The cover image was created by the transcriber, and is placed in the public domain.

THE BODY AT WORK

A.

B.

C.

D.

Fig. 1.—Photomicrographs of Cells of the Cortex of the
Cerebellum and Cerebrum.

[For description see p. x.]

Frontispiece.

THE BODY AT WORK

A TREATISE ON THE PRINCIPLES
OF PHYSIOLOGY

BY
ALEX HILL, M.A., M.D., F.R.C.S.

SOMETIME MASTER OF DOWNING COLLEGE, CAMBRIDGE

WITH 46 ILLUSTRATIONS

LONDON

EDWARD ARNOLD

1908

[All rights reserved]

PREFACE

Few subjects are as well provided with text-books as physiology; yet it may be doubted whether the interests of the amateur of science have been adequately cared for. From his point of view there are certain obvious drawbacks to even the most admirable of text-books. Writing for medical students, their authors assume that their readers have passed through two years of preliminary training in physics, chemistry, and biology; they take for granted that they will have the privilege of supplementing their study of the theory of physiology with practical work in a laboratory; they treat all parts of the subject with equal thoroughness. In this book I have endeavoured to describe the phenomena of life, and the principal conclusions which have been drawn as to their interdependence and as to their causes, in language which will be understood by persons unacquainted with the sciences upon which physiology is based. I have omitted all reference to experimental methods and to the technique of the science, save when a knowledge of the means by which information has been obtained is essential to a comprehension of its bearing. I have passed over such sections of the subject as are generally considered unsuitable for ordinary discussion. And since this book neither aims at being an introduction to the systematic study of physiology, nor poses as an aid in the preparation for professional examinations, I have treated with some thoroughness the more recondite and the more suggestive results of recent research, and have tried to indicate the trend of modern thought regarding problems as yet unsolved. I have endeavoured to reflect the intrinsic interest of the science apart altogether from its medical applications.

An author who attempts the popular exposition of a science must stand sufficiently far away from his subject to lose sight of its details, whilst keeping its outlines clearly in view. The difficulty of finding such a position is probably greater in the case of physiology than in that of any other science. Few of its conclusions are indisputable—even those which seem to be most in accord with the balance of evidence. If my treatment of any vexed questions is unjustifiably dogmatic, this will, I trust, be attributed to the desire to present a definite picture, and not to forgetfulness of considerations which seem to call for qualified statements. All physiologists will agree that a book which recorded every piece of evidence which is difficult to reconcile with the views generally adopted would not only extend to an inordinate length, but would leave a very indefinite impression on the mind of the reader.

In many cases the value of a conclusion depends upon the reputation for insight and accuracy of the physiologist who recorded the observations upon which it is based. It is no want of appreciation of the genius of the workers who have contributed most largely to the advance of the science which has led me to omit, save in a few classical instances, the names of all authorities. It is solely due to a desire to lighten this book of all details not essential to the comprehension of the propositions which it sets forth.

The illustrations are reproductions of blackboard drawings. A few of them have already appeared in my Physiologist’s Notebook and Primer of Physiology; but the large majority are now printed for the first time.

ALEX HILL.

November, 1908.

CONTENTS

LIST OF ILLUSTRATIONS

NOTE ON THE FRONTISPIECE

Four photomicrographs of cells or parts of cells of brain-tissue, coloured by the chrome-silver method ([cf. p. 293]).

A. Cell of Purkinje from the cerebellum of a man aged 45. At the bottom of the photograph is seen the rounded cell-body, with the commencement of its axon. The summit of the cell-body bears an elaborately branched system of dendrites, spread out in the plane of the section.

B. A single basket-cell of the cortex of the cerebellum (very highly magnified). The oval cell-body gives origin to four dendritic processes which branch. Thorns are to be seen on the larger process which ascends on the right. From the same process, near its origin, springs a delicate axon which thickens as it proceeds to form a basket at the right hand lower corner of the photograph. Two other branches of the same axon, which form baskets around other Purkinje-cells, are faintly visible, although out of focus.

C. Seven or eight pyramids from the cortex of the cerebrum of a hedgehog. A little below the centre of the photograph is seen a large pyramid with a single thorny apical process which bifurcates, several basal dendrites and an axon. In the upper part of the photograph are seen the apical processes of a number of pyramids of which the bodies were not included in the section.

D. The margin of the cortex (subiculum cornu Ammonis) from the same specimen. A single row of pyramids extends across the photograph. They are remarkable for the richness of branching of their basal processes, which has earned for the cells which comprise this sheet the name of “double pyramids.”

All four sections were cut vertically to the surface.

Fig. 2.—Diagram showing the Relative Positions of the Organs
of the Chest and Abdomen.

The ribs from the first to the tenth have been cut across in the lateral line. The eleventh and twelfth ribs do not reach sufficiently far forwards to be cut. With the exception of a short segment near its junction with the ascending colon, the small intestine has been removed. The trachea is seen to divide into bronchi beneath the arch of the aorta. The right lung has three, the left two lobes. The kidneys are situate behind all the other viscera. On their upper ends rest the two suprarenal capsules. The lower edge of the right lobe of the liver follows closely the line of the ribs and costal cartilages. Below the left lobe of the liver the stomach comes to the anterior abdominal wall. The transverse colon (large intestine) comes to the anterior wall below the stomach. Below the latter the wall is in contact chiefly with coils of small intestine. The vermiform appendix rests on the posterior wall. Spleen and pancreas are not shown in the diagram.

THE BODY AT WORK

CHAPTER I
PROLEGOMENA

Physiology is the science of the body at work. It is the study of life. Anatomy records how plants and animals are constructed. It maps and measures. Physiology ascertains what they do, endeavours to explain how they do it, and conjectures why.

A knowledge of structure is essential to the right understanding of function; but the physiologist does not contemplate structure with a view to divining possibilities of action. He has no interest in structure as such. To him it is a matter of perfect indifference whether the tendon of a muscle is at its origin or its insertion. He would rather not know which end of the muscle terminates in a tendon. It is waste of his time to notice such a fact, save for the negative, the protective value of the information. If he did not know how the muscle and tendon are related, he might possibly imagine the muscle as doing something of which it is incapable. Observers of living things are often credited with studying structure with a view to determining function. The reverse is the true order of thought and observation. Living things perform certain acts. Having no inherent knowledge of our own microcosm which enables us to say how it works, we cannot, by reflecting upon our own internal operations, explain its various activities. Nor can we make use of the results of introspection when endeavouring to account for the acts of other beings. Our knowledge of how things are done is altogether extrapersonal, objective. It is the result of trial, failure, success in the use of apparatus, our own essays, or those of others. The body is a combination of organs—a term used somewhat loosely to designate any piece of the animal mechanism which has a distinct function to perform. The physiologist studies the results of the activity of an organ. He watches it in action, and endeavours to explain the process by which it produces its effects. Then follows the anatomist, who, taking it to pieces, examines it with the utmost thoroughness which scalpel and forceps or microscope allows, with a view to ascertaining whether its structure will support the physiologist’s hypothesis as to its mode of action. This in the vast majority of cases has been the history of scientific progress. The physiologist has preceded the anatomist in drawing inferences as to the manner in which things are done. The anatomist, after a further examination of structure, has either admitted the plausibility of his explanation, or has interposed the objection that the part was incapable of working in the way supposed.

This comparison of anatomy and physiology must not be pushed too far. Enough has been said to emphasize the distinction between them. The one treats of form, the other of function. The one looks at structure, the other at action. Anatomy in its limited and logical sense has nothing to do with the uses of a part; its business is to measure it. Physiology has nothing to do with the measurements of parts; its duty is to watch for movement. Every living thing may be contemplated either in its statical or in its dynamical aspect. Physiology looks at it from the latter point of view.

Surveying his province, the physiologist asks himself: “Who are my subjects? What am I to find out about them? What methods, in addition to direct observation, may I use to obtain this information?” His oversight embraces all living things. It is no longer reasonable to make a distinction between human and animal physiology, or between the physiology of animals and the physiology of plants. No human being can take all science for his field. If he contents himself with scratching its surface, he will assuredly raise but a meagre crop, and that mostly weeds. But he is far behind the spirit of his age if he declines to sow in his own little patch seeds of thought which have blossomed in other localities, however remote. The man whose purpose in studying physiology is to obtain a knowledge of the working of the healthy human body, in order that he may know how to set right the accidents, perversions, and premature decay to which human flesh is prone, would remain an empiric of the most rigid type did he not apply to the elucidation of his problems all conclusions reached from the study of other organisms which are likely to prove pertinent. There would be no science of human physiology had observation and experiment been limited to Man. There would be no science of medicine, it may be added, had not the mode of working of the human body, and the influence of drugs upon it, been inferred from the results of experiments upon animals—experiments which could never have been made upon men. Blisters, blood-letting, mercury-poisoning, would still be the physician’s remedies for all human ills. “Give the watch a good shaking. It sometimes does good. If that fails, I cannot advise you what to do, as I know nothing about the working of a watch.” Even though we open the living human body, as must be done for the purpose of making good such defects as are amenable to surgical treatment, and for a little while observe its wheels go round, we are unable, from fear of damaging the wheels, to introduce the mechanical tests which would tell us how and why they revolve. The man must be allowed to recover with uninjured organs. But, thanks to anæsthetics, there is no test which may not be applied to a live animal with as much propriety as to a dead one. Anæsthetics abolish the distinction, in its ethical applications, between life and death, because we are under no obligation, as in the case of the human being, to allow an animal to recover. Many experiments upon animals will be recorded in this book, and since the book is intended for the general public, who have been singularly misled regarding the nature and methods of vivisection, an opportunity is taken thus early of insisting that anæsthetics have made all things, not only possible, but legitimate. It is unnecessary to commence the description of each experiment with the statement that the animal was first placed in a condition of complete anæsthesia, or to end it with the statement that it was destroyed before it had recovered from the effects of the anæsthetic. The reader may take these facts for granted. In discussing the propriety of operating upon a living but unconscious animal, we are playing a word game as old as Plato’s day. What is life? What is the relation of the personality to the animal machine which it occupies and operates? For a few minutes a heart removed from the body continues to beat. In a physiological sense it is alive, although the body from which it was removed is dead. Yet the personality does not reside in the heart, as many generations of philosophers believed. It is merely an accident that the body dies when the co-ordinating mechanism, the heart, ceases to pump blood through its vessels. Nor is the personality limited to the brain. Without the sense-organs which place the brain in relation with the body, and owing to the movements of the body—by which the sources of sensations of smell, sight, hearing are ascertained—with the world of which it forms a part, there would be no personality, no Ego. Is it, then, coextensive with the body which exhibits it? A soldier returning crippled from the wars does not finish out his days with his personality curtailed. We are no nearer than was Plato to a definition of life. Such a discussion soon takes us out of the realm of science. Science is limited to the sphere in which the whole is greater than the part. Take away consciousness, and personality ceases. Guarantee that consciousness shall never return. The animal is dead. When considering the propriety of vivisection we must regard life and consciousness as inseparable. There can be no question of right or wrong in regard to experiments on a dead animal, even though a sensitive mind, from association, shrinks from contemplating them. A person who dislikes the idea of dissecting a dead animal is influenced by purely subjective and personal considerations; nor is he prompted by sympathy with an unconscious animal when he recoils from the spectacle of its still moving organs. The term “vivisection” conveys too large a meaning. A negative term is needed, some word which will hold the emotion of pity in check. Pity is misplaced when devoted to the unconscious subjects of physiological experiment; and, happily for animals, as for Man, anæsthetics suspend conscious life. Only a person who has undergone a surgical operation can understand how resolutely the intellect declines to adopt as part of itself things which have not come within its own experience. The nurse’s testimony, that a long interval separated the placing of the mask upon the face and the commencement of that dull half-consciousness which gradually reawakened into interest in one’s surroundings cannot be set aside. The nurse says that during that interval knife, saw, and cautery were busy at their work. Her story is accepted, but it is not believed. All physiological operations are conducted under anæsthetics. In by far the larger number the experiment is continued until life terminates, under anæsthetics. The only ground upon which an objection to vivisection can be based is the ground that it involves the infliction of pain, and it is with regard to this that the greatest misapprehension exists in the public mind. Only in experiments which have for their object the study of the effects of the removal of a certain part, the diversion of a duct, the elimination of the control of a particular nerve, is there any possibility, under existing conditions, that an animal will suffer. In such experiments as these, observations cannot commence until after the animal has recovered. The operation is conducted under anæsthetics, and with the utmost precautions, to prevent any disturbance of the animal’s general health. The injury is in almost all cases of a comparatively limited nature, and it is certain that it involves very little pain to the animal when it has recovered from its anæsthesia, since, thanks this time to aseptic surgery, there is no inflammation or other secondary trouble.

The field of physiology embraces the phenomena exhibited by all living things, whether plants or animals. The vegetable physiologist works in one part, the comparative physiologist in another. The work of the human physiologist is more limited in scope. Yet there are few problems relating to Man’s mechanism concerning which the physiologist can have direct knowledge. His theories are based upon the results obtained by experimenting upon animals.

CHAPTER II
THE BASIS OF LIFE

Protoplasm was defined by Huxley as “the physical basis of life.” It is the material substance which lives. There is no life in anything which does not consist of, or is not supported upon, or permeated by a system of filaments of protoplasm. Huxley’s definition indissolubly links in thought protoplasm and life. But it is doubtful whether the definition is in any sense axiomatic. The adjective “physical” has too narrow a range. If the biologist could say to the chemist, “Here is a substance which was alive. If I could restore to it the energy which it has lost, if I could impart to it the movement which I recognize as life, it would again be alive,” he would offer the chemist a substance susceptible to the methods of his science, something which he could analyse. If, approaching the physicist with a group of chemical products, he could say, “Into these protoplasm broke up on dying. I cannot assure you that while it was alive they were combined into molecules within your meaning of the term. There may be no such ‘substance’ as protoplasm in the sense in which you understand the word, but so long as this mass lived these various familiar compounds were bound together in a supermolecular form. Death was their falling apart. If I could cause them to recombine, they would be alive,” he would give the physicist a problem within the range of his methods. The physicist could devise a method for measuring these units. The science which can weigh an electron, the thousandth part of an atom, need not fear failure in its attempt to gauge the size of units of structure composed of groups of heavy molecules, albumins, globulins, and other proteins,[1] with the inclusion, perhaps, of fats, sugars, inorganic salts. But herein lies the biologist’s dilemma. He cannot assert that there exists a homogeneous substance, protoplasm. He cannot assert that there exists a definite tectonic grouping of heterogeneous substances which, so long as it is maintained, constitutes a physical basis capable, and alone capable, of exhibiting the phenomena of life. Protoplasm is still a hypothetical substance—a name. Truly, in the absence of nitrogen-containing compounds of very complicated chemical constitution there is no life. All living things yield on chemical analysis approximately the same nitrogenous substances. No one can say whether the capacity for living is dependent upon the molecular—that is to say, the chemical—constitution of the basis, or whether it is dependent upon the arrangement of its molecules, its form. It is even open to question whether instability, the capacity for incessant change, both in chemical composition and in form, be not the condition which differentiates living matter from dead. “Physical basis” is too hard a term for this elusive concept of the matter which exhibits life.

If it were possible by a process of elimination to ascertain the substances which must be present in protoplasm, the physiologist might formulate a reasonable hypothesis as to the nature of this “basis.” But there is no part of any living thing, or, at any rate, no part which is not microscopic in its dimensions, which can be pointed out as protoplasm and nothing besides. It is impossible to isolate anything which can be described as pure protoplasm. Nor is it possible, by comparing various tissues which are acknowledged to be rich in protoplasm, to ascertain what chemical substances are common to them all.

If it were feasible, by analysing a number of specimens of protoplasm, to make sure that, although x is absent from one, y from another, and z from a third, some one thing, P, is always present, then P might be regarded as the physical basis, even though it were evident that P alone was not protoplasm. Protoplasm would be P combined with either x, y, or z. Globulins and albumins and other proteins are always present, but in varying proportions; but it is impossible to make certain that either of these chemical substances is more important than the rest. Nor is it possible to assert of either that it is essential.

Chemically, protoplasm is a mixture of substances, chiefly proteid, in a condition in which it is capable of manifesting the phenomena of life. But whether it be more complex and of heavier molecule than either globulin, nucleo-protein, albumin, fibrin, or any other of the nitrogenous compounds which take its place when it is dead; or whether it be as simple as either of these, but differ from them all in its instability, in the constant flux of its atoms, which causes it at one time to incline towards one of them, at another time to another, are questions which cannot at present be answered.

The uncertainty as to the chemical nature of protoplasm is responsible for an unfortunate irregularity in the use of the term. It is ex hypothesi the most active, the most living part of an animal cell. If the cell has a nucleus and an envelope, the protoplasm must lie in the space between the two. This part of the cell is therefore often termed, without qualification, the “cell-protoplasm.” Frequently the abuse of the word is carried still further. Young cells, leucocytes, nerve-cells, etc., which have no envelope, consist of a nucleus embedded in soft cell-substance. The latter is termed its protoplasm. The cell is described as consisting of nucleus and protoplasm, the term assuming an anatomical signification. Not only is such a use of the term bad, because it indicates a confusion of thought, but it brings with it a train of ambiguities. What are the limits of the protoplasm? If the cell-body be firmer towards its exterior than it is within, is the denser substance protoplasm, or is it not? It has not the qualities which are attributed to protoplasm in so marked a degree as has the substance which it surrounds. Hence a distinction is made. The one is “ectoplasm,” the other “endoplasm.” Within the cell-body are many collections, often in the form of granules, of substances which have not the protoplasmic attributes. They constitute the “deuteroplasm” of certain cytologists. But these enclosed substances may be as far removed from protoplasm as starch grains. It is absurd to use the termination “plasm” for such well-defined products of cell activity as these. The subject is, unfortunately, obscured by conflicting terms. Nomenclatures which were invented with the object of giving definiteness to our ideas have served but to perplex them. The term “protoplasm” should be reserved as a synonym for the substance which is most alive, the substance in which chemical change is most active, the substance which has in the highest degree a potentiality of growth. Anatomical distinctions are better expressed in anatomical terms. We shall treat of such distinctions when considering the organization of the cell.

In the meantime it may be well to consider the attributes which appear to belong to this most living substance. Its chemical composition can be inferred only from the compounds found on analysis to be present in a mass of organized substance which there is reason for thinking was rich in protoplasm while it was alive. The compounds found vary within certain limits. The quantity of water associated with these compounds is still more variable. Water is essential to the existence of protoplasm. Its power of combining with water in variable quantities is one of its characteristics. Tissue rich in protoplasm yields on an average about 75 per cent. of water. Part of the protoplasm within a cell holds more water associated with it, part less.

Closely associated with its power of holding water is its tendency to assume an architectural form. In large vegetable cells, such as those of the hairs within the flowers of Tradescantia, the protoplasm may be seen, under the microscope, arranged in threads containing granules which are incessantly streaming up and down them. The spaces between the threads are filled with water. Such mobile protoplasm cannot be said to have a structural form. But in the greater number of cells, and especially in animal cells, the protoplasm is disposed in a network, with usually a tendency for the strands of the network to set in lines. In attempting to define these very variable networks, the microscopist is obliged to speak with caution. He finds it very difficult to distinguish between appearances which he is justified in regarding as inherent in the cell-substance, whether alive or dead, and appearances which he may have induced by the action of reagents whilst preparing the tissue for examination. Rarely can he assert that he sees a network in a living cell. When examining a dead cell, he is bound to recognize that the preservatives and hardening reagents which he used may have caused the proteins to coagulate in a particular pattern. If he obtains the same pattern with several different methods, he infers that the appearance which he sees is that of a structure existing in the living cell; but he is never quite sure that it is not an arrangement produced by reagents after death.

The tendency of protoplasm to dispose itself in the form of a network or sponge-work is of the greatest interest in its bearing upon the theory of its activity in effecting chemical change. The body itself, as we shall find later, is a network of tissues enclosing lymph. The lymph in the tissue-spaces contains foods and waste products in solution. The tissues are constantly taking from it the former, and discharging into it the latter. Every cell is, microscopically, a tissue. The strands of its protoplasm are perpetually sorting foods from its cell-juice, adding to its cell-juice waste products. By diffusion, foods, including oxygen, pass from lymph to cell; waste products, including carbonic acid, pass from cell to lymph. If water be added to gum, the gum swells. The mixture is homogeneous. Diffusion takes place slowly through the mucilage. When water is taken up by protoplasm, the protoplasm swells; but the mixture is not homogeneous. The protoplasm expands as a wet sponge expands, although the relation of the enclosing reticulum to the water which it encloses is far more complicated. It is, as it were, a sponge made of gum. Some water is combined with the protoplasm; the remainder fills its spaces. There is an active surface relation between the free water and the protoplasmic threads. As water rises in a capillary tube, as it passes from the inside to the outside of a flannel shirt, so it circulates within the cell.

Irritability is a property commonly attributed to protoplasm, but it is a little doubtful whether there be not again some danger of an illogical use of terms. An amœba, one of the unicellular organisms found in ponds, has the power of moving. If a piece of a water-plant—the stalk of duck-weed is a suitable object—be examined with the microscope, these little animals are usually to be found upon its surface. They feed upon algæ more minute than themselves. When they come in contact with something suitable for food, their body-substance flows around it. The food is coagulated. So much of it as is digestible is digested; the remainder is extruded. Constantly parts of the body-substance are protruded, other parts retracted, in the search for food. Such movement is a response to stimulus. Stimuli received at one part of the body-substance are transmitted to another. The body-substance is irritable. It acknowledges stimuli; it conducts them. But if the amœbæ are watched until, owing to lack of oxygen or other cause, they die, their irritability comes to an end. It is a phenomenon of life. Again the physiologist is in a dilemma. Either protoplasm is not protoplasm when death has supervened, or protoplasm is not irritable as such. It is somewhat paradoxical to ascribe to the physical basis of life a property which depends upon its being alive.

Yet the influence on protoplasm of anæsthetics makes it difficult to understand how it can be either physically or chemically a substance which loses its form or changes its constitution whenever it ceases to display the usual evidences of its existence. Chloroform and similar agents suspend irritability. Yet irritability returns as their influence passes off. They appear to hold it in check without—at any rate visibly—changing the nature of the irritable substance.

All parts of the minute body-substance of an amœba are equally irritable. In higher animals irritability is concentrated in the nervous system. The form of irritability to which consciousness is adjunct is restricted to the cortex of the great brain.

Chloroform and similar agents are termed “anæsthetics” because they abolish the irritability of the cortex of the great brain, before their effects upon other parts of the nervous system are sufficiently pronounced to endanger the working of the animal machine. Pain ceases to be felt before the dose of anæsthetic is sufficient to suspend the irritability of the centres of reflex action. All protoplasm, whether animal or vegetable, is susceptible to the influence of these agents. They cause it to enter into a state which resembles death in all respects save the impossibility of revival. There is a great demand in the Paris flower-market for white lilac in the winter. The plant cannot be forced until after a period of rest. By withholding water and placing the bushes in a cool, shady place, horticulturists endeavour to send them prematurely into their winter sleep. Recently it has been found that from three to four weeks can be gained by placing the bushes for a couple of days in an atmosphere charged with the vapour of ether. Some change of state is evidently produced in protoplasm by anæsthetics. It ceases to be capable of receiving or transmitting stimuli. But we cannot picture the change as being sufficiently pronounced to justify the hypothesis that so long as it is irritable protoplasm is a complex substance which is resolved, as it loses its irritability, into simpler compounds familiar to the chemist. Perhaps it would be more correct to say, we cannot picture these chemical substances as reuniting into protoplasm when the effect of the anæsthetic passes off. Rather are we driven to think of living matter as a mixture of many substances in a state of molecular interchange, and to suppose that the activity of this interchange is diminished by anæsthetics.

Chemical activity is a property of protoplasm. In its network combinations and decompositions are effected more extensive in range than any which a chemist can cause to occur in his laboratory. From ammonia, carbonic acid, and water, a plant makes albumin. A chemist cannot make albumin, no matter how complex may be the nitrogenous substances which he endeavours to cause to combine. Albumin is resolved by animals into water, carbonic acid, and urea. Cells of the gastric glands set a problem which puzzles the chemist by making hydrochloric acid from sodic chloride without the intervention of a “stronger” acid. Many other illustrations of the same kind might be cited. Although the tissues of animals act chiefly as destroying agents, their protoplasm is not without constructive power. There is apparently no limit to the capacity for synthesis of plants. The chemistry of living things may be divided into two provinces, absolutely antagonistic in the series of reactions which they comprise. The one series is constructive, synthetic; the other destructive, analytical. Construction involves the locking up of energy. It is endothermal. Destruction results in the setting free of energy. It is exothermal. To accomplish synthesis energy must be added. Plants obtain it from the sun’s rays. Animals disperse energy, set free by the analysis of substances formed in plants, in maintaining their bodies’ warmth and movement.

The chemistry of the laboratory and the chemistry of protoplasm present certain contrasting features. A chemist reaches the compound which he wishes to form by effecting a series of interchanges. For example, he wishes to form uric acid by uniting a nucleus contained in lactic acid with urea. First he introduces chlorine and ammonia into the molecule of lactic acid. He makes trichlorlactamide. Then he heats (supplies energy to) a mixture of trichlorlactamide and urea. Two of the chlorine atoms carry off hydrogen atoms from the urea. A third leaves the trichlorlactamide with its ammonia. Water also breaks away. Uric acid remains.

In this example the trichlorlactamide may be said to exchange its chlorine and ammonia for urea. When he planned the reaction, the chemist foresaw what would happen. He knew that if he weakened the grip of the lact radicle upon them, chlorine and hydrogen, chlorine and ammonia, oxygen and hydrogen, would take the opportunity of getting away together. The lact radicle and urea would be left with dangling arms, which must “satisfy their affinities” by linking up. It would be rash to assert that any reaction is impossible to Nature’s chemistry; but it may safely be said that the reactions which protoplasm effects are, so far as we know them, of a different type from this laboratory example. Uric acid is the chief excrement of birds. It is made in the liver. If the liver is shut off from the circulation, lactate of ammonia is excreted in the place of uric acid. It is therefore, in all probability, lactate of ammonia which the liver transforms into uric acid. We cannot pretend to say how this is done, although an empirical formula for the change might be drafted easily enough.

Lactate of ammonia has the formula NH₄C₃H₅O₃. Uric acid, C₅H₄N₄O₃, contains a much higher percentage of nitrogen. It could be produced from lactate of ammonia by the condensation of the nitrogen-containing nucleus and the addition of a sufficient amount of oxygen to complete the oxidation of the superfluous carbon and hydrogen into carbonic acid and water. It is of little interest to count the number of atoms concerned in this process. If a bird be fed upon urea, or even upon various salts of ammonia, its liver will change them into uric acid. Lactate of ammonia is the nitrogen-containing compound with which the liver has normally to deal. It can handle almost any other combination of nitrogen with equal ease. In the protoplasm of the liver the atoms in the molecule of lactate of ammonia are rearranged. The molecules are condensed; water is set free; oxidation occurs. It seems almost as if molecules, when in contact with protoplasm, lose their individuality. Their atoms fall into new groups. Chains which the chemist finds so difficult to break—chains from which he can remove a link only by insinuating another and a stronger—are, when in contact with protoplasm, groups of isolated links. The links rearrange themselves. They join into new circlets, larger, smaller, more open, closer. As grains of sand on a metal plate group themselves in harmony with the vibrations caused in the plate by drawing a violin bow across it, so the atoms answer to the forces which set protoplasm vibrating. There is no waste of force. The chemist may need to enclose sawdust and lime in a crucible heated in an electric furnace if he wishes to compel them to combine as carbide. He supplies energy enormously in excess of the amount which the new compound will lock up. Under the influence of protoplasm the reactions which occur are exactly proportional to the amount of energy supplied. Or, if it be a reaction by means of which energy is set free, it occurs spontaneously. No energy is absorbed in setting it going. All the energy liberated is effective. The chemist very frequently needs to heat a substance in order to cause it to decompose, even though it be falling from a less stable to a more stable state.

Vital chemistry and mineral chemistry are so widely different in their methods that one is tempted to think of them as different in kind. We find it very difficult to look at both from the same point of view. Men’s minds are preoccupied with the things that they have to do for themselves. The chemistry of the laboratory is seen as a science circumscribed by the laboratory walls. If it were possible to stand outside, it would be evident that it is only a part of the science of molecular change. Matter changes its state under the influence of force. Many rearrangements are effected by the chemist which do not occur in nature. He has an almost infinite range of action. Yet many of the rearrangements of matter and force which are occurring in the dandelion on his window-sill (if the fumes of sulphuretted hydrogen have not killed it) he is unable to reproduce. It is largely a question of waste. Nature works with greater precision than the chemist; but the chemist could do all that Nature does if he had but the same control of force.

We have spoken of the reactions which occur in protoplasm as divisible into two great series—the one ascending, constructive, endothermal; the other descending, destructive, exothermal. In the one series energy is locked up; in the other series it is set free. Synthesis and analysis are names applied to the two series respectively. Synthesis is characteristic of plants, although analysis is also perpetually occurring. Plants fix carbon from the air and liberate oxygen. They also respire, setting free carbonic acid. Analysis is characteristic of animals, although synthesis is not excluded.

