Nutrition

NUTRITION

BY the term nutrition, employed in its widest sense, is understood the process, or rather the assemblage of processes, concerned in the maintenance and repair of the living body as a whole, or of its constituent parts or organs. The term has, however, usually been limited in systematic treatises on physiology to a study, mainly statistical, of the relations which exist between a living being and the medium which it inhabits, embracing a determination of the gains and losses of the organism under the different conditions to which it may be exposed. Such a statistical study has already been pursued in the article Dietetics, and we shall therefore in the present article, restricting our attention to the animal kingdom, consider nutrition in the more general sense above referred to, including—(1) a study of the function of digestion; (2) a sketch of the processes concerned in the absorption of matter into the blood; (3) an account of the chemical processes which have their seat in the tissues and organs of the body; (4) an account of the processes whereby redundant matters, or such as are the products of waste, are removed from the animal economy; (5) a reference to the transformations of energy which are associated with the exchange of the matters of the body; (6) a brief reference to the processes of growth, decay, and death.

With the exception of the chemical processes concerned in respiration, which will be treated of at length under that head, this article will therefore include a short discussion of the chemical operations of the body generally, and particularly as they are exemplified in the case of man.

General Introductory Considerations.— There is no conception which we can form in reference to a living being, however rudimentary its structure, which is so general as the following a living animal, so long as it manifests those attributes which characterize it as living, is the seat of continual transformations of potential into kinetic energy.

Such transformations are connected with oxidation of organic matters which, primarily derived from the vegetable kingdom, have been assimilated, i.e., have been converted into the substance of the animal, and are effected through the agency of oxygen gas introduced into the body in the process of respiration. The act of living is an act of combustion in which the animal body actually burns, and the energy at the disposal of the body, and which is employed in raising its temperature or effecting the movements which are essential to its continued life, is energy which was potential in the organic constituents burned. The main products of the combustion of the body are carbonic acid and water, besides certain other less completely oxidized substances, which are the analogues of the sooty and tarry products of combustion in a furnace. Of these products some, as carbonic acid and a part of the water formed, are removed from the body almost as soon as they are formed, while others are thrown off at intervals.

It follows from what has been stated that the act of living necessarily implies not only transformation of energy but actual waste of the matter of the body, and that if an animal is continuously to manifest the phenomena of life it must be supplied with oxidizable organic matter to take the place of that which has been oxidized. Accordingly, animal life is impossible unless the creature, besides receiving continual supplies of oxygen gas, receives at intervals supplies of food. The food of an animal consists (1) of oxidizable organic matters which, although they may have been derived in part or wholly from some other animal body, have primarily been built up through the instrumentality of vegetable organisms,—these organic matters belong to a few well-defined groups: (2) of mineral matters, including large quantities of water, which form an important part of the substance of the body, and the presence in and passage of which through the organism is essential to the physical processes which have their seat in it.

In brief, the animal body is the seat of processes of disintegration associated with the manifestation of kinetic energy, and of processes of integration in which oxidizable matters take the place of the oxidized constituents. If life is to continue, in a sense, indefinitely it is essential that the processes of integration and disintegration should balance, i.e., that the receipts of the body in assimilable oxidizable matter should balance the expenditure of the body both in matter and energy. There are, it will be observed, very close analogies between an animal and such a mechanism as a steam-engine, the energy at the disposal of both being primarily derived from the oxidation of combustible matters. Some of the most salient points of difference must, however, not be lost sight of. (1) The waste of the essential parts of such a machine as a steam-engine is insignificant, and bears no definite relation to the work done. The kinetic energy of the machine is primarily due to oxidation processes taking place in the furnace, and in no respect to changes in the substance of the machine. The animal, on the other hand, wastes continuously in all its parts and organs, and much of its energy is derived immediately from material which has become part and parcel of the various mechanisms. (2) Any substance capable of being rapidly oxidized (burned), and thus of generating heat, may be used as fuel for a steam-engine, provided its combustion admits of being conducted with safety in its furnace, whilst the substances which can form the food of animals belong to a limited number of groups, which include but a comparatively small number of bodies. The constituents of food have not only to supply energy to the body, but they must further be capable of prior conversion into the very substance of the animal body, into its very “flesh and blood.”

Moreover, the constituents of food must be free from all traces of the peculiar substances which we term “poisons,” and which by their presence have the power of impairing and arresting the action of various organs of the body.

I.— Function of Digestion. Hunger and Thirst.— These terms are used to express peculiar sensations which are produced by and give expression to general wants of the system, satisfied respectively by the ingestion of organic solids containing substances capable of acting as food, and by water or liquids and solids containing water.

Hunger is a peculiarly indefinite sensation of craving or want which is referred to the stomach, but with which is often combined, always indeed in its most pronounced stages, a general feeling of weakness or faintness. The earliest stages are unattended with suffering, and, leading the animal to wish and seek for food, are characterized as “appetite for food.” Hunger is normally appeased by the introduction of solid or semi-solid nutriment into the stomach, and it is probable that the almost immediate alleviation of the sensation under these circumstances is in part due to a local influence, perhaps connected with a free secretion of gastric juice. Essentially, however, the sensation of hunger is a mere local expression of a general want, and this local expression ceases when the want is satisfied, even though only liquid and no solid food is introduced into the stomach, or even though no food be introduced into the stomach, the needs of the economy being satisfied by the introduction of food through other channels, as, for example, when food which admits of being readily absorbed is injected into the large intestine.

Thirst is a peculiar sensation of dryness and heat localized in the tongue and throat. Although thirst may be artificially produced by drying, as by the passage of a current of air over the mucous membrane of the above parts, normally it depends upon an impoverishment of the system in water. And, when this impoverishment ceases, in whichever way this be effected, the sensation likewise ceases. The injection of water into the blood, the stomach, or the large intestine appeases thirst, though no fluid is brought in contact with the part to which the sensation is referred.

The sensations the causes of which we have briefly attempted to trace lead us, or when urgent compel us, to take food and drink into the mouth. Once in the mouth, the entrance to the alimentary canal, the food begins to undergo a series of processes, the object of which is to extract from it as much as possible of its nutritive constituents. It cannot be sufficiently emphasized that food in the alimentary canal is, strictly speaking, outside the confines of the body; as much so as the fly grasped in the leaves of the insectivorous Dionea is outside of the plant itself. The mechanical and chemical processes to which the food is subjected in the stomach and intestines are processes which have their seat and conditions outside the body which it is destined to nourish, though unquestionably the body is no passive agent, and innumerable glands have to come into action in order to supply the chemical agents which shall dissolve and render assimilable those constituents of the food which are capable of being absorbed into the organism, and of forming part and parcel of its substance.

Structure of the Organs of Digestion in Relation to their Function.— The processes to which the food is subjected, though manifold, are divisible into two great groups: (1) the food must be subjected to the action of certain juices which dissolve insoluble alimentary matters, and modify these no less than certain of the soluble alimentary substances; and (2) it must be mechanically mixed with those juices, and propelled more or less slowly from beginning to end of the alimentary canal. In accordance with this twofold function the alimentary canal is divisible into two distinct but intercalated anatomical tubes,—(1) an internal tube of mucous membrane, and (2), investing this closely, an external muscular tube.

The musculo-membranous double tube thus formed is not, indeed, regularly tubular throughout. At the beginning it forms the irregular cavity of the mouth, which contains the tongue and the masticatory teeth. Thence it passes through the fauces and beneath the pendulous uvula and soft palate into the pharynx. Afterwards it proceeds as a regular tube, the oesophagus, or gullet, until the level of the diaphragm is reached,—the muscular partition between the thorax and the abdomen. Having passed through this structure, the narrow tube of the oesophagus suddenly dilates at the cardiac orifice into the bag called the stomach, at the further or pyloric orifice of which the tube resumes its narrow uniform calibre, and forms successively the duodenum, the jejunum, and the ileum,— parts of the small intestine, of which, in man, the duodenum takes up twelve fingers’ breadth, the ileum the lower three-fifths, and the jejunum the remainder of the total length of 20 feet. The small intestine diminishes somewhat in calibre from duodenum to ileum, and at the lower end of the latter opens suddenly into the much wider large intestine, which it joins, not at the extreme end, which is a cul-de-sac, the caput caecum coli, but at a point a little lower down. The margins of the aperture by which the small opens into the large intestine point or project into the latter in such a manner that, while they readily permit the passage of matters from small to large intestine, any backward movement of the contents of the large intestine would have the effect of compressing the lips of the opening and closing it; this arrangement constitutes the so-called itio-caecal valve. Connected with the caput caecum coli is a small diverticulum like a narrow glove finger, called the vermiform appendage. The first and greater part of the large intestine is known as the colon, the last as the rectum. The total length is from 5 to 6 feet. Its lower orifice is called the anus.

Both muscular and membranous (mucous) tubes are continuous from mouth to anus, and at these, the superior and inferior orifices, the mucous membrane which constitutes what we have hitherto termed the membranous tube is continuous with the skin which covers the general surface of the body. This mucous membrane is covered throughout at its free surface by an epithelium, and gives lodgment to glands, whose characters differ in different parts of the tube in accordance with the function of the part. Below the epithelium is a connectée tissue analogous to the cutis vera of the skin, which in parts has the character of ordinary fibro-areolar tissue, but in all parts from the stomach downwards has the character of so-called adenoid connective tissue, as it is found in the follicles of lymphatic glands. Its meshes support a τich supply of fi ne blood-vessels,lymphatic vessels, and doubtless also of delicate nervous filaments.

Besides these elements there are found numerous small bundles, or in parts even sheets, of involuntary muscular fibres, which probably give to the mucous membrane the power of limited self-contraction, of such a nature as to further the flux and reflux of fluids in the myriad lymphatic vessels of the part, and perhaps to influence in no small degree the outpouring of the secretion of certain of the glands. To the fairly continuous tract or sheet of involuntarymuscle which lies at the base or deepest part of the mucous membrane or mucosa the term of muscularis mucosae {tunica) is applied.

In addition to the glands which lie embedded in and open upon the surface of the mucous membrane of the alimentary canal, others of larger size and not in immediate relation with its walls communicate with the interior of the tube by ducts which open into it, and which pour into it their secretion; such glands are the salivary glands, the pancreas, and the liver.

The muscular tube in the greater part of its extent consists of two layers of involuntary, non-striated, pale, muscular fibres,—an inner layer whose fibres encircle the tube, and an outer one whose fibres run parallel to the long axis of the tube. But this is not the arrangement of every part. There is an apparent rather than a real exception in the stomach, where some layers of fibres of the circular coat course over the dilated walls of the alimentary tube in an oblique direction, giving rise to an oblique layer. In the oesophagus or gullet, besides the typical circular and longitudinal layers, there is at the upper part a second longitudinal layer which takes up a position internal to—that is, nearer the mucous membrane than—the circular layers. In the upper part of the gullet also the muscular fibres are not unstriped, but, although certainly involuntary, are striated like voluntary muscles.

In the mouth the muscular tube is most irregular and most defective, for the mucosa is in parts directly applied to the bony boundaries, as over the hard palate and gums; in another part it invests the muscular prominence of the tongue; whilst in other regions it lies upon the constrictors of the pharynx and the inner aspect of certain other muscles, as those of the cheeks, lips, and floor of the mouth. The membranous tube is united to the muscular tube by a loose layer of connective tissue containing many blood-vessels and lymphatic vessels and nerves for the supply of the mucosa; it is often called the submucosa.

The mucous membrane is the seat of various secreting glands, which lie embedded in its substance and open upon its surface,— simple or branched tubular recesses running through the depth of the layer, lined by epithelium, continuous with, though not always resembling, that of the surface, and opening at the surface by minute pores. In the mouth, pharynx, and oesophagus those form the acinous or racemose glands, which, according to certain subordinate features which they present, and also according to certain of the characters of the fluids which they secrete, are separated into mucous and serous glands. In the stomach they are represented by the simple or branched tubular gastric glands. In the duodenum we find them as simple tubular deep sockets, the glands or crypts of Lieberkühn, and also as the compound acinous glands of Brunner, which dip below the level of the mucosa and lie in the submucosa. In the jejunum, ileum, and large intestine they appear again as the crypts or follicles of Lieberkühn.

The membranous tube is not everywhere exactly concentric and conterminous with the muscular tube. In the mouth and pharynx it is almost entirely so, but at the gullet the muscular tube so tightly encloses the membranous that the latter is forced into longitudinal plications to find room for itself. In the stomach the membranous layer is raised into ridges or rugse, which intersect and give the surface a honeycombdike aspect. In the upper part of the small intestine the membranous tube is raised into deep annular or, more correctly, crescentic folds, running across the direction of the gut like incomplete diaphragms, or a series of membranous ledges; these are the valvulae conniventes. In the colon the two tubes are so disposed as to form a regular series of saccules or pouches, adding largely to the capacity of the gut. All these foldings greatly increase the superficies of the membranous tube. A further enlargement is effected in the small intestine in an exceedingly interesting fashion; the surface of the mucosa is thickly studded with innumerable fine short projections resembling the pile of velvet. These are invested by surface epithelium, and amongst them, at their feet, open the before-mentioned crypts of Lieberkuhn. They are the so-called villi. Each contains a lymphatic vessel, blood-vessels, and involuntary muscular fibres, all supported by adenoid connective tissue like that of the mucosa below; the lymphatic is in the axis of the villus, the muscles form the next layer, and the blood-vessels lie immediately beneath the epithelium. When the muscular layer of the villus contracts it must of necessity compress the lymph-vessel, whilst causing no impediment to the flow of blood.

We have described the mucosa of the stomach and intestines as containing a framework of adenoid reticular tissue like the tissue of lymphatic follicles. It is, indeed, identical with this,—a network of branched cells with oval nuclei, the meshes of which are crowded with lymph-corpuscles with round nuclei At certain points in the intestines the adenoid tissue of the mucosa presents local nodular enlargements; the mucosa at these points becomes so much thicker that it swells up at the free surface beneath the epithelium into rounded eminences about as large as millet-seeds or the heads of small pins; and at the under surface of the mucosa it dips into the submucous tissue in a similar manner. At the base of this nodule of adenoid tissue in the submucosa there is usually a network of wide, thin-walled, lymphatic vessels. Many of these rounded masses are scattered irregularly over the small and large intestines as the solitary follicles or glands, but at the lower end of the ileum they form little colonies, often covering an area an inch or more in length, situated at that part of the intestine which is remote from the attachment of the mesentery. They then constitute the so-called Peyer s patches.

Nodular adenoid masses are, however, not limited to the adenoid mucosa of the intestines. They are occasionally, though rarely, found in the stomach; they exist beneath the mucous membrane of the tongue, and a colony of them forms the mass of the tonsil on each side,—the almond-shaped body situated between the posterior and anterior pillars of the fauces.

The intrinsic nerves of the alimentary tube consist of two systems of nervous networks with ganglion-cells lying at the nodes; one is found in the submucous layer {plexus of Meissner'), the other lies between the longitudinal and circular muscles {plexus of Auerbach, or plexus myentericus).

