Vitamins-Clinical Syndromes PDF

VITAMINS-CLINICAL SYNDROMES Mr. Z. Ngwira University of Zambia, School of Medicine, Dept. of Pathology and Microbiology OVERVIEW Vitamins are a group of organic nutrients required in small quantities for a variety of biochemical functions They cannot be synthesized...

VITAMINS-CLINICAL SYNDROMES Mr. Z. Ngwira University of Zambia, School of Medicine, Dept. of Pathology and Microbiology OVERVIEW Vitamins are a group of organic nutrients required in small quantities for a variety of biochemical functions They cannot be synthesized by the body and must therefore be supplied in the diet (as originally defined). They are classified according to their solubility as either fat soluble or water soluble Fat soluble vitamins are vitamin A, D, E and K B complex and vitamin C are water soluble vitamins FAT SOLUBLE VITAMINS Fat soluble vitamin require bile acid for their digestion Like fatty acids, they are transported in blood as chylomicron via the portal vein to the liver Fat soluble vitamins are also transported in lymph to the liver. The lipid-soluble vitamins are apolar hydrophobic compounds that can only be absorbed efficiently when there is normal fat absorption FAT SOLUBLE VITAMINS Fat soluble vitamins are stored in the liver and adipose tissue. There is usually a great chance of toxicity than deficiency of the fat soluble vitamins Good sources of fatty soluble vitamins is the fatty part of food and liver WATER SOLUBLE VITAMINS Water-soluble vitamins are not toxic, and the amounts stored in the body are usually small and therefore must be continually supplied in the diet. Water soluble vitamins have a lesser tendency to be retained for long period of time in the body and greater loss by urinary excretion Water soluble vitamins function as coenzymes for several important enzymatic reactions in both mammals and microorganism VITAMIN A Vitamin A is product of β-carotene; chemically known as retinol Dietary Sources  animal – derived foods, such as meat, liver, kidney and fish oils.  Other sources are full cream milk, butter, fortified margarines, oranges , vegetables and green leafy vegetables. BIOCHEMICAL FORMS
Vitamin A can exist in three different oxidation states, namely retinol, retinal, and retinoic acid. Retinol is the storage & transport form, retinal the active form in the retina, and retinoic acid the form required to regulate gene expression during embryogenesis and epithelial differentiation. Vitamin A is stored as retinol in lipid droplets of hepatocytes, and transported as retinol in plasma, bound to a specific retinol-binding protein (RBP). BIOCHEMICAL FUNCTIONS OF RETINOL / VITAMIN A Retinal, in its 11-cis conformation, is covalently bound to its apo-protein, opsin, to form the visual pigment, rhodopsin (the light receptor of retinal cells). Vitamin A is essential for normal mucopolysaccharide synthesis and mucus secretion. FUNCTIONS OF VITAMIN A β-carotene is an antioxidant and prevent heart attack Bone growth Reproduction Cell division and differentiation Healthy Skin Cholesterol synthesis requires vitamin A Regulate Immune System FUNCTIONS OF VITAMIN A VITAMIN A DEFICIENCY The deficiency symptoms of vitamin A are not immediate, since the hepatic stores can meet the body requirements for quite sometime (2-4 months). The deficiency manifestations are related to the eyes, skin and growth. Deficiency manifestations of the eyes : Night blindness (nyctalopia) is one of the earliest symptoms of vitamin A deficiency. Prolonged deficiency irreversibly damages a number of visual cells. VITAMIN A DEFICIENCY Severe deficiency of vitamin A leads to xerophthalmia. This is characterized by dryness in conjunctiva and cornea and keratinization of epithelial cells. lf xerophthalmia persisits for a long time, corneal ulceration and degeneration occur. This Results in the destruction of cornea, a condition referred to as keratomalacia, causing total blindness VitaminA deficiency blindness is mostly common in children of the developing countries. OTHER DEFICIENCY MANIFESTATIONS

