Vitamin D deficiency, description.pptx

ppt on vit d

1. Vitamin D Metabolism & deficiency Dr. Suraj Sharma DNB General Medicine Resident

2. Overview Organic compounds required in the diet in small amounts to perform specicific biological function for normal maintenance of optimum growth & health of the organism Chemically similar substance that possess qualitatively smilar vitamin activity. Example : Retinol, Retinal, Retinoic acid are vitamer of Vitamin A Pyridoxine, Pyridoxal & Pyridoxamine are vitamer of vitamin B6 VITAMIN VITAMERS

3. History Hopkins ( beginning of 20 th century ) coined the term ‘Accessory Factor’ to the unkown & essential nutrient present in the natural foods. Funk (1913) : Vitamin (Greek : Vita – life ) accessory factor with belief that all of them were amines. McCollum & Davis (1915) : Introduced Vitamin A, B, C & D (as a anti – rickets factor )

4. HISTORY : Hopkins ( beginning of 20th century ) coined the term ‘Accessory Factor’ to the unkown & essential nutrient present in the natural foods. Funk (1913) : Vitamin (Greek : Vita – life ) accessory factor with belief that all of them were amines. McCollum & Davis (1915) : Introduced Vitamin A, B, C & D (as a anti – rickets

5. Classification of Vitamins Fat (Lipid) soluble : Vitamin A, D,K & E Their availability in diet , absorption, & transport are associated with fat. Stored in liver & adipose tissue. Exess consumption leads to toxicity. Water soluble: Vitamin C & Vitamin B Complex Heterogenous group of compound.Exess consumption excreted in Urine Hence no toxicity

6. Vitamin D Sunshine Vitamin Functions Like a hormone Sterol in structure Active form : Calcitriol : Vitamin D Provitamins : Vitamin D2 : Ergocalciferol (Plant) Vitamin D3 : Cholecalciferol (Animal)

7. Metabolism Absorption : from small intestine with the help of Bile Transport : Through lymph Bound to Vitamin D binding protein & Albumin Storage : Liver (Major)

8. Synthesis of vitamin d Precursor: 7- Dehydrocholesterol Enzymes: 25 – Hydroxylase : Liver 1- alpha Hydroxylase : Kidney 25 Hydroxycholecalciferol/Calcidiol : 2 hydroxyl group Major Storage & Circulatory form of Vitamin D. 1-25 dihydroxycholecalciferol/Calcitriol : 3 hydroxyl group Both the hydoxylase enzyme require Cytochrome P450, NADPH & O2 for hydroxylation process.

9. Synthesis of vitamin d

10. Regulation of 1,25 DHCC Concentration of 1,25 DHCC is regulated by plasma level of Calcium & Phosphate. Low Calcium level stimulate PTH which in turn activates 1- Hydroxylase Low Phosphate directly activates 1- Hydroxylase

11. 24,25 Dihydrocholecalciferol (24,25 dhcc) Another Metabolite of Vitamin D Synthesized in Kidney by 24-Hydroxylase Exact function not known When Calcitriol (1,25 DHCC) Concentration adequate, 24-Hydroxylase axts leading to the synthesis of less important compound 24,25 DHCC Maintains the Homeostasis .

12. Biochemical function Calcitriol (1,25 DHCC) : active form of Vitamin D Regulates Plasma level of Calcium & Phosphate Ats on 3 different Organs Intestine : Increase absorption of Calcium Bone : Bone formation Kidney : Decrease excretion of calcium & phosphate

13. Mechanis m of Action Calcitriol transported through circulatory system Vitamin D binding protein & Albumin Diffuse into Nucleusof target cell & bind to Vitamin D receptor (VDR) VDR associates with Retinoic Acid receptor (RXR) forms complex : VDR-RXR complex VDR-RXR binds to DNA sequence called as Vitamin D responsive elements ( VDREs ) to modulate the expression of gen

14. ACTION ON INTESTINE Action similar to Steroid hormone Calcitrion bind to Cytosolic receptor : Calcitriol-receptor complex Complex approches to nucleus & interact with a specific DNA leading to synthesis of Calcium Bindng Protein ( CALBINDIN ) Calbindin : increases the calcium uptake from intestine.

15. ACTION ON BONE Calcitriol along with PTH (Parathyroid hormone) increase the mobilixaion of Calcium & Phosphate from the bone, leads to elevation in Plasma Calcium & Phosphate levels. In Osteoblast of bone, Calcitriol stimulates Calcium uptake for deposition of Calcium Phosphate : Bone formation.