The whole of the intestines, and the stomach as well, are sustained in the abdominal cavity by sheets of delicate membrane, formed by folds of peritoneum, and called, in the case of the intestinal portion of the tube, the mesentery. Between the layers of the mesentery run the vessels and nerves for the supply of the bowel. In addition to blood-vessels there are numerous thin-walled lymphatic vessels called lacteals, which are fed by the rich network of lymphatic vessels of the mucosa and submucosa, and which run in the mesentery to the back of the abdominal cavity. Here they are collected into a large lymphatic reservoir, the receptaculum chyli, from which a duct, the thoracic duct, proceeds along the side of the vertebral column to open into the venous system at the junction of the subclavian and jugular veins on the left side of the neck. The lacteal and lymphatic vessels, whose course has been briefly sketched, are interrupted at many points by the presence of lymphatic glands. These may be simply regarded as labyrinthine systems of vessels into which the simple afferent lymphatic or lacteal vessels open, and each of which is surrounded and penetrated by adenoid connective tissue, like that of the intestinal mucosa. After a meal the lacteal vessels are filled with a milky fluid, the chyle. They were discovered by Aselli in the year 1626.

It must not be thought that the glands of the mucous membrane of the alimentary canal are alone engaged in the preparation of the solvent digestive fluids. Other organs there are lying away from the alimentary canal which pour their secretions into it by ducts at various points. In the neighbourhood of the mouth there are three pairs of salivary glands. The parotid glands lie outside the cheek over the lower jaw, just in front of the meatus of the ear. The ducts of this pair course along the cheeks and pierce them opposite the second upper molar tooth on each side; these are the two ducts of Stenson. A second pair of glands, the submaxillary, lies beneath the ramus of the lower jaw and beneath the floor of the mouth; their ducts run forward to open beneath the tongue; these are the ducts of Wharton. The third pair, the sublingual, lies on the floor of the mouth, beneath the mucous membrane anterior to the openings of the duets of Wharton.

The ducts of these glands are numerous and open by many apertures on the floor of the mouth, some opening into the ducts of Wharton. These constitute the ducts of Rivinus.

About three or four inches below the pylorus the ducts of two large glands open into the small intestine by a common orifice; these are the ducts of Wirsung, or pancreatic ducts, from the pancreas on the left, and the common bile-duct from the liver on the right.

Movements of the Alimentary Canal.— When food is introduced into the mouth it is submitted to the operation of mastication. The incisors or cutting teeth divide it into portions of suitable size, which are thrust under the broad faces of the molar or grinding teeth by the alternate movements of tongue and cheeks. Softer portions of food are crushed between tongue and hard palate, especially such as are taken for their sapid properties to please the palate and increase the flow of saliva. Mastication consists of movements of the lower jaw upon the upper, viz., (1) vertical movements brought about by the temporal and the internal pterygoid and masseter muscles on the one hand, and by the digastric, mylo-hyoid, and other depressor muscles attached to the lower jaw on the other; (2) horizontal movements, forwards and backwards, effected by the external pterygoid muscles; when one of these muscles alone contracts, the forward movement of the chin is changed to a forward and lateral movement by the rotation of the jaw around the opposite condyle as a pivot; after being moved forward the jaw is retracted by the horizontal fibres of the temporal muscle; (3) grinding movements effected by a combination of the various muscles already mentioned.

That the tongue and cheeks are not frequently nipped between the teeth is an indication of the perfect co-ordination of a very complex series of movements. The controlling sensations are chiefly conveyed along the fibres of the fifth cranial nerve. The motor fibres of the same nerve supply the chief but not all the muscles of mastication.

After the food has been reduced to a proper consistency by the combined influence of the mechanical movements of the jaws, tongue, and cheeks, and the action of the saliva, it is rolled into a mass or bolus ready for swallowing. The bolus is pushed on the dorsum of the tongue, which is hollowed into a shallow trough to receive it. It is easy to conceive how this shape of the tongue is brought about when we consider that the tongue is provided with vertical fibres, with horizontal antero-posterior fibres, and with horizontal lateral fibres, in addition to its extrinsic muscles. The tip of the tongue is then raised against the hard palate in such a manner as to form an angle in which the bolus lies. By the approximation of the tongue to the palate the angle is lessened and the bolus is, in consequence, driven backwards. This constitutes the first stage in the act of swallowing, and is a voluntary act, At the end of the first stage the morsel of food has passed beyond the level of the anterior pillars of the fauces. The acts of the second stage are very complicated, and probably are entirely involuntary. The posterior pillars of the fauces approach one another in the middle line, and the uvula falls into the space left between them. The fleshy curtain thus extemporized is then drawn up towards the hind wall of the pharynx, which is drawn a little forwards and upwards to meet it. Thus the passage into the nose is completely shut. Meanwhile the vocal cords of the larynx draw near to one another; the epiglottis is pushed backwards over the larynx, and the whole larynx is drawn suddenly upwards and forwards beneath the root of the tongue. In this manner the entrance into the respiratory passages is protected. Finally, the anterior pillars of the fauces are made to meet over the tongue in order to prevent the regurgitation of the food. There is but one way open to the bolus; the sudden drawing forward of the larynx and the base of the tongue in fact “cuts the ground” from under the ball of food, which thereupon falls into the grasp of the “constrictors” and enters upon the third and final stage in the act of deglutition. This, even more certainly than the second stage, is purely involuntary. The constrictors contract from above downwards and force the morsel of food into the upper portion of the oesophagus. Once in the gullet, the mass of food is driven downwards by the so-called “peristaltic” movements of the tube—the circular fibres contract one after another from above downwards, lessening the calibre of the tube in successive stages, whilst the longitudinal fibres seem to have the function of drawing the tube over the bolus as a stocking is drawn over the foot.

Deglutition is a reflex act, in so far as it is involuntary, the centre for which lies in the medulla oblongata; destruction of this centre implies incapacity to swallow. The centre, though normally under the influence of the higher centres, may, however, act quite independently of these, as is evidenced by the fact that animals in which the cerebral hemispheres were absent have occasionally survived for a short time, and have still been able to suck and swallow. Although the excised gullet often exhibits a true peristalsis, which doubtless depends upon a local nervous mechanism, the normal movements in the body seem to be regulated from the medulla oblongata.

At the entrance of the stomach the food meets the barrier opposed by the contracted cardiac orifice; the contraction must be overcome before the food can gain admittance. The relaxation is certainly an active process under the control of the medulla oblongata through the vagus nerve, since section of the vagi causes a block to the progress of food from the oesophagus into the stomach.

In the stomach the food is detained for a period which varies very greatly with its digestibility, but which in the human subject is not often longer than four or five hours. It is subjected to a rubbing and rolling action of the stomach-walls and a modified peristalsis, which causes the food to move slowly from the cardiac orifice along the greater curvature to the pylorus, whence it returns along the small curvature to the cardiac end again, The gastric movements are slight at first, but gradually increase in vigour. The pylorus is tightly closed at the beginning of a meal, but becomes more and more relaxed as digestion proceeds, so that, whilst at first only the finer parts of the gastric contents can pass, afterwards the coarser parts and even solid lumps of imperfectly-digested aliments are permitted to escape into the duodenum. We possess little accurate knowledge as to the nervous mechanism of the stomach. Are the movements caused immediately by the local nervous ganglia situated in its walls? Or does the impulse to move descend directly from the encephalic centre along the pneumogastric nerves 1 All that we know is ( 1 ) that movements of an excised stomach are induced with great difficulty, (2) that stimulation of the vagus will often cause movements of the stomach, and (3) that section of the vagi impedes the passage of food out of the stomach. The movements of the stomach have been said to cease altogether during sleep.

When the gastric contents, to which the term chyme is often applied, pass through the pylorus into the duodenum, they begin to move onward by the pure peristaltic action of the small intestines. The powerful annular fibres contract one after another, driving the food onward, as water may be squeezed along an india-rubber tube by the compression of the hand. The longitudinal fibres contract in such a manner that the intestine is drawn over the advancing mass. The movements always occur (in health at least) in a direction from the stomach to the ileo-caecal valve; here they stop and never pass as a continuous wave to the large intestine.

Peristalsis may be exhibited by an excised intestine independently of any extrinsic nervous apparatus. Stimulation of the vagus nerve, as a rule, excites the intestinal movements, while excitation of the splanchnic nerves tends to still them. When the blood stagnates in the intestinal vessels active peristalsis ensues. As the splanchnic nerves are also the vaso-motor nerves of the intestines, excitation of them produces constriction of the blood-vessels and comparative bloodlessness.

After passing through the ileo-caecal valve the intestinal contents, which have been very greatly diminished in amount owing to the process of absorption that has gone on, quickly assume the characteristic appearance of faeces. The undigested and insoluble parts of the food, mixed with mucus, with epithelial débris, and with some substances derived from the secretions of the alimentary canal, notably with some biliary products, must be cast out; this is effected by the act of defecation. The anus is normally kept firmly closed by the contraction of two sphincter muscles,—the external, which is one of the skeletal muscles, and the internal, which is formed by a special development of the lowest rings of the circular layer of muscles of the intestine. In the act of defecation these sphincters are relaxed, while the contraction of the rectum forces its contents downwards. The levatores ani are brought into play by the will and exert an action similar to that previously referred to as performed by the longitudinal fibres of the intestine. Of special influence in aiding the expulsion of the contents of the bowel is the contraction of the abdominal muscles which follows a preliminary fixation of the diaphragm by a deep inspiration.

The act of defecation is essentially a reflex act. The centre which presides over the sphincters of the anus lies in the lumbar portion of the spinal cord. This centre is under the control of the brain, under the influence of which its activity is either increased or inhibited.

Vomiting, or the ejection of the contents of the stomach through the mouth, is an act of considerable complexity; (1) the cardiac orifice of the stomach is relaxed or, to be accurate, thrown open by the operation of some reflex nervous mechanism with which the vagus is connected; (2) contraction of the muscular coat of the stomach occurs; (3) the abdominal walls are powerfully compressed, and the diaphragm is at the same time strongly fixed by closure of the glottis. As concurrent phenomena in ordinary vomiting may be mentioned the sense of nausea and the free flow of saliva which occurs during and indeed before the act.

Vomiting may, within certain limits, be inhibited by taking a series of deep and rapid inspirations at a time when the sense of nausea is becoming unbearable.

True vomiting seems to be impossible without the aid of the abdominal muscles, as, for example, when the abdomen is laid open. In such conditions emetics cause active opening of the cardiac orifice and movements of the stomach-walls, but not the full and free expulsion of the contents. Vomiting is usually a reflex act, the centre for which lies in the medulla oblongata near the centre for respiration, though it is reasonable to suppose that it may occur not only as a reflex act but as a result of direct stimulation of the centre or centres associated with it.

Secretions of the Alimentary Canal.—Production of the Alimentary Juices.— We have described the movements of the alimentary tube by which the food is triturated and agitated, and finally propelled from mouth to anus. One object of these movements is to mix together the food and certain solvent juices which are poured upon the food at various points. We have now to give an account of these juices and their properties. They are produced in, or by the agency of, the epithelium cells lining the interior of glands which are either situated in the walls of the alimentary canal or which empty their secretion into it. Though these cells derive the materials necessary to their metabolic activity from the blood, the substances which they elaborate and which are characteristic of the secretions that they help to form are not found in the blood, but are products of the activity of the protoplasm of the cells themselves. The act of secretion is a function of the living cell, and not a mere act of filtration or diffusion through the vascular walls to the cell-substance. It often involves the elaboration of entirely new substances. The act of secretion is, or may be, under the control of the nervous system; it may be started, inhibited, and the products of the secretion may be variously modified, by the stimulation of distant nerves. In some glands certainly, and possibly in all, the elaboration of the specific secretion of the gland takes place in two well-defined stages, and the two stages are indicated by differences in the anatomical appearances of the gland-cells.

The characteristic constituents of the several juices which are specially concerned in the chemical changes of the alimentary canal are certain so-called “unorganized” ferments, which we shall, following the suggestion of Kühne, denominate enzymes. Like all ferments, these are capable, under suitable circumstances, of initiating specific changes in certain bodies with which they are brought into contact, changes which may be incommen-surably great when contrasted with the magnitude of the mass of the ferment engaged. “Unorganized” or, as they have also been called, “unformed” ferments differ, however, from the “organized” or “formed” in that, whilst they are the products of the activity of living cells, when once formed they cease to be living, are unconnected with any organized form, and have no power of reproduction or increase.

The enzymes for the most part exert their action unimpaired in the presence of certain bodies which kill the great majority of organized ferments; thus salicylic acid does not hinder peptic and tryptic digestion, whilst it prevents the putrefactive changes which are very apt to occur in the latter case, and which are connected with the development of organized ferments. Certain enzymes, as the diastatic ferment of saliva and pancreatic juice, are, however, destroyed by salicylic acid.

As will be shown in detail in the sequel, the secreting cells of glands which produce enzymes exhibit marked differences corresponding to different states of activity. In the case of the secreting cells of the pancreas the cells appear to produce and store up for a time a body, a zymoyen, from which subsequently the tryptic enzyme trypsin is set free. The progress of research may perhaps establish the existence of zymogens corresponding to the other enzymes.

Usually the glandular organs which produce the alimentary juices contain stored up within them their characteristic enzymes, which may be extracted by digesting the comminuted organ in water, or still better in glycerin, which dissolves them nearly all, and furnishes solutions which preserve their activity long unimpaired. Enzymes are all insoluble in strong alcohol, so that the tissues from which they are to be extracted may be first dehydrated by digestion in absolute alcohol and afterwards extracted with glycerin. Solutions of enzymes are rendered inactive by boiling or by exposure to a temperature above 70° C. The principal enzymes of the alimentary canal belong either to the group of proteolytic or to that of diastatic or amylolytic ferments: the enzymes of the first group (pepsin and trypsin) dissolve proteids and effect their more or less perfect decomposition; the enzymes of the second class (as ptyalin and the diastatic ferment of the pancreas) dissolve starch and produce from it a series of bodies which will be discussed in reference to the action of saliva on starch.

Besides the proteolytic and amylolytic ferments, there occur in the alimentary canal a curdling ferment, an inverting ferment, and perhaps a fat-decomposing ferment.

All enzymes exert a more energetic action at a moderately high than at a low temperature, though the influence of a rise in temperature is more marked in some cases than in others. The reaction of the medium in which they are placed influences remarkably the activity of certain enzymes; thus pepsin, the proteolytic ferment of the stomach, is inactive in neutral or alkaline solutions, the presence of a free acid being essential to its activity, whilst trypsin, the proteolytic ferment of the pancreas, acts with feebleness in solutions which are neutral or faintly acid, since it needs for the full exercise of its powers a decidedly alkaline medium. The enzymes appear to possess the power of rapidly inducing, at the temperature of the animal body, in bodies subjected to them similar chemical operations to those which can be brought about with great slowness by prolonged heating with dilute mineral acids, or by the prolonged action of boiling water or superheated steam. These operations are of the nature of hydrolytic decompositions, that is to say, such as are connected with the union of the elements of water with the decomposing body.

Salivary Glands and Secretion of Saliva.— There are no secreting glands in the body which have been subjected to so elaborate a study as the salivary glands, whether we consider their structure or the circumstances which influence or accompany the act of secretion. We shall therefore give the results of researches on these glands at much greater length than those referring to the other glands concerned in the preparation of the alimentary juices.

As has been already said, the saliva is secreted by several glands of which the ducts pour their secretion into the cavity of the mouth, where it is mingled and constitutes the “mixed saliva.” The chief of these glands are the parotid, the submaxillary, and the sublingual glands, though their secretion is mixed with that of small glands (mucous and serous) scattered through the mucous membrane of the mouth and tongue, which are included under the term “buccal” glands.

