M. Grace Eggleton

The effect of ethyl alcohol and some other diuretics on chloride excretion in man

Evidence as to the nature of the diuresis following ingestion of ethyl alcohol (ethanol) suggests that it is similar to the diuresis following ingestion of water. In view of the lack of absolute proof of their identity, however, a further comparison of the two has been made in respect of certain properties by which a water diuresis can be differentiated from other types of diuresis. One such property is the response of the kidney in respect of excretion of chloride; an increased rate of urine flow is in general associated with an increased output of chloride, but, in a water diuresis, the great increase in rate of flow is accompanied by a diminished chloride output (Eggleton, 1943). The results of a series of class experiments on the effect of exercise on renal function, when different diuretics were used to promote urine flow, suggested that alcohol and water had the same effect in diminishing excretion of chloride (Eggleton, 1945), whereas tea increased it. The matter has now been investigated more fully and under more standardized conditions, without the additional effects of exercise.

Glucose and phosphate excretion in the cat

The mode of reabsorption of phosphate by the kidney of the cat differs from that in man and dog in that no maximal rate (Tm value) is attained (Eggleton & Habib, 1950). Glucose and phosphate reabsorptions appear to be interrelated in man and dog, and it seemed of interest, therefore, to see whether they are inter-related also in the cat. Little is known of the mode of reabsorption of glucose in this animal, though from the results of Gammeltoft & Kjerulf-Jensen (1943), who used a high plasma-glucose concentration in studying the mode of excretion of fructose and galactose in various species, it would seem that glucose has no Tm value.

Determination of the metabolic rate of alcohol.

THE rate at which alcohol is oxidized in the body is measured approximately by the rate at which it disappears, since the proportion excreted is small and regular; and the rate at which it disappears is equal to the body weight multiplied by the rate of change of concentration in the whole body. In man, however, the rate of change of concentration can be measured only in the blood. Hence, it is of importance to know the relation between the concentration in the blood and the concentration in the whole body at the same moment. If this relationship is not reasonably constant, the extent and time relations of any variation must also be known. The proportion of the body in alcohol equilibrium with the blood (i.e. the mean concentration in the whole body expressed as a fraction of the blood concentration) has been designated r by Widmark [1932] and is derived from the change in blood alcohol concentration in the following manner (see Fig. 2). The straight line joining the experimental points is extrapolated back to zero time, giving the theoretical initial concentration in the blood (CO): the amount of alcohol injected and the weight of the subject are measured; then

Excretion of para‐aminohippurate by the kidney of the cat

The kidney of the cat has been shown to behave differently from that of man or the dog in its manner of excreting thiosulphate (Eggleton & Habib, 1949), and an investigation has therefore been made to determine the manner in which para-aminohippurate (PAH) is excreted. In both man and dog, this substance is actively secreted by the tubule cells (Smith, Finkelstein, Aliminosa, Crawford & Graber, 1945); at low concentrations in the plasma, it is almost completely removed from the blood during its passage through the kidney, so that its clearance provides a measure of the minimal renal plasma flow, and at higher concentrations, a maximal rate of secretion is rapidly attained, this value providing a measure of tubular function (Tm).

The mode of excretion of creatinine and inulin by the kidney of the cat.

Inulin is used at present for the measurement of glomerular filtration rate (G.F.R.) in most species of laboratory animal, including man, and the evidence in favour of the hypothesis that it is freely filtered at the glomerulug and neither secreted nor reabsorbed by the tubule cells is apparently strong (Smith, 1937). Certain other substances have the same clearance as that of inulin in certain species, e.g. creatinine and ferrocyanide in the dog, but not in man, and creatinine has been used for measurement of G.F.R. in the cat (Eggleton & Habib, 1949a), since its clearance was found to be independent of changing creatinine concentration in the plasma. This clearance has now been compared with that of inulin over as wide a range of concentrations of the two substances as possible and with the concentrations both increasing and decreasing. The two clearances were identical under certain conditions, but under others the creatinine/inulin clearance ratio varied between 0-65 and 1-7. When the two are not identical, the evidence suggests that creatinine clearance is the more probable measure of filtration rate.

