Renal Ammonia Balance. A Kinetic Treatment

Abstract

Ammonia is transported into, within, and out of the mammalian kidney largely by passive means; it is suggested that the transport out may be effected exclusively by non-ionic diffusion to equilibrium. The principal objectives of this communication are to present a general kinetic equation which indubitably describes correctly any steady state of renal ammonia balance, to describe by means of a first-order kinetic equation the relations necessarily obtaining between the determinants of renal ammonia balance postulating diffusion equilibrium of NH₃ in the kidney, and to indicate how the postulates expressed by the first-order equation can be tested against experiment through implementation of the terms of the equation for any given steady state. In particular, a detailed treatment has been developed for the particular case of ordinary physiological conditions in normal adult man, using a special equation derived from the general quantitative equation with the aid of certain assumptions appropriate to such conditions. The pH and (NH₃) of voided urine must generally exceed the urinary values at the papilla as a result of postpapillary increase of urine pH [and hence of urinary (NH₃)], caused by delay in dehydrating H₂CO₃ newly formed in the distal nephron. Application of a reasonable correction for this postpapillary increase of urine pH and (NH₃), applied to the data for voided urines of normal adults, accomplishes satisfactory congruence between the theoretical values yielded by the special equation and experimental estimates of the (NH₃) of both high-flow papillary urine and of renal cortical tissue water as functions of the pH of high-flow papillary urine. The correction is based on an assumed value for papillary Pco₂which cannot be greatly in error in the case of high-flow urines. A larger error would affect similar corrections in the case of low-flow urine, in particular because CO₂reabsorption beyond the papilla probably causes additional postpapillary rise, of appreciable but ¹ Supported in part by a research grant (AM-08114) from the National Instituteof Arthritis and Metabolic Diseases. ² Supported 1962–1963 by a Graduate Traineeship of the National Institute ofArthritis and Metabolic Diseases, and 1965–1966 by a Special Research Fellowship of the U.S. Public Health Service. unknown magnitude, of the pH of such urine. The values of various correction terms will first be known exactly when measurements of the Pco₂of the human renal papilla as a function of varying urine flow rate and pH become available. Meantime the general agreement between theoretical and estimated (NH₃) of the renal cortex and of the high-flow urines [including the most acid high-flow urine, where (NH₃) of voided urine must be so close to that of papillary urine that a correction is hardly required] supports the soundness of the postulates and assumptions on the basis of which the kine...

Renal ammoniagenesis in an early stage of metabolic acidosis in man.

“…The importance of acidemia has also been outlined in the intact rat with acute metabolic acidosis, whereas urine pH seemed to be meaningless (17). Moreover, no correlation was detected between ammonia production and urine pH both in dog and in man under normal acid-base balance and in chronic NH4Cl-induced acidosis (1,42,43). It has been shown that intracellular pH of rat tubular cells is linearly correlated with extracellular pH (44).…”

Effect of Reduced Renal Mass on Ammonium Handling and Net Acid Formation by the Superficial and Juxtamedullary Nephron of the Rat

“…Although the rate of ammonium production cannot be determined from the data presented in this work, an estimate of differences in the production of ammonia by renal cortical tissue in the two groups of animals can be obtained by calculating the pNH3 of the cortex. If it is true that ammonia entry into the tubule lumen is due to nonionic diffusion of the free base NH3 where protonation and entrapment occurs (30), and that NH3 is in equilibration throughout all structures located in the cortex (31,32), then given the in situ pH and ammonium concentration of fluid obtained near the end of the proximal tubule, the pNH3 of the renal cortex can be calculated with the following formula (33,34) (35) and the solubility coefficient (a) of 0.626 (34), cortical pNH3 averaged 1,267±234 mmHg X 10-6 in the RK group, twofold the value in the sham-operated group (658±70 mmHg X 10-6). If intracellular pH fell during acidosis (36) and if ammonia entry was due solely to diffusion and no increase in synthesis occurred, then one would expect that the cortical pNH3 of the RK group would be lower than that of the sham-operated group.…”