CHAPTER VIII

EXCRETION

Many things enter into the alimentary canal. If an analysis were made of a day’s food and drink, from the cup of tea on waking to the cocoa or other potion which is regarded as a necessary preliminary to settling for the night, it would be found that a great variety of substances were included in the food or taken as adjuvants to food. All these things, differing widely in chemical constitution, must leave the body. Some are not digested. They do not, properly speaking, enter into the diet. Such are the cellulose of vegetables, especially skins, husks, woody fibres; elastic fibres of meat; horny substances, etc. The quantity varies greatly, according to the nature of the diet. About 2 ounces (weighed dry) is the average. With this indigestible refuse is included undigested food, if the diet be excessive, and a variety of substances secreted by the liver, such as cholesterin and bile-pigment, some residues of the secretions of the alimentary canal, and products of bacteric fermentations. All food which is digested and absorbed is oxidized. It leaves the body by the lungs, the kidneys, or the skin. Foods, as already stated, are classified as proteins, carbohydrates, and fats. The chief excreta are carbonic acid, water, and urea. Carbonic acid makes its exit from the lungs; water from the lungs, the kidneys, and the skin; urea from the kidneys. The three great groups of foods and the three great groups of excreta overshadow in amount all the other substances which pass through the system. A balance-sheet in which proteins, carbohydrates, and fats appear on one side, carbonic acid, water, and urea on the other, is substantially correct. The energy which is set free by burning in a calorimeter the items entered on the debit side, after deducting that yielded by burning the urea (carbonic acid and water are incapable of further oxidation), gives a day’s income. Other constituents of the diet are so small in quantity as to be negligible in making up the body’s accounts. The chemical changes which they undergo add practically nothing to its capacity for work. Yet some of them are essential to the maintenance of health. Of such are common salt (sodic chloride), alkaline and earthy carbonates, sulphur, phosphorus, etc. These things, together with some products of action of the bacteria in the alimentary canal, the final stage of hæmoglobin, imperfectly oxidized nitrogenous substances, and other soluble substances which enter with, or are formed from the food, are removed by the kidneys. We speak of the elimination of waste products, as excretion. Not that there is any physiological distinction between excretion and secretion. Both terms refer to the selection or production and the discharge of materials by cells. If the product discharged has a useful function to perform—if it be a digestive ferment, for example—it is said to be secreted. If it is of no further use to the economy, we say that it is excreted—got rid of. In some cases either term is equally appropriate. The sebum prepared by the sebaceous glands is useful as a lubricant of the skin. It is thrown off. We may speak of the glands as either secreting or as excreting this fatty substance.

=The Kidney.=—From worms upwards, all animals possess organs for the removal of waste products in solution. This statement might, indeed, be widened so as to include animals even lower than worms. All animals which have a cœlomic cavity—a space between the alimentary canal and the body-wall—have organs for the removal of soluble waste. The segmental organs of worms are obviously the same organs as the kidneys of mammals; the latter are distinguished from their prototypes by greater concentration of structure and specialization of function. The kidney is the oldest of organs, if its antiquity be estimated as the length of time during which it has had a form practically identical with that which it now presents. The lungs are of late appearance in the animal scale. Alimentary canal, heart, brain, have passed through many transformations. The kidney assumed its permanent form very far back in the history of the animal kingdom. The most primitive animal which has a digestive cavity, and vessels in which the products of digestion circulate, needs an organ which provides for the overflow from the body-fluids of all substances which are injurious or effete.

The kidney is an aggregation of long urinary tubules. The head of each tubule is dilated into a globular capsule, into which a tuft of bloodvessels depends. This is the sink into which the waste-water of the blood drips. The long urinary tubules are lined with cells well qualified by form and constitution to search the blood in the capillaries which border them, for substances which, not being easily diffusible, have to be forcibly dragged from it and added to the water trickling down the pipe which connects the rain-water head with the sewer. The hydrostatic conditions of this apparatus—the provision for greater or less flow of blood through the tufts (glomeruli) which hang in the capsules, and for longer or shorter exposure of the blood to the purifying activity of the epithelium of the renal tubules—will be described after a very brief account has been given of the structure of the organ.

The outer border of the kidney is convex, its inner border concave. The concavity is termed the “hilus.” The central depression of the hilus is embraced by the expanded end of the ureter—the tube which carries the secretion of the kidney to the bladder. The renal artery and the renal nerves enter, and the renal vein leaves, the kidney at the hilus.

If a kidney be split longitudinally, it will be noticed that its outer part, the cortex, is darker in colour than its inner part, the medulla (Fig. 9). The glomeruli already referred to occur in the cortex. The medulla is occupied by radiating tubules, collected into groups. Those of each group converge towards a common duct. From twelve to eighteen ducts open into the expanded end of the ureter, each at the apex of a pyramid. If the section of the kidney be examined with a lens, it will be seen that narrow rays from the medulla extend into the cortex. The cortex is therefore made up of interdigitating pyramids of dark substance, consisting of glomeruli and the contorted tubules, about to be described, and of lighter substance, consisting of straight tubules continuous with those of the medulla.

