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intercalated cell

Renal PhysiologyRenalUrinary

Summary

Intercalated cells are specialized cells in the late distal tubule and collecting duct that regulate acid-base balance. Type A (alpha) cells secrete H+ via apical H+-ATPase and H+/K+-ATPase and reabsorb HCO3- via basolateral Cl-/HCO3- exchanger (AE1); type B (beta) cells do the reverse, secreting HCO3-.

Detail

LOCATION: Late distal convoluted tubule, connecting tubule, and cortical/medullary collecting duct, interspersed among principal cells. Type A cells also extend into the outer and inner medullary collecting duct.

TYPE A (alpha) INTERCALATED CELLS - Function: Acid secretion (urine acidification) and HCO3- reabsorption. - Apical: H+-ATPase (vacuolar) and H+/K+-ATPase (also reabsorbs K+). - Basolateral: Cl-/HCO3- exchanger (AE1/band 3) moves HCO3- into blood. - Intracellular carbonic anhydrase (CO2 + H2O -> H+ + HCO3-) generates the H+ and HCO3-. - Urinary buffers: secreted H+ is buffered by NH3 (-> NH4+, "ammonia trapping") and phosphate (titratable acid). - Stimulated by acidosis, hypokalemia (H+/K+-ATPase upregulation), and aldosterone (stimulates H+-ATPase; aldosterone also acts on principal cells).

TYPE B (beta) INTERCALATED CELLS - Function: Bicarbonate secretion and H+ reabsorption (active in metabolic alkalosis). - Apical: Cl-/HCO3- exchanger (pendrin); Basolateral: H+-ATPase.

CLINICAL CORRELATES - Distal (Type 1) RTA: Defective H+ secretion by alpha-intercalated cells (e.g., Sjögren syndrome, amphotericin B toxicity, lithium, SLE, AE1 or H+-ATPase mutations). Findings: non-anion gap (hyperchloremic) metabolic acidosis, urine pH >5.5, hypokalemia, nephrocalcinosis/calcium phosphate kidney stones (alkaline urine + hypercitraturia loss, hypercalciuria). - Type 4 RTA (hypoaldosteronism/aldosterone resistance): Reduced aldosterone effect decreases H+ secretion by alpha cells (and K+ secretion by principal cells) -> hyperkalemia, non-anion gap acidosis; impaired ammoniagenesis from hyperkalemia. Seen in diabetic nephropathy, ACE inhibitors, spironolactone, trimethoprim. - Hypokalemia: H+/K+-ATPase activation causes K+ retention but worsens H+ secretion -> metabolic alkalosis. Hyperkalemia has the opposite effect. - Hyperaldosteronism: Increased H+ secretion -> metabolic alkalosis with hypokalemia. - Carbonic anhydrase inhibitors (acetazolamide) reduce H+ available (mainly in the proximal tubule, but also affect intercalated cell function) -> non-anion gap metabolic acidosis.

HIGH-YIELD CONTRAST WITH PRINCIPAL CELLS - Principal cells: Na+ reabsorption (ENaC), K+ secretion (ROMK), water reabsorption (ADH-regulated aquaporin-2); targets of aldosterone, ADH, amiloride/triamterene (ENaC blockers), and spironolactone/eplerenone (MR antagonists). - Intercalated cells: acid-base handling (mitochondria-rich).

MNEMONIC: "Alpha = Acid secretion" (Type A); "Beta = Bicarbonate secretion" (Type B).

Sources

  • First Aid for the USMLE Step 1 (Renal: Physiology, Acid-base)
  • Costanzo Physiology
  • Boron & Boulpaep Medical Physiology
  • Robbins and Cotran Pathologic Basis of Disease (Renal tubular acidosis)
  • Pathoma (Renal: Acid-base disorders)

Reviewed by Medusa editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.