Effect on growth : Vitamin A deficiency results in growth retardation due to impairment in skeletal formation. Effect on reproduction : The reproductive system is adversely affected in vitamin A deficiency. Degeneration of germinal epithelium leads to sterility in males. Effect on skin and epithelial cells : The skin becomes rough and dry. Keratinization of epithelial cells of gastrointestinal tract, urinary tract and respiratory tract is noticed. This leads to increased bacterial infection. VitaminA deficiency is associated with formation of urinary stones. The plasma level of retinol binding protein is decreased in vitamin A deficiency. VITAMIN A TOXICITY Toxicity occur as a result of ingestion of excess vitamin or as a side effect of inappropriate therapy Symptoms of acute toxicity: nausea and vomiting, abdominal pain, drowsiness and head ache. In chronic toxicity, there is:  Fatigue  Insomia  Bone pain  Loss of hair  Desquamation and discoloration of skin  Hepatomegally  Head ache  Abdominal and joint pain. MEASUREMENT Measurement of retinol is the most common means of assessing vitamin A status in the clinical setting. measured by high-performance liquid chromatography (HPLC). VITAMIN D Vitamin D is a fat-soluble steroid hormone found in two forms: vitamin D3 (cholecalciferol) found in animals and vitamin D2 (ergocalciferol) found in plants Vitamin D occurs naturally in fatty fish, liver, and egg yolk. Milk unless it is artificially fortified, is not a good source of the vitamin. The RDA for adults is 5 mg of cholecalciferol, or 200 international units (IU) of vitamin D. VITAMIN D FUNCTIONS Calcitriol (1,25-DHCC) is the biologically active (form of vitaminD.lt regulates the plasma Ievels of calcium and phosphate. Calcitriol acts at 3 different levels ( intestine, kidney and bone to maintain plasma calcium( normal 9 -11 mg/dl) VITAMIN D FUNCTIONS VITAMIN D DEFICIENCY Deficiency of vitamin D causes rickets in children and osteomalacia in adults. derived from an old English word ‘wrickken', meaning to twist. Osteomalacia is derived from greek (osteon-bone; malakia-softness). Vitamin D deficiency results from: (1) insufficient dietary vitamin D, (2) insufficient production of vitamin D in the skin because of limited sunlight exposure, (3) inadequate absorption of vitamin D from the diet (as in the fat malabsorption syndromes) or (4) abnormal conversion of vitamin D to its bioactive metabolites. VITAMIN D DEFICIENCY 2. Renal rickets (renal osteodystrophy): This disorder results from chronic renal failure and, thus, the decreased ability to form the ac ti v e f orm of the v i tam i n 1 , 2 5 - d i OH cholecalciferol 
VITAMIN D–DEFICIENCY SYMPTOMS—BOWED LEGS AND BEADED RIBS OF RICKETS HYPERVITAMINOSIS D
Toxic effects of hypervitaminosis D include demineralization of bone (resorption) and increased calcium absorption from the intestine, Ieading to elevated calcium in plasma (hypercalcemia). Prolonged hypercalcemia is Associated with deposition of calcium in many soft tissues such as kidney and arteries. High consumption of vitamin D is associated with loss of appetite, nausea, increased thirst, loss of weight etc. MEASUREMENT Two forms are most commonly measured in the clinical laboratory: 25(OH)D3 and 1,25(OH)2D3. 25(OH)D3 is the major circulating form of vitamin D; its measurement is a good indicator of vitamin D nutritional status, as well as vitamin D intoxication. Quantitation of the metabolites of vitamin D is performed using radioimmunoassay (RIA) or HPLC VITAMIN E  consist of eight naturally occurring tocopherols, of which α-tocopherol is the most active.  Vitamin E (tocopherols) is a terminal electron acceptor found in the cell membrane and, therefore, blocks free radical chain reactions.  It protects membrane phospholipids against lipid peroxidation by free radicals formed by cellular metabolism. FUNCTIONS OF VITAMIN E
