested with coats of cellulose. This latter material, which requires previous treatment with sulphuric acid before it will give the blue reaction on the addition of iodine, is apparently not acted upon by saliva. Hence the saliva can only get at the grauulose by travers- ing the coats of cellulose, and the conversion of the former is thereby much hindered and delayed. § 185. The conversion of starch into sugar, and this we may speak of as the amylolytic action of saliva, will go on at the ordinary temperature of the atmosphere. The lower the temperature the slower the change, and at about 0° C. the conversion is indefinitely prolonged. After exposure to this cold for even a considerable time the action recommences when the temperature is again raised. Increase of temperature up to about 35°-40°, or even a little higher, favors the change, the greatest activity being said to be manifested at about 40°. Much beyond this point, however, increase of temperature becomes injurious, markedly so at 60° or 70° ; and saliva which has been boiled for a few minutes not only has no action on starch while at that temperature, but does not regain its powers on cooling. By being boiled, the amylolytic activity of saliva is permanently destroyed. The action of saliva on starch is most rapid when the reaction of the mixture is neutral or nearly so ; it is hindered or arrested by a distinctly acid reaction. Indeed, the presence of even a very small quantity of free acid, at all events of hydrochloric acid, at the temperature of the body, not only suspends the action but speedily leads to permanent abolition of the activity of the juice. The bearing of this will be seen later on. The action of saliva is hampered by the presence in a concentrated state of the product of its own action — that is, of sugar If a small quantity of saliva be added to a thick mass of boiled starch, the action will after a while slacken, and eventually come to almost a standstill, long before all the starch has been converted. On diluting the mixture with water, the action will recommence. If the products of action be removed as soon as they are formed, dialysis for example, a small quantity of saliva will, if sufficient time 250 THE TISSUES AND MECHANISMS OF DIGESTION. be allowed, convert into sugar a very large, one might almost say an indef- inite, quantity of starch. Whether the particular constituent on which the activity of saliva depends is at all consumed in its action has not at present been definitely settled. On what constituents do the amylolytic virtues of saliva depend ? If saliva, filtered and thus freed from much of its mucin and from other formed constituents, be treated with ten or fifteen times its bulk of alcohol, a precipitate is formed containing, besides other substances, all the proteid matters. Upon standing under the alcohol for some time (several days), the proteids thus precipitated become coagulated and insoluble in water. Hence, an aqueous extract of the precipitate, made after this interval, contains very little proteid material ; yet it is exceedingly active. Moreover, by other more elaborate methods there may be obtained from saliva solutions which appear to be almost entirely free from proteids and yet are intensely amylo- lytic. But even these probably contain other bodies beside the really active constituent. Whatever the active substance be in itself, it exists in such extremely small quantities that it has never yet been satisfactorily isolated ; and indeed the only clear evidence we have of its existence is the manifesta- tion of its peculiar powers. The salient features of this body, this amylolytic agent, which we may call ptyalin, are then : 1st, its presence in minute and almost inappreciable quan- tity. 2d, the close dependence of its activity on temperature. 3d, its perma- nent and total destruction by a high temperature and by various chemical reagents. 4th, the want of any clear proof that it itself undergoes any change during the manifestations of its power — that is to say, the energy necessary for the transformation which it effects does not come out of itself; if it is at all used up in its action, the loss is rather that of simple wear and tear of a machine than that of a substance expended to do work. 5th, the action which it induces is probably of such a kind (splitting up of a mole- cule with assumption of water) as is effected by that particular class of agents called " hydrolytic." These features mark out the amylolytic active body of saliva as belong- ing to the class of ferments;1 and we may henceforward speak of the amylolytic ferment of saliva. The fibrin-ferment (§ 20) is so called because its action in many ways resembles that of the ferment of which we are now speaking. § 186. Mixed saliva, whose properties we have just discussed, is the result of the mingling in various proportions of saliva from the parotid, submaxillary, and sublingual glands with the secretion from the buccal glands. These constituent juices have their own special characters, and these are not the same in all animals. Moreover, in the same individual the secretion differs in composition and properties according to circum- stances ; thus, as we shall see in detail hereafter, the saliva from the sub- maxillary gland secreted under the influence of the chorda tympani nerve is different from that which is obtained from the same gland by stimulating the sympathetic nerve. 