The Body at Work: A Treatise on the Principles of Physiology

by Alex Hill

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.

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.