Abstract. Inflow of preformed ammonia in arterial blood, renal production of ammonia, outflow of ammonia in renal venous blood, and urinary excretion of ammonia were measured during the infusion of 15NH4Cl into one renal artery of dogs with chronic metabolic acidosis. Our results show that the specific activity of ammonia measured in the urine and that calculated in the renal pool agree within 95%. Pool specific activity is obtained by dividing the rate of infusion of isotope by the pool turnover rate, i.e., the sum of the rate of ammonia output in the urine and that in renal venous blood. An average of 35% of urinary ammonia is derived from arterial ammonia in these experiments.We conclude that ammonia is distributed evenly throughout all phases of the kidney within a period less than the transit time of blood through the kidney. Furthermore, from the proportion of urinary ammonia we found to be derived from preformed arterial ammonia (35%), and from our previous demonstration that 73% of urinary ammonia derives from deamidation and/or deamination of plasma glutamine, alanine, glycine, and glutamate, we can account for all of the ammonia that leaves the kidney in renal venous blood and in urine. IntroductionThe thesis that the mechanism of renal secretion of ammonia is passive, nonionic diffusion was suggested in 1948 by Pitts (1) in explanation of the proportionality between urinary hydrogen ion concentration and the rate of excretion of ammonia. The free base, NH3, is lipid soluble, uncharged, and penetrates cell membranes readily, whereas the ammonium ion, NH4+, is water-soluble, charged, and relatively nonpenetrating (2). Thus NH3, formed in tubular cells from precursors delivered in arterial blood, diffuses into acid

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Renal excretion, reabsorption, utilization, and peritubular transport of α-ketoglutarate were measured in the anesthetized dog under conditions of normal acid-base balance and in metabolic and respiratory acidosis and alkalosis. In the normal dog, the reabsorption of α-ketoglutarate is Tm limited. Chronic metabolic acidosis, induced by the feeding of ammonium chloride, and acute respiratory acidosis, induced by breathing CO2-O2 mixtures, increase Tm values significantly. Acute respiratory alkalosis, induced by hyperventilation and acute metabolic alkalosis, induced by the infusion of THAM (tris (hydroxymethyl) aminomethane), reduce Tm values significantly. Comparable states of acute metabolic alkalosis, induced by the infusion of sodium bicarbonate, do not reduce Tm to an extent comparable to that induced by hyperventilation or the infusion of TIIAM. For a variety of reasons, Tm of α-ketoglutarate seems to be more responsive to changes in intracellular than in extracellular hydrogen ion concentration. Transport of α-ketoglutarate into tubular cells both from tubular lumen and from peritubular fluid is probably active, i.e., against electrochemical gradients. It is suggested that both processes are affected by alterations of pH of intracellular fluid.

Certain characteristics of the ammonia secretory mechanism in the dog have been studied by the method of Chinard. Ammonium chloride or acetate and creatinine were rapidly injected into one renal artery and a series of urine samples were collected separately from the two ureters. In acidosis, injected ammonia appears in the urine earlier than does creatinine, indicating that some fraction enters the tubule from the blood downstream from the glomerulus. The maximum rate of excretion of ammonia relative to the dose administered is usually less than that of creatinine, indicating that filtered ammonia is in part reabsorbed from the tubular urine. Finally, the excretion of ammonia is much prolonged relative to creatinine, indicating that it continues to be added to the tubular urine from cellular stores built up from both filtrate and peritubular blood. In alkalosis, the time course of excretion of creatinine is unchanged from that observed in acidosis. However, the excretion of ammonia is abolished. That which enters the tubule in the filtrate is completely reabsorbed. These data are consistent with the view that ammonia diffuses freely in both directions across the renal tubular epithelium as free base and distributes among tubular urine, tubular cells, and peritubular blood in accordance with their respective hydrogen ion concentrations.