Clinical Chemistry - 14 Vitamins and Trace Elements

CLINICAL CHEMISTRY VITAMIN K VITAMINS & TRACE ELEMENTS • • OUTLINE • • Vitamins o Vitamin A o Vitamin D o Vitamin E o Vitamin K o Vitamin C o Vitamin B Complex Trace Elements o Conditions Leading to Deficiency o Iron o Chromium o o o o o o o o o o Copper Cobalt Fluorine Iodine Manganese Molybdenum Selenium Zinc Methods of Measurement Cystic Fibrosis VITAMIN C • • • • VITAMINS • • • • Organic molecules required for metabolism Co-enzymes/cofactors Essential vs. Non-essential vitamins Fat soluble vs. Water soluble VITAMIN A • • • • • • Retinol Carotenoids mRNA synthesis Visual system Increased Levels o Liver damage o Excessive intake Decreased Levels o NIGHT BLINDNESS o Growth retardation o Dermatitis o Fat malabsorption VITAMIN D • • • • • • Calciferol “Sunlight vitamin” Cholecalciferol/Vitamin D2 Bone Formation and Neuromuscular Activity Increased Levels o Hypercalcemia o Renal damage o Heart damage Decreased Levels o Hypoparathyroidism o Liver disease Tocopherol Antioxidant, neurologic function Partners: VLDL and Chylomicrons Decreased Levels o Normocytic normochromic anemia o Abetalipoproteinemia o Fat malabsorption o Platelet aggregation Ascorbic acid Collagen synthesis Reducing agent Scurvy VITAMIN B COMPLEX • • • • • • B1 (Thiamine) B2 (Riboflavin) B3 (Niacin) B5 (Pantothenic acid) B6 (Pyridoxal phosphate) B12 (Cyanocobalamin) TRACE ELEMENTS • • • • • • • • • VITAMIN E • • • • Menaquinone Coagulation factors o Protein C o Protein S o Factor II o Factor VII o Factor IX o Factor X • Elements found in the body in low concentrations Inorganic compounds/elements that are necessary for metabolism Required only in small amounts Constitutes <1 mcg/g of wet tissue and 0.01% of dry body weight Have specific in vivo metabolic functions that cannot be effectively done by other elements Functions contribute to biochemical and physiologic functions of cells, tissues, organs Consists of metals, except for selenium, halogens, fluoride and iodine Distribution in tissues Classification based on function o Essential ▪ Have biological or physiologic function in body ▪ Functional/Important types of trace elements ▪ Deficiency can impair biological processes ▪ Replacement of deficiency can correct deficiency ▪ Metalloenzyme - Often associated with enzymes • Trace elements act as activators ▪ Metalloproteins - linked with proteins o Non-essential ▪ Insignificant due to no role in biologic process ▪ Considered to be clinically significant, most nonessential trace elements are toxic ▪ Can cause damage to the cells, tissues leading to sequelae Classification based on concentration on plasma/serum o Trace elements ▪ Iron, copper, zinc ▪ Concentration is mg/dL o Ultra trace elements ▪ Selenium, chromium, manganese ▪ Concentration is less than mcg/L CONDITIONS LEADING TO DEFICIENCY • • • • Decreased intake o Trace elements are mostly derived from diet (exogenous) Impaired absorption o Low absorption = low concentration o Low absorption causes increased excretion Increased excretion o Due to impaired functions, renal diseases Genetic abnormalities o Cause deficiency or impaired function • • IRON • • • • • • • • • • A common metallic element 4th most abundant element in earth’s crust Most abundant transition metal Forms o Ferrous (Fe2+) - reduced form is the biologic form ▪ Form that is absorbed in the SI ▪ Become bound to protein (metalloprotein) o Ferric (Fe3+) - not absorbable ▪ Requires conversion/reduction to ferrous form to be absorbed in the SI ▪ Vit C (ascorbic acid) - important to promote reduction of ferric to ferrous ▪ In intestinal epithelium, there is the enzyme ferric reductase which is responsible for conversion of ferric to ferrous Iron in plasma can be a prooxidant o Prooxidant - can be harmful to the body ▪ Contributes to lipid peroxidation ▪ Promotes atherosclerosis ▪ Cause DNA damage and neurodegenerative diseases (Alzheimer’s) o Antioxidant - antagonist of prooxidant Iron is usually low in