1 Ferments may, for the present at least, be divided into two classes, commonly called organised and unorganised. Of the former, yeast may be taken as a well-known example. The fermentative activity of yeast which leads to the conversion of sugar into alcohol, is dependent on the life of the yeast-cell. Unless the yeast-cell be living and functional, fermentation does not take place ; when the yeast-cell dies fermentation ceases ; and no substance obtained from the fluid parts of yeast, by precipitation with alcohol or other- wise, will give rise to alcoholic fermentation. The salivary ferment belongs to the latter class ; it is a substance, not a living organism like yeast. It may be added, however, that possibly the organized ferment, the yeast for instance, produces its effect by means of an ordinary unorganized ferment which it generates, but which is immediately made away with. SALIVA AND GASTRIC JUICE. 251 In man pure parotid saliva may easily be obtained by introducing a fine canula into the opening of the Stenonian duct, and submaxillary saliva, or rather a mixture of submaxillary and sublingual saliva, by similar catheterization of the Whartonian duct. In animals the duct may be dissected out and a canula introduced. Parotid saliva in man is clear and limpid, not viscid ; the reaction of the first drops secreted is often acid, the succeeding portions, at all events when the flow is at all copious, are alkaline ; that is to say, the natural secretion is alkaline, but this may be obscured by acid changes taking place in the fluid which has been retained in the duct, possibly by the formation of an excess of carbonic acid. On standing the clear fluid becomes turbid from a precipitate of calcic carbonate, due to an escape of carbonic acid. It con- tains globulin and some other forms of albumin, with little or no mucin. Potassium sulphocyanate may also sometimes be detected, but structural elements are absent. Submaxillary saliva, in man and in most animals, differs from parotid saliva in being more alkaline, and from the presence of mucin more viscid ; it contains salivary corpuscles, that is bodies closely resembling if not iden- tical with leucocytes, and, often in abundance, amorphous masses. The so- called chorda saliva in the dog, that is to say, saliva obtained by stimulating the chorda tympani nerve (of which we shall presently speak), is under ordinary circumstances thinner and less viscid, contains less mucin and fewer structural elements than the so-called sympathetic saliva, which is remarkable for its viscidity, its structural elements, and for its larger total of solids. Sublingual saliva is more viscid and contains more salts (in the dog about 1 per cent.) than the submaxillary saliva. The action of saliva varies in intensity in different animals. Thus in man, the pig, the guinea-pig, and the rat, both parotid and submaxillary and mixed saliva are amylolytic ; the submaxillary saliva being in most cases more active than the parotid. In the rabbit, while the submaxillary saliva has scarcely any action, that of the parotid is energetic. The saliva of the cat is much less active than the above ; that of the dog is still less active, indeed is almost inert. In the horse, sheep, and ox, the amolytic powers of either mixed saliva or of any one of the constituent juices are extremely feeble. Where the saliva of any gland is active, an aqueous infusion of the same gland is also active. The importance and bearing of this statement will be seen later on. From the aqueous infusion of the gland, as from saliva itself, the ferment may be approximately isolated. In some cases at least some ferment may be extracted from the gland even when the secretion is itself inactive. In fact, a ready method of preparing a highly amylolytic liquid tolerably free from proteid and other impurities is to mince finely a gland known to have an active secretion, such, for instance, as that of a rat, to dehydrate it by allowing it to stand under absolute alcohol for some days, and then, having poured off most of the alcohol and removed the remainder by evaporation at a low temperature, to cover the pieces of gland with strong glycerin. Though some of the ferment appears to be destroyed by the alcohol, a mere drop of such a glycerin extract rapidly converts starch into sugar. Gastric Juice. § 187. There is no difficulty in obtaining what may be fairly considered as a normal saliva ; but there are many obstacles in the way of determining the normal characters of the secretion of the stomach. When no food is 252 THE TISSUES AND MECHANISMS OF DIGESTION. taken the stomach is at rest and no secretion takes place. When food is taken, the characters of the gastric juice secreted are obscured by the food with which it is mingled. The gastric membrane may, it is true, be arti- ficially stimulated, by touch, for instance, and a secretion obtained. This we may speak of as gastric juice, but it may be doubted whether it ought to be considered as normal gastric juice. And indeed, as we shall see, even the juice which is poured into the stomach during a meal, varies in compo- sition as digestion is going on. Hence the characters which we shall give of gastric juice must be considered as having a general value only. Gastric juice, obtained in as normal a condition as possible from the healthy stomach of a fasting dog by means of a gastric fistula, is a thin, almost colorless fluid with a sour taste and odor. In the operation for gastric fistula an incision is made through the abdominal walls, along the linea alba, the stomach is opened, and the lips of the gastric wound securely sewn to those of the incision in the abdominal walls. TJnion soon takes place, so that a permanent opening from the exterior into the inside of the stomach is established. A tube of proper construction, introduced at the time of the operation, becomes firmly secured in place by the contraction of healing. Through the tube the contents of the stomach can be received, and the mucous membrane stimulated at pleasure. When obtained from a natural fistula in man, its specific gravity has been found to diflfer little from that of water, varying from 1.001 to 1.010, and the amount of solids present to be correspondingly small. In animals pure gastric juice