The secretion of urine as studied on the isolated kidney

Abstract

Broadly speaking, there are two main avenues of approach in the attempt to unravel the complicated processes which determine the function of any individual organ. On the one hand, we may study its reaction in the intact animal to comparatively small environmental changes—a method of inestimable value, since it is one which may readily be applied to man ; on the other hand, we may remove the organ and study its reaction under grossly artificial conditions. In the former case, we sacrifice simplicity and full control to a close approximation to normality in environment ; in the latter case, we sacrifice normality in environment in order to obtain greater simplicity and a higher degree of experimental control. The former may be referred to as the analytic method of experimentation, the latter as the synthetic. On the one hand, we attempt to dissociate the medley of influences which share in determining the normal function of the organ, and to relegate to each its particular office in maintaining this normality ; on the other hand, we attempt to associate these influences in such a degree and in such a manner as to bring the isolated organ back to an environment and function comparable to the normal. We have used the latter method in an attempt to throw more light on the mechanism of urinary secretion in mammals. In order that the mammalian kidney may be kept alive in the isolated state, it is obvious from a consideration of its relatively enormous oxygen consumption—a consumption per gram per minute which may exceed that of the heart(10) (68)—that an efficient means of supplying this want must be at hand. Perfusion experiments such as those of Ludwig(1) in which a dog’s kidney was perfused with a solution containing 3 per cent. gum and 1 per cent. NaCI, can only hope to throw some light on the mechanical conditions obtaining in the dead organ. In 1890, Jacoby(2) perfused the isolated kidney of the dog with defibrinated blood by means of a pump and arterialised the blood by means of a current of air. With v. Sobieranski(3) he succeeded in obtaining a very slow urine flow by this means, but the fluid secreted invariably contained protein in considerable amounts. Three years later an improvement(4) in the form of apparatus was introduced in that an artificial pulmonary circulation was maintained by means of a second pump, the arterialised blood being then sent to the kidney as before. This improvement in technique, however, failed to give results of any promise. Similarly, Pfaff and Vejux Tyrode, (5) perfusing the dog’s kidney with defibrinated blood, invariably obtained blood and protein in the fluid issuing from the ureter. They claim to have shown that this untoward result was due to the toxic action of defibrinated blood. On defibrinating an animal the urine simultaneously secreted contained blood and protein, but this rapidly disappeared on removing the defibrinated blood, and replacing it with normal blood from another dog by bleeding this animal directly into the other’s venous system. Hirudin was tried and gave better results, but the experiments were not continued. The experiments of Sollmann(6) were performed with dog’s kidneys in the dead or dying condition. These were perfused with saline or highly diluted defibrinated blood in an attempt to study the mechanics of the organ. In 1903, Brodie(7) described an apparatus for the perfusion of isolated organs with oxygenated and defibrinated blood. He noticed, as had Pfaff and Vejux Tyrode, that vasoconstriction quickly set in under the conditions of experiment, but that(8) this could be overcome by the addition of chloral or amyl nitrite to the blood. A urine flow up to 16 c. c. per 15 minutes was obtained. Again, Hooker, (9) in a study of the influence of pulse pressure upon renal function, perfused dog’s kidneys by means of a pump with defibrinated blood through which oxygen was bubbled. He obtained a “ filtrate, neutral to litmus.” No other details of its composition are given. Up to this time it is clear that little success had been forthcoming in attempts to keep the isolated mammalian kidney alive, much less to function in a capacity approaching normal.

The time course of salt-induced hypertension, and why it matters

“…[50][51][52] This phenomenon refers to the increase in urinary sodium excretion induced by an elevation of renal perfusion pressure and the corresponding fall in urinary sodium excretion that can be produced by reducing renal perfusion pressure. This relationship between renal perfusion pressure and urinary sodium excretion (the acute pressure-natriuresis relationship) is often used to define the salt-excreting capacity of the kidney at a given point of time and has been assessed in isolated perfused kidneys 53,54 as well as those of intact anesthetized 55 and conscious animals. 56 Pressurenatriuresis provides an important mechanistic link between blood pressure and salt excretion, and contributes to the regulation of both of these variables.…”

Observations on the fate of indolalkylamines in the organism

“…It may be of interest to recall here that an abrupt liberation of platelet 5-HT, such as occurs for example in the defibrination of the blood, imparts to the dog's blood a powerful constrictor action on the renal vessels, which disappears only after the defibrinated blood has circulated for 10-20 min through the lung or the liver (Starling & Verney, 1925;Herrick & Markowitz, 1929). It should be stressed that the quantity of 5-HT which provokes this powerful vasoconstriction could be renewed every 2 hr, if the daily urinary output is 450,ug HIAA/dog, or at least every 20 min if the higher estimates (3000,ug/ dog/24 hr) given by Titus & Udenfriend (1954) are correct.…”

Proceedings of the Physiological Society, 2‐3 July 1976, Historical Demonstrations

“…Gaddum Verney's work on the kidney began at University College London with the perfusion of the isolated kidney by the heart-lung preparation (Starling & Verney, 1925); the urine produced by the perfused kidney was of large volume and dilute. The control of diabetes insipidus by injection of extract of the posterior lobe of the pituitary had been described.…”