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 anhydride | Urea | Ammonia | ||
|---|---|---|---|---|
| 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.