seems to be equally poor in solids, the higher estimates which some observers have obtained being probably due to admixture with food, etc. Of the solid matters present about half are inorganic salts, chiefly alka- line (sodium) chlorides, with small quantities of phosphates. The organic material consists of pepsin, a body to be described immediately, mixed with other substances of undetermined nature. In a healthy stomach gastric juice contains a very small quantity only of mucin, unless some submaxillary saliva has been swallowed. The reaction is distinctly acid, and the acidity is normally due to free hydrochloric acid. This is shown by various proofs, among which we may mention the conclusive fact that the amount of chlorine present in gastric juice is more than would suffice to form chlorides with all the bases present, and that the excess, if regarded as existing in the form of hydrochloric acid, corresponds exactly to the quantity of free acid present. Lactic and butyric and other acids when present are secondary products, arising either by their respective fermentations from articles of food, or from the decomposition of their alkaline or other salts. In man the amount of free hydrochloric acid in healthy juice may be stated to be about 0.2 per cent., but in some animals it is probably higher. § 188. On starch gastric juice has no amylolytic action ; on the con- trary, when saliva is mixed with gastric juice any amylolytic ferment which may be present in the former is at once prevented from acting by the acidity of the mixture. Moreover, in a very short time, especially at the tempera- ture of the body, the amylolytic ferment is destroyed by the acid, so that even on neutralization the mixture is unable to convert starch into sugar. On dextrose healthy gastric juice has no effect. And its power of con- verting cane-sugar seems to be less than that of hydrochloric acid diluted to the same degree of acidity as itself. In an unhealthy stomach, however, containing much mucus, the gastric juice is very active in converting cane- sugar into dextrose. This power seems to be due to the presence in the mucus of a special ferment, analogous to, but quite distinct from, the SALIVA AND GASTRIC JUICE. 253 ptyalin of saliva. An excessive quantity of cane-sugar introduced into the stomach causes a secretion of mucus, and hence provides for its own conversion. On fats gastric juice has at most a limited action. When adipose tissue is eaten, the chief change which takes place in the stomach is that the pro- teid and gelatiniferous envelopes of the fat-cells are dissolved, and the fats set free. Though there is experimental evidence that emulsion of fats to a certain extent does take place in the stomach, the great mass of the fat of a meal is not so changed. Such minerals as are soluble in free hydrochloric acid are for the most part dissolved ; though there is a difference in this and in some other re- spects between gastric juice and simple free hydrochloric acid diluted with water to the same degree of acidity as the juice, the presence either of the pepsin or of other bodies apparently modifying the solvent action of the acid. The essential property of gastric juice is the power of dissolving proteid matters and of converting them into a substance called peptone. Action of gastric juice on proteids. The results are essentially the same, whether natural juice obtained by means of a fistula, or artificial juice, i. e. an acid infusion of the mucous membrane of the stomach, be used. Artificial gastric juice may be prepared in any of the following ways : 1. The mucous membrane of a pig's or dog's stomach is removed from the mus- cular coat, finely minced, rubbed in a mortar with pounded glass and extracted with water. The aqueous extract filtered and acidulated (it is in itself somewhat acid), until it has a free acidity corresponding to 0.2 per cent, of hydrochloric acid, contains but little of the products of digestion, such as peptone, but is fairly potent. 2. The mucous membrane similarly prepared and minced is allowed to digest at 35° C. in a large quantity of hydrochloric acid diluted to 0.2 per cent. The greater part of the membrane disappears, shreds only being left, and the some- what opalescent liquid can be decanted and filtered. The filtrate has powerful digestive (peptic) properties, but contains a considerable amount of the products of digestion (peptone, etc.) arising from the digestion of the mucous membrane itself.1 3. The mucous membrane, similarly prepared and minced, is thrown into a com- paratively large quantity of concentrated glycerin, and allowed to stand. The mem- brane may be previously dehydrated by being allowed to stand under alcohol, but this is not necessary, and a too prolonged action of the alcohol injures or even de- stroys the activity of the product. The decanted clear glycerin, in which a com- paratively small quantity of the ordinary proteids of the mucous membrane are dissolved, if added to hydrochloric acid of 0.2 per cent, (about 1 c.c. of the glycerin to 100 c.c. of the dilute acid are sufficient), makes an artificial juice tolerably free from ordinary proteids and peptone, and of remarkable potency, the presence of the glycerin not interfering with the results. Before proceeding to study the action of gastric juice on proteids, it will be useful to review very briefly the chief characters of the more important members of the group. The more important proteids which we have thus far studied are : 1. Fibrin, insoluble in water and not really soluble (i. e., without change) in saline solutions. 2. Myosin, insoluble in water, but soluble in saline solu- tions, provided these are not too dilute or too concentrated. 3. Globulin (including paraglobulin, fibrinogen, etc.), insoluble in water, but readily soluble in even very dilute saline solutions. 