lt is closely associated with reproductive functions and prevents sterility. Vitamin E Preserves and maintains germinal epithelium of gonads for proper reproductive function.  Protects erythrocytes membrane from oxidative stress  lt is required for cellular respiration through electron transport chain (believed to stabilize coenzyme Q). FUNCTIONS OF VITAMIN E Vitamin E protects liver from being damaged by toxic compounds such as carbon tetrachloride lt works in association with vitaminsA , C and beta-carotene, to delay the onset of cataract. Major sources are oils and fats particularly wheat germ oil and sunflower oil, grains, and nuts. lt is also present in meat, milk, butter and eggs. DEFICIENCY SYMPTOMS

The symptoms of vitamin E deficiency vary from one animal species to another. In many animals, the deficiency is associated with sterility, degenerative changes in muscle, megaloblastic anaemia and changes in central nervous system Severe symptoms of vitaminE deficiency are not seen in humans except increased fragility of erythrocytes and minor Neurological symptoms, VITAMIN E TOXICITY Toxicity is rare Measurement The most widely distributed and most biologically active form of vitamin E is alpha -tocopherol, which is the form commonly measured in the laboratory using HPLC methods. VITAMIN K Vitamin K is a phylloquinone which is a coenzyme in formation of γ –carboxyglutamate in enzymes of blood clotting and bone matrix formation Vitamin K, occurs in three forms” Vitamin K1 (phylloquinone) is present in plants. Vitamin K2 (menaquinone) is produced by the intestinal bacteria and also found in animals. Vitamin K3 (menadione) is a synthetic form. lt is required for the production of blood clotting factors, essential for coagulation( in German-Koagulation; hence the name K for this vitamin).  VITAMIN K Vitamin K confers calcium-binding properties to certain proteins and is important for the activity of four clotting factors: prothrombin, factor VII, factor IX and factor X. Main dietary sources are green vegetables, margarines, and plant oils DIETARY DEFICIENCY  Vitamin K deficiency is very uncommon and most cases are associated with other disorders.  Destruction of intestinal flora by antibiotics may also result in vitamin K deficiency.  Newborn infants frequently exhibit vitamin K deficiency because the vitamin is not transported well across the placenta and the sterile gut of the newborn does not have bacteria to produce it. DIETARY DEFICIENCY Deficiency of vitamin K can be serious, because it can lead to catastrophic bleeding. Toxicity Administration of large doses of vitamin K produces hemolytic anaemia and jaundice, particularly in infants. The toxic effect is due to increased breakdown of RBC MEASUREMENT In most laboratories, vitamin K is not assayed; however, prothrombin time is used as a functional indicator of vitamin K status. PT is assessed by adding a portion of tissue thromboplastin to recalcified plasma and measuring the clotting time against a normal control sample WATER SOLUBLE VITAMIN B COMPLEX AND VITAMIN C WATER-SOLUBLE VITAMINS The water-soluble vitamins are: a) The B Complex 1. Thiamine (B1) 2. Riboflavin (B2) 3. Nicotinamide or niacin (B3) 4. Pyridoxine (B6) 5. Folate (B9) 6. Cobalamins (B12) 7. Biotin (B7) and 8. Pantothenate (B5) b) Ascorbate (vit C) THIAMINE (VITAMIN B1) Thiamine pyrophosphate (TPP) is the biologically active form of the vitamin, formed by the transfer of a phosphate group from ATP to thiamine. Sources: Pork, whole grains, watermelon and legumes are the richest. Thus, whole wheat bread is a good source of the vitamin, whereas white bread prepared from milled grain is low in thiamine. THIAMINE FUNCTION Act as a co-enzyme in the normal metabolism of carbohydrates and in branched-chain