Effect of acute metabolic acidosis and alkalosis on acetate and citrate metabolism in the rat.

An enhanced urinary excretion of citrate after administration of alkali and a diminished citrate excretion after administration of ammonium chloride were first observed by Ostberg in 1931 (1). More recently, it has been pointed out that the quantity of citrate excreted in the urine is not a direct consequence of acidification or alkalinization of the urine as believed by Ostberg, but rather is related to systemic pH (2). Hypercitraturia is associated with alkalosis and hypocitraturia with acidosis. This correlation appears to be independent of the mechanism of production of the altered acid-base balance. Thus, urinary citrate is diminished in diabetic acidosis (1, 3, 4), as a result of the intracellular acidosis of potassium depletion (5, 6), and in the metabolic acidosis induced by acetazolamide (2, 7, 8), as well as by administration of NH4Cl, CaCl, and HCl. Increased excretion of citrate in the urine has been observed during respiratory alkalosis (4, 6, 9) as well as during metabolic alkalosis. Two hypotheses have been proposed to explain this effect of altered acid-base balance on urinary citrate excretion. One hypothesis holds that alterations of pH influence the synthesis of citrate and its subsequent secretion by renal tubules (10). This implies that the intracellular pH of the renal tubular cell influences substrate metabolism in the Krebs citric acid cycle with subsequent transport of metabolites from the renal cell into the tubular urine. The second hypothesis, based on data obtained by conventional clearance techniques (11, 12), suggests that acidosis results in