4. Albumin, serum-albumin, soluble in water in the absence of all salts. 5. Acid-albumin, into which globulins and myosin are rapidly converted by the action of dilute acids, 1 These, however, may be removed by concentration at 40° C. and subsequent dialysis. 254 THE TISSUES AND MECHANISMS OF DIGESTION. the particular acid-albumin into which the myosin of muscle is changed, being sometimes called syntonin. If the reagent used be not dilute acid, but dilute alkali, the product is called alkali-albumin. The two bodies, acid-albumin and alkali-albumin, are very parallel in their characters, and may readily be converted, the one into the other, by the use of dilute alkali or dilute acid respectively. Their most important common characters are insolubility in water and in saline solutions and ready solubility in dilute acids and alkalies. 6. Coagulated proteids. As we have seen, when fibrin suspended in water, serum-albumin in solution, acid-albumin or alkali- albumin suspended in water, or paraglobulin suspended in water or dis- solved in a dilute saline solution, are heated to a temperature which for the whole group may be put down at about 75° to 80° C., each of them be- comes coagulated, and after the change is insoluble in water, saline solu- tions, dilute acids, etc., in fact in everything but very strong acids. Myosin and fibrinogen undergo a similar change at a lower temperature, viz., about 56° C. We may, for present purposes, speak of all these proteids thus changed under the one term of coagulated proteids. To the above list we may now add two other proteids, viz. : 7. A kind of albumin which forms the great bulk of the proteid matter present in raw " white of egg," and which, since it differs in minor characters from the albumin of blood and of the tissues, is called egg-albumin. 8. The peculiar proteid casein, an important constituent of milk. This may perhaps be regarded as a naturally occurring alkali-albumin, since it has many resem- blances to the artificial alkali-albumin ; but for several reasons it is desir- able to consider it as an independent body. Egg-albumin, like serum-albumin, becomes coagulated at a temperature of about 75° to 80° C., and though casein as it naturally exists in milk is not coagulated on boiling, when separated out in a special way, and sus- pended in water in which it is insoluble, it becomes coagulated at about 75° to 80° C. It will be observed that all these proteids form, as regards their solubili- ties, a descending series in the following order : coagulated proteids ; fibrin ; acid-albumin with alkali-albumin, and casein ; myosin, globulin ; serum- albumin with egg-albumin. We must now return to the action of gastric juice. If a few shreds of fibrin, obtained by whipping blood, after being thor- oughly washed and boiled and thus by the boiling coagulated, be thrown into a quantity of gastric juice, and the mixture be exposed to a tempera- ture of from 35° to 40° C., the fibrin will speedily, in some cases in a few minutes, be dissolved. The shreds first swell up and become transparent, then gradually dissolve, and finally disappear with the exception of some gran- ular debris, the amount of which, though generally small, varies according to circumstances. If raw, that is, unboiled, uncoagulated fibrin be employed the same changes may be observed, but they take place much more rapidly. If small morsels of coagulated albumin, such as white of egg, be treated in the same way, the same solution is observed. The pieces become trans- parent at their surfaces ; this is especially seen at the edges, which gradually become rounded down ; and solution steadily progresses from the outside of the piece inward. If any other form of coagulated albumin (e. g., precipitated acid- or alkali-albumin, suspended in water and boiled) be treated in the same way, a similar solution takes place. The readiness with which the solution is effected, will depend, cceteris paribus, on the smallness of the pieces, or rather on the amount of surface as compared with bulk, which is presented to the action of the juice. SALIVA AND GASTRIC JUICE. 255 Gastric juice then readily dissolves coagulated proteids which other- wise are insoluble, or soluble only, and that with difficulty, in very strong acids. When proteids which are soluble in water, or in dilute acid, are treated with gastric juice, no visible change takes place ; but nevertheless, it is found on examination that the solutions have undergone a remarkable change, the nature of which is easily seen by contrasting it with the change effected by dilute acid alone. If raw white of egg, largely diluted with water and strained, be treated with a sufficient quantity of dilute hydrochloric acid, the opalescence or turbidity which appeared in the white of egg on dilution (and which is due to the precipitation of various forms of globulin accompanying the egg-albumin in the raw white) disappears^ and a clear mixture results. If a portion of the mixture be at once boiled, a large deposit of coagulated albumin occurs. If, however, the mixture be exposed to 50° to 55° C. for some time, the amount of coagulation which is produced by boiling a specimen becomes less, and, finally, boiling produces no coagulation whatever. By neutralization, however, the whole of the albumin (with such restrictions as the presence of certain neutral salts may cause) may be obtained in the form of acid-albumin, the filtrate after neutralization containing no proteids at all (or a very small quantity). Thus the whole of the albumin present in the white of egg may be, in time, converted, by the simple action of dilute hydrochloric acid, into acid-albumin. Serum-albumin similarly treated undergoes in course of time a similar conversion into acid-albumin, and we have already seen (§ 59) that solutions of myosin or of any of the globulins