VITAMINS.ppt
- 9. Beri beri Deficiency:- thiamine Symptoms:- anorexia , dyspepsia, heaviness and weakness. Types :- wet beri beri:- cardiovascular manifestation edema of legs, face, trunk, serous cavities and distended neck veins , weak heart muscles, calf muscles are swollen, BP increase , fast pulse, death - Dry beri beri:- CNS manifestations - Diffculties in walking - Sensory distrubance - Paralysis, become bedridden -infantile beriberi:-infants born to mothers suffering from thiamine def.
- 10. Wernicks-korsakoff syndrome Known as cerebral beri beri Encephalopathy Cerebellar ataxia Nystagmus Psychosis Polyneuritis :- chronic alcoholics Sym.- lactic acidosis Alcohol inhibits absorption of thaimine Treatment :- needs large doses of thiamine.
- 13. Sources :- liver, egg, fish, green leafy vegetables, milk . Synthesize by the intestinal flora Requirements :- adults :- 1.5 mg/day Pregnancy ,lactation and old age:- 0.2-0.4 mg/day
- 15. Angular stomatitis ;-- infected corners of mouth Proliferation of bulbar conjunctival capillaries
- 17. Sources :- liver, egg, fish, green leafy vegetables, milk . Requirements :- normal = 20 mg/day Lactation :- 5 mg/day Toxicity :- given orally produces transient vasodilatation of the cutaneous vessels and histamine release Causes ;- itching, burning, tingling.
- 23. Coenzyme ;- PLP RDA :- 2-2.2 mg/day Sources :- egg yolk, fish, milk ,meat, wheat, corn , cabbage. Drug induced B6 deficiency - Isoniazid :- for TB - Penicillamine :- for RA ( rheumatoid arthritis )
- 25. Vitamin B6 Vitamin B6 to a family of 3 related compounds; - pyridoxine (alcohol), pyridoxal (aldehyde) pyridoxamine. Coenzyme :- pyridoxal phosphate (PLP).
- 26. RDA :- 2-2.2 mg/day Sources :- egg yolk, fish, milk ,meat, wheat, corn , cabbage. Drug induced B6 deficiency - Isoniazid :- for TB - Penicillamine :- for RA ( rheumatoid arthritis )
- 29. Biochemical functions Transamination 1. These reactions are catalyzed by aminotransferases transaminases) which employ PLP as the coenzyme, For example: Alanine + alpha ketoglutarate alanine transaminase Pyruvate + Glutamic acid
- 31. Decarboxylation eg;- 1. Glutamate → gamma aminobutyric acid(GABA). GABA is an inhibitory neurotransmitter, and convulsions may occur in B6 deficiency, especially in children. (convulsion ) 2. Histidine → histamine, which is the mediator of allergy. 3. 5-hydroxy tryptophan → serotonin 4. Cysteine → taurine 5. Serine → ethanol amine
- 32. . Metabolism of Sulfur-containing Amino acids 1. Homocysteine + Serine Cystathionine synthase Cystathionine 2. Cystathionine → Homoserine + Cysteine (Enzyme Cystathionase) Both these reactions require PLP. Hence in vitamin B6 deficiency homocysteine in blood is increased. Therefore, pyridoxine is used in homocysteinemia.
- 33. Heme Synthesis Aminolevulinic acid synthase is a PLP-dependent enzyme. So, in B6 deficiency, anemia may be seen. Production of Niacin Tryptophan PLP Niacin (one vitamin is necessary for synthesis of another vitamin). 3-hydroxykynurenine Kynureninase 3-hydroxyanthranilic acid Glycogenolysis Phosphorylase enzyme (glycogen to glucose-1-phosphate) requires PLP.
