Overview

α-intercalated (type A) cells secrete H⁺ into the lumen via an apical vacuolar H⁺-ATPase and H⁺/K⁺-ATPase (which also reabsorbs K⁺ in hypokalaemia). Intracellular carbonic anhydrase II generates the H⁺ from CO₂ and water; the matching HCO₃⁻ exits basolaterally through the Cl⁻/HCO₃⁻ exchanger AE1 (band 3 protein) — so every H⁺ secreted adds a new HCO₃⁻ to the blood. They can lower urine pH to ≈4.5 and are stimulated by acidosis and aldosterone.

β-intercalated (type B) cells are the mirror image: an apical Cl⁻/HCO₃⁻ exchanger (pendrin) secretes HCO₃⁻ into the urine and basolateral H⁺-ATPase returns H⁺ to the blood; they are activated in metabolic alkalosis. Non-A, non-B cells also exist in the connecting tubule.

Location: Connecting tubule, cortical and outer medullary collecting ducts (fewer in the inner medulla).

Anatomy

Histology: Darker-staining cells with abundant mitochondria and apical microplicae, interspersed among principal cells.

Function

H⁺ secretion and new HCO₃⁻ generation (α)
K⁺ reabsorption via H⁺/K⁺-ATPase (α)
HCO₃⁻ secretion in alkalosis (β)
Cl⁻ reabsorption (β, pendrin)

Clinical significance

Distal (type 1) renal tubular acidosis

Failure of α-intercalated H⁺ secretion (autoimmune — Sjögren syndrome, SLE; amphotericin B; AE1 or H⁺-ATPase mutations) → normal-anion-gap metabolic acidosis with urine pH >5.5, hypokalaemia, hypercalciuria, nephrocalcinosis and calcium phosphate stones.

Pendred syndrome

Pendrin mutations cause sensorineural deafness and goitre; the renal phenotype appears mainly with alkali loads or diuretics.

Test yourself

A child has a normal anion gap metabolic acidosis, urine pH persistently >5.5, hypokalaemia and nephrocalcinosis. Which cells are most likely defective?

Podocytes
Principal cells of the collecting duct
Proximal tubule cells
α-intercalated cells of the collecting duct

Answer: α-intercalated cells of the collecting duct

Distal (type 1) renal tubular acidosis results from failure of α-intercalated cells to secrete H⁺ (H⁺-ATPase, H⁺/K⁺-ATPase, AE1), so urine cannot be acidified below ≈5.5. Proximal (type 2) RTA is a HCO₃⁻ reclamation defect; type 4 is hypoaldosteronism with hyperkalaemia.