are with remarkable rapidity converted into acid-albumin. Thus simple dilute hydrochloric acid of the same degree of acidity as gastric juice, merely converts these proteids into acid-albumin, the rapidity of the change differ- ing with the different proteids, being in some cases very slow, and requiring a relatively high temperature. If the same white of egg or serum-albumin be treated with gastric juice instead of simple dilute hydrochloric acid, the events for some time seem the same. Thus after a while boiling causes no coagulation, while neutraliza- tion gives a considerable precipitate of a proteid body, which being insoluble in water and in sodium chloride solutions and soluble in dilute alkali and acids, at least closely resembles acid-albumin. But it is found that only a portion of the proteid originally present in the white of egg or serum-albumin can thus be regained by precipitation. Though the neutralization be carried out with the greatest care it will be found, on filtering off the neutralization precipitate, that is, the acid-albumin, that the filtrate, as shown on employ- ing the various tests for proteid (see § 15) or on adding an adequate quan- tity of strong alcohol, still contains a very considerable quantity of proteid matter ; and, on the whole, the longer the digestion is carried on, the greater is the proportion borne by the proteid remaining in solution to the precipi- tate thrown down on neutralization ; indeed, in some cases at all events, all the proteid matter originally present remains in solution, and there is no neutralization precipitation at all, or at most a wholly insignificant one. § 189. The proteid matter, thus remaining in solution after neutraliza- tion differs from all the proteids which we have hitherto studied, inasmuch as, though existing in a neutral solution, it is not coagulated by heat, like the egg-albumin or serum-albumin from which it has been produced ; the solution, after the neutralization precipitate has been filtered off, remains quite clear when boiled. The only other solutions of proteids which do not coagulate on boiling are solutions of acid- or alkali-albumin ; but these solu- tions must be acid or alkali respectively ; the acid-albumin or alkali-albumin is insoluble in a neutral solution, and when simply suspended in water is 256 THE TISSUES AND MECHANISMS OF DIGESTION. readily coagulated at a temperature of 75° C. This new proteid matter of •which we are speaking is soluble in neutral solutions, indeed in distilled water, and can under no circumstances be coagulated by heat. Upon examination we find that the new proteid matter thus left in solu- tion consists of at least two distinct proteid bodies. If to the solution ammo- nium sulphate be added, part of the proteid matter is precipitated while part is still left in solution. The proteid body thus thrown down is called albu- mose (there are several varieties of albumose, but these need not now detain us). It approaches albumin in nature by reason of the fact that it will not diffuse through membranes ; that it differs, however, widely from that proteid is shown by its solutions not coagulating on boiling. The body which is not thrown down by ammonium sulphate is called peptone; it differs from albu- mose in being diffusible, for it will pass through membranes. The diffusion is not nearly so rapid as that of salts, sugar, and other similar substances ; indeed solutions of peptones may be freed from salts by dialysis. But it is very marked as compared with that of other proteids ; these pass through membranes with the greatest difficulty, if at all. Peptone is insoluble in alcohol, and may be precipitated from its solutions by the addition of an adequate quantity of this reagent ; but for this purpose a very large excess of alcohol is needed, otherwise much of the peptone remains in solution. It may be kept under alcohol for a long time without undergoing change, whereas other proteids are more or less slowly coagulated by alcohol. A useful test for peptone is furnished by the fact that a solution of peptone, mixed with a strong solution of caustic potash, gives on addition of a mere trace of cupric sulphate in the cold a, pink color, whereas other proteids give a violet color. In applying this test, however, care must be taken not to add too much cupric sulphate, since in that case a violet color, deepening on boiling, that is, the ordinary proteid reaction (see § 15), is obtained. There are reasons for thinking that there are several kinds, or at least more than one kind, of peptone ; but we may for the present regard the sub- stance as one. For a long time albumose was confounded with peptone, and many of the commercial forms of "peptone" consist largely of albumose; indeed, the two are closely allied and have many reactions in common, the most striking differences being that peptone is diffusible, while albumose is not, or hardly at all, and that peptone is not, like albumose, precipitated by ammonium sulphate. The amount of albumose appearing in a digestion experiment, relative to the amount of true peptone, depends on the activity of the juice, and other circumstances. We may regard albumose as a less complete product of digestion than peptone. The precipitate thrown down by neutralization after the action of gastric juice on egg- or serum-albumin resembles, in its general characters, acid- albumin. Since, however, it probably is distinguishable from the body or bodies produced by the action of simple acid on muscle or white of egg, it is best to reserve for it the name of parapeptone, which was originally applied to it. Thus the digestion by gastric juice of solutions of egg-albumin or serum- albumin results in the conversion of all the proteids present into peptone, albumose, and parapeptone, of which the first may be considered as the final and chief product, and the other two as intermediate products, occurring in varying quantity, possibly not always formed, and probably of secondary importance. When fibrin, either raw or boiled, or any form of coagulated proteid is dissolved and seems to disappear under the influence of gastric juice, the same products, peptone, albumose, and parapeptone make their appearance. The same bodies result when myosin or any of the globulins are subjected to the action of the juice ; and acid-albumin or alkali-albumin is similarly converted into albumose and peptone. SALIVA AND GASTRIC JUICE. 