- 34. Deficiency manifestation 1. Neurological Manifestations In children, B6 deficiency leads to convulsions due to decreased formation of GABA. PLP is involved in the synthesis of sphingolipids, so B6 deficiency leads to demyelination of nerves and consequent peripheral neuritis. 2. Dermatological Manifestations niacin deficiency which is manifested as pellagra. Another manifestation is the irregular indentations in nails. 3. Hematological Manifestations In adults, hypochromic microcytic anemia may occur due to the inhibition of heme biosynthesis. 4.Other metabolic disorders Xanthurenic aciduria and homocystinuria will respond to vitamin B6 therapy. Ethanol is converted to acetaldehyde, which inactivates PLP. Hence, B6
- 35. Pantothenic acid Anti dermatitis factor Metabolic role as COA( coenzyme A) Consists of two component :- pantoic acid & β- alanine RDA :- 5-10 mg Sources :- egg , liver , meat, milk etc. Synth. :- by bacterial flora in intestines
- 36. Biochemical function CHO A.A F.A Acetyl COA TCA cycle TG Cholesterol K.B Detoxication
- 37. Rxn Pyruvate to acetyl COA Ketogulatrate to succinyl COA Fatty acid to Acyl COA
- 38. Difciency Burning foot syndrome- Burning, pain, numbness in the lower extremities Staggering gait Sleep disturbances Seen in prison camps, chronic alcoholic renal dialysis patients .
- 39. Biotin Anti-egg white injury factor Consist of imidazole ring with thiophene ring Act as coenzyme for carboxylation reactions Various metabolic Rxn:- - TCA & gluconeogenesis - FA synthesis ( acetyl COA to Malonyl COA) - Propionyl COA to methylmalonyl COA
- 40. Coenzyme Activity of Biotin Biotin acts as a coenzyme for carboxylation reactions. Biotin Requiring CO2 Fixation Reactions 1. Acetyl-CoA Carboxylase This is the rate limiting reaction in the biosynthesis of fatty acids Acetyl-CoA + CO2 + ATP → Malonyl-CoA + ADP + Pi 2. Propionyl-CoA Carboxylase Propionyl-CoA + CO2 + ATP → Methyl malonyl-CoA + ADP + Pi 3. Pyruvate Carboxylase Pyruvate + CO2 +ATP → Oxaloacetate + ADP + Pi Biotin-Independent Carboxylation Reactions • Carbamoyl phosphate synthetase • Addition of CO2 to form C6 in the purine ring • Malic enzyme, converting pyruvate to malate.
- 41. RDA :- 200-300 mg Sources :- bacterial flora of the gut - liver, yeast, peanut, milk, egg yolk BIOTIN ANTAGONISTS - Avidin , protein present in egg white has great affinity to biotin - Intake of raw egg may cause biotin deficiency - Avidin is heat liable and boiling of egg will neutralize the inhibitory activity. - One mole. Of avidin can bind with four mole. Of biotin.
- 42. Deficiency Dermatitis Atrophic glossitis Hyperesthesia Muscle pain Anorexia Hallucinations Split nail
- 48. Folate trap
- 49. RDA ;- 200 microgram/day Pregnancy & lactation ;- 300-400 Dietary sources:- green leafy vegetables , whole grains, liver, kidney and eggs
- 51. Reduced DNA synthesis In folate deficiency, THFA is reduced and thymidylate synthase is inhibited. Hence dUMP is not converted to dTMP. So dTTP is not available for DNA synthesis. Thus, cell division is arrested Drugs: Anticonvulsant drugs (hydantoin, Dilantin, phenobarbitone) will inhibit the intestinal enzyme so that folate absorption is reduced. Folate trap: The only way for the regeneration of free THFA is the homocysteine methyl transferase, with the help of vitamin B12. When B12 is deficient, this reaction cannot take place, leading to folate deficiency. . Homocysteinemia Folic acid deficiency may cause increased homocysteine levels in blood. Plasma homocysteine levels above 15 mmol/L will increase the risk of cardiac diseases
- 52. . Histidine load test or FIGLU excretion test Histidine is normally metabolized to formiminoglutamic acid (FIGLU) from which the formimino group is removed by THFA. Therefore, in folate deficiency, FIGLU is excreted in the urine. This test is rarely done nowadays Folic Acid Therapy In macrocytic anemia, the therapeutic dose is 1 mg of folic acid per day orally. Folic acid alone should not be given in macrocytic anemia; because it may aggravate the neurological manifestation of B12 deficiency. So, folic acid and vitamin B12 are given in combination to patients.
- 53. Reduced DNA synthesis:- ( macrocytic anemia;- peripheral blood picture in folate deficiency - Magaloblastic anemia:- vita. B12 deficiency Hyper-homocystenemia :- homocysteine level above 15 mmol/l -Increase risk of coronary artery disease. Faliure to convert homocysteine to methoinine . Folic acid therapy :- 1mg folic acid /day
- 55. Folate antagonists Sulfonamides:- Sulfa drug has structural similarity with para- aminobenzoic acid (PABA) which is a constituent of folic acid. So sulfa drugs will competitively inhibit the synthesis of folic acid in bacteria. Pyrimethamine;- is an antimalarial drug Aminopterin and Methotrexate - Inhibit dihydrofolate reductase & block the formation of THF - So, synthesis of purines and DNA impaired - Blockage of cell proliferation occur. - Used for the treatment of cancer.
