Fig. 3.

A schematic diagram illustrating the underlying kidney tubule defects causing the different types of renal tubular acidosis (RTA). Distal (type 1) RTA is caused by either impaired hydrogen (H⁺) secretion by vacuolar (v) H⁺-ATPase or H⁺/K⁺-ATPase or increased H⁺ permeability of luminal membrane by α-intercalated cells of the collecting duct, which leads to a reduction in net H⁺ secretion. Proximal (type 2) RTA is caused by defects in bicarbonate (HCO₃^–) reabsorption in the proximal tubule, due to either impaired HCO₃^– transport across the basolateral membrane or inhibition of carbonic anhydrase (CA) activity. Hyperkalemic (type 4) RTA is caused by aldosterone deficiency or resistance, which leads to reduced Na⁺ (sodium) reabsorption by principal cells of the collecting duct and decreased transepithelial voltage, leading to diminished H⁺ secretion by α-intercalated cells and K⁺ secretion by principal cells. AE1 kidney anion exchanger, ENaC epithelial Na⁺ channel, MR mineralocorticoid receptor, NHE3 Na⁺/H⁺ exchanger 3, ROMK apical membrane K⁺ channel