Calcium/Vitamin D Logic

Vitamin D is a fat-soluble prohormone obtained from dietary sources (D2/ergocalciferol from plants, D3/cholecalciferol from animal sources) and cutaneous synthesis (UVB radiation converts 7-dehydrocholesterol in the skin to cholecalciferol). Vitamin D undergoes two hydroxylation steps: first in the liver by 25-hydroxylase to form 25-hydroxyvitamin D (calcidiol, the storage form measured clinically), then in the kidney by 1-alpha-hydroxylase to form 1,25-dihydroxyvitamin D (calcitriol, the active hormone). Calcitriol binds to the vitamin D receptor (VDR) in enterocytes, upregulating calbindin and TRPV6 calcium channels to increase intestinal calcium absorption from 10-15% (without vitamin D) to 30-40% (with adequate vitamin D). PTH stimulates renal 1-alpha-hydroxylase, linking the PTH and vitamin D axes. The NP must understand this pathway to logically evaluate why calcium is abnormal: is it a vitamin D production problem (limited sun, liver disease, CKD), an absorption problem (malabsorption, bariatric surgery), or a regulatory problem (PTH disorder)?