Calcium-sensing receptor (CaSR) mutations - FHH vs familial hypocalcaemia
Core concept
- CaSR = class C G-protein-coupled receptor, the body's calciostat
- Agonists: calcium, magnesium, and the polycations barium, gadolinium, neomycin, spermine
- Signals via Gq/11 -> PLC -> IP3 -> inc intracellular Ca and Gi -> dec cAMP
- Two principal sites
- Parathyroid chief cell - activation SUPPRESSES PTH (the inverse of most endocrine receptors)
- Renal thick ascending limb - activation inhibits paracellular Ca and Mg reabsorption -> calciuria
- Also: proximal tubule, DCT, inner medullary collecting duct (inhibits ADH action), C cells (inc calcitonin), stomach, intestine, bone, brain
- -> the direction of the mutation predicts everything
- Loss of function (inactivating) - gland "feels" hypocalcaemic -> inc PTH set-point + renal Ca retention -> hypercalcaemia with LOW urine calcium
- Gain of function (activating) - gland "feels" hypercalcaemic -> dec PTH + renal Ca wasting -> hypocalcaemia with HIGH urine calcium
3 more sections, plus exam facts
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