A mathematical model of distal nephron acidification: diuretic effects

Through their action on the distal nephron (DN), diuretics may produce systemic acid-base disturbances: metabolic alkalosis with thiazides or loop diuretics and metabolic acidosis with amiloride. Enhanced acid excretion may be due to a local effect on the diuretic target cell (a shift of Na reabsorption from NaCl transport to Na/H exchange), or an effect at a distance: namely, increases in luminal fluid flow or luminal Na concentration may enhance more distal proton secretion. Both local and distance effects are supported by micropuncture data. In the present work, mathematical models of the distal convoluted tubule (DCT)/connecting tubule (CNT) (Wein-stein AM, Am J Physiol Renal Physiol 289: F721–F741, 2005), and cortical and medullary collecting ducts (CD) (Weinstein AM, Am J Physiol Renal Physiol 283: F1237–F1251, 2002) have been concate-nated to yield a model of rat DN. Among the segments of this DN, the DCT-CNT is responsible for the major portion of distal acidification