On the pathogenesis of metabolic alkalosis in hyperaldosteronism

Abstract

Hypersecretion of aldosterone is generally considered to be the proximate cause of metabolic alkalosis in primary aldosteronism and has also been invoked as an important factor in the genesis and maintenance of alkalosis in the postoperative patient. Direct evidence supporting these two concepts is lacking, however. In our study we have examined the role of aldosterone excess in metabolic alkalosis by administering the hormone in settings closely analogous to those encountered clinically. First, to simulate primary aldosteronism we gave 1,000 μg/day of d-aldosterone for three months to volunteer subjects ingesting a diet containing normal quantities of sodium, potassium and chloride. This quantity of hormone, although in excess of that usually secreted by patients with primary aldosteronism, produced a rise of only 1 to 3 mEq/L in plasma bicarbonate concentration. Since the metabolic fate of endogenous and that of exogenous hormone seem to be similar, it would appear that aldosterone excess per se is not the proximate cause of metabolic alkalosis in primary aldosteronism. Second, we sought to simulate secondary aldosteronism as it is encountered in the postoperative state by giving 1,000 μg/day of d-aldosterone to subjects with experimental gastric alkalosis and restricting the dietary intake of either sodium or potassium. Administration of sodium chloride to a potassium-restricted group and of potassium chloride to a sodium-restricted group in each instance resulted in prompt restoration of normal acid-base equilibrium. The explanation for the failure of exogenous aldosterone to induce or sustain significant metabolic alkalosis in situations which mimic primary and secondary aldosteronism remains uncertain. However, analysis of data from the published cases of primary aldosteronism raises the possibility that the severity of potassium depletion occurring in response to a given degree of aldosterone excess may play an important role in determining whether significant alkalosis will occur.