amino acid metabolism. TPP serves as a coenzyme in the oxidative decarboxylation of α-keto acids, and in the formation or degradation of α-ketols by transketolase Important in - Producing energy from carbohydrates - proper nerve function - stabilizing appetite - promoting growth and good muscle tone THIAMINE DEFICIENCY The clinical syndrome of thiamine deficiency is termed ‘beri-beri’, and organs most severely affected are those with highly active aerobic metabolism, i.e. heart and nervous system. Beri-beri may thus manifest as: Wet beri-beri, where the emphasis is on the cardiovascular system (cardiac failure with peripheral vasodilation). Patients may present with Edema, enlarged heart, heart failure and Weak muscles. THIAMINE DEFICIENCY Dry beri-beri, where symptoms are mainly neurological symptoms (CNS), and include: - peripheral neuropathy, paralysis , irritability, poor arm/leg coordination The symptoms of beri-beri are often mixed in which case it is referred to as mixed beri-beri. o Infantile beriberi, symptoms include Restlessness, Sleeplessness, tachycardia, vomiting, convulsions, and, if not treated, death. THIAMINE DEFICIENCY Wernicke-korsakoff syndrome: This is the disorder commonly association with chronic alcoholism and is due to dietary insufficiency or impaired intestinal absorption of the vitamin. Some alcoholics develop the Wernicke-Korsakoff syndrome Its characterized by apathy, loss of memory, and a rhythmical to-and-fro motion of the eyeballs. Toxicity symptoms: none reported MEASUREMENT OF THIAMINE (VITAMIN B₁) Measure the activity of the enzyme transketolase in erythrocytes for thiamine deficiencybefore and after the addition of TPP. Thiamine deficiency is present if the increase in activity after the addition of TPP is greater than 25%. Thiamine, as well as TPP, can also be detected directly in whole blood, tissues, foods, animal feed, and pharmaceutical preparations by high-performance liquid chromatography (HPLC). RIBOFLAVIN (VITAMIN B2) T h e t w o b i o l o g i c a l l y a c t i v e f o r m s a r e f la v i n mononucleotide (FMN) and f lavin adenine dinucleotide (FAD) formed by the transfer of an AMP moiety from ATP to FMN. FMN and FAD are each capable of reversibly accepting two hydrogen atoms, forming FMNH2 or FADH2. FMN and FAD are bound tightly-sometimes covalently-to f lavoenzymes that catalyze the oxidation or reduction of a substrate. RIBOFLAVIN (VITAMIN B2)  Sources include milk, liver, eggs, meat, and leafy vegetables. Strict vegetarians who exclude milk from their diet may have a marginal intake of riboflavin. The vitamin is readily destroyed by ultraviolet components of sunlight.  The body stores of a well-nourished person are adequate to prevent riboflavin deficiency for 5 months. RIBOFLAVIN DEFICIENCY  Riboflavin deficiency not associated with major human disease may occur with other nutritional deficiencies, alcoholism, and chronic diarrhea and malabsorption.  Deficiency signs: Deficiency symptoms include dermatitis, cheilosis (fissuring at the corners of the mouth), and glossitis (the tongue appearing smooth and purplish),general weakness and eye abnormalities.  no known toxicity. RIBOFLAVIN DEFICIENCY 48 Riboflavin Deficiency
Riboflavin Deficiency
(Cheilosis) (Glossitis  NIACIN (VITAMIN B3)
Two types nicotinic acid and nicotinamide. Significant sources: All protein-containing foods(rich in Tryptophan) Milk, eggs, meat, poultry, fish, Whole-grain and enriched breads and cereals, Nuts Nicotinamide is required for the biosynthesis of NAD+ and NADP+ (it is the ‘N’ of NAD+) that are coenzymes for numerous metabolic steps. NIACIN B3 Niacin deficiency result in pellagra; a condition characterised by photosensitive dermatitis and depressive psychosis; and sometimes loss of appetite. High level of niacin are used to treat hypercholesterolemia/ hyperlipidaemia Excessive niacin intake result in excessive sweating, abdominal