The urinary tubules are the separate pieces of apparatus of which the kidney consists. The problems connected with a single tubule are therefore the problems of the kidney as a whole. These structures are all exactly alike. The description of any one of them applies to all. Each begins as a capsule containing a glomerulus. The wall of the bulb—which is merely a thin basement membrane covered by epithelial scales—is involuted by the tuft of bloodvessels. The vessels do not penetrate its capsule. Between the tessellated epithelium which covers the tuft and the similar epithelium which lines the capsule there is a space communicating by a narrow aperture with the next portion of the tubule—termed its “contorted” part, because it is twisted about like a tangled thread in the cortex of the kidney. The contorted tubule is of relatively large calibre. The cells which line it are irregular in form and indistinct in outline. The basal half of each cell, between its nucleus and the basement membrane, is vertically striated, or “rodded,” as it is usually termed. Such an arrangement of the protoplasm of a cell is commonly associated with a habit of absorbing fluid. It would seem to indicate in this case that the cells take water and various substances dissolved in water from the direction of the basement membrane. After a time the contorted portion of the tubule, although still sinuous, becomes more nearly straight—the “spiral portion”—and assumes a radial direction. In the zone between the cortex and the medulla, the spiral portion tapers into an exceedingly slender tubule which, after running some distance in the direction of the hilus, turns back again towards the cortex, making a loop, known as the “loop of Henle.” The ascending limb of this loop is of larger calibre than the descending limb. The descending limb is lined by flattened epithelium, each cell so thin that (in microscopic sections as ordinarily prepared) its nucleus bulges into the lumen of the tube. The cells of the ascending limb are more nearly cubical in form. On reaching the cortex, the tubule again becomes contorted. The second contorted portion narrows into a “collecting portion,” which joins a ductule. The ductules unite together, until at last a single duct is formed which opens at the apex of a pyramid. The cells of the ductules are cubical or columnar. Their cell-substance is clear, whereas that of the cells lining other parts of the tubule is cloudy in appearance.

Such a tubule, viewed as a hydrostatic mechanism, presents three portions, evidently fitted for different functions: (1) The glomerulus is an apparatus which allows of the rapid exudation of water from blood. (2) The contorted portions of the tubule present the appearance of a secreting mechanism. The large soft, cloudy cells which line them are eminently fitted to take from the blood, or rather from the lymph which fills the tissue-spaces which intervene between the walls of the capillary bloodvessels and tubules, the various substances which they excrete. (3) The loop of Henle is a remarkable piece of apparatus, the purpose of which has been a subject of much controversy. Looking at it from the point of view of hydrostatics, it seems safe to conclude, from its extremely narrow bore, that it raises the pressure of the fluid in the glomerulus and first contorted portion; but it may have other functions also.

A consideration of the arrangement of the bloodvessels of the kidney bears out the conclusion that the secreting apparatus is divisible into at least two separate portions, possibly into three. The glomeruli are supplied by short and relatively wide arterioles. Each arteriole breaks up, as soon as it enters the capsule, into a bunch of capillary vessels, which, in the same abrupt manner, reunite to form a venule. On leaving the capsule, this little vein behaves in a fashion for which the only parallel is to be found in the portal system of the liver. Instead of uniting with a larger vein, it again breaks up into capillary vessels, which supply the contorted tubules and loops of Henle. The medulla of the kidney is supplied by long arterial capillaries of the usual type. The short arterioles of the glomeruli are controlled by nerves which, constricting them, or allowing them to dilate—possibly by actively causing them to dilate—rapidly diminish or increase the amount of blood passing through their tufts of capillary vessels. Here, therefore, is a mechanism by which the glomeruli can be suddenly flushed with blood—a condition favourable to exudation into the urinary tubules. The interposition of a second set of capillaries prevents this sudden flushing from unduly disturbing the pressure in the vascular system as a whole. In the renal-portal capillaries of the kidney the blood-pressure is fairly constant and, presumably, low. The use of the term “renal-portal” is justifiable, not only on the ground that the vessels of the kidney behave like those of the portal system of the liver, but also owing to the very significant fact that in fishes and amphibia the kidney actually has a double blood-supply. In such an animal as the frog the glomeruli are supplied with arterial, the tubules with venous, blood. The glomeruli receive branches from the renal artery, the tubules from a portal system derived from veins of the abdomen and hind-legs.

Sir William Bowman, who in 1842 gave the first detailed description of the microscopic structure of the kidney, concluded that, whereas “the tubes and their plexus of capillaries are probably the parts concerned in the secretion of that portion of the urine to which its characteristic properties are due (the urea, lithic acid, etc.), the Malpighian bodies [_i.e._, the glomeruli] may be an apparatus destined to separate from the blood the watery portion.”

