Calcitriol and intestinal calcium absorption

Effect · TRPV6 Calbindin-D9k VDR-RXR

1,25-dihydroxyvitamin D is the active hormone of the axis. Through the nuclear VDR-RXR heterodimer it raises duodenal and jejunal calcium absorption from roughly 10-15% of intake to 30-40%, using apical TRPV6, cytosolic calbindin-D9k and basolateral PMCA1b, and raises phosphate absorption through NaPi-IIb.

Traced from the start

Detail

Half-life: 4-6 hours, far shorter than 25(OH)D, which is why calcitriol is a poor measure of vitamin D status
Gut calcium: Apical TRPV6, then calbindin-D9k across the cell, then basolateral PMCA1b and NCX1; fractional absorption rises from about 10-15% to 30-40%
Gut phosphate: Absorbed through NaPi-IIb, so calcitriol raises serum phosphate as well as calcium: the one arm of the response that is not phosphate-lowering
Feedback: Calcitriol suppresses PTH gene transcription and parathyroid growth directly, stimulates FGF23, and induces CYP24A1 to limit itself
Bone: Needed for normal mineralisation chiefly by supplying calcium and phosphate; in excess it also supports resorption

When it goes wrong

Vitamin D deficiency

Calcium absorption falls and PTH rises to defend serum calcium at the skeleton's expense: osteomalacia with a raised alkaline phosphatase and Looser zones

Hypoparathyroidism or chronic kidney disease

Calcitriol or alfacalcidol is prescribed rather than cholecalciferol, because the 1-alpha-hydroxylation step is precisely what has been lost

Granulomatous disease, lymphoma or calcitriol overtreatment

Hypercalcaemia and hypercalciuria with a suppressed PTH

Practise this structure

1 question in the bank tagged Vitamin D.

A 63-year-old woman reports several months of bone pain and difficulty climbing stairs. She has no focal neurological deficit. Serum calcium is 2.19 mmol/L (2.1…

Clinical rotations · common