Urine acidity in alcohol diuresis in man

Available evidence suggests that the diuresis following ingestion of ethyl alcohol is of the same nature as water diuresis mediated by the pituitary gland (Eggleton, 1942b). In an effort to establish further points of similarity or difference between the two types of diuresis, a class experiment on the effects of exercise on urinary excretion was performed identical with those previously reported (Eggleton, 1942a, 1943) except for the substitution of alcohol as the diuretic in place of water or tea. The main results of the experiment confirmed those obtained when water had been used as the diuretic, but one unexpected difference suggested that alcohol per se might lead to the excretion of an acid urine. The matter has therefore been investigated in a number of subjects by observing the pH of the urine during water diuresis and during alcohol diuresis under strictly comparable conditions.

The effect of exercise on chloride excretion in man during water diuresis and during tea diuresis

In studies on the effect of exercise on urinary excretion in man, some diuretic is habitually used to facilitate frequent sampling of urine. Water has been most usually employed in this connexion, but tea was used in one major work on the subject [MacKeith, Pembrey, Spurrell, Warner & Westlake, 1923]. Comparison of results obtained under the action of these two different diuretics is unreliable, owing to the different conditions prevailing in the different sets of experiments, especially in regard to the severity and duration of the exercise undertaken. An attempt has now been made to differentiate the changes in urinary excretion due to the exercise and those due to the diuretic employed, by experiments under more comparable conditions.

Renal function in the primitive mammal Aplodontia rufa, with some observations on squirrels

Aplodontia rufa or mountain beaver is the oldest known group of living rodents, its time range extending from late Palaeocene to Recent; it is found only in the Northwest Pacific region of the U.S.A. In zoological classification, the family Aplodontidae is one of eight included in the suborder Sciuromorpha of the order Rodentia; the other seven families cover squirrels, marmots, beavers, mice and all rats, including the desert rat. The last named is one of the mammals of which the kidney has the greatest ability to conserve water, while that of Aplodontia, as shown by the results presented below, appears to be the least efficient. Our attention was drawn to the animal by the report of Pfeiffer, Nungesser, Iverson & Wallerius (1960) that its kidney was very primitive; 70 % of the nephrons examined lay entirely in the cortex, and of the remainder only one sixth had long loops of Henle, none of which had a thin segment. It seemed likely, therefore, that this animal would be unable to excrete a concentrated urine, as already suggested by Nungesser, Pfeiffer, Iverson & Wallerius (1960), and experimental corroboration of this would be yet further evidence that the present view of the importance of the loop of Henle in water reabsorption is correct. This investigation incorporates also some preliminary results on the concentrating capacity of the kidney in three species of squirrels.

The state of body water in the cat.

In the course of an investigation into the relationship between chloride concentration in skin and in plasma, hypertonic sodium chloride solution was injected. The resulting increase in chloride concentration in the plasma water enabled calculation to be made of the volume of water in the body in which the added chloride appeared to become distributed. It proved to be significantly less than the generally accepted figure for total body water. This, consequently, was measured in addition by determining the volume of water into which urea would diffuse.

Urinary excretion of phosphate in man and the cat

The dominating factor controlling phosphate excretion when the concentration of this ion in the blood plasma has been artificially raised is, both in man (Ollayos & Winkler, 1943) and in the dog (Harrison & Harrison, 1941; Pitts & Alexander, 1944), this concentration itself; since the tubule cells can only reabsorb a limited amount of phosphate, the clearance rises as the concentration in the plasma is increased. When extra phosphate is not given, factors other than variation in the concentration in the plasma can be observed to affect the clearance. In fact, the variation in such concentration is so small under normal conditions that much can still be learned by following the changes in rate of phosphate excretion in place of the more complex determination of changes in absolute clearance values. Thus Haldane (1921) observed a large increase in phosphate excretion when the body had been acidified by ingestion of ammonium chloride. Havard & Reay (1926) noted a similar effect after severe exercise, the increased excretion long outlasting the very small and fleeting increase in plasma phosphate concentration; the increase in phosphate output under these conditions was confirmed by Eggleton (1942). The mechanism of this action in the kidney is not yet understood. Attempts to correlate the changes observed in phosphate output under other experimental conditions have led to no very definite results. Most workers are agreed that rate of urine flow is not concerned, though Dean & McCance (1948) have recently revived the suggestion on finding a significant correlation between the two in newborn infants. The probable explanation of this will be discussed later. In view of the fact that there is a limit to the amount of phosphate which can be reabsorbed from the tubules, it would seem highly probable that many changes in phosphate excretion normally observed might be explained as due to variation in the amount of phosphate filtered: a change in glomerular filtration rate (G.F.R.) would have a similar effect to that produced by a change in plasma phosphate concentration. Experimentswere designed, therefore, to induce relatively large variations in G.F.R., in urine pH