Makindo Medical Notes

Aldosterone is a steroid hormone produced by the zona glomerulosa of the adrenal cortex. It plays a crucial role in regulating sodium and potassium balance, blood pressure, and fluid homeostasis in the body. Aldosterone acts primarily on the kidneys, but it also has effects on other tissues such as the heart and blood vessels.

Synthesis and Regulation of Aldosterone

• Synthesis:
  • Aldosterone is synthesized from cholesterol through a series of enzymatic reactions in the adrenal cortex.
  • The key enzymes involved in aldosterone synthesis include cholesterol desmolase, 21-hydroxylase, and aldosterone synthase.
• Regulation:
  • The primary regulators of aldosterone secretion are:
    • Renin-Angiotensin-Aldosterone System (RAAS):
      • Renin, released by the juxtaglomerular cells of the kidney in response to low blood pressure or low sodium levels, converts angiotensinogen to angiotensin I.
      • Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE) primarily in the lungs.
      • Angiotensin II stimulates the adrenal cortex to secrete aldosterone.
    • Plasma Potassium Levels:
      • High plasma potassium levels directly stimulate aldosterone secretion to enhance potassium excretion.
    • Adrenocorticotropic Hormone (ACTH):
      • ACTH can stimulate aldosterone production, although its effect is more pronounced on cortisol synthesis.
    • Sodium Levels:
      • Low sodium levels can indirectly stimulate aldosterone release through the activation of RAAS.

Mechanism of Action

• Aldosterone acts on target cells by binding to mineralocorticoid receptors (MR) in the cytoplasm.
  • The aldosterone-MR complex translocates to the nucleus, where it binds to specific DNA sequences, activating the transcription of aldosterone-responsive genes.
  • This leads to the synthesis of proteins involved in sodium reabsorption and potassium excretion.

Effects of Aldosterone

• Kidneys:
  • Aldosterone acts primarily on the distal convoluted tubules and collecting ducts of the nephron.
    • Increases sodium reabsorption, leading to increased water retention and elevated blood pressure.
    • Enhances potassium excretion, maintaining electrolyte balance.
    • Increases hydrogen ion excretion, contributing to acid-base balance.
• Cardiovascular System:
  • Aldosterone can promote fibrosis and inflammation in the heart and blood vessels, contributing to cardiovascular diseases such as hypertension and heart failure.
• Other Effects:
  • Aldosterone also affects other tissues, including the intestines, salivary glands, and sweat glands, by enhancing sodium reabsorption and potassium excretion.

Clinical Relevance

• Hyperaldosteronism:
  • Characterized by excessive aldosterone production, leading to hypertension, hypokalemia, and metabolic alkalosis.
  • Primary hyperaldosteronism (Conn's syndrome) is often caused by an adrenal adenoma or bilateral adrenal hyperplasia.
  • Secondary hyperaldosteronism can result from conditions such as heart failure, liver cirrhosis, and nephrotic syndrome.
• Hypoaldosteronism:
  • Characterized by insufficient aldosterone production, leading to hyperkalemia, hyponatremia, and hypotension.
  • Can be caused by adrenal insufficiency (Addison's disease) or resistance to aldosterone action (pseudohypoaldosteronism).
• Aldosterone Antagonists:
  • Medications such as spironolactone and eplerenone block the effects of aldosterone, used in the treatment of conditions like hypertension, heart failure, and hyperaldosteronism.

Summary

Aldosterone is a crucial hormone for maintaining sodium and potassium balance, blood pressure, and fluid homeostasis. Its regulation involves multiple factors, including the renin-angiotensin-aldosterone system, plasma potassium levels, ACTH, and sodium levels. Understanding the physiology of aldosterone is essential for diagnosing and managing disorders related to its imbalance, such as hyperaldosteronism and hypoaldosteronism.