257 It is obvious that the effect of the action of the gastric juice is to change the less soluble proteid into a more soluble form, the change being either completed up to the stage of peptone, the most soluble of all proteids, or being left in part incomplete. This will be seen from the following tabular arrangement of proteids according to their solubilities : Soluble in distilled water. Aqueous solutions not coagulated on boiling : Diffusible Peptone. Not diffusible Albumose. Aqueous solutions coagulated on boiling Albumin. Insoluble in distilled water. Readily soluble in dilute saline solutions (NaCl 1 per ) pi i r cent, ) f u Soluble only in stronger saline solutions (NaCl 5 to 10 ) M percent.) j My(M Insoluble in dilute saline solutions. Readily soluble in dilute acid (HC1 0.1 percent.) in j Acid-albumin. thecold- -IcLt' Soluble with difficulty in dilute acid, that is at high ) temperature (60° C. ) and after prolonged treatment V Fibrin, only j Insoluble in dilute acids, soluble only in strong acids . Coagulated proteid. Milk when treated with gastric juice is first of all " curdled." This is the result partially of the action of the free acid, but chiefly of the special action of a particular constituent of gastric juice, of which we shall speak here- after. The curd consists of a particular proteid matter mixed with fat ; and this proteid matter is subsequently dissolved with the same appearance of pep- tone, albumose, and parapeptone as in the case of other proteids. In fact, the digestion by gastric juice of all the varieties of proteids consists in the con- version of the proteid into peptone, with the concomitant appearance of a certain variable amount of albumose and parapeptone. § 190. Circumstances affecting gastric digestion. The solvent action of gastric juice on proteids is modified by a variety of circumstances. The nature of the proteid itself makes a difference, though this is determined probably by physical rather than by chemical characters. Hence in making a series of comparative trials the same proteid should be used, and the form of proteid most convenient for the purpose is fibrin. If it be desired simply to ascertain whether any given specimen has any digestive powers at all, it is best to use boiled fibrin, since raw fibrin is eventually dissolved by dilute hydrochloric acid alone, probably on account of some pepsin previously present in the blood becoming entangled with the fibrin during clotting. But in estimating quantitatively the peptic power of two specimens of gastric juice under different conditions, raw fibrin prepared by Gru'tzner's method is most convenient. Portions of well-washed fibrin are stained with carmine and again washed to remove the superfluous coloring matter. A fragment of this colored fibrin thrown into an active juice on becoming dissolved, gives up its color to the fluid. Hence if the same stock of colored fibrin be used in a series of experiments, and the same bulks of fibrin and of fluid be used in each case, the amount of fibrin dissolved may be fairly estimated by the depth of tint given to the fluid. Fibrin thus colored with carmine may be preserved in ether. 17 258 THE TISSUES AND MECHANISMS OF DIGESTION. Since, if sufficient time be allowed, even a small quantity of gastric juice will dissolve at least a very large if not an indefinite quantity of fibrin, we are led to take, as a measure of the activity of a specimen of gastric juice, not the quantity of fibrin which it will ultimately dissolve, but the rapidity with which it dissolves a given quantity. The greater the surface presented to the action of the juice, the more rapid the solution ; hence minute division and constant movement favor diges- tion. And this is probably, in part at least, the reason why a fragment of spongy filamentous fibrin is more readily dissolved than a solid clump of boiled white of egg of the same size. Neutralization of the juice wholly arrests digestion ; fibrin may be submitted for an almost indefinite time to the action of neutralized gastric juice without being digested. If the neu- tralized juice be properly acidified, it may again become active ; when gas- tric juice, however, has been made alkaline, and kept for some time at a temperature of 35° C., its solvent powers are not only suspended but actually destroyed. Digestion is most rapid with dilute hydrochloric acid of 0.2 per cent, (the acidity of natural gastric juice). If the juice contains much more or much less free acid than this, its activity is distinctly impaired. Other acids, lactic, phosphoric, etc., may be substituted for hydrochloric ; but they are not so effectual, and the degree of acidity most useful varies with the different acids. The presence of neutral salts, such as sodium chloride, in excess is injurious. The action of mammalian gastric juice is most rapid at 35°-40° C. ; at the ordinary temperature it is much slower, and at about 0° C. ceases altogether. The juice may be kept, however, at 0° C. for an indefinite period without injury to its powers. The gastric juice of cold- blooded vertebrates is relatively more active at low temperatures than that of warm-blooded mammals or birds. At temperatures much above 40° or 45° the action of the juice is im- paired. By boiling for a few