Of the chemical processes which occur in plants very little is known. Few halting-places between raw materials and finished products can be marked. The final products are sugars and starches, oils, proteins, and a vast number of other substances—alkaloids, glucosides, etc. Condensation, dehydration, and deoxidation are the methods by which the synthesis of these compounds is accomplished. These methods are adopted simultaneously in varying degree. The large group of bodies known as sugars and starches are, with few exceptions, built on the C₆H₆ model; in fruit-sugar, C₆H₁₂O₆, six atoms of carbon are linked to one another and to six molecules of water. The formula of starch is (C₆H₁₀O₅)ₙ. Not only has water been removed from the molecule, but an unknown number of molecules have been linked together. This condensation and dehydration is effected whenever sugar carried in cell-sap is deposited as starch in seeds or tubers. These compounds are hexatomic. The chemist pictures them as made by the union in the first place of six atoms. As small drops unite to form larger ones, so small molecules, under the direction of the protoplasm of plants, close together.

The reactions which characterize animal protoplasm are of a different kind. They belong to the descending series. Close molecules are unfolded. Water is incorporated with them. Hydrogen and carbon are oxidized into water and carbonic acid. The conversion into sugar of glycogen or of starch may be taken as an illustration of expansion. Starch, (C₆H₁₀O₅)ₙ, becomes maltose, C₁₂H₂₂O₁₁, and then dextrose, C₆H₁₂O₆. The grouped molecule of starch opens out. The breaking of the double molecule of maltose into two molecules of dextrose is a further illustration of progress towards simplicity. Hydration, union with H₂O, accompanies this expansion. Hydrolysis is the secret of almost all digestive acts. Starch is hydrolysed into sugar, fat hydrolysed into glycerin and fatty acid, proteins hydrolysed into peptones.

All the chemical transformations which protoplasm is able to accomplish are of the nature of fermentations. The term fermentation was first applied to the effervescence which occurs in grape-juice when its sugar is being converted into alcohol, carbonic acid gas, and certain substances which appear in relatively small quantities. It was discovered later that the yeast which effects this change is a unicellular plant. The term “fermentation” was extended to the production of vinegar from alcohol, and eventually to all such reactions as are carried out by living organisms, or by the secretions or products of living organisms, without the destruction of the agent which is effective in the process. A ferment is an organic body which brings about changes in other bodies without itself undergoing change. At the end of the process, however prolonged, there is as much ferment as there was at the beginning, and its chemical nature is the same. Rennin has been made to curdle nearly a million times its weight of milk, pepsin to digest half a million times its weight of fibrin. As the ferment is not consumed, there is no relation, except one of speed, between the ferment and the quantity of fermentable substance which it is able to transform. We said that a ferment is an organic body. It is necessary to introduce the qualification “organic,” because certain reactions termed “catalyses” which occur in mineral chemistry resemble fermentations in respect of the non-destruction of the agent which serves as intermediary. If a solution of cane-sugar containing a very small quantity of sulphuric acid is boiled, the cane-sugar is “inverted.” It is changed into a mixture of fruit-sugar and levulose. The ferment invertin of the gastric juice and of intestinal juice produces a similar effect; and just as invertin remains unchanged, so also the sulphuric acid is found in the mixture unchanged in nature and in amount after an unlimited inversion of cane-sugar. Great stress was formerly laid upon the similarity between fermentation and catalysis. It has now been shown that catalytic actions are not necessarily of the same nature as fermentation, although the results and, as far as is visible, the means are similar. For example, finely divided platinum (or, better, palladium) causes an indefinite quantity of oxygen and hydrogen to unite. The reaction comes within the category of catalyses. But it is widely different from a fermentation. The metal causes hydrogen to condense, and actually absorbs it into its surface layer. In the liquid form hydrogen cannot resist combination with oxygen. This may be termed a “physical phenomenon,” adopting the common distinction between chemistry and physics. There is no reason for thinking that fermentations can be explained in so simple a way. They may, however, be grouped under the designation “catalyses.” As the initial conditions and final results are similar, it is inevitable that fermentations and catalyses should obey the same “laws” as to mass action, speed, effect of accumulation of products of action, and the like; but it does not follow that invertin and sulphuric acid produce their effects in the same way. Fermentations are instances of catalysis, but all catalytic actions are not fermentations.

So far from dwelling upon the resemblance between fermentation and the catalysis of mineral chemistry, chemists nowadays incline to regard fermentation as essentially a reaction of life. It is very difficult, when attempting to present ideas which are new to thought, to adapt, without ambiguity, existing words. It would be absurd to talk of a substance removed from yeast or bacteria or blood-corpuscles by a process which involves cooling with liquid air, grinding with powdered glass, solution in water, precipitation with absolute alcohol, and resolution in water, as alive. Yet, unlike any known mineral product, it is easily killed. Ferments are not destroyed by cold, but their activity is arrested. They are most active at about the body temperature. Their activity is annihilated by heating them, in solution, to the temperature at which albumin coagulates—a little over 50° C. Although they are not alive, their behaviour very closely resembles that of living matter. They can be obtained only from living things. They produce their effects even though they are present in almost infinitely small quantity. It is impracticable to make a chemical analysis of a ferment, owing, in the first place, to the very small amount available for analysis, and, in the second place, because of the impossibility, with existing methods, of obtaining a ferment pure. The amount of ferment present in even a great mass of yeast, or in many pounds of salivary gland or pancreas, is extremely small. However prepared, it is always accompanied with proteid substances. It is impossible to say whether ferments, like proteins, have heavy nitrogen-containing molecules. The fact that they are not diffusible suggests that they have.

It would be straining language to term fermentation a phenomenon of life; worse, to define life as a sequence of fermentations. Yet it is safe to say that all the chemical changes carried out by living organisms are fermentations. Fermentation and the chemistry of life are almost synonymous terms.

A very large number of ferments are already known. Each has its own specific work to do: “To every fermentable substance is fitted a ferment, as a key to a lock.” It will be understood, from what has been already said regarding our inability to determine the composition of any ferment, that we cannot say whether or not these various ferments differ one from another in chemical constitution. They are classified according to their action, and not according to their nature. Those which build up are termed “synaptases” (συνάπτω, I unite); those which decompose, or hydrolyse, “diastases” (διάστασις, separation). The termination “ase” is added to the name of the substance upon which the ferment acts, except in cases in which other terms have already become so general as not to be displaceable: amylase, hydrolysing starch; sucrase, inverting cane-sugar; protease, hydrolysing proteins. Unfortunately, there is little uniformity in this nomenclature; amylopsin, invertin, pepsin, are terms used as often as those terminating in “ase.” As a distinguishing termination, “in” or “sin” is less desirable than “ase,” owing to the fact that it has been appropriated already as the termination of the names of albuminoids—e.g., gelatin, chondrin, mucin.

The various ferments are substances which protoplasm sets aside for specific purposes. Primitively, contact with the substance to be fermented determined the nature of the ferment assigned to the task. There are reasons for thinking that protoplasm still retains its power of making a suitable response; cases may be cited in which the lock presented to protoplasm shapes the wards of the key. In such cases the fermentable substance provokes the formation of the ferment. But, for the most part, in situations where particular ferments are regularly needed, protoplasm has acquired the habit of making such ferments and no others. The cells of salivary glands accumulate ptyalin, the cells of gastric glands accumulate pepsin, during the intervals between meals.

The capacity of protoplasm for producing a new ferment when it is needed is shown by such examples as the following: Blood-plasm contains a variety of proteid substances. If a solution of white of egg be added to it, the mixture is clear and uniform. Yet egg-albumin is treated by the blood as a foreign body, a poison. When injected into the veins of a living animal, some of it is excreted by the kidneys, some destroyed in the blood-stream. If several successive doses of egg-albumin are injected into an animal (it is most convenient to inject it into the peritoneal cavity), the power of the blood to destroy the intruder is greatly increased. If now a specimen of blood be taken, and the plasma or serum mixed with egg-albumin, the mixture is no longer clear. The egg-albumin is precipitated. The blood of the animal thus “prepared” has developed a ferment, termed a “precipitin,” which throws down egg-albumin. If instead of egg-albumin, which, although a foreign body, is comparatively innocent, a substance which is distinctly poisonous, toxic, be injected into an animal, the first dose, if a large one, will prove fatal. If, however, the first dose be small, and succeeding doses progressively larger, the animal acquires the power of tolerating a quantity of the poison much larger than would have proved fatal in the first instance. A classical example of this, because it afforded an opportunity of directly observing under the microscope the difference between “unprepared” blood and blood from an immune animal, is the acquisition by a mammal of the power of tolerating the injection of the blood of an eel. Eel’s blood contains a toxin which destroys the red blood-corpuscles of a mammal. The dissolution of the blood-corpuscles may be watched with the microscope. If successively increasing doses of serum of eel’s blood be injected into the body of a rabbit, the rabbit acquires the power of resisting the toxin. Further than this, the serum of the immune rabbit injected into a rabbit which has not been prepared confers immunity upon the latter. If the blood of the prepared animal be mixed with the blood of an unprepared rabbit and with eel’s serum, and the mixture examined under the microscope, it will be seen that red blood-corpuscles are no longer dissolved. The immune serum is able to save the blood-corpuscles of the unprepared blood from destruction. During its course of preparation the rabbit developed an antitoxin.

If germs of diphtheria are injected into the blood of a horse, the first injections give rise to marked febrile symptoms. After a number of injections the horse becomes completely tolerant of the virus. Not only does its blood develop sufficient antitoxin to protect it against the toxin of diphtheria, however large may be the quantity injected into its system, but the serum of the prepared horse, when injected beneath the skin of a child suffering from diphtheria, carries with it sufficient antitoxin to destroy the toxin which has gained admission to the child’s blood.

Many more instances might be cited of this capacity of developing “antibodies” of protoplasm. The leucocytes of the blood are incessantly adapting their chemistry to the needs of the economy. All the tissues, it may be supposed, possess the power of developing resistant ferments; but the leucocytes ([Fig. 4]) are the undifferentiated cells, the maids-of-all-work. They have not specialized as makers of ptyalin or makers of pepsin. They are not completely given up to lifting weights, like muscles, or carrying messages, like nerves.

Bacteria are the world’s scavengers. To them ultimately belongs the task of reducing organic matter to the salts which plants reorganize. The cycle of life would be broken if bacteria were suppressed. No sooner has an animal fallen than these little agents commence their beneficent task of resolving its carcass into air and soil. Birds and insects may interrupt their work. They may steal portions of the derelict, use them for fuel, or patch them between their own ribs. But they, too, will soon lie breathless on the ground; and the bacteria are always ready to finish their interrupted task. Why should they wait until the slight change occurs, important to us, but of little consequence to them, which marks the transition of living protoplasm into dead proteins? There is nothing in the constitution of protoplasm which makes it harder to break up than protein. There is no quality inherent in living matter which makes it resistant of decay. We resent the officiousness which prompts bacteria to obtain entrance into the ship while it is still under full sail, with a view to commencing the work of demolition. Deep in our minds lies the conviction that it is contrary to the rules of Nature. We are especially annoyed at the many ruses bacteria adopt to disguise their personalities. The bacteria of the soil we can keep at a proper distance. But bacteria of the stream, bacteria of milk, bacteria of the breath that would betray us with a kiss! It is hard to recognize that they are fairly and squarely playing their part. Birds and insects we can beat off with our hands. Our invisible enemies are everywhere. They are constantly insinuating themselves through scratches in the skin, through abrasions in the mouth, through surfaces of the intestine left unprotected owing to the desquamation of its epithelium. But if we are constantly open to attack, we are policed by myriads of zealous leucocytes, ever ready to reduce the invaders to impotence. The germs which have found entrance fire off a toxin. The leucocytes reply with an antitoxin. There is absolutely no limit to the power of protoplasm to protect itself, if only it be not taken by surprise. It can resist any organic poison if it is allowed a sufficient time to produce the antipoison. The ferment of pancreatic juice, trypsin, is a poison which is unlikely to find its way into the blood. When injected it produces disastrous results owing to its immense activity in digesting proteins. An animal “prepared” by the injection of successive doses of trypsin develops an antitrypsin. Injection of pancreatic juice no longer does it any harm. Tapeworms which live in the intestines are bathed in pancreatic juice; they are constantly exposed to its digestive action. They are not digested, because they secrete an antibody which prevents the development of the activity of trypsin. It is not in this case, strictly speaking, antitrypsin. It is antikinase, a substance which, if extracted from the bodies of tapeworms and added to pancreatic juice, renders it incapable of digesting albumin. The antikinase does not destroy trypsin, but destroys kinase, the co-operation of which is essential to its activity.

Not only has protoplasm the power of meeting with an antiferment any ferment which might prove prejudicial to its own integrity; but after it has been once attacked it continues to defend the vulnerable spot. Its tactics are, it must be confessed, somewhat like those of the dusky warrior who, during his first lessons in the art of boxing, made a point of covering with his fist the place where he had just been hit; but even its power of remembering its last injury is of supreme value to the human race. Before the age of sanitary science, and even, in certain backward communities, in these days of its beneficent rule, conditions producing disease were not necessarily set right as soon as the epidemic was over. The close-packed inhabitants of a ghetto were continuously exposed to germs of typhoid fever, small-pox, whooping-cough. But after their protoplasm had once responded to the need for the production of an antigerm, it either continued for many years to keep a stock in hand, or it kept the recipe within easy reach. The memory of protoplasm is amazing. It is commonly said that vaccination is an absolute protection for seven years. There is no doubt but that the immunity from small-pox which it induces, if gradually lessening, lasts for life. The disease, if it attacks a person who has been vaccinated in infancy, is relatively harmless.

Inoculation, vaccination, is the boxing-master’s method of utilizing the self-protective instinct of the dusky warrior. Knowing that his pupil will for a long while continue to cover an injured spot, he asks himself: “Where is he most likely, when it comes to a serious contest, to be hit?” Then he gives him a gentle tap in that particular place. Does he need to know how to defend himself against small-pox? Give him cow-pox. Is he likely to receive a knock-down blow from typhoid fever? Just show him what it feels like to have a gentle shake. Educate his protoplasm to make antityphoid ferment, by giving him the typhoid germ in such an attenuated form that it cannot do him any harm.

The chemistry of protoplasm is a science which is growing rapidly, or, to speak less arrogantly and more correctly, our knowledge of the ways of protoplasm, the Chemist, has greatly increased during the last few years. We can but watch protoplasm at work. Our experiments, so called, are but windows which we open in the walls of his laboratory. We cannot take the work out of his hands. The methods of mineral chemistry are useless in this search for knowledge. And, naturally, the longer we watch, the more details do we discover in what seemed at first a generalized procedure. We recognize that several manipulations are required in the carrying out of a reaction which hitherto we believed to take place in a single stage. This is not the place in which to give an account of a subject regarded as belonging, owing to its applications, to the province of pathology. But Nature is one, however many be the companies into which we divide the explorers of her secrets. We have attempted the merest outline of the observations made up to the present, and have submitted the results for the sake of the light which they throw upon the way in which ferments are prepared as they are wanted to meet the needs of normal every-day digestion and metabolism, rather than for the purpose of showing the methods by which protoplasm combats disease.

Amongst the chemical phenomena of life is respiration. Respiration in this very general sense means oxidation. The force which is exhibited in living is obtained from the union of organic materials with oxygen under the direction of protoplasm. This is true of plants as well as of animals. It is true even of the subdivision of bacteria, termed anaerobic, because they cannot live in air. They secrete ferments which enable them to decompose compounds which contain oxygen, in order that they may use the oxygen for respiration. It might have been supposed that green plants which are receiving radiant energy from the sun would convert this energy into the forces which enable protoplasm to display the phenomena of life. But this is not so. The energy which green plants obtain from the sun is used in constructive metabolism, and not in maintaining life. Life-force, if we may use the expression, is derived from the oxidation of the substances which the sun’s rays enable the plant to make. A plant, equally with an animal, respires. The distinction between the constructive metabolism of a plant and its respiration may be brought out in a striking way by administering to it sufficient anæsthetic to stop the former without stopping the latter. It may be paralyzed without being killed. If a water-weed—potamogeton is the most convenient—enclosed in a bell-glass filled with water and inverted over a dish of water, is placed in sunshine, bubbles of gas rise from the plant. They accumulate at the top of the bell-glass. If the gas be removed and analysed, it is found to be oxygen with a small admixture of carbonic acid. If a second bell-glass containing water-weed be exposed under the same conditions in all respects, save that a small quantity of chloroform is added to the water, the gas that collects at the top of the bell-jar will be much less in amount. It will be found to be carbonic acid without admixture of oxygen. The power which chlorophyll possesses of decomposing carbonic acid with fixation of carbon and liberation of oxygen is suspended by the anæsthetic; whereas respiration is not interfered with.

Lastly, we must attribute to protoplasm a capacity of growing. The activity of protoplasm depends upon constant molecular interchange. It incorporates molecules of food. It excorporates molecules of waste. If food is abundant and “vitality” exuberant, it takes in more than it gives out. It grows.

If we attempt to formulate a definition of protoplasm, we find that our ideas are far from clear, owing to want of knowledge. The questions, What is protoplasm? What is life? are equally unanswerable. Their definition is reciprocal. Protoplasm is the substance, the material, which exhibits life. Life is the complex of phenomena exhibited by protoplasm. All parts of the body are alive, in their degree. The nucleus of a cell lives, as well as its cell-body. Its capsule may be less alive—that is to say, less vibrant—than the soft cell-substance which it encloses; but it lives. So-called intercellular substance, or matrix, is alive. In growing cartilage the matrix does not behave as a dead substance. It does not crack and gape under the pressure of the dividing and multiplying cell-bodies which it contains. If the windows of a house were endowed with the power of spontaneously enlarging, the walls would be crushed. They would bulge, break, tumble. The matrix of cartilage offers as little resistance to the enlargement of the cells which it encloses as the plasma of blood to the multiplication of blood-corpuscles. It grows with the cell-bodies, and must be considered as divisible into areas, each of which is the periphery of a cell. Muscle is alive. So, too, are bone, teeth, hair, nails. But as we proceed outwards we find the quality of aliveness growing less and less apparent, until at last we acknowledge that it is unrecognizable. Vibrations diminish in amplitude and in rapidity, until the material of which the body is made appears to be at rest.

Biologists apply the term “protoplasm” to the most living substance of which plants and animals are composed. It may be that there is an entity, protoplasm. It may be that in certain situations this exists in an unmixed state. It may be that the degree of aliveness of a tissue or constituent part of a tissue varies as the quantity of protoplasm which it contains. The tendency of protoplasm to dispose itself in a reticulum in the meshes of which other substances accumulate favours such a view. The cells of the deeper layers of the skin are rich in it. The superficial layers are composed chiefly of keratin. It is possible that the network opens out, and its strands grow thinner and thinner, as keratin accumulates. But it cannot be demonstrated that this is the case. There is no completely satisfactory reason for concluding that the life of a cell of the skin resides in its protoplasmic network, while its keratin is inert.

Many attempts have been made to prove that living cells contain something which dead cells do not contain; but no evidence which will bear sifting has, as yet, been adduced in support of this thesis.

CHAPTER III
THE UNIT OF STRUCTURE

Immediately after its discovery in the seventeenth century, the compound microscope was applied to the study of minute plants and animals, their organs and tissues. In this connection and for this purpose the microscope has steadily improved, until perfection has almost been attained. Calculations based upon the physical properties of refracting media show that the limits of the assistance which it can give to the eye have been very nearly reached. One of the first results of the application of the microscope to the study of parts of plants was the discovery of their cellular structure. Robert Brown, looking at slices of cork, saw that its tissue is divided into compartments. It is difficult to ascertain who it was that first used the word “cell.” The resemblance of a slice of vegetable tissue or the surface view of a petal of a flower to honeycomb is so striking that the same comparison probably occurred to the mind of everyone who saw it. Further study with better instruments showed that the cells are not empty. Each cell contains cell-juice, or cell-substance, and in the centre of the cell-substance a miniature cell, the nucleus. Naturalists therefore extended the connotation of the term. A cell was no longer a space with enclosing walls; it had contents. A nucleus was invariably a constituent of the cell. The cell was regarded as an anatomical unit, consisting of a wall, cell-contents, and nucleus. In 1839 Theodor Schwann, using his microscope in the study of animal tissues, recognized the similarity between animals and plants. Animals also, he discovered, are aggregations of cells. He enunciated the Cell Theory. Philosophers are always ready to generalize. It is their business. Seeing that vast numbers of organisms are single cells, that they feed, breathe, divide, and reproduce their kind—in fact, carry out all the functions of life—as isolated cells, they conceived the idea that a visible plant or animal is a community of cells, each an organism in itself. As bees are units of a swarm, as men and women are units of a state, cells are units which for the sake of mutual protection remain associated in a multicellular body. The physiological or sociological aspects of this conception we shall consider shortly; but the anatomical basis of the cell theory was laid without a sufficient testing of the facts upon which it rests; or, rather, one ought to say that, although the axiom, enunciated by Virchow when he applied the cell theory to tumours and other morbid growths, Omnis cellula a cellulâ, holds good, the applications of the theory which certain of its later exponents have made are not necessary sequents.

Every plant, every animal, commences its existence as a single cell. An organism which is permanently unicellular divides. Each of the separate cells into which it divides is a new individual. Higher plants set aside certain cells as ovules, which in due course, after conjugation with pollen grains, grow into plants. In the same way the ova of animals, by repeated cell division, reproduce the species. The individual commences as a single cell. Its complicated body, composed of various organs and various tissues, is formed by the multiplication of cells. Each of the innumerable cells of which it is composed has the structure, and may therefore be presumed capable of performing all the various functions, of a unicellular organism. But it does not follow that the cells retain their individuality. Even unicellular plants (e.g., the extraordinary vinegar and tan fungi, myxomycetes) may for a time merge their individuality in a common mass formed by the aggregation of many cells.

The cells of higher plants are not always, or even generally, anatomically distinct. Their protoplasm, the essential part of every cell, is united with the protoplasm of neighbouring cells by threads which traverse the cell-walls. The cells of the connective tissues of animals are united into a web, or syncytium. This is especially noticeable during early stages of growth. Nerve-cells are connected together by conducting filaments (neuro-fibrillæ). It is possible that nerve-cells and the muscle-fibres which they innervate are from the beginning united by nerve-filaments—that the nerve-cell and muscle-cell grow apart without severing this thread-like connection. Certain anatomists regard the nerve strand which connects a cell in the central nervous system with a number of muscle-fibres, placed, it may be, at a great distance from the nerve-cell, as the bridge which has never been broken in the process of cell division and displacement, which made one primitive cell into a nerve-cell and a group of muscle-cells. Muscle-fibres are not separate cells, but cell complexes. Each muscle-fibre contains scores, in some cases hundreds, of nuclei ([Fig. 16]). It is a cylinder, perhaps 2 inches long, in which cell division is incomplete. Tendons are bundles of exceedingly slender fibres which lie side by side, like silk threads in a skein. The row of cells which gives rise to a tendon undergoes incomplete cell division. Their nuclei divide, and a small quantity of soft body-substance is set apart for each nucleus. The rest of the mass consists of fused cells. It constitutes a continuous rod, which becomes fibrillated as it grows. Vegetable cells are separated by cell-walls. Animal cells tend to develop intermediate partitions; but the partitions are so thick that they can no longer be described as walls. In cartilage the cell-bodies are embedded in a great mass of intercellular substance, or matrix. In this intercellular substance elaborate developments may take place. Elastic fibres may make their appearance in it to form elastic cartilage, as in the case of the epiglottis. In these various instances, although it is perfectly true that tissues are formed by cell division, the cells are not, strictly speaking, separate units. They are not completely divided one from another. It is impossible to recognize their anatomical boundaries.

But there is a much more serious difficulty in applying the cell theory—the difficulty of deciding what are the essential parts of a cell. Long ago it was recognized that many animal cells—white blood-corpuscles, for example—have no cell-wall. It was therefore decided that cell-body and nucleus are the only essential parts. But what is to be said of the red blood-corpuscles of mammals? ([Fig. 4]). Are they cells? They have neither cell-walls nor nucleus; nor does their substance present the structure which is usually associated with the “body-substance” of cells. They are not produced, if the view held by many histologists be sound, by cell division, in the ordinary sense of the term, but appear as spots, gradually growing into discs inside the body of a blood-forming cell. The discs are extruded when they reach their full dimensions. Yet the tissue, blood, is composed of these blood-discs and the intermediate substance blood-plasm. Mammalian blood might be dismissed as a non-cellular fluid secretion containing formed elements, if it were not for its history. In all animals below mammals the red corpuscles are cells with nuclei and cell-bodies. The absence of nuclei in mammals is due to the recognition by Nature of the fact that, as the blood-cells will never be called upon to divide, it is a waste of material to provide each of them with a nucleus. Not only would the nucleus be useless, but it would take up space, diminishing the capacity of the corpuscle for carrying hæmoglobin. The process of cell division is in consequence curtailed. There are, it is true, other ways of looking at this problem. The cells which line the bloodvessels stand in some sort of nutritive relation with the blood. When the lining cells of the bloodvessels are injured or inflamed, the blood clots. But here again it is somewhat straining a point to say that these lining cells are the cells of the blood, and the blood a kind of intercellular substance; especially as a distinction would have to be made between mammals with non-nucleated blood-corpuscles and birds with complete blood-cells.

The physiologist, if he is to feel sure of his ground, needs to know the minute anatomy as well as the naked eye anatomy of the body. But what is there that he does not need to know? He must be chemist, physicist, biologist, pathologist, and expert in various other branches of science. Microscopic anatomy, or histology, as it is commonly termed, will be called upon in this book only when it has evidence to give which bears directly on physiological problems. We have dwelt at some length upon the cell theory because the physiologist needs starting-points. He needs to have in his mind a conception of the fundamental structure of the body. Protoplasm is the material which lives. We begin with protoplasm albeit our conception of protoplasm is so difficult to formulate that we are obliged to admit that in using the term we are almost guilty of playing with words. Protoplasm is the most living substance. The substance which is most alive always presents itself to us as an imperfectly transparent, viscous material, which proves on analysis to contain a large quantity of certain proteins mixed with various organic and inorganic compounds. Protoplasm is organized into, or distributed amongst, cells, which in any given tissue present a fairly uniform size. What determines the size of cells? Speaking generally, cells are small—say about 0·01 millimetre in diameter. In early stages of growth, cell division occurs as soon as the cell attains to something like this size. It would seem that when nutriment is abundant cells add to their protoplasm more than they lose. Having attained certain dimensions at which the conditions most satisfactory for cell life reach their limit, cell division occurs. The big drop falls into two smaller drops, each of which grows more rapidly than the big one was growing at the time when it began to divide. But if there be an optimum size for nutritive purposes, this limit is suspended in many cases, and for various reasons. Take the ovum itself as an example. It is vastly bigger than the cells into which it divides. The yolk of a hen’s egg is, when first formed, a single cell. By the time the egg is laid cell division has already set in. In the embryo there are cells which surpass the average dimensions—the unexplained “giant cells” which appear in the liver as soon as it can be recognized as such ([cf. p. 65]). These disappear from the liver, but are for a time evident in the spleen. The large cells found in the marrow of bone, some with a great single nucleus, others containing a bunch of separate nuclei, also show that there is no fixed limit of size. It is generally considered that the giant cells of marrow—or, at any rate, those which are multinucleated—are leucocytes which are engaged in scooping out the bone; consuming the hard tissue on the inner surface of the hollow cylinder in order that, by deposition of new material on the outside of the cylinder, the size of the whole bone may be increased—leucocytes battening on bone which, owing to interference with its blood-supply, is breaking down. They have not time to divide. Nourishment is superabundant. Although much too large for a vigorous standard of cell life, they continue to grow, putting off the duty of cell division until the supply of nutritious food begins to run short.

The most remarkable variations in size are to be found amongst the cells of the nervous system. It may be given as one of the most distinctive characters of nervous tissue that its cells have no fixed or standard dimensions. A nerve-cell enters into connection with other nerve-cells and with muscle-fibres by means of branches, or cell-processes, as they are termed. The cells may be globular, as in the sympathetic system, or star-shaped. Each cell gives off a certain number of processes, which divide like the branches of a tree, and one process which may run for a very long distance without dividing. This latter thread-like process places it in communication either with a distant part of the central nervous system or with the muscle-fibres which it controls. By means of such a thread a cell in the spinal cord may be connected with muscle-fibres of the hand or of the foot. The thread is really a bundle of filaments (neuro-fibrillæ) which separate to supply a number of muscle-fibres. It is, in its whole length, a part of the cell in which it originates. The size of the cell varies as the number of filaments in this bundle (termed the “axon”), and possibly also as their length. Hence it comes about that nerve-cells may be amongst the smallest, or they may be the very largest, in the body. The so-called “granules” of the cortex of the cerebellum and of the cerebrum are almost as small as red blood-corpuscles ([Fig. 23]). Each of them has five or six minute branched processes and an exceedingly delicate axon. The large cells of the cerebral cortex, which send their axons far down the spinal cord, and the large cells of the spinal cord which supply the muscles of the body, have a diameter ten or twelve times as great as that of a granule. But larger still are the nerve-cells which supply the electric organs of the torpedo and other electric fishes ([p. 295]); and largest of all are the cells which innervate the curious “fishing-rods” of the strange angler fish (Lophius piscatorius). It is difficult, owing to their irregular shape, to say how large these cells are; but they are visible to the naked eye.

