Absorption of vitamin D requires bile acids to form micelles in the small intestine and allow transport through the lymph system. Phosphate reabsorption also increases as a result of vitamin D action in the kidney.
Vitamin D Physiology
• Vitamin D3 (cholecalciferol) is produced endogenously through the action of ultraviolet light, which induces photolysis of 7-dehydrocholesterol in the skin.
• Exogenous vitamin D3 from animal sources (cholecalciferol) and Vitamin D2 (ergocalciferol) from plant sources are absorbed and contribute to the endogenous pool of vitamin D.
• Absorption of vitamin D requires bile acids to form micelles in the small intestine and allow transport through the lymph system.
• For the purposes of simplicity, cholecalciferol (D3) and ergocalciferol (D2) shall be grouped under the rubric of vitamin D, but they are not equivalent therapeutically.
• Vitamin D exists in minute concentrations and is mostly bound (85%) to vitamin D–binding protein, also known as Gc globulin, with a much smaller proportion bound to albumin (15%).
• The initial step in the activation of vitamin D involves 25-hydroxylation in the liver.
• The final activation step occurs in the kidney via the action of the 1-??hydroxylase.
• This final hydroxylation step is the rate-limiting reaction and regulated negatively by 1,25[OH]2D); Ca2+; and phosphate.
• Positive regulators of 1-??hydroxylase include PTH, calcitonin, insulin-like growth factor 1 and y-interferon.
• Deactivation of vitamin D occurs via the action of 24-hydroxylase.
Deactivation of vitamin D occurs via the action of 24-hydroxylase.
Vitamin D Actions
• Kidney: 1,25(OH)2D increases the expression of Ca2+ channels, intracellular calcium-binding proteins (calbindins-D28k), and increases the activity of the basolateral Na+/Ca2+ exchanger.2 Collectively, these effects promote increased transcellular calcium transport in the kidney.
- Phosphate reabsorption also increases as a result of vitamin D action in the kidney.
- 1,25(OH)2D suppresses the action of 1-?-hydroxylase and induces 24-hydroxylase activity, thus providing negative feedback regulation.
• Intestine: 1,25(OH)2D increases the expression of epithelial Ca2+ channels, intracellular calcium-binding proteins (calbindins-D9k), and augments Na+/Ca+ exchange, thus, promoting calcium absorption from the gastrointestinal tract.
- To a much smaller degree, vitamin D enhances paracellular uptake of calcium via a voltage dependent mechanism.
• Bone: 1,25(OH)2D induces maturation of osteoblasts resulting in the synthesis of matrix proteins and mineralization of bone.
• 1,25(OH)2D promotes osteoclastogenesis; mature osteoclasts are essential for bone remodeling.
• Peptide chain synthesized by the parafollicular (or C cells) of the thyroid gland.
• Secretion is under the control of the calcium-sensing receptor. High circulating calcium levels increase calcitonin secretion.
• Kidney: Receptors are expressed on the proximal renal tubule. Activation of these receptors reduces calcium and phosphate reabsorption.
• Bone: Calcitonin induces apoptosis of osteoclasts reducing bone resorption, thus, reducing the calcium and phosphate concentration in plasma.