Roles and mechanisms of urinary buffer excretion

Abstract

Excretion of acid (or generation of bicarbonate) by the kidneys is necessary for acid-base homeostasis. Most of this acid is excreted in the form of ammonia and titratable acid, the latter representing the amount of acid required to titrate the urine buffers from the plasma pH to urine pH. The transport of ammonia in the kidney is now recognized to entail more than simple nonionic diffusion of NH3 and trapping of NH4+. NH4+ transport in the kidney probably occurs by passive diffusion and by transport on the Na+-H+ exchanger, the Na+-K+-2Cl- transporter and on Na+-K+-ATPase. NH3 diffusion is stimulated by an acid disequilibrium pH in various nephron segments. Also, diffusion equilibrium of NH3 in various regions of the kidney has now been disproved. These various mechanisms of ammonia transport are considered in terms of their possible changes with acid-base disturbances. Phosphate is the most predominant urine buffer; its urinary excretion increases with acidosis. The mechanisms probably involve a decrease in the preferentially transported species, HPO4(2-), and a direct effect of pH on proximal tubule apical phosphate transport. With chronic acidosis, changes in the activity of the apical Na+-phosphate transporter occur. These effects of systemic acid-base balance interact with parathyroid hormone and dietary phosphate status to alter phosphate reabsorption. Citrate transport in the kidney is analyzed because of its sensitivity to systemic pH and because of the possible influence on systemic acid-base status in certain circumstances. Alterations in citrate excretion with acid-base disturbances depend on changes in the concentration of the transported species, citrate2-, and on changes in renal metabolism.

Function of human Rh based on structure of RhCG at 2.1 Å

“…NH þ 4 secretion in the kidneys is critical to systemic acid-base homeostasis (37)(38)(39). In humans, inability to appropriately dispose of excess H þ in urine results in distal renal tubular acidosis that depresses arterial blood pH (<7.35), and in extreme cases results in kidney stones, rickets, and renal failure (40,41).…”

Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.

“…The factors that are responsible for the renal adaptation to metabolic acidosis are at present incompletely settled. In recent reviews (25)(26)(27) it is generally accepted that acidosis itself exerts major effects on proximal and distal parts of the nephron to increase proton secretion and bicarbonate absorption, ammonia production and excretion, and phosphate and titratable acid excretion. However, the control of this important kidney function by hormonal factors must be considered.…”

Acid-Base Homeostasis

“…The transport of the produced NH 4 1 along the nephron and into the urine is a complex process that is still a topic of intense study (Figure 6). Most of the NH 4 1 produced is excreted into the urine rather than added to the venous blood; this is particularly true with acidosis-the proportions into urine and blood are almost even in normal conditions (13,67). Therefore, during acidosis, both total NH 3 production and secretion into urine are increased.…”

“…The capacity of the nephron to excrete acid as free protons is limited as illustrated by the fact that the concentration of protons (H 1 ), even at a urine pH 4.5, is ,0.1 mEq. However, the availability of urine buffers (chiefly phosphate) results in the excretion of acid coupled to these urine buffers (13). Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid.…”