The salivary glands all belong to the group of acinous or compound racemose glands. According to the researches of Heidenhain, they may, however, be divided into two groups, which he has denominated serous or albuminous and mucous glands, according to the structure of the cells of their acini, their chemical characters, and the nature of the secretion which they elaborate.

To the group of serous glands belong the parotid of man and the majority of animals, the submaxillary gland of the rabbit, and some of the glands of the tongue; to that of mucous glands belong the submaxillary and sublingual glands in most animals, some of the glands of the tongue, and the oesophageal glands. Glands belonging to the former of these classes secrete a fluid containing some, though it may be only a small quantity, of a proteid coagulable by heat, and resembling, if not identical with, serumalbumin; the mucous glands, on the other hand, as their name implies, secrete a liquid free from albumin, but containing more or less mucin.

In the serous glands the epithelium lining the acini is composed of comparatively small, rounded, or polygonal cells, of which the outlines are not very distinct until acted upon by certain reagents. No cell-wall is present; the protoplasm, which is not coloured by carmine, presents many dark granules, and surrounds an irregularly saccular or rounded nucleus which is coloured by carmine.

In the mucous glands the characteristic (mucous) cells of the alveoli are large and clear, very faintly granular, with a rounded or oval nucleus near their periphery surrounded by a trace of protoplasm. They possess a cell-wall, and a strongly refracting process which springs from the cell in the neighbourhood of the nucleus.

In addition to the characteristic mucous cells there are found in the alveoli of most mucous salivary glands when examined in a state of rest, situated at some parts of the periphery, i.e., lying more internal than, or nearer to, the membrana propria than the mucous cells, half-moon-shaped aggregations of small cells, possessed of a round nucleus easily stained with carmine, and containing albumin; to these aggregations the term of demilunes or lunulae of Gianuzzi has been applied. In some cases we find alveoli in which these small cells are not arranged in demilunes, but form a row of cells lying external to the mucous cells, and completely encircling them (see fig. 3).

As has been said, in certain mucous glands the mucous cells are supplemented by the cells of the demilunes, though there are other mucous glands, as those of the tongue, where the typical mucous cells alone occur. There are glands, and the submaxillary of man is an example, which are termed mixed glands, inasmuch as some of the acini have all the characters of serous, others of mucous glands. The submaxillary gland of the guinea-pig possesses, according to Klein, a structure undistinguishable from that of the pancreas.

We shall not enter, in this place, into a detailed description of the innervation of any one of the salivary glands, but shall confine ourselves to the following statements.

Each salivary gland is supplied by at least three classes of fibres, viz., secretory, vaso-constrictor, and vaso-dilator fibres, of which the first and the third are conveyed to the glands in branches of cerebral nerves; these are, the chorda tympani for the submaxillary and sublingual, and the auriculo-temporal (which, however, derives them through communications with the otic ganglion from the glossopharyngeal nerve) for the parotid. The second class, the vaso-constrictor or vaso-motor fibres, run in sympathetic trunks. When, therefore, one of the cranial branches supplying a gland is stimulated there occur two acts, viz., secretion and simultaneous dilatation of blood-vessels; that these two acts are not absolutely interdependent is proved by the fact that certain drugs paralyse the one set of fibres, but leave the other intact. When, on the other hand, the sympathetic filaments supplying the gland are stimulated, the blood-vessels of the gland contract, and there is produced a small quantity of saliva differing in physical characters and chemical composition from that obtained under the circumstances first referred to. Accord ing to Heidenhain, however, in each of the two kinds of nerves supplying a salivary gland there exist, besides the vascular nerve-fibres, secretory and trophic fibres, though the number of one or other of these classes may be insignificant,— the secretory predominating in the cranial nerve branches, the trophic in the sympathetic. Stimulation of secretory fibres leads, according to Heidenhain, to an increased flow of water, stimulation of the trophic to an increased secretion of specific substances and to an increased production of protoplasm.

When a salivary gland passes from the state of rest into that of activity it is at once the seat of an increased blood flow, which is associated with the dilatation of the bloodvessels of the organ. Under these circumstances, the blood leaving the gland presents a florid arterial colour, instead of the venous colour which characterizes the blood of the organ when at rest. This vascular dilatation is explained by the coming into action of the before-mentioned vasodilator fibres; it is independent of the act of secretion.

As was shown in a now classical investigation of Ludwig, when the salivary glands are thrown into activity there is a rise in temperature, so that the temperature of the saliva leaving the submaxillary gland may exceed by l o- 5 C. that of the blood flowing to the gland. This rise in temperature cannot be explained by a study of the chemical characters of the salivary secretion, but is doubtless the result of the increased metabolic changes which necessarily accompany the act of secretion in the gland-cells, and which chiefly affect their protoplasm.

That the secretion of saliva (and indeed secretion in general) is not a mere act of filtration was proved by Carl Ludwig when he showed that saliva can be secreted by a gland though the pressure within it is many times higher than that of the blood circulating through the arteries which supply it. On many grounds it may be positively asserted that the secreting cells are the primary agents in the withdrawal from the blood of the water necessary for the secretion, though the exact nature of the process is yet unknown; similarly, on the grounds stated below, we know that within the protoplasm of the glandcells are formed the characteristic soluble constituents of the secretion.

The researches made during the last few years by Heidenhain, and fully confirmed by a large number of observers, have demonstrated that in the salivary glands, as indeed in all secreting glands, structural and perfectly obvious microscopic changes occur, which stand in close relation to the different conditions of functional activity.

The resting gland-cell is large, but possesses comparatively little protoplasm, and therefore comparatively little matter which can be stained by colouring bodies, especially by carmine; it contains instead a store of material which has been elaborated in, or at the expense of, the protoplasm. This material does not constitute the specific matter of the secretion, but is its antecedent. That it differs chemically in the case of the mucous glands is proved by the fact cited by Heidenhain, and discovered by Watney and Klein, viz., that, whilst mucin is stained by haematoxylin, its antecedent (mucigen) is not affected by that colouring matter; in all otheι∙ respects the two bodies are identical. When, however, a gland passes into a state of activity, as, for example, by the irritation of its so-called secretory (trophic?) nerves, the gland-cells undergo the following changes, which may proceed simultaneously though not necessarily so :—the stored-up matter previously referred to is converted into soluble constituents of the secretion, and at the same time there occurs a growth of the protoplasm of the cells, at the expense doubtless of the richer supply of lymph which during the secretory act bathes the gland.

The period of activity in so far as the gland-cell is concerned is indeed a period of removal of ready-made constituents of secretion, in some cases, as in the mucusbearing cells of the mucous glands, a period of destruction of cells laden with such constituents; but at the same time in all cases a period in which the protoplasmic constituents of the cells generally increase, and active proliferation of secreting cells occurs.

Whilst -we have in a few sentences sketched the general characters of the changes which glands undergo during secretion, our picture is wanting in all details, and the reader is referred for further information to works on histology and physiology.

Glands of the Stomach and Secretion of Gastric Juice.— In vol. vii. p. 225 a brief description has been given of two kinds of glands which are found embedded in the mucous membrane of the stomach, and which are concerned in the preparation of the secretion of this organ, the so-called gastric juice. The first kind of glands, the “mucous glands of the stomach,” so called from their having been formerly erroneously supposed to be engaged in the secretion of mucus only, are situated chiefly at the pyloric end (figs. 4, 5) of the stomach. The second kind, the so-called “peptic glands,” owe their name to the view that they alone secreted the digestive gastric juice, and are found in most animals in the mucous membrane of other parts of the stomach than the pylorus. The pyloric glands are tubular glands, simple or compound, composed of a basement membrane lined by two kinds of epitheliumcells, (1) cylindrical epithelium-cells confined to the neck of the gland, (2) cylindrical or cubical epithelium-cells lining the part of the tube below the neck, and which, though not very different in form from the cells of the neck, possess an entirely different function. The peptic glands of the older writers, now usually called “glands of the fundus,” present three varieties of epithelium-cells. I heir neck is lined by cylindrical epithelium similar to that of the neck of the pyloric glands. The deeper part of the glands is lined by small cubical “central” cells, below which and interposed between them and the basement membrane is a discontinuous layer of large ovoid “border” cells, the so-called “peptic cells” of older writers.

During active digestion the cubical cells of both pyloric glands and glands of the fundus become swollen and granular; after a period of rest they return to their original size and assume a comparatively clear appearance. The ovoid cells also swell during digestion, but in other respects remain unchanged.

When the stomach is inactive, i.e., in the fasting condition, its mucous membrane is pale and the organ contains no fluid; the mucous membrane in the pyloric region presents an alkaline reaction. When, however, food enters the stomach, or the mucous membrane is subjected to mechanical stimulation, an acid juice, the so-called gastric juice, is poured out, the act of secretion being accompanied by a reddening of the mucous membrane.

Evidence appears to be most conclusive in support of the view that the three kinds of epithelium-cells found in the stomach and its glands possess entirely separate functions. The epithelium-cells which line the interior of the stomach, and which, like those of the neck of both kinds of glands, are cylindrical in shape, appear to be mucusforming cells. The cubical cells which are found in the deeper parts of the pyloric glands appear functionally to be identical with the central cells of the glands of the fundus, both being engaged in forming the chief ferment of the gastric juice, viz., pepsin, whilst the ovoid cells of the glands of the fundus are the sole elaborators of the acid of the gastric juice. The glands which possess these acid-forming cells have of late been termed (Langley) oxyntic glands (o£w«tv, to rendeι - acid).

No accurate estimate can be formed of the amount of gastric juice secreted during twenty-four hours. It has been calculated to be between 20 and 30 pints.

Secretion of the gastric juice may occur after all the nerves going to the stomach have been divided, though it is for a time arrested after division of the pneumogastric nerves. It is probable that the process of gastric digestion is essentially under the control of an intrinsic nervous mechanism situated in the mucous membrane, though this is normally influenced by the higher nerve centres.

Liver and Secretion of Bile.— The structure of the liver has already been sufficiently described (vol. vii. p. 229 sq.), and need not be further alluded to in this place. The secretion of the liver, the bile, is being continually formed, though not always at the same rate. In animals possessed of a gall-bladder it is stored in the intervals of digestion in this reservoir. When food is taken into the stomach the bile begins to be secreted in larger quantities, the maximum being reached about six hours after the meal. As the so-called acid “chyme,” to be afterwards referred to, passes the opening of the bile-duct in the duodenum, it is probable that a stream of bile is poured upon it by the reflex contraction of the gall-bladder. During the time when bile is being secreted much heat is evolved in the liver. The bile, as will be shown in the sequel, should be looked upon as a liquid containing only certain, for the most part useless, by-products resulting from great chemical operations going on in the liver. Little is known as yet of the exact changes which occur in the liver-cells during activity, nor of the manner in which the nervous system influences the secretion of bile.

Pancreas and the Secretion of Pancreatic Juice.— The pancreas possesses a structure which presents great resemblance to that of serous salivary glands, and its alkaline secretion was until lately looked upon as closely resembling the saliva.

The secreting cells of the pancreas, which differ but little microscopically from those of such a salivary gland as the parotid, exhibit very marked differences, which correspond to different states of functional activity. During a period of glandular repose the cellscon-tain innumerable granules, which are congregated at that side of the cell which lies towards the centre of the acini(fig. 6, B). The outer or peripheral portion of the cells —the smaller part of the resting cell—is clear. After a period of glandular activity the granular half of each cell is found to have diminished greatly (fig. 6, A); the whole cell is clear and distinctly smaller than before, and its behaviour towards colouring matters is very different. The pancreas, when perfectly fresh and just removed from the yet warm body of an animal which is killed, does not contain, ready formed, all ferments which will in the sequel be referred to as characterizing the pancreatic juice. If we treat the gland, for instance, with glycerin, which possesses the power of extracting and dissolving all the ferments, we fail to obtain a solution which possesses the power of digesting ρroteids; but, instead, we find a substance in the solution from which, by the addition of a little acetic acid, the proteolytic ferment may be formed.

The cells of the pancreas thus elaborate a substance which is the antecedent of the proteolytic ferment, and which yields it when it passes into the pancreatic ducts; it is customary to speak of this body as zymogen or fermentformer, because it gives rise to one of the chief enzymes or ferments of the juice. The secretion of pancreatic fluid is slight except during digestion. After the taking of a full meal the secretion is suddenly exalted, reaching its maximum two or three hours afterwards. The secretion then diminishes until a period which extends from the fifth to the seventh hours, when a rise occurs, which lasts to between the ninth and eleventh hours after food. The secretion then gradually sinks, until it absolutely ceases. Stimulation of the gastric mucous membrane starts the secretion of pancreatic juice; it is arrested during nausea and vomiting, as also when the central end of the divided pneumogastric is stimulated.

Intestinal Glands and their Secretion.— The mucous membrane of both the small and the large intestine contains embedded in its substance innumerable simple tubular glands, the so-called crypts or glands of Lieberkühn, which are lined by a single layer of cylindrical epithelium continuous with and resembling that covering the exposed surface of the intestine. Very little is known as to the function of these glands, whose office is probably widely different in different sections of the intestinal tube, particularly in the large as distinguished from the small intestine. We do know that the epithelium-cells of these glands are capable of forming mucus, and that in the small intestine they are doubtless the source whence is derived the so-called intestinal juice or “succus entericus” which is poured into the intestine in large quantities under particular circumstances, as, for instance, when all the nerves supplying the gut are divided.

Physical and Chemical Properties of the Several Alimentary Juices.

The mixed saliva of man is, when perfectly fresh, a clear, transparent, viscid liquid, which, on microscopic examination, is found to contain cells of squamous epithelium derived from the mouth, besides certain globular cells derived from the salivary glands and called “salivary corpuscles.” Its reaction is alkaline; it has a specific gravity of about l ’ 003, and contains about five or six parts per thousand of solid matters. Its solid constituents consist (1) of certain saline matters transuded from the blood and, in addition, of a small quantity of a soluble sulphocyanide, detected by the reddish tinge caused by the addition of solution of ferric chloride to the saliva; (2) small quantities of soluble proteids, coagulable by heat; (3) mucin, to which saliva owes its viscidity, and which is thrown down when the liquid is acidulated with acetic acid; (4) a ferment or enzyme called ptyalin, salivary diastase, or the diastatic ferment of saliva. The last-mentioned is the most important constituent. It possesses the power of rapidly rendering cooked starch soluble, though its action on raw starch is but very slight. Not only does it dissolve starch, but it progressively decomposes the complex starch molecules into isomeric bodies of less complexity. Starch has a chemical composition which may be represented by the empirical formula (C 12 H 10 O 10 ) n , the exact value of n being yet a matter of doubt. The salivary diastase, under suitable conditions, as has been said, first converts insoluble into soluble starch (hence it is sometimes termed an amylolytic ferment) which, it has been surmised, probably has the composition (C 12 H 10 O 10 ) 10 . This soluble starch, like the insoluble body, gives a beautiful blue colour with iodine. By the further action of the ferment the soluble starch yields a series of dextrins which are isomeric with starch, though they possess smaller molecular weights and different reactions, and at the same time a sugar which, from its identity with that which is produced in the process of malting of barley, is called “maltose,” and which, though possessing many of the reactions of grape-sugar, is an isomer of cane-sugar; when crystallized it has the composition C 12 H 22 O n + H 2 O.

