Makindo Medical Notes

⚡ Aldosterone is a mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex. It regulates sodium (Na⁺) and potassium (K⁺) balance, blood pressure 🩸, and fluid homeostasis 💧. Although its main actions are renal, it also affects the heart and blood vessels.

🧬 Synthesis & Regulation

• Synthesis: Derived from cholesterol via key enzymes (cholesterol desmolase, 21-hydroxylase, aldosterone synthase).
• Regulators:
  • 🌀 RAAS: Angiotensin II → powerful stimulus for aldosterone secretion.
  • 🟤 Plasma potassium: ↑ K⁺ → ↑ aldosterone release.
  • 🧠 ACTH: Minor effect (mainly regulates cortisol, but stimulates aldosterone transiently).
  • 🧂 Sodium: Low Na⁺ indirectly activates RAAS → aldosterone release.

⚙️ Mechanism of Action

• Aldosterone diffuses into target cells → binds to mineralocorticoid receptors.
• The complex moves to the nucleus → activates transcription of genes coding for Na⁺ and K⁺ transport proteins (e.g. ENaC channels, Na⁺/K⁺-ATPase).
• Result → Na⁺ reabsorption (water follows), K⁺ and H⁺ excretion.

💡 Effects

• Kidneys:
  • ↑ Na⁺ reabsorption → ↑ water retention → ↑ BP.
  • ↑ K⁺ excretion → prevents hyperkalaemia.
  • ↑ H⁺ secretion → links to metabolic alkalosis.
• Cardiovascular system: Can promote fibrosis and vascular remodelling (important in HF and hypertension).
• Other tissues: Intestines, sweat glands, salivary glands → conserve Na⁺, excrete K⁺.

⚠️ Clinical Relevance

• Hyperaldosteronism (Conn’s syndrome, adrenal hyperplasia):
  • HTN + hypokalaemia + metabolic alkalosis.
  • Secondary causes: heart failure, cirrhosis, nephrotic syndrome (due to excess RAAS activation).
• Hypoaldosteronism:
  • Leads to hyperkalaemia + hyponatraemia + hypotension.
  • Seen in Addison’s disease, or resistance states (pseudohypoaldosteronism).
• Aldosterone antagonists: 🩺 Spironolactone, Eplerenone → block MR receptor, reduce fibrosis, used in HTN, HF, Conn’s.

📚 Exam Tips

• Conn’s triad: HTN + hypokalaemia + alkalosis.
• Spironolactone side effects: gynaecomastia, hyperkalaemia.
• Clue in OSCE: Resistant hypertension with low renin + high aldosterone → think Conn’s.

📝 Summary

Aldosterone maintains Na⁺, K⁺, BP, and acid-base balance. Its secretion is controlled by RAAS, K⁺ levels, ACTH, and Na⁺ status. Excess causes hypertension + hypokalaemia; deficiency causes hypotension + hyperkalaemia. Therapeutically, aldosterone antagonists are vital in managing heart failure and resistant hypertension.