All physiologists are in accord in regarding the glomeruli as the principal seat of exudation. There is great diversity of view as to the function of the tubules. In 1844 Ludwig advanced the opinion that all the constituents of the urine pass through the glomeruli in a large excess of water, and that in the course of the tubules this excess of water is reabsorbed. This theory was based, among other considerations, upon the extreme thinness of the epithelium which covers the glomerular tufts; he judged that water would filter through it very readily. A large amount of experimental work has been directed to the solution of these two problems—viz., (1) Do urea and other similar substances pass through the glomeruli? (2) Is water returned from the tubules to the venous system? Our views as to the functions of the kidney as a whole will not be greatly influenced by the answers that may eventually be given to these questions; yet their discussion is of very great interest, owing to the nature of the evidence which may be marshalled on either side.

There is, perhaps, no other organ in the body the problems with regard to which seem to be so nearly plain questions of hydrostatics. It is easy to make a model of a urinary tubule and its blood-supply. If such a model were shown to a sanitary engineer, and he were asked to explain the working of the drainage system of the body, and especially to answer the two questions which we have propounded, he would say that there could be no doubt as to the part of it through which most water enters the tube, the glomerulus. He could give no opinion as to whether urea, uric acid, and other substances of a like nature, accompany the water until he had tried the experiment of separating blood from water containing the inorganic salts of urine by a permeable membrane—the blood being at such a pressure as the physiologist told him he might expect it to have in renal arterioles, the water at such a pressure as he might expect it to have at the upper end of a urinary tubule. He would find that urea, and still more uric acid, is very reluctant to pass through the membrane. Again, when asked whether water, in which urea and other things were dissolved, would leave the tubule—say from the loop of Henle—to pass back into the blood, he would repeat his experiment with a membrane. This time he would allow the urine and the blood to be at the same pressure (or, possibly, would assign a higher pressure to the former), and he would dilute the urine to make the conditions agree with those which Ludwig supposed to exist; but his experiment would prove to him that, unless the urine were very dilute indeed, water would still tend to pass into it from the blood, and not _vice versa_. And here it may be remarked that the results of these experiments might have been predicted by calculation. When Ludwig advanced his theory, osmosis was a mysterious phenomenon. Its laws have since been accurately ascertained. Given the molecular weights of bodies in solution and their degree of concentration, the direction in which they will pass through a membrane can be predicted. The force with which water will tend to pass from one solution to another can be calculated. Urine as secreted contains far more urea, sodic chloride, and other salts than blood. It has a much higher degree of concentration. The concentration of blood is 0·55; that of urine, 1·85. Water passes from a less concentrated to a more concentrated solution, not _vice versa_. As a solution of a problem in hydrostatics Ludwig’s hypothesis is untenable.

=Osmosis.=—Cells of all kinds, both vegetable and animal, are limited, or surrounded by a layer of cell-substance which is firmer than, and probably different in constitution from, the substance in the interior of the cell. This outer layer is a living membrane. The nutrition and growth of the cell are dependent upon the capacity of its limiting membrane for regulating the ingress and egress of water and of substances dissolved in water. The phenomena of osmosis—that is to say, of the passage of water and of solutions through membranes—are of such high importance in relation to the life of the tissues that it may be permissible to make a further digression for the purpose of describing them (_cf._ pp. 40, 128). A very simple apparatus will suffice to exhibit a phenomenon which will give an idea of the meaning of osmosis. If the top of a glass funnel, covered with a piece of bladder, so fastened to its edge as to make it water-tight, be fixed in an inverted position in a glass vessel, the glass vessel filled with water, and the funnel filled to the same level with a solution of sugar, it will soon be evident that water is passing through the membrane into the funnel. The level of the sugar-solution will rise in the tube of the funnel. If, instead of water outside the funnel and sugar-solution inside it, a strong solution of sugar be placed in the funnel and a weaker solution outside it, water will leave the weaker for the stronger solution, and sugar the stronger solution for the weaker. If some of the solution in the funnel be removed from time to time so that the pressure in it is kept down to the same level as that outside it, water will continue to enter through the membrane and sugar to leave the contents of the funnel until the concentration of sugar is the same on the two sides. The fluids will then be of identical composition, and therefore isosmotic. In the further consideration of the phenomena of osmosis, a distinction must be made between permeable and hemipermeable membranes. Suppose in the first instance that a permeable membrane is used. Let it be so placed as to separate two watery solutions of different constitution, yet of the same osmotic pressure. By their being of the same osmotic pressure is meant that they are of the same molecular concentration. The liquid A contains certain salts in solution; but the liquid B may contain the same salts in quite different proportions. It so happens, however, that the salts are so balanced that the total tension of the salts in A is equal to the total tension of the salts in B. At first there may be some change in level in the two liquids, owing to differences in rates of diffusion through the membrane of the various salts which they contain; but after a time the levels of the two liquids will be the same. To outward appearance, nothing will have happened. Nevertheless, if the experiment has been continued for a sufficient length of time, it will be found that great changes have occurred in the constitution of the two liquids. At the commencement, although their total tensions were equal, the proportions in which the various salts were distributed in A, and therefore their partial tensions, were very different to their proportions and partial tensions in B. At the end of the experiment each of the several salts is equally divided between A and B, supposing the volume of A to equal that of B. This experiment shows that the molecules of substances in solution are free to move. They behave like gases. Gases diffuse through a membrane until their partial tensions are the same in the two spaces which the membrane separates. The æther in which physicists picture gases as dissolved offers no resistance to the migration of their molecules; neither does the solvent—water, for example—prevent the movement of salts which are distributed through it.

