Related Subjects:
|Metabolic acidosis
|Lactic acidosis
|Acute Kidney Injury (AKI) / Acute Renal Failure
๐ฉบ The Renin-Angiotensin System (RAS) is a hormone cascade essential for controlling blood pressure, electrolyte balance, and vascular tone.
๐ก Key concept: it converges on production of angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release.
โ๏ธ Components of the RAS
- Renin: Enzyme from juxtaglomerular cells (JGA), released when BP falls, NaCl at macula densa is low, or SNS (ฮฒ1) is activated. Converts angiotensinogen โ angiotensin I.
- Angiotensinogen: Substrate glycoprotein made in the liver.
- Angiotensin I: Inactive decapeptide, converted by ACE to angiotensin II.
- ACE: Angiotensin-converting enzyme (mainly in lung endothelium).
- Angiotensin II: Octapeptide effector acting via AT1 receptors โ vasoconstriction, aldosterone release, thirst, ADH release.
- Aldosterone: Mineralocorticoid from adrenal cortex โ โ Naโบ & water reabsorption, โ Kโบ excretion.
๐ Stepwise Mechanism
- Trigger: Low BP, low NaCl, or sympathetic drive โ renin release.
- Conversion: Renin converts angiotensinogen โ angiotensin I.
- Activation: ACE (lungs) converts angiotensin I โ angiotensin II.
- Actions of Ang II:
- Vasoconstriction โ โ systemic vascular resistance.
- Aldosterone secretion โ Naโบ & water retention.
- ADH release โ water reabsorption.
- Stimulates thirst.
- Cardiac & vascular hypertrophy/remodelling.
- Negative feedback: Ang II inhibits further renin release.
๐งช Regulation
- Feedback: High Ang II & high Naโบ suppress renin release.
- Baroreceptors: Renal afferent arterioles sense perfusion pressure.
- Hormones: Natriuretic peptides oppose RAS.
๐ Clinical Relevance & Drug Targets
- Hypertension: RAS overactivity common.
โ Rx: ACE inhibitors, ARBs, direct renin inhibitors, mineralocorticoid receptor antagonists (e.g. spironolactone).
- Heart Failure: RAS drives vasoconstriction + fluid retention.
โ Blocking RAS reduces afterload, preload, and remodelling.
- CKD: Chronic RAS activation causes glomerular hypertension & fibrosis.
โ ACEi/ARB slow progression and protect proteinuric kidneys.
๐ Summary Table
| Step | Location | Drug Target |
|---|
| Renin release | JGA (kidney) | Renin inhibitors (aliskiren) |
| Ang I โ Ang II | Lung endothelium (ACE) | ACE inhibitors (enalapril, ramipril) |
| Ang II action | AT1 receptor (vessels, adrenals) | ARBs (losartan, valsartan) |
| Aldosterone effects | Kidney (DCT/CD) | MR antagonists (spironolactone, eplerenone) |
๐ Take-Home
The RAS is a cascade with renin as the rate-limiting step and Ang II as the major effector.
Therapies targeting the RAS are central in hypertension, CKD, and heart failure management.