The anatomical unit of structure is the cell. Cells are the bricks of which the body is built. Some are large, others small, as befits the part which they take in the construction of the body. If the tissue be merely a supporting tissue, connective tissue, cartilage, bone, its cells are uniform in size and small. If it have functions to perform which in some cases are carried out best by small cells, in other cases by large ones, the cells are adapted in size to the work that they have to do. Of the various kinds of wandering cells, some—the bone-forming cells (osteoblasts), for example—are small; others—the bone-eating cells (osteoclasts)—relatively large. Nerve-cells, like telephone exchanges, are large or small according to the size of the area which each supplies.

All animals of complex organization, from starfishes and sea-urchins to Man, are inhabited by motile cells. In addition to the bricks which enter into the construction of its fabric, each fixed in its place and definitely united to its neighbours, the animal contains leucocytes which wander through its tissue-spaces or float down the streams of lymph or blood. We are disposed to speak of these wanderers as inhabitants of the body, to distinguish them from the elements which enter into the construction of their habitation. It is difficult to avoid the temptation of describing the body as a habitation. Allegorical as Aristotle’s distinction between body and soul—between the habitation and that which inhabits—may seem, when contrasted with the exact language of modern science, it would save many a periphrasis if we might still use the monosyllable “soul.” The fixed tissues constitute a unity, bound together by nerves. The work done by glands and muscles is done in response to directions conveyed by nerves. It is impossible to say where the control of the nerves ceases—to point out any fixed tissue which is not co-ordinated with other tissues, nor susceptible to the influence of the environment as impressed upon the central nervous system, through the medium of sense-organs. The fixed tissues constitute a habitation for the “soul.” They share in a common life. The wandering cells are as independent of control as the parasites which occasionally find entrance into the body. Each must have a soul of its own in Aristotle’s sense. Like parasites, they carry on all the business of nutrition, respiration, cell division, without reference to the needs of the fixed tissues. They take what they require from the lymph as it leaves the intestines loaded with the products of digestion; they take it from the lymph in the tissue-spaces; they take it from the blood. When nutriment or oxygen runs short, they do not share the privations of the fixed tissues. Only indirectly is their well-being affected by that of the body as a whole; only accidentally is the death of the body the occasion of their death. The same might be said of such parasites as the “blood-worms” of Egypt, or the trypanosomes (the cause of “sleeping sickness”) of Equatorial Africa. Occasionally, in the rare disease lymphocythæmia leucocytes multiply exceedingly, not, apparently, in response to a call for their presence in large numbers, but in defiance of the needs of the economy, and with baneful results. To the indispensable services which wandering cells render, frequent reference will be made. In the present connection, and while we are searching for the principles of construction of the animal body, it would be desirable, if we could do so, to define the status of wandering cells. If they entered the body from without, they would be parasites of commensal type, intruders who share in the food and shelter of the body in return for service. But they do not enter from without. They are cells of the growing body which, detaching themselves from the cells which are forming tissues, assume a wandering life. They are not to be recognized in the embryo until development is considerably advanced. Their origin is far from clear, but histologists believe that, although they are not recognizable as wandering cells in the earliest stages of growth, they, or rather their parent cells, are set apart at a very early date. Probably they are not formed in the embryo proper, but in the “extra-embryonic area,” from which they emigrate into the embryo. In this sense they come in from outside. But, after all, the extra-embryonic area equally with the embryo is a product of the ovum. Looking at the body as a whole, we recognize a common life, a soul in Aristotle’s sense, which inhabits the framework of fixed tissues; and at the same time we see a multitude of independent cells, each an organism in itself, produced, like amœbæ, from similar independent cells by cell division, absorbing the body-fluids, consuming invading germs and fragments of decaying tissues, dying, disintegrating, in their turn absorbed. Wandering cells are autonomous in the largest sense.

All multicellular plants and animals are formed by division of a primitively single cell, the segments remaining in contact. As the scale of life is ascended, the cells which are massed together in the body, whether of a plant or of an animal—we are still unable to find any word other than body for the thing as a whole—tend more and more to differ in appearance. Some are large, others small. Some have cell-walls; others have none. Some remain “protoplasmic”; others are largely composed of “metaplasm.” Better terms are wanted to connote “most living substance” and “less living substance” respectively. It would be easy to coin suitable words, but, alas! the nomenclature of physiology is already hopelessly encumbered, and there is little prospect that a bad word will die when a good one is available in its stead. Differences in structure indicate differences in function. A division of labour has set in. The cell starts with capacities for every function. Its particular situation renders it desirable that it should cultivate one capacity at the expense of the rest. It specializes in a particular direction. If it happens to be placed in the centre of the body on the course of the bloodvessels which bring to the embryo food and oxygen from its mother, it develops a great capacity for taking up food. It accumulates in its substance a vast quantity of nutriment which it cannot consume, holds it, and passes it on into the blood-stream as it is required. Thus the liver is formed. In the embryo it attains to a great size, equal to about one-half the whole body-weight; but whether storing food be its chief function at this stage, or whether the other special functions for which it is responsible are equally important, remains a question for further research. In subsequent life its main work is to store food. After birth, when the child prepares its own food by processes of digestion in its stomach and intestines, the blood-supply of the liver is so modified that the blood from the digestive organs is passed through it. Now and for the rest of life the liver is the storehouse of food, the larder of the body. It is a reservoir from which supplies are distributed as required. A liver-cell retains many primitive characters. It is soft and destitute of envelope. But under the microscope it appears, unless it be taken from a starving animal, unlike any other cell ([Fig. 7]). It is always loaded with masses of glycogen. Sometimes it contains fat globules also. This is perhaps the simplest of all instances of specialization of function. An amœba can take up food. Presumably it always absorbs as much as it can get, the simple law of growth with cell division making it impossible for it ever to get too much. The cells which in the liver are so fortunate as to be placed on the route along which food is carried into the body retain the appetite of an amœba, but lose its capacity for growth and cell division. They return to the blood-stream, when it is deficient in food, the stores which they took up when food was in excess.

The specialization of a gland-cell is opposite in kind to that of a liver-cell. It takes up no more food than it requires, but it has developed a great capacity of producing from the food a substance which would no doubt be needed for its own purposes were it an isolated cell, but which the gland-cell places at the service of the body as a whole. An amœba can digest proteid substances. A cell of the pancreas produces the ferment necessary for the digestion of proteins, and secretes it into the alimentary canal.

To take another instance of specialization. An amœba responds to stimulation by changing its shape. It contracts in one direction, expands in another. A muscle-fibre has developed the capacity of contraction at the expense of all other functions. During the course of its growth it changes from a round cell into one that is elongated. The elongation is in the direction in which it acts with greatest efficiency. Its cell-substance is very highly specialized in order that it may have the maximum capacity of contraction in this direction.

Sensory cells develop to a maximum the capacity of responding to external force; nerve-cells, the capacity of conducting the impulses generated in sensory cells. The body is a republic in which every citizen develops to the highest degree the capacity of doing the thing which his situation makes it desirable for him to do.

The possibility of isolated cell life, and the necessity within certain limits of cell division, have led biologists to dwell too much upon the independence of the separate cells of which the body is composed. Protoplasm organizes itself into cells, but cells are not necessarily anatomically distinct. They may be the partially separate elements of a syncytium, or there may be but the faintest traces of cell separation. The objection to looking upon cells as isolated, self-complete units does not hold good to the same extent when they are viewed from a physiological standpoint. A cell is an administrative area. For purposes of nutrition, respiration, and cell division it is autonomous. It is responsible for its own local affairs. If a part is cut off from it, this part loses its vitality; this, at least, is the conclusion drawn from the atrophy of the axons of nerves when they are cut off from the cells of which they are outgrowths. Apparently we must understand by “the cell,” when speaking of the cutting off of a part, the portion of the cell which retains the nucleus; although we must be careful not to lay too much stress upon the nucleus as the centre of cell life. Red blood-corpuscles, as already pointed out, have no nuclei, and yet they live. Cell growth, estimated by mere increase in size, does not depend upon the nucleus. Many cells of the skin and its appendages increase considerably after the nucleus shows changes which clearly indicate that it is far advanced towards decay. But increase in protoplasm, cell growth in a legitimate sense, and especially cell division, are dependent upon the presence of an active nucleus. While, therefore, histologists no longer formulate the cell theory in the restricted terms in which it was enunciated some years ago, they still regard the cell as the unit of structure and unit of function. The body is built of cells, and whatever is done by the body as a whole is done by its individual cells.

CHAPTER IV
THE FLUIDS OF THE BODY

From one-fourth to one-third of the whole body is fluid. If the skin be regarded as a water-tight bag, three-fourths or rather less of its contents are solid, one-fourth liquid; and even its apparently solid contents, the tissues, contain much water. Water is an essential constituent of protoplasm. It is also present in cell-juice. The estimate given above does not include the fluid within the cells, but only the fluid with which the cells are bathed. In a general sense this extracellular fluid, excluding blood, is termed lymph. It occupies the spaces of a gauzy “connective tissue,” which connects, or separates—the terms are equally appropriate—muscles, nerves, glands, and other tissues of specialized function. Nowhere, except, in a fashion, in the spleen, does blood come in contact with a cell. The lymph which more or less surrounds them is the bath from which cells receive their food and oxygen, into which they excrete carbonic acid and tissue-waste. The network of lymph-spaces is traversed by capillary bloodvessels with walls composed of flattened connective-tissue cells. Such cells are usually spoken of as elements of an “endothelium.” As the epithelium covers the surface of the body, so endothelium lines its cavities. Endothelial cells are thin scales or tiles with sinuous borders dovetailed one into another. That the tiles which form the walls of capillary vessels are not cemented together in any proper sense is shown by the facility with which white blood-corpuscles, leucocytes, by their amœboid movements, push them asunder when making their way from the blood-stream into the tissue-spaces, or vice versa. They offer no more resistance to a leucocyte than a pair of curtains hanging in front of a door offers to a child. Yet so long as the endothelial cells are alive they keep their edges in such close apposition as to constitute a continuous membrane which shuts off blood from lymph. They are always close enough together to prevent red blood-corpuscles from escaping from the capillary vessels; but their resistance to the passage of the different constituents of plasma varies greatly. The membrane which they compose is more complete and less pervious, or less complete and more pervious, in accordance with the nature of the tissues which surround it, and their varying needs. The blood-passages of the liver may be described as filters. The escape of red blood-corpuscles into lymphatic vessels is prevented, but they offer practically no resistance to the plasma. Plasma—“lymph,” as it is termed as soon as it is outside bloodvessels—passes through the walls of the capillaries of the liver unchanged in constitution. Where they traverse glands (other than the liver), muscles, skin, and various other structures, the walls of capillary vessels, while offering practically no resistance to water and diffusible salts which can pass through membranes, prevent proteid substances from passing from blood to lymph, except in extremely small quantities. In this way an exquisite balance is automatically maintained. Water and salts pass out as they are needed. But they never pass out in excess, because the protein-containing blood-stream tends to keep them in, in virtue of the same attractive force which enables it to suck in the oxidized products thrown into the lymph by the tissues. Whatever a tissue needs it takes from the lymph. Suppose that bone is being formed. Large quantities of lime and phosphates are needed for the calcification of the cartilage in which it is modelled. The cartilage absorbs lime and phosphates from the lymph which bathes it. Lime salts and phosphates immediately begin to diffuse from blood into lymph. The hurrying blood-stream brings up further supplies from the walls of the intestine, products of digested milk and other foods. Lymph contains (although not in the same proportions) everything which blood contains. Many an analogy may be found in the world of economics, although no illustration would be sufficiently complete. From the lymph tissues take the fuel that they need, the oxygen with which to burn it, the foods for their own repair, the raw materials for their arts. Into it they throw their smoke, their drainage, the slag and refuse of their factories. The blood replaces the supplies as they disappear. It absorbs all waste. Lymph occupies streets, market-place, passages, corridors. The blood-stream is a closed system, rolling down the streets and through the market-place, on its never-ceasing circuit from port and mine to open air and open sea. From the alimentary canal it picks up food and fuel; the lungs give it oxygen, and disperse its carbonic acid; the kidneys purge it of non-gaseous waste.

Fig. 3.—A Ductule and Two Acini of a Mucous Gland of the Mouth, with a
Muscle-fibre cut Longitudinally; Capillary Bloodvessels and Connective Tissue.

Stellate connective-tissue cells form a labyrinth of intercommunicating lymph-spaces which separate the gland-cells and the muscle-fibre from the walls of the capillary bloodvessels. The capillaries contain circular red blood-corpuscles and nucleated leucocytes. Some of the leucocytes are squeezing their way either out of a capillary into a lymph-space or vice versa. A granular leucocyte is to be seen in a lymph-space at the bottom of the picture.

The facility with which the constituents of blood pass out to the lymph, and the constituents of lymph pass into the blood, depends upon the condition of the walls of the capillary vessels. Water and substances dissolved in water might pass through the wall of a capillary vessel in either of three ways—by filtration, by osmosis, or by secretion. A filter is a porous barrier, which allows water and all substances dissolved in water to traverse it. The solution passes through unchanged in composition. Only solid particles are kept back. The rapidity with which fluid passes through a filter varies as the difference between the pressure on the one side and the pressure on the other. A membrane does not allow of filtration. Water and things dissolved in water pass through it by osmosis. Some things it will not allow to pass; such, for example, as gum, mucin, white of egg. To others it offers resistance in varying degrees. Most of the things that can diffuse through a membrane are capable of crystallization; but the membrane exercises some control over the passage of even crystallizable substances when in solution. If a membranous tube containing water in which proteins, sugar, and various salts are dissolved is hung in a basin of pure water, the proteins remain in the tube; the sugar and the salts pass through its wall into the surrounding water. But they pass at different rates. Those of small molecular weight pass more quickly than those whose molecule is heavy. After a time a condition of equilibrium is established. No more salts pass out of the tube. If now the contents of the tube and the contents of the basin are analysed, it will be found that the tube contains all the proteins, some of the sugar, and some of each of the salts, although not in the proportions in which they were present at the commencement of the experiment. The water in the basin contains some sugar and some of each of the salts, but not in the same proportions in which they are found in the tube. As a matter of fact, the same number of molecules would be present, per unit volume, on each side of the membrane—in the tube and in the basin. In this respect the percentage composition of the two solutions would be the same. But some of the molecules being heavy, others light, the weight of salts which unit volume of the solution in the tube would contain would not be the same as the weight of salts in unit volume of the solution in the basin. A membrane exerts a discriminating action on the substances which pass through it. Secretion is osmosis in disguise. It may be even filtration in disguise. A gland-cell (like an amœba) takes things up and passes them out without regard to their osmotic equivalent. It seems to exercise a choice. It seems to act in disregard of the laws both of filtration and of osmosis. So, at least, it appears to us when we are looking at the result in ignorance of what has happened inside the living cell. The passage from blood to lymph and vice versa through the wall of a capillary vessel is in certain situations or at certain times a mere process of filtration; at others a process of restricted filtration. If the wall is behaving as a perfect membrane, it is a process of diffusion, or osmosis. It seems unnecessary to regard it, in any case, as a process of secretion. The more widely the capillaries are dilated, the less resistance do they offer to exudation. The narrower their calibre, the greater is the restraint which they place on the escape or entrance of fluid. When the skin of the palm of the hand is not sufficiently thick to protect the soft tissues beneath it from the injurious effects of the prolonged pressure of an oar or an axe, the capillary vessels of the under-skin dilate; more lymph transudes; the skin is raised up as a blister. The same thing happens when the capillaries are dilated and paralyzed by scalding water. The fluid of a blister has much the same constitution as blood-plasm, except that it contains less proteid substance. These results might be regarded as purely mechanical—the direct effects of pressure or heat upon the membranous capillary wall. But the “vital” element is more important. The capacity of endothelium to act as a barrier depends upon its nutritive condition—its vital integrity, as it might be termed; which no doubt in the last resort means its chemical relation to the fluids which bathe it. Now and again blebs, like blisters, are formed on the skin—the herpes which appears about the mouth; urticaria, which is more generally distributed; and various other cutaneous disorders. Frequently a connection can be traced between these eruptions and the consumption of a particular food. An attack of urticaria results not uncommonly from eating lobster, mussels, rook-pie, or some few other articles of diet. Various things—bad fish, for example—may produce the same effect; but shell-fish have an especially evil reputation. If extract of lobster or of mussels be injected into the blood of an animal, the amount of lymph which leaves the blood is markedly increased. The extract acts as a poison upon the endothelium of the capillary walls. It increases its permeability in all conditions in which lymph escapes in undue quantity from the blood-stream, or escapes more rapidly than it is absorbed; the nutritive condition of the endothelium is disturbed. Its unusual permeability is due in part, no doubt, to the dilatation of the capillary tube, the stretching of its membranous wall; but it is due also to the diminished vigour of the endothelial cells. They have lost to a certain extent their capacity for holding their edges in perfect apposition.

When the circulation is sluggish, owing to the inefficiency of the heart, the tissues become œdematous. In other words, lymph accumulates in the tissue-spaces. When the skin of a healthy person is pressed, it returns to its natural position as soon as the pressure is removed. If there is a tendency to dropsy—for ages the term “hydropsia” has been thus familiarly clipped—the finger leaves a pit behind it when pressed upon the skin. It is some little time before the lymph in the connective-tissue sponge readjusts the surface. Excessive escape of lymph from the blood, or its insufficient return into the blood, may also be the result of obstruction to the flow in the great veins. When the veins of the leg are varicose, the weight of the column of blood in the distended vessels impedes its circulation. After standing, the tissues about the ankle become œdematous. The œdema disappears on lying down. A hardening (cirrhosis) of the liver impedes the circulation of the blood which comes to it through the portal vein from the walls of the alimentary canal. The capillaries of the stomach and intestine are distended. Lymph accumulates in the abdominal cavity, producing ascites, another form of dropsy.

It is almost hopeless to attempt to disentangle the various factors which disturb the balance between blood and lymph—excessive outflow from blood, deficient inflow from lymph, stretching of the endothelium of the capillary tubes, imperfect nutrition and consequent imperfect apposition of the endothelial scales, increased permeability of the scales. The exudation which accompanies inflammation would seem to be due to the diminished vitality of the endothelium rather than to a mechanical factor, such as increased blood-pressure in the capillaries, and their consequent distention. Ascites is, apparently, a purely mechanical result of the resistance offered to the passage of blood through the liver; but pleurisy, the accumulation of lymph in the space between the lungs and the chest-wall, cannot be explained in the same way. There is no undue pressure on the vessels in which the blood circulates through the inflamed pleura (the investing membrane of the lungs and lining membrane of the chest), yet the walls of the capillaries fail to maintain a proper balance between blood and lymph.

Hitherto we have spoken of the lymphatic system as a labyrinth of communicating spaces containing stagnant fluid, which is kept in a fitting state by egress and ingress out of and into blood. Such a mental picture is substantially correct. But the system is complicated by the presence of lymphatic vessels. Cells of the connective-tissue sponge-work arrange themselves side by side. They flatten into endothelial scales. The borders of the scales close up. They form lymphatic channels, wider than blood-capillaries, but strictly comparable in every other respect. The lymph capillaries unite into larger vessels. The larger vessels are connected by cross-branches; they form plexuses. Their walls are strengthened with fibrous tissue. Like the veins, they are abundantly provided with valves, which check any tendency to a backward flow on the part of the fluid which they contain. Lymphatic plexuses surround and accompany the larger bloodvessels. They are disposed on the surface of muscles and glandular tissues. They are abundant beneath the skin. Nearly three centuries ago the lymphatic vessels of the mesentery, which collect products of digestion, especially fat, from the walls of the alimentary canal, were recognized owing to the milkiness of their contents after a meal. They were, on this account, termed “lacteals.” Other lymphatic vessels, owing to their transparent walls and colourless contents, are not easily seen; but they are readily injected with mercury or other fluids which render them conspicuous. In the upper part of the thigh, in the armpit, or in the neck, they are about large enough to admit a crow-quill. Those from the lower limbs, from the viscera, and from the walls of the abdomen converge to a receptacle which lies in front of the spinal column. The receptaculum chyli is continued upwards as the thoracic duct, which pours the lymph into the great veins of the left side of the neck and of the left arm just where they join together.

The thoracic duct provides for the overflow of lymph from the spaces of the body. There is no circulation of lymph. Lymph from the liver and from the intestines is constantly draining into the thoracic duct, and thus returning to the blood-stream by a short direct route, entering it without the necessity for reabsorption through the walls of capillary vessels. By no means all of this fluid has exuded from the blood-stream. Much of it is water which was poured into the stomach as gastric juice, and into the intestines as the secretions of the pancreas and other glands, or imbibed through the mouth and absorbed by the lymphatics of the alimentary canal. The remainder of the water taken up from the alimentary canal enters its bloodvessels. The diluted blood flows to the liver, loaded with digested products which the liver will store. As the blood parts with them the additional water which has served for their transport exudes from the capillaries of the liver into lymphatics, which empty it into the thoracic duct. Large quantities of water are used in washing out digested products. Secreted into the alimentary canal by the digestive glands, it passes out through its wall as the vehicle of digested products. Collected by lymphatic vessels, it is either carried directly into the thoracic duct, or passed from lymph into blood, carried by blood to the liver, again transferred from blood to lymph, and borne by the lymphatic vessels of the liver to the thoracic duct.

Water exuded from blood into lymph may be reabsorbed into the blood near the place where it was poured out, or it may reach the blood via the thoracic duct. It would seem that the former is the natural, the latter the emergency route; the former the course taken when an organ is tranquil, the latter a necessity when the organ is active. If the large lymphatic vessels of a limb are cut, no lymph escapes from them so long as the limb is at rest. When the muscles contract lymph begins to flow. If the limb is flexed and extended by hand, lymph flows. If the muscles are squeezed or massaged, lymph flows. As the flow is set up both by active contraction of the muscles and by passive movements in which the muscles do not take part, it clearly must be due to external pressure on the lymphatic vessels. As they are provided with valves, squeezing them converts them into pumps. The fluid which they contain is bound to go forwards. Additional fluid is squeezed into them from the tissue-spaces. To a large extent, therefore, the outflow of lymph from contracting muscles is to be explained as the result of the pressure which the swelling muscles exert upon the lymphatic vessels within their sheaths. But there is another factor which must not be overlooked, although it cannot readily be estimated. When a muscle is actively contracting its bloodvessels dilate. There is a greater exudation of lymph; and reabsorption by blood is not equal to the exudation. The surplus leaves the limb by the lymphatic vessels. A gland is never at rest. In the intervals between the ejection of its secretion its cells are preparing materials for the next outflow. Lymph is always flowing from a gland; its amount increases as the activity of the gland increases. More lymph leaves the blood when the gland is exceptionally active than when it is relatively quiet. Some of it is not reabsorbed into the blood. A certain proportion of the waste products of the active gland are hurried away by the overflow system in the direction of the thoracic duct.

Lymph is the reservoir of nutriment upon which every cell in the body draws. It is improbable that in health and under normal conditions the activity of any organ is ever restricted for want of sufficient food. As food is removed from lymph, it is instantly replaced by fresh food from the blood. There is some evidence—not very clear—that the removal of waste products offers greater difficulty than the renewal of supplies of food. When the activity of muscles has been excessively prolonged they ache. It has been supposed that their unwillingness to do more work is due, not to the exhaustion of the food which they use up when contracting, but to the inadequacy of the lymph and blood to carry off all refuse. This, at least, is the explanation of fatigue which is usually offered, although it is difficult to understand why the arrangements for removing waste products which have worked to perfection for eight hours should during the ninth hour become rapidly ineffective.

If a frog’s muscle, cut out of the body, has been made to contract until it refuses to work any longer, it again responds to stimulation after a solution of salt has been passed through its bloodvessels. The salt-solution brings no food; the only thing it can do is to wash away waste products. But this experiment upon a tired, isolated muscle does not necessarily throw light upon the nature of fatigue in muscles under normal conditions. The isolated muscle is using up, in contracting, food which it has stored. Cut off from the circulation, it has no means of getting rid of the lactic acid and other products into which food is changed. They may well have accumulated to a poisonous extent long before all the food has been used up. Hardly more cogent is the argument based upon the benefit which a tired man experiences from hot baths, massage, and the like. They take away the feeling of tiredness, but it does not follow that this result is due to the removal of waste products. Quickening the circulation of blood brings about renewal of the lymph. Renewal of lymph means fresh supplies of food as well as removal of waste products. Even human muscles are not perfect as machines. They will not work for an unlimited spell. There comes a time when they must have rest. Something goes wrong in the admirable adjustment which has hitherto provided exactly the right amount of food and exactly the necessary freedom from the products of action. A feeling of fatigue is the signal that the apparatus is not in a condition to work longer; but whether this feeling is due to a dislocation of the balance of supply and loss, or to some deterioration of the apparatus which calls for rest and renovation, it is at present impossible to say. It is not due to the exhaustion of muscle food. A more powerful stimulus, the urgency of fright or some other strong emotion, or an electric current applied directly to the muscle or its nerve, will still induce vigorous contraction. The muscles of a hare that has been coursed until it can run no farther still contain glycogen, muscle food.

Glycogen is stored in the liver. Fat, if it is assimilated in excess of the needs of the body, accumulates in the connective tissues. Proteins, if in excess, are either destroyed by oxidation, or partly destroyed and partly converted into fat. Increasing the amount and richness of the food does not, if nutrition is already at its best, improve the quality of the blood. The surplus of food is either stored or burnt. The composition of lymph is unaffected. Its quality is not improved by taking more food than enough. A perfect balance is maintained. Every cell is able, when conditions are normal, to obtain as much nutriment as it needs. It cannot get more. It cannot lay by food and shirk work. If it did it would grow. Reaching its optimum size, it would divide. Additional tissue would be formed. But when it does more work it needs more food; and it is a matter of common experience that the system is so adjusted that food is supplied to the tissues, not reluctantly, but with a slight tendency towards generosity. Working harder than usual, they find the lymph by which they are bathed somewhat richer in the materials that they need than the necessities of the case demand. They are able not merely to obtain all they want, but a little more. Activity favours growth.

Many attempts have been made to show that if a part of the body has more than its share of food it grows to an excessive size. John Hunter grafted a cock’s spur into its comb. It grew to monstrous dimensions. Such a result favours the view, but it is not quite conclusive. Undoubtedly the comb was richly supplied with blood, but it does not follow that the cells of the spur were able in their new situation to take advantage of this supply. Besides, the spur when projecting from the head was not subject to the accidents to which it was exposed whilst on the leg. Its size was not kept down by friction. Nor was it as hard and compact as it would have been in its normal situation. It is scarcely possible to devise any experiment that would be satisfactory now that the relations between blood and lymph and lymph and tissues are understood. In certain pathological conditions, however, hypertrophy is the result of the hyperæmia of chronic inflammation; and there is little doubt that, if we could arrange for a certain group of cells to receive lymph richer in food and freer from waste products than the perfect adjustment of supply to needs normally allows, the cells would grow.

Under perfectly healthy normal conditions growth can be induced only by use. Nature supplies the fuel which is used during activity, and a balance of food available for the construction of additional machinery. The muscle which is called upon to do work develops a greater capacity for work.

When nutrition is not at its best, the growth of muscle may be favoured by external pressure which squeezes lymph out of its tissue-spaces, and therefore leads to increased exudation from the blood. It is not improbable that in badly nourished tissues the circulation of blood is somewhat torpid and the lymph stagnant. A feeble circulation usually results in some œdema. The muscles, or rather the connective tissue which envelops and penetrates them, feels doughy, instead of being, as it should be, firm and elastic. Under these conditions massage is undoubtedly of service. Squeezing the muscles displaces lymph, and, if the pressure is properly directed, drives it along the lymphatic vessels. Fresh lymph exudes from the capillary bloodvessels, and the muscle-fibres, surrounded with a more abundant supply of nutriment, benefit, as, in a vigorous person, they benefit from use.

Lymph is an exudate from blood. Its composition therefore depends upon that of blood-plasma, but it tends to differ from it owing to the influence of two causes. In the first place, the walls of the capillary bloodvessels restrict exudation. Red blood-corpuscles cannot pass through them. Proteins which are non-diffusible are, according to the circumstances of the tissues, held back to a greater or to a less extent. The pseudo-capillaries of the liver let them pass, as has already been said. The capillaries of the limbs restrict their passage to such proportions as, it may be supposed, are absolutely necessary for the nutrition of the tissues. In the second place, tissues remove food from lymph and add to it waste products. Hence the lymph issuing from a limb, after full contact with the tissues, contains less of the former and more of the latter—less sugar, for example, and rather more oxidized nitrogenous substances, lecithin and other things termed collectively “extractives,” because they can be extracted from dried blood or lymph by ether. The reaction of lymph is alkaline. After a time it coagulates, but coagulation is slower, and the clot less firm than in the case of blood.

