Lec 9 Vitamin 2

34
Vitamin A (retinol) Metabolites: are retinaldehyde and retinoic acid Function retinaldehyde is important of vision retinoic acid for the cell growth and differentiation retinoid synthetic molecule

description

Lec 9 Vitamin 2

Transcript of Lec 9 Vitamin 2

  • Vitamin A (retinol)

    Metabolites: are retinaldehyde and retinoic acid

    Function

    retinaldehyde is important of vision

    retinoic acid for the cell growth and differentiation

    retinoid synthetic molecule

  • Vitamin A (retinol)

    plays a role in

    iron utilization

    humeral immunity

    T cellmediated immunity

    natural killer cell activity phagocytosis

  • Vitamin A (retinol)

    Metabolism

    The liver contains 90% of the vitamin A is bound

    to retinol-binding protein transthyretin

    trimolecular complex specific cell-

    surface receptors bound to a series of

    cellular retinol-binding proteins, function as

    transporting agents as well as co- ligands for

    certain nuclear receptors that act as transcription factors.( retinoid-mediated gene transcription) receptors for cell proliferation and differentiation

  • * The trimolecular complex [retinol (vit.A) + retinol-binding protein (RBP) + transthyretin(TTR)] prevents the glomerular filtration of the low molecular weight RBP (and so vit.A). * Transthyretin (TTR) is a carrier for retinol-binding protein, and also thyroxine (T4). [This is how transthyretin gained its name, transports thyroxine and retinol] * RBP plays an important role in transporting retinol in circulation, and delivering it to the cells by binding to specific cell-surface receptors, releasing retinol to the cell after binding with the receptor, then recirculate as the apo-form of BPR. Thus

    RBP is involved in multiple molecular interactions: it binds

    retinol and interacts with TTR and the cell-surface receptor

  • Vitamin A (retinol)

    Dietary source

    animal source: liver and fish (excellent source)

    plant source : dark-green vegetable and fruits

    by the splitting of carotenes.

  • Vitamin A (retinol)

    Deficiency

    1. chronic dietary deficit (developing countries)

    Southern Asia, Sub-Saharan Africa, some areas of Latin America

    More than 125 million preschool-age children with vitamin A deficiency, ~4 million have an ocular manifestation of deficiency .

    A quarter of a million children each year developed blindness.

  • Vitamin A (retinol)

    2. Malabsorption: celiac disease, short bowel syn.

    3. Zinc deficiency: interfere with vitA mobilization from the liver

    4. Alcohol : interfere with conversion of retinol to retinaldehyde in the retina (dehydrogenase)

    5. Drugs : interfere with the absorption of vitA

    neomycin, cholestyramine (bile acid sequestrant, so it can also bind fat-soluble vitamins interference with absorbtion.

  • Vitamin A (retinol) Clinical features night blindness (loss of dark adaptation)

    and may develop to complete blindness (endemic blindness).

    conjunctival xerosis (dryness) (xerophalmia) (because of loss of mucus secreting cells)

    Bitot's spots (white patches of keratinized epithelium on the sclera)

    Keratomalacia (softening of the cornea) leads corneal ulceration and necrosis result in corneal scarring

    increased risk of infection dysentery respiratory disease.

  • Downloaded from: StudentConsult (on 29 October 2011 12:19 AM)

    2005 Elsevier

  • * Vit.A deficiency in children is dangerous, and increases mortality, because vit.A is essential to maintain intact epithelia tissue as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems.

  • Prevention of deficiency : 1- A pregnant woman is advised to eat dark-green leafy vegetables, and yellow fruits retinol in babys liver. (she shouldnt take vit.A supplements (high doses), because they have serious side effects< and are teratogenic to the baby). 2- 60 mg retinol as palmitate is given to pre-school children leads to a decrease in mortality by gastroetnteritis, respiratory infections, and also measles.

  • Toxicity : 1- Repeated moderate of high doses liver damage, hyperostosis (excessive growth of bone), and teratogenecity.

    2- Acute overdose nausea, headache, elevated intracranial pressure, skin desquamation. 3- Excessive intake of carotenes causes benign condition (hypercarotenaemia), in which skin pigmentation occurs and gradually fates when intake is stopped

  • Vitamin A (retinol)

    Diagnosis

    1.Serum retinol level

    2.Test of dark adaptation

    3.Impression cytology of the conjunctiva

    4.Store assessment by liver BX

  • Vitamin A (retinol)

    Treatment

    30mg IM or 60mg orally

    Vitamin A supplementation can markedly reduce risk of child mortality where deficiency is widely prevalent.

    NB. Used in patient with M3 leukemia (acute promyelocytic leukaemia) and cystic acne (cream).

