Renin-angiotensin-aldosterone system - components and physiological effects
Core concept
- Cascade
- Angiotensinogen (liver) - substrate, always in excess
- Renin (juxtaglomerular cells) - rate-limiting step
- Angiotensin I -> ACE (pulmonary endothelium) -> Angiotensin II
- Ang II -> AT1 receptor (Gq) on vasculature, adrenal, kidney, brain
- Three stimuli for renin release - all sensed at the juxtaglomerular apparatus
- dec renal perfusion pressure - afferent arteriolar baroreceptor
- dec NaCl delivery to the macula densa (distal tubule)
- Sympathetic beta-1 stimulation of JG cells
- Inhibited by: Ang II (short loop negative feedback), ANP, high NaCl delivery, beta-blockers, NSAIDs, adenosine
- Angiotensin II effects
- Efferent arteriolar constriction >> afferent -> maintains GFR when renal perfusion falls
- Systemic vasoconstriction -> inc BP
- Proximal tubule Na/H exchanger -> inc Na and HCO3 reabsorption
- Adrenal zona glomerulosa -> aldosterone
- Posterior pituitary -> ADH; hypothalamus -> thirst
- Cardiac and vascular hypertrophy and fibrosis (the target of ACEi/ARB mortality benefit)
- Aldosterone -> mineralocorticoid receptor in principal cells of the collecting duct
- inc ENaC and Na/K-ATPase -> Na reabsorption, lumen-negative potential
- -> K+ secretion (ROMK) and H+ secretion (alpha-intercalated cells)
- -> hypokalaemia + metabolic alkalosis when in excess
3 more sections, plus exam facts
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