As the composition of lymph depends upon the source from which, and the conditions under which, it has been obtained, it is unnecessary to state the results of a chemical analysis. It suffices to say that lymph contains all the substances which are present in the plasma of blood, but not necessarily in the same total amount or in the same relative proportions. Speaking generally, leucocytes are present in about the same numbers as in blood—6,000 to 8,000 to the cubic centimetre; but leucocytes are everywhere present: in blood, in the lymph, in lymph-vessels, in the tissue-spaces. As they are not passively floating bodies like red blood-corpuscles, but active migratory organisms, they tend to accumulate in one situation and withdraw from another, in accordance with the opportunities which the different localities afford. They desert effused lymph, blisters, ascitic fluid, and the like. They are not found in the lymph in the pericardium. There are fewer in the lymph coming from the intestines after a meal than in the same lymph during the intervals between meals. Their departure from effused lymph might easily be explained. It is not so easy to account for their comparative absence from the lymph in the lacteals when it is heavily charged with fat and other products of digestion. Such leucocytes as are present at this time are loaded with fat granules which they have stolen from the chyle, as the lymph in the lacteals is usually termed. One would need to be very intimate with a leucocyte before one ventured to give reasons for all its movements. Lymph contains the same proteid substances as blood, and in the same relative proportions, but usually in smaller quantity.

Incidental reference has been made to the great lymph-spaces—peritoneal, pleural, and pericardial. The brain and spinal cord are separated from their outer membranes by a lymph-space. There are also spaces within the brain—the ventricles—and a central canal in the spinal cord. The aqueous and vitreous humours of the eye are also lymph-spaces, although the latter contains some remnants of tissue. The joint cavities are lymph-spaces. So also are the bursæ which surround tendons or separate them from bones. It is not, however, justifiable to include all these cavities in a single category, either from the point of view of their purpose, their mode of formation, or the nature of their contents. The peritoneal, pleural, and pericardial spaces are parts of the great primitive body-cavity, or cœlom. The two first are potential rather than actual. Normally they contain just sufficient fluid to moisten the apposed surfaces of the endothelium which lines their walls and covers the organs which they contain. There is no fluid in them which can be collected and labelled “peritoneal” or “pleural” fluid. The purpose of the spaces is to allow of movement without friction—in the one case of the intestines, in the other of the lungs. It is possible to take a spoonful or so of fluid out of the space which surrounds the heart. It has the usual composition of lymph. It contains proteins, but is not spontaneously coagulable. Leucocytes are absent, a fact which probably accounts for its not clotting. The fluid inside the cerebro-spinal system is extremely dilute. Its principal salt—its principal constituent, indeed—is sodic chloride. It contains hardly a trace of proteins, and these in a modified condition—proteoses. It also contains pyro-catechin, a benzoic alcohol. This substance has long been recognized as a constituent of cerebro-spinal fluid, owing to the fact that, like sugar, it reduces copper salts when heated with them in an alkaline solution. It appears to be one of the products of proteid decomposition. Although exuded as lymph from the bloodvessels of the chorioid plexuses, the composition of cerebro-spinal fluid has been profoundly changed by the activity—it might almost be called the digestive activity—of the epithelium which lines the cerebro-spinal canal. There is a theory that the ancestors of all vertebrate animals were organized on a very different plan from that of their distant descendants. Our cerebro-spinal canal was their stomach and intestine. It would appear that the lining epithelium of these organs, although disused for millions of years, cannot resist the temptation to digest the lymph which they contain! The fluid in joints contains mucin (the essential constituent of mucus), or a substance resembling mucin. In this case the joint-membrane has added something to lymph without removing or destroying any of its other constituents.

Other illustrations might be given showing how the plasma of blood is altered in composition while it is passing out of, or after it has passed out of, capillary bloodvessels. Perhaps it would be more logical to start on the outer side of the walls of the capillaries; since blood may, very properly, be regarded as a tissue, dependent, like all other tissues, upon diffusion from lymph for the nutrient materials that it needs. In the wall of the alimentary canal it receives supplies via the lymph. It drops them in the liver, its garde-manger, to pick them up again as they are wanted. The torrent of lymph which the thoracic duct discharges into the veins of the neck conveys the fat which could not traverse the walls of the capillary bloodvessels, and much of the reserve of food which the blood had deposited in the liver. Only about one-quarter of the fluid of the body (one-thirteenth of the body-weight) is included within the blood-system; but this enclosed fluid, owing to the fact that it is kept in circulation by the heart, replenishes and purifies the much larger quantity which does not circulate. The unenclosed lymph has in particular situations a chemical composition which varies widely from that of the blood. Imagine a marsh through which a river flows—the vast plains of water-plants on the Nile above Fashoda, for example. There is a constant interchange between the flowing water of the river and the stagnant water of the marsh. In any given part of the marsh the quality of the water will depend upon what it has been able to take from, and what it has given back to, the river; upon what the water-plants have taken from it, and what they have added to it. Boats which cannot penetrate the walls of reed keep to the open channel of the Nile. Fish swim, now in the river, now in the narrow passages and open pools of the marsh. So it is, in a way, with the fluid in the spaces and cavities of the lymphatic system and in the bloodvessels which traverse them, and with its migratory inhabitants. In our extravagant analogy read leucocytes for fish. Fish have two reasons for wandering from river to marsh. Amongst the water-weeds they hunt for food; they seek quiet places in which to breed. In this matter the analogy holds good. A leucocyte may be overtaken with cell division anywhere—in the blood-stream or in a lymph-vessel. But cell division very rarely occurs except in certain favoured spots. The breeding-places chosen by leucocytes are sheltered situations in connective tissue where the blood-supply is abundant, and the eligibility of such a spot is much increased by its being near to a field where their services are likely to be called for. The nests of connective tissue made by the leucocytes are of three kinds, termed respectively diffuse adenoid tissue, lymph-follicles, and lymphatic glands. The connective tissue beneath the mucous membrane of the whole of the respiratory tract—trachea, bronchi, and bronchioles—is diffuse adenoid tissue. It presents no special structure, but its spaces are packed with leucocytes in various stages of cell division, and young leucocytes, or lymphocytes, as they are usually named. Some of the lymphocytes make their way into the blood or into the lymph. Others, acquiring their full dimensions, scour the epithelium which lines the respiratory tract for germs and other foreign bodies which are drawn into the tract with inspired air. They may be seen pushing aside the cells of the lower strata of the epithelium, on their way to the surface, or returning to the subepithelial connective tissue with germs, or particles of soot, or débris of epithelial cells which they have taken into their substance ([Fig. 4, B]).

The tonsils are examples of follicular lymphoid structures. They lie one on either side of the entrance to the gullet, between the two folds (the anterior and posterior pillars of the fauces) by which the soft palate is continued to the side of the tongue. Normally the tonsil is not visible, but when inflamed it may project sufficiently to be seen; and its surface may then be covered with mucus and pus. It is liable to become enlarged in childhood, owing to chronic inflammation. A section of the tonsil shows it to consist of clusters of lymph-follicles lying beneath the mucous membrane. The term “follicle” is unfortunate. It conveys no idea of the form or structure of one of these masses of lymph-cells; and it is, besides, applied to things of an entirely different character—for example, the pits of mucous membrane which sink down between the masses of lymphoid tissue in the tonsil. The expression “follicular tonsillitis” does not refer to the lymph-follicles, but to the epithelial pits. It is a condition in which a drop of pus is to be seen in the mouth of each of the pits. A lymph-follicle is a small rounded clump of connective tissue, denser on its periphery than in its centre. Its bloodvessels are disposed chiefly on the periphery. Lymphatic streamlets arise in the centre. Its outer portion is closely packed with dividing lymph-cells and young leucocytes, which as fast as they are formed migrate towards the centre, and eventually escape from the follicle by the lymphatic vessels. The connective tissue which invests and separates the follicles is full of leucocytes. Removal of the tonsils is followed by no ill effects. They are not essential to our well-being. Nevertheless, they have important functions to perform. They are barracks crowded with leucocytes, which guard the pass into the alimentary canal. Their leucocytes incessantly patrol the mucous membrane, capturing germs, removing fragments of injured epithelium, striving to make good the mischief to which this part of the alimentary canal is peculiarly liable. The enlargement of the tonsil which results from frequent sore throat is a response to the demand for an increase in the supply of these little scavengers, in order that they may cope, not only with objectionable things outside the walls, but with the still more pernicious germs which during an attack of sore throat succeed in breaking through the epithelium. It is the invaders which elude the vigilance of the leucocytes that cause fever and other general symptoms. Other notable groups of lymph-follicles are found in the middle portion of the small intestine, where they form oval patches, about three-quarters of an inch long by half an inch broad—Peyer’s patches. The leucocytes which are developed in them search the walls of the intestine for germs. During an attack of enteric fever the patches become inflamed, and one of the greatest risks which the patient runs is the risk of ulceration of a patch and the perforation of the intestinal wall.

The abundant provision for the multiplication of leucocytes shows that the destruction of these cells must occur on an equally large scale. Every day large numbers die. Where this occurs, and how their dead bodies are removed, is not certainly known. Doubtless they are eaten by their fellows, their substance oxidized, and the products—carbonic acid, water, and nitrogenous waste—thrown into the lymph. There is some reason for thinking that a part of the nitrogenous waste is excreted in the form of uric acid ([cf. p. 216]). The daily production, and consequent destruction, of leucocytes shows that their metabolism is a factor which cannot be overlooked when we are making up the body’s accounts.

The fixed tissues receive their nutriment in a digested condition. Leucocytes digest it for themselves. In many cases, although not in all, the cells of fixed tissues last throughout life, so far as their outer form is concerned, although their molecules are oxidized and replaced by new material. It is not improbable, therefore, that there is a difference between the metabolism of the fixed tissues and the metabolism of leucocytes. The whole of a wandering cell, its nucleus included, breaks down and has to be removed. We do not know that this occurs in the case of a fixed cell. On the strength of evidence which points, apparently, to a chemical relationship between nuclear substances and uric acid, it has been inferred that the two chief nitrogenous products which are excreted by the kidney are divisible into the one which in the main represents the oxidation of fixed cells, urea, and the other, uric acid, largely derived from the oxidation of wandering cells.

The valiant leucocytes do their best to cope with all the rubbish, whether living or dead, that needs removal. They flock to any situation in which germs are numerous or tissue has been destroyed. If all goes well they take the foreign matter into their substance—dead tissue is matter foreign to the body—and either digest it in the course of their ordinary progress, or retreat with it, if they cannot digest it, to the nearest lymphatic gland. But in their efforts to reach objectionable matter they are apt to wander too far from the healthy lymph from which they obtain oxygen for their own respiration. Unable to breathe, they die. They lose the power of extruding pseudopodia. Their extensible, prehensile processes are drawn in. Assuming a globular form, they float helplessly in what once was lymph. Their body-proteins are largely changed to fat. As “pus cells,” they are thrown off in the discharge from an ulcer, or accumulate in the cavity of an abscess. A pus cell is a dead and fattily degenerated leucocyte.

The third kind of breeding-place of leucocytes, a lymphatic gland, has a more elaborate structure than the tissues with which we have already dealt. Lymphatic glands are about the size of beans, and of the same shape. They are found in the course of lymphatic vessels in situations where they are not exposed to pressure, such as the back of the knee, the groin, the front of the elbow, the armpit, in the neck above the collar-bone, and on either side of the sterno-mastoid muscle, behind the angle of the jaw. There are a number in the abdomen and in the thorax. Each lymphatic gland is invested by a strong fibrous capsule. Its artery enters, and its vein and efferent lymphatics leave, the concave side (the hilus) of the gland. The lymphatic vessels which bring lymph to it pierce the capsule on its convex side. It is divisible into two parts: (1) The adenoid tissue which surrounds the artery and its branches; (2) the open network of “lymph-ways” which invest this adenoid tissue. Leucocytes divide in the adenoid tissue. The young lymphocytes drop out into the lymph-ways. As a stream of lymph, brought by the afferent vessels, is always flowing into the lymph-ways, and out by the efferent vessel or vessels, the lymphocytes are carried with it towards the thoracic duct. A lymphatic gland is therefore an organ for adding leucocytes to lymph in the course of the lymph-stream. It has, however, another and equally important function. Leucocytes which have picked up germs or other foreign matter pass on with the lymph to a lymphatic gland. After entering its lymph-ways they leave the lymph-stream, squeeze into the adenoid tissue of the gland, and there come to rest with their burden. They remain in the gland until the foreign matter is digested, or, if it be indigestible, until they undergo dissolution, when the particles of soot or pigment are deposited from their débris in a harmless state. When the skin is tattooed, much of the Indian ink and other pigment remains where it was inserted with the needle, but some of it is picked up by leucocytes and carried to the nearest lymphatic gland.

Lymphatic glands are barriers which stop the spread of infection. They are the stations to which our police carry captured germs. The skin of the heel is abraded. Germs from the soil, or elsewhere, which have accumulated in a dirty stocking—owing to the warm moisture enclosed by an impervious boot, the woollen covering of the foot is a peculiarly healthy place for germs—enter the opened lymph-spaces of the subcutaneous tissues. Leucocytes hasten to the spot. They seize the invaders with their pseudopodia, engulf them in their body-substance, enter lymphatic vessels, and are rolled away by the lymph-stream. The instinct which brings them in ever-increasing numbers to the breach in the protecting skin can be explained only in terms of force. From our own conscious action to the causes which determine the movements of a leucocyte, or of an amœba, is so deep a drop that we prefer to recognize in the latter a merely chemical attractive force. “Chemiotaxis” we term the influence which draws leucocytes to the place where food is abundant; although it is also the place, one must admit, where in the interests of the body as a whole they run great risk of asphyxiation. It is appetite which draws a schoolboy to a bun-shop; a sense of duty prompts a fireman to risk his life in a chamber filled with smoke. We have no desire to humanize a leucocyte; but it is difficult to emphasize too strongly its independence. It would be absurd to use terms which imply that a leucocyte has a self-directive power; yet it is equally misleading to describe its migration to the seat of injury, its retreat with ingested germs to a lymphatic gland, its wriggling from the lymph-ways of the gland into the shelter of its adenoid tissue, in terms which imply that the forces which direct it are known, and their mode of action understood. The success which attends the inroads of germs is due to their amazing capacity for multiplication when they reach lymph or blood. It is useless to attempt to form an idea of the rapidity with which they divide, since we have no data upon which to base calculations. If the leucocytes fail to deal with the first few that enter, germs soon swarm within the lymph-vessels. This leads to an inflammation of the walls of the vessels, which may then be seen as red lines beneath the skin. These red lines lead upwards towards the nearest lymphatic gland. The glands in the space behind the knee are not usually affected when the focus of infection is in the foot. The red lines can be traced up the inner side of the knee and the front and inner side of the thigh to the groin. The glands in this situation swell until they can be easily felt. If the mischief is in the hand, the gland at the elbow may be affected, but most of the lymphatics pass by it on their course to the glands in the armpit. If a sore throat is the source of infection, the glands beneath the angle of the jaw enlarge. Thus various glands block the further progress of infection. In doing this their resources may be strained to the uttermost; they may enlarge, become tender, grow soft, fill with pus, break down and discharge the pus without the aid of a surgeon’s knife, although as soon as pus is recognizable within them it is wise to let it out. If germs pass through these first stations into the lymph-vessels beyond them, abscesses are formed in other situations. A condition of “blood-poisoning,” so called, is set up.

The readiness with which leucocytes sacrifice themselves in their efforts to remove germs and decaying tissue is a matter of almost every-day experience. The fatty matter produced in the sebaceous glands of the skin normally overflows on to the surface. It serves to render the skin supple and impervious to water. Germs get into one of the sebaceous glands of the face or of the eyelid. The contents of the gland begin to decompose. Leucocytes enter it for the purpose of removing the putrescent substance. They lose their vitality and turn into pus corpuscles. The pimple or the stye bursts, and pus and fatty matter are discharged together.

That the conversion of leucocytes into pus cells is due to want of oxygen has been shown by the following experiment: A minute piece of phosphorus is placed beneath the skin. Leucocytes gather round the spot with a view to removing the tissue which the phosphorus has destroyed. But phosphorus has so strong an affinity for oxygen that it exhausts the supply in the area of tissue which surrounds it. The leucocytes die before reaching the tissue immediately adjacent to the piece of phosphorus. Their dead bodies form round it a raised ring of pus cells. We can explain this readiness of leucocytes to sacrifice themselves in their efforts to reach foreign matter which needs to be removed, only by saying that the attraction of the food is greater than the repulsion of lymph destitute of oxygen. An amœba placed in comparable circumstances gives up the quest of food, however strongly chemiotaxic, and retreats towards water which contains oxygen sufficient to provide for its respiratory needs.

Blood.—A portion of the body fluid is enclosed within vessels and kept in circulation by the heart. The heart pumps blood into the aorta. This trunk gives off large arteries, which in turn divide until the finest capillary vessels are reached. The capillary tubes reunite to form veins, which, with the exception of those which collect food from the digestive organs, convey the blood right back to the heart. The veins which drain the stomach and intestines (the organs in which food is prepared for absorption) and the spleen (the organ in which worn-out red blood-corpuscles are in a sort digested) break up in the liver into a second set of small vessels. The pseudo-capillary vessels of the liver reunite to form the hepatic veins, which add the blood that has passed through that organ to the rest of the blood which is passing up the inferior vena cava to the heart. A second capillary circulation is found in the kidney also.

The heart is four-chambered ([Fig. 10]). Its left ventricle drives the blood round the systemic or greater circulation, the blood returning to the right auricle. The right ventricle drives the blood through the lesser or pulmonary circulation, from which it returns to the left auricle. The walls of all bloodvessels, except capillary tubes, are sufficiently thick to prevent the escape of any of the constituents of blood. To support the pressure of the blood which they contain, the arteries and the larger veins need walls of considerable thickness. The walls of the capillaries allow an interchange between blood and lymph in the manner already described ([cf. p. 39]).

Blood fresh from the lungs, whether still in the pulmonary veins or in the systemic arteries, is scarlet in colour. Venous blood is darker and purple-red, the depth of its tint varying with the extent to which it has parted with its oxygen. It looks less opaque than arterial blood. With this exception, the physical properties and chemical composition of blood are remarkably constant in all parts of the body. Arterial blood contains more oxygen, venous blood more carbonic acid. Other chemical differences can be recognized, but they are relatively very small. The constancy in the constitution of blood is its most notable character. Bleeding, unless excessive, does not greatly affect it. The number of corpuscles is of course diminished, but even these are replaced with great rapidity. The plasma, after bleeding, soon recovers its proteins and salts. A similar readjustment occurs if normal saline solution (water containing 0·9 per cent. sodic chloride), or even a strong solution of salt, is injected into the blood. Within certain limits it is very difficult to disturb the balance of its constituents. It gets rid of substances added in excess, or replaces substances removed, with remarkable facility. If sugar (glucose) be injected into a vein, it escapes through the capillary walls into the lymph. After a short interval the lymph contains more sugar than the blood. If an excess of protein, whether of a kind foreign to the blood or its own serum-albumin, be injected, it is removed by the kidneys. The blood has various sources from which it can draw out reserves of anything that is lacking, and various ways of getting rid of anything that is in excess. It draws upon the lymph in the tissue-spaces for water. It discharges salts into the lymph. It also takes salts from the lymph. It draws upon the liver for sugar, and probably for proteins also. In a starving animal the blood still contains sugar long after fresh supplies have ceased to reach it from the intestines. The lungs remove its carbonic acid. The kidneys free it from everything which cannot be otherwise removed. It is essential to the well-being of the organism as a whole that a uniform standard of composition should be maintained by the blood.

Fig. 4.—Red Blood-Corpuscles presenting, some the Surfaces, others the Edges, of their Discs, together with Single Representatives of Four Types of Leucocyte.

A, the most common type, highly amœboid and phagocytic. Its protoplasm is finely granular, its nucleus multipartite. B, a leucocyte closely similar to the last, but larger, and containing an undivided nucleus. It is shown with a cluster of particles of soot in its body-substance. C, a young leucocyte, or “lymphocyte.” D, a coarsely granular leucocyte. Its granules stain brightly with acid dyes—e.g., eosin or acid fuchsin.

Composition.—The structural composition of the blood, and the relation of its several constituents to each other, is best studied under the microscope. A thin transparent membrane in which blood is circulating through small vessels—the web between the toes of a frog’s foot, the mesentery, the membrane of a bat’s ear—affords an opportunity of observing blood in circulation. In any of the smaller vessels, whether artery or vein, a column of red corpuscles is seen moving in the axis of the stream. This column is surrounded by a layer of clear plasma. Amongst the red corpuscles a few leucocytes may be detected floating placidly down the current. Others are seen in the peripheral layer of plasma, tending to creep along the wall of the vessel rather than submit to be moved forward, as passive objects, by the current. If an irritant be applied to the membrane, the vessels dilate; yet, notwithstanding their wider calibre, the current becomes slower. The red corpuscles mass together. Apparently their constitution is slightly altered by this commencing inflammation, in such a manner that they cease to be clean, independent discs which slide past each other like small boats on a river; they exhibit a tendency to stick one to another. In the capillary vessels leucocytes may now be observed, not merely creeping along the inner surface of the endothelium, but squeezing themselves between its scales; making their way out of the vessel into the tissue-spaces through which the vessel passes. Such an observation gives the clue to the functions of the several constituents of the blood. The red corpuscles carry oxygen in chemical combination with their colouring matter. From them it passes into solution in the plasma; from the plasma through the walls of the capillary vessels into lymph; the tissues take it from the lymph as they require it. As fast as it is removed from lymph it is renewed from plasma. Carbonic acid excreted by tissue cells is dissolved in lymph. From lymph it is transferred to plasma. The reception of carbonic acid by these fluids is not quite so simple as the transference of oxygen from blood to lymph. It is aided by the presence of alkaline carbonates which are always ready to form “acid” salts: not acid to litmus-paper—the blood is always alkaline—but containing more than one unit of acid to one of base. Sodic carbonate has the formula Na₂CO₃. With an additional molecule of carbonic acid it becomes Na₂CO₃CO₂(HO)—bicarbonate. When in solution it can hold still more carbonic acid. If carbonic acid were merely dissolved in lymph and plasma, it would be impossible for the blood to carry it away with sufficient rapidity; just as it would be impossible for blood to bring sufficient oxygen were it not for the colouring matter (hæmoglobin) which forms a temporary, easily divorced union with it. But from a physical point of view it comes to the same thing. As the tension of oxygen in plasma falls, it dissolves more from the hæmoglobin. When the tension of oxygen in lymph is less than its tension in plasma, the former borrows from the latter. If the tension of carbonic acid in lymph is higher than in blood, it passes to the blood. The rapidly circulating blood at frequent intervals traverses the lungs. The whole blood of the body is exposed to air in the lungs once every minute. Oxygen tension being higher in pulmonary air than in venous blood, this gas is taken up. Carbonic acid tension being higher in venous blood than in pulmonary air, this gas escapes. The plasma in the capillary vessels which traverse the tissues exchanges gases with the lymph with very great rapidity.

The specific gravity of blood varies from 1·056 to 1·059. The corpuscles are heavier than the plasma. Its reaction to test-paper is alkaline, owing to the presence of bicarbonate of soda and disodic phosphate. The alkalinity is greatest when the body is at rest; it is diminished by severe muscular exercise. Blood contains about 5,000,000 red corpuscles, and 7,000 or 8,000 leucocytes, to a cubic millimetre. Red blood-corpuscles are biconcave discs destitute of nucleus, and, so far as can be seen, devoid of any investing membrane. Seen in profile they appear biscuit-shaped, because the centre is hollowed out. Their largest diameter is 7·5 micromillimetres (¹/₃₂₀₀ inch)—a measurement of great importance to anyone who works with a microscope, because it serves as a standard by which to estimate the size of other objects. They are soft, but fairly tough and highly elastic. In circulating blood a corpuscle may occasionally be seen to catch on the point where two capillary vessels unite. It bends almost double under the pressure of the column of corpuscles behind it, and then springs forward.

A red corpuscle is a vehicle for hæmoglobin. If blood is diluted with water, or if it is alternately frozen and thawed, the hæmoglobin separates from the corpuscles, which can then be seen as colourless discs. Hæmoglobin constitutes 40 per cent. of the weight of a moist corpuscle, or 95 per cent. of its weight after it has been dried. This is an enormous charge for a corpuscle to carry, and the question of how it carries it has been much discussed. It is not in a crystalline state. A corpuscle examined by polarized light is not doubly refractive. Microscopists know that if there were any crystals in the corpuscle it would appear bright on a dark ground when the Nicholl prisms are crossed. It cannot be in solution, since the water which the corpuscle contains would not suffice to dissolve it. It must be combined with some constituent of the corpuscle. But whether it is uniformly distributed throughout the disc, or in a semifluid form enclosed in spaces in a sponge-work; or whether the corpuscle is a hollow vesicle enclosing fluid hæmoglobin—a view which was long ago maintained, and has recently been revived—are questions which still await further evidence.

Red blood-corpuscles, properly so called, are found only in vertebrate animals, although invertebrate animals, from worms upwards, possess genuine blood, and in some of them it contains hæmoglobin, or a similar pigment in the form of globules. These might be likened to the non-nucleated corpuscles of mammals, but it must be remembered that the non-nucleated cells of mammals have been evolved from the nucleated blood-corpuscles of birds, reptiles, amphibians, and fishes. Below fishes red blood-cells are not found. Hæmoglobin is usually dissolved in the blood of invertebrate animals. It is impossible to trace any relationship between the coloured globules of invertebrates and the blood-cells of fishes. The coloured globules must be regarded as deposits or accretions of hæmoglobin held together by a proteid substance.

The nucleated red corpuscles of submammalian vertebrates multiply by cell division while circulating in the blood-stream. A good subject in which to look for dividing corpuscles is the blood of a newt in spring-time, when rapidly increasing activity calls for an additional supply. There is nothing to distinguish the method of division of a nucleated blood-corpuscle from that of any other cell.

The life-story of the red blood-corpuscles of mammals is one of the most fascinating that the histologist has to tell. He wishes that he could tell it with assurance; but, unfortunately, there are many uncertainties, due to conflicting testimony, in its earlier chapters. It is unlikely that a blood-corpuscle lives for long. A month or six weeks is probably the term of its existence. The rapidity with which the stock is replenished after bleeding shows that there must be ample provision in the body for making blood-corpuscles. The rate at which they disappear after they have been added in excess shows that there is an equally effective mechanism for destroying them. If half as many again as the animal already possesses be injected into its veins, the number is reduced to its normal limit in about ten days. It is clear that they can be made and can be destroyed with great facility, and it seems a legitimate inference that production and destruction are constantly taking place. Regarding the way in which they are destroyed there is no uncertainty. We shall refer to this subject when describing the functions of the spleen. But how are they made? We can sketch their history in outline, but the evidence is conflicting with regard to all matters of detail.

In early stages of embryonic life all red blood-corpuscles are nucleated, as they are permanently in birds and the other classes of vertebrates below mammals. In embryonic mammals they multiply by division whilst circulating in the blood, just as in the newt. But it is generally believed that this is not the most important source of new ones. During the earliest stages of growth they are being formed in enormous numbers. Such instances of division as can be seen in circulating blood appear to be all too infrequent to account for their rapid multiplication, and there can be no doubt but that a more complicated method of production is more important. Their formation is described as taking place “endogenously.” Certain cells termed “vaso-formative,” or “vaso-sanguiformative,” reach a considerable size, and become stellate in form, or branched. Their nuclei divide without the cell dividing. Each nucleus accumulates a little hæmoglobin round it. A space filled with fluid appears inside the cell. The nuclei project into this space. Then they drop off with their envelopes of hæmoglobin. The outer shell of the big vaso-formative cell becomes the wall of a capillary bloodvessel. By its branches it links up with other vaso-formative cells, making a network of vessels. The fluid inside it is the plasma of the blood. The nuclei and their envelopes are blood-corpuscles. This, if it be a true story, is a comprehensive way of making bloodvessels and blood at the same time. Doubts have been thrown upon its accuracy, but many leading histologists strenuously maintain that this description is correct.