minutes the activity of the most powerful juice is irrevocably destroyed. The presence in a concentrated form of the products of digestion hinders the process of solution. If a large quantity of fibrin be placed in a small quantity of juice, digestion is soon arrested; on dilution with the normal hydrochloric acid (0.2 per cent.), or if the mix- ture be submitted to dialysis to remove the peptones formed, and its acidity be kept up to the normal, the action recommences. By removing the prod- ucts of digestion as fast as they are formed, and by keeping the acidity up to the normal, a given amount of gastric juice maybe made to digest a very large quantity of proteid material. Whether the quantity is really un- limited is disputed ; but in any case the energies of the juice are not rapidly exhausted by the act of digestion. § 191. Nature of the action. All these facts go to show that the digestive action of gastric juice on proteids, like that of saliva on starch, is a ferment- action ; in other words, that the solvent action of gastric juice is essentially due to the presence in it of a ferment-body. To this ferment-body, which as yet has been only approximately isolated, the name of pepsin has been given. It is present not only in gastric juice, but also in the glands of the gastric mucous membrane, especially in certain parts and under certain conditions which we shall study presently. The glycerin extract of gastric mucous membrane, at any rate of that which has been dehydrated, contains a minimal quantity of proteid matter, and yet is intensely peptic. Other methods, such as the elaborate one of Briicke, give us a material which, though containing nitrogen, exhibits none of the ordinary proteid reactions, and yet in concert with normal dilute hydrochloric acid is peptic in a very high degree. We seem, therefore, justified in asserting that pepsin is not a proteid, but it would be hazardous to make any dogmatic statement con- SALIVA AND GASTRIC JUICE. 259 cerning a substance obtained in so small a quantity at a time that its exact chemical characters have not yet been ascertained. At present the manifestation of peptic powers is our only safe test of the presence of pepsin. In one important respect pepsin, the ferment of gastric juice, differs from .ptyalin, the ferment of saliva. Saliva is active in a perfectly neutral medium, and there seems to be no special connection between the ferment and any alkali or acid. In gastric juice, however, there is a strong tie between the acid and the ferment, so strong that some writers speak of pepsin and hydrochloric acid as forming together a compound, pepto- hydrochloric acid. In the absence of exact knowledge of the constitution of proteids, we cannot state distinctly what is the precise nature of the change into pep- tone ; the various proteids differ from each other in elementary composition quite as widely as does peptone from any of them. Judging from the analogy with the action of saliva on starch, we may fairly suppose that the process is at bottom one of hydration ; and this view is further sug- gested by the fact that peptone closely resembling, if not identical with, that obtained by gastric digestion, may be obtained by the action of the strong acids, by the prolonged action of dilute acids especially at a high tempera- ture, or simply by digestion with superheated water in a Papin's digester, that is to say, by means of agents which, in other cases produce their effects by bringing about hydrolytic changes ; beyond this we cannot at present go. § 192. All proteids, as far as we know, are converted by pepsin into pep- tone. Concerning the action of gastric juice on other nitrogenous sub- stances more or less allied to proteids, but not truly proteid in nature, our knowledge is at present imperfect. Mucin, nuclein, and the chemical basis of horny tissues are wholly unaffected by gastric juice. The gelatiniferous tissues are dissolved by it ; and the bundles and membranes of connective tissue are very speedily so far affected by it that at a very early stage of digestion the bundles and elementary fibres of muscles which are bound together by connective tissue fall asunder ; moreover, both prepared gelatin and the gelatiniferous basis of connective tissue in its natural condition, that is without being previously heated with water, are by it changed into a substance so far analogous with peptone that the characteristic property of gelatinization is entirely lost. Chondrin and the elastic tissues undergo a similar change. § 193. Action of gastric juice on milk. It has long been known that ah infusion of calves' stomach, called rennet, has a remarkable effect in rapidly curdling milk, and this property is made use of in the manufacture of cheese. Gastric juice has a similar effect: milk when subjected to the action of gastric juice is first curdled and then digested. If a few drops of gastric juice be added to a little milk in a test-tube, and the mixture ex- posed to a temperature of 40° C.,the milk will curdle into a complete clot in a very short time. If the action be continued the curd or clot will be ulti- mately dissolved and digested. Milk contains, besides a peculiar form, or peculiar forms of albumin, fats, milk-sugar, and various salines, the peculiar proteid casein. In natural milk casein is present in solution, and " curd- ling" consists essentially in the soluble casein being converted (or more probably as we shall see presently, split up) into an insoluble modification of casein, which as it is being precipitated carries down with it a great deal of the fat and so forms the " curd." Now casein is readily precipitated from milk upon the addition of a small quantity of acid, and it might be supposed that the curdling effect of gastric juice was due to its acid reaction. 