Cortical collecting duct principal cell: ENaC and potassium secretion
Collecting duct · 2-3% Na+ ENaC/ROMK Aldosterone Amiloride
Aldosterone-regulated fine control of sodium and potassium: sodium entering through the epithelial Na+ channel makes the lumen electronegative, which drives potassium secretion through ROMK. This is the mechanism behind every hyperaldosteronism picture and every potassium-sparing diuretic.
Traced from the start
- Glomerular filtration barrier
- Proximal tubule: Na+/H+ exchange and bicarbonate reclamation
- Thick ascending limb of Henle (NKCC2)
- Early distal convoluted tubule: thiazide-sensitive NaCl cotransporter
- Cortical collecting duct principal cell: ENaC and potassium secretion
Detail
- Reabsorbs
- ~2-3% of filtered Na+ via ENaC; a small amount, but it is where final Na+ excretion (0.1-1% of the filtered load) is set
- Secretes
- K+ through ROMK (and flow-activated BK channels) down the electrical gradient created by ENaC (lumen ~-40 mV); K+ secretion rises with distal Na+ delivery, tubular flow, aldosterone and alkalosis
- Transporter
- Apical ENaC and ROMK; basolateral Na+/K+-ATPase
- Hormone
- Aldosterone via the mineralocorticoid receptor (11-beta-HSD2 shields it from cortisol) induces SGK1, more ENaC, ROMK and Na+/K+-ATPase; ANP inhibits Na+ reabsorption via cGMP; ADH modestly increases ENaC
- Diuretic
- Potassium-sparing: amiloride and triamterene block ENaC from the lumen; spironolactone and eplerenone antagonise the mineralocorticoid receptor; natriuresis is weak (up to ~3% of filtered Na+) but they blunt K+ and H+ loss from upstream diuretics
When it goes wrong
Primary hyperaldosteronism (Conn adenoma or bilateral adrenal hyperplasia)
Resistant hypertension with hypokalaemia and metabolic alkalosis and suppressed renin; screen with the aldosterone:renin ratio
Spironolactone or amiloride combined with an ACE inhibitor, ARB, NSAID, trimethoprim or CKD
Hyperkalaemia; spironolactone also causes gynaecomastia (eplerenone does not)
Liddle syndrome (gain-of-function ENaC)
Early-onset hypertension with hypokalaemic alkalosis and low renin AND low aldosterone; responds to amiloride, not spironolactone; liquorice or 11-beta-HSD2 deficiency gives the same picture by letting cortisol act on the receptor
Low distal Na+ delivery (volume depletion) or hypoaldosteronism (Addison disease, ACE inhibitor, heparin, type 4 RTA)
Impaired K+ secretion and hyperkalaemia; loop and thiazide diuretics do the opposite by raising delivery and flow
Practise this structure
1 question in the bank tagged Aldosterone.