One other illustration of the phenomena of osmosis will suffice to give an idea of the laws by which they are governed. In the case just cited the membrane was permeable to all the salts in solution. When the phenomena of osmosis were first investigated, a distinction was drawn between substances which will pass through membranes—crystalloids—and substances which cannot pass—colloids. We have already had occasion to note that, whereas albumin is a colloid which does not diffuse, its hydrate, peptone, is a crystalloid which does. The term “crystalloid” indicates that substances which can be crystallized are diffusible. Substances which are diffusible are therefore allied to those which crystallize. The nature of the membrane used to test diffusibility was not at first taken into account. Now a distinction is drawn between membranes which are permeable to all diffusible substances, and membranes which are permeable to the solvent, but impermeable to the substances which it dissolves. The latter are termed “hemipermeable.” Imagine now that water is separated from a solution of sugar by a membrane which stops sugar, but is permeable to water. Water will pass through the membrane into the solution of sugar. The level of the solution will rise. Pressure will be needed, and a very considerable pressure, to prevent its rising—to prevent endosmosis, that is to say. The force needed to resist osmosis is directly proportional to the degree of concentration of the solution. If the solution contain 1 per cent. of sugar, a pressure of 500 millimetres of mercury is needed; if it contain 2 per cent., a pressure of 1,000 millimetres; if 6 per cent., of 3,000 millimetres.

In the next experiment separate two solutions, A and B, by a hemipermeable membrane. Let A contain one salt only—X; let B contain several salts—X, Y, Z. Water will pass from A to B, or _vice versa_, unless the osmotic pressure of the salts which the solutions contain is the same. The osmotic pressure will be found to be the same if the total number of molecules dissolved in A equals the total number of molecules dissolved in B. If in A there be N molecules of X (per unit volume), and if in B there be nX, n′Y, n″Z, the osmotic pressure will be the same provided n + n′ + n″ = N. This, it will be seen, is a very different matter from equality of percentage composition. Some molecules are light; others are heavy. The percentage weight of X + Y + Z in B may be very different from the percentage weight of X in A. To estimate the osmotic pressure of a mixed solution, it is not sufficient to add together the percentages of the various salts which it contains. “Concentration,” in the sense in which it was used in regard to blood and urine, refers to the number of molecules of dissolved substances in a given volume, not to their weight.

It would be undesirable to attempt in this place to enter upon the theory of osmosis. Enough has been said to suggest to the reader that he should, when endeavouring to apply its laws to the explanation of physiological phenomena, bear the following facts in mind: Some membranes are permeable to water and to the crystalloids which it dissolves; others, although permeable to water, are impermeable to substances in solution. Some substances are diffusible through permeable membranes; others are not. Osmosis of water occurs from the solution of lower to the solution of higher concentration. Diffusion of crystalloids is their escape, owing to their own molecular movements, from a situation in which they are denser to a situation in which they are less dense. It must be added, however, that various circumstances prevent the reduction of the laws of osmosis to simple terms—the tendency of salts to dissociate when in solution, their bases and acids acting as independent “ions,” is an example of the complications which produce apparent departures from these laws. It must further be added, and with emphasis, that, important though it be that anyone who attempts to explain the interchanges which occur between the various fluids of the body should be conversant with the laws of osmosis, it is impracticable, and in some cases misleading, to rigidly apply them. Living membranes and dead membranes do not necessarily control diffusion in the same manner. Still less do the laws which govern diffusion through dead membranes hold good, without qualification, to living cells.

To return to the sanitary engineer whose opinion we asked regarding the mode of working of the drainage system of the kidney. Probably he would deny that the problems came within his province. “They are not physical, but vital,” he would say. “I know nothing about the vital action of the cells which line the tubule.” Objection may be taken to the form of expression, albeit he was fully justified in declining to discuss the question any further. He does not know enough about the internal structure of a cell to be able to predict the phenomena of osmosis which will occur within it. No one can say what capacity living cells may have of taking substances from the blood, returning some of them, and excreting others. This unknown capacity leads to results which, when they do not appear to be in accordance with the laws of physics, are commonly termed “vital.” The term is a stumbling-block which has tripped up generations of physiologists. The expressions “vital action” and “physical phenomena” have been used as if they were antithetical, whereas all vital actions are physical phenomena. “Vital” in this sense connotes “as yet unknown.” Yet, in truth, there is abundant excuse for the use of a term which covers ignorance, so long as its connotation is not extended until it assumes a positive, antiphysical sense. “Physical” and “vital” are expressions which point a contrast constantly present to a physiologist’s mind. He knows perfectly well that the passage of water and salts through a membrane, and their passage into and out of a living cell, are equally phenomena of osmosis. But the former process he can test and measure in his laboratory; the latter he can but observe in much obscurity in the living body. He cannot make a model of a living cell. In the case of the salivary gland, as we have already seen, living cells take water from lymph, and discharge it as saliva in apparent opposition to osmotic force. They reverse the direction of the flow which would occur were lymph and saliva separated by a membrane. But a cell is not a membrane. It is an extremely complicated structure with an elaborate architecture of its own. As well might we compare the distribution of water by a County Council water-cart and its passage through a brewery. According to all the laws of hydrostatics, the water which flows into a brewery should leave it through its drains. Its exit in barrels on drays is antiphysical. When the physiologist can explore the living cell, he will discover that the imbibition and extrusion of water, the selection, retention, and discharge of salts, are phenomena as strictly physical as their passage through a dialyser in his laboratory. In the meantime he can but contemplate the cell with a certain degree of awe. His best devised model of a urinary tubule may lead him into error, for the simple reason that he cannot line it with living cells. A living cell has a power which upsets all calculations, falsifies all experimental findings. Its protoplasm can isolate and place out of action any of the substances which enter it. If observations eventually prove to us that water passes from the urinary tubules into the blood, “in the face of osmotic force,” we shall be constrained to explain this antiphysical phenomenon as due to the action of living cells. The cells, we shall say, take up fluid from the urinary tubules, fix its urea and other salts in their protoplasm, discharge its water into the venous blood, return the urea and other salts to the urine. Given this property of protoplasm, such a process is strictly in accordance with physical laws.

