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Collecting duct intercalated cells: acid-base fine control

Collecting duct · H+-ATPase AE1 Pendrin NH4+

Alpha-intercalated cells secrete protons against a steep gradient (urine pH can fall to ~4.5) and generate the new bicarbonate that replaces daily non-volatile acid; beta-intercalated cells do the reverse in alkalosis. This is the site of distal renal tubular acidosis.

Traced from the start

  1. Glomerular filtration barrier
  2. Proximal tubule: Na+/H+ exchange and bicarbonate reclamation
  3. Thick ascending limb of Henle (NKCC2)
  4. Early distal convoluted tubule: thiazide-sensitive NaCl cotransporter
  5. Collecting duct intercalated cells: acid-base fine control

Detail

Alpha cell
Apical vacuolar H+-ATPase and H+/K+-ATPase secrete H+; carbonic anhydrase II generates HCO3- that exits via basolateral AE1 (Cl-/HCO3- exchanger, band 3)
Buffers
Secreted H+ leaves as titratable acid (HPO4 2- to H2PO4-, ~30 mmol/day) and as NH4+ (NH3 trapped in the lumen, ~40 mmol/day, rising several-fold to over 200 mmol/day in chronic acidosis); free H+ is negligible
Beta cell
Apical pendrin (Cl-/HCO3- exchanger) secretes HCO3- during metabolic alkalosis; basolateral H+-ATPase
Hormone
Aldosterone stimulates the H+-ATPase directly and indirectly (lumen-negative potential from ENaC), hence the alkalosis of hyperaldosteronism; hypokalaemia upregulates H+/K+-ATPase (K+ reclaimed, H+ lost)
Diuretic
None specific; potassium-sparing diuretics reduce H+ secretion (mild acidosis), loops and thiazides increase it (alkalosis)

When it goes wrong

Distal (type 1) RTA: H+-ATPase or AE1 defects, Sjogren syndrome, amphotericin B, lithium, obstructive uropathy

Normal anion gap metabolic acidosis with urine pH stuck above 5.5, hypokalaemia, hypercalciuria with nephrocalcinosis and calcium phosphate stones, rickets or osteomalacia; positive urine anion gap (low NH4+); can be severe (HCO3- under 10 mmol/L)

Type 4 RTA: hypoaldosteronism (diabetic hyporeninaemic hypoaldosteronism, ACE inhibitors, spironolactone, heparin, Addison disease) or ENaC blockade (trimethoprim, amiloride)

Hyperkalaemia with mild normal anion gap acidosis and acidic urine (under 5.5), because hyperkalaemia suppresses ammoniagenesis

Vomiting or diuretics with volume and chloride depletion

Metabolic alkalosis is maintained because Cl- depletion stops beta-cell pendrin from dumping bicarbonate; saline-responsive with urine Cl- under 20 mmol/L

Practise this structure

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