The changes which are brought about by the action of the salivary ferment on the starchy constituents of food are hastened by a temperature near that of the mammalian body. Boiling destroys the diastatic power, as also does the presence of strong acids or alkalies. A very feeble acid reaction does not absolutely stop the characteristic action.

Whilst the saliva of man and some few animals possesses the remarkable diastatic ferment just referred to, this is absent from the saliva of the majority of animals, so that we are forced to conclude that the saliva is an alimentary juice which subserves mechanical rather than essential chemical functions.

Gastric Juice.— This is a thin colourless or straw-coloured liquid of strongly acid reaction, and of a mawkish taste. Its specific gravity varies between 1 ’ 001 and l ’ 010, and it contains from ∣ to 1 per cent, of solid matters.

The gastric juice contains (1) free hydrochloric acid, (2) certain mineral matters, and (3) a ferment or enzyme called pepsin. It has been much disputed whether the gastric juice contains the hydrochloric acid in a free condition, but the question may be considered to have been settled in the affirmative by many facts, amongst which one of the most striking is that the gastric juice behaves towards certain organic colouring matters as only liquids do which contain free mineral acids. The pepsin, which has never been separated in a pure condition, is soluble in water, weak spirit, and glycerin, and confers upon all these solvents its characteristic property, viz., that of dissolving, in the presence of a dilute free acid, and at a suitable temperature, insoluble proteids, and of converting these into soluble and diffusible modifications termed peptones. Peptones differ from other albuminous or proteid bodies in their greater diffusibility, as well as in their much higher solubility in pure water. They are not coagulated by heat or by nitric acid, and are not thrown down by many mineral salts which precipitate other soluble proteids.

Gelatin under the same conditions is converted into an ungelatinizable modification, the so-called gelatin-peptone. Boiling destroys the activity of solutions of pepsin. If their reaction ceases to be acid, and, further, if the acid reaction be not due to a free acid, no action is exerted upon proteids. A temperature approximately the same as that of the mammalian body is that most favourable to gastric digestion. The accumulation of the products of gastric digestion, viz., peptones, hinders the continued activity of the juice. Pepsin, though probably containing nitrogen, is not a proteid body.

In addition to pepsin the gastric juice contains an entirely independent ferment which is called the “curdling ferment” or the “rennet ferment,” because of its power of rapidly inducing at the temperature of the body the coagulation of the casein of milk, which it converts into cheese. Unlike pepsin, this ferment will act in solutions which contain no trace of free acid.

The following table (Hermann) shows the average composition of the gastric juice of man, the dog, and the sheep. [table]

Bile.— Bile is a bitter liquid of golden-red colour in man and carnivorous animals, but green in herbivorous animals. It is commonly viscid owing to admixture with mucus derived from the walls of the gall-bladder and hepatic ducts. Its reaction is neutral or faintly alkaline. It contains about 14 per cent, of solid constituents. (1) It includes the sodium salts of certain so-called bile-acids, which in man are glycocholic and taurocholic acids. The former has the formula C 26 H 43 NO 6 , and is readily decomposed into glycin, C 2 H 5 NO 2 , and an acid termed cholic acid, C 24 H 40 O 5 ; the latter has the formula C 9t3 H 4 -NSO 7 , and can be split up into a base called taurin, C 2 H 7 NSO 3 , and into cholic acid. (2) It contains bile-colouring matters, of which the chief is a red one termed bilirubin, C 16 H 18 N 2 O 3 , with which is closely connected the green colouring matter of the bile of herbivores, termed biliviridin, C 16 H 18 N 2 O 4 ; bilirubin is unquestionably derived from the decomposition of the blood-colouring matter or haemoglobin. (3) It has fats, and a body called cholesterin, which belongs to the class of alcohols and has the composition C 90 H 44 O + H 2 O. (4) It includes saline matters which are rich in sodium salts. Whilst the bile-acids and the bile-colouring matters are formed in the liver itself, the cholesterin of the bile is probably derived entirely from the blood, which obtains it from the nervous organs, in the white matter of which it is abundantly present.

The proportion of the constituents of the bile present in this liquid is shown by the following analyses. [table]

The amount of bile secreted by man has been estimated at from about 136 grains to about 309 grains per kilogramme (2 ’ 20 lb) of body-weight; but in certain cases, through abnormal circumstances, the total amount of bile secreted in twenty-four hours has been found to be less than this, viz., to vary between about 16 and 21 oz.

The action of the bile in digestion, it must be admitted, seems trifling and out of proportion to the size of the gland and the amount of the secretion. It is a weak solvent for fats; it has the power of emulsifying fats, especially, perhaps, when added to the pancreatic juice; and it may help the passage of fat through animal membranes. At least it is certain that, when filter-paper is wetted with bile, oils filter through it more readily than when it is wetted with water. The most important use of the bile is, however, as an adjuvant to pancreatic digestion. The pancreatic juice, as will be stated more particularly below, contains a ferment which is either a proteid body or inseparably connected with a proteid body. Strangely, though this ferment possesses the power of dissolving proteids under suitable circumstances, in the presence of pepsin and any free acid it is itself destroyed. It would then be acted upon by the pepsin passing into the duodenum from the stomach if the conditions were favourable. To prevent this untoward accident the alkaline bile is poured over the acid contents of the stomach as they pass the duodenum; these are neutralized, and a precipitate is thrown down which mechanically entangles the pepsin that may be in the mixture. Although the definable uses of the bile are small, the part which it plays in the economy is of essential importance. Animals whose bile is allowed to escape externally soon grow lean and ill-conditioned. The fat which should be absorbed in the alimentary canal remains in part in the faeces, which acquire a peculiar putrescent odour.

Pancreatic Juice.— If we except the gastric juice, the chemical action exerted by the pancreatic juice is the most potent and useful of any of the digestive secretions.

When freshly secreted and perfectly normal, the pancreatic juice is a clear viscid liquid of strongly alkaline reaction and highly coagulable by heat. Its solid constituents may reach the proportion of 10 per cent.

It contains (1) water, (2) various albuminous bodies which cause the liquid to be coagulable by heat, and of which one is intimately connected, or indeed perhaps identical, with the ferment trypsin, (3) a number of ferments, (4) traces of products of digestion, as leucin and tyrosin, (5) salts. The ferments of the pancreatic juice are the following :—(1) a proteolytic ferment termed trypsin, (2) a diastatic ferment, (3) a ferment which acts on fats, (4) a curdling ferment (?).

The first-named ferment, unlike pepsin, which is quite inactive under this condition, acts most energetically in solutions which contain a free alkali or an alkaline carbonate, although it possesses some action when the reaction is neutral or even faintly acid. Like pepsin, trypsin dissolves insoluble proteids and converts them into peptones; it possesses, however, an activity which surpasses that of pepsin, inasmuch as it splits up certain of the peptones formed into simpler bodies, such as leucin, C 6 H 13 NO o , and tyrosin, C 9 H 11 NO 3 , the former of which is an organic body allied to the fatty acid group, and the latter to the aromatic group. According to the views of Kühne, the molecule of an albuminous or proteid body is capable of being broken up under the influences of such ferments as pepsin and trypsin into the allied bodies of smaller molecular weight, the peptones, which, though possessing general and common reactions, may by their behaviour towards certain chemical agents as well as towards ferments be subdivided into two groups, a Aeww-group and an αn∕i-group. Kühne believes that both pepsin and. trypsin decompose the proteids with the production of so-called hemi-peptones and anti-peptones, and that, whilst neither pepsin nor trypsin can further decompose anti-peptones, trypsin possesses the power of splitting up hemi-peptones into simpler bodies.

The amylolytic or diastatic ferment of the pancreatic juice resembles that of the saliva in its action. Whilst the saliva of most animals contains no such ferment, the pancreatic juice of all animals is very rich in diastatic ferment, so that the action of the pancreatic juice on starch is much greater than that of saliva.

The fat-decomposing ferment—sometimes, though erroneously, called the “emulsifying ferment ”—of the pancreas is present in exceedingly small quantity and is very readily destroyed, so that its existence has sometimes, though erroneously, been denied. It breaks up the neutral fats in part into their respective fatty acids and glycerin. This slight acidification unquestionably facilitates the formation of an emulsion of the remaining fats.

All these ferments are influenced by temperature in nearly the same manner as the ferments of saliva and gastric juice. Boiling destroys them absolutely, cold retards their activity, the body temperature is very favourable to them. The most suitable medium for them is the alkaline juice in which they occur, and the alkalinity of which is due to sodium carbonate.

The following is an analysis of the pancreatic juice of the dog :— [table]

Intestinal Juice.— This juice, which is also called not unfrequently by its Latin name succus entericus, is a thin, yellowish, alkaline, albuminous liquid of specific gravity l , 01, concerning which we possess very little certain information. It has been said to act upon fibrin alone of the albuminous bodies; it not only contains a small quantity of a diastatic ferment but probably also a so-called inverting ferment, possessing the power of converting cane-sugar into grape-sugar.

Fate of Food-Stuffs in the Alimentary Canal.— The food which is introduced into the mouth is an exceedingly complex substance. Leaving out of account those substances which are insoluble and incapable of absorption, and which are also not amenable to the influences of the digestive juices, we may classify the true food-stuffs as follows.

(1) Albuminous matters, including (a) the true proteids, such as albumen of egg, casein of milk, myosin of muscle, fibrin of blood, &c., and (⅛) the albuminoid bodies, such as gelatin from tendons and bones, chondrin from cartilages, and elastin from various elastic structures; (2) hydrocarbons or fats, of which those chiefly used for food are stearin, olein, and palmitin; (3) carbohydrates ; (4) the various inorganic salts ; (5) water. The third group includes the amyloids or starch-like bodies, the saccharoses like cane-sugar, the glucoses like the grape-sugar and fruit-sugar found in honey and in ripe fruits, the sugar of milk, &c. In addition to these may be mentioned allied bodies, cellulose, pectin, arabin, mucilage, &c., which in some animals, or in some conditions, are certainly digestible. In a subdivision of the same group we may place the various vegetable acids, lactic, acetic, citric, malic, &c., which are essentially foods.

It may be premised that the fate which befalls a given example of ingested food does not depend solely upon the theoretical power of the digestive juices to act upon it. Thus digestible food may be imperfectly digested owing to being passed into the stomach in lumps and masses, which the juices cannot permeate and the stomach' cannot crush; or starch may be so incorporated and encapsuled with fat that the saliva and even the pancreatic juice may fail to reach it ; or digestion from one cause or another may be so prolonged that fermentative changes, to which most samples of food are inevitably liable from containing organized ferments or “germs/’ may have time to begin and to alter materially the sequence of events. Hence we shall feel no surprise that much food escapes altogether the action of digestion. The most perfect and economical feeding is that in which the least quantity of food is passed through the alimentary canal unchanged. When, however, the just quantity is taken, and the digestive organs are sound, the following is the order of the changes which occur.

Food placed in the mouth at once excites the flow of mixed saliva and mucus. Solid food is broken up, rubbed together with the juices of the mouth and entangled air-bubbles, and rolled into a slimy bolus. Soluble constituents of it thus have an opportunity of becoming dissolved at once; sugar, dextrin, vegetable acids, and many inorganic salts would, in part at least, pass into solution in the mixed saliva. The process of mastication, besides triturating the food and mixing it with the alkaline saliva, permits it to become raised nearly to the body-temperature, in which condition the dextrin and the starches readily fall a prey to the ptyalin, and begin to be converted into dextrins and maltose. This change is very rapidly effected —it begins instantly if the starch is already boiled; so that, unless the food is “bolted,” a considerable quantity of soluble dextrin and sugar is formed before the bolus is swallowed. The act of deglutition passes the softened bolus into the stomach, where already a certain quantity of acid gastric juice is ready to receive it. The presence of food in the stomach is a greater stimulus to the gastric flow than its presence in the mouth: the juice is more rapidly secreted, but still it is comparatively poor in pepsin and still more so in free acid; but after a time, as more food is added, and as the first-coming food begins to be dissolved and absorbed, the proportion of pepsin is increased. The movements of the stomach mix intimately the acid juice and the alkaline food; the first effect of this is a neutralization of the mass, but, as the secretion of juice goes on for some time after the last portion of an ordinary meal has been swallowed, the mass becomes more and more acid. The amylolytic action of the swallowed saliva is gradually checked, and the still unchanged starch remains unchanged so long as it lingers in the stomach.

Such saline and other dissolved matters as are still soluble in slightly acid solutions remain dissolved, and, with the water which is swallowed, may pass at once into the blood-vessels by absorption. Other salts, as the carbonates and phosphates of the alkaline earths, become dissolved in the presence of an acid. The gelatigenous tissues—connective tissue holding together in its meshes fibres of muscle, globules of fat, strands of nerve, Ac.—are dissolved. The skins or pellicles of the fat-vesicles suffer the same fate. The elastic sarcolemma is now thought to be similarly affected. As a consequence the proteid and fatty portions of the organs referred to escape and fall into smaller fragments. Muscular fibres readily split into fibrillae and disks, and are then in the very best physical condition for the free play of the gastric juice. The fat escapes, flows together to form larger globules, but is otherwise unchanged. Cane-sugar, which is of no use to the organism until it is converted into maltose or glucose, finds in some slight degree the condition for this conversion in the combined action of the gastric juice and the gastric mucus, although we are still in great doubt as to where the greatest conversion takes place. The all-important change which the food undergoes in the stomach is, however, the change of its proteid element into the more diffusible form of peptones, about which it will be enough to say that it is not a mere solution of proteid in a dilute acid, although this may be the first step in the operation, but probably a decomposition of the original proteid molecule. The obvious effect of gastric digestion is to reduce the food to a grey pulpy mass called chyme, in which condition it passes into the duodenum along with more refractory or less perfectly digested portions of food such as may still remain in the stomach at the end of the normal period of gastric digestion.

The presence of food in the stomach, as has been remarked, is of itself a stimulus to the secretion of bile and pancreatic fluid; by the time, therefore, that the chyme passes into the duodenum, a considerable quantity of the fresh juices is prepared for it. Not only so; the contact of the acid chyme with the duodenal membrane at once brings on a reflex contraction of the ducts and gall-bladder of the liver, by which a sharp stream of alkaline fluid is at once poured out, wherewith the chyme is drenched. So far as the mixture is made perfect and the point of neutralization is reached, a precipitate of parapeptones and peptones is formed, carrying down with it the active pepsin. But the acidity of the chyme is not at once overcome; not until the middle of the small intestine is reached does the acid reaction entirely disappear; and we may therefore assume that a kind of exotic gastric digestion may go on in the parts of chyme which still remain acid. But whenever the reaction ceases to be strongly acid the pancreatic juice takes up the work of digestion. Proteids are changed into soluble peptones, and the conversion of starch into dextrin and maltose begins again with redoubled vigour. Fats are seized upon, resolved into glycerin and their fatty acids, and emulsified both by bile and by pancreatic fluid. The resulting fatty acids combine with the alkalies of the mass to form soaps, which in turn aid the process of emulsification. The chyme, which, from being grey, became of a golden-orange colour when saturated with bile, acquires a decidedly cream-like appearance from the emulsion that is formed.

