Skin to liver to kidney, with calcitriol acting mainly on the gut
Expansion
Pathway
- Skin: 7-dehydrocholesterol plus UVB gives cholecalciferol (D3). Dietary D2 and D3 contribute
- Liver: 25-hydroxylation to 25-hydroxyvitamin D, the storage form and the one measured clinically
- Kidney: 1-alpha hydroxylation to calcitriol, the active hormone. This step is tightly regulated
Actions: increases intestinal absorption of calcium and phosphate (its main effect), permits bone mineralisation, and suppresses parathyroid hormone.
Regulation: 1-alpha hydroxylase is stimulated by parathyroid hormone, hypocalcaemia and hypophosphataemia, and inhibited by FGF23 and calcitriol itself.
Deficiency causes rickets in children and osteomalacia in adults, with bone pain, proximal myopathy, low calcium and phosphate, raised alkaline phosphatase and secondary hyperparathyroidism.
Clinically important consequences of the pathway: in chronic kidney disease the renal step fails, so alfacalcidol or calcitriol is needed rather than plain cholecalciferol; in liver disease the 25 step is impaired; and in sarcoidosis granulomatous macrophages express unregulated 1-alpha hydroxylase, causing hypercalcaemia.