Mechanisms in Hyperkalemic Renal Tubular Acidosis

Factors involved in hyperkalemic acidosis. (A) Proper function of the ENaC at the apical surface of principal cells is necessary for K⁺ secretion by ROMK in these same cells and H⁺ secretion by adjacent intercalated cells. Inherited or acquired loss of ENaC function or its regulation by aldosterone via the mineralocorticoid receptor (MR) gives rise to hyperkalemic acidosis. (B) Hyperkalemia raises intracellular pH by exchange with protons, impairing enzymes involved in ammoniagenesis. (C) Ammoniagenesis in the proximal tubule is chiefly by deamidation of filtered or secreted glutamine (Gln). Ammonia (NH₃) diffusing into the nascent urine assists in buffering H⁺; both NH₃ and NH₄⁺ undergo further reabsorption in the medullary loop followed by distal nephron movement into the final urine. Glu, glutamate; aKG, α-ketoglutarate.