Figure 1.

Renal chloride handling: The majority of filtered chloride is reabsorbed in the proximal tubule via both passive and active transcellular mechanisms involving Cl⁻/base exchangers and Na⁺/H⁺ exchangers. Acetazolamide (ACTZ), by inhibiting carbonic anhydrase, indirectly promotes proximal chloride reabsorption. In the thick ascending limb of the loop of Henle, chloride is reabsorbed through the Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2), the pharmacologic target of loop diuretics such as furosemide. In the distal convoluted tubule, thiazide-sensitive Na⁺/Cl⁻ cotransporters and Cl⁻/HCO_3⁻ exchangers mediate further reabsorption. The collecting duct finalizes chloride handling via pendrin and sodium-dependent Cl⁻/HCO_3⁻ exchangers in intercalated cells. Sites of action for furosemide, thiazides, acetazolamide (ACTZ), and mineralocorticoid receptor antagonists (MRAs) are highlighted. Abbreviations: ACTZ: acetazolamide; ATP: Adenosine Triphosphate; ENaC: epithelial sodium channel; MRA: mineralocorticoid receptor antagonist; NKCC2: Na⁺/K⁺/2Cl⁻ cotransporter. This figure is an original illustration created by the authors for educational purposes.