Opal E. Hepler

Renal Phosphatase in Experimental Nephropathies.

The specific function of the rich phosphatase content of the kidney is still unknown. Since the kidney is almost invariably involved in metastatic calcification and is often the site of pathologic calcification it seemed possible that by comparing the location of the deposits of lime salts in these conditions with that of the phosphatase something might be learned concerning the relation of this enzyme to renal function. For this purpose we studied phosphatase, acting optimally at a pH of about 9.0 on sodium glycerophosphate, in the kidneys of normal dogs and of dogs in which a toxic nephrosis has been produced by uranium nitrate, potassium bichromate and bichloride of mercury. We compared sections stained for phosphatase by Gomoris 1 method with the quantity of the enzyme obtained in aqueous extracts of the cortical tissue of the same kidneys as determined by Bodanskys chemical method. We soon found, however, that in kidneys in which pathologic calcification was present, there was no correlation between the quantity of phosphatase revealed by the chemical method and the microscopic picture in the Gomori-stained sections. We therefore stained 3 consecutive sections of kidneys of the dogs used in these experiments, one with routine hematoxylin and eosin, one with Gomoris 1 stain for phosphatase and one for calcium phosphate only by von Kossas method. The routine sections revealed the location of necrotic or otherwise damaged tubular epithelium. Sections stained by Gomoris method showed all of the calcium phosphate present in approximately quantitative relations. Normally, phosphatase is present in the marginal zone, next the lumen, of the epithelium lining the proximal convoluted tubules. It is most abundant in the first two-thirds or three-fourths of these tubules, that is, in the labyrinth; less abundant in the straight terminal portion, that is, in the medullary rays and in the outer stripe of the outer zone of the medulla.

Effect of Hyperthyroidism on Sympathetic Nervous System

Much has been written concerning the influence of the sympathetic nervous system upon the thyroid; relatively little on the effect of excessive thyroid secretion upon the sympathetic. The general statement is made that “the thyroid gland appears to sensitize the whole or part of the sympathetic nervous system,” 1 and this is suggested as “the most plausible way of explaining” the retracted upper lids, the exophthalmos and the dilated pupils of exophthalmic goiter. Most of the experiments reported in the literature indicate that in the state of hyperthyroidism, the sympathetic nervous system is more sensitive to adrenalin. In the course of a series of experiments undertaken for another purpose we have made a number of observations which apparently do not support this view. Nine normal dogs served as controls. Seven dogs were fed 10 gm. of desiccated thyroid daily for from 9 to 14 days immediately preceding the experiments. These animals became very excitable, suffered from diarrhea and lost from 0.61 to 5.0 kg. in weight, or from 3.5 to 32.6% of the original weight. Under ether anesthesia, cannulæ were placed in the trachea and carotid artery and the femoral and jugular veins were exposed, in each animal. The reaction of each dog to one cc. of a fresh 1 to 30,000 solution of adrenalin was determined. The abdomen was then opened and a small rubber tube was placed in position for mechanically constricting the hepatic veins by the method described by Simonds and Brandes. 2 This tube was left loose so that no constriction of the hepatic veins took place at this time. In Table I is shown the rise in blood pressure induced by corresponding doses of adrenalin in normal and hyperthyroid dogs.

Effect of Mechanical Obstruction of the Hepatic Veins upon Guanidine Content of the Blood.

Increase in the guanidine content of the blood has been reported in tetany following parathyroidectomy (Burns and Sharpe, 1 Koch, 2 and Paton and Findley 3 ); in hypertension (Major and Weber 4 ); in Laennecs cirrhosis of the liver and in Bantis disease (Ellsworth 5 ); in eclampsia (Minot and Cutler 6 ); and in poisoning with carbon tetrachloride and chloroform (Minot and Cutler 7 ). In the last 3 of the above conditions there is an acute severe damage to the liver. Injury to the liver can be induced by mechanical obstruction of the hepatic veins. It appeared to be worth while, therefore, to compare the effects of injury to the liver induced by this method on the guanidine content of the blood with those obtained by Minot and Cutler in cases of liver injury caused by acute poisoning and eclampsia. Under complete ether anesthesia and with rigid aseptic precautions we mechanically obstructed the hepatic veins by the method described by Simonds and Brandes. 8 Samples of blood were taken before the operation and 24, 48 and, in some instances, 72 hours after the operation. Guanidine was determined by the method described by Major and Weber. 9 The average of our normal determinations was 0.347 mg. of guanidine per 100 cc. of blood, with a maximum of 0.417 mg. and minimum of 0.303 mg. The figures given by Minot and Cutler 7 are the only determinations on normal dogs that we have been able to find. Their average was 0.374, with a maximum of 0.48 and a minimum of 0.29. Our experiments involved a study of 16 dogs. Of these, 8 showed either a definite decrease or no change in the guanidine content of the blood; 4 showed increase of less than 0.1 mg. in 24 hours with a return to normal in 48 hours; one showed a slight decrease in 24 hours with a return to approximately normal in 48 hours; while only 2 showed a definite increase (from 0.340 to 0.444 mg. and 0.340 to 0.466 mg., respectively).