Expansion
25-hydroxylation in the liver, 1-alpha hydroxylation in the kidney
Expansion
- Skin: 7-dehydrocholesterol plus ultraviolet B gives cholecalciferol (vitamin D3); some comes from the diet
- Liver: 25-hydroxylation gives 25-hydroxyvitamin D, the storage form and the one measured clinically. Largely unregulated
- Kidney (proximal tubule): 1-alpha hydroxylation gives 1,25-dihydroxyvitamin D (calcitriol), the active form. Tightly regulated
The renal step is stimulated by parathyroid hormone, hypocalcaemia and hypophosphataemia, and inhibited by FGF23 and by calcitriol itself.
Calcitriol actions: increases calcium and phosphate absorption from the gut, promotes bone mineralisation, and suppresses parathyroid hormone.
Clinical consequences:
- Chronic kidney disease impairs the 1-alpha step, so measured 25-hydroxyvitamin D may be normal while active hormone is deficient; these patients need alfacalcidol or calcitriol, not plain cholecalciferol
- Liver disease impairs the 25 step
- Sarcoidosis and other granulomatous disease produce extra-renal 1-alpha hydroxylase, causing hypercalcaemia