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Enough has been said regarding the theory, or want of theory, of the action of the kidney. Turning now to matters of observation, it can easily be shown that the epithelium of the tubules has the power of excreting into the urine highly complex materials which diffuse with difficulty. If a substance soluble in blood, but insoluble in urine, an alkaline salt of indigo, for example, be injected into the vascular system, it is rapidly excreted by the kidney. The indigo is precipitated even before it comes in contact with the acid urine. If the animal be killed a short time after the administration of the indigo, the contorted portions of its tubules and the ascending limbs of the loops of Henle are strongly coloured blue. An ammoniacal solution of carmine may be used for a similar experiment; but the results are not nearly so sharply limited to the large-celled portions of the tubules. Even the glomerulus is coloured red, a fact which has been interpreted as showing that, although the greater part of the carmine is excreted into the tubules, some of it accompanies the water which exudes from the blood through the glomerular tufts.

The practical identity in structure of the kidney in birds and reptiles and mammals would seem to have an important bearing on this controversy. The urinary excretion of birds consists almost exclusively of uric acid. As seen under the microscope, it is a semi-solid white deposit, made up of crystals, supposing no special precautions have been taken to obtain it fresh. The water, pigment, and salts which are essential elements of the excretion of mammals are practically absent. Yet the kidney of a bird presents the same arrangement of glomeruli and tubules as the kidney of a mammal, although the glomeruli are relatively smaller. Uric acid diffuses with great difficulty. If it is, so to speak, washed through the glomeruli, and the water which dissolved it reabsorbed by the tubules, an enormous quantity of water must pass through the kidney in order that it may carry the uric acid in its stream. If uric acid be excreted by the epithelium of the tubules, it is difficult to account for the presence of glomeruli, since no water leaves the kidney. Crystals of uric acid are to be seen in a section of the kidney, not only in the cells of the tubules, but also in the glomeruli; but it may well be that in both situations crystallization has been induced during the preparation of the section. It jars an histologist’s conception of the constitution of a secreting cell to contemplate the formation within its network of protoplasm, and the extrusion from it, of sharp-angled crystals. As a matter of fact, it is not in its crystalline form that uric acid is excreted by birds, but as quadri-urates—_i.e._, salts containing only one-fourth of their “normal” complement of base; crystalline spheres or amorphous deposit, not angular crystals. These quadri-urates decompose very quickly, setting free crystals of uric acid. It must be confessed that, in whatever way one attempts to account for the excretion of uric acid by birds, the similarity of structure of their kidneys and those of mammals is difficult to reconcile with the wide difference in consistency and in chemical composition of the excrement.

Reflecting upon all the evidence bearing upon the mechanism of the mammalian kidney, the majority of physiologists come to the following conclusions: The greatest outflow of water occurs in the glomeruli. The water is accompanied by salts, including a small quantity of urea. The contorted and spiral portions of the tubule and the ascending limbs of Henle’s loops add to the urine the remainder of the urea, together with various bodies still less readily diffusible.

It may be that the chief function of the loops of Henle is to oppose resistance to the passage of fluids, thus heading up the secretion, and favouring the osmosis of water into it from the blood of the glomerular capillaries. It is possible that the calibre of the slender descending limbs is influenced by external pressure, their partial occlusion being increased, and the pressure in them raised, when the organ is very active and its intermediate zone turgid with blood.

Various drugs influence the secretion of the kidney. In some cases their action seems to be mainly hydrostatic. They change the rate of flow by altering blood-pressure. Digitalis increases the force of the heart. The heart beating more strongly, blood-pressure rises. Higher blood-pressure is accompanied by a more copious secretion. This action of digitalis is far more marked when the heart is out of order than when it is healthy. In heart-disease the blood-pressure is unduly low, and the tissues become water-logged in consequence. When the blood-pressure is restored and a brisker capillary circulation established, water and waste products, which have accumulated in lymph, pass, as they ought to do, into the veins. Carried into the general circulation, they overflow from the kidney.

