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Defficiency states of. VITAMIN D. dr mukesh kumar. What is Vitamin D?. Vitamin D is a fat-soluble pro-hormone Sterol derivative 2 forms of vitamin D Vitamin D2 (Ergocalciferol) Vitamin D3 (Cholecalciferol) Pro-hormone is converted into its biologically active metabolite: calcitriol
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Defficiency states of VITAMIN D dr mukesh kumar
What is Vitamin D? Vitamin D is a fat-soluble pro-hormone Sterol derivative 2 forms of vitamin D Vitamin D2 (Ergocalciferol) Vitamin D3 (Cholecalciferol) Pro-hormone is converted into its biologically active metabolite: calcitriol Vitamin D may be obtained from the diet and through skin exposure to sunlight (UV light)
Uses for Vitamin D Maintains structural integrity of bones & bone growth by regulating use of calcium + phosphate (bone turnover) Maintains serum calcium homeostasis Research shows that Vitamin D may play a role in immune function and protection from chronic diseases
Synthesis and Metabolism Ergocalciferol (D2) synthesized in plant and fungi when ergosterol undergoes photolysis under UV light Cholecalciferol (D3) synthesized in skin of animals by photolysis of 7-dehydrocholesterol Bioactivation occurs through 2 steps Hydroxylation in liver produces calcidiol Hydroxylation in kidney produces calcitriol
Mechanism of Action Calcitriol is transported through the circulatory system by vitamin D binding protein and albumin Diffuses into the nucleus of target cells and binds to Vitamin D receptor (VDR) VDR associates with Retinoic Acid X receptor (RXR) – forms VDR-RXR complex VDR-RXR binds to DNA sequences called Vitamin D Response Elements (VDREs) to modulate the expression of >50 genes
Mechanism of Action VDRE regulated gene expression leads to: Increased dietary calcium and phosphorus absorption in small intestine Increased renal reabsorption of calcium Increased renal excretion of phosphate Increased resorption of bone to increase serum calcium levels
Sources of Vitamin D- Food Less than 10%! Natural Food Sources: Egg Yolk 20-25/yolk Shrimp 152/100gm Tuna 224-332/100gm Canned salmon 624/100gm Fortified Food Sources: Vitamin D milk 400/L Formula 400/L Cereal 40/serving Yogurt 89/100gm
Sources of Vitamin D - Sun UV light converts cholesterol in skin into D3 Dark skinned people require a longer duration of sun exposure for adequate production of Vitamin D Less UV light is available in the winter months, higher latitudes, and with cloud cover and air pollution
Vitamin D sources Fortified foods (milk and orange juice) Fish liver oil Cod liver oil contains over 1000IU/tablespoon Fatty fish (salmon, tuna) Liver, beef Sunlight exposure 5-30 minutes in direct sunlight at mid-day Supplements
Recommended Dietary Allowances *Adequate intake rather then RDA Retrieved from Health Canada. (2010, December 13). Vitamin D and Calcium: Updated Dietary Reference Index
Why do breast fed babies need supplemental Vitamin D? Breast milk contains little vitamin D • 25-78 IU/day • Rates of vitamin D deficiency in breastfed infants up to 78% in winter Limited sun exposure : infants less than 6 months should be kept out of direct sunlight
Why do breast fed babies need supplemental Vitamin D? High rates of Vitamin D maternal deficiency • Pittsburgh study at birth: • Black women • 29% deficient • 54% insufficient • White women • 5% deficient • 42% insufficient
Preventing Vitamin D deficiency • Breastfed and partially breastfed infants should be supplemented with 400 IU/day of vitamin D beginning in the first few days of life. • Supplementation should be continued unless the infants is weaned to at least 1L/day of vitamin D-fortified formula or fortified milk. TriViSol contains 400 IU per ml
Vitamin D Deficient States • Rickets • Peak incidence 3-18 months • Defective bone growth due to lack of mineralization at growth plate • Hypocalcemic seizures • Growth failure, lethargy, irritability • Delay in gross motor development, bone pain
Vitamin D Deficient states Rickets Bowing or widening of physis Costochondral beading (rachitic rosary) Craniotabes Delayed closure of anterior fontanel Dental abnormalities Flaring of ribs at diaphragm
Vitamin D Deficiency Inadequate exposure to sunlight (UV rays) Inadequate intake from diet Deficiencies in GI tract absorption Kidney or liver disorders Retrieved from: http://emedicine.medscape.com/article/412862-overview
Rickets (children) Pathophysiology Rickets is failure of bone to mineralize Growth plates of bone continue to enlarge while the load on the limbs continues to increase In the absence of mineralization, limbs become bowed Symptoms Characterized by stunted growth and deformed bones In infants, rickets may result in the delayed closure of fontanelles (soft spots on baby’s head)
Treatment • Vitamin D and calcium supplements • Corrective surgery or bracing for skeletal deformities
Vitamin D Deficient States • Adult Vitamin D deficiency implicated in • Increased infections • Autoimmune diseases (Multiple Sclerosis, Rheumatoid arthritis) • Cancer • Type 2 Diabetes • Bipolar disorder, schizophrenia • Type I Diabetes in childhood • Maternal Vitamin D status associated with adverse outcomes of pregnancy – miscarriage, preeclampsia, preterm birth
Osteomalacia (adult) Pathophysiology Impaired bone mineralization Adult bones are in constant state of turnover and new bones are brittle and thin Symptoms Bone pain (lower spine, pelvis, hips, legs, ribs) May result in muscle weakness Treatment Vitamin D supplements Treating conditions affecting vitamin D absorption and metabolism
Osteoporosis Pathophysiology Rate of bone loss is greater than rate of bone formation – gradual loss of bone mass Bone strength is compromised – increased risk of fracture Symptoms Non-specific chronic back pain Height loss Bone fractures occur more easily
Treatment and Prevention • Maximizing/maintaining existing bone mass density • Calcium and vitamin D supplements, weight-bearing exercise • Minimize risk of falls
Laboratory diagnosis Vitamin D status- 25(OH)-D levels • Deficiency <37.5 nmol/mL • Insufficiency 37.5-50 nmol/mL • Sufficiency >50 (?) nmol/mL Severe deficiency states associated with: Ca,PO4, Alk Phos, PTH
Summary Slide Vitamin D (fat-soluble, pro-hormone): ergocalciferol (D2) and cholecalciferol (D3) • converted to active hormonal form, calcitriol by metabolism in liver and kidney • Targets: bone, kidney and GI tract • Function: maintains serum calcium levels & integrity of bones growth via calcium regulation Deficiency – leads to rickets, osteomalacia and osteoporosis • Lack of calcium leads to impaired bone mineralization and loss of bone mass • Treatment: Increase vitamin D and calcium intake, and increase bone mass density