At a certain period all nucleated red corpuscles disappear from mammalian blood. Non-nucleated corpuscles take their place. How are the latter formed? For a short stage of embryonic life nucleated cells containing blood-pigment are seen, or are supposed to be seen, in the liver—there is, unfortunately, great difficulty in distinguishing them with certainty from young liver-cells; later they are seen in the spleen; throughout the whole of life they are to be seen in the marrow of bone. The nucleated cells give origin to the non-nucleated corpuscles. It is hardly legitimate to call these cells persistent embryonic corpuscles. Yet the chain which connects the cells which in the embryo are capable of dividing into pairs of nucleated red blood-corpuscles, and the cells which, assuming the rôle of parent cells, do not accumulate hæmoglobin for their own purposes, but for the benefit of the red corpuscles which split off from them, is probably unbroken. In this sense they are persistent embryonic corpuscles which have deserted the blood-stream, and have taken shelter in certain tissues which are particularly favourable for cell division. The situations in which they hide themselves are singularly suggestive. In the liver there is an abundant supply of nutriment, more abundant than in any other part of the body of the embryo. Later, in the spleen, red blood-corpuscles are being destroyed. Materials available for making new ones must therefore be set free. The inside of a hollow bone is a peculiarly sheltered situation. The fat cells of marrow accumulate there after a time; but within some bones the marrow develops very little fat; hence it shows the red colour, which is due to its abundant bloodvessels. This “red marrow” is the most important seat of the manufacture of red blood-corpuscles in adult life. Unfortunately, when we try to answer the question, How are they formed? we are obliged to speak with caution. Some histologists assert that the nucleated cells divide, and that one of the two daughter cells accumulates hæmoglobin, and loses—that is to say, extrudes—its nucleus. Others maintain that the nucleated cells become irregular in form; that hæmoglobin accumulates in the projecting portion of the cell; that this projecting portion breaks off as a non-nucleated corpuscle. It would be indiscreet at the present time to pronounce in favour of either of these reports, although the decision is of theoretical importance. If the former account be true, red blood-corpuscles are nucleated blood-cells which have lost their nuclei. If the latter account be in accordance with fact, it is hardly justifiable to regard them as cells. They are parts of cells which finish their existence independently of the cell body and nucleus to which they belong. As circumstantial evidence, favouring the theory that cell division is normal and the nucleus subsequently lost, may be pleaded the existence in marrow, and also in the embryonic liver and spleen, of certain very peculiar cells. These cells have long been known as giant cells, and all attempts at accounting for them have broken down. They are relatively of immense size: their diameter may be twenty times as great as that of a red blood-corpuscle. Each contains a huge irregular, bulging nucleus. Hence the cells are termed “megacaryocytes” (big-nucleus cells). They must not be confounded with the polycaryocytes (cells with several nuclei), which eat up degrading bone, although it must be confessed that megacaryocytes and polycaryocytes appear to be genetically connected. It is supposed that megacaryocytes consume the nuclei which red corpuscles extrude during the process of their conversion from nucleated cells. Traces of nuclei, or things which often look like nuclei, are found in their body-substance. Their own overgrown misformed nuclei appear to be the result of an excess of nuclear food. It is certainly remarkable that megacaryocytes are not found below mammals. They do not occur in any animal in which red blood-corpuscles retain their nuclei. Polycaryocytes are found in numbers in the bones of growing birds. They are evidently scooping out bone from situations in which it has to be displaced in order that the shape of the bone as a whole may be changed. But there are no megacaryocytes in birds. On the other hand, megacaryocytes are present in the liver, and later in the spleen, of mammals at the periods when blood-formation is occurring most actively in these organs. From the liver they disappear early. In most mammals they disappear from the spleen about the time of birth; but in some—the hedgehog, for example—they are found in the spleen throughout the whole of life.

Hæmoglobin is a substance which has the property of uniting with oxygen to form oxyhæmoglobin—a compound from which the oxygen is, again, very readily withdrawn. It is extremely soluble, but may be made to crystallize by adding alcohol to blood, after setting the hæmoglobin free from the corpuscles by freezing and thawing. From the blood of Man and most other animals it crystallizes in the form of rhombic prisms, whether in the oxidized (oxyhæmoglobin) or non-oxidized condition. The addition of oxygen does not affect its crystalline form; although crystalline, it is absolutely non-diffusible. This is due to the great size of its molecule, which is probably larger than that of any other substance which is capable of crystallizing.

The percentage composition of hæmoglobin conforms closely with that of albumin and other proteins, with this most important difference: it contains a definite proportion of iron—0·336 per cent. That the percentage of carbon, hydrogen, nitrogen, sulphur, and oxygen should agree with that commonly found in proteins is inevitable, since it may be split into a part which contains all the iron, hæmatin, and a proteid part resembling albumin; and the latter constitutes 96 per cent. of its weight.

There is no doubt but that its value as a vehicle of oxygen depends upon the presence of iron. In the matter of taking up and dropping oxygen, hæmatin behaves somewhat in the same manner as hæmoglobin; whereas if iron be removed from hæmatin the “iron-free hæmatin” loses its respiratory value. It is almost certain that a molecule of hæmoglobin contains a single atom of iron. On this supposition its molecular formula may be calculated. It is not quite the same for all animals, although the variations are slight. For the blood of the horse it is as follows:

C₇₁₂H₁₁₃₀N₂₁₄S₂FeO₂₄₅.

This means a molecular weight of 16708. We give the figures, because the properties of hæmoglobin will be better understood if its prodigious molecular weight is borne in mind. In a sense, the reason for the great size of its molecule is not far to seek. The atomic weight of iron (Fe = 56) is much greater than that of either of the other elements contained in hæmoglobin. The molecule needs to be very great to float an atom of iron. As it is, the corpuscles are heavier than the plasma which surrounds them, in the proportion of about 13 to 12. Although hæmoglobin is a crystallizable substance, its immense molecule is absolutely non-diffusible. It cannot pass through a membrane. This is of no consequence as regards the relation of hæmoglobin to the walls of the capillary bloodvessels, since it is contained in corpuscles; but it is of great importance as regards its relation to the discs which carry it. A very small quantity of enveloping substance suffices to prevent it from diffusing into the plasma of the blood. The great molecules are held together and isolated from the fluid in which they float by a minimal amount of insoluble globin.

The iron needed for the making of hæmoglobin is obtained both from meat and vegetables. The constituents of an ordinary diet provide from 2 to 3 centigrammes of iron a day. The whole of the blood contains about 4·5 grammes. When corpuscles are being destroyed in the spleen, the iron which their pigment contains is largely reabsorbed and rendered available for further use. The iron in a mixed diet is more than sufficient to counterbalance any loss. Milk contains extremely little iron. Before birth the liver and spleen accumulate a store of iron which lasts until the end of the nursing period, unless this be unduly prolonged. If it be prolonged, the child is apt to become anæmic. Iron has been administered in the treatment of anæmia ever since its presence in the red clot of blood was recognized a hundred and fifty years ago. Physicians are agreed that in the anæmia of young people it is of value; but observations made with a view to obtaining definite data as to the increase in number of blood-corpuscles which results from the administration of iron, without any other alteration in the diet or the habits of the patient, have not given accordant results. Some observers have obtained an increase with organic compounds of iron, others with inorganic compounds; some are in favour of small doses, others of very large ones. As in the treatment by drugs of other abnormal conditions, it is difficult to isolate the effect of the drug from the effects of improvements in the general regimen. Yet physicians agree that iron accentuates the beneficial effects of fresh air and improved diet.

When the surface of the body is struck, the effect of the blow is marked at first by redness. There is nothing to show that small bloodvessels have been ruptured and blood effused beneath the skin. Next day the injured area is reddish-purple. The bruise turns blue, green, yellow, and eventually disappears. In the process of absorption, oxyhæmoglobin undergoes decomposition. First its proteid constituent is removed, leaving a coloured pigment containing iron, termed “hæmatin”; soon reduced by loss of oxygen to hæmochromogen. When Sir George Stokes first described the spectrum of blood ([cf. p. 185]), he showed that as hæmoglobin may exist in an oxidized and in a non-oxidized condition, distinguished by their spectra, so also may the coloured residue which is left after the proteid constituent has been removed from hæmoglobin. This coloured residue he termed, when oxidized, “hæmatin”; when not oxidized, “reduced hæmatin.” Stokes’s reduced hæmatin is now termed “hæmochromogen.” Hæmochromogen stands for the coloured nucleus of hæmoglobin. Although it is not present in hæmoglobin as hæmochromogen—hence we must not speak of hæmoglobin as made of a protein, x, plus hæmochromogen, y—it is to its coloured residue that hæmoglobin owes its value as a carrier of oxygen. Later, iron is removed from hæmochromogen, leaving hæmatoidin, a substance often found at the seat of old hæmorrhages, where it may remain unchanged for a very long time. Hæmatoidin is apparently identical with the yellow pigment of bile, bilirubin. The green colour which shows itself in the bruise seems to indicate that the more oxidized bile-pigment, biliverdin, is formed in the first instance. Red corpuscles, when destroyed in the spleen, pass through transformations similar to those which blood undergoes when effused beneath the skin. Their protein is used by the phagocytes which eat them. Their iron is reserved for the use of the blood-forming cells of the red marrow of bone. The pigment which remains as the residue of hæmoglobin is carried by the splenic vein to the liver, which secretes it as bile-pigment. So much of the bile-pigment as is reabsorbed by the wall of the alimentary canal is eventually excreted as the pigment of urine.

Such is the history of the changes which blood-pigment undergoes within the living body. To a certain extent its chemistry can be followed in the laboratory; but it must be remembered, when we are treating of the chemistry of a substance as complex as hæmoglobin, that the products which can be obtained from it in the laboratory are not necessarily those into which it is transformed in the body. In the laboratory oxyhæmoglobin is easily changed into methæmoglobin, a substance of the same percentage composition, but with its oxygen more firmly fixed. Methæmoglobin can be decomposed into a proteid substance and hæmatin. Hæmatin, when acted on by reducing agents, becomes hæmochromogen. Hæmochromogen, when subjected to such a reducing agent as a mixture of tin and hydrochloric acid, gives rise to coloured bodies closely resembling bile-pigments—not as they are secreted by the bile, but as they appear in the urine. It is impossible to prove that the changing colours of a bruise indicate a sequence of chemical transformations from hæmoglobin to bile-pigment, but it is not improbable that such a description is correct. The test commonly used to ascertain the presence of bile-pigment, i.e., bilirubin, is the play of colours which it exhibits when oxidized by fuming nitric acid. From yellow it turns to green, to blue, and then to purple, more or less reversing the colours of the bruise. It is fairly certain that effused blood undergoes changes along lines which, if not identical with those through which blood passes on its road to bile-pigment, are at any rate very similar.

Coagulation of Lymph and Blood.—Two or three minutes after blood has been shed it begins to clot. In ten minutes the vessel into which it has been received may be inverted without spilling the blood. After a time the jelly, holding all the corpuscles, shrinks from the sides of the jar. It squeezes out a transparent, straw-coloured fluid—serum. The clot continues to contract until, in a few hours, about one-half of the weight of the blood is clot, the other half serum. Lymph coagulates like blood, but most specimens clot more slowly, and the product is less firm.

When the process is watched through the microscope—a few drops of the almost colourless, transparent blood of a lobster afford an excellent opportunity of studying the formation of the clot—innumerable filaments of the most delicate description are seen to shoot out from many centres. They multiply until they constitute a felt-work. In the case of blood obtained from a vertebrate animal, this felt-work holds the corpuscles in its meshes. Its filaments exhibit a remarkable tendency to contract. They shorten as much as the enclosed corpuscles allow.

The filaments may be prevented from entangling the corpuscles by whipping the blood, from the instant that it is shed, with a bundle of twigs or wires. The fibrin collects on the wires, while the corpuscles remain in the serum. If this fibrin is washed in running water until all adherent serum and corpuscles are removed, it appears as a soft white stringy substance which, when dried, resembles isinglass.

Clotting is a protection against hæmorrhage. As it oozes from a scratch or tiny wound, blood clots, forming a natural plaster which prevents continued bleeding. It has little if any influence in resisting a strongly flowing stream of blood. But a clean cut through a large vessel is an accident which rarely happens as the result of natural causes. It is not the kind of injury to which animals are liable. When an artery is severed by a blunt instrument, the muscle-fibres of its wall contract. They occlude the vessel. The blood clots at the place where the vessel is injured, and plugs it. This happens also when a surgeon ties an artery. He is careful to pull the ligature sufficiently tight to crush its wall. His sensitive fingers feel it give. He stops before the thread has cut it through. As will be explained later, the clotting of blood is promoted by contact with injured tissue. If in tying an artery its wall be not crushed, the blood in it may remain liquid. When it is skilfully tied, the blood clots, forming a firm plug which is practically a part of the artery, by the time that the silk thread used in tying it is thrown out, owing to the death of the ring of tissue which it compressed. After a tooth has been extracted, the cavity is closed and further bleeding stopped by clotted blood.

When large vessels have been severed, the copious hæmorrhage which follows induces fainting. For a short time the heart stops, or beats very feebly. The blood-pressure falls. The bloodvessels contract. A clot has time to form. An emotional tendency to faint at the sight of blood is a provision for giving the various causes which stop bleeding an opportunity of coming into play. It is a useful reflex action, always supposing that the person who is liable to it faints at the sight of his own blood. Amongst other reasons for the greater fortitude of women—they are far less subject to this emotional reflex than men—might be alleged the circumstances of life of primitive people. It was the part of their women-folk to dress wounds, not to receive them.

The phenomenon of coagulation has attracted attention from the earliest times. It was a phenomenon that needed explanation, and culinary experience suggested analogies close at hand. Hippocrates attributed the clotting of blood to its coming to rest and growing cold. The blood which gushed from a warrior’s wound formed a still pool by his side. It set into a jelly as it cooled. Until the second quarter of the nineteenth century this theory was deemed sufficient. It then occurred to two men of inquiring mind to institute control experiments. John Davy placed a dish of blood upon the hob. William Hunter kept one shaking. In both experiments the blood clotted more quickly than it did in vessels of the same size, containing the same amount of the same blood, left upon the table.

Even before this date an observation had been made regarding the circumstances in which clotting occurs, which has thrown much light upon the causes of the phenomenon. In 1772 Hewson gently tied a vein in two places. At the end of a couple of hours he opened the vein. The blood was still liquid, but clotted in a normal manner after it was shed. Scudamore showed that blood clots more slowly in a closed than in an open flask. A new theory, as little trustworthy as Hippocrates’, was based upon these observations. Blood clotted because it was exposed to air. A record of all observations of the circumstances of coagulation, and of all the theories to which they have given rise, would make an exceptionally interesting chapter in the history of human thought. It would bring into singular prominence stages in the development of what is now known as the “scientific method.” Not that Science has a method of her own. Philosophers of all classes would follow the same method if their data allowed of its application. The peculiarity of the data with which Science deals is that they can be brought to a test of which the data of historical, or political, or economic theory are not susceptible. They can be confronted with control experiments. The control experiment is the alphabet and the syntax of the scientific method. No hypothesis is admissible into the pyramid of theory until it has passed this test. A natural phenomenon is observed. Every measurement which is applicable is taken and recorded—time, weight, temperature, colour. Scientific observation implies the tabulation of all particulars which are capable of statistical expression. Reflecting upon the relation of the phenomenon to other phenomena of a like nature, the philosopher—it is the philosophy of physiologists which interests us—formulates an hypothesis as to its cause. At this point the real difficulty of applying the scientific method begins. It is easy to formulate hypotheses. It is very difficult to devise control experiments. An experiment must be arranged which will provide that, while all other conditions in which the phenomenon has been observed to occur are reproduced, the condition which was ex hypothesi its cause shall be omitted. This digression into the philosophy of science may seem to be somewhat remote from our line of march, but it may perhaps hasten our progress in the comprehension of the story of physiology. There is no other science in which the control experiment plays an equally important part. Unless this is realized, the whole trend of experimental work will be misunderstood. Scudamore explained coagulation as due to contact with air. Based on the observations we have cited, no hypothesis could have seemed more reasonable. With a view to checking this hypothesis, blood was received into a tube of mercury. It coagulated in the Torricellian vacuum. Scudamore’s hypothesis, like many earlier and later, when confronted with a control experiment, was turned away, ashamed.

Clotting is a property of plasma. Red corpuscles play no part in the process. Coagulation does not occur in a living healthy vessel. It occurs when the vessel, and especially when its inner coat, is injured. It is hastened by contact with wounded tissues, especially with wounded skin. Contact with a foreign body also starts coagulation. If a silk thread is drawn through a bloodvessel, from side to side, fibrin filaments shoot out from the thread, as well as from the wound inflicted on the vessel by the needle which was used to draw it through.

Plasma contains a substance which sets into fibrin. It has been termed “fibrinogen.” It is present in lymph, and in almost all forms of exuded lymph. If sodium chloride (common salt) is added to plasma until it is half saturated—until it has dissolved half as much as the maximum quantity which it can dissolve—fibrinogen is thrown down as a flocculent precipitate. It can be redissolved and reprecipitated until it is pure. When fibrinogen was separated from plasma a step was taken towards the explanation of coagulation. Under certain conditions fibrinogen sets into fibrin. The question which then presented itself for solution was as follows: What is the substance which, by acting upon or combining with fibrinogen, converts it into fibrin? The clue to the solution of this question was obtained from the consideration of certain observations made by Andrew Buchanan in 1830, but long neglected, because their significance was not understood. Buchanan had observed that some specimens of lymph exuded into a lymph-space—the peritoneal cavity, for example—will clot; others will not. He noticed that they clot when, owing to puncture of a small bloodvessel during the process of drawing them off, they are tinged with blood. Determined to ascertain which of the constituents of blood is effective in rendering non-coagulable effusions capable of clotting, he added to them in turn red blood-corpuscles, serum, and the washings of blood clot. Either of the two latter was found to contain the clot-provoking substance. Thirty years later a German physiologist prepared fibrinogen from effused lymph by precipitating it with salt. He also treated serum in a similar way, precipitating a protein which he termed fibrinoplastin. When these two substances were dissolved and the solutions mixed, he obtained a clot, which he regarded as a compound of fibrinogen and fibrinoplastin. Subsequently he found that the mixture did not always clot, but he discovered that if he coagulated blood with alcohol, and washed this residue, the washings added to the mixed solution just referred to invariably produced a clot. Thinking that the substance which he obtained from his alcohol-coagulated blood could not be proteid, he termed it “fibrin-ferment.” He neglected the control experiment. He failed to ascertain whether or not all three substances were needed. Had he tried adding fibrin-ferment to fibrinogen, he would have discovered that the further addition of fibrinoplastin was unnecessary. He did not ascertain, as he might have done, that the weight of fibrin formed is somewhat less, not greater, than the weight of fibrinogen used. (Fibrinogen gives off a certain quantity of globulin when it changes into fibrin.) He was also wrong in supposing that the water which he added to alcohol-coagulated blood dissolved no protein. His “fibrin-ferment” is always associated with a protein. Since it may also be obtained from lymphatic glands, thymus gland, and other tissues which contain lymphocytes, it has been inferred that it is itself a protein, of the class known as nucleo-proteins. The fact that it is destroyed at so low a temperature as 55° C. has been supposed to confirm the theory that it is a protein. But with regard to the chemical nature of fibrin-ferment, as of all other ferments, we are at present in the dark. Under ordinary circumstances, when blood clots, the fibrin-ferment, or plasmase, or thrombin—it has received various names—is set free by leucocytes. Fluids which contain fibrinogen clot on the addition of a “ferment” which is either secreted by leucocytes or set free from leucocytes when they break up—as they are very apt to do, as soon as the conditions upon which their health depends are interfered with.

Freshly shed blood contains minute particles, termed “platelets,” in diameter measuring about a quarter that of a red blood-corpuscle. When the inner coat of a vessel is injured, platelets accumulate at the injured spot. They form a little white heap, from which coagulation starts. Evidently they supply the ferment, or a precursor of the ferment. As yet their origin has not been traced. They are too large to be the unchanged granules of granular leucocytes, but that they are in some way derived from leucocytes seems probable.

The further study of coagulation has shown that the conditions under which it occurs are more complicated than the simple explanation just given would seem to imply. This explanation holds good, so far as it goes, but facts connected with the details of the process have recently been brought to light which warn the physiologist that as yet his theory of coagulation is incomplete.

The presence of salts of lime has an important relation to coagulation. If blood is received into a vessel in which has been placed some powdered oxalate of potash, or soap, or any other chemical which fixes lime, the blood does not coagulate. All other conditions are as usual, but lime is withdrawn from the plasma. The non-coagulation of oxalated plasma was interpreted as indicating that lime, under the influence of fibrin-ferment, combines with fibrinogen to form fibrin; that fibrinogen altered by fibrin-ferment combines with lime. This hypothesis was based upon the analogy of the curdling of milk. Milk cannot curdle if lime be absent. If rennin (milk-ferment), prepared from milk from which lime has been removed, be added to a solution of caseinogen (the coagulable protein of milk), also prepared from lime-free milk, no curd is produced. The addition of a few drops of a solution of chloride of lime results in the immediate curdling of the mixture. Evidently rennin so alters caseinogen as to bring it into a condition to combine with lime. But the analogy does not hold good for blood. In the case of plasma, lime acts, not upon fibrinogen, but upon the fibrin-ferment—or rather upon a precursor of fibrin-ferment—in such a way as to render it effective. Leucocytes produce a prothrombin, which in contact with lime salts is converted into thrombin, which coagulates fibrinogen.

Fibrinogen is the substance which fibrin-ferment combined with salts of lime changes into fibrin. Yet even now the story is not complete, if the theory of coagulation is to be brought up to date. A perfectly clean cannula is passed into an artery of a bird. If it be thrust well beyond the place where the vessel has been cut, if the vessel be tied so gently as to avoid injury to its inner coat, and if the blood which first passes through the cannula be allowed to escape, the blood subsequently collected will not clot. It contains fibrinogen, lime salts, and fibrin-ferment, ordinarily so called; but the ferment is ineffective. The addition to the blood of a fragment of injured tissue, or of a watery extract of almost any tissue, immediately sets up coagulation. This observation brings fibrin-ferment into line with other ferments. Digestive ferments are secreted as zymogens, which require to be influenced by a kinase before they acquire fermentative activity. So, too, must thrombogen be changed into thrombin, under the influence of thrombokinase, before it can act upon fibrinogen. Almost all tissues yield the kinase which actuates fibrin-ferment. The utility of this provision is manifest. A bird’s blood contains everything necessary to form a clot with the exception of thrombokinase. The injury which brings the blood into contact with a broken surface supplies this ferment of the ferment. Fibrin-ferment, rendered active, at once changes fibrinogen into fibrin. The same interaction is necessary before the blood of a mammal is susceptible of clotting. But a mammal’s blood is even readier to clot than is the blood of a bird; for not only will a broken surface provide it with thrombokinase, but the leucocytes contained within the blood, when injured, also yield it. And the leucocytes are exceedingly sensitive of any change of circumstance; on the slightest indication that conditions are not normal they set free, perhaps owing to their own disintegration, the kinase which turns thrombogen into thrombin.

There is a constitutional condition, fortunately rare, in which blood does not coagulate. A person subject to this abnormality is said to suffer from hæmophilia. It is alleged that this condition is due to deficiency of lime in the blood; and the deficiency of lime is said to be due to excess of phosphates. The subject suffers from phosphaturia. His kidneys get rid of the superabundance of phosphates by excreting them in combination with lime. If this explanation be correct, there is a chronic insufficiency of lime in the blood, because it is being constantly withdrawn in the process of removing phosphates.

The difficulty in the way of establishing a complete theory of the coagulation of blood increases when the phenomena of incoagulability are considered. Blood may be rendered incapable of clotting in a variety of ways. Leeches and other animals which suck blood have the capacity of rendering it incoagulable. If the heads are removed from a score of leeches, thrown into absolute alcohol, dried, ground in a pepper mill, extracted with normal saline solution, a dark turbid liquor is obtained. This liquor, after filtration and sterilization at a temperature of 120° C., injected into the veins of an animal, renders its blood incoagulable.

The preparation sold by druggists under the name “peptone,” when injected into the veins of a dog, renders its blood incoagulable. Commercial “peptone” is a mixture of many substances. Its anticoagulation-effect is not due to the peptone which it contains. It has been supposed to be due to imperfectly digested albumin and gelatin (proteoses), but products of bacteric fermentation (toxins and ptomaines) are more probably the active bodies. Not only is the peptonized blood of a dog incoagulable, but if this blood be injected into the veins of a rabbit (an animal upon which the direct injection of peptone has no effect), it diminishes the coagulability of the rabbit’s blood. If peptonized blood be mixed in a beaker with non-peptonized blood, it prevents the coagulation of the latter. There is little doubt but that the poison, whatever it may be, acts upon the leucocytes; and there are some reasons for thinking that the poison is not contained in the “peptone,” but is secreted by the liver of the animal into which the “peptone” has been injected.

A still more remarkable property in relation to coagulation must be assigned to leucocytes. The blood of a dog which has been rendered incoagulable by injection of peptone recovers its coagulability after a time. If a further injection of “peptone” be made, the animal is found to be immune. Injection of “peptone” no longer renders its blood incoagulable. In a similar manner the blood develops a power of resisting the action of agents which induce its coagulation whilst circulating in the vascular system. Nucleo-proteins contained in extracts of lymphatic glands and other organs when injected into the veins of living animals cause their blood to clot, provided they are injected in sufficient quantity. If they are injected in quantity less than sufficient to induce coagulation, they render the animal immune to their influence. A larger quantity given to an animal thus prepared fails to take effect. This brings the phenomena of coagulation and resistance to coagulation to the verge of chemistry. They extend into the domain in which pathology reigns. Tempting though it be to record other facts with regard to these phenomena which recent investigation has brought to light, it is probably judicious to leave the problem at the frontier. Across the frontier lies a fascinating land, rich with unimaginable possibilities for the human race. Settlement is rapidly proceeding in this country, which is charted, like other border-lands, with barbarous names: “antibodies,” “haptors,” “amboceptors,” “toxins,” “antitoxins,” and the like—finger-posts to hypotheses which show every sign of hasty and provisional construction. But certain facts stand out, in whatever way theory may, in the future, link them up. The virus of hydrophobia, modified by passing through a rabbit, develops in human beings, even when injected after they have been infected, the power of resisting hydrophobia. The serum of a horse which has acquired immunity to diphtheria aids the blood of a child, which has not had time to become immune, in destroying the germs of this disease. It is a contest between the blood and offensive bodies of all kinds which find entrance to it, whether living germs or poisons in solution; with victory always, in the long-run, on the side of the blood, provided its owner does not die in the meantime. And not only is the blood victorious in the struggle with any given invader, but having repulsed him, it retains for a long while a property which neutralizes all further attempts at aggression on his part. In the past, physicians have fought disease with such clumsy weapons as mercury, arsenic, and quinine. Now they anticipate disease. In mimic warfare with an attenuated virus the blood is trained to combat. Smallpox which has been passed through the body of a cow is suppressed by the blood’s native strength. The exercise develops skill to deal with the most virulent germs of the same kind. In cases in which physicians cannot anticipate disease in human beings, they train the blood of animals to meet it; and, keeping their serum in stock, they can, when the critical moment arrives, reinforce the fighting strength of the patient with this mercenary aid.

The Spleen.—The spleen is placed on the left side of the body, and rather towards the back. It rests between the stomach and the inner surface of the eighth, ninth, tenth, and eleventh ribs. It is quickly distinguished from other organs by its brown-purple colour, a sombre hue to which it owed its evil reputation with the humoralists. The liver’s yellow bile tinged man’s mental outlook, preventing him from seeing objects in their natural brightness; but the spleen made black bile, which, mounting to the brain, displayed its malign influence upon the action of that organ, as, or in, the worst of humours.

The spleen is invested with a capsule of no great toughness. Inside the capsule is “spleen-pulp.” When the fresh organ is cut across, it is seen that, although most of the pulp is of the colour of dark venous blood, it is mottled with light patches. In some animals—the cat, for example—these whitish patches are small round spots, regularly arranged at a certain distance from the capsule. The distinction into “red pulp” and “white pulp” marks a division into two kinds of tissue with entirely different functions. The white pulp is lymphoid tissue, lymph-follicles developed in the outer or connective-tissue coat of the branches of the splenic artery. Its function is to make lymphocytes, of which, for reasons which will shortly appear, the spleen needs an abundant supply. The constitution of the red pulp is entirely different, and peculiar to the spleen. The branches of the splenic artery divide in the usual way into smaller and still smaller twigs until the finest arterioles are reached; but these arterioles do not give rise to capillary vessels. At the point at which in any other organ their branches would attain the calibre of capillaries, the connective-tissue cells which make their walls scatter into a reticulum. They are no longer tiles with closely fitting, sinuous, dovetailed borders, but stellate cells with long delicate processes uniting to constitute a network. The blood which the arterioles bring to the pulp is not conducted by closed capillary vessels across the pulp to the commencing splenic veins. It falls into the general sponge-work. The venules commence exactly in the same way as the arterioles end. Stellate connective-tissue cells become flat tiles placed edge to edge. The endothelium of an arteriole might be likened to a column of men marching shoulder to shoulder, three or four abreast; the connective tissue of the pulp, to a crowd in an open place. The column breaks up into a crowd. On the other side the crowd falls into rank as the endothelium of veins. The capsule and the red pulp are largely composed of muscle-fibres. These relax and contract about once a minute. By their contraction the blood is squeezed out of the sponge.

If the spleen be enclosed in an air-tight box (an oncometer), from which a tube leads to a pressure-gauge—a drum covered with thin membrane on which the end of a lever rests, or a bent column of mercury on which it floats—the pressure-gauge shows the changes in volume of the spleen. The long end of the lever, which records the variations of pressure in the gauge, may be made to scratch a line on a soot-blackened surface of travelling paper. A record of the variations in volume of the organ, which can be studied at leisure, is thus obtained. It shows that the spleen is sensitive to every change of pressure in the splenic artery. Small notches on the tracing correspond to the beats of the heart. Larger curves record the changes of blood-pressure due to respiration. A long slow rise and fall marks the rhythmic dilation and contraction of the spleen itself.

One of the three large arteries into which the cœliac axis divides delivers blood to the spleen direct from the aorta. The splenic vein joins the portal vein shortly before it enters the liver. Thus the spleen is placed on a big vascular loop which directs blood, not long after it has left the heart, from the aorta, through the spleen, to the liver.

