THE MECHANISM OF THE EXCRETION OF AMMONIA IN THE DOG

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Abstract
Experiments were performed to investigate the mechanism of excretion of ammonia and other weak bases in the dog. Excretion of these substances (ammonia, quinine, Atabrine, SN 8439 and SN 5228) diminishes as urine pH rises when the change is effected by the infusion of NaHCO3. Alkalinization of the urine by the injection of KC1 or acetazoleamide results in a similar diminution in ammonia and quinine excretion. Effect on the excretion of SN 8439 is less marked. The accumulation of organic bases in the urine is apparently dependent upon the differential permeability of the tubule cell membrane to the lipid soluble and insoluble members of the ion pairs. These substances diffuse across the membrane as the free base (or singly charged member in the case of Atabrine, SN 8439 and SN 5228) and accumulate in the urine as the less permeating lipid insoluble species. In the acid range of urine pH accumulation is limited by the maximal rate of intracellular production in the case of ammonia and by the maximal rate of diffusion out of cells in the case of the exogenous bases. Consequently, alterations in urine flow do not affect the rate of excretion. In more alkaline urines, however, urine flow influences excretion rate so that diffusion of the bases between cells and tubule urine presumably approaches equilibrium. In either instance, the relationship between urine pH and rate of excretion rather than concentration of base indicates that final abstraction of water occurs at a site distal to that at which weak electrolyte content is determined. Amino acids augment ammonia excretion by enhancing the rate of production of ammonia and by elevating the intracellular concentration. It was not possible to distinguish between the various mechanisms which could account for the rise in urine pH noted in these experiments. In any event, base conservation was not effected, since in general the rise in ammonia excretion did not appreciably exceed the sum of the fall in titratable acid plus the rise in bicarbonate excretion. Excretion of ammonia and weak bases is not ascrib-able to active transport of these substances into the urine but to passive diffusion conditioned by the acidification of the urine.