- 58. Absorption of B12 requires the intrinsic factor . Otherwise used as extrinsic factor becoz. Derived from external sources . IF is secreted from parietal cells. - One mole. Of IF is attached with 2 mole. Of B12.
- 59. Absorption of Vit. B12
- 62. Sub acute combined degeneration -damage to nervous system Demyelination :- affecting cerebral cortex as well as spinal cord. so., sensory & motor tracts affected. Assessment :- serum B12 Peripheral smear homocystinuria
- 63. Treatment :- 100- 1000 microgram by intramuscular injections. RDA :- 1-2 mcg/day Sources :- liver , curd.
- 67. Tryptophan metabolism Tyrosine metabolism Iron ” Hb & folic acid metab.:- increase iron absorption by keeping it in the ferrous form. Help in the formation of ferritin( storage form)& mobilization of iron. Help in reconversion of metHb to Hb Steroid synthesis:- syn. Of corticosteroid. Antioxidant property , sparing action of other vitamin like A, E & some B-complex. Cataract :- concentrated in the lens of eye.
- 69. Anemia :- microcytic , hypochromic anemia - Causes ;- loss of blood by hemorrhage - Decreased absorption of iron - Infantile scurvy :- Barlow’s disease - b/w 6-12 months of age
- 71. What is the difference between fat- soluble and water-soluble vitamins? Fat-soluble are stored in the liver and fatty tissues. These are not readily excreted from the body. Water-soluble vitamins travel in the blood and are stored in limited amounts. These are readily excreted from the body through urine.
- 72. What does RDA mean? Recommended Dietary Allowances These are suggested levels of essential nutrients considered adequate to meet nutritional needs of healthy individuals.
- 73. Digesting and Absorbing Water- Soluble Vitamins
- 74. All absorption takes place in the small intestine Fat-soluble vitamins Are absorbed in the duodenum Storage Vitamin A is mainly stored in the liver Vitamins K and E are partially stored in the liver Vitamin D is mainly stored in the muscle tissue Vitamin Absorption and Storage
- 76. RDA Three components :- retinol, retinal ,retinoic acid Children 2000 – 3500 I.U. Men 5000 I.U. Women 4000 I.U.
- 78. Sources Animal Sources Eggs Meat Cheese Milk Liver Kidney Cod fish oil Plant sources •Carrots •Sweet Potatoes •Apricots •Broccoli •Spinach •Pumpkin
- 79. Hypervitaminosis A leads to toxic symptoms: Dry, itchy skin Headaches and fatigue Hair loss Liver damage Blurred vision Loss of appetite Skin coloration
- 83. Functions 1. visual cycle :- vit. A is component of the visual pigments of rod and cones cells. -
- 84. Vitamin A and vision Vit. A is necessary to form rhodopsin (in rodes, night vision) and iodopsins (photopsins, in cones – color vision) - visual pigment. Retinaldehyd is a prosthetic group of light-sensitive opsin protein. In the retina, all-trans-retinol is isomerized to 11-cis-retinol → oxidized to 11-cis-retinaldehyd, this reacts with opsin (Lys) → to form the holoprotein rhodopsin. Absorption of light → conformation changes of opsin → photorhodopsin.