It is still an interesting question whether pancreatic proteolysis ever, in health, goes beyond the formation of peptones, as it may certainly do in artificial digestion in the laboratory. Some leucin and tyrosin undoubtedly appear in the small intestine; but, inasmuch as they are bodies which, if formed, would be rapidly absorbed, it is impossible to say whether any considerable amount of proteid matter sutlers this fate, or whether leucin and tyrosin are formed, as it were, accidentally, from the too long staying of an excess of proteid in the alimentary canal. Leucin and tyrosin are never found in the faeces.

As the remnant of food passes down the intestine, changes allied to putrefaction invariably occur. Lactic acid is always to be detected in the small intestine, and the amount of it increases as the ileo-caecal valve is approached. Possibly the butyric acid fermentation likewise occurs as a constant, if not an essential, phenomenon of intestinal digestion. At least the gases of the small intestine always contain a small amount of hydrogen; but if we are to gauge the butyric acid fermentation by the amount of hydrogen detected, we must assume it to be of very small proportions. We are so ignorant of the nature of the enteric or intestinal juice that we need not here speculate as to the changes in the remnant of food which the addition of it may bring about. Let it suffice to say that the intestinal contents pass through the ileo-caecal valve with none of the odour and little of the appearance of faecal matter. While in the large intestine they become reduced in bulk, and approach a solid consistency by the abstraction of water from them. Their reaction becomes distinctly acid once more; but now, from inward processes of putrefaction and fermentation which were started already in the small intestine, putrefactive gases may arise, light carburetted hydrogen, carbonic acid, sulphuretted hydrogen, nitrogen, and hydrogen. The faeces themselves are commonly acid; besides the indigestible parts of food, such as horny matter and cellulose (the denser sorts at least), and the undigested but digestible overplus of starch, proteid, &c., they contain derivatives from the bile which cause the characteristic colour, and some final decomposition products of elements of food, such as indol.

II.— Absorption of Nutritive Matters into the Blood.

The complex processes of digestion result in the conversion of insoluble and indiffusible food-stuffs into soluble and diffusible sugars and peptones. These, with the soluble saline matters, the finely-divided or emulsified fats and water, are (if we except the small quantity of soaps formed in the course of pancreatic digestion, and the small amount of soluble leucin and tyrosin evolved in the same process) the only contents of the alimentary canal capable of entering the organism from the outer world. They are not indeed the only soluble and absorbable bodies in the intestine; a large part of the digestive juices themselves are reabsorbed, and may possibly do duty over again in their respective secretions. But these are not foods. How, it may now be asked, do these soluble or finely-divided substances pass the confines of the body? F rom what has already been said about the organs of digestion it will be evident that, from the stomach downwards, the alimentary cavity is separated from an infinite number of thin-walled vessels by a delicate layer of columnar epithelium and a filmy basement membrane. There seems at first sight to be no difficulty in understanding how water and dissolved and diffusible matters may pass these barriers with the greatest readiness by physical processes of diffusion which are so simply imitated in the laboratory. We know also that, in fact, solutions do with the greatest ease and rapidity pass through such a membrane as the conjunctiva, by the readiness with which the pupil may be dilated on putting a drop of atropinized fluid beneath the eyelid. But it is by no means clear that the process is so simple in the living intestine. A fresh specimen of epithelium scraped from the interior of the mouth of a pig may be bathed in a solution of colouring matter and yet admit no trace of the colour into the substance of its cells so long as they remain alive. It is only when they cease to be living protoplasm that the physical processes of diffusion come into play and that the cell-substance takes up the colour. Guided by this simple observation we shall hesitate to assume, because we have water containing soluble sugars, salts, and peptones on one side of the epithelium of the alimentary tract, while on the other we have fluids differently constituted, that therefore we must needs have a process of transfusion tending to the passage of the dissolved substances from one side to the other. This “absorption” of matters, even simple saline solutions, at the surface of the intestine may be, and most probably is, a vital operation. Be the nature of the process what it may, it is easy to conceive how fluids at least arrive at the interior of the blood and the lymph capillaries of the alimentary mucous membranes. The case of the particles of emulsified fat presents more difficulty; but even here there are only two possibilities open to us. Either the fine globules pass through the columnar cells, or they pass between them; if they pass through them they must traverse the thick striated inelastic end of the cells in a manner λvhich it is somewhat difficult for us to picture; if they only pass between the cells it is difficult to explain why so many of the acutest observers have described the occurrence of fat-particles within the epithelial cells of recent preparations of intestinal mucous membranes.

Once through the epithelial layer the absorbed matters pass into the blood-vessels or the lymphatics in some way the details of which are as yet mere matters of speculation, The axial lymphatic vessels of the villi—the so-called lacteal radicles—have a special interest, since villi are pre-eminently the absorbent rootlets of the body. As soon as they become filled, the layer of muscular fibres investing them contracts and empties the contents of the lacteal towards the deeper vessels of the mucosa. The subsequent expansion of the radicle will evidently favour the refilling of it.

It is very disputable where absorption takes place. The filtrate obtained from the contents of the stomach yields very little peptones, the inference being that much has already become absorbed by the gastric capillaries, haemic or lymphatic. There seems to be no reason why water, salines, and dissolved sugars should not also be taken up at the same place. In the large intestine water at least is absorbed, for the contents become drier as they pass along the bowel. But it is the small intestine chiefly which is the scene of most extensive absorption of digested products; here fats are demonstrably taken into the organism; and here, doubtless, more than elsewhere, peptones, sugars, and other soluble bodies suffer the same fate.

Blood-vessels and lymph-vessels are both sharers of the work, though to what extent each is employed is a matter of surmise rather than of observation. The lacteals certainly absorb the largest part of the fat, though, as the relative amount of fat in the portal vein increases after a meal, fat must also be absorbed by the blood-capillaries, The material absorbed into the portal vein is at once submitted to the smaller circulation of the liver and the activity of the liver-cells; that absorbed into the lacteals traverses many lymphatic glands before it reaches the thoracic duct and the general circulation at the root of the neck. Thus in both ways of absorption the raw material is immediately passed into certain organs before it reaches the common stock of blood. That changes are effected in the constitution of the just-received food-stuffs during their stay in these organs there is every reason to believe; for, on the one hand, the blood issuing from the liver in the hepatic veins differs from the blood entering it by the portal vein; and, on the other, the contents of the thoracic duct differ from the contents of vessels nearer the absorbent radicles, as, for example, the contents of the mesenteric lacteals. The nature of these changes must be discussed in the next section.

III.— Chemical Processes in the Tissues and Organs of the Body.

While it is probable that the liver modifies the recently-digested raw material of food before it reaches the common stock of the blood, it is quite unknown what (or, indeed, if any) difference exists between the action of the liver on blood laden with raw material immediately after a meal and its action on blood traversing its capillaries during a fast. Does the liver exert an action on recently-imported fat, peptones, and sugar in any sense different from the action it exerts on fatty, albuminous, and sugary matters as they exist in the common stock of blood? Or—which is the same question—do the fats, albuminous matters, and sugars of the portal blood differ at all from the fats, albuminous matters, and sugars of ordinary blood? While this question remains unanswered it will be well to consider the liver as like any other tissue drawing on the common source of nutriment, the blood, for its own particular purposes, and not as an organ akin to the special digestive organs, devoted to the elaboration of food for the benefit of the other tissues.

It need not be so, however, with the lymphatic structures with which the chyle of the lacteals comes into contact before it is poured into the blood. Chyle from the thoracic duct at its entrance into the veins is of course mixed with the general lymph of the body,—the juice of the tissues which is collected in the lymph-vessels and carried back to the blood. It is a milky fluid which coagulates on standing, the clot of which after some time becomes tinted red at the surface from the presence of immature red corpuscles. The coagulum consists of fibrin resembling that of the blood. Other constituents of chyle are white corpuscles, oil-globules coated with albuminous matter, i.e., emulsified, and exceedingly fine fatty granules usually spoken of as the “molecular basis of chyle.” Chyle obtained from vessels nearer the intestines has very little fibrin, very few white corpuscles, and no red corpuscles. It is probable, therefore, that the raw matters of digested food are undergoing a process of manufacture into blood during their passage through the lymphatic glands to reach the thoracic duct.

When once they arrive at the blood, the imported materials of food are lost beyond our power to follow them individually. The question now becomes one of the interchanges between the blood generally and the tissues. That such an interchange occurs there can be no doubt; for if all food be withheld from an animal the tissues rapidly grow less in quantity, while the blood maintains a fairly constant composition. If such an animal be fed, the tissues regain their former weight, and may even store up an overplus of matters, while again the blood remains of approximately constant composition. The tissues can both take away from the blood and give to the blood such matters as are necessary. But the matters taken from the blood are not in the same form as the matters given up to the blood. When blood is made to circulate through living tissues of whatever kind the blood entering the tissue always has a different composition from the blood which leaves it. The tissues, therefore, are laboratories in which materials abstracted from the blood are transformed. To these chemical operations of transformation which occur in living tissues the term “metabolic” has been applied, a term first used by Schwann, and happily reintroduced by Michael Foster.

What now becomes of the products of the metabolic activity of the tissues? We have hitherto considered the tissues as taking matter from the blood, changing the form of it, and giving it back to the blood; but this is far from being the true account of the process. It does indeed represent all that we know of the metabolism of many tissues. In muscle, for example, matters are drawn from the blood, converted to other shapes within the tissue, and sooner or later cast out into the blood-current again. The same may be said of nerve-tissue and possibly of some other tissues. In secreting glands the case is different. Some only of the products of tissue-metabolism are returned to the blood; others are poured into the ducts of the glands as the glandular secretion, and so leave the body altogether. This happens, for example, in the digestive glands, the milk-glands, and the kidneys. In a third order of tissues the case is different again, for here some of the products of metabolism may be retained in the tissue for an indefinite time. This occurs in certain tissues which have been called storage tissues, and of which fat is a typical example. Lastly, the liver is a complex organ whose metabolic products are disposed of in all three ways,—part being cast at once into the blood, part being accumulated in the tissue itself as glycogen and passing into the blood at intervals as the body needs it, and a third part being poured into the biliary ducts in order that it may escape into the intestine. It will be well, therefore, to recognize three methods of the disposal of metabolic products, and to classify the tissues accordingly.

Metabolism of Muscular Tissue.— To arrive at a knowledge of the chemico-vital changes occurring in any tissue we must compare the matters entering the tissue with the matters issuing from it. It is only from such a comparison that we can infer the changes which go on within the tissue. In the case of muscle there is yet another method by which we can obtain inferences as to the nature of the metabolic changes. We have reason to believe that the tissue-changes of active muscles are simply the exaggerated form of changes which constantly occur. If we may assume this, a comparison of the chemical composition of muscle before and after a period of activity will help us to a knowledge of the changes that occur in muscular action, and, by implication, a knowledge also of the common metabolic changes of the tissue. Now a comparison of muscle before and after action shows that during activity the quantity of CO 2 becomes very largely increased; at the same time the muscle becomes of acid reaction from the development of lactic acid; the amount of bodies soluble in water decreases, while the amount of bodies soluble in alcohol increases; the amount of glycogen decreases, while that of sugar increases; and, finally, bodies develop which have a strong affinity for oxygen. If we compare the matters entering and issuing from muscular tissue we shall find that muscle gives up much CO 2 during activity, that the issuing blood is rich in reducing substances, and that it acquires sarcolactic acid. The circumstance of most importance in this comparison is that carbon dioxide is liberated in large amount without the immediate interaction of oxygen; the CO 2 is produced from some body in the muscle which already contains within itself the O necessary for its formation. The fact of next important^ is the absence of all indications of a large expenditure of nitrogen. Relying on these discoveries, physiologists have supposed that the metabolic changes of muscle follow some such course as the following. Non-nitrogenous organic material, along with oxygen, is absorbed into the tissue from the blood. In the tissue-cells it is elaborated with nitrogenous matter already in the tissue into a complex body called inogene substance, containing a nitrogenous factor linked to carbon, hydrogen, and oxygen. During the life of the tissue, and to a much greater extent during muscular activity, this inogene substance is split up into a nitrogenous portion and a non-nitrogenous portion, of which the former is retained in the tissue to be again worked up into inogene substance, while the latter is resolved into more stable bodies which escape. The full number of the effete bodies is not at present known to us; it doubtless includes more than carbon dioxide and sarcolactic acid, but these are the only bodies whose existence has been definitely determined.

Metabolism of Glandular Organs.— Of late years very much light has been shed on the processes of glandular cells, but it has been chiefly on their anatomical aspect. We know very little, indeed, of the nature of the chemical changes going on within the glandular cells, because, although we can ascertain approximately the composition of those products of the changes which escape into the glandular duct, we as yet know so little of those products which escape into the blood. We know, however, that mucin is capable of being formed in the interior of epithelial cells out of some non-mucous antecedent. We also have some reason for supposing that the gastric glandular cells—the border-cells—select phosphate of sodium and sodium chloride from the blood, and these bodies have been shown to be capable of interacting in such a way as to yield free hydrochloric acid. In the secretion of milk it is tolerably certain that the fat and the casein are both formed out of proteid matter within the glandular cells. Even the milk-sugar has been thought to be elaborated out of some non-saccharine substance, or even out of some substance that is not a carbohydrate. In the case of the pancreas we know nothing of the actual chemical decompositions that occur, but we do know that they occur in two well-marked stages. In the first a body is formed which is stored in the gland-cells, as the inogene substance is supposed to be stored in muscle; in the second this body is resolved into other but still complex bodies, of which the trypsin ferment of the secretion is one. Among the glandular organs we may mention the kidney, respecting whose secretive activity it is far from certain that it entirely consists of physical filtration or powers of mere selection. No doubt many of the constituents of urine are simply filtered off from the blood, while others are undoubtedly abstracted owing to some peculiar attraction which the renal cells exert upon them. But there is some reason to think that others may be formed within the kidney-tissues as products of cell-metabolism. As yet we have no definite knowledge concerning the nature of the metabolic changes.

Metabolism in the Storage Tissues.— Of these the first that we shall describe is adipose tissue or fat. Fat appears to be accumulated in ordinary connective-tissue corpuscles. What metabolic changes occur in connective-tissue corpuscles which are not accumulating fat we do not know; but under certain conditions of overfeeding the metabolism is so varied that fat is deposited within the cell. At first it appears in the form of fine granules; these soon coalesce to globules, which afterwards enlarge by the confluence of granules subsequently formed. The exact changes of which this fat is the outcome, or one of the products, are entirely obscure. It is enough if we can establish the probability that fat may be derived from the proteid protoplasmic matter of the fat-cell. We are not here guided, as in the case of muscle, by analysis of the blood approaching the adipose tissue and the blood leaving it. Nevertheless, there is little doubt that fat may be derived from the proteid elements of food through the activity of living tissue-cells. That proteid matter readily lends itself to a decomposition of which fat is one product is seen in the formation of fat-like “adipocere” in the nitrogenous tissues of dead bodies which have been for some time buried or immersed in water; and it is likewise seen in the process of “ripening” in cheese, in which the fat increases while the albuminous matter diminishes. But in addition to these general facts, suggestive though they are, there are not wanting proofs of a more particular kind that fat may result from proteid decompositions. If dogs are fed on starch and fat with no proteid food at all, the carbon stored up in the body can all be accounted for by reference to the fat of the food and the proteid matter of the body which, in the state of starvation, came to be disintegrated. In many other cases it seems clear that the fat stored up by animals during fattening unquestionably comes in part from the nitrogenous matters of food. But a consideration of the relative amount of carbon and nitrogen contained in proteids and in urea, which is the final product of the oxidation of proteid matter, would alone lead us strongly to suspect such an origin of fat. If all its nitrogen reappeared in the form of urea, 300 grains of proteid would give rise to 100 grains of urea. But 100 grains of urea contain but 20 grains of carbon, whereas 300 grains of proteid matter yield 159 grains of carbon. What has become of the deficit of carbon Ί If it has not been burnt off as carbon dioxide, it must remain within the body in Some non-nitrogenous form.