It is a little difficult to realize the abundance of the body-fluids. From one-quarter to one-third of the whole body-weight is due to lymph, using this term in its most general sense. The waste products of tissues collect in the lymph. The blood circulating through capillary vessels which traverse lymph-spaces takes up water and waste products. Its just composition is maintained by the eliminating activity of the kidneys.

Even in the diuretic action of digitalis we see indications of something more than an alteration of the hydrostatics of the blood-supply of the kidney. The brisker circulation carries waste products to the liver; the liver transforms nitrogenous refuse into urea; urea stimulates the renal epithelium. It would be a mistake to lay too much stress upon the direct effect of the drug upon the blood-pressure in the kidney. Other illustrations throw the mere hydrostatics of the problem into the background. Adrenalin (extract of suprarenal capsule) causes a severe contraction of the small arteries, which raises the general blood-pressure considerably; but the increased blood-pressure is not accompanied by diuresis, because the glomerular arterioles share to a full extent, perhaps to a disproportionate extent, in the general constriction. In migraine and certain other disorders it frequently happens that the blood-pressure in the aorta is unduly high, yet very little fluid enters the renal tubules. If a “saline diuretic,” potassic nitrate, sodic acetate, or some other drug of the same kind, be administered, a copious flow is established, the blood-pressure is relieved, the distressing symptoms disappear. Then, again, certain diuretics, such as “sweet spirits of nitre,” tea, gin, etc., may bring about a flow out of all proportion to the alteration they produce in the hydrostatics of the circulation. The diuretic action of these various drugs is clearly due to increase in permeability of the renal epithelium. And, of all stimulants to secretion, urea, the natural stimulant, is the most effective. If a kidney be removed from the body, a cannula inserted into its artery, and defibrinated blood caused to circulate under pressure through the organ, water may or may not drip from the ureter. On addition of urea to the blood, a copious excretion is set up. In explaining the mode of working of the kidney, as, indeed, in explaining that of every other organ of the body, the mechanical aspects of the problem must be kept in the background. When we are contemplating the plan of construction of the kidney, the hydrostatics of the circulation attract attention; but alterations in hydrostatic conditions are not the initiating cause of a greater or less flow of urine. The chemical condition of the blood circulating through the kidney is the initiating cause. When the presence in it of urea demands a more copious flow, the hydrostatic conditions are adjusted to this need. In the case just cited of the isolated kidney, it might be urged that the flow caused by urea is a mechanical effect. The cells of the contorted portions of the urinary tubules remove urea from the blood. They secrete it into the tubules. The solution of urea, being headed up towards the glomeruli, owing to the resistance offered to its passage down the tubules by the narrow, descending limbs of Henle’s loops, surrounds the capillary tuft. Urea rapidly attracts water from the blood. A copious flow is the result. But it is just this contrast between the capacity of removing urea possessed by living cells, and the passage of urea in solution from one side to the other of a membrane, which justifies the retention of the expression “vital.” Mechanical conditions are those which we can imitate in a model; vital conditions, those which at present we are unable to reproduce.

=Nitrogenous Waste.=—Meat, fish, eggs, milk, vegetable-albumins, are the sources of nitrogen. The kidney is the organ which eliminates it from the body. Since all nitrogenous food which is digested is eventually reduced to simple, soluble compounds which appear in the urine (the quantity thrown off in perspiration is so small as to be negligible), the proportion which the nitrogen of the urine bears to the nitrogen in the food is a measure of the efficiency of digestion. A certain quantity of the nitrogen eliminated is in the form of uric acid, creatinin, and other compounds of a like order; but these less oxidized substances, though always present in some degree, are not, in Man and other mammals, the normal end-products of nitrogenous metabolism. Urea is the final and simplest product. It is therefore sufficient to estimate the quantity of urea excreted, and to compare the nitrogen which it contains with the nitrogen ingested in the form of “animal food.” About nine-tenths of the nitrogen ingested should be accounted for by urea. When alimentation is excessive or digestion imperfect, the proportion is less than this; some nitrogenous food is not absorbed; some that is absorbed is imperfectly oxidized.

=Urea= is characteristically an animal product. Inorganic chemistry deals with stable, organic chemistry with unstable, compounds. Not that there is any boundary between inorganic and organic chemistry. They are merely terms which it is convenient to use to indicate the groups of atoms which occupy the chemist’s attention at the time. Nor is stability an attribute of certain groups, instability an attribute of others. Stability is relative, not absolute. But admitting these terms as convenient indications of degree, it may be said that inorganic chemistry has to do with such substances as carbonates, nitrates, ammonia; organic chemistry, with compounds in which carbon is not satisfied with oxygen, as it is in carbonic acid; nitrogen not satisfied with oxygen, as in nitric acid, or with hydrogen, as in ammonia. Carbonic acid (anhye)drid has the formula CO₂; ammonia, the formula NH₃. Urea is a combination of the two compounds. It is carbonic acid in which one (divalent) atom of oxygen is replaced by two (monovalent) atoms of ammonia. It is ammonia in which two (monovalent) atoms of hydrogen are replaced by one (divalent) atom of carbonic acid.

