Aldosterone Physiology
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Direct answer
Aldosterone acts on the principal cells of the late distal tubule and collecting duct to retain sodium and excrete potassium: induced gene expression (SGK1) inserts epithelial sodium channels (ENaC) on the apical membrane and Na-K ATPase pumps basolaterally, so sodium reabsorption lugs potassium secretion through ROMK channels out of the same cells. Its stimuli are angiotensin II (volume depletion), a direct effect of raised plasma potassium, and ACTH only permissively; ANP and dopamine inhibit it. The mineralocorticoid receptor cannot itself distinguish aldosterone from cortisol — 11-beta-hydroxysteroid dehydrogenase type 2 in the kidney converts cortisol to inactive cortisone, and loss of that protection explains liquorice-induced apparent mineralocorticoid excess.
What you must remember
- Site and mechanism: late distal tubule and collecting duct principal cells; apical ENaC and ROMK, basolateral Na-K ATPase; sodium moves down its gradient in, potassium follows the electrochemical gradient out — "sodium follows water, potassium follows sodium".
- Stimuli in rank: angiotensin II (through volume and the RAAS), plasma potassium as little as 0.1 mEq/L rise, and ACTH as a minor permissive factor; sodium restriction raises it, and dopamine plus ANP restrain it.
- Potassium disposal: aldosterone is the major handler of a potassium meal — it also drives potassium into cells and stool, so hyperkalaemia both stimulates secretion and is treated by it.
- Escape phenomenon: in primary hyperaldosteronism, sodium retention self-limits within days through pressure natriuresis and ANP release, so oedema is absent and serum sodium stays near normal; the potassium and proton loss continue unabated.
- Conn syndrome pattern: hypertension with hypokalaemic metabolic alkalosis, suppressed plasma renin activity (the diagnostic split — high aldosterone, low renin), polyuria from nephrogenic diabetes-like concentrating defect.
- Secondary hyperaldosteronism: high renin plus high aldosterone in heart failure, cirrhosis and nephrotic states, where effective arterial volume is low so escape does not occur — these patients get oedema and ascites.
- Pharmacology at the target: spironolactone and eplerenone block the receptor (potassium-sparing, gynaecomastia with spironolactone), amiloride and triamterene block ENaC directly.
- 11-beta-HSD2 and the MR: cortisol and aldosterone bind the mineralocorticoid receptor equally well; renal 11-beta-HSD2 deactivates cortisol, and its inhibition by glycyrrhetinic acid (liquorice) produces sodium retention, hypertension and hypokalaemia with low aldosterone.
How to work through a hypokalaemic hypertensive patient
A 38-year-old with blood pressure 164/102 mmHg, serum potassium 2.9 mEq/L, bicarbonate 32 mEq/L and mild polyuria. The combined alkalosis and hypertension localise the problem to mineralocorticoid action on the distal nephron. Measure plasma renin activity and aldosterone: high aldosterone with renin suppressed to near zero defines primary hyperaldosteronism — the adenoma (Conn) or bilateral hyperplasia, the commonest specifically treatable secondary hypertension and far more prevalent than the old textbook "1%" (contemporary series suggest 5-10% of hypertension clinics, though figures vary with screening).
The escape phenomenon explains the surprises in the case: despite kilograms of retained sodium, the patient has no oedema because pressure natriuresis and ANP cap the volume gain, and serum sodium remains normal or only mildly high — the damage is hypertension plus uncontrolled potassium and proton wasting (muscle weakness, cramps, arrhythmia risk, nephrogenic polyuria from chronic hypokalaemia impairing the concentrating mechanism). Contrast the heart-failure patient with secondary hyperaldosteronism: renin is high because effective arterial volume is low, escape fails because the arterial underfilling persists, so the same aldosterone produces generalised oedema and ascites — the reason spironolactone earns its place in ascites and heart-failure regimens at low doses, watched for hyperkalaemia.
Where students slip
The persistent myth is that aldosterone directly "holds water"; it holds sodium, and water follows osmotically until escape mechanisms brake the volume. The second slip is listing ACTH as a major regulator — remove the pituitary and aldosterone control by angiotensin II and potassium continues, though rare ACTH-driven ectopic aldosterone problems do not exist precisely because the glomerulosa obeys the volume axis. The exam-worthy subtlety is the cortisol-MR overlap: patients eating large amounts of liquorice present with an apparent mineralocorticoid excess — hypertension, hypokalaemia, low renin and low aldosterone — because glycyrrhetinic acid inhibits 11-beta-HSD2 and lets cortisol occupy the receptor; quoting this mechanism in viva reliably earns the extra mark.
Frequently asked questions
How does aldosterone cause potassium excretion?
By increasing ENaC-mediated sodium reabsorption it makes the tubular lumen electronegative, driving potassium out through ROMK channels of principal cells, while increased basolateral Na-K ATPase reloads the cells with potassium to secrete.
Why does primary hyperaldosteronism not cause oedema?
The escape phenomenon: retained sodium expands volume enough to trigger pressure natriuresis and ANP release, which cap weight gain — though hypertension and potassium wasting continue.
What separates Conn syndrome from secondary hyperaldosteronism biochemically?
Both have high aldosterone, but Conn has suppressed renin (autonomous adrenal production), whereas secondary hyperaldosteronism has high renin driven by low effective arterial volume, as in cirrhosis or heart failure.
Why does chronic hypokalaemia cause polyuria?
Prolonged potassium depletion impairs sodium-potassium-2-chloride transport in the thick ascending limb and down-regulates aquaporin-2 responsiveness, producing a nephrogenic concentrating defect resistant to desmopressin.
How does liquorice mimic aldosterone excess?
Glycyrrhetinic acid inhibits renal 11-beta-hydroxysteroid dehydrogenase type 2, so cortisol is no longer converted to cortisone and occupies the mineralocorticoid receptor — sodium retention and hypokalaemia with low aldosterone and renin.