Previous studies (1-4) on the response of normal human subjects to the administration of mineral acids or acidifying salts have established that: 1) Extracellular bicarbonate concentration and pH are reduced; and 2) there is a prompt increase in the renal excretion of the administered anion accompanied at first mainly by sodium, potassium, and small amounts of ammonium. Ammonium excretion rises slowly, and after a few days replaces most of the fixed cation in the urine.Little is known about the mechanisms regulating this renal response, or how it might be modified. Furthermore, although it is evident that the moiety of administered hydrogen not immediately appearing in the urine as ammonium or titratable acid must be accounted for by changes in body buffers, no description has been made of the internal distribution of the retained hydrogen ions. It was pointed out many years ago (5, 6) that buffers other than those in whole blood must be important in this process, but there are no quantitative data on the relative importance of red cell, plasma, interstitial fluid, and cellular buffers.In the present study, acidifying salts were administered to healthy subjects who had previously been depleted of sodium. The purposes of this investigation were : 1) To attempt a quantitative description of the internal distribution of the retained hydrogen ion and thereby clarify the relative importance of the various body buffers in the extrarenal adjustments to acid loading; and 2) to 1 This study was supported in part by grants from the National Heart Institute of the National Institutes of Health, U.S.P.H.S., the Greater Boston Chapter of the Massachusetts Heart Association and from the Research and Development Bcard, Surgeon General's Office, Department of the Army.2 Presented in abstract at the 45th annual meeting of the American Society for Clinical Investigation, May, 1953. determine how sodium depletion might modify the nature of the cation diuresis, and particularly how it might change the renal ammonium response.
METHODSFive balance studies were carried out on five healthy male medical students. Sodium depletion was produced over a period of four to five days by a low-sodium diet (10 to 20 mEq. per day) and a total of one to three inj ections of a mercurial diuretic. During this period the subjects lost an average of 2.4 Kg. (range: 1.7 to 2.7 Kg.). The low-sodium diet was continued and the balance study was begun with a control period of at least four days, during which time serum concentrations and urinary excretion of electrolytes were approximately constant. Following this, three subjects were given ammonium chloride (721 to 1028 mEq. of chloride) and two subjects ammonium sulfate (400 and 504 mEq. of sulfate) in divided oral doses over a two to three-day period. In each instance a post-treatment period of one or more days was obtained. The subjects were allowed to continue their usual activities during the period of study but were instructed to avoid exertion.Urine inorganic sulfate was determined gravimetrical...