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Vitamin A

Vitamin A. Dr.S.Chakravarty MD. Classification :. Properties of fat soluble vitamins:. They require fatty medium and bile salts for absorption. They are stored in body at various places. Eg VitA in ITO cells All the fat soluble vitamins have iso-prenoid units in their structure.

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Vitamin A

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  1. Vitamin A Dr.S.Chakravarty MD

  2. Classification :

  3. Properties of fat soluble vitamins: They require fatty medium and bile salts for absorption. They are stored in body at various places. EgVitA in ITO cells All the fat soluble vitamins have iso-prenoid units in their structure. They predominantly act through specific nuclear receptors like hormones. Deficiencies manifest after years in normal individuals or early with people suffering from liver disease.

  4. Vitamin A Carotenoids – Beta carotene (plant source) - Antioxidant Retinoids Retinol – Reproduction (maturation of sperm and OVA) Retinal – vision Retinoic acid – growth and differentiation Retinyl esters – storage , transport and (animal source)

  5. Forms of Vitamin A: Beta – carotene Retinol Retinal Retinoic acid Acid Alcohol Aldehyde Fatty acids Retinyl esters Storage form in liver

  6. Sources of Vitamin A Liver(and Liver oils ) ,eggs, milk Yellow fruits – Mango, papaya, apricots Vegetables – Carrots, pumpkin, sweet potatoes Green leafy vegetables

  7. Deficiency Vitamin A Adequacy • vision • Cell differentiation • Maintains Surface epithelium • Reproduction • Embryogenesis • Immunity • Growth retardation • Dysfunction (M&F) • Night blindness • Epithelial Metaplasia • Impaired innate & acquired defenses • Keratinisation of epithelium - alopecia

  8. Retinoic acid: Regulates cellular differentiation: Embryonic – RAR and RXR receptors – differentiation of tissues (morphogenesis) Epithelial (Conjunctival, GIT, Respiratory) – differentiation of epithelium – maintains the mucous tracts. Immune stem cells – regulation of immune response Osteoid (osteoblasts, -clasts) – regulation of osteoid cells( DON’T CONFUSE WITH VIT D)

  9. SquamousMetaplasia: Retinoic acid maintains healthy cells in the mucous membranes. Without vitamin A, the normal structure and function of the cells in the mucous membranes are impaired.

  10. Squamousmetaplasia: Intestines – Diarrhoea Respiratory tract – URTI and LRTI Why: Poor IgA production Decreased mucociliary clearance Eye – Conjunctival and Corneal changes Why: Poor Tearfilm production – Abnormal zei’s, Moll’s and mebomian glands Keratinization of cornea

  11. Bitot’s spot Eye changes: Corneal xerosis XN-Nightblindness X1A-Conjunctival xerosis X1B-Bitot’s spots X2-Corneal xerosis X3-Corneal ulceration Keratomalacia

  12. keratomalacia Eye changes: Corneal ulcer

  13. Squamouskeratinization

  14. Retinal in Night vision: Opsin--- recycling Isomerization Photon

  15. Rhodopsin is totally desensitized due to over stimulation by photons during day: (wash out of rhodopsisn) Absent rhodopsin due to wash out Rods during the day : ROD cells (+) Glutamate Bipolar cells GABA (-) Optic nerve

  16. Few Photons (night) Transducin pathway: Rhodopsin Trans cis retinalretinal Gα β PDE phosphodiesterase γ Gtprotein (Transducin) C-GMP 5-GMP (+) (-) Ligand gated Na channel Na+ Na+ Hyperpolarization Glutamate

  17. Only few photons during night, so enough rhodopsin will be present Rods during the night : Rhodopsin present ROD cells Glutamate Ganglion cells GABA Optic nerve Signal transduction

  18. Mechanism of night vision Rhodopsin acts like a receptor Sodium channels (cGMP) dependent  depolarization (-30 milli volts at rest). 11 cis Retinal – trigger  trans retinal  g protein (transducin)  PDE  inactivates cGMP decrease cGMP hyperpolarization Becomes hyperpolarized (-35 mV) and decrease Glutamate release.

  19. Hypervitaminosis A Hyper carotenemia– false diagnosis of jaundice Teratogenic – birth defects Skin irritation, bone pain etc. Pseudo tumor cerebri-blurred vision, nausea, vomiting, vertigo, headaches, and increased pressure in the skull. Liver cirrhosis –ITO cells Bone mineral loss

  20. Other Uses of vitamin A: Dermatological : Reduce cell proliferation Epidermal differentiation Inhibit sebaceous gland activity Iso-tretinoin (13-cis retinoic acid) -Severe acne treatment Acitretin- Psoriasis treatment Highly teratogenic – not for pregnant women Cancer treatment : ATRA (all trans retinoic acid) – Treatment of acute Promyelocytic leukemia t(15:17) (AML –M3)vitamin receptor on promyelocyte

  21. Treatment of acute Promyelocytic leukemia: Pathogenesis

  22. Several clinical trials have suggested that retinoic acid can induce remission in patients with a/c pro myelocytic leukemia. Such remission is related to the ability of retinoic acid to promote which of the following? • Differentiation of leukemic cells • Differentiation of Monocytes into macrophages • Generation of cytotoxic T lymphocytes • Production of interferons • Repair of DNA damage

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