Carbonic Urea Ammonia anhydride NH₂ / CO₂ CO NH₃ \ NH₂

Urea is an amide—carbonic diamide. It very readily takes water into its molecule, changing into carbonate of ammonia. N₂H₄CO + 2H₂O = (NH₄)₂CO₃. This change is rapidly brought about by the influence of bacteria in urine exposed to the air.

In thinking of the transformations which proteid substances undergo in the system, it is legitimate to regard their nitrogen as from the first united with hydrogen in the form of ammonia. Not that the grouping is so simple as this. An albumin is not an amide. But in the dance of atoms of its great molecule as it progresses through the system—forming part of the blood, taken up by the cells as floating protein, incorporated in the protoplasm of the cells, shaken into smaller aggregates in the muscles—nitrogen and hydrogen are partners. They leave the body hand in hand. Gusts of oxygen atoms enter through the lungs; use blood-corpuscles as carriages; dismounting, they traverse lymph, forcing their way into the interior of the cells; they join in the dance. With their strong arms they detach carbon atoms and hydrogen atoms from the huge albumin chain. As carbonic acid and water they bear them to the lungs. But nitrogen clings to hydrogen. Oxygen cannot detach its grasp. Out of the molecule of albumin this firmly united couple slips, without contributing anything to the energy which moves the body and keeps it warm. Nitrogen is not a source of energy. It even saves a portion of the hydrogen of albumin from combustion. Urea burnt in a calorimeter has a balance of energy to give up.

Many attempts have been made to ascertain the stages through which proteins pass on their road to urea. The search for intermediate compounds is probably futile, since there is no sufficient reason for supposing that proteins disintegrate in stages, each a step less complex than the food and a step nearer to urea. Every nitrogenous extractive found in the tissues is, of course, on its road to urea. It will be removed as urea, unless indeed, like uric acid or creatinin, it has to be excreted without further change. But it appears to be impossible to discover in the tissues any nitrogenous compounds which occur in sufficient quantity to justify us in regarding them as inevitable halting-places on the downward road (_cf._ p. 146).

The metabolism of albuminous substances, like other oxidations, takes place chiefly in muscles. Very little is known regarding the nature of the products. Urea is not amongst them. Whatever they may be (_cf._ p. 267), they are carried to the liver, in which they are turned into urea.

The metabolism of the body is not normally derived from the oxidation of nitrogenous foods. Failing a sufficient supply of other kinds of food, they may be used as sources of energy; but we must picture them as splitting into carbonaceous and nitrogenous portions. If, after the reserve of glycogen in the liver has been brought low by abstention from carbohydrates and fats, nitrogenous food is consumed, and the muscles are then called upon to do severe work, the amount of carbonic acid and water given off rises at once. The excess of urea derived from the nitrogenous food which was destroyed for the purpose of liberating the energy which the muscles expended makes its appearance some time later. If the diet contains a sufficiency of carbohydrates, muscular work does not increase urea. The output of urea is exceedingly steady. It is not increased by muscular work, nor diminished, beyond a certain limit, by absence of food. The tissues are constantly throwing off nitrogen-containing molecules, which, if the body is not to waste, must be as constantly renewed.

=Uric Acid.=—When nitrogenous metabolism has reached the bottom, when albuminous substances have been shaken into the simplest and most stable compound or compounds which the muscles are capable of making (we know not whether the end-products be one or many), they are carried to the liver by the blood. The mammalian liver converts them into urea; the liver of birds and reptiles changes them into uric acid. Uric acid is not, however, completely absent from the urine of carnivorous animals. In Man the amount excreted is about 0·8 gramme per diem, but subject, even in perfect health, to considerable variations (0·2 gramme to 1·4 gramme). There is no reason for thinking that uric acid is made in the liver of mammals. On the contrary, it seems to be either an end-product of the disintegration and oxidation of leucocytes (_cf._ p. 53), or, like certain other more complex nitrogenous compounds which appear in very small quantities in the urine, the relic of albuminous food which has missed the broad down-path, via muscles and liver, to the kidney. It is a troublesome burden for lymph and blood, and, unfortunately, the kidney finds difficulty in throwing it out. Uric acid has a pernicious way of accumulating in tissue-spaces, producing all the malevolent symptoms of gout. During an acute attack of gout the quantity of uric acid in the system may be largely increased. It may be so abundant in the blood that, when a sample is allowed to cool, uric acid begins almost immediately to crystallize out. Speaking generally, it is right to ascribe gout to an over-production of uric acid; but it must be remembered that the balance between elimination and production is very delicately adjusted. During an attack of gout the amount excreted in the urine is not increased; frequently it is less than usual. The clearing up of the attack is accompanied by abundant excretion of urates, or lithates (λίθο, stone), as they used to be called, because the “stones” which are found in the bladder consist largely of uric acid. From this it appears that faulty distribution and inadequate excretion have more to do with the development of the symptoms of gout than over-production. In a previous chapter (p. 140) we gave as the predominant cause of gout acid fermentations in the stomach. It does not, by any means, follow, however, that we were right in correlating imperfect digestion with an excessive formation of uric acid. It may well be that the gouty symptoms to which hampered peptic digestion gives rise are due in larger measure to a disturbance of the composition of the body-fluids which renders them unfit to carry uric acid to the kidneys in such a form, or in such relation to the fluid in which it is dissolved, as will insure its escape into the urinary tubules. The interference with the efficient working of the system caused by accumulation in it of uric acid gives a particular interest to all that is known regarding the nature and origin of this substance.