The peculiar construction of the splenic pulp which brings the blood more or less to rest within its sponge-work, and the transmission to the liver of the blood which leaves the spleen, indicate that it is an organ in which blood itself receives some kind of treatment. It is not passed through it, as it is through all other parts of the body, in closed pipes. The spleen is a reservoir, or a filter-bed, into which blood is received.

Fig. 5.—A Minute Portion of the Pulp of the Spleen,
very highly magnified.

Stellate connective-tissue cells form spaces containing red blood-corpuscles and leucocytes. In the centre of the diagram is shown the mode of origin of a venule. It contains two phagocytes—the upper with a nucleus, two blood-corpuscles just ingested, and one partially digested in its body-substance; the lower with two blood-corpuscles.

The red blood-corpuscles of mammals are cells without nuclei, and with little, if any, body-protoplasm. They are merely vehicles for carrying hæmoglobin. We should deny to them the status of cell, if it were possible to prescribe the limit at which a structural unit ceases to be entitled to rank as a cell. They are helpless creatures, incapable of renewing their substance or of making good any of the damage to which the vicissitudes of their ceaseless circulation render them peculiarly liable. It is impossible to say with any approach to accuracy how long they last, but probably their average duration is comparatively short. The spleen is a labyrinth of tissue-spaces through which at frequent intervals all red corpuscles float. If they are clean, firm, resilient, they pass through without interference. If obsolete they are broken up. In the recesses of the spleen-pulp, leucocytes overtake the laggards of the blood-fleet, attach their pseudopodia to them, draw them into their body-substance, digest them. The albuminous constituent of hæmoglobin they use, presumably, for their own nutrition. The iron-containing colouring matter they decompose, and excrete in two parts; the iron (perhaps combined with protein); the colouring matter, without iron, as the pigment, or an antecedent of the pigment, which the liver will excrete in bile. Hæmoglobin is undoubtedly the source of bilirubin, and general considerations lead to the conclusion that it is split into protein, iron, and iron-free pigment in the spleen; but the details of this process have never been checked by chemical analysis. Neither bile-pigment nor an iron compound can be detected in the blood of the splenic vein. The only evidence of the setting free of iron in the spleen is to be found in the fact that the spleen yields on analysis an exceptionally large quantity of this metal (the liver also yields iron), and that the quantity is greatest when red corpuscles are being rapidly destroyed.

As a rule, it is very difficult to detect leucocytes in the act of eating red corpuscles; but under various circumstances their activity in this respect may be stimulated to such a degree as to show them, in a microscopic preparation, busily engaged in this operation. The writer had the good fortune to prepare a spleen which proved to be peculiarly suitable for this observation ([Fig. 5]). His method was an example of the way in which a physiological experiment ought not to be conducted. Having placed a cannula in the aorta of a rabbit, just killed with chloroform, he was proceeding to wash the blood out of its bloodvessels with a stream of warm normal saline solution, when the bottle from which the salt-solution was flowing overturned. Fearing lest an air-bubble should enter the cannula, he hastily poured warm water into the pressure-bottle, and threw in some salt, in the hope that it would make a solution of about 0·9 per cent. The salt-solution was allowed to run through the bloodvessel for rather more than an hour. When sections of the spleen were cut, after suitable hardening, every section was found to be packed with leucocytes gorged with red corpuscles. Some of the corpuscles had just been ingested; from others the hæmoglobin had already been removed. It may be that, for some unknown reason, the destruction of red corpuscles was occurring in this particular rabbit with unusual rapidity at the time when it was killed; but it seems more probable that the animal’s leucocytes were provoked to excessive activity by changes in the red corpuscles brought about by salt-solution which was either more or less than “toxic.” As a score of attempts to reproduce the experiment, with solutions of different strengths, have failed, it is impossible to be sure that this is a valid explanation.

There must be something in the condition of worn-out red corpuscles which either makes them peculiarly attractive to predatory leucocytes or renders them an exceptionally easy prey. It does not require much imagination to picture the drama which is enacted in the spleen. Slow-moving leucocytes are feeling for their food. The majority of red corpuscles pass by them; a few are held back. The leucocytes, like children in a cake-shop, cannot consume all the buns. A selection must be made, and preference is given to the sticky, sugary ones. Red corpuscles when out of order show a tendency to stick together. When blood is stagnating in a vein, or lying on a glass slide in a layer thin enough for microscopic examination, its red discs are seen after a time to adhere together in rouleaux. The parable of a child in a cake-shop is not so fanciful as it may appear.

The differentiation of function of organs is not as sharp as was formerly supposed. Evidence of their interdependence is rapidly accumulating. The activity of various organs is known to result in the formation of by-products termed “internal secretions,” which influence the activity of other organs, or even of the body as a whole. The spleen enlarges after meals. This may be merely connected with the engorgement of the abdominal viscera which occurs during active digestion, or it may indicate, as some physiologists hold, that an internal secretion of the spleen aids the pancreas in preparing its ferments. The spleen enlarges greatly in ague and in some other diseases of microbial origin. This has been regarded as evidence that it takes some part in protecting the body against microbes. But whatever may be the accessory functions which it exercises, they are not of material importance to the organism as a whole, seeing that removal of the spleen causes no permanent inconvenience either to men or animals. Its blood-destroying functions are taken on by accessory spleens, if there be any, and by lymphatic glands. The marrow of bone also becomes redder and more active. Under certain circumstances, red corpuscles, or fragments of red corpuscles, are to be seen within liver-cells; but it is uncertain whether blood-destruction is a standing function of the liver.

CHAPTER V
INTERNAL SECRETIONS

Thyroid Gland.—On either side of the windpipe, rather below the thyroid cartilage (Adam’s apple), lies a somewhat conical mass of tissue. The two masses are connected by an isthmus; lobes and isthmus make up the thyroid gland. The whole weighs about an ounce. In health it is so soft that only the finger of an anatomist could detect it through the skin and the thin flat muscles which connect the hyoid bone and the thyroid cartilage with the breast-bone. It makes no visible prominence on the front of the neck. The thyroid gland is, however, liable to enlargement, especially amongst the people who live in certain districts. In the Valais, “goitre,” as it is termed, is so frequent that anyone walking up the Rhone Valley is sure to meet a number of persons—for the most part women—whose swollen necks overhang their collar-bones, like half-filled sacks. Goitre is even more common in the Valle d’Aosta, on the Italian side of the Alps. In England this condition, comparatively rare, is known as “Derbyshire” or “Huntingdonshire” neck.

In the majority of cases the tumour in the neck develops slowly, and does not reach its full dimensions until after middle life. Goitre in this form, although inconvenient, causes no serious discomfort. But when it appears in early life, it is associated with an extraordinary complex of malformations and ill-performed functions. The condition into which a goitrous child sinks is known as cretinism. With the exception of the skull-case, its skeleton does not attain to its proper proportions; and, since the soft parts do not equally submit to arrest of growth, the dwarf is heavy and ungainly, with large jowl and protuberant abdomen. The appearance of distortion is extraordinarily heightened by hypertrophy of the skin and the subcutaneous connective tissue. Ears, eyelids, nose, lips, fingers, are thick and heavy. The hair and nails are coarse. The skin is folded, wrinkled, rough.

The bodily ungainliness of a cretin has its counterpart in the deformity of his mind. He is an idiot whose deficiency is chiefly marked by apathy.

Cretinism exhibits itself in varying degrees. The description that we have just given would not be accurate for all. For the sake of brevity, we have chosen a case which might be that of a goitrous cretin of a certain type, or that of a cretin whose thyroid gland, in lieu of showing what looks like overgrowth, has failed to properly develop. Nothing is more remarkable with regard to this organ than the fact that the condition associated with its overgrowth and the effects of its atrophy, or inadequate growth, are the same. A consideration of the function of the gland will suggest an explanation of this seeming paradox.

The inconvenience caused by goitre induced surgeons, about twenty-five years ago, to remove the tumour in simple uncomplicated cases. Owing to the accessibility of the gland, the operation is both safe and easy; but its removal was found to be followed by symptoms of a very serious nature, especially overgrowth and œdema of subcutaneous tissue, muscular twitchings and convulsions, mental dulness. About the same date, physicians recognized that the disease myxœdema—so called because the œdema is not watery, as in dropsy, but firm and jelly-like—is due to deficiency of the thyroid gland.

No other organ of the body has so weird an influence upon the well-being of the whole. No other organ has an equally mysterious ancestral history. Assuredly the thyroid gland was not always such as we see it now. In prevertebrate animals it must have been quite different, both in structure and in function. From fishes upwards, however, its structure is always the same. It is composed of spherical vesicles or globes. Every globe is lined by a single layer of cubical epithelial cells. Its cavity is filled with a homogeneous semi-solid substance known as “colloid.” The globes are associated into groups or lobules. They are in contact with large wide lymphatic vessels. The organ has a lavish supply of blood. It is also well supplied with nerves. Colloid is the secretion of the epithelial cells which line the globes. As these globes have no openings, the secretion must be passed by osmosis into the lymphatic vessels. There is abundant reason for believing that by this route the products of the gland reach the blood, and are distributed by the blood to all the tissues of the body. And here it is important to notice that associated with the thyroid gland are certain very small masses of tissue termed “parathyroids.” There may be four of these—two on the course of the large arteries which supply the thyroid gland from above, two related with the almost equally large arteries which supply it from below; but the number varies. The parathyroids do not contain vesicles. They are solid masses of epithelial cells, traversed by bloodvessels and lymphatics. Yet, like the epithelial cells of the vesicles, they secrete colloid. Granules of this substance are to be seen within their cells. We cannot pass over the parathyroids without this reference, since, small though they are, they seem to be quite as important as the thyroid gland itself, judging from the effects which follow their removal.

In all vertebrate animals the thyroid gland has the characters which we have described. What was it like in the ancestors of the vertebrate races? Its microscopic appearance in vertebrates, the only animals in which we know it, is so anomalous as to convince an histologist that it is a makeshift; it looks like an organ which, at a period no longer visible through the mists of time, had a quite different function to perform. This function it has lost—some other organ has taken it on—yet it must do something which is useful to the organism. Otherwise it would not have been preserved. It has been retained for the sake of its by-function, for the sake of the internal secretion which it produces. This is now the only work it has to do.

What was its prime function? It is an axiom of biology that an animal in its individual development recapitulates, albeit with many omissions and abbreviations, the ancestral history of its race. The thyroid gland appears in the embryo as a diverticulum of the anterior wall of the pharynx. It is remarkable in being a single, median, unpaired diverticulum, whereas almost all other organs are bilaterally symmetrical. The parathyroids are formed on the two sides in connection with certain of the branchial pouches. In its earliest development the thyroid gland resembles any other gland—a salivary gland, for example. Until a late stage it retains its connection with the back of the mouth. Occasionally indications of this primitive connection persist throughout life. In most cases the place where the duct of the thyroid gland used to open is clearly marked. At the back of the tongue—too far back to be seen without the aid of a dentist’s mirror—there is a V-shaped row of large papillæ (papillæ circumvallatæ). Just behind the meeting-point of the two limbs of the V a pit is to be seen—foramen cæcum. This pit is the vestige of the mouth of the duct of the thyroid gland which opened into the pharynx in the ancestors of fishes. It is an inconceivably long time since fishes diverged from other races of animals. We do not know which of the various orders of invertebrate animals now existent most nearly resembles our prepiscine ancestor. The organ which has developed into the thyroid body of mammals may possibly have disappeared from all the other descendants of the common stock from which vertebrates and their nearest relatives in the invertebrate sub-kingdom were evolved; but it is much more likely that it has been preserved, and is still performing its prime function in the higher invertebrate animals. Probably it is a functional organ in a cuttle-fish or a scorpion or a worm, but so unlike the thyroid gland of vertebrates that we fail to recognize its homology. There are other instances in the body of the persistence of an organ long after it has fallen into such ruin that not even archæologically-disposed biologists can guess what it was like, or what purpose it served in the days when it was at the height of its efficiency; but perhaps there is none other which so pregnantly illustrates the physiological doctrine of functional interdependence. Nature shows herself amazingly conservative in retaining primal organs—the pituitary body, the thymus gland, the thyroid gland, the suprarenal capsules—organs which millions of years ago forgot the very rudiments of their craft; but her conservatism is not mere force of habit. Although she no longer has any use for the wares which she created these pieces of apparatus to make, she cannot do without their refuse. Even the vermiform appendix may have its use. Dr. Gaskell’s theory of the thyroid gland involves a transformation so fantastic that it would provoke a smile of incredulity were we to set it forth without a prologue far more lengthy than our space permits. Yet Dr. Gaskell may be right. We can but guess as to the nature of the prime functions of the thyroid and parathyroids. For many geological epochs they have not been exercised. But whatever else they did when they were indispensable constituents of the organism, their activity was accompanied by the secretion of colloid. Colloid is not made by other organs; therefore the otherwise obsolete thyroids are retained. It is of course not impossible that, in a certain degree, Nature, like a thrifty housewife, finds a new use for superseded apparatus; but we are probably justified in believing that the use is never really new. Not wanting the organ for its original specific purpose, Nature relegates to it alone work which hitherto it had shared with other of her tools.

A comparatively short while ago the attention of physiologists was wholly concentrated upon the obvious or prime functions of organs. Muscles contracted. The stomach digested. The pancreas secreted pancreatic juice. The brain made thought. Now they understand, to put it somewhat metaphorically, that gastric juice is made in the calves of the legs; the ferment of pancreatic juice in the small intestine; thought of a certain emotional quality in the large intestine. The chemistry of the laboratory is far behind the body’s chemistry. We cannot detect in the blood coming from contracting muscles the stimulant—possibly a precursor of pepsin—to which the stomach reacts, although the magical benefit of exercise seems to prove that there is a chemical connection between the activity of the muscles and the activity of the glands of the alimentary canal. It has been proved by experiment that a substance produced in the epithelium of the small intestine is the messenger upon whose call depends the potency of pancreatic juice. The clearing of the brain effected by a judicious pill shows that poisons of some kind are absorbed into the blood from an overloaded large intestine. None of the organs lives altogether for itself. The chemical products which it throws off, absorbed by the blood, regulate the activity of other organs. Formerly the several parts of the body were looked upon as independent. Their activity was regarded as a direct response to the commands of the nervous system. If it varied in kind, the variations were supposed to depend upon the quality of the nervous impulses which reached the organ. Evidence is rapidly accumulating that many exhibitions of function are evoked by the calls of “hormones,” or chemical messengers, not by command of the nerves.

Internal secretions, using the expression in its general sense, are necessary for the co-ordination of the work of the various parts of the animal mechanism. Colloid is the internal secretion of the thyroid gland and of the parathyroids. Unlike most other internal secretions, it is a substance easily analysed, and startlingly definite in its chemical characteristics. It is composed mainly of a protein which contains iodine. From this protein a substance termed “iodothyrin” may be obtained, of which no less than 10 per cent. is iodine; but it is uncertain whether iodothyrin is preformed in the gland. The exact nature of the active substance of the internal secretion of the thyroid gland matters little. Whether it be iodothyrin or a protein, its activity depends upon the fact that it contains iodine in large quantity. Iodine amounts to from 0·3 per cent. to 0·9 per cent. of the weight of the whole thyroid gland in Man.

Iodine is very widely distributed in Nature. It is present in the air, in rain-water, in herbage. It is also present in all parts of the body, although in quantities which are infinitely minute. It is found in sea-water, and is relatively abundant in marine plants. There is no reason for supposing that it is deficient in districts in which goitre is common. It would appear more likely that the soil has properties which result in the fixing of iodine in a form in which it is not available for plant-food, and that in consequence animals are unable to obtain a sufficient supply. Careful analyses have shown that the thyroid glands of sheep bred in mountainous districts where goitre is common contain but one-thirtieth part as much iodine as the thyroid glands of sheep bred in places where goitre is rare. In ancient times burnt sponge and seaweed were esteemed useful in the treatment of goitre. Later, iodide of potassium given internally, and tincture of iodine as an outward application, were the approved remedies. It is now known that myxœdema and certain forms of goitre may be checked, and even cured, by administering uncooked thyroid gland or even tabloids of dried extract. Fortunately, it is not necessary to inject it subcutaneously; the iodine-containing compound is so stable as to resist the action of gastric juice.

Iodine stored in the thyroid and parathyroid glands is distributed to all the tissues. The remarkable symptoms which indicate that the tissues are not receiving an adequate supply may occur under either of two conditions. Iodine may be deficient in the food, or the thyroid gland may be incompetent; the former is the commoner cause. And here we see the explanation of the formation of a goitre. By increasing the size of the organ which selects iodine, Nature attempts to obtain and store an adequate supply for distribution to the tissues.

Cretinism has been observed in animals. If attention were directed to this inquiry, it might be found that it is not so exceedingly rare as would be judged from the few observations that have been recorded. A cretin, if a wild animal, falls an easy prey. If a domesticated animal, little trouble is taken to insure its survival. A myxœdematous pig is a dwarf with coarse, sparse hair, thick, warty hoofs, large jowl, heavy ears. It is apathetic. A piglet presenting these characteristics is not altogether uncommon in a litter. Among chickens and pigeons, also, individuals appear which might, judging from their uncouth appearance and mental dulness, be suffering from cretinism. The only way of proving that this is the case is to feed them on thyroid glands; it does not matter from what animal the gland is obtained. Operative cretins, produced by removing the thyroid gland soon after birth, recover their natural characters on a diet containing a daily allowance of thyroid gland. The coarse hairs, or wiry towsled feathers, fall off, and are replaced by a smooth, supple growth. The thickened skin becomes soft and pliant. Mental apathy gives place to alertness. They make up for lost time by growing more rapidly than other animals of the same age, which have not been operated upon, although they never surpass the normal stature.

Suprarenal Capsules.—Each of the kidneys is capped by a pyramidal body weighing about ⅛ ounce. Small though it be, this organ is essential to life. As Dr. Addison was the first to discover, in 1855, its disease results in a cycle of symptoms which invariably has a fatal termination. A college friend of the writer suffered from “slackness.” Before he had finished a set of tennis, he abandoned the game, and spent the rest of the afternoon lying on the grass, wrapped in a rug. After hall, although he earnestly desired to conquer the subtleties of the Greek grammar, he fell asleep over his books. As his countenance was not ruddy merely, but bronzed like that of a man who has just returned from a yachting cruise, he was the butt of many a joke. Although already a qualified medical man, who had been in practice—he had come to the University with a view to adding the degree of M.D. to his M.R.C.S.—he had no suspicion that he was ill. Thought he wanted “freshening up.” Took a trip across the Atlantic. Stumbled over a rope on landing; broke his thigh. Spent two months in a New York Hospital, but the bone did not mend. At last, the surgeons, growing anxious, sent him back to London. He was seen by a leading physician, who told him that he was suffering from Addison’s disease. Two months later he died of failure of the heart. Disease of the suprarenal capsules is usually of tuberculous origin. Its symptoms: muscular weakness and excessive liability to fatigue; abnormal pigmentation of the skin; lowered blood-pressure, and consequent sensitiveness to cold; cardiac weakness. As the pigmentation of the skin and mucous membrane is not invariable, and since it may occur without disease of the capsules, it is not improbable that it is due to disease of the abdominal sympathetic ganglia, which are usually affected at the same time as the capsules.

The suprarenal capsules are composed of columns of epithelial cells, which radiate from a large vein in their centre. They are abundantly supplied with blood and with nerves. The cells near the vein are much larger than those in the peripheral portions of the columns. Amongst them are nerve-cells resembling those of the sympathetic system.

The history of the suprarenal capsules is almost as obscure as that of the thyroid gland. In the embryo they are relatively very large—larger at one period than the kidney. At this period bloodvessels are formed in them with great rapidity by a curious process of boring through and channelling out of their cells. There are other facts connected with their development in the individual and their varying form in different classes of vertebrate animals which point to a “previous existence,” but there is nothing to indicate that they were ever open glands. In all vertebrates they are closed masses of cells, the only function of which, so far as we know, is to produce an internal secretion; but the importance of this chemical messenger in bringing about the proper working of other organs is almost startlingly evidenced by the collapse which follows disease, or removal of the organ which produces it.

The suprarenal capsules yield a substance which has been termed “adrenalin.” It contains nitrogen, is crystallizable and dialysable; but its chemical relationships have not been made out as yet. It is not destroyed by boiling, nor by digestion with gastric juice. Injected into a vein, it causes, amongst other effects, an immense rise in blood-pressure, even though the amount injected be extraordinarily small. Applied locally as a wash or spray, a solution of 1 part in 10,000 produces marked blanching of the surface; and it is useful, in consequence, as a means of checking bleeding in small operations, especially those on the eye or the nose. It is a most energetic poison. Even ¼ milligramme is sufficient to kill a rabbit. In short, adrenalin acts like the most powerful drugs known to physicians; and this drug, manufactured by the suprarenal capsules, is constantly added to the blood. Disastrous consequences follow a failure in the regular supply.

The tone of the vascular system is maintained by adrenalin. The nature of its influence upon muscles is not known, but probably the complete loss of muscular strength, which is one of the most noticeable symptoms of disease of the suprarenal capsules, is an indirect result of the lowering of blood-pressure. The muscles, it must be remembered, make up about one-third of the weight of the body of a muscular man. For the exchange of their waste products for food, they are dependent upon an efficient circulation. They are unable to display their normal vigour when the vascular system is not up to its work.

The Pituitary Body is another ductless gland of dubious history. It is a round body, the size of a small marble, which occupies a deep recess in the floor of the skull, beneath the centre of the brain. It is composed of epithelial cells collected into irregular groups. No homologue of the pituitary body can be found in the invertebrate sub-kingdom. Its strange mode of development in vertebrate animals—it is present in them all, from fishes to mammals—and the mystery in which its prevertebral existence is hidden, provoke to speculation. We must be content to state that it is undoubtedly masquerading under an assumed name. “Pituitary body” is reminiscent of a long-abandoned theory that it secretes fluid into the upper chamber of the nose.

Disease of the pituitary body is associated with a perversion of growth even stranger than that due to disease of the thyroid gland. The condition has been termed “acromegaly,” to indicate that all extremities—toes, fingers, nose, lips, tongue—undergo enlargement.

With these three organs—the thyroid gland, the suprarenal capsules, and the pituitary body—we must leave the subject of internal secretions. Each of these organs is a ductless gland. Each has a history which the zoologist is unable to transcribe. The document is a palimpsest, the earlier script so faint as to be illegible beneath the dark letters which a new era has written over it. Even the modern script is smudged and blotted. The laws which it sets forth seem, as a rule, to be destitute of sense, but a sinister meaning is evident at times. We are tempted to regard these codes as obsolete, until the mischief which follows their suppression calls our startled attention to the fact that they are, in the most lively sense, extant. Myxœdema, Addison’s disease, acromegaly, are ominous warnings that the three ductless glands are no mere monuments of a past epoch, which owe their survival to Nature’s indolence. They teach us that we must not attribute the persistence of such organs to a conservatism which resists innovation, or suppose that they would long ago have been wiped off the statute-book if her inertia could have been overcome. Undoubtedly Nature gives us many excuses for adopting this attitude of mind. The “chestnuts” on a horse’s legs, the “dew-claws” of a dog’s foot, are vestiges which would have disappeared if every part of the body had to establish its claim to be regarded as useful before it became entitled to share in the common supply of food; so, at least, we are disposed to think. But, tempting though it be to attribute to sheer conservatism the retention of an organ which has been superseded in its original functions, and for which we cannot recognize any new use, it is a temptation which must be severely checked. It is safer to suppose that the fact that it has been retained is prima-facie evidence that the body has need of it.

There can be no doubt as to the importance of the internal secretions of the three chief ductless glands. What about other organs—the glands which make external secretions, for example? Does each of them make also an internal secretion which influences the activity of other organs? It is very difficult to prove the production of internal secretions by such organs as the salivary glands, the pancreas, the kidneys, because all the effects which result from their removal may be due to the suppression of their external secretions. It is almost impossible to distinguish the consequences which might be due to the abolition of an internal secretion from those which ought to be attributed to the loss to the body of the chief functions of the organ. Certain physiologists are inclined to think that all organs—not only the glands, but the liver, spleen, muscles, etc.—produce chemical messengers which are discharged into the blood; and recent discoveries tend to justify this view. As the time approaches when milk will be wanted for the nourishment of offspring, it begins to appear in the breast. Hitherto this has been attributed to nervous control. It is now known that the secretion is provoked by a chemical messenger. If this messenger, extracted from the organ in which it is formed, be injected into the veins of an animal which has no call to secrete milk, it sets up a condition of activity in its mammary glands. Such an illustration of the possibilities of chemical, as distinguished from nervous, control inclines us to attribute the harmonious working of the body in large measure to the mutual influence of its several parts, instead of invoking in every case, as used to be the custom, the directing power of a somewhat bureaucratic nervous system.

It is curious to note that an internal secretion is essentially a drug. Faith in drugs has suffered eclipse in latter days, and with good reason. The medicines of fifty years ago so little resembled Nature’s pharmacy that there is cause enough for astonishment at the credulity of a generation that believed them to be charms by the exhibition of which they could direct the working of the body. To be quite just, our forebears did not exactly adopt this view. They still believed in remedies. Docks grew in the same hedgerow as nettles. Therefore the juice of the dock was an antidote to nettle-stings. Washerwomen found wasps vexatious, but, fortunately, “blue-ball” cured the pain of their stings, and prevented the swelling which otherwise would have occurred.

A new pharmacology is rapidly developing. The physiological action of every substance likely to be of service as a drug is put to the proof. Having ascertained what is wrong, and knowing exactly what effects his drugs are capable of producing, the physician devises the adjustment which he may attempt without risk of making matters worse. He then seeks, if possible, a chemical messenger near akin to the messenger whom Nature herself would send; at least, this is the ambition of the modern pharmacologist.

CHAPTER VI
DIGESTION

The Canal.—The prospect presented by a widely open mouth is too familiar to need description, but a few details may be pointed out. The teeth are, or should be, thirty-two in number. Starting from the middle line of either jaw, the two first are incisors, with chisel-shaped cutting edges. If they meet, as they ought to do, their edges are ground flat. The third tooth is the canine, with a more or less pyramidal crown. Then two premolars, or “milk-molars,” as they are often termed, because they are the only grinding teeth of the first dentition. Twenty is the full complement of teeth in a child. Lastly, three strong grinders—the molar teeth. The third molar, or wisdom-tooth, is evidently disappearing in the human race. In civilized people, whose brains are large and jaws small, it does not appear until about the twentieth year. Sometimes it tries to squeeze through the gum of a jaw not large enough to carry it, and causes trouble by becoming “impacted” beneath the ascending ramus. Not infrequently it fails to appear. It may be truly said that the increasing wisdom of the human race is responsible for the postponement of its development, although this is hardly the circumstance to which it owes its name. A fold of mucous membrane—the frenulum linguæ—connects the under side of the tongue with the floor of the mouth. On either side of this may be seen the opening of a duct common to the submaxillary and sublingual salivary glands. The opening of the duct of the parotid gland is not so easy to find. It pierces the mucous membrane of the cheek opposite to the base of the second molar tooth of the upper jaw. The parotid gland lies just below the ear, behind the jaw. The saliva which it secretes is a watery fluid containing little beside salt and a weak ferment. It serves to moisten the food as it is being crushed by the molar teeth. The submaxillary and sublingual secretions contain, in addition to the ferment, ptyalin, mucus which the tongue mixes with the masticated food as it forms it into a bolus suitable for swallowing. The dorsal surface of the tongue is covered by papillæ, which rasp the food against the palate. Of these the greater number are pointed, or filiform. The remainder are flat-topped, or fungiform. The two varieties may be distinguished with a lens, especially on the sides of the tongue. Usually the fungiform papillæ are the redder. In fever, when the tongue is densely furred, they stand out as bright red spots. The back of the tongue is crossed by a V-shaped row of papillæ of larger size, each surrounded by a slight fossa and a vallum, and hence termed “circumvallate.” Very minute organs of sense—taste-bulbs—stud the mucous membrane which lines the fosse.

The hard palate ends in a muscular curtain—the soft palate—the central portion of which—the uvula—depends lower than the rest. On either side the soft palate splits into two folds; the anterior, continued to the side of the tongue; the posterior, to the pharynx. These folds, since they bound the gateway into the pharynx, which is known as the “fauces,” are termed the “pillars of the fauces.” The tonsil lies between the anterior and posterior pillars of the fauces, but does not appear as a prominence unless inflamed or enlarged.