  • Vitamin D

    Synthesis and Metabolism

    steroid hormone involved in mineral ion homeostasis (calcium and phosphate)

    can be synthesized In response to ultraviolet radiation of the skin (a photochemical cleavage from 7-dehydrocholesterol).

    source

    animal sources(vitD3): dairy products, fish oils egg yolks

    plant sources (vitamin D2): cereals

  • Vitamin D

    Causes of the deficiency Vitamin D deficiency

    Impaired cutaneous production

    decrease dietary

    Malabsorption

    Accelerated loss of vitamin D

    Increased metabolism (barbiturates, phenytoin, rifampin)

    Impaired enterohepatic circulation

    * Anti-epileptic drugs (AEDs) can also cause a deficiency in 25(OH)D, even at sub-therapeutic serum levels of the drug, so theoretically it can be worthwhile to supplement calcium and vitamin D even before initiation of antiepileptic therapy.

  • Vitamin D Clinical features 1. Asymptomatic (Mild to moderate deficiency) 2. Osteomalacia (defective bone mineralization) Muscle and bone pain Malaise Fragility fracture (pseudofractures or Loosers zone) Proximal myopathy (waddling gait) Bone tenderness 3. Rickets ( growth retardation, bone deformities)

  • Looser zone

  • Looser zone

  • Vitamin D Diagnosis 1. Biochemical tests decrease serum 25(OH)D low or normal s. Ca. , ph. increasing PTH levels increase alkaline phosphatase 2. Radiological tests of oteomalacia decrease in cortical thickness osteopenia of the skeleton pseudofractures, or Looser's zones in the ribs

    and pelvis and long bones and vertebra 3. Bone biopsy

  • Vitamin D

    Treatment

    VitD 50,000 IU weekly for 312 Weeks followed by maintenance therapy (800 IU daily).

    Calcium supplementation include 1.52.0 g /d

    800 IU of vitamin D, with calcium supplementation, decreases the risk of hip fractures in elderly women.

  • Vitamin E ( tocopherols) Function

    acts as antioxidant and radical scavenger which protects low-density lipoprotein and polyunsaturated fats in membranes from oxidation, and especially effective for protecting nerve cells, red blood cells, and immune system function; aiding in the prevention of and healing of neurological disorders, chronic viral illness and anemia. Several studies have been performed in relation to fertility health, revealing its importance for reproductive function and health.

    Absorption and Metabolism

    After absorption, vitamin E is taken up from chylomicrons by the liver, and a hepatic tocopherol transport protein mediates intracellular vitamin E transport and incorporation into very low-density lipoprotein (VLDL).

  • Vitamin E ( tocopherol)

    Dietary source

    widely distributed in the food supply High: sunflower, soybean and corn oils

    meats, nuts, and cereal grains

    small amounts : fruits and vegetables.

  • Vitamin E ( tocopherol)

    Causes of the deficiency:

    1. Dietary deficiency ( does not exist).

    2. prolonged malabsorptive diseases.

    3. prolonged cholestasis

    4. abetalipoproteinemia cannot absorb or transport vitamin E.

    5. A familial form of isolated vitamin E deficiency (defect in the tocopherol transport protein).

  • Vitamin E ( tocopherols)

    Clinical features

    axonal degeneration of the large myelinated axons and results in posterior column

    Peripheral neuropathy

    Sensory ataxic gait

    Ophthalmoplegia

    skeletal myopathy

    pigmented retinopathy

  • Vitamin E ( tocopherols)

    Diagnosis

    low blood levels of tocopherol

    Treatment

    8001200 mg of tocopherol per day.

  • Vitamin k

    Function

    vitamin K1, phylloquinone, from vegetable and animal sources

    vitamin K2, menaquinone, synthesized by bacterial flora and found in hepatic tissue

    Vitamin K3, menadion, synthetic

    required for the carboxylation of glutamic acid, which is necessary for calcium binding to -carboxylated proteins such as prothrombin (factor II); factors VII, IX, and X; protein C; protein S).

  • Vitamin k

    Dietary Sources

    green leafy vegetables (spinach)

    liver

    vegetable oils : olive, soybean oils. * Its also synthesized by bacteria in the colon ( intestinal flora), so intestinal disorders and broad spectrum antibiotics will affect the flora decrease vit.K supply by the flora.

  • Vitamin k

    Causes of the deficiency

    1. small-intestinal disease (e.g., celiac disease)

    2. cholestatic liver disease (obstructive jaundice).

    3. Broad-spectrum antibiotic treatment (especially with anticoagulant drugs as warfarin) killing intestinal flora decreased normal vit.K supplement by the flora G.I.T bleeding (because of the drugs and low vit.K level which is needed for coagulation).

    3. drug therapy, the antiobesity drug orlistat (Absorption of fat-soluble vitamins and other fat-soluble nutrients is inhibited, because orlistat acts by inhibiting the gastric and pancreatic lipase).

  • In new born, primary deficiency results from : 1- Inefficient placental vit.K transferring.

    2- Neonatal bowel has not yet acquired the flora. 3- Breast milk contains little amounts of vit.K.

    So, vit.K supplements are given to the new born babies routinely to prevent haemorrhigic diseases of the new born .

  • Vitamin k

    The diagnosis

    elevated prothrombin time or reduced clotting factors

    vitamin K may also be measured directly.

    Treatment

    Vitamin K deficiency is treated using a parenteral dose of 10 mg.

  • Thanks