If fat may be derived from proteids in the body, it is now equally certain that in some animals at least fat may come from carbohydrates of the food. Lawes and Gilbert have conclusively shown that as much as 40 per cent, of the stored-up fat in well-fattened pigs could not possibly have come from the nitrogenous parts of the food, and that it must have been derived from the carbohydrates.

All these facts render it very probable that the fat-forming tissues pick out from the blood albuminous or non-nitrogenous matter, transform it, retain the fatty element and discharge the rest. But it must not be forgotten that fat of food may, on finding itself in the blood, be taken up by appropriate tissue-cells and stored up without undergoing further change. Even this, although it seems so probable, may not at once be assumed to occur in such a simple manner. It is true that, if an animal be fed on fat resembling the fat of its own tissues, it might be assumed that the fat which it stores is simply absorbed by the tissue-corpuscles as an amoeba absorbs its food. But if this were really the manner of the process we should expect that allied fats substituted for the natural fat would be equally well taken up and stored, This, however, is not at all the case. Dogs fed on a mixture of palmitin and olein, but no stearin, are found on analysis to have stearin in their body-fat; just as dogs fed on palmitin and stearin, but no olein, are found to have an abundance of olein stored up. And, even when fed on spermaceti, a dog was found to present mere traces of it in the fat accumulated in its tissues during the experiment. In short, all facts go to show that the accumulation of fat does not take place without some display of formative or transformative energy.

The last tissue whose metabolism we shall discuss is the hepatic tissue of the liver. Hitherto we have considered the liver as a digestive gland secreting the bile for the purposes of digestion; but the liver has other functions which overshadow entirely its function as a digestive organ. It seems to have the power of accumulating amyloid material very much as adipose tissue accumulates fat, It would probably be a mistake to regard these two functions of the liver as altogether independent of one another, although it is necessary to state that a direct dependence has not yet been established, There can, however, be little doubt that the hepatic tissue draws to itself a variety of matters from the blood flowing into it by the portal vein and hepatic artery, and elaborates these constituents into various products, some of which escape into the blood again, others of which appear as the bile, while a third order remain in store within the substance of the liver. But, although these products are probably associated more or less intimately in their origin, they have, in the natural development of physiology, been studied independently of one another for the most part,

If an animal be richly fed on starchy or saccharine food it is found, within a short time of the digestion of the food, that the liver contains a large quantity of a starchy body called glycogen (C 6 H 10 O 3 ) n . In order to obtain glycogen from liver-substance it is necessary to make use of the tissue of an animal just killed, for the starchy body undergoes an extremely rapid post-mortem conversion into a sugar. Liver taken quickly from the still warm body of a rabbit is rapidly divided into small pieces and plunged at once into briskly boiling water. The high temperature prevents the post-mortem change and leaves the glycogen in a condition to be separated. The pieces of liver may then be pounded with sand and water, and the mixture acidulated and filtered. From the filtrate the glycogen may be precipitated by alcohol, and the precipitate may be purified by boiling in caustic potash and afterwards neutralizing and reprecipitating with alcohol. Or the albuminous matters may be thrown down by a solution of mercuric iodide in iodide of potassium before precipitating the glycogen with alcohol. Glycogen so prepared is a white amorphous powder resembling starch in chemical composition; it is colourless and tasteless. Its aqueous solution is milky, and generally opalescent.

Other tissues and organs besides the liver have been found to contain glycogen. For example, muscles contain some glycogen, which diminishes during muscular activity, while it has been detected in the tissues of embryos and of young animals, as well as in newly-formed pathological growths.

There can be little doubt that glycogen is manufactured mainly out of carbohydrates conveyed to it in the portal vein. If a rabbit be starved for some days, the whole of the glycogen disappears from the liver; but the store is at once, in the course of a few hours, replenished if starch or sugar of whatever sort (cane, grape, or milk) be introduced into the alimentary canal, The metabolic powers of the liver-cells in respect of glycogen-production are not, however, limited to starches or sugars. If glycerin be injected into the intestines the amount of glycogen in the liver is at once increased. But some preparation of the glycerin is necessary before the liver-cells are able to appropriate it; and this preparation is accomplished in the true digestive organs, since glycerin introduced into the blood by subcutaneous injection does not bring about any increase in the glycogen of the liver. Even albuminous bodies, such as fibrin and albumin, freed from all trace of amyloid matter, seem in the case of carnivorous animals to yield glycogen in the laboratory of the hepatic tissue. The same may be said of gelatin. Now it is easy to form a chemical conception of the manner in which such a body as grape-sugar leads to the storing of glycogen, for the dehydration of the sugar would be all the change required for the conversion. But we can at present form no picture of the operation in the case of glycerin and of the albuminous matters; and the fact that these substances also are amenable to the livercells should make us hesitate to assume at once that in the case of sugar the process is the simple one of dehydration, We must wait for further light to be shed upon the interdependence of what we may for the moment call the biliary metabolism and the glycogenic metabolism of liver - cell before we speculate as to the exact nature of the changes.

The liver has, beyond a doubt, the faculty of manufacturing an amyloid body out of various raw matters brought within the range of its activity, and of storing it up for future use. The use to which it is put has been the subject of much speculation and experimental inquiry. The amyloid matter when drawn upon may leave the liver in the form in which it exists there, or it may be converted into some other modification and afterwards transferred to the blood. The fact that other tissues besides the liver contain glycogen and the fact that some, as muscle, seem to make use of glycogen in the act of contraction, have been thought to s⅛ιpport the hypothesis that the glycogen is conveyed by the blood to their tissues and then consumed. According to this theory the hepatic metabolism ends in the production of glycogen, which merely waits to be cast out into the blood-current at the call of the body generally. Against this hypothesis, as a complete explanation of the use of liver-glycogen, it may be urged that the glycogen of muscle at least disappears on starvation long before the store of glycogen in the liver has been used up. Moreover, the glycogen of muscle is by no means invariably present, and is certainly not indispensable to the activity of the tissue. λVe may therefore conclude that the use of glycogen by the tissues (when we judge of it by the case of muscle) is not constant enough or important enough to account for the large store of glycogen in the liver. But, if the hepatic glycogen does not leave the liver as such, it must undergo some other change in the liver; and the circumstance above referred to, that glycogen so readily becomes converted into sugar post mortem, at once leads us to inquire whether a similar conversion is not normally effected during life. The inquiry becomes of especial value when we remember that the blood contains a constant proportion of sugar in its composition, which argues such a constancy of supply as could not be due to the direct importation of sugar during the irregular periods of the daily meals. As the amount of sugar in the blood is constant, the periodic introduction of carbohydrate into the organism must be followed by some temporary storing of it in some organ from which it may be constantly, and without intermission, doled out. Now the body contains in many parts the means of the conversion of starches into sugar. The salivary or pancreatic juices with the utmost readiness at the body-temperature change glycogen into a sugar. Many tissues, as well as blood, are said to effect the same conversion, although it is denied that the blood does so unless the bloodcorpuscles have been first destroyed. The liver itself, as we have already seen, may bring about the same change, at least after death; but the activity of the converting substance may be prevented by subjecting it to a temperature of boiling water. If the liver contain the ferment-like body during life, unless its activity be restrained in some way or other, the glycogen λvhich is formed in the liver will be speedily changed into sugar. In regard to the existence of this starch-converting body it is significant that, while it certainly may arise in the blood when the blood-corpuscles are destroyed, the liver is known to be the seat of an extensive destruction of blood-corpuscles. Considerations of this sort, however, are of little cogency; it would be a strong presumption of the existence of the ferment in question if sugar could be proved to be normally present in the hepatic tissue during life, but the experimental proof of this is beset by great difficulties, and discordant results have been obtained by the different observers. Claude Bernard, to whose researches we owe so much of our knowledge on this interesting question, detected small but perceptible quantities of sugar in quite fresh liver-substa nee; but other observers, among whom Dr Pavy is to be reckoned the first, have failed to find even a trace. Further, Bernard was able to make out a decided difference between the amount of sugar contained in the portal vein and the hepatic vein respectively when there was no starch or sugar in the food to load the portal vein. In such circumstances the blood issuing from the liver by the hepatic vein was found to contain a small quantity of sugar in excess of the blood entering the portal vessels. The most accurate and reliable investigations have, however, conclusively proved that this difference does not exist. The matter, therefore, still awaits some crucial test not yet devised. In the meantime we may accept the hypothesis of a conversion of liver-glycogen into soluble sugar as one which, however probable, is not supported by sufficient evidence. Amongst those who have rejected this hypothesis some have had recourse to qjher assumptions to account for the fate of glycogen in the body; and it has been suggested that glycogen undergoes conversion into fat either in the liver itself or partly there and partly in some other tissue. This suggestion has little direct evidence to support it. It is true that animals, especially the pig, have the poλver of storing up fat in their bodies which they cannot have obtained otherwise than from the carbohydraceous constituents of their food. It is also true that the hepatic tissue is often found to contain fat in considerable quantities. But it is easy to see how these facts admit of simple explanation without assuming a conversion of glycogen into fat within the liver-cells. The chemical nature of such a conversion is difficult to imagine; but it would be rash to assume that the metabolic powers of animal protoplasm are not sufficient to accomplish it.

With regard to the metabolism of liver-tissue which leads to the production of bile we possess but little direct knowledge. The secretion of bile is not a mere act of filtration of already-formed matters from the blood; but we have at present no conception of the chemical changes which occur in the interior of the liver-cells in the elaboration of bile. There is strong reason to think that the bile-pigments are derived from the colouring matter of blood, not only from the circumstance of the large destruction of blood-corpuscles which takes place in the liver but also from the resemblance or identity of bilirubin and haematoidin, a body derived from extravasated blood. A large number of facts point very clearly to the conclusions (1) that the liver is an organ in which chemical changes of great magnitude and importance have their seat, (2) that their operation consists in great part in decomposition of proteids.

The high temperature of the blood which leaves the liver, and which is the hottest blood of the body, is the chief proof of the correctness of the first of these conclusions, whilst the second rests upon many considerations. The bile-acids unquestionably do not exist in the blood, but are the results of proteid metabolism within the liver-cells. There are strong grounds for believing that urea, CH 4 N 2 O 1 , as well as uric acid, has its principal origin in the liver, which is equivalent to localizing the chief seat of proteid metabolism in this organ.

Diabetes.— In connexion with the glycogenic function of the liver it is necessary to refer to a disease which is of special interest to physiologists, from the ease with which the symptoms may be artificially reproduced. The disease itself may be defined as the appearance of large quantities of sugar in the urine, while the total amount of the urine excreted is also increased. Now diabetes of a temporary nature may be produced in animals in a variety of ways. If certain fibres of the medulla oblongata near what is known as the vaso-motor centre be divided, as they may be by means of a special instrument, without producing any serious abnormal motor or sensory symptoms, there follows very speedily the excretion of large quantities of sugar in the urine. It is evident that this result is due in some way to an abnormal influence of the nervous system. The path by which the abnormal influence is transmitted has been carefully traced down the spinal cord to the first thoracic sympathetic ganglion; if this path be interrupted at any point symptoms follow similar to those caused by the local injury to the medulla oblongata. The circumstance that interruption of this nervous pathway at any point causes the appearance of sugar in the urine at once leads to the suspicion that the escape of sugar is not directly caused by the shock of the operation or injury. We are rather brought to the conclusion that the natural absence of sugar from the urine is due to a restraining influence of the nervous system acting continually in a manner to be discussed hereafter, and that the division of the path by which the continual restraint is exercised merely intercepts the inhibitory influence. This is confirmed by the observation that the medulla is in communication with certain afferent nerves, through which also the restraint may be removed. These nerves are the vagi; division of them leads to a transient appearance of sugar in small amount in the urine; but stimulation of their cerebral ends brings about the escape of sugar to a remarkable degree. This clearly can only be due to an inhibition by afferent nerves very similar to the inhibition of the heart which follows stimulation of the cerebral end of the abdominal sympathetic nerve in the frog.

The intercepting of this hypothetical restraint by the anatomical section of nerves is not the only way of artificially bringing about diabetes. Sugar may appear in the urine during the action of curare and after a suitable dose of morphia, and also after the injection of dilute saline solutions into the blood-vessels. The probable relationship of these various methods of causing diabetes will be referred to later.

There can be no question that diabetes is a disease affecting the glycogenic function of the liver. In many cases of natural or pathological diabetes, if all carbohydrates be withheld from the patient, the urine becomes free or almost free from sugar; and in like manner, if an animal be starved until there is every reason to suppose that its liver has become free from glycogen, and afterwards it be subjected to the operation for producing artificial diabetes, no sugar appears in the urine. Similarly, if an animal be drugged with arsenic, which leads to a rapid loss of all the glycogen of the liver, and afterwards poisoned with curare, the latter drug no longer brings about diabetes. In short, if the liver contains no glycogen no sugar can appear in the urine. This being so, in what special way is the glycogenic function modified in diabetes? If we assume that the function of the liver is to seize upon all sugar passing along the portal veins from the intestinal canal and store it up as glycogen, in order that it may be piecemeal returned to the blood to be burnt off’ in distant organs, we can easily review the various conceivable ways in which diabetes might be caused. It must, in the first place, be premised that the blood is unable to contain more than a certain percentage of sugar. When this percentage is overtopped the excess of sugar escapes in the urine. Of this there is direct experimental proof in the facts that if sugar be slowly injected into the jugular vein, no escape of it by the kidneys takes place, because the organism can make use of a small excess of sugar; but if it be injected quickly diabetes ensues from the too rapid accumulation of it in the blood. Accepting this, we can readily see that diabetes might be caused (1) by the failure of the liver to pick out the sugar in the portal vein in order to store it, (2) by an unusually large escape of glycogen from the liver in the form of sugar, (3) by the failure of the distant organs whose function it is to burn off the daily quantum of sugar.

