It is chloride depletion alkalosis, not contraction alkalosis

Abstract

Maintenance of metabolic alkalosis generated by chloride depletion is often attributed to volume contraction. In balance and clearance studies in rats and humans, we showed that chloride repletion in the face of persisting alkali loading, volume contraction, and potassium and sodium depletion completely corrects alkalosis by a renal mechanism. Nephron segment studies strongly suggest the corrective response is orchestrated in the collecting duct, which has several transporters integral to acid-base regulation, the most important of which is pendrin, a luminal Cl/HCO(3)(-) exchanger. Chloride depletion alkalosis should replace the notion of contraction alkalosis.

Figure 1.

In the CCD during reduced Cl⁻ delivery to that segment in CDA, pendrin activity is increased but secretion of HCO₃⁻ is inhibited by insufficient Cl^- for anion exchange. HCO₃⁻ reabsorption may be partly maintained by Na⁺/H⁺ exchange by the electrical coupling between the principal cell and the H⁺-secreting A cell (although it is morphologically less active than normal¹⁷) and by the remainder of the collecting duct in the medulla. Coupled Na⁺/K⁺ exchange causes kaliuresis. After Cl⁻ delivery to the cortical collecting ducts increases, HCO₃⁻ secretion occurs and medullary HCO₃⁻ reabsorption diminishes, allowing correction of the hypochloremic alkalosis. In our rat studies, bicarbonaturia occurred within minutes of Cl⁻ administration intravenously and Cl⁻ did not increase in the urine until correction of serum [Cl⁻] was nearly complete. (Both H⁺ and HCO₃⁻ are produced in the A- and B-type cells by carbonic anhydrase, and during acute acid-base changes, pendrin and H⁺ ATPase shuttle back and forth from cytosol to the luminal or basolateral membrane¹⁸).