FAT SOLUBLE VITAMINS A & D

FAT SOLUBLE VITAMINS A & D

1. By Dr KHALED ALGARIRI International Medicine School – MSU January 2018 FAT SOLUBLE VITAMINS A & D

2. INTRODUCTION The word "vitamin" comes from the Latin word vita, means "life". Vitamins are chemicals found in very small amounts in many different foods. “vitamins have been defined as organic compounds which are required in minute amounts to maintain normal health of organisms

3. INTRODUCTION

4. VITAMIN A CHEMISTRY Vitamin A occurs in two forms in food

5. Active vitamin A- The Active form of vitamin is retinol , an alcohol which can be converted to other forms 2. Provitamin A- , substances that are transformed into vitamins in the body Beta-carotene is the most abundant and widespread provitamin A. One need to eat approximately six times as much beta-carotene to get the same amount of vitamin A as in retinol. Carotenoids are not toxic even at high doses for long times. VITAMIN A

6. SOURCES OF VITAMIN A Liver, fish, and eggs are excellent food sources for preformed vitamin A; • Vegetable sources of provitamin A carotenoids include dark green and deeply colored fruits and vegetables. • Moderate cooking of vegetables enhances carotenoid release for uptake in the gut. • Carotenoid absorption is also aided by some fat in a meal

7. DIGESTION AND ABSORPTION Dietary Vitamin A, from animal sources is available in the form of r etinyl esters, which is hydrolyzed to retinol and fatty acid by pancreatic hydrolases . The absorption of retinol requires the presence of bile salts In the intestinal cells, retinol is esterified back and secreted with chylomicrons

8. β-Carotene is cleaved in the intestinal mucosa by carotene dioxygenase , yielding retinaldehyde,which is reduced to retinol,esterified and secreted in chylomicrons together with esters formed from dietary retinol. The intestinal activity of carotene dioxygenase is low, so that are latively large proportion of ingested β -carotene may appear in the circulation unchanged. FATE OF CAROTENES Transport from liver to tissue The vitamin A from the liver is transported to peripheral tissue as Trans retinal by RBP(retinol binding protein )

9. FUNCTIONS OF VITAMIN A Vitamin A is essential for vision (especially dark adaptation) Immune response Bone growth Reproduction Maintenance of the surface linings of the eyes , epithelial cell growth and repair, andthe epithelial integrity of the respiratory,urinary , and intestinal tracts. Vitamin A is also important for embryonic development and the regulation of adult genes. Antioxidants : β - carotenes

10. VITAMIN A DEFECIENCY CAUSES Inadequate intake Impaired absorption Impaired storage & transport Increased excretion [RBP] Alcoholism

11. CLINICAL MANIFESTATIONS Nightblindness : due to retinal injury -Vitamin A has a major role in photo transduction. Vitamin A deficiency leads to alack of visual pigments; this reduces the absorption of various wavelengths of light, resulting in blindness Bitot spots : Areas of abnormal squamous cell proliferation and keratinization of the conjunctiva can be seen in young children with vitamin A deficiency .

12. CLINICAL MANIFESTATIONS Keratomalacia : In advanced deficiency; the cornea becomes hazy and can develop erosions, which can lead to its destruction. Xerophthalmia : results from keratinization of the conjunctiva . Infections Hyperkeratosis of skin Growth retardation

13. LABORATORY BIOCHEMICAL INVESTIGATIONS Serum retinol level- Normal range is 28 to 86 μg / dL (1 to 3 μmol /L). The level decreases in vitamin A deficiency. Serum RBP level Serum zinc level is useful because zinc deficiency interferes with RBP production. An iron panel is useful because iron deficiency can affect the metabolism of vitamin A . Albumin levels are indirect measures of vitamin A levels. Complete blood count (CBC) with differential if anemia , infection, or sepsis is a possibility. An electrolyte evaluation and liver function studies should be performed to evaluate for nutritional and volume status.

14. VITAMIN D Vitamin-D is a fat soluble vitamin Vitamin – D is a sterol, it contains steroid nucleus ( Cyclopentanoperhydrophenanthrene ring) Vitamin – D function like a hormone Forms of vitamin D: Vitamin D in the diet occurs in two forms Vitamin D2 ( Ergocalciferol ) Vitamin D3 ( Cholecalciferol )

15. Sunlight Ergosterol (in plants) 7-Dehydrocholesterol Vitamin D3 Cholecalciferol) Sunlight dermal tissue of animals

16. Vitamin D2 ( Ergocalciferol ) Vitamin D3 Cholecalciferol

17. 1,25-dihydroxyvitamin D3 25-hydroxyvitamin D3 In the liver cholecalciferol is hydroxylated at the 25 position by a specific enzyme 25-hydroxylase to form 25-hydroxy-cholecalciferol ,requires cyt. p450 & NADPH . In the kidney it is further hydroxylated at 1 st position by 1-hydroxylase present in the proximal convoluted tubules. it requires Cyt P450, O2 and NADPH 24-25 dihydroxy cholecalciferol may be formed by hydroxylation of 25-HCC at 24 th position. ACTIVATION OF VITAMIN-D

18. 24,25 – DHCC is another metabolite of vitamin D It is synthesized in kidney by 24 - hydroxylase Calcitriol concentration is adequate, 24 – hydroxylase acts leading to the synthesis of a less important compound 24,25 – DHCC To maintain calcium homeostasis, synthesis of 24,25 – DHCC is important 24,25 - Dihydroxycholecalciferol

19. Calcitriol (1,25 – DHCC) acts at three different levels to maintain plasma calcium Action on intestine: Calcitriol increases the intestinal absorption of calcium and phosphate In the intestinal cells, calcitriol leads to the synthesis of a specific calcium binding protein This protein increases calcium uptake by intestine VITAMIN D FUNCTIONS

20. Action on bone: Calcitriol is essential for bone formation. Calcitriol along with parathyroid hormone increases the mobilization of calcium and phosphate from the bone causes elevation in the plasma calcium and phosphate Action on kidney: Calcitriol is also involved in minimizing the excretion of calcium and phosphate through the kidney by decreasing their excretion and enhancing reabsorption

21. Children - 10 μ gm /day Adults - 5 μ gm /day Pregnency,lactation -1200 μ gm /day Recommended dietary allowance (RDA) Sources of vitamin D

22. Absorption : vitamin D2 and D3 form mixed micelles by combining with bile salts & through the mucosal cells of small intestine they are absorbed by passive transport Transport: vitamin D is transported from intestine to the liver by binding to vitamin D binding globulin Storage: 25 – hydroxycholecalciferol is the major storage and circulatory form of vitamin D ABSORPTION & TRANSPORT

23. RICKETTS in CHILDREN OSTEOMALACIA IN ADULTS Deficiency of vitamin-D

24. LABORATORY BIOCHEMICAL INVESTIGATIONS Serum Calcium level Serum Phosphate level Thyroid hormones Tests Serum Alkaline phosphatase Serum Acid phosphatase

25. Vitamin D is stored mainly in liver . Vitamin D is most toxic in overdoses . Toxic effects include demineralization of bones and increased calcium absorption from intestine, leading increased plasma calcium ( hypercalcemia ). Hypercalcemia is associated with deposition of calcium in many soft tissues such as kidney and arteries It leads to formation of stones (renal calculi) High consumption is associated with loss of appetite, nausea, increased thirst, and loss of weight . VITAMIN D TOXICITY

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