- 85. The Visual Cycle
- 88. Dark adaption mechanism Person shifts from bright light to dim area- leads difficulty in seeing . Due to resynthesis of rhodopsin & vision is improved. Increased in vita. A dificiency. Red light bleaches rhodopsin to a lesser extent. photosensitive cells Rods cones ( for dim light vision) ( bright light & color vision)
- 89. Causes Decreased intake Obstructive jaundice Cirrhosis of liver Severe malnutrition Chronic nephrosis Investgation :- Dark adaption test Vitamin A Normal level:- 25-50mg/dl
- 90. Deficiency of vitamin A: Deficiency leads to a variety of disorders of the eyes and this affect the vision, some of the disorders are – 1)Night blindness: The person cannot see the objects in dim light and in nights. Bitot’s spot:- seen as greenish white triangular plaques adherent to conjuctiva. 2)Xeropthalmia : conjuctiva becomes dry, thick, wrinkled. Losses its transperancy. Dryness spreads to cornea. 3) Keratomalacia( softening of the cornea) :- Xeropthalmia persists for long time , leads Keratomalacia . Occur degeneration of corneal epithelium
- 92. 4)Skin become scaly, rough and is covered with papillae (Small eruptions). 5)Reproductive functions may also be effected in vitamin ‘A’ deficiency. National Institute of Nutrition, Hyderabad has evolved a method giving a large dose (5 – 6 drops) of Vitamin-A once in six months to prevent blindness in children
- 95. RDA Children = 10 mcg/day Adult = 5-10 mcg/day Pregnancy = 10mcg/day
- 96. Vitamin D3 can be obtained in diet, or derived from cholesterol in a reaction that requires UV light. Active form :- calcitriol UV light spontaneous liver enzyme 25-hydroxylase Vitamin D3 calcitriol
- 99. calcium PTH
- 100. Why it is called prohormone Synthesized in one tissue and is transported in blood to act on other tissues. It include autocrine and paracrine actions Its effect in kidney can be act as autocrine.
- 104. Rickets Insufficient mineralization of bone Bones become soft Weight bearing bones are bent Bow legs, knock knees , pigeon chest. Type :- Renal rickets Loss of hair (alopecia) Osteomalcia :- seen in adult bones are softened due to mineralization Increased osteoporosis Bone fractured
- 105. Hypervitaminosis D Symptoms:- Weakness Hypertension Weight loss Polyuria Hypercalacemia
- 108. RDA Males = 10mg/day Females = 8 mg/day Pregnancy = 10mg/day
- 109. For absorption bile salts requires ,occur in small intestine , transported in plasma. Function :- Antioxidant Anti – atherogenic – oxidation of LDL & in the development of atherosclerosis. Antisterility
- 110. Protects cell membranes and other fat-soluble parts of the body (LDL cholesterol) from oxidation May reduce the risk of heart disease May also discourage development of some types of cancer Promotes normal growth and development Promotes normal red blood cell formation Acts as anti-blood clotting agent Plays some role in the body’s ability to process glucose Also been known to aid the process of wound healing role
- 111. Role of Vit E as antioxidant Act as natural antioxidant by scavenging free radicals and molecular oxygen. Prevent peroxidation of PUFA in cell membrane. Protection of RBC membrane from oxidants. Prevent oxidation of LDL. Oxidised LDL is more atherogenic than native LDL. Terminate free radical lipid peroxidation.
- 113. Neurological deficiency :- neuropathy, demyelization of nerves , cerebellar ataxia retinal pigment degeneration A betalipoproteniemia .
- 118. Absorption :- require bile salt. Transported in blood in chylomicrons & VLDL. Stored in liver.( less amount)
- 120. Role of γ-carboxylate glutamate in clotting factors γ-carboxyl group of clotting factors such as prothrombin chelates Ca++ ions & so helps in binding of blood clotting factors to platelet cell membrane through –ve charged phospholipids . In vitamin K deficiency , this carboxylation does not occur & leads to coagulation failure .
- 122. Causes Premature infants & new born babies - Unable to store vitamin K - chronic liver diseases - malabsorption from intestine - Prolonged use of antibotics - Prolonged use of warfarin ( anticoagulant drug)
- 125. LIPOIC ACID Vitamin like compound, perform many important functions. Sulphur containing fatty acid called 6,8- dithiooctanoic cid( Alpha lipoic acid). Fat and water soluble. Metabolic role: As a coenzyme of Pyruvate dehydrogenase complex(PDH Complex). As a coenzyme of Alpha keto glutarate dehydrogenase complex. Also required for the action of enzyme sulfite
- 126. Antioxidants Group of compounds that neutralizes free radicals, helping to counteract the oxidation that takes place in cells Includes Vitamins E Vitamins C Selenium Flavonoids Carotenoids
- 127. Defn: Substances that fight off free-radicals in our bodies. Free radicals are compounds within our bodies that may lead to chronic disease and/or are involved in cell tissue damage. Examples of vitamins that contain antioxidants are… C, E, and Beta Carotene.
