Lec7 Vitmain E and K PDF

# Case 1 A 45-year-old male presented to the OPD with complaints of generalized weakness, decreased sensation in hands and feet, blurred vision, improper gait. He has a history of Crohn's disease, for which he underwent a small bowel resection. He is a smoker and consumes alcohol occasionally. On E...

# Case 1 A 45-year-old male presented to the OPD with complaints of generalized weakness, decreased sensation in hands and feet, blurred vision, improper gait. He has a history of Crohn's disease, for which he underwent a small bowel resection. He is a smoker and consumes alcohol occasionally. On Examination he had impaired proprioception, positive Romberg's sign, delayed tendon reflexes, and decreased bilateral visual acuity. CBC revealed mild anemia. # Case 2 A 3-day-old baby, delivered at home, was brought to the ER with complaints of sudden onset of unconsciousness, bleeding from nose, umbilical stump and buccal mucosa with petechiae over the skin. Her mother took antitubercular drugs during pregnancy for the treatment of Tuberculosis. # OBJECTIVES - By the end of this lecture, the students will be able to explain the following about Vitamin E and K: - Food sources - Dietary requirement - Absorption and excretion - Functions - Deficiency and clinical manifestation # VITAMIN E (TOCOPHEROLS) - Lipophilic and hydrophobic vitamin. - Four compounds are found which differ from each other in number or position of methyl group - 1. Alpha tocopherol - 2. Beta tocopherol - 3. Gamma tocopherol - 4. Delta tocopherol Alpha tocopherol is the most active form of Vitamin E # VITAMIN E - CHEMISTRY The chemical structure of alpha-tocopherol is shown in the figure. It consists of a chroman ring and a phytol radical. # FOOD SOURCES - Plant sources: Cottonseed oil, sunflower oil, margarine, lettuce, cabbage, soya bean. - Animal sources: Egg, fish, shrimps, fish liver oil # How much is required? - The Recommended daily allowance RDA is: - Children: 10-15 IU/day - Adults: 20-25 IU/day # ABSORPTION AND EXCRETION - Absorbed from jejunum and ileum of small intestine in the presence of bile salts - The transportation from intestine is carried out through lipoproteins to the storage tissues. - Storage: Muscle and adipose tissue - Excreted via urine and faeces - Vitamin E does not cross the placenta efficiently but is readily available in breast milk # Metabolic Functions of Vitamin E ## Powerful Antioxidant The diagram shows how Vitamin E acts as an antioxidant to protect cell membranes from damage by free radicals. Free radicals can damage phospholipids, which are essential components of the cell membrane. Vitamin E can neutralize free radicals, preventing them from damaging phospholipids. # FUNCTIONS - Potent chain-breaking antioxidant: inhibits the production of reactive oxygen species molecules when fat undergoes oxidation and during the propagation of free radical reactions - Integrity of cell membranes: Vitamin E increases the orderliness of the membrane by preventing it from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. - Regulation of Platelet Aggregation: inhibit platelet aggregation and release prostacyclin from the endothelium, thereby inhibit and control clotting # FORMATION OF FREE RADICALS The diagram shows some of the ways in which free radicals can be formed in the body. These include: - UV light - Ionizing radiation - Smoking - Metabolism - Inflammation - Air pollution # Vitamin E does not work alone - Vitamin C, selenium and glutathione are required for the antioxidant effect of vitamin E because they work together synergistically to regenerate each other. When vitamin E neutralizes free radicals, it becomes a radical itself. However, vitamin C and glutathione can help restore the antioxidant properties of vitamin E by converting it back to its antioxidant form # ROLE OF VIT E AS ANTIOXIDANT The diagram shows the role of Vitamin E as an antioxidant. It shows how Vitamin E can terminate the chain reaction initiated by free radicals. # VITAMIN E PROTECTS AGAINST DISEASES - Cardiovascular diseases - Alzheimer's disease - Cancers - Cataracts - Nervous system disorders # DEFICIENCY ## Causes - Dietary deficiency is rare - Cystic fibrosis: Failure of pancreas to secrete pancreatic enzymes --> fat malabsorption - Abetalipoproteinemia: Inborn error of lipoprotein production and transport - Chronic cholestatic hepatobiliary disease, - Short-bowel syndrome # Clinical presentation/manifestation - Patients with vitamin E deficiency may show signs and symptoms of hyporeflexia that progress to ataxia, including limitations in upward gaze. - Patients may present with profound muscle weakness, blurred vision, visual-field constriction. - Patients with severe, prolonged vitamin E deficiency may develop complete blindness, cardiac arrhythmia, and dementia. - Hemolytic anemia: As a result of increased susceptibility of RBCs to hemolysis due to peroxides. - # Toxicity of vitamin E - Vitamin E is the least toxic of the fat-soluble vitamins - no toxicity has been observed at doses of 300 mg/day (UL = 1,000 mg/day). # VITAMIN K - Lipophilic and hydrophobic vitamin. - Three compounds have the biological activity of vitamin K - Phylloquinone (Vitamin K1), the normal dietary source, found in green vegetables - Menaquinones (vitamin K2), synthesized by intestinal bacteria. - Menadione synthetic compounds that can be metabolized to phylloquinone # FOOD SOURCES - Plant sources: Cauliflower, cabbage, spinach, alfalfa, soyabeans, tomatoes. - Animal sources: Egg yolk, liver # How much is required? - The adequate intake for vitamin K is 120 mg/day for adult males and 90 mg for adult females. - The average daily allowance is 50-100 mg/day. - Requirement increases in -- - Liver disorders - Patients on prolonged antibiotic therapy, bile acid sequestrants (Cholestyramine, colestipol) and Orlistat (weight loss medication) # ABSORPTION AND EXCRETION - Absorbed from jejunum and ileum of small intestine in the presence of bile salts - The transportation from intestine is carried out through chylomicrons - Storage is limited to only small amounts in the liver. - Vitamin K does not cross the placenta efficiently [1] - Excreted via faeces only. # Vitamin K Cycle The diagram shows the Vitamin K cycle, which involves the reduction of vitamin K epoxide (KO) to vitamin K hydroquinone (KH) by the enzyme VKOR. Vitamin K hydroquinone is then used by the enzyme gamma-glutamyl carboxylase (GGCX) to convert glutamic acid (Glu) residues in proteins to gamma-carboxyglutamic acid (Gla) residues. The carboxylation reaction requires CO2 and O2. # FUNCTIONS - Blood clotting/coagulation - Activation of prothrombin (Factor II), VII, IX and X - Bone mineralization - Activation of anticoagulants - Protein C and S # ACTIVATION OF ANTICOAGULANTS - PROTEIN C AND S - Vitamin K also activates Protein C and protein S which are anticoagulant proteins that provide control and balance in the coagulation cascade --> Prevent uncontrolled clotting # VITAMIN K ANTAGONISTS - Dicumarol and Warfarin, inhibit coagulation through antagonist action of vitamin K. - Warfarin prevents the recycling of vitamin K by inhibiting two important reactions and creating a functional vitamin K deficiency - Warfarin is a competitive inhibitor of Epoxide reductase. - In the presence of Warfarin, vitamin K epoxides cannot be reduced, they accumulate and are excreted. # DEFICIENCY ## Causes - Reduced intake of leafy greens and fermented products ---- Very rare, as it is also produced by gut microbes - Malabsorptive conditions: Celiac disease, sprue, steatorrhea, inflammatory bowel disease (Crohn's disease and ulcerative colitis), cystic fibrosis, pancreatitis - Biliary obstruction - Chronic liver disease - Prolonged use of antibiotics: Cephalosporins, sulfonamides, anti tubercular drugs, anti convulsants ---- disrupting the gut bacteria responsible for synthesizing vitamin K. - Blood thinners: Warfarin, Dicumarol - Hemorrhagic disease of the newborn/Vitamin K deficiency - Bleeding VKDB # Clinical manifestation/presentation - Bleeding from nose, gut, mucus membranes - Bone pain, recurrent fractures, osteoporosis