The pharynx hangs as a bag from the base of the skull. It, like all the rest of the alimentary tract, is lined by mucous membrane. “Mucous membrane” is not a happy term. It does not denote that the epithelium secretes mucus. It may or may not possess this property. Nor does it imply that it has a different origin from the skin—that it arises from hypoblast, the inner layer of the rudiment from which the embryo grows. The term is applied to all internal, and therefore moist, surfaces, whether they arise from hypoblast, as in the case of the lining of the greater part of the alimentary tract, or whether they are involutions of epiblast as in the case of the mouth and also of the extreme lower end of the alimentary tract. Almost the whole of the alimentary canal is, in the first instance, a tubular cavity in the interior of the embryo, lined by hypoblast. This cavity communicates with the yolk-sac, but has no openings on the exterior until it joins up with two epiblastic pits—one the stomodæum, or mouth-cavity, at the anterior end; and the other the proctodæum, at the posterior end of the body. The distinction between the middle closed portion of the alimentary canal and its two secondary openings suggests morphological speculations, into which we have not space to enter, as to the ancestry of the vertebrates. The majority of anatomists believe that the primitive canal is represented in the middle portion, and that, in prevertebrate animals, it opened to the exterior in a different way. The pharynx is 4½ inches long. It is enclosed by three thin muscles, which overlap from below upwards—the constrictors of the pharynx. The anterior attachment of the superior constrictor is to the jaw; of the middle constrictor to the hyoid bone; of the inferior constrictor to the thyroid cartilage. Above the soft palate the nasal chambers communicate with the pharynx by the posterior nares. Below the hyoid bone, which is easily felt in the neck as a bony arch just above the thyroid cartilage (Adam’s apple), the windpipe, or trachea, joins the pharynx by a single pear-shaped orifice—the rima glottidis. When we consider the mechanism of swallowing, we shall study the arrangements which prevent food, passed through the fauces, from entering either the nasal chambers above or the windpipe below and in front. At the level of the lower border of the thyroid cartilage the pharynx becomes the relatively narrow œsophagus. This tube, which lies behind the trachea, and slightly to its left side, passes with a straight course to the abdomen. It traverses the chest, lying behind the heart, pierces the diaphragm, and just beneath it joins the stomach. Its length is about 9 inches. The stomach is a sickle-shaped bag. It has two apertures—the cardiac orifice, or junction with the œsophagus; and the pyloric orifice, or junction with the small intestine. It is so folded on itself that these two apertures are not more than 4 inches apart. Its outline may be drawn on the body-wall with a piece of charcoal from a point an inch below and an inch to the left side of the lower end of the breast-bone, the position of the cardiac orifice, to a point about 4 inches below the end of the breast-bone, and an inch or two to the right side of the mid-line of the body, the position of the pyloric orifice, with a slight curvature to represent the upper border; to represent the lower border the same two points are joined by a bold curve, bulging upwards to the nipple, outwards to the side of the body, and downwards some distance on the abdomen ([cf. Fig. 2]).

Fig. 6.

The stomach has been cut across a short distance from the pyloric valve, and removed, to show the viscera which lie behind it. The descending aorta and the vena cava rest upon the vertebral column. They are crossed by the pancreas and the transverse portion of the duodenum. The head of the pancreas is enclosed by the curvatures of the duodenum. The ducts of the liver and pancreas are seen entering the descending duodenum side by side.

Such an outline represents the form and position of the stomach when distended; but it is to be understood that its dimensions depend upon the amount of its contents. It is capable of holding about 7 pints. The junction of œsophagus and stomach is closed by a muscular ring, or sphincter muscle—the cardiac sphincter; the junction of stomach and intestine is guarded by a much stronger pyloric sphincter. The average diameter of the small intestine is about 1½ inches. It is wide enough, therefore, to admit two fingers. The length of the tube is about 22 feet. Its first part is termed the “duodenum,” because its length equals the breadth of twelve fingers—i.e., about 9 inches. The remainder is divided arbitrarily into jejunum and ileum. The duodenum makes three sharp curves. First it inclines upwards and to the right, then vertically downwards, then horizontally to the left, and finally forwards. The ducts of the liver and pancreas open by a common orifice into the descending portion. Its horizontal portion is bound firmly to the vertebral column. After this the whole of the small intestine is supported by the mesentery, a double fold of peritoneum which allows it to hang freely in the abdominal cavity. The mesentery is attached to the back of the body-wall. Commencing on the left side of the second lumbar vertebra, its line of attachment inclines obliquely downwards and to the right, across the vertebral column, for about 6 inches. Measured from its attached edge to the edge which bears the intestine, it has a width of about 8 inches. Its free border has, as already said, a length of 22 feet. Its measurements being as just stated, it is clear that it must be folded backwards and forwards upon itself, like a goffered frill. In the right groin the small intestine joins the large intestine, or colon. It does not, as might have been expected, simply dilate into the large intestine, but enters it on its mesial side, its orifice being guarded by the ileo-colic valve. In other words, the large intestine projects downwards beyond this orifice, as the cæcum coli. In many animals the cæcum is of great length and capacity. In the human embryo it begins to assume a similar form; but a very small portion only (the so-called “cæcum” of human anatomy) dilates to the calibre of the colon. The real cæcum retains throughout life its embryonic calibre. It has a length of about 3½ inches, and a diameter of not more than ¼ inch. This is the “vermiform appendix,” of ill fame, which must be looked upon as one of Nature’s misfits. Its great liability to become inflamed is commonly explained as due to the tendency of such articles of food as pips, the fibre of ginger, flakes from the inside of enamelled saucepans, etc., to become lodged in its cavity. But whether this explanation be correct or no—and there are reasons for thinking it somewhat fanciful—it is much to be wished that the process of evolution would hasten the disappearance of this functionless vestige of a cæcum. As there is no tendency towards the inheritance of characters due to mutilation, and since the surgeon’s knife now prevents this death-trap from claiming its toll of possible parents, we must look upon the rudimentary cæcum, with its liability to inflammation, as a permanent burden on the human race. In justice to the appendix, however, it must be pointed out that it has acquired its criminal reputation during the past twenty years. The frequency of appendicitis has increased so enormously during this period that it ought to be possible to correlate its prevalence with the introduction of the cause upon which it chiefly depends.

The colon has a length of about 5 feet. Its greatest width, about 3 inches, is at its commencement, but it is everywhere much wider than the small intestine. Whereas the wall of the small intestine is smooth externally, the wall of the colon is sacculated. Three muscular bands constrict it longitudinally; circular bands at intervals of about 1 inch or 1½ inch throw it into pouches. It ascends on the right side, lying far back against the body-wall, to which it is bound by peritoneum, which in this part of its course covers only its anterior surface. Having touched the under side of the liver, it loops forwards and to the left side, crossing the middle line just above the umbilicus. On the extreme left side it touches the spleen, getting very near to the back of the abdominal cavity. It then descends on the left side, again bound to the body-wall by peritoneum, although not so closely as on the right side, until it reaches the inner lip of the crest of the hip-bone. From here onwards the fold of peritoneum which attaches it allows it a free movement. This portion of the large intestine, the sigmoid flexure, may even fall over into the right groin. Lastly it curls backwards into the pelvis, as the rectum.

Movement of the contents of the alimentary canal may be favoured by judicious pressure, or massage. From the description of the situation of its several parts given above, it will be understood that if the right hand be placed on the abdomen immediately beneath the ribs, with the fingers well round to the left side, the stomach will be covered. Pressure from left to right will tend to drive its contents towards the pyloric valve. The small intestine is so irregular in its course as to preclude the possibility of following it with the hand. Pressure first on one side and then on the other, with a general tendency to work from above downwards, tends to press forward its contents; but, owing to its circular form and strong muscular walls, it is not in much need of help. Very different is the position of the large intestine in this respect. Its calibre is much greater, its wall is sacculated, its contents comparatively firm. If the palm of the hand be placed above the right groin and pressure directed upwards, the cæcum coli and ascending colon are emptied. If pressure be directed from the extreme right side just below the ribs, across the middle line to the left side, the transverse colon is emptied. The descending colon needs pressure from above downwards on the left side; the sigmoid flexure, pressure above the left groin, downwards, and towards the middle line.

The inner wall of the œsophagus is smooth, save for the wrinkles into which it is thrown when not distended; but from the cardiac orifice of the stomach onwards the mucous membrane of the alimentary canal exhibits folds and other projections which serve many purposes. They serve to delay the food, keeping it longer in contact with the secreting surface. They increase the area pitted with tubular glands; they increase also the area through which absorption of the products of digestion occurs. On the inner surface of the stomach the folds produce a reticulated pattern. In the upper portion of the small intestine, especially the duodenum, there are prominent transverse shelves (valvulæ conniventes). No definite folds occur below the upper three-fourths of the small intestine, with the exception of the constrictions of the transverse colon already referred to, which affect the whole thickness of its wall. Throughout the whole of the small intestine the mucous membrane projects in finger-like processes, or villi, which give it a characteristic velvety appearance. The villi are longest in the duodenum.

Lymph-follicles occur at intervals in the intestine. In the ileum they are collected into patches (Peyer’s patches), on the side opposite to the line of attachment of the mesentery. They serve both for the supply of phagocytes, which hunt any germs that have penetrated the mucous membrane, and also as stations to which germ-laden phagocytes retreat.

The wall of the intestine is composed of mucous membrane, submucous tissue, and muscle. The mucous membrane is everywhere pitted with tubular glands, termed in the stomach “gastric glands,” and in the intestines, both small and large, “crypts of Lieberkühn.” Their relation to the wall might be exemplified by taking a block of dough about 6 inches thick and pushing a pencil vertically into it almost down to the table on which it rests. The holes should be made as close together as possible, since, especially in the stomach, extremely little tissue intervenes between the tubes of gland-cells. If the piece of dough were placed upon a folded cloth, the cloth would represent the muscularis mucosæ, a layer properly regarded as a constituent of the mucous membrane. The fibres of this coat are disposed in two or three sheets, the fibres of one sheet crossing those of the next. By their contractions they squeeze the ends of the crypts, and probably wobble them about, expelling their secretion. Beneath the muscularis mucosæ is a layer of connective tissue, the submucosa, which contains abundant lymphatic channels, bloodvessels, and nerves. At the pyloric end of the stomach, the tubes of gland-cells tend to pierce the muscularis mucosæ. In the first part of the duodenum, certain tubes, having pierced this layer, branch in the submucosa. A layer of racemose glands is thus formed—the glands of Brunner. Outside the submucosa is the muscular coat proper, composed of plain muscle-fibres, except in the upper part of the œsophagus, where the fibres are striated. It consists of an inner and an outer sheet, the fibres being disposed circularly in the inner, longitudinally in the outer sheet, with a slight departure from this regular arrangement in the wall of the stomach. On its outside the canal is invested by peritoneum, a layer of flattened epithelial cells supported by connective tissue. The abdominal wall also is lined with peritoneum. The smooth moist surface of the peritoneum covering the intestines glides on the peritoneum lining the abdominal wall. Between the two is a “potential” space. In dropsy, fluid accumulates within this space. In a healthy condition the apposed surfaces are merely moist.

The movements of the intestines are of two kinds. At all times they exhibit swaying movements, in the production of which the longitudinal fibres play the chief part, although the circular fibres also contract. The object of this undulation is to thoroughly mix the contents of the gut with its secretions. If pills of subnitrate of bismuth are administered, and their progress observed by the aid of Röntgen rays, they are seen to oscillate backwards and forwards on their way down the canal. The slower vermicular movement which squeezes the contents forwards is called “peristalsis.” It resembles the progressive contraction of an elastic tube which may be effected by drawing it through a ring, but is rather more complicated. At the point at which it is occurring the circular coat is sharply contracted. Above this it is also somewhat contracted; below it is relaxed. The longitudinal fibres, using the constricted portion as a point d’appui, pull up the segment of the intestine which lies immediately below it, drawing it off the contents of the tube as a glove from a finger.

When food is swallowed, it falls down the œsophagus, aided by slight peristalsis. As soon as sufficient has accumulated on the upper surface of the cardiac valve of the stomach, the valve relaxes; at the same time a stronger peristalsis of the lower portion of the œsophagus squeezes its contents into the stomach. Food remains in the stomach until it has reached a certain stage of digestion, the chief object of which is its subdivision into small particles. Until this stage is reached, the pyloric valve is firmly closed. The contractions of the wall of the stomach drive its contents round and round—down the greater and up the lesser curvature—mixing them thoroughly with the gastric juice ([cf. p. 124]). As the acidity of the mixture increases, the peristaltic contractions of the stomach become more vigorous, until, the pyloric valve relaxing, the food is little by little driven into the duodenum.

The alimentary canal has an abundant supply of nerves from the vagus and the sympathetic systems. It contains also within its own wall an enormous quantity of nerve-fibres and nerve-cells. They are disposed as two plexuses, one in the submucosa, the other between the circular and longitudinal muscular coats. In a specimen successfully stained with methylene-blue, they are so abundant as to give the impression that every plain muscle-cell may have its own separate nerve-twig. Nevertheless, the contraction of the muscle-cells may take place independently of all nerve-influence—independently, even, of the local mechanism, the plexus referred to above. Nicotin applied to the wall of the intestine paralyses the local nerves; yet rhythmic contractions still occur. They are, however, no longer progressive. They do not drive the contents of the intestine forwards. Co-ordinated contraction is observed so long as the local mechanism is intact, even though all external nerves have been cut. The intestines have their own nerve cells and fibres, which, acting as a linked system of reflex centres, provide for the harmonious contraction of their walls. External nerves, sympathetic and splanchnic, convey impulses which either intensify the movements or inhibit them, as need may be.

In the matter of its nerve-supply, the alimentary canal stands apart from the other organs of the body. It may be supposed that it presents a more primitive condition. Its muscular fibres have the power of contracting spontaneously. The pressure of the contents of the tube acts as a stimulus. When the fibres are stretched, they contract. When the tube is dilated, its muscles endeavour to restore it to its normal calibre. Such direct action would not, however, provide for the forward passage of its contents. To bring about peristalsis, a nervous mechanism is needed, as abundant and complicated as that which ensures the progress of a slug or a worm. To deal satisfactorily with the various contents of the tube—liquid, solid, gaseous—the mechanism must be capable of complicated adjustments. The dilated portions of the tube—stomach, cæcum coli, rectum—require special arrangements of muscle and nerve. Nor is the canal altogether independent of the rest of the body. To a large extent its work is carried on without regard to the activities of other organs, yet it is not wholly free from the control of the central nervous system. It is regulated by means of both afferent and efferent nerves of the vagus and sympathetic. Even the brain has something to say with regard to the way in which it shall contract. It is a matter of common experience that emotional influences may affect the movements of the stomach and intestines—“His bowels yearned.”

Normally, vomiting is due to irritation of the endings of the vagus nerve in the stomach, although the afferent impulses may have other sources. Touching the upper surface of the epiglottis with the finger will provoke the reflex. So also will stimulation of the olfactory nerves by a foul smell. In this latter case the emotion of disgust to which the odour gives rise brings about the reflex action. A flow of saliva precedes the act of vomiting. A deep inspiration is then taken, in order that for a time the lungs may be independent of a fresh supply of air. The glottis is closed, the diaphragm fixed. Contraction of the abdominal wall presses the stomach against the diaphragm; its cardiac sphincter relaxes, and its contents are squirted into the œsophagus, which undergoes a forcible retrogressive peristalsis.

It is interesting to note the difference between carnivora and herbivora in regard to vomiting. Carnivora swallow fur and other indigestible materials, as well as many unwholesome things which they need to be able to return. A dog can, apparently, vomit at will. Never, while in a state of nature, do herbivora need to return the contents of the stomach. No provision is made for vomiting. A heifer which has strayed into a dewy clover-field is not unlikely to die from the effects of distension of its paunch, if relief be not given by opening it with a knife. In a horse the cardiac sphincter is strong, the pyloric weak. Pressure on the stomach tends to drive its contents through the pyloric valve into the duodenum, not backwards into the œsophagus. The stomach is not so placed as to allow of its being compressed between the wall of the abdomen and the diaphragm. Horses cannot vomit. It is a mistake to suppose that they suffer from sea-sickness. In rough weather they sweat, their limbs tremble, they go off their feed; but these symptoms are probably due to the fatigue which results from excessive anxiety to maintain their balance, and to fear. We can never know their feelings, but there is no reason for supposing that they experience the sensation of nausea.

Vomiting is a frequent symptom of cerebral disturbance. The fluctuations of pressure which the brain experiences as it rocks about on its “water-bed” within the skull is the cause of sea-sickness. Yet the motion of a ship may produce violent headache without nausea, the brain only, not the stomach, appearing to be troubled by the motion. Not that headache is a pain “inside the head.” Nor is it properly described as a pain in the scalp, although the messages which are felt in consciousness as headache originate in the endings of the nerves of the skin which covers the skull. The excessive sensitiveness of these nerves is due to vaso-motor conditions, usually the dilation, occasionally the constriction, of the bloodvessels of the scalp. But the vaso-motor condition is sympathetic with the disturbance of the brain; and the special urgency or efficiency of the messages from the skin results from their being delivered into excited brain-tissue. Nausea and headache are equally symptoms of the irritability of the brain caused by the motion of the ship. In one case messages from the stomach, in the other case messages from the scalp, acquire undue importance, owing to the agitated condition of the brain-tissue through which they pass. Not uncommonly the voyager, who wakes in the morning reconciled to the changes of pressure which he has experienced while recumbent, finds, when he stands upright, that the base of his brain is as sensitive as ever. Visual sensations also contribute to the brain-disturbance. So, too, do the movements of endolymph in the semicircular canals ([cf. p. 335]). It is, indeed, possible that this last factor is more important than the variations in pressure on the surface of the brain. Probably it accounts for the after-image of rolling which almost everyone experiences for at least a day after leaving the ship. Its cause being cerebral, the tendency to sea-sickness can be controlled by drugs which, like the bromides, chloral, alcohol, etc., deaden the brain.

Salivary Glands.—The secretion which accumulates in the mouth is the combined product of the sublingual, submaxillary, and parotid glands. It is a very thin, watery solution containing not more than 0·5 per cent. of solid substance. If red litmus-paper is moistened with saliva, it becomes blue, showing that the secretion is alkaline. It contains a ferment, ptyalin, which digests starch. The action of this ferment can be demonstrated by holding in the mouth for half a minute some warm starch mucilage—boiled arrowroot, for example. It quickly loses its viscidity owing to the conversion of starch into sugar. Chemically this change may be demonstrated by adding iodine-water to a specimen of the starch before and after action. Before the starch is taken into the mouth the iodine turns it blue (a characteristic reaction for starch). After it has been exposed to the digestive action of the saliva, iodine fails to colour the mixture, which now contains no starch. All the starch has been converted into dextrin and sugar. If unboiled arrowroot is placed in the mouth, some sugar is produced, but the process of conversion is very slow. It is almost impossible to digest raw starch in the mouth sufficiently to render it insusceptible to the colouring action of iodine. The sugar produced by the action of ptyalin is of the same nature as that which appears during the malting of barley. It is therefore termed “maltose.” It closely resembles grape-sugar, but is not identical with it.

The Secretion of Saliva.—The accessibility of the salivary glands, and especially of the submaxillary, has led to their being used for a very large number of experiments. They have been studied with the aim of coming to an understanding of the mechanism of secretion in general. The glands consist of tubes of gland-cells, each tube suspended in a basket of connective tissue, in a bath of lymph ([cf. Fig. 3]). Innumerable capillary bloodvessels traverse the lymph-bath. The arteries which carry blood to the gland are supplied with nerves, which regulate their calibre, and therefore determine the amount of blood which passes through the capillaries into which they break up. The glands also are supplied with nerves which influence their functional activity. Nutrient substances and oxygen pass out of the blood into the lymph. Carbonic acid passes into the blood from the lymph. Waste products are either carried away in the lymph-stream, or make their way through the walls of the capillaries into the blood. Many problems present themselves for solution. How does the amount of work done by the gland affect its supply of blood? Does the quantity of saliva secreted vary directly with the pressure of lymph in the spaces by which the gland is surrounded? Is this pressure wholly dependent upon the pressure of the blood? Are the substances secreted by the gland supplied as such by the blood, or does the gland make the ptyalin and mucus which it secretes? If it makes its secernable products, what materials does it abstract from the blood for the purpose of their manufacture? Does it use the whole of these materials, whatever they may be, or does it use part only and return the residue to the lymph? Does it make its products only when it is actively secreting, or is it always making them, and storing them in its cells in order that it may have a supply to discharge when called upon by the stimulation which results from the presence of food in the mouth? Is their discharge merely a washing out due to the rush of fluid which occurs when the bloodvessels are dilated, or can the gland-cells expel their products in response to nervous action? In what way do the nerves of the gland influence secretion? Do they call for increased production, or increased output, or both? These are some of the problems which the exposed situation of the submaxillary gland allows physiologists to tackle.

By means of a very simple operation, the ducts of one or both parotid or submaxillary glands can be brought to the skin, and made to pour their secretions on to the surface instead of into the mouth. The flow under various circumstances can be watched. The saliva can be collected and measured.

The nerves of the submaxillary gland are easily isolated. A nerve leaves the seventh (or facial), crosses the drum of the ear, comes out through a minute crevice in the skull, and runs for some little distance as a separate nerve before it applies itself to the lingual branch of the fifth, which runs along the side of the tongue. Owing to its passage across the tympanic cavity (drum of the ear), it is termed “chorda tympani.” As its fibres are very small, they can be recognized wherever they form a part of the lingual nerve. They leave the lingual to go to a ganglion, the submaxillary ganglion, from which the gland is supplied. The gland also receives branches from the sympathetic nerve which ascends the neck. The last-named branches accompany the facial artery. Stimulation of either of these nerves causes the gland to secrete. The flow of saliva which follows stimulation of the chorda tympani is much more copious than that which follows stimulation of the sympathetic, and as a rule it contains far less organic matter, although about the same amount of mineral salts. Under normal conditions the activity of the chorda tympani is brought into play in a reflex manner by impulses which travel up the nerves of taste (the lingual and glosso-pharyngeal) to the cerebro-spinal axis; but almost any other nerve will serve as an afferent path. The gland may also, as we shall presently explain, be called into activity by the cortex of the brain.

It is certain that in the case of the submaxillary gland secretion is not the direct result of increased blood-pressure. It is not a case of filtration from the blood through certain membranes and cells into the salivary duct. Atropin (belladonna) dilates the bloodvessels, increasing blood-pressure, but it stops secretion. After belladonna-poisoning, the mouth, like the skin, is hot and dry. Other drugs there are which provoke a certain amount of secretion, even after the bloodvessels going to the gland have been tied. It is possible, by stimulating the chorda tympani, to obtain a pressure in the fluid in the duct very much greater than that in the bloodvessels which supply the gland. Here we have clear proof that secretion is not filtration. Filtration is the passage of fluid through a filter-bed from a higher to a lower pressure. In filtration, moreover, soluble diffusible salts accompany the water. The saliva contains only half as much of these diffusible salts as the blood. Therefore the gland tissue stops half the salts. Secretion is an active process carried out by the gland-cells, under the influence of nerves, in opposition to the laws of filtration. The gland-cells determine how much water shall pass through them and what percentage of salts shall accompany the water.

How does a gland-cell make the substance which it secretes? There is no reason for supposing that the ptyalin or the mucus which the salivary glands secrete is present in the blood, either ready formed, or, as it were, half formed, in combinations which can be easily broken up. All the evidence obtainable points to the conclusion that the gland-cells take out of the lymph proteid materials from which they manufacture the peculiar substances which they secrete. During rest, granules accumulate in the cells. During activity they disappear. It has been shown in the case of the gastric glands that these granules consist of the special ferment which the gland secretes, in an inactive form. It may be that it is combined with a substance which prevents it from exerting its digestive action on the cells within which it is made; damped, as gunpowder is damped during transit. Or it may be that it is not a finished ferment; it may need a further addition to its molecule. During activity, while the granules disappear, proteins accumulate at the bases of the cells, giving to a tube of gland-cells the appearance of a peripheral non-granular zone. This proteid substance must have come from the lymph, and the inference seems inevitable that the cells have taken into their protoplasm a supply of material which will serve for the manufacture of additional granules. Each gland-cell is therefore an independent unit. By its own activity it takes up materials from the lymph, out of which it manufactures its own special products. It stores its products until they are wanted. Then by its own activity it extrudes them into the lumen of the gland-tube. It has, indeed, been shown that, when the nerve going to a salivary gland is stimulated, the gland shrinks, notwithstanding the great dilation of its bloodvessels. Under the influence of the stimulation the granules in the gland-cells imbibe water, swell up, and escape from the cells. The cells discharge their accumulated stores, in the first instance, more rapidly than they take up materials (even fluid) from the blood. For its knowledge (if the term may pass) of what is wanted the gland-cell is dependent upon messages which reach it through the nervous system. These messages take origin in the endings of the sensory nerves of the mouth, pass up to the brain, and are reflected down the nerves to the gland. So accurate is the information conveyed to the glands, that when a horse transfers the work of mastication from one side of its mouth to the other, as it is in the habit of doing about every quarter of an hour, the flow of saliva from the parotid gland on the masticating side is increased; on the other side it is diminished. Two or three times as much saliva is poured out on the one side as on the other.

Not only is the amount of saliva poured out in response to stimulation proportional to the needs of mastication, but the kind of saliva is adapted to the nature of the food. In a dog—and this is an observation which can be made only on an animal which lives on a mixed diet—it is possible to determine the amount of the two kinds of saliva secreted and the relation of flow to food. When meat is given to the animal, the submaxillary gland yields its secretion; when it is fed on biscuit, abundance of the watery parotid saliva is poured forth. A mouthful of sand also causes the parotid saliva to flow, in order that the sand may be washed out of the mouth.

More remarkable than the response to direct stimulation is the effect produced by the sight and smell of food. When meat is shown to a dog, submaxillary saliva begins to flow; when it is offered bread, parotid saliva is secreted. And the activity of the glands is not merely a nervous reflex independent of the animal’s mind. The moment the dog realizes that it is being played with—that there is no intention of giving it the coveted food—the flow of saliva ceases. An emotion may check secretion when every physiological condition is demanding it. This is the explanation of the Rice Ordeal. Dry rice provokes a flow of saliva in the mouth of all save the guilty man. Response to mental impressions is a matter of the greatest consequence in the physiology of digestion. It holds good in the case of the secretion of gastric juice equally with that of saliva. The sight and smell of food sets the juice flowing into the stomach, and the more desirable the food, the more attractive its appearance, the more stimulating its smell, the more rapidly does the secretion flow. Here we touch upon a theme which hardly needs exhaustive treatment. It is not the stoutest people who eat the most, although an impartial survey of one’s well nourished friends will show them to be persons who “take kindly to their victuals.” A small quantity of food perfectly digested is more nourishing than much food which the digestive organs do not efficiently prepare for assimilation. Good digestion waits on appetite; and appetite, in civilized man, is something more than a mere physical need of food. The hunger which leads to the bolting of food without pleasurable anticipation, without mastication, without any consideration of the quality of the viands, is a harmful craving which ends in imperfect assimilation. It is more profitable to toy with a hors d’œuvre than to engulf, unthinking, a plateful of beef. But we have said enough to suggest reflections to those who take no thought as to what they shall eat or what they shall drink; and few who take thought need to be convinced.

The Stomach.—The sight and smell of food, its presence in the mouth, and the performance of mastication, which induces a secretion of saliva, gives rise at the same time to a flow of gastric juice. It is psychic stimulation and the act of eating which cause gastric juice to ooze from the gland-tubes of the stomach at the commencement of digestion, not the stimulation of nerve-endings by food which has passed down the œsophagus. As a consequence of gunshot wounds, or as the result of operations performed for the purpose of relieving patients whose œsophagus has become blocked, numerous cases have been recorded in which a fistulous opening into the stomach has made it possible to study the interior of this organ. Such cases present an opportunity of watching the digestion of various foods introduced through the opening, and of collecting gastric juice for purposes of analysis. A similar condition has been established in animals by operative means. The œsophagus having been cut, and the cut end sutured to the margins of an aperture in the skin, food taken by the mouth escaped by this opening instead of passing into the stomach. A similar opening was made into the stomach for the insertion of food, and for the purpose of studying the effects of reflex stimulation of the gastric glands. As soon as food was introduced into the mouth, gastric juice began to flow. The advantage of this experimental method lies in the fact that the juice secreted was a pure juice—not mixed with food, as in all the earlier experiments in which, the stomach being opened without diversion of the œsophagus, the presence of food within it was the stimulus which led to secretion. No juice flowed in the absence of stimulation; nor was the secretion normal in composition when provoked by a mechanical stimulus, such as the tickling of the gastric mucous membrane by a feather.

My lord the stomach! He is not the only, nor is he the chief, agent in digestion; but with him rests the decision as to whether the food offered to the alimentary tract is suitable in quality and quantity. He is offended if it be not offered with all the circumstance and ceremony which becomes his rank. As an intimation that he is about to receive food, he accepts the news from the mouth that its nerve-endings are subject to mechanical stimulation. But the chewing of indiarubber would produce a like effect. The stomach, therefore, confers with the organs of taste and smell. If their report is favourable, he argues that the substance which the teeth are crushing will justify an outflow of gastric juice. He responds most generously when prolonged mastication assures him that he may trust to receiving the food in a sufficiently subdivided state. At our peril we neglect to propitiate my lord. Not always debonair when treated with consideration, he is morose or petulant when slighted. Never content with lip-service, he exacts the labour of teeth and tongue and palate. The tribute we offer may be of the best—savoury, wholesome, well cooked, well chewed—but if it be not tendered with some degree of love, if thoughts are concentrated on other things, if no attention is devoted to the meal, if no sense of liking accompanies our offering, my lord the stomach on his part affords the viands an indifferent reception. In consulting our own tastes we are to a large extent consulting the needs of the stomach. Ravenous and excessive feeding is not an exhibition of taste; it is a return to the instinct of the savage, who was never sure that he would get his full share, and was afraid to trust that another meal would be obtainable when nature declared it due. Some degree of epicureanism is favourable to digestion. The flow of gastric juice in the stomach occurs reflexly in response to the emotion of appetite, to stimulation of the nerves of taste and smell, to the obscure sensations which accompany the activity of the muscles of mastication.