- 128. Free Radicals
- 129. Antioxidants, such as vitamin E and C, selenium, flavonoids, and carotenoids, help counteract the damaging effects free-radicals Oxidative stress occurs when free radicals accumulate faster than the body can neutralize them Contribute to chronic disease and conditions Fruits, vegetables, and whole grains are excellent sources of antioxidants
- 130. Antioxidants proprties . May be useful in prevention of myocardial infarction and stroke. Can mop up free radicals in brain tissue and thus can prevent conditions like multiple sclerosis, Alzheimer's disease. Helps in reducing LDL. Stimulate production of glutathione.
- 131. MINERAL METABOLISM
- 132. Inorganic elements Classification:- Macrominerals- required >100mg/day Microminerals- required < 100mg/day
- 133. Classification Macrominerals Microminerals Sodium Potassium Calcium Phosphorus Magnesium Sulphur Chlorine Chromium Cobalt Copper Fluoride Iodine Iron Manganese Molybednum Selenium Zinc
- 134. Metabolism of sodium, potassium and chlorine They grouped together because they maintain:- Electrical neutrality Osmotic pressure Water and acid-base balance. Sodium- Extracellular fluid(cation) Potassium- Intracellular fluid(cation)
- 135. Sodium: 135-145mEq/L Chloride: 95-105mEq/L Potassium: 3.5-5.5mEq/L Normal levels ( electrolytes )
- 136. Sodium Sodium is the principal cation present in extracellular fluids Total body sodium-4000mEq 50% in bones, 40% in ECF, 10% in soft tissues Major cation in blood & plasma. Extracellular conc. Is maintained by Na-K ATPase pump. Mainly present as NaCl or NaHCO3. Higher conc. In blood than in cells.
- 137. Sources:- Tabel salt(NaCl) is major source Other sources- vegetables, nuts, eggs and milk. Readily absorbed in GIT, by active transport in epithelial cells. Excretion:- kidney is the major source of excretion About 800gm/day is filtered by Glomerulus in that 99% is reabsorbed by tubules. Reabsoprtion is controlled by Aldosterone
- 138. Regulation of Sodium in Blood
- 139. functions include: osmotic equilibrium acid-base balance carbon dioxide transport cell membrane permeability muscle irritability
- 140. Disorders Hyponatremia: ↓ sodium levels Causes:- Use of Diuretics Excessive sweating Chronic renal failure Renal tubular acidosis Congestive heart failure Addisson disease(adreno-cortical insufficiency) Diarrhoea, Vomiting
- 141. Mild: Headache, Muscle cramps Moderate to Severe: Low blood pressure and Circulatory failure Clinical features
- 142. Hypernatremia: ↑ sodium levels Causes:- Cushing syndrome ( excess aldsterone) Prolonged adminstration of steroids hormones( ACTH/Cortisone/Sex hormones) Severe dehydration(only water) (Burns, Diabetes insipidus) Excess sodium intake C/F:- Increased blood volume and Hypertension.
- 143. Potassium (K) Total body potassium-3500mEq 75% in skeletal muscle Major Intracellular cation Daily requirement: 3-5gm/day Sources- vegetables, fruits(Banana, Orange), meat, legumes and milk Tender coconut water(major source)
- 144. Absorption and Excretion Readily absorbed in GIT, by passive transport in epithelial cells. Normal level: 3.5-5.5mEq/L Excretion:- three routes- GIT, skin and urine(major route) During absorption of sodium there is obligatory loss of potassium.
- 145. Factors that enhances the transport of potassium in to the cell are:- Insulin Aldosterone Alkalosis Factors causing potassium to move out of cell: Acidosis Lack of insulin Severe cell damage
- 146. Maintain osmotic pressure and water balance. Maintain acid-base balance. Involved in neuromuscular activity of cardiac and skeletal muscle. Involved in transmission of nerve impulses. Involved in biosynthesis of Proteins. Pyruvate Kinase needs potassium Function
- 147. Hypokalemia: ↓ potassium levels Causes:- Prolonged Vomiting and severe Diarrhoea Renal tubular acidosis Conn’s syndrome ( excess aldosterone causes K loss) Cushing syndrome Alkalosis Administration of Steroids C/F:- Muscle cramps, ECG changes, Vomiting, fatigue, respiratory failure . Disorders
- 148. Hyperkalemia: ↑ potassium levels Causes:- Cell damage Addison’s disease ( deficiency of aldosterone) Diabetes mellitus Violent muscle contraction Acidosis Renal failure C/F:- Cardiac arrest, Cardiac arrhythmia, Muscle weakness, ECG changes, CNS toxicity.