It is not improbable that there may be different sorts of diabetes arising from different causes. Thus it has been said that the diabetes of curare-poisoning appears even when the liver has previously been emptied of glycogen by starving the animal. When we reflect that muscles are the organs especially affected by curare, the fact (if it be a fact) just mentioned at once suggests that the sugar which appears in the urine during curare-poisoning is due to some defect in the muscular tissue, in consequence of which the glycogen normally used up by it fails to be used and passes back into the blood. Further, the failure of glycogen-using organs may be due to no disqualification of theirs for tlιe work of utilizing normal glycogen, but to some abnormal constitution of the glycogen (or the sugar) offered to them. Again, the diabetes caused by copious injection of dilute saline solutions into the blood-vessels may be due to the large destruction of blood-corpuscles which follows such injections, and the consequent production of a large quantity of the starch-converting substance which is known to arise in the disintegration of blood-cells. But the common form of artificial diabetes —“puncture diabetes,” as it is sometimes called—the diabetes of anatomical nervous lesions, is undoubtedly due to defects in the hepatic apparatus brought about by the injury. Thus the puncture of the medulla oblongata is of no avail to cause diabetes if the liver has first been deprived of its glycogen by starving the animal experimented upon. It is, however, far from necessary to suppose that the puncture diabetes is due to any incapacity of the livercells for their usual metabolic changes; this may be the cause of some kinds of pathological diabetes, but it is almost certainly not the cause of the traumatic variety, and for the following reason. If sugar be freely administered to an animal in which the diabetic nervous lesion has been established, although it is impossible to load the liver with glycogen as, in such conditions, it would become loaded during health, yet a certain amount of glycogen does become stored in the liver. The liver seems still to possess the power of converting the sugar of food into a store of starch, but not the fulness of opportunity which it has in health.

The conditions which deprive the liver of the opportunity of storing glycogen are to be sought in an altered vaso-motor mechanism. The circumstance that the “diabetic centre” in the medulla coincides with part of the general vaso-motor centre at once leads to the vaso-motor theory of diabetes; but it may be admitted that this consideration is almost the strongest support of the theory. How a vaso-motor paralysis brings about diabetes λve have as yet no clear picture. Perhaps it is by permitting such a rapid current of blood through the vessels that there is not time enough for the usual transmutations. If we may assume this to be the method by which diabetes is produced, then the vaso-motor theory receives much support from the following consideration. Inasmuch as diabetes is caused by a local (hepatic) dilatation of blood-vessels leading to a superabundant torrent of blood, if means be taken to provide other channels for the blood and so relieve the superabundance, diabetes should be prevented. This may be done by dividing the splanchnic nerves and dilating the enormous vascular tracts of the abdominal organs. In these circumstances the diabetic puncture makes but a trivial change in the circulation of the liver compared with that which it makes when the blood-pressure is normal; and, as might have been foretold from the vaso-motor theory, no diabetes follows. If diabetes from nervous lesions is a vaso-motor phenomenon, other forms of artificial diabetes are not so. Arsenic and antimony seem to destroy the power of the hepatic cells to manufacture glycogen; sugar ingested with the food passes, in consequence of the failure, directly into the blood and out of it into the urine. Ligature of the bile-duct also rapidly leads to profound disorganization of the hepatic tissues, in consequence of which imported sugar passes the portal system unheeded and escapes by the kidneys.

Metabolism of the Blood.— We have hitherto regarded the blood as subordinately related to the great processes of the body, as playing the mechanical part of a carrier, and as if it had no direct interest in the metabolic operations themselves; the reader, however, need scarcely be reminded that, but for the respiratory exchanges between the blood on the one hand and the anatomical elements of the tissues on the other, all metabolic processes would be impossible. In the article Respiration, and in treating the particular section “the respiration of the tissues,” the influence of those exchanges on metabolism will be carefully considered.

The older physiologists regarded the blood as the very seat of the chemical changes of the body,—a view which is almost entirely opposed to that which we now hold, and which is disproved by many facts.

We have little or no evidence that the blood exhibits transformations of matter such as we have been discussing in the case of the tissues generally. There are few such transformations known to us in which carbonic acid is not one of the most abundant end-products of the change, and therefore, when we find that blood removed from contact with the tissues and freed from carbon dioxide produces very little of this body, although an abundance of oxygen be supplied to it, we have the right to suspect strongly that it is due to the absence of any active metabolism.

It is not certain that blood (or lymph), without the intervention of some other tissue, has even the power of converting non-coagulating albumins fresh from the digestive organs into the characteristic fibrin-formers. It is true that when lactate or caprate of soda is injected into the blood of an animal it is readily oxidized; but this may easily be due to the operation of some organ through which the blood passes, and which finds the bodies referred to suitable to its own metabolic processes; and this view of the case is further strengthened when we find that formiate of sodium, which also is a readily oxidized body, passes through the same ordeal unchanged.

Nevertheless, the blood is to a certain extent an active living tissue. The white corpuscles, at least, are definite living structures whose life-history, could we but decipher it, would be found to be a history of constant metabolic processes. Towards these elements of the blood the fluid plasma must behave as towards any other tissue-element, supplying them with raw material, and receiving from them the end-products of their internal chemical decomposition; and therefore the blood, as a whole, must be classed among the metabolic tissues. The production of the anatomical elements of the blood does not concern us here; it may suffice to say that the white cells are added to the blood or lymph from certain structures of which the spleen, thymus body, lymphatic glands, and mucosa of the alimentary canal are the chief, and that probably the red corpuscles are developed from the white ones. It may also be pointed out that there are certain parts of the body— e.g., the spleen, liver, marrow of bones, &c.—where there is evidence to show that red corpuscles undergo rapid and wholesale destruction, either for the production of some secretion, or possibly because the corpuscles have become old and unfit for work, and their invaluable constituent, iron, is wanted for younger and more active corpuscles.

IV.— Processes of Excretion.

The blood, as has been more than once said, is subject to continual additions and subtractions on the part of the tissues. The subtractions effected by the tissues are made good in part by the importation of fresh material of food from the alimentary canal. The analogous counterbalancing operations which serve to check the accumulation of used-up tissue-substance in the blood take place in certain organs called excretory. In a strict sense, all organs which cast out material from the body are excretory; the digestive glands, for example, pour their secretions into the alimentary canal, i.e., outside the strict limits of the body. But so much of their constituents are reabsorbed before the alimentary canal is traversed that they may, for practical purposes, be regarded as never having left the body. Even the constituents of tears, when these do not fall over the cheeks or escape at the nose, are reabsorbed from the nasal mucous membrane. With respect to the alimentary secretion, it is merely a small proportion of the bile which remains in the faeces that is to be regarded as truly excretory in the sense of being utterly lost to the organism. If excreta are those substances which the body rejects utterly, then we may reckon as excreta (1) the urine, (2) the sweat and oily secretions of the skin, (3) the milk, (4) certain elements of bile contained in the faeces, (5) the gaseous and watery losses at the lungs, (6) the exuviated horny scales of skin and nails and hair, (7) the products of the generative organs, but not those constituents of faeces which are but the undigested remains of food. Among these (if we except the milk and the generative secretions whose elaboration is so peculiar and exceptional) the urine and the excretory products of the lungs and skin are those of paramount importance. The excretion from the lungs will be treated under Respiration ; we shall therefore here concern ourselves with the excretion of kidneys and skin.

Kidneys and their Excretion.— Urine is a clear ambercoloured fluid, somewhat acid in reaction, with a peculiar aromatic odour and bitter saline taste. Its specific gravity varies, consistently with health, within wide limits, being affected very greatly (a) by the quantity of liquid consumed by the individual in a given time, (6) by the greater or less activity of the secretion of sweat. Whilst the average specific gravity may be stated to be about 1Ό20, it is often temporarily much lower and occasionally considerably higher. As a rule the specific gravity is higher in summer than in winter. The average quantity of urine passed by a healthy adult may be reckoned at 52 fluid ounces, though it is affected by the same causes as those which influence the specific gravity no less than by individual peculiarity and other circumstances.

The urine is essentially a watery solution of certain organic matters, of which much the most abundant and important is urea, and of mineral salts, of which the most abundant is common salt (sodium chloride).

Urea.— A well-nourished man passes, on an average, about 33 grammes (500 grains) of urea in twenty-four hours. This body, which has the composition CH 4 N 2 O, is looked upon by chemists as carbamide, i.e., it is the amide of carbonic acid, and on this view may be written CO(NH 2 ) 2 . It is isomeric with ammonium cyanate. This body represents the chief product of the metamorphosis of albuminous or proteid substances in the body.

Even during starvation the destruction of proteid matter continues, and the amount of urea may reach about 230 to 310 grains. The quantity is, however, specially and directly affected by the amount of proteid matter contained in the food ; so that, for instance, by consuming a sufficient quantity of meat certain persons have excreted as much as 1540 grains of urea. The excretion of urea, which is a measure of the metamorphosis of proteids in the body, is not, as was formerly supposed, directly influenced by the amount of mechanical work done by the body, the greater activity of the muscles not being necessarily accompanied by their greater waste; indirectly, however, the excretion of urea is increased by bodily exertion, inasmuch as man and other animals appear instinctively to desire and to need a larger quantity of proteid food when much work is to be done than when the body is comparatively at rest.

It was formerly believed that urea was a direct result of the oxidation of proteids in the body. The view actually held is, that it is the product of a synthesis occurring in the body in which a body or bodies resulting from the oxidation of the proteids take part. It has recently been shown that when salts of ammonia are introduced into the system the nitrogen of the ammonia is excreted as urea; in this case it is obvious that a synthesis must have occurred in which the ammoniacal salt introduced has taken a part no less than some other body. It has, for instance, been surmised that in the oxidation of the proteid molecule cyanic acid arises, and that in the presence of ammonia ammonium cyanate is formed, which in the organism, as outside, may be changed into urea; or, again, that cyanic acid is formed, which, uniting with the elements of water, gives rise to urea, carbonic acid being separated in the reaction.

Uric acid combined with bases exists in small quantities in the urine of man, about 7 to 10 grains being passed by an adult in twenty-four hours, though individual peculiarities appear to affect in a remarkable manner the excretion of this constituent (maximum limits of quantity '3086 to 15'43 grains). In some animals, as in snakes and birds, uric acid and its salts represent the chief nitrogenous excretory product, i.c., take the place of the urea of the urine of man and carnivorous animals.

Uric acid has the composition C 5 H 4 N 4 O 3 . Its constitution is yet involved in great doubt, in spite of the most profound and extensive researches which have been made on its more or less immediate relations, and in spite of the fact that its synthesis has recently been effected. It may be looked upon in all probability as a derivative of cyanic acid, CN0H, and glycocin, C 8 H 5 NO 2 , anil there are many facts which seem conclusively to show that in the system it does not arise directly from a decomposition of proteids, but is the result of a synthesis in which derivatives of these bodies take a part.

Xanthin, C 5 H 4 N 4 0 2 , hypoxanthin, C 5 H 4 N 4 0, and guanin, C 5 H 5 H 5 O, are immediate derivatives of uric acid, of which the first is a constant constituent of urine, and the second occurs in certain states of disease.

Hippuric acid, C 9 H 9 NO 2 , benzo-amido-acetic acid, is present in small quantities in the urine of man (about 15 grains a day), but is the chief nitrogenous constituent of the urine of herbivorous animals. It is formed whenever benzoic acid, or a body which can yield benzoic acid in the organism, is ingested.

In addition to the organic matters already enumerated the urine contains small quantities of other bodies, amongst which may be mentioned (1) colouring matters, of which one alone is known with any degree of accuracy, and is termed urobilin, a derivative proximately of the biliary colouring matters, and more remotely of the blood-colouring matter, and (2) minute traces of ferments.

As has already been said, the chief salt of the urine is common salt; there are, however, also excreted in the urine considerable quantities of phosphates and sulphates. The two latter salts represent in part similar salts introduced as such into the system, but in part they are the products of oxidation of organic bodies which contain sulphur and phosphorus respectively; to the former belong the proteids, to the latter certain phosphorus - containing fatty bodies of great complexity, which occur widely diffused throughout the body, but particularly in the white matter of the great nerve-centres and in the nerves.

The changes which urine undergoes after it is passed may be briefly referred to. The faint acid reaction proper to freshly-drawn urine is increased, probably in consequence of an acid-fermentation process started by the mucus accidentally present. The visible effect of this is the deposit of acid urates or free uric acid. In a short time, especially if the urine be kept at a warm temperature, the acid-fermentation is overwhelmed by a fermentation for which organic germs are needed, and which leads to the resolution of urea into carbonate of ammonia. The reaction becomes alkaline, and the smell strongly ammoniacal. Precipitates of ammonia, urate, and ammonio-magnesian phosphate are deposited, the odour becomes putrefactive and multitudes of micro-organisms develop whose germs have been derived from the surrounding air.

Kidney.— The urine is excreted continuously in the kidneys, two organs situated at the back of the abdominal cavity. The fluid is continuously poured by two ducts called ureters into a common reservoir situated in the pelvis, and known as the urinary bladder. From this reservoir the urine is intermittently ejected by the urethra. The two kidneys never secrete symmetrically; they exhibit an alternation of vascular and secretory activity. Similar variations have been observed in the different portions of one kidney,—first one and then another region of the kidney will be found to be in full activity. Nevertheless, when one kidney is extirpated or unfitted for its function, the other may be capable of the whole work of excretion.

The excretory portion of the kidney, like the secretory portion of all glandular organs, consists of tubes of basement membrane lined with cells of peculiar attributes and surrounded by capillaries for blood and lymph, which allow their fluids to come into close communication with the secreting cells. The complex disposition of the tubes, of which there are hundreds in each kidney, has been traced after an infinite amount of patient research. An account of the arrangement of the tubuli uriniferi falls beyond the scope of the present article.

Excretion of Urine.— A review of the constituents of the urine discloses that the function of the kidneys is to separate from the blood chiefly (1) nitrogenous crystalline bodies which are undoubtedly the end-products of the oxidation of nitrogenous bodies, and (2) inorganic salts and water. We have now to describe the probable manner in which this separation is effected. Ever since the whole course and form of the renal tubules became mapped out, and the existence of a double system of capillaries was established, it has been the habit of physiologists to regard the excretion of urine as a twofold operation. Sir William Bowman, so long ago as 1842, in the course of a histological investigation of the structure of the kidney, came to the conclusion that the watery portions of the urine are excreted in the capsule, while the solid parts are removed from the blood surrounding the lower parts of the renal tubule. Ludwig, about the same time, advanced the theory that the whole of the urine is separated from the blood in the glomeruli, but that it is separated in an extremely λvatery condition, the object of the complicated renal tubules being to permit of the reabsorption of the water, and to bring the urine into a suitable state of concentration for removal from the body. The progress of investigation has completely vindicated the theory proposed by Bowman, which now rests not merely on inference from anatomical structure, but upon a sound basis of physiological facts.

Not only is the process twofold in respect of the two classes of constituents secreted; it may be twofold also in respect of the processes of the act. There is at least much reason for thinking that the water is separated from the blood mainly, though not entirely, by a physical process of filtration, while some, if not all, of the specific' elements of the urine are secreted by a peculiar selective or elaborative action of living epithelial cells. The reason for supposing that the excretion of water is mainly a process of filtration is the simple one that the flow of urine seems, in a general way, to obey the same laws of pressure as the flow of water through a filter. For example, whatever tends to increase the blood-pressure in the branches of the renal artery tends to increase the flow of urine in a given time. If the heart beats more quickly than usual more urine is excreted. If cold contracts the superficial vessels of the skin, and drives a larger quantity of blood upon the kidney, or if the same result ensues from moderate stimulation of the splanchnic nerves, the blood-pressure in the renal artery becomes raised, and an enlarged secretion follows. If the spinal cord be divided in the lower part of the cervical region, the great fall of blood-pressure which results is associated with suppression of the excretion of urine. Further, if the pressure in the ureters be allowed to reach the value of 10 to 40 mm. (’ 3937 to 1 ’ 5748 inches) of mercury the transfusion of fluid from the blood is prevented. Now the blood-pressure in the renal artery is about 120 to 140 mm. (4 ’ 7244 to 5 ’ 5118 inches) of mercury. Secretion stops, therefore, long before the pressure in the glandular ducts reaches that of the glandular vessels,—a relationship between pressure and secretion the very reverse of that which obtains in the case of the salivary gland. These facts sufficiently justify the conclusion that the secretion of water in the kidney is a process of filtration. But there are other facts which demand the assumption that even the separation of -water is in part an act of living protoplasm. The free ingestion of water by drinking is one of the most certain ways of producing a copious flow of urine; and yet there is no evidence to show that in most cases this effect is brought about by a raising of the blood-pressure. On the contrary, if one animal be bled into the veins of another there is no increase produced in the amount of urine excreted, and it is difficult to imagine that the bloodpressure may be more easily raised by the drinking of water, however freely, than by introducing into the bloodvessels of one animal the quantity of blood proper to two. In such cases we must assume that the outflow of water from the blood is due to the activity of living cells aiding the normal influence of pressure.

