1. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

3. Vitamin D Part - ii

4. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Importance of vitamin D Vitamin D is an area of active research and controversy. There have been studies to suggest that it might help prevent colon, prostate, and breast cancers. There is also some research that it might help prevent and treat Diabetes, Heart Disease, High Blood Pressure, and Multiple sclerosis.

5. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN However The results of many of these studies are either preliminary or under debate. Without other long-term research, even many of the researches who conducted these initial studies are cautious about recommending vitamin D for the prevention of these diseases.

6. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Learning Objectives Sources Dietary Requirement Absorption/Transport Regulation Functions Causes of Deficiency Deficiency Diseases

7. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Sources, Absorption and metabolism Vitamin D 3 is obtained from two sources: 1. Vit D 3 is obtained from diet or food supplements. 2. From the conversion of 7-dehydro cholesterol in the skin by ultraviolet light to pre Vit- D 3 which then slowly equilibrates to Vit- D 3

8. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Dietary Sources Exogeneous sources: provide preformed vit. D3 & D2 Animal sources generally supply Vit D3 Liver Kidney Fatty Fish Egg yolk Milk and Milk Product D2 is got from plants sources

9. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Sun exposure ( Endogenous source) Vitamin D is produced when skin is exposed to sunshine. The amount of vitamin D that your skin makes depends on such factors as the season. (i.e., there's usually less sunshine in winter months), The time of day (the sun's rays are most powerful between 10 am and 3 pm),

10. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Other Factors include: The amount of cloud cover / Air pollution, and Place of Living( congested cities) It's the UV (ultraviolet) light in sunlight that causes your skin to make vitamin D.

11. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Factors affecting Vit. D synthesis The amount of Vit D formed by the action of sunlight on the skin is dependent on 1. Intensity of light 2. Length of exposure 3. Skin pigmentation

12. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Daily requirement 400 iu (10ug) of Vit D per day promote optimal calcium absorption and enhance growth Higher level is recommended for infants and children

13. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Recommended Dietary Allowances Infants0 – 0.510  g 0.5 – 1.010  g Children1 – 3 10  g 4 – 610  g 7 – 1010  g

14. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN AdultsMaleFemale 11 – 1410 10 15 – 1810 10 19 – 227.5 7.5 23 – 505 5 51+5 5 Pregnancy + 5 Lactation + 5 Recommended Dietary Allowances

15. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Absorption Vit D3 is readily absorbed from small intestine. Require s bile salts for absorption. D2 is not readily absorbed. After absorption gets released in to blood bound to a globulin. Reaches the liver where it is stored after 1 st hydoxylation. (Calcidiol) Some is stored in extra hepatic tissues like kidneys and adrenal gland. When required this is released in to circulation.

16. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Formation of Calcitriol D3 is precursor of Calcitriol. Hydroxylation converts D3 to Calcitriol. Renal hydoxylase is the enzyme for this activation. Which require Mg++ ions, Cytochrome P450, molecular oxygen and NADPH. Some activity of this hydoxylase is also reported in placenta.

17. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Regulation of formation of Calcitriol Low level of PO4 in blood plasma directly stimulate the renal enzyme. Low level of Calcium activates it through PTH Feed back inhibition High level of Calcitriol regulates its own production by inhibiting the enzyme activity.

18. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Functions It is a steroid and functions like other steroid hormones. It is not dietary essential when there is adequate exposure to ultraviolet light 1. Vit D plays a major role in the regulation of calcium and phosphate metabolism by promoting their intestinal absorption, influencing the process of bone mineralization.

19. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN 2. Vit D exerts its anti ricket action by making the intestinal mucosa permeable to calcium and phosphorus and facilitating the active transport of calcium across cell membranes. Functions

20. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Cause of deficiency Nutritional deficiency Decreased endogenous synthesis. Both are common Pathological and physiological deficiencies are also seen. Genatic deficiency of Hepatic Hydroxylase Genatic deficiency of Renal Hydroxylase Hypoparathyroidism Fats malabsorption Anticonvulsant drugs/ Corticosteroids

21. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN IMPORTANT DEFICIENCY DISORDER Severely low levels of vitamin D can result in a osteomalacia in adults, and rickets in children. If left untreated, both conditions lead to soft, brittle bones, bone pain, and muscle pain and weakness. Osteoporosis is associated with reduced bone density, which leads to an increased risk of bone fractures in old age especially females

22. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Effects of deficiency 1. A deficiency of Vit D causes impaired intestinal absorption of calcium and phosphorus and faulty mineralization of teeth and bones. 2. Skeletal malformation result from the inability of the softened bone to withstand weight bearing. In children this bone condition is termed rickets.

23. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Other factors that can lead to Vitamin D deficiency Age. The skin's ability to make vitamin D reduces with age. Mobility. People who are homebound or are rarely outside (e.g., in nursing homes and other facilities) are not able to use sun exposure as a source of vitamin D.

24. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Other factors that can lead to Vitamin D deficiency Skin color Dark-colored skin is less able to make vitamin D than fair-colored skin. Human breast milk A poor source of vitamin D and Infant formulas often do too. Therefore infants, particularly those who are breastfed exclusively, are at risk of developing vitamin D deficiency.

25. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Other symptoms of rickets include Delayed closure of the fontanelles (suture lines in the skull) especially in premature infants Projection of sternum (pigeon breast). Spinal curvature. Bowing of the legs and Enlargement o the costochondral junction. Effects of deficiency

26. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Nutritional Rickets

27. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

35. Medical conditions that can cause Vitamin D deficiency Vitamin D deficiency can be caused by specific medical conditions such as: Kidney and liver diseases. These diseases reduce the amount of an enzyme needed to change vitamin D to a form that is used in the body. Lack of this enzyme leads to an inadequate level of vitamin D in the body. Cystic fibrosis and celiac disease. These diseases do not allow the intestines to absorb enough vitamin D.

36. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Medical conditions that can cause Vitamin D deficiency Gastric bypass surgery This weight-loss surgery removes part of the stomach and/or the intestines. Reducing the size of these organs lowers the amount of vitamin D- containing nutrients that can be absorbed. Obesity A body mass index greater than 30 is associated with lower vitamin D levels. It is thought that the fat actually holds onto the vitamin D, and does not allow it to be released into the blood stream.

37. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Medicines that can cause Vitamin D deficiency Vitamin D levels can be lowered by certain medicines which include: Laxatives Steroids Cholesterol-lowering drugs Seizure control drugs (eg, phenobarbital and phenytoin), Anti TB drug (rifampicin) and A weight-loss drug

38. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN In adults this bone condition is termed as osteomalacia and is caused purely by lack of Vit D and calcium. Particularly prevalent among pregnant and lactating oriental women. Effects of deficiency

39. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Vit D is involved in neuro- muscular activity and its deficiency causes tetany characterized by convulsions, muscle twitching and sharp flexion of the wrest and ankle joint. Effects of deficiency

40. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Effects of deficiency This condition may also result from parathyroid disease or from insufficient dietary intake or intestinal absorption of calcium or Vit D Dental caries are more prevalent among children with poor intakes of Vit D, calcium and phosphorus.

41. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Toxic Effects Precisely not known. It is potentially lethal vitamin. Toxicity symptoms include : 1. Polyurea 2. Nocturia 3. Weight loss 4. Diarrhea & 5. Nausea

42. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Calcification of soft tissues such as a. Blood vessels b. Heart c. Stomach d. Bronchi & e. Kidney Severe toxicity results in

43. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Conditions associated with too much vitamin D Symptoms of too much vitamin D include: Nausea and vomiting Itching Increased thirst and urination Poor appetite Constipation Weakness Weight loss Confusion Heart rhythm problems Kidney damage

44. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN How often vitamin D level be checked Routine checks of vitamin D levels are not currently recommended. However, you as a doctor might need to check your patient’s levels if he/she have medical conditions, risk factors for vitamin D deficiency or are taking certain medications as already discussed. Sometimes vitamin D levels can be checked as a cause of symptoms such as long-lasting body aches and a history of falls or bone fractures without significant trauma.

45. Thanks

46. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Assessment Explain the role of PTH and Calcitonin in Ca ++ homeostasis? Total Body contents of Ca, po4 and Mg Distribution of various minerals and their % Conc. In Bone /Blood/ ECF/soft tissues. Normal Plasma level of these minerals Limits of intestinal absorption. How calcium is absorbed from the GIT. What are important functions of Phosphorous. How hypophoshatemia develope.

47. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Assessment Vitamin D is both a vitamin and Hormone. Explain. Differences between Vitamin D 2 & D 3 in tabulated form. Difference in Calcidiol and Calcitriol. How vitamin D gets converted into functional form. What are important Functions of Vit.D. How deficiency of Vit. D develops. What are the common sources of Vit. D. How is dietary Vitamin D absorbed and transported