Overview
This lecture explains the renin-angiotensin-aldosterone system (RAAS), focusing on its physiology, roles in blood pressure and volume regulation, and its pathological activation in chronic diseases like heart failure.
Physiology of RAAS Activation
- The RAAS maintains blood pressure and blood volume, especially during scenarios like hemorrhage.
- Reduced blood flow to the kidney activates release of renin from specialized juxtaglomerular cells.
- The kidney nephron has sensors: baroreceptors (pressure sensing) and macula densa (sodium sensing).
- Juxtaglomerular apparatus is made up of pressure (juxtaglomerular cells) and sodium sensors (macula densa).
- Renin release is stimulated by low kidney perfusion, low sodium at the macula densa, and increased sympathetic nervous activity (via beta-1 adrenergic receptors).
RAAS Cascade and Hormonal Actions
- Renin, released into circulation, converts liver-derived angiotensinogen into angiotensin I.
- Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE) mainly on pulmonary capillary endothelium.
- ACE also degrades bradykinin, a vasodilator.
- Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release from the adrenal cortex (zona glomerulosa).
Effects of Angiotensin II and Aldosterone
- Angiotensin II constricts veins (increasing venous return and cardiac output) and arterioles (raising diastolic blood pressure).
- Aldosterone acts on principal cells in the nephron, increasing sodium and water reabsorption and promoting potassium secretion.
- Angiotensin II stimulates ADH (antidiuretic hormone) release, increasing water reabsorption in the nephron’s collecting ducts.
- Angiotensin II increases thirst and enhances sympathetic nervous system activity, further raising blood pressure.
Pathological Activation of RAAS
- Chronic reduction in renal perfusion (e.g., heart failure) causes sustained RAAS activation.
- Chronically elevated angiotensin II and aldosterone induce pathological cardiac remodeling (hypertrophy, fibrosis) and vascular changes.
- These changes worsen heart failure and vascular disease.
Key Terms & Definitions
- RAAS (Renin-Angiotensin-Aldosterone System) — Hormonal system regulating blood pressure and fluid balance.
- Renin — Kidney enzyme triggering RAAS activation by converting angiotensinogen to angiotensin I.
- Juxtaglomerular apparatus — Nephron structure detecting blood pressure and sodium, releasing renin.
- Macula densa — Nephron region sensing sodium concentration.
- Angiotensinogen — Liver-produced protein, precursor to angiotensin I.
- ACE (Angiotensin-Converting Enzyme) — Lung capillary enzyme converting angiotensin I to angiotensin II.
- Angiotensin II — Potent vasoconstrictor and stimulator of aldosterone/ADH.
- Aldosterone — Adrenal hormone promoting sodium and water reabsorption.
- Cardiac remodeling — Structural changes in the heart due to chronic RAAS activation.
Action Items / Next Steps
- Review the mechanism of ACE inhibitors and angiotensin receptor blockers as heart failure treatment.
- Prepare questions for discussion on RAAS-related drug actions for next session.