A patient with hypoparathyroidism has low serum calcium, high phosphate, and low PTH. Administration of PTH would restore normal calcium through which renal mechanism?

• A PTH directly inhibits the Na+-Ca2+ exchanger in the loop of Henle, increasing calcium reabsorption
• B PTH binds collecting duct receptors and activates AQP2 insertion, increasing water reabsorption that concentrates calcium
• C PTH decreases GFR to reduce calcium filtration load, thereby conserving calcium
• D PTH stimulates 1-alpha-hydroxylase in the proximal tubule, converting 25(OH)D to 1,25(OH)2D (calcitriol), enhancing intestinal calcium absorption; PTH also increases distal tubular calcium reabsorption and inhibits proximal tubular phosphate reabsorption ✓

Explanation

PTH restores serum calcium through multiple coordinated mechanisms. In the kidney, PTH binds to receptors on proximal tubule cells, activating adenylyl cyclase (cAMP) and PKA, which: (1) stimulates 25-hydroxyvitamin D 1-alpha-hydroxylase, converting 25(OH)D3 to the active 1,25(OH)2D3 (calcitriol) — this in turn upregulates intestinal TRPV5/6 Ca2+ channels and calbindin D9k, increasing intestinal Ca2+ absorption; (2) inhibits NaPi-IIa and NaPi-IIc cotransporters in the proximal tubule, causing phosphaturia (lowering serum phosphate); and (3) in the distal tubule and thick ascending limb, PTH upregulates apical TRPV5 Ca2+ channels, increasing transcellular Ca2+ reabsorption. PTH also mobilises Ca2+ from bone by stimulating osteoclastogenesis (RANKL/OPG pathway via osteoblasts). Options B–D are incorrect mechanisms.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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