Uric acid has the formula C₅H₄N₄O₃. It is a more complicated and a more stable body than urea. The deposits of guano in Peru contain uric acid (the excrement of birds) which has remained practically unchanged for years—for centuries, perhaps. Its chemical nature is not completely understood. It can be readily made to yield urea; and it can be formed by conjugating urea with a nucleus derived from lactic acid (_cf._ p. 13). Its formula is therefore commonly represented as that of a diureide—a substance containing two urea radicles:

{ HN——CO { | CO { C——NH } { | } CO { HN——C——NH }

But notwithstanding this inclusion in its molecule of two radicles of urea, it is safe, when one thinks of the contrast between urea and uric acid, to lay stress, in the case of the former, on the binding of nitrogen to hydrogen; in the case of the latter, on the binding of nitrogen to carbon.

Uric acid is soluble with difficulty; it crystallizes in rhombs. It forms salts, normal and acid. Those which appear in the urine are always acid salts. As a treatment for “stone,” lithia water has long had a reputation which it probably deserves, the acid urate of lithium being the most soluble salt of uric acid which the kidney can secrete. When uric acid is in excess in urine, brown crystals of uric acid are deposited as “gravel” soon after it is passed. Even when not in excess, uric acid crystals appear after a sufficient time. In other cases uric acid, when in excess, is thrown down in the form of a cloud of acid urates of sodium and other bases, which renders the urine turbid. These urates are redissolved when the water is warmed.

The more fortunate of human beings need never concern themselves with the chemical history of uric acid. It is always present in their body-fluids. It is excreted by the kidney. Its formation is of no greater interest than that of creatinin and other nitrogenous compounds which escape the almost universal reduction to urea. Persons who have a uric acid diathesis are in a very different plight. Every scrap of evidence bearing upon its origin is of supreme importance. Unfortunately, the evidence collected as yet is scanty, and its application for remedial purposes impracticable.

The only disease in which uric acid is invariably in excess is leucocythæmia. This is a condition or habit marked by the presence in the blood of a very great number of white blood-corpuscles and a paucity of red ones. The connection between this disease and the production of uric acid is made plain by certain experiments in diet. If flesh which contains relatively a large proportion of cell-nuclei is eaten, the uric acid excreted is markedly increased. Sweetbread, especially “neck sweetbread”—_i.e._, thymus gland—is a mass of comparatively small cells with large nuclei. If thymus gland be substituted for all other meaty foods, the quantity of uric acid appearing in the urine is doubled. A large increase in the quantity of ordinary meat or fish consumed also increases uric acid, because all meat-fibres contain nuclei. If egg-albumin be taken instead of meat, uric acid is not increased. A sudden excess of muscular work leads to an increase in uric acid, owing presumably to the unusual activity of the tissues. This used to be very noticeable in the case of young men during the first few days of “training” under the old system; but it may have been due to the generous consumption of chops and steaks, rather than to the increase in physical work, and consequent destruction of tissue. Nuclei contain nucleo-proteins, which split into proteins and nuclein. Chemically, it is reasonable to attribute to nuclein the parentage of uric acid; a plausible line of descent can be traced. The association of leucocythæmia with the production of uric acid is probably due to the destruction of leucocytes which are present in abnormal numbers (_cf._ p. 53).

Such is the evidence at present in the hands of physiologists. Naturally, physicians have endeavoured to turn it to account. Patients have been recommended to avoid animal foods which contain nucleo-proteins—to take, instead of meat and fish, eggs, milk, cheese, vegetable-albumins. Certain physicians contend that such a diet is followed by the happiest results; others, equally competent, and perhaps less biassed by “medical theory”—the most dangerous of handicaps for anyone who practises an art which must ever remain empirical—are satisfied that equally good results are obtained by excluding from the diet eggs, milk, and cheese. Physiological discoveries suggest treatment. Modern medicine is in the fullest sense applied physiology. But treatment based upon theory must be controlled by unprejudiced observation. It is possible that the gouty diathesis may be held in check in certain cases by the exclusion from the diet of certain kinds of nitrogenous food. The experience of generations has taught us that the injudicious use of such articles of diet as fruit, pastry, sugar, which do not contain nitrogen, is the main factor in inducing an attack of gout; that imperfect digestion, sluggish circulation, insufficient activity on the part of the kidneys, lead to the accumulation in tissue-spaces of the _fons et origo malorum_. Even sweetbread, which with the precision of a chemical experiment increases the production of uric acid by a healthy person, is not necessarily found unwholesome by those who are inclined to gout. It is amongst the most digestible of all meat foods, and easy digestion covers a multitude of metabolic sins.