The regulation of renal acid secretion: New observations from studies of distal nephron segments (original) (raw)

1986, Kidney International

Forty years ago, in a landmark paper, Pitts and Alexander [1] proposed that the renal excretion of acid is accomplished by 'a single fundamental process based primarily on the exchange of H ions for Na ions". Ten years later, Schwartz, Jenson and Relman [21 demonstrated that the acute infusion of sodium sulphate in humans ingesting a low sodium chloride diet was associated with a dramatic fall in urine pH, although systemic acid-base balance was not changed. The observation that hydrogen ion excretion can increase without a fall in blood pH has been relentlessly pursued by Schwartz and his colleagues [2]. Many meticulous chronic steady-state experiments have provided results which have been explained by a "non-homeostatic" hypothesis, elegantly presented by Schwartz and Cohen [3]. This view, to which we will hereafter refer as the cation exchange hypothesis, states that it is not blood pH but changes in sodium delivery, sodium avidity, and subsequent "Na-H exchange" of the distal nephron which determine the rate of renal hydrogen ion secretion. Chloride depletion or chloride substitution with less permeable anions are considered to also influence the rate of "Na-H exchange". Some of the situations studied by Schwartz and his colleagues include: alkalinization of systemic blood in chronic metabolic alkalosis, the different degrees of acidosis observed with chronic infusion of mineral acids of different anions, the normal bicarbonate concentration observed during vasopressin-induced volume expansion, and the induction of metabolic alkalosis by the administration of potassium and a non-reabsorbable anion to sodium and potassium depleted animals [4-8]. All have been explained on the basis of altered intrarenal sodium handling, subsequent stimulation of hydrogen ion secretion, and enhanced bicarbonate reabsorption. It is important to emphasize that this cation exchange hypothesis characterizes distal nephron H secretion as being uninfluenced by blood pH, but responsive primarily to Na handling and anion movements. Not surprisingly, such a comprehensive approach has strongly influenced current views on the renal regulation of acid-base balance. Recently, new studies have been completed which enable us to reconsider whether the regulation of hydrogen ion secretion "Na-H exchange" does not refer to any single mechanism but rather to some linkage (direct or indirect) between Na absorption and H secretion