The gastric juice secreted in a day amounts probably to about 8 or 9 pints. To this we must add, when considering the quantity of fluid which passes through the stomach, the saliva, which certainly reaches as much as 2 pints, and the beverages taken with food.

Gastric juice collected in the manner described above is a clear, colourless, inodorous fluid. It is very acid, and so powerfully peptic as to digest its own weight of coagulated white of egg. Its solid constituents amount to 0·5 per cent. They consist of the two ferments pepsin and rennin, with traces of proteins and mucin, and various inorganic salts. Its acidity is due to free hydrochloric acid to the amount of 0·2 per cent. This acid is more or less in combination with the pepsin. In pure gastric juice hydrochloric acid is the only acid present; but when mixed with food the juice contains other acids also, especially lactic.

When food first reaches the stomach, the alkaline saliva which accompanies it neutralizes the acidity of the gastric juice. For some time, probably about half an hour, the conversion of starch into sugar is still carried on by the ptyalin of the saliva, owing chiefly to the difficulty which the gastric juice encounters in permeating the masses of masticated food. The Bacillus acidi lactici is always present in the stomach. It converts some of the sugar into lactic acid; of this a small quantity is further changed into butyric and acetic acids, with the formation of carbonic acid and hydrogen gas. After a while the lactic acid is absorbed, and hydrochloric acid alone remains.

The secretion by the gastric glands of so powerful a mineral acid as hydrochloric has always aroused interest. How is it possible for the gland-cells to produce it without injury to them selves, or for the stomach to contain it without self-digestion? Many chemical and physical theories have been advanced in the belief that they rendered the process of its production less difficult to understand. All such theories are, however, inadequate to explain the secretion as a discontinuous process, which occurs only as a response to demand. That the source of the acid is the sodic chloride which the gland-cells take from the blood does not need assertion, but we cannot picture the process by which this exceedingly stable compound is decomposed otherwise than on the assumption that weaker acids, or, rather, acid salts, are also absorbed by the cells, and that, in accordance with the laws which govern the composition of salts in solution, an exchange of acids occurs. If sodic chloride and any acid salt—acid phosphate of sodium, for example—are in solution in water, the salts do not retain their form as we know them when isolated by crystallization. The mixture contains “free” hydrochloric as well as “free” phosphoric acid. It may be assumed that within secreting cells a similar exchange of acids takes place. By a process which we term “vital,” the acids are kept apart, and the hydrochloric acid is extruded by the cells. In the present state of knowledge this vital action is mysterious; but it is no more mysterious than the isolation of pepsin, or any other metabolic event which occurs within a cell.

The proteolytic ferment pepsin is active only in an acid medium. Yet apart from its digestive function as an ally of pepsin, hydrochloric acid by itself also exerts a valuable disintegrating action on certain constituents of the food. Possibly the most important results of the presence of free hydrochloric acid in the great chamber into which food is first received are due to its disinfective property. It destroys all the putrefactive germs which accompany the food, and many germs which, if introduced into the blood, would give rise to disease. It also destroys the germs which multiply in the stomach towards the end of each interval between two meals. When withdrawn from the body, gastric juice will keep an indefinite time, if evaporation of the acid be prevented.

Pancreas.—In structure the pancreas presents a marked resemblance to the salivary glands. Probably this resemblance is merely superficial. Minute examination reveals points, apparently of great morphological importance, in which they differ. In the gland-tubes of the salivary glands, and, indeed, in all glands with the exception of the pancreas, secreting cells project into the lumen. The secreting cells of the pancreas are invested internally by a layer of flattened scales (intra-acinar cells). They lie, therefore, between the basement membrane which invests them externally and this second layer of flattened cells which separates them from the lumen of the tube. At a very early date in embryonic life the gland-cells of the pancreas are filled with highly refracting granules. As this occurs long before any digestive action is called for, it may be taken as indicating that the pancreas has functions which other glands—the salivary, for example—do not possess. These granules do not, however, appear in all parts of the tubes. Certain portions of the tubes remain undeveloped—fail, that is to say, to acquire a secreting function—even in adult life. Such patches of cells, not disposed in gland-tubes, are known as islands of Langerhans. When the pancreas is over-stimulated by artificial means, leading to its extreme exhaustion, large portions of its glandular substance return to this primitive condition. The gland-cells not only discharge their stores of granules, but they lose the greater part of their cell-protoplasm. It would seem that, in their effort to meet the demand for ferments, they use up their own cell-substance in their manufacture. Having exhausted their coal, they stoke the furnace with the looms and furniture of the mill. It may be that other glands would do the same if it were possible to stimulate them as strongly as the pancreas can be stimulated. The result is probably due to the extreme susceptibility of the pancreas to the action of secretin, a substance made in the intestine. Secretin can be isolated and injected into the blood. We shall refer again to this chemical stimulation of the pancreas when tracing the progress of food through the alimentary canal.

The secretion of the pancreas is a clear, colourless, alkaline liquid of syrupy consistence. The quantity of juice secreted is relatively small, but the organic substances which it contains are in a concentrated form. They constitute as much as 10 per cent. of the pancreatic juice. Proteins are present, if the juice be fresh. If it has stood for any length of time, they are found as peptones. The digestive ferments of pancreatic juice are the most powerful which are secreted into the alimentary canal.

Bile.—In its most important functions the liver has no relation to digestion. It is a storehouse of absorbed food. This organ will therefore be treated in a separate chapter. The bile which the liver secretes into the alimentary canal has no chemical action on any of the constituents of food, with the exception of a feeble tendency to digest starch. Yet it is in some degree accessory to digestion. Poured into the second portion of the duodenum through an orifice common to the liver and the pancreas, it mingles with the semi-digested food, or “chyme,” which, about two hours after a meal, passes through the pyloric valve. Gastric digestion has converted the greater part of the proteid constituents of the food into peptones or intermediate stages. The proteoses or propeptones—a name is needed for the intermediate products of proteid digestion which does not commit us to any theory as to their chemical constitution—are quickly peptonized by the pancreatic juice. But portions of the proteins have escaped the action of gastric juice, or have at most been affected by its acid only; these are precipitated by the bile-salts on the mucous membrane of the small intestine, which is raised into projecting flanges for the purpose of delaying the passage of the chyme, in order that it may be thoroughly submitted to the digestive action of pancreatic juice. Bile-salts also favour the digestion of fat, and its passage through the intestinal wall. The action of bile-salts in spreading fats is well known to artists. Ox-gall is smeared upon glass when it is desired to apply oil-paints to its surface. When mixed with oil, it causes its emulsification, or breaking up into microscopic globules. In the absence of bile, but little fat passes into the lymph-vessels which convey digested food from the intestine to the thoracic duct, and so to the great veins of the neck. Its action is mechanical. It favours the digestion of fats by rendering them easily amenable to hydrolysis by pancreatic juice.

Bile as secreted by the liver is a clear, limpid fluid of low specific gravity; but during its stay in the gall-bladder it is concentrated by absorption of water, and mucin is added to it. It contains “bile-salts” of complex constitution. These salts favour the solution of certain by-products of cell-metabolism, cholesterin and lecithin; substances which are formed in many cells, both in animals and plants. Cholesterin occurs most abundantly in nerve-tissue and in blood-corpuscles. Lecithin also is a by-product of the metabolism of nerve-tissue. Protoplasm appears to be incapable of oxidizing these substances, as it does other products of metabolism. Other substances of equally complex constitution are reduced to urea if they contain nitrogen; to water and carbonic acid if nitrogen be absent. Cholesterin and lecithin have to be eliminated without further change. Some of the cholesterin is excreted by the sebaceous glands of the skin. It is the chief constituent of “lanoline” prepared from sheep’s wool; an unguent which owes its valuable properties to the resistance which cholesterin offers to cell action, and therefore to the action of living ferments. Bacteria cannot turn it rancid. The sebaceous glands have the power of directing metabolism into a channel in which cholesterin is the chief product, but apparently all cells make it in small quantity. The bile-salts carry cholesterin and lecithin into the alimentary canal, from which they are not reabsorbed. Some of the bile-salts are lost to the body, but the remainder re-enter the circulation, and recommence their work as vehicles for these inoxidizable and insoluble substances. In the gall-bladder cholesterin is apt to separate out from the bile in the form of gall-stones; but whether this is due to an excess of cholesterin in the bile, or to an abnormal, inflammatory condition of the lining membrane of the gall-bladder, is still an open question.

Bile also contains bile-pigments. Their colour varies in different animals, and changes according as the bile is exposed to the air, or subject to the action of reducing agents. If oxidized, the colour is green (biliverdin); if reduced, brownish-yellow (bilirubin). Bile-pigment is formed from hæmoglobin, the colouring matter of the blood, after the removal of its iron. Worn-out red blood-corpuscles are destroyed in the spleen, in the manner already described, but it is uncertain whether the conversion of the hæmoglobin thus set free into bilirubin occurs in the spleen, or whether this chemical change is reserved for the liver. Physiologists incline to the view that the liver is the seat of the change.

Intestinal Juice.—The mucous membrane of the alimentary tract, as far down as the middle of the rectum, is, as previously stated ([p. 102]), studded with tubular glands. They secrete a light-yellow fluid, alkaline in reaction, and opalescent. Its most important property is due to a ferment which converts cane-sugar into a mixture of dextrose and levulose, and changes maltose—the sugar produced by the action on starch of saliva and pancreatic juice—into dextrose. It is in the form of dextrose that sugar is carried about the body and assimilated by the tissues.

Intestinal juice also contains a ferment, erepsin, which shakes to pieces the heavy molecules of peptones and partly formed peptones. Under its influence they break up into comparatively simple bodies containing the radicle of ammonia. Substances containing an NH₂ group—one H of NH₃ (ammonia) having been given up, in order that the group may have a “free arm” with which to link on to the other component parts of the molecule—are termed “amides.” The amides which are most characteristic of the action of erepsin are leucin, an amidated fatty acid; and tyrosin, an amidated aromatic acid. The tendency of proteins to break up along these two lines—the fatty acid line and the aromatic acid line—is of considerable interest. The one line is represented by acetic acid, CH₃COOH; the other contains the hexone radicle, C₆H₆. Benzoic acid, C₆H₅COOH, is representative of the latter. It used to be thought that proteins which were shaken into simple bodies such as amides were lost to the economy. Their downward career was a foregone conclusion. There could be no arresting it before they brought up at the bottom—as urea, CO(NH₂)₂—the diamide of carbonic acid. It was even supposed that this disintegration of proteins was a provision for getting rid of the surplus animal food which we consume. Physiological chemists now take quite a different view. They believe that the epithelial wall of the intestine through which these substances are absorbed, or the liver, to which they are carried by the portal blood-stream, has the power of recombining these fragments into the complex protein edifice. It is even thought that disintegration is a necessary preliminary to the rearrangement of the sub-groups. A large variety of proteins is ingested as food. Many of them, especially the vegetable proteins, are quite foreign to the body. By the activity of pancreatic juice and erepsin, they are broken into small and relatively stable groups of atoms, which are again fitted together into the particular forms of protein which are of use to the economy.

The Story of a Meal.—The chemistry of digestion will be understood most readily if the constituents of a meal are traced from their entrance into the mouth to their absorption through the wall of the alimentary canal, or abandonment as indigestible.

We may describe as a typical meal one consisting of bread, vegetables, cane-sugar, meat, milk, fat, and cheese. In the mouth the various foods are crushed and mixed with the alkaline secretions of the salivary glands. A certain amount of the cooked starch contained in the bread is changed into maltose. In the stomach the digestion of starch is continued for a time, but a large part even of the cooked starch awaits the action of pancreatic juice. A certain amount of cane-sugar is converted into dextrose and levulose, which are rapidly absorbed into the blood; but this action is due to hydrochloric acid, and probably affects a comparatively small part of the cane-sugar swallowed. Fat is quite unaltered in the stomach. All proteins are attacked by pepsin, but some yield to digestion more readily than others. Gluten of bread, like all vegetable proteins, is comparatively resistant; but since it is presented to the action of pepsin in small quantities and in a spongy form—very suitable for digestion—it is probable that most of it is peptonized in the stomach. Chemists experimenting with gastric juice taken from the stomach, and reproducing the conditions as to temperature, removal of products of action, etc., as closely as it is possible to reproduce them in the laboratory, find that the various foods take different times to digest. The proteins of meat are more quickly peptonized when raw than after coagulation by heat. The same is true of white of egg. Amongst different varieties of cooked flesh, beef is more quickly peptonized than fish. The casein of milk is more quickly peptonized than any other protein; and it also is no exception to the rule that digestibility is diminished by cooking. Similar data may be obtained for all foods. They are no doubt useful indications of the course of action which we may expect to occur within the stomach, but we can never be sure that my lord will obey the ruling of the chemist. Practice with a captive golf-ball is a useful preparation for the game; but there are conditions on the links which cannot be reproduced on the lawn. In an artificial stomach the clean fibre of raw fish digests more slowly than raw beef. Even when the beef is roasted and the fish fried or boiled in the ordinary way, the beef disappears through the dialyser (the bag of membrane suspended in a vessel of warm water in which experimental digestion is carried out) more quickly than the fish. Nevertheless, the living stomach is better disposed towards a mixed meal containing a certain weight of fish than towards a meal in which, the other constituents remaining the same, beef takes the place of fish. Important conclusions may, no doubt, be drawn from observations of the time occupied in the peptonization of pure food—i.e., fibrin, white of egg, clean meat, etc.—under conditions simulating those which are present in the stomach; but they must be accepted with many reservations. In the stomach it is not pure substances, but mixtures, that the gastric juice has to deal with. And here a most important factor comes into play, to which further reference will be made later on. The amount and quality of the secretion of the gastric glands depends upon the nature of the food. Hence a food, or a combination of foods, which digest readily in the laboratory may take a long time to disappear from the stomach, and vice versâ. Digestibility depends upon the nature of the food. It depends also upon its physical state. To take simple illustrations: Cheese contains coagulated casein, one of the most easily digestible of proteins, but the casein is intimately mixed with fat, upon which gastric juice can make no impression. Even when finely divided, the particles of casein are protected from the action of the juice by fat. In the same way the meat of pork is as digestible as mutton, but the fat of pork is quickly melted and very liquid. In the process of cooking the muscle-fibres become saturated with fat.

It is not the function of the stomach to complete digestion. Its business is to initiate it. Food which reaches the stomach in fragments is reduced to a condition in which its digestion will be readily completed by pancreatic juice. Gastric digestion produces a much larger proportion of intermediate products, proteoses or propeptones, than does digestion in the duodenum. Such intermediate products are quickly dealt with by pancreatic juice. Artificial tests of relative digestibility do not, as a rule, take the amount of propeptones formed in a given time into account. When considering the digestion of a typical meal, we must bear in mind that it is not the duty of the stomach to pass as much sugar, peptone, and fat as possible into the blood. In fact, very few of the products of digestion are absorbed by the bloodvessels of the stomach. The impermeability of its mucous membrane is shown by the fact that hardly any of the water swallowed passes through the stomach-wall. Practically all the water ingested leaves the stomach through the pyloric valve. Various salts, some sugar, and peptones are taken up by the vessels of the stomach; but the bulk of all the different kinds of food passes into the duodenum in a semi-digested state. The function of the stomach is to carry digestion through a preliminary stage. The process will be completed in the small intestine. It is to be noted that, although water is not absorbed by the stomach-wall, alcohol passes through it with great rapidity. The same is true of the various crystalline nitrogenous bodies found in meat-extracts, and also of the essential principles of tea and coffee, which chemically belong to the same class. All these substances are degradation products of proteins produced by oxidation, far advanced along the road to urea. In this selective absorption we see proof of the activity of the cells of the mucous membrane. They take up the substances which it is desirable to remove from the contents of the stomach. Some may be wanted by the body for its immediate use; others are better out of the way, because they are prejudicial to the progress of digestion.

When contemplating the activity of the cells of the gastric mucous membrane, we feel the need of an adjective which shall express our recognition of the fact that they have a power which we cannot confer upon our clumsy mechanical imitation stomach. They can discriminate. “Vital” is the only term available, though much abused. Using it without prejudice, as lawyers say, we speak of the “vital activity” of the cells when we wish to imply that things happen in a living stomach for which we cannot make provision in a model. Of the many substances which make their appearance as digestion proceeds, some are absorbed, others left in the mixture.

The mucous membrane shows its power of controlling digestion in yet another way. In the neighbourhood of the pylorus its structure is unlike that which it presents elsewhere. The gastric glands are short, and tend to branch. Their lining cells are all of the same kind. Over the greater part of the inner wall of the stomach the tubes are long. They do not branch. The cells which line them are of two kinds: small cubical cells (the term refers to their form as seen in section), similar to those of the pyloric glands; large oval cells, placed with their longest axes in the same direction as the axis of the gland-tube. These oval cells do not project into the bore or lumen of the tube, but are displaced from it by the cubical cells. They rest on the investing, or basement, membrane. All parts of the gastric mucous membrane secrete pepsin, although the pyloric portion produces very little; the area which contains oval cells alone secretes hydrochloric acid. If a short time after a meal an extract is made from some of the mucous membrane near the pylorus, by pounding it with salt-solution and sand to break up its cells, this extract, when filtered and injected into the blood, stimulates the glands of the cardiac end of the stomach. Under its influence they pour out both pepsin and hydrochloric acid. The extract contains a substance which acts as a chemical messenger. It is a representative of a class of bodies which play a most important part in co-ordinating the activities of the various organs. Hitherto physiologists have concerned themselves with the visible or “external” secretions of glands. They have shown how the production of these secretions is controlled by the nervous system. Recently they have discovered that another set of influences has to be taken into consideration. Glands, and possibly all other tissues, take from the blood the materials out of which they make their characteristic secretions, or, if they do not discharge secretions, the substances which they require for the building of their own structures, and return to the blood “internal secretions” which act as stimuli to other tissues with which they are linked in harmonious co-operation. The active principles of internal secretions have been termed “hormones”—from ὁρμάω, I announce. The glands of the pyloric mucous membrane secrete a hormone which calls upon the rest of the membrane to pour out gastric juice ([cf. p. 89]).

What induces the cells of the pyloric mucous membrane to produce the gastric hormone? Their activity in this respect evidently depends upon the presence in the stomach of partially digested proteid substances. The cells judge, as it were, when these substances come into contact with them, that there is more work for the great bag of the stomach to do. They call upon the part which is most active in secreting gastric juice to pour it out quickly and get the business of digestion over. Meat-extracts, which contain the products of protein disintegration, have a similar influence in promoting the formation of the hormone. Hence, no doubt, the general custom, found from experience to be beneficial, of commencing dinner with soup; although it must be remembered that the rapid absorption of meat-extracts makes them peculiarly valuable as restoratives. They afford very little energy, but what they have to give is quickly placed at the disposal of the economy. Persons whose stomachs are unduly irritable are advised to avoid soup. It leads to undesirable activity on the part of the gastric glands, and especially of the acid-secreting cells. Well chewed bread also encourages the production of the hormone.

Here it may be well to call attention to the evident division of the stomach into two parts—the large bag, or cardiac portion, which hangs down; and the smaller, funnel-shaped pyloric end, which is almost vertical. The distinction between these two parts is faintly visible in the resting stomach, but even opening the abdomen tends to obliterate it. That it is much more evident during active digestion has been shown by adding subnitrate of bismuth to the food, and throwing the shadow of the stomach on a screen with Röntgen rays. When this is done, it is seen that the two parts work in different ways. Food is churned round and round in the cardiac portion, and pressed towards the pylorus. Its fluid products, mixed with the abundant secretion of the gastric mucous membrane, are wrung out of it by the pyloric funnel. They are squeezed towards the pylorus, which opens at intervals to let them through. If lumps of solid matter reach it, the pyloric valve closes tightly, until the undigested food has fallen back into the dependent bag. Dyspeptics are sometimes unpleasantly conscious of the contractions of the pyloric funnel. In fact, putting aside pain due to gastritis, all the discomfort of dyspepsia is felt on the right side. Flatus accumulates beneath the pyloric valve. The valve will not open to let it pass. The pyloric portion of the stomach contracts strongly. Notwithstanding the general trend of movement in the opposite direction, the gases are squeezed back into the larger bag, and escape through the cardiac orifice.

Tables have been prepared showing the length of time which various articles of food take to digest. They are based in part upon observations made upon the living stomach in cases in which it has been possible to examine its contents through a fistulous opening; in part upon the results of artificial digestions carried out in the laboratory. It is hardly too much to say that such observations are absolutely without value as tests of the relative digestibility of the several articles of diet consumed as parts of an ordinary meal. The fact that the commencement of the flow of gastric juice depends upon mental stimuli, and its continuance upon hormones, shows how difficult it must be to reproduce the conditions which obtain in a healthy living body. The most wholesome of foods taken by itself may be longer in digesting, or may produce more irritation, than many less desirable things taken in judicious combination. Crushed chicken, hastily swallowed, sometimes proves more difficult of digestion than meat so cooked and served as to stimulate appetite and to demand mastication.

Returning to the story of a meal, vegetables pass almost unaltered through the stomach. Some of the scanty proteins which they contain are peptonized, but unless they are very well masticated or cooked until they are soft, and therefore easily pulped by the churning action of the stomach, the gastric juice has to reach the proteins through cell-walls. None of the digestive juices are able to dissolve the cellulose of vegetable cell-walls. Blocks of vegetable tissue pass down the whole length of the alimentary canal in the form in which they were left by the teeth. Hence the extreme indigestibility of ill-chewed cucumber or apple. The pyloric valve of the stomach is forbidden to allow any lumps of food to pass until the very last stage of gastric digestion. Pieces of ill-masticated vegetable tissue lie for a long time in the stomach, irritating the ends of the gastric nerves, until at last the time comes for them to be shot through the pylorus into the duodenum. Many salts which vegetables contain, especially the earthy carbonates and phosphates, are dissolved by the acid of the gastric juice.

Meat consists of muscle-fibres supported by connective tissue. In the stomach the gelatiniferous connective tissue is dissolved, setting the fibres free. Further, the fibres being surrounded by a membrane of the same nature—sarcolemma—this is removed; and although it may be hardly justifiable to speak of “Krause’s membranes” ([cf. Fig. 10]) as gelatiniferous septa, the fibres are certainly composed of segments—Bowman’s discs, sarcous elements—into which they break up under the action of gastric juice. As a result, meat-fibre is reduced to a finely divided granular condition. The capacity of gastric juice for dissolving collagen (the substance of which connective tissue is composed) may be regarded as its most characteristic, as it is one of its most valuable, properties. Collagen, when boiled or acted on by acids, takes water into its molecule, becoming gelatin. Under the influence of gastric juice gelatin is rapidly hydrolysed into diffusible gelatin-peptone. Pancreatic juice is unable to act upon collagen, unless it has been previously boiled, or swollen by the action of dilute acids.

Fat is composed of vesicles of oil supported by connective tissue. Gastric juice, by dissolving the connective tissue and the collagenous walls of the vesicles, sets the oil free. The oil, even though it be as firm as suet when cold, is liquid, or almost liquid, at the temperature of the body.

Thus, with the exception of raw vegetables, the hard fibre of cooked vegetables, elastic tissue of meat, and a few other indigestible substances, the meal is reduced in the stomach to a cream-coloured, fatty, strongly acid “chyme.” In this condition it enters the duodenum, where it at once comes into contact with an alkaline secretion. The passage of acid chyme down this portion of the canal provokes the discharge of gushes of bile and pancreatic juice. By precipitating partially digested proteins and “acid-albumin” bile renders the mixture thicker and sticky. It colours it yellowish-brown. Under the influence of pancreatic juice the remaining proteins and proteoses are rapidly converted into peptones, some of which are shaken down by the violent action of erepsin into simpler bodies, such as leucin and tyrosin, etc. The chyme becomes alkaline, grey, and thin. All undigested starch is changed into maltose, and this into dextrose. Cane-sugar is converted into dextrose and levulose. These sugars are absorbed into the blood. Milk-sugar, if not converted into lactic acid, remains as lactose (C₁₂H₂₂O₁₁), in which condition it is absorbed without “inversion.” Fats are split by a ferment of the pancreatic juice into fatty acid and glycerin; some of the fatty acid combines with alkali to form soap, but of this we shall have more to say later on.

The duct common to the liver and the pancreas opens into the second part of the duodenum. The organs which produce bile and pancreatic juice are comparatively remote from the place where their secretions come into contact with the food. By what mechanism are they thrown into activity when the assistance of their secretions is required? As in the case of the stomach, the agent is a hormone, a chemical messenger. The hormone, termed “secretin,” is formed by the cells of the mucous membrane of the duodenum when acid comes in contact with them. It is absorbed by the blood, which carries it to the pancreas and the liver. When it reaches the pancreas, it acts as a most powerful stimulant to the discharge of accumulated ferments, and to the production of an additional supply. It stimulates the liver to pour forth bile. At present we are in ignorance as to the chemical nature of this hormone. It is not a proteid substance, nor is it a ferment. If scrapings from the mucous membrane of the duodenum be crushed with sand and hydrochloric acid, the mixture boiled, neutralized with carbonate of soda, and filtered, the clear, colourless liquid which results has a powerful effect upon the pancreas, when injected, in even small quantities, into the blood. Apparently, the cells of the duodenal mucous membrane are constantly producing and accumulating a substance which is converted into secretin when acted on by acid. It is not necessary for the acid to stimulate the living cells. If the mucous membrane is ground up with sand and salt-solution, the filtrate is inactive but an active extract is obtained by treating the crushed cells with HCl. It changes some substance which they contain (provisionally termed “prosecretin”) into the efficient hormone.

In the lower portion of the small intestine any maltose that remains is converted into diffusible dextrose. A very large amount of water has been poured into the canal in the various digestive juices. This, together with water drunk, is absorbed in the large intestine. At the lower end of the alimentary canal nothing remains but indigestible substances taken with food, chiefly cellulose, and the pigments and other bodies which, as already said, are eliminated in bile.

The absorption of water is checked by the ingestion of extremely soluble salts, such as sulphate of magnesia, the heavy molecule of which diffuses with difficulty. We attribute the fact that sulphate of magnesia remains in the intestine, and prevents water from diffusing out of it, to its slowness in passing through a membrane, because this is what would happen in dialysis;[2] but we must remember that the living wall of the intestine is not a membrane. The cells which line the intestine take up substances far less easily diffusible than the sulphate of magnesia which they refuse. Nevertheless, speaking generally, it is the less diffusible salts which act as aperients, the more diffusible which are absorbed. The forward passage of the contents of the alimentary canal is hastened by castor-oil. The peristalsis of the intestines is stimulated by certain drugs, such as jalap or the burnt products of tobacco. Another class of drugs, of which aloes is an example, increases the secretion of the intestines, small or large. Certain purgatives, such as calomel, podophyllin, etc., used to be regarded as cholagogues. It was supposed that they increased the flow of bile. This is an error. Their action is complicated, but it affects chiefly the peristalsis of the intestine. The poor misunderstood liver still suffers from the libels of primitive medical science. It is the most innocent of organs, in no way responsible for derangements of digestion. It carries out its functions without haste and without delay. With the possible exception of salicylate of soda, no drug is known which can stimulate it to a more rapid output of bile.

Absorption.—All the cells which line the alimentary canal are capable of absorbing food, if it is presented to them in a suitable form. In a suitable form means, speaking generally, in a diffusible condition, although it must not be supposed that the epithelial cells are incapable, under certain circumstances, of taking up non-diffusible substances, just as a unicellular organism—an amœba—can take in food. If soluble proteins, such as white of egg or acid-albumin, are injected into the large intestine, a very considerable proportion of the substance so injected is absorbed. It is possible, indeed, to supply in this way the whole of the nitrogenous food needed by the system, none entering by the mouth. If milk is injected, a certain amount of the fat also is retained. It can be shown that such absorption takes place when no digestion of the food occurs in the colon. The food is taken up by the epithelial cells in the form in which it is injected.

The organs specially devoted to absorption are the villi, which project into the contents of the small intestine. Each is a conical process about 0·5 millimetre long. The villi are longest in the upper half of the small intestine. Below this level they decrease in number and size. A villus is completely covered with epithelial cells of short, columnar form. The free border of each cell is slightly hardened, forming a disc or cap which appears striated in optical section—an indication, as some think, that it is traversed by pores. Others hold that the appearance of striation is due to minute cilia-like projections which beset the free border of each cell. In worms and other invertebrates the cells carry motile projections of not inconsiderable size, which no doubt free their surfaces from the unassimilable matter which tends to accumulate upon them. Possibly they help to fix particles which are suitable for absorption. In mammals the presence of cilia has not been demonstrated. The extreme minuteness of the striæ seems to point to their being merely indications that the border is permeable to fluids, including droplets of fat.