16. ACTION ON KIDNEY Calcitriol decreases excretion & enhancing reabsorption of Calcium & Phosphate.

17. VITAMIN D IS HORMONE Vitamin D3 (Cholecalciferol) :Synthesized in skin Active form produce in kidney Target Organ : intestine , Bone & Kidneys Action is similar to Steroid Hormone : Binds to intracytoplasmic receptor & complex binds to DNA to stimulate the synthesis of Calcium Binding Protein. Synthesis is Self regulated by feedback Mechanism : Calcitriol decreases its own synthesis

18. Recommended dietary allowance (rda)

19. Dietary sources Exposure of Skin to sunlight Consumption of natural food Good sources : fatty fish, fish liver oils, egg yolk etc Milk is not a good source

20. DEFICIENCY OF VITAMIN D Rickets in Children Osteomalacia in adults Vitamin D is also called as antirachtic Vitamin. Causes: Insufficient exposure to sun light Strict vegetarians Chronic alcoholics Liver & Kidney disease Dark skin pigment adversly influences the synthesis of Vitamin D Religious : purdah system : cover the entire body

21. RICKETS English word ( Wrickken : to Twist ) Mineralization defect Clinical features : 1)Craniotabes 2)Frontal bossing 3)Delayed closure of fontanells 4)Rachtic rosary 5)Harrison groove 6)Genu varum : Bow legs 7)Coxa vara 8)Enamel Defect 9) Generalised muscle weakness

22. CLASSIFICATION OF RICKETS

23. Classification of Rickets Vitami D deficiency/ Resistant Calcipenic Rickets Phosphopenic Rickets

24. Osteomalacia Greek word ( osteon : bone & malakia : softness ) Mineralization defect Adult counterpart of Rickets Osteoid/Osteon : > 1 (O steoid: immatured bone & Osteon : mineralized bone ) Biopsy is Gold std. Investigation Triradiate Pelvis

25. OSTEOPOROSIS Bone mass decrease Normal mineralisation Generally in old age Silent Disease : Asymptomatic until Fracture occurs Complications: Fracture MC location: spine/ vertebral fracture Gradual increase in dorsal Kyphosis Loss of height Back pain

26. Osteomalacia vs osteoporosis

27. Osteomalacia vs osteoporosis

28. Osteomalacia vs osteoporosis

29. Dual-energy x-ray absorptiometry (DEXA): Useful for evaluating BMD Most accurate and reliable for predicting fracture risk Radiation dose lower than that for quantitative CT Measures bone mineral content and soft tissue component

30. Indication of DEXA Scan Early Menopause Prolonged Amenorrhea HRT Osteopenia on Xray Long term /High dose steroids Chronic liver Disease Hemodialysis Hyperparathyroidism Hypogonadism Malabsorption syndrome Thyroid Dysfunction Follow up/ previous abnormal DEXA Scan All women >65 All men > 70 Radiographic evidence of Osteopenia & Vertebral Deformity Loss of height, Thoracic Kyphosis Presence of Risk Factor

31. INTERPRETATION OF DEXA Z-scores (age- and gender-matched controls) should be used instead of T-scores (30-year-old adult controls) • Osteopenia is defined as a Z-score between −1.0 and −2.0 • Osteoporosis is defined as a Z-score below −2.0

32. Treatment Bisphosphonates Vitamin D Uprise D3 : Cholecalciferol Bio D3 XT : 1-25 DHCC PTH anal ogue: Teriparatide ( 1-34 PTH ) stimulates Osteoblasts Strontium Renelate : Dual activity stimulates Osteoclasts & inhibit Osteoblasts Romosuzumab : Sclerostin inhibitor Sclerostin: Stimulates Osteoclasts & inhibit Osteoblasts Denosumab : RANK ligand receptor inhibitor Calcimimetics : Calcium sensing recceltor (CaSR) agonist Cinacalcet SERM : Raloxifene Calcitonin Thiazids

33. Bisphosphonates Drug of choice : DOC Inhibit osteoclasts Highly Toxic to esophagus Preventive measures: Empty stomach With glass of water Should not lie down for 30 min Alendronate , Risendronate : Orally Zolendronate : IV once yearly ADR: Esophagitis Osteonecrosis of Mandible Zolendronate: Renal failure

34. VITAMIN D RANGE Vitamin D level : 40 – 80 ng/ml Toxicity : > 150 ng/ml Higher Vitamin D status in Body is protective against Prediabetes (insulin sensitivity : increases) , Metabolic Syndrome .

35. Vitamin d toxixity