260 THE TISSUES AND MECHANISMS OF DIGESTION. But this is not the case, for neutralized gastric juice, or neutral rennet, is equally efficacious. The curdling action of rennet is closely dependent on temperature, being like the peptic action of gastric juice favored by a rise of temperature up to about 40° C. Moreover the curdling action is destroyed by previous boiling of the juice or rennet. These facts suggest that a ferment is at the bottom of the matter; and, indeed, all the features of the action support this view. Moreover, as a matter of fact, a curdling ferment may be extracted by glycerin and by the other methods used for preparing ferments. The fer- ment, however, is not pepsin, but some other body ; and the two may be separated from each other. It might be thought that the rennet-ferment, rennin we may call it, acted by inducing a fermentation in the sugar of milk, giving rise to lactic acid which precipitated the casein by virtue of its being an acid. But this view is disproved by the following facts which show that the ferment produces its curdling effect by acting directly on the natural casein itself. Casein maybe precipitated unchanged, that is, capable of redissolving in water (the presence of calcic phosphate being assumed) by saturating milk with neutral saline bodies (such as sodium chloride or magnesium sulphate) ; and by being pre- cipitated and redissolved more than once may be obtained largely free from fat and wholly free from milk-sugar. Such solutions of isolated'casein freed from milk-sugar may be made to curdle like natural milk by the addition of rennin, showing that the milk-sugar has nothing to do with the matter. Moreover, the precipitate thrown down from milk by dilute acids, lactic acid included, is itself unaltered or very slightly altered casein, not curd, and with care may be so prepared as to be redissolved into solutions which curdle with rennin, like solutions of casein prepared by means of neutral salts. When isolated casein is curdled by means of reunin, two proteids, it is stated, make their appearance, one which is soluble and allied to albumin, and another which is insoluble and forms the curd. Curdling, therefore, according to this result appears to be the splitting up by a ferment of a more complex body ; and it is interesting to observe, as perhaps throwing light on the somewhat analogous formation of the fibrin, that this curdling action will not take place if calcic phosphate be wholly absent from the mixture. The calcic phosphate appears to play a peculiar part in determining the insolubility of the curd, for there is evidence that in the absence of calcic phosphate the ferment has power to attack the casein and split it up, but that both products remain in solution ; if calcic phosphate be present, the one, viz., the curd,1 becomes insoluble. Rennin is abundant in the gastric juice and in the gastric mucous mem- brane of ruminants, but is also found in the gastric juice of other animals, and either it, or what we shall presently have occasion to speak of as the antecedent of the ferment or zymogen, is present also in the mucous membrane of the stomach of most animals. A very similar if not identical ferment has also been found in many plants. THE ACT OF SECRETION OF SALIVA AND GASTRIC JUICE AND THE NERVOUS MECHANISMS WHICH REGULATE IT. § 194. The saliva and gastric juice whose properties we have studied, though so different from each other, are both drawn ultimately from one 1 It might be useful, in order to distinguish the curd from the natural soluble casein, to call the former tyre/in (rvpoi, cheese), and so reserve the name of casein for the latter. SECRETION OF SALIVA AND GASTRIC JUICE. 261 common source, the blood, and they are poured into the alimentary canal, not in a continuous flow, but intermittently as occasion may demand. The epithelial cells which supply them have their periods of rest and of activ- ity, and the amount and quality of the fluids which the cells secrete are determined by the needs of the economy as the food passes along the canal. We have now to consider how the epithelial cell manufactures its special secretion out of the materials supplied to it by the blood, and how the cell is called into activity by the presence of food, it may be as in the case of saliva at some distance from itself, or by circumstances which do not bear directly on itself. In dealing with these matters in connection with the digestive juices, we shall have to enter at some length into the physiology of secretion in general. The question which presents itself first is : By what mechanism is the activity of the secreting cells brought into play ? While fasting, a small quantity only of saliva is poured into the mouth ; the buccal cavity is just moist and nothing more. When food is taken, or when any sapid or stimulating substance, or indeed a body of any kind, is introduced into the mouth, a flow is induced which may be very copious. Indeed the quantity secreted in ordinary life during 24 hours has been roughly calculated at as much as from 1 to 2 litres. An abundant secretion in the absence of food in the mouth may be called forth by an emotion, as when the mouth waters at the sight of food, or by a smell, or by events oc- curring in the stomach, as in some cases of nausea. Evidently in these iiir stances some nervous mechanism is at work. In studying the action of this nervous mechanism, it will be of advantage to confine our attention at first to the submaxillary gland. § 195. The submaxillary gland is supplied with two sets of nerves. These are represented in Fig. 81, which is a very diagrammatic rendering of the appearances presented when the submaxillary gland is prepared for an experiment in a dog, the animal being placed on its back and the gland exposed from the neck. The one set, and that the more important, belongs to the chorda tympani nerve (ch. £iv,t