While the secretion of water cannot wholly be ascribed to physical processes, there is no doubt that the secretion of some other bodies is a selective act of living protoplasm taking place independently of, or it may be in opposition to, physical processes. The first substance whose secretion was experimentally proved to be due to the renal epithelium was sulphindigotate of soda, or indigo-carmine. If this substance be injected into the blood-vessels of an animal in which the blood-pressure has been so far lowered by division of the spinal cord below the medulla that the flow of urine has stopped altogether, it can be traced in a short time into the epithelium of the renal tubules, and through them into the lumen of the duct. The absence of the usual flow of water has left the granules stranded at the place where they entered the renal system of tubes. No trace of the substance was found by the original observer, Heidenhain, in the glomeruli or capsules; but it may be stated that later experimenters have succeeded, by injecting the drug freely and pursuing it over longer intervals, in tracing it into the glomerular cells also.

Sulphindigotate of soda is not a normal constituent of the urine; but there is little doubt that what happens in the case of this body happens also in the case of some of the usual constituents. Thus, uric acid has been detected within the epithelium of the renal tubules; and by a comparatively new and beautiful observation it is placed beyond doubt that urea also enters the secretion at the same cells rather than through the glomeruli. This proof was rendered practicable by the discovery that in the frog the kidney is supplied with blood from two separate and distinct sources. The renal artery supplies the glomeruli with blood, while the so-called renal portal vein, a branch from the femoral vein which runs along the outer border of the kidney, supplies the capillary network surrounding the uriniferous tubules. If the renal artery be tied and the blood-supply shut off from the glomeruli, sugar when introduced into the circulation is not excreted with urine, although it readily is when the vascular supply of the kidney is untouched. But in the same circumstances, when the action of the glomeruli is eliminated, urea is readily excreted. Urea and sugar are therefore removed from the blood by different organs; or at least the renal epithelium of the tubules can excrete urea, although it cannot excrete sugar. At the same time that urea is being excreted a copious flow of water is determined, which most presumably escapes at the point where the urea is excreted. This fact is significant when we remember that ligature of the renal artery usually stops the flow of water, and that sulphindigotate of soda injected into the circulation when the glomeruli are tied out of it may be traced into the same epithelium, but gives rise to no flow into the bladder.

The renal epithelium, then, has the power of attracting to itself and removing from the blood certain elements which the latter already contains. It may now be asked whether the kidney has the power of elaborating any of the components of its excretion from antecedent forms which it obtains from the blood. In other words, is the kidney a simple separating or straining mechanism, or are the constituents of the urine, like the constituents of bile or saliva, elaborated in the course of metabolic changes going on within the secreting epithelium?

This question has already been touched in discussing the metabolism of liver-cells. There is little doubt that the kidney exhibits some metabolic activity. Inasmuch as the blood of herbivorous animals contains no trace of hippuric acid, this must presumably be formed within the kidney. If blood containing sodium benzoate and glycocin be passed through the vessels of a fresh kidney, hippuric acid arises. The kidney, therefore, must be assumed to be capable of elaborating hippuric acid out of simpler antecedent forms. But it is not certain that it has any further power. With regard to urea, it appears certain that the activity of the kidney is confined to straining it of! from the blood. Normal blood contains about 1 part of urea in 4000, while the blood of the renal vein contains less than this. Urea, therefore, is separated from the blood in the kidney. If the kidneys be extirpated, or if their blood-vessels be ligatured so as to exclude them from the circulation, or if the ureters be tied (the effect of which is speedily to unfit the kidney-epithelium for the work of excretion), then the amount of urea increases in the blood up to 1 part in 300 or 400, while much urea is voided in the fluids ejected from the stomach and intestines during such experiments. Similar experiments in birds have led to similar results in the case of uric acid. All these facts point to the conclusion that urea and the allied bodies in urine are derived proximately from the blood rather than elaborated in the kidney itself. We are therefore justified in regarding the kidneys as almost exclusively an apparatus for purifying the blood from the injurious products of the cell-metabolism of other organs and tissues.

Excretions of the Sweat-Glands.— The second great excretory system is that of the skin, which supplements in important particulars the excretory functions of the kidneys. This function of the skin is effected in great measure by certain glands, called sweat-glands, opening on the surface of the skin. There are, indeed, other glands besides the sweat-glands connected with the skin, viz., the sebaceous glands, which open chiefly into the sacs of hair-follicles and secrete an oily material which keeps the surface of the skin supple and water-tight. The sebaceous secretion resembles in its formation the secretion of milk. Inasmuch as it is not reabsorbed, it is a true excretion; but there is reason to believe that the material removed from the blood is elaborated out of complex fat-yielding molecules contained in the blood very much as the milk is secreted. We know very little either of the nature of the bodies excreted or of the processes of their formation. The chief excretory products of the skin are furnished by the sweat-glands, and constitute sweat. In addition, hotvever, there is constantly being thrown off from the skin a certain quantity of carbonic acid.

Nature of Sweat.— It is impossible to collect sweat for analysis under perfectly normal conditions; either the body must be subjected to great heat to adduce a copious flow, or a part of the body must be enclosed in an airtight bag of india-rubber. In both cases the conditions are abnormal. So far as can be ascertained, sweat is a colourless clear fluid of acid reaction and characteristic odour. The odour varies with the part of the skin from which the sweat is obtained. It consists of water containing 1 ’ 81 per cent, of solids. The solids are (1) sodium chloride and other inorganic salts, (2) urea and other nitrogenous bodies, (3) fats and cholesterin (which are not altogether due to contamination with sebaceous matter), (4) fatty acids (formic, acetic, butyric, <fcc., but not lactic), (5) a trace of pigment. In addition to these bodies the skin excretes a small amount of carbon dioxide. Although the excretion of the skin is small in amount (if we except the water), if the escape of it be prevented by varnishing the skin death very quickly ensues. This is probably due to the retention of some poisonous substance, the nature and production of which are very little understood.

In concluding these remarks on excretory organs it may be pointed out that the lungs (looked at as excretory organs), the kidneys, and the skin are all engaged in the great task of ridding the system of its superfluous matters, and that each supplements the action of the others. The lungs are the great excretors of carbonic acid, which is the chief oxidation product of the body, though they share with the kidneys and skin the task of getting rid of water. The kidneys have thrown upon them the task of removing from the system nearly the whole of the nitrogenous waste products and the superabundant salts, besides being the greatest excretors of water. The skin, on the other hand, looked upon as an excretory organ, is second in importance to the kidneys as a remover of water, and comes next to the lungs in separating carbonic acid. The skin, it must be remembered, however, has many functions besides those of an excretory organ, for, besides being an organ of sense, it takes the chief part in regulating the temperature of the animal body.

V.— Transformations of Energy associated with the Exchange of the Matters of the Body.

The chemical changes which occur in all the tissues and organs of the body are, it has been stated, in the main, processes of oxidation, in which energy that was potential in the organic compounds and the oxygen that takes part in them become in great part kinetic. This energy takes the form of mechanical work and heat; the mechanical work is in part expended within the body itself and ultimately takes the form of heat; in part, however, it is expended upon the objects of the external world, and, though even then ultimately transformed into heat, this is not heat which is available for the purposes of the body. There can be no doubt, however, that a large portion of the total heat evolved in the body is the immediate result of chemical operations, and has not in the first instance taken the form of mechanical work.

In the article Dietetics (q.υf attention has been drawn to the amount of energy which is stored up in the organic matters constituting the food of animals, and which can approximately be estimated by determining the amount of heat which the organic matters evolve when burned in a calorimeter. An approximate estimate is thus formed of the energy which is at the disposal of the animal or man whose diet is subjected to study. Thus it has been calculated that the available energy derived from the oxidation of the organic matters of the food of a well-fed man amounts to about 2,700,000 units of heat, the unit chosen being the amount required to heat 1 gramme of water 1 C. When the man is doing no external work this energy ⅛ dissipated from the body almost entirely as heat, and, according to the calculations of Helmholtz, the losses of heat are approximately distributed as follows :— [table]

The total income and expenditure of energy of an average man in twenty-four hours is thus calculated to correspond to the amount of heat required to raise 595 lbs of water from the temperature of melting ice to that of boiling water.

Where, it will be asked, does this transformation of energy chiefly have its seat? The answer to this question is that it is firstly in the muscles, then in the glands of the body. At all times, whether in rest or activity, heat is evolved, but the quantity increases in the case both of glands and of muscles as they pass from the former into the latter condition. In the resting body, it has been remarked, the losses of energy are represented by the loss of heat, for the mechanical work done within it takes the form of heat within the body itself. It is difficult, nay, impossible, to calculate the amount of energy which in the first instance takes the form of mechanical work in the body, and which is always transformed into heat. The case of the heart is one in which, however, an approximate calculation can be made. Upon fairly reliable data it has been calculated that the work expended by the heart of a man in twenty-four hours amounts to not less than 627,768 foot-pounds, an amount of work which is equivalent to nearly 45 poundunits of heat, and which represents the energy evolved as heat in the complete combustion of about 386 grains of carbon.

These calculations enable one to form some idea of the magnitude of the nutritive processes which have their seat in the muscular substance of the heart; and to a less degree the same is the case with all the other muscles which are engaged in so-called opus vitale, that is, in the performance of internal work absolutely essential to the continuance of the life of the organism.

The proportion of the total energy of the body which takes the form of mechanical work varies within very wide limits. Assuming that the conversion of potential into kinetic energy in equal times were a constant quantity, it would follow that all external work done diminished the amount of heat set free from the body. To a certain extent it is probable that such a relation exists. It is, however, to be remembered that when external work has to be done there is invariably an increased consumption of organic constituents of food, and therefore an increased store of available energy. The working animal consumes more O and produces more CO 2 than the resting animal. Different animals, like steam-engines of different construction, vary in the proportion borne by the external work they are capable of performing to the total energy which becomes kinetic. Experiments made with the separate muscles of animals, no less than observations on the relation between the external mechanical work done by and the total heat evolved in the body of animals, have, however, shown that animals are more economical machines than the most perfect steam-engines. Whilst the latter cannot convert more than one-eighth of their available energy into work, the animal may yield as much as one-fifth of its energy in the form of available external work.

VI.— Growth, Decay, and Death.

In the adult body in a state of health the income of matter balances as nearly as possible the expenditure, and therefore the weight of the body and its dimensions remain nearly constant, and the same is approximately true of the different organs and tissues which compose the body, as well as of the anatomical elements which enter into their formation. Even when the conditions to which the organism is subjected undergo great variations—as, for instance, when from a state of rest it passes into a state of great activity, or when the temperature of the medium which it inhabits undergoes great changes—and when, to meet these variations in external circumstances, the rate of the exchanges of matter has to undergo great fluctuations, the weight of the body remains nearly constant. This remarkable result is one which doubtless depends upon a great many factors which are for the most part hidden from us.

In the growing body matters are, however, very different; in it normally the income must be always so much in excess of the expenditure that an accumulation of capital may occur, and that the body may increase in weight and in dimensions. The growing body is always the seat of a more active exchange of matter than the fully-developed body, i.e., weight for weight, it requires more food and oxidizes it more rapidly.

The increase of weight and of dimensions occurs in part by addition of matter to, and increase in weight and in dimensions of, individual organs and their constituent anatomical elements; in part, however, it is due to an actual multiplication of anatomical elements occurring at a rate which greatly exceeds that which occurs in the adult body. To what an extent this multiplication occurs and how it gradually diminishes is evident when we reflect that the whole organism was originally derived from a single cell, the ovum.

Upon what depends this tendency to multiplication of anatomical elements, and this tendency to increase in size of individual anatomical elements or of organs, until a certain approximate limit has been attained, is absolutely unknown. We know to a certain extent that the process of growth depends upon and is influenced by certain circumstances, as amount of food, temperature, blood-supply to the particular organ, and so on, but yet the knowledge is wanting which would tell us why, when a certain limit has been attained, the processes of income and expenditure balance and growth ceases.

That the nervous system has a great influence upon nutrition and therefore upon growth is certainly known, and in great measure explicable. By its control over the blood-supply to organs and tissues the nervous system exerts a remarkable influence, as well as by its relations more or less direct upon the anatomical elements through nerve-fibres, which, inasmuch as they appear to influence in a direct manner the nutrition of anatomical elements, have been surmised to exist, and have received the name of “trophic fibres.” Yet, even apart from the influence exerted by the nervous system, it appears to be a property of individual anatomical elements that, consistently with health, they shall only develop at a certain rate and attain a certain magnitude.

Scarcely less mysterious than the primary causes of growth is the fact that every organism having arrived at maturity remains in a state of apparent structural and functional integrity for a term which possesses an approximately constant mean value for each species, and then sooner or later necessarily passes into a condition of gradually lessening efficiency, which ultimately terminates in death. Were the animal organism a machine undergoing a constant though very slow process of waste, its decay and ultimately its death would be more obvious than they actually are. The organism, however, differs from the machine in that its matter is continually the seat of change, and that during long periods (⅛.e., during healthy adult life) the processes of gain and loss of matter appear to be going on with perfect evenness and equality. Why, then, the ultimate deterioration resulting in waste and then in death? The answer is that the organ as a whole unquestionably does suffer by work, and, though at first the degree of impairment is so slow as to be imperceptible, it doubtless is a continuous process.

A general impairment of the mechanism of the body as it passes from the age of mature or adult life into old age is evidenced (1) by a diminished rate in the exchange of matter of the body; (2) by a diminished power manifested by the organism as a whole, as well as by each of its individual organs, to accomplish work; (3) by a general loss of weight of the body and of its essential tissues and organs, though the weight of the body as a whole may increase by the development and storage of fat; (4) by a tendency to structural change of organs or parts of organs whose proper function is essential to life, as, for example, of the circulatory, respiratory, and nervous apparatuses; (5) by a readiness to be injuriously affected by external circumstances, which at an earlier period produce no obvious effect upon the body or only temporary impairment of its functions. The gradual and general deterioration of the organism thus evidenced is usually interrupted by the supervention of some process impairing so greatly the functions of a vital organ that the organism as a whole ceases to perform the functions which characterize it as living, and death results. Whatever the remote cause of death, the proximate cause is in every case an arrest of the circulation of the blood, putting an end to the exchanges of matter and energy which are the most characteristic of the accompaniments of life. (a. g.*)