No abstract

In the preceding papers (1, 2), we have described the phenomena produced by the cessation of injections of suprarenal cortical extract in the suprarenalectomized adult dog, which has been maintained in a normal state of nutrition, with well healed incisions, for a period of several weeks after suprarenalectomy. We have pointed out that death in such an animal, if injections of the hormone are not resumed, is due to a condition of shock produced by loss of body fluid. The observed sequence of events is: hemoconcentration, which becomes more and more marked; progressive loss of body weight; anorexia; lowered body temperature and basal oxygen consumption; muscular weakness; vomiting and diarrhea; and ultimate failure of the circulation, as indicated by diminished blood flow and fall in blood pressure. These symptoms are associated with a progressive rise in blood nonprotein nitrogen (urea) concentration, a drop in plasma chlorides, and, as we have recently shown (1), a fall in plasma total base. The present communication is concerned with an analysis of the factors producing this hemoconcentration and of the train of phenomena which then follows it. 1 1 We wish to acknowledge the assistance of Dr. Mary Buell in organizing the chemical procedures involved in the manufacture of the cortical extract and in the selection and setting up of analytical methods used in the studies herein reported.We are indebted to Miss Margaret Strauss who has made lactic acid, inorganic phosphorus, and calcium estimations on a series of animals before and during insufficiency.

From previous studies (1, 2, 3, 4, 5) it now seems clear that one of the most striking changes found in the urine after the injection of parathyroid extract is the immediate increase in the absolute amount and in the concentration cf inorganic phosphate. Goadby and Stacey (6) have also emphasized the increased excretion of phosphate after the administration of parathyroid extract. In agreement with our experience, these observers did not find at any time an increase in the level of inorganic phosphorus in the plasma, but occasionally noted a fall of that level after the excretion of increased amounts of inorganic phosphate in the urine.They were unable to prevent the rise in excretion of urinary phosphorus by lowering the level of inorganic phosphate in the plasma with glucose administered at the time of the parathormone injection. The work of Goadby and Stacey, together with ours, serves to direct attention to the behavior of the kidneys in response to parathyroid extract.In 1934, while studying the phosphate excretion by the kidney, one of us (5) observed that, when urine specimens were taken hourly before and after the administration of parathyroid extract, the pH showed a tendency to shift definitely to the alkaline side during the first hours after the extract was given. In order to examine this effect further it seemed advisable, although the bicarbonate of urine may be roughly estimated from the pH, to determine accurately the bicarbonate content of the urine before and after giving parathyroid extract and to compare the magnitude of any change found with that of the inorganic phosphate.At the same time estimations of pH, sodium, 1 This work was aided by a grant from the council on Pharmacy and Chemistry of the American Medical Association. potassium, ammonium, phosphate, and chloride ions were made. As previous estimations have shown no significant alteration in urinary calcium, in experiments of the duration of the present ones, urinary calcium determinations were not done. EXPERIMENTALThe subjects of the experiment were four male patients; three (G., S., K.) were convalescent from respiratory infections and ready for discharge from the hospital, the fourth, M., was a patient who had been operated upon for hyperthyroidism and who had developed hypoparathyroidism after operation. All patients were fasted and kept in bed for 12 hours before and throughout the duration of the experiment. Each patient was given 100 cc. of water by mouth each hour. Urine specimens in the three convalescent subjects were collected under oil, those of M. were not. The specimens were collected hourly for three hours before and four hours after the intravenous injection of 4 cc. of parathyroid extract (Lilly).The analyses were made by standard methods as follows: pH by the quinhydrone electrode (13)