distress and hepatocellular damage. NIACIN (VITAMIN B3) Pellagra, the clinical syndrome resulting from niacin deficiency , is associated with three Ds Diarrhea (Abnormal, frequent evacuation of watery feces) dementia (Impairment of memory. With cerebral, spinal lesions, irritability and anxiety) dermatitis (Red, itchy, dry thickened, pigmented skin in hands, feet, wrist, and knees). Niacin deficiency may also result from alcoholism. DERMATITIS OF PELLAGRA NIACIN (VITAMIN B3) Toxicity symptoms dilation of blood vessels and potentially painful tingling and rash (“niacin flush”) Excessive sweating Blurred vision Liver damage, impaired glucose tolerance DIAGNOSIS OF NIACIN DEFICIENCY A history of dietary inadequacy of available niacin and of the amino acid, tryptophan, a precursor of nicotinic acid Blood or urinary niacin levels PYRIDOXINE (VITAMIN B6) Made up of three related compounds: pyridoxine, occurring mainly in plants; and pyridoxal and pyridoxamine, which are present in animal products Dietary sources : meat, poultry, fish, potatoes, and vegetables; dairy products and grains contribute lesser amounts. Functions as Part of coenzymes PLP (pyridoxal phosphate) and PMP (pyridoxamine phosphate) used in amino acid and fatty acid metabolism VITAMIN B6  Important in: Synthesis of hemoglobin, red and white blood cells - Synthesis of neurotransmitters - reducing muscle spasms, cramps, and numbness - Activate enzymes needed for metabolism of CHO, fat, protein - maintaining proper balance of sodium and phosphorous in the body - conversion of tryptophan to niacin (B-3)  VITAMIN B6  Vitamin B6 deficiency rarely occurs alone; it is more commonly seen in patients deficient in several B vitamins.  Deficiency signs: nervousness, insomnia, loss of muscle control, muscle weakness, Microcytic hypochromic Anemia (decreased heam synthesis) , arm and leg cramps, water retention and skin lesions. Reduce immune response VITAMIN B6  Toxicity  Vitamin B6 has low toxicity because of its water- soluble nature; however, extremely high doses may cause nerve damage causing numbness and muscle weakness leading to an inability to walk and convulsions Assessment Serum PLP is the primary active pyridoxal form and is used as the primary index of whole-body pyridoxal levels. FOLATE B9 (FOLIC ACID)  Food folates are primarily found in green and leafy vegetables, fruits, organ meats, and yeast  Large quantities of folate are also synthesized by bacteria in the colon.  Function as Part of coenzymes THF (tetrahydrofolate) and DHF (dihydrofolate) used in DNA synthesis and therefore important in new cell formation  Needed for normal red blood cell synthesis  Important for rapidly dividing cells (very important in early pregnancy FOLATE DEFICIENCY  The major clinical symptom of folate deficiency is megaloblastic anemia.  Deficiency signs: Mental confusion, weakness, fatigue, irritability, headache and anemia  Deficiency in pregnancy causes neural tube defects.  Toxicity is rare DIAGNOSIS Full blood count Serum folate Erythrocyte folate Measuring both serum and erythrocyte levels is helpful because serum levels indicate circulating folate and erythrocyte levels better approximate stores VITAMIN B12 (COBALAMIN)  The primary dietary sources for vitamin B12 are from animal products (e.g., meat, eggs, and milk).  Liver stores last for several years.  