Clark D. West

THE MECHANISM OF GLYCOSURIC DIURESIS IN DIABETIC MAN

Although diuresis has long been recognized as one of the important physiologic aberrations of the diabetic state, its exact nature has not been fully explained. Cushny assumed that the unabsorbed sugar in the renal tubule limits the reabsorption of water through offering osmotic resistance. Thus hyperglycemia leads to glycosuria which in turn causes diuresis (1). Other authors have assigned an important role to an increased electrolyte excretion (2, 3), while others have implicated the acidosis (4). It would appear that all three mechanisms, glycosuria, salt loss, and acidosis, may contribute to the copious urine flow of diabetic patients. It is well known that large electrolyte losses may occur in the uncontrolled diabetic patient (5-8), but the mechanism of the losses has been the subject of some disagreement. While Peters and his associates (4) maintained that the dehydrating effect of acidosis per se was more important than the glycosuria, others have stated the reverse to be the case. Hendrix and his co-workers (2) found large losses of inorganic base in depancreatized, non-acidotic dogs, with polyuria and glycosuria, fed large amounts of glucose. Atchley and his colleagues (3) found in human diabetics deprived of insulin that the initial loss of base was not dependent on ketosis or acidosis, but accompanied the sudden appearance of marked glycosuria. The interpretation of the foregoing studies is rendered difficult by the consideration that during the development of diabetic acidosis, vomiting, marked dehydration, shock, lowered blood volume, and diminished renal blood flow and glomerular

AN APPRAISAL OF METHODS OF TISSUE CHLORIDE ANALYSIS: THE TOTAL CARCASS CHLORIDE, EXCHANGEABLE CHLORIDE, POTASSIUM AND WATER OF THE RAT

Recent evidence (1, 2) promises to establish even more firmly the older concept that chloride in muscle is predominantly extracellular (3-5). On this premise investigators may find further credence in the use of chloride for the study of exchanges of fluid and electrolyte between the extraand intracellular phases of this tissue. Obviously a method of high accuracy for the determination of tissue chloride is necessary if knowledge concerning body cell composition is to progress. Concern as to the accuracy of present methods arises when one considers the normal values for the chloride content of muscle, as obtained in various laboratories. Perusal of the literature reveals values for normal rat muscle ranging from 3.13 to 6.41 mEq. per 100 grams of fat free, dry solid (6, 7). Although the homogeneity of the tissue samples and/or the methods of determination may be questioned, the argument remains that as yet no means are at hand for ascertaining whether all the chloride in tissue has been measured (8). Apart from the analyses of isolated tissues, investigations by many workers have sought to determine the extracellular volume and electrolytes in the whole animal by measuring the volume of distribution of various substances that either follow the distribution of chloride or do not penetrate cell water. If these data are to be compared with the volume of distribution of an isotope of chloride or bromide in the whole animal (9), it is important that we know how closely the volume of distribution of C136, C138, or Br predicts the true total body chloride.

Effect of desoxycorticosterone on distribution of water and on electrolyte excretion during enforced hydration in the dog and rat.

Enforced hydration was produced in dogs and rats by simultaneous administration of Pitressin and of water loads totaling 15% or more of body weight in the dogs and 19% in the rats. The effect of desoxycorticosterone on the distribution of the added water was determined in the dogs by means of bromide and antipyrine spaces and chloride balance. In both species the modifying effect of DCA on the natriuresis and chloruresis of enforced hydration was studied. In the normal dog, the retained water load was distributed evenly throughout total body water. Addition of DCA to the water loading and Pitressin regimen resulted in a disproportionate expansion of the chloride space and in the production of edema. In the dog, DCA appears to exert a direct effect on the distribution of a water load which can be demonstrated in the absence of electrolyte retention. Edema was not noted with DCA administration to rats subjected to the water loading-Pitressin regimen, suggesting a species difference with respect to this action of the hormone. In both the dog and rat, the natriuresis and chloruresis associated with overexpansion of body fluid volume produced by water loading was neither inhibited nor enhanced by the administration of DCA. In certain of the dogs receiving DCA, the timing of the natriuretic and chloruretic response differed from that seen in normal animals but the deviations were neither consistent nor reproducible.