Vitamin D Dr.S.Chakravarty ,MD

Vitamin D (yeast) Vitamin D2 : Ergosterol (pro D2)  Ergocalciferol (D2) added to milk and dairy. (Human) Vitamin D3 : Pro (7-dehydrocholesterol)  Pre (9,10-secosterol)  (D3) cholecalciferol. 7-Dehydrocholesterol is present in epidermis and dermis. Short exposure of UV light 290-315nm converts pro to pre vitD3  enters blood circulation and equilibrates to D3.

Sunlight Prolonged exposure to sunlight leads to conversion of previtamin D3 to Lumisterol and Tachysterol. Seasonal variation – more UV at the end of winter in cold countries. Geographical variations Other Considerations :- Sunscreens :-In labs tests with Sunscreen lotions block UV and decrease production of vitamin D3. But because people who use more sunscreen spend more time in the sun, so naturally they will have higher vitamin D levels.

Activation of vitamin D3 : skin

X CIRRHOSIS , LIVER FAILURE 7-Dehydrocholesterol Dietary source required if insufficient exposure to UV light. SKIN :-UV Light CHOLECALCIFEROL X CIRRHOSIS , LIVER FAILURE LIVER :- 25 hydroxylase HYPOCALCEMIA 25 hydroxycholecalciferol (+) X CRF, END STAGE RENAL DIASEASEc +PARATHYROID KIDNEY :- 1 α hydroxylase(induce ) 1,25 dihydroxy cholecalciferol Vit D Kidney :- Vit D : Retention of Ca+2 PTH :- Conserves Ca+2 at expense of PO4-3 Bone :- Osteoclasts ; Ca+2 Mineralization(with PTH) Duodenum: Increase calcium uptake from intestine

Calcium metabolism: Calcium is stored as calcium-hydroxy-appetite crystals in bone. 99% present in bone – which maintains serum calcium levels of (9-10.5 mg/dl) 5 mg is ionized calcium – physiologically important 3.5 -4 mg is bound to serum albumin (0.8mg /gm of albumin) 1mg exists as bound to anions (citrate).

Functions of calcium: Intracellular Extracellular Second messenger Muscle contraction Membrane excitability Degranulation and release of hormones. Co-factor in enzyme activity. Nerve impulse transmission Coagulation cascade Maintains intracellular conc. Deposition of calcium in bone from diet.

Role of vitamin D in calcium homeostasis: Vitamin D binds selectively to retinoic acid X receptor (RXR) by a Zinc finger motif -- mRNA production  synthesis of Epithelial calcium receptor Calbindin --- in intestines leading increased calcium absorption. Role of PTH: Stimulate Osteoblast to produce RANK-L and alkaline phosphatase  binds to RANK receptor on monocyte to form osteoclasts  HCl secretion and demineralization of bone. Receptor Activator of Nuclear Factor κ B

What happens in Hypocalcemia : Increase in PTH secretion and decrease calcitonin. Increased distal tubular re-absorption of calcium and excretion of phosphate: Increase 1α-hydroxylase activity of kidney. Increase 1,25 dihydroxy cholecalciferol  increased absorption in the small intestine. Increased Osteoclastic activity bone resorption and increased calcium in circulation.

During Hypercalcemia : Release of calcitonin  inhibits the activity of osteoclasts Decrease in PTH and Decreased 1,25 -Dihydroxycholecalciferol  decreased renal and intestinal absorption. Bone formation due to supersaturation of calcium and phosphate.

Vitamin D deficiency: Hypocalcemia and hypophosphatemia : poor mineralization and stunted growth Rickets : children Widening of growth plate – rachitic rosary at the costchondral junction. Craniotabes – ping pong skull Bow legs or knocked knees – bending of long bones due to poor mineralization. Reduced radio-opacities on long bones. Lax muscles – protruberant abdomen.

Osteomalacia Seen in adults Looser’s zone or pseudofractures seen in scapula, pelvis and femoral neck. Soft, flexible, brittle, deformed bones Progressive weakness Pain in pelvis, lower back, and legs

Other functions of VIT D: Regulation of cell growth – Cancer prevention Regulation of immune function – prevents autoimmune disease Regulation of blood pressure – prevents heart disease

Hypervitaminosis D: Similar to features of hypercalcemia: Constipation, polyuria, polydipsia, confusion Calcinosis of soft tissues – metastatic calcification. Renal stones

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