Absorption is complex - requires gastric intrinsic factor, and intact ileal function  Therefore, total vegetarian diets are likely to be deficient or low in vitamin B12. FUNCTIONS OF VITAMIN B12 Vitamin B12 is required in humans for two essential enzymatic reactions: the remethylation of homocysteine to methionine and the conversion of methylmalonyl CoA to succinyl CoA that is produced during the degradation of some amino acids, and fatty acids with odd numbers of carbon atoms When the vitamin is def ic ient, abnormal fatty acids a c c um ul a t e a nd be c o m e i nc o r po ra t e d i nt o c e l l membranes, including those of the nervous system. This may ac c ount for some of the neurologic manifestations of vitamin B12 deficiency. VITAMIN B12 DEFICIENCY Deficiency may be nutritional (vegans), or due to malabsorption (pernicious anemia, gastrectomy, ileal resection, small bowel bacterial overgrowth). Deficiency symptoms - Anemia (pernicious anemia) - Nerve damage - hypersensitive skin Toxicity symptoms: none reported ASSESSMENT OF B12 STATUS Serum B12 is the best measure of whole body B12 status. Low levels reliably reflect B12 deficiency. competitive protein-binding RIAs used for Vit B12 measurement PANTOTHENIC ACID  Dietary sources include liver and other organ meats, milk, eggs, peanuts, legumes, mushrooms, salmon, and whole grains.  Chief functions in the body: Pantothenic acid is a component of CoA, which functions in the transfer of acyl groups.  Deficiency ; not well characterized in humans.  Toxicity symptoms: none reported BIOTIN (B7) Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of activated carbon dioxide. plays an integral role in gluconeogenesis, lipogenesis, and fatty acid synthesis. Distribution of biotin: Biotin is present in almost all foods, particularly liver, milk, and egg yolk DEFICIENCY OF BIOTIN Biotin def ic iency does not occur naturally because the vitamin is widely distributed in food. Also, a large percentage of the biotin requirement in humans is supplied by intestinal bacteria. However, the addition of raw egg white to the diet as a source of protein induces symptoms of biotin def iciency, namely, dermatitis, glossitis, loss of appetite, anaemia and nausea. Raw egg white contains a glycoprotein, avidin, which tightly binds biotin and prevents its absorption from the intestine. BIOTIN Toxicity symptoms: none reported  Diagnosis Biotin levels in whole blood and serum chemiluminescent, and photometric assays are now available but rarely used in hospital laboratories. ASCORBIC ACID (VITAMIN C) The active form of vitamin C is ascorbic acid. is a strong reducing compound that has to be acquired via dietary ingestion. Major dietary sources include fruits (especially citrus) and vegetables (e.g., tomatoes, green peppers, cabbage, leafy greens, and potatoes. ASCORBIC ACID Vitamin C has a well-documented role as a coenzyme in hydroxylation reactions, for example, hydroxylation of proline in procollagen to hydroxyproline to enable proper folding into a mature collagen triple-helix. Vitamin C is, therefore, required for the maintenance of normal connective tissue, as well as for wound healing. Vitamin C also facilitates the absorption of dietary iron from the intestine and its mobilization from tissue stores. VITAMIN C FUNCTIONS strong antioxidant. reduces the risk of cancer, cataract, and coronary heart diseases. lmmunological function: Vitamin C enhances the synthesis of immunoglobulins (antibodies) and increases the phagocytic action of leucocytes. Bone formation lron and hemoglobin metabolism Peptide and corticosteroid hormone synthesis DEFICIENCY OF VITAMIN C Weight loss fatigue and joint pain Anemia (hypochromic microcytic anemia despite adequate iron stores, simply because of failure to mobilize stored iron) scurvy (bruising easily, bleeding gums, and tendency for bones to fracture) Atherosclerotic plaques Muscle degeneration and pain reduced resistance to colds and infections slow healing of wounds and fractured bones DEFICIENCY  SCURVY  Fragile capillaries- internal hemorrhages.  Poor dentine formation  Gum bleed- gums are swollen, spongy bleeds on pressure  Poor mineralization of bones VITAMIN C Toxicity symptoms Megadose ingestion of vitamin C (50 mg ascorbate will be excreted during this period, while in scurvy, excretion is considerably reduced - often to less than 1mg. This test has the advantage of diagnosing & treating scurvy simultaneously The End