plasma majority is found in RBCs o Of the total 3-5 g of iron, 2-2.5 g is in hemoglobin, 130 mg is in myoglobin, 8mg in tissue, 3-5 mg in plasma (free and bound) Stored in the liver, spleen, and bone marrow in the form of ferritin and hemosiderin Carrier Proteins o Apoferritin: binds to ferrous form of iron in the intestinal mucosa o Ferritin: ferrous form of iron for storage ▪ Low serum ferritin is diagnostic for iron deficiency anemia (IDA) o Apotransferrin: protein part that binds with ferric form of iron for transport all throughout the body o Transferrin: transport ferric form of iron Regulatory Peptide Hormones o Regulates the iron level in circulation o Ferroportin: responsible for the exportation of iron from the cell o Hepcidin: regulates iron absorption in the upper GIT by modulating the activity of ferroportin Serum iron levels are falsely elevated by hemolysis and affected by diurnal variation. o Avoid hemolyzed sample o Diurnal variation ▪ High level in morning, lowest conc. at nighttime ▪ Nocturnal - opposite of diurnal variation • • • • • Increased Level: o Iron Poisoning (Overdose) o Hemochromatosis (↑ deposition of iron in vital organs) ▪ Assoc. with DM due to accumulation Fe in pancreas which can damage the beta cells o Viral Hepatitis (↑ iron metabolism) o Non-Iron Deficiency Anemias (E.G.: Thalassemia, Aplastic anemia, Megaloblastic anemia, Sideroblastic anemia, Hemolytic anemia, Pernicious anemia) Decreased Level: o Iron-deficiency anemia ▪ Most common type among pediatrics ▪ Common in impoverished communities o Malnutrition o Malignancy o Chronic infection o Nephrotic Syndrome Total Iron Binding Capacity (TIBC) o It refers to the amount of iron that could be bound by saturating transferrin and other minor-iron binding proteins present in the serum or plasma sample. o Inversely proportional to serum iron o Formulas: TIBC = UIBC + Serum Iron ▪ TIBC (µg/dL) = serum transferrin (mg/dL) x 1.2521 o Increased: IDA, hepatitis, iron-supplemented pregnancy o Decreased: non-IDA and nephrosis Unsaturated Iron Binding Capacity (UIBC) o A measure of reverse iron binding capacity transferrin o Formula: UIBC = TIBC - serum iron Percent Saturation o An index of iron storage. o It is also known as: transferrin saturation o It is the ratio of serum iron to TIBC o % saturation is directly proportional to serum iron o Increased: iron overdose, hemochromatosis, sideroblastic anemia, non-IDA anemias o Decreased: IDA , malignancy, chronic infection, anemia of chronic disease. o % Saturation = total iron (ug/dL) x100 TIBC (ug/dL) o IDA - condition where % saturation is at its lowest Serum transferrin o Transferrin is the principal iron transport protein. o Formula: TIBC (ug/dL) x 0.70 = mg/dL o Present in various organs: spleen, bone marrow Laboratory Reference Values o Iron (Male: 60-75 ug/dl, Female: 50-170 ug/dl) o Total Iron Binding Capacity (TIBC) (250-425 ug/dl) o Transferrin (200-360mg/dl) o Transferrin saturation (20-50%) o Ferritin (Male: 20-250 ug/L, Female: 10-120 ug/L) CHROMIUM • • • • • Function: enhances insulin action o Important in glucose and lipid metabolism Part of the glucose tolerance factor Only hypoglycemic agent in the body Deficiency: Insulin resistance, Impaired glucose tolerance, Hyperlipidemia Toxicity: Skin ulcers, Renal and hepatic necrosis COPPER • • • Function: cellular respiration o Important for collagen synthesis (in vivo) Deficiency: Menke’s kinky hair syndrome, Muscle weakness Toxicity: intereferes with absorption of zinc & iron in SI COBALT • • • Function: Hemoglobin synthesis, Component of Vit. B12 o Important in RBC synthesis, development, & maturation o Important in erythropoiesis Deficiency: Anemia, Growth depression Toxicity: Heart failure, Hypothyroidism • • METHODS OF MEASUREMENT • • • • • • FLUORINE • • • • Function: prevent dental caries & other dental issues o Important in dental health care Fluoride - commercial form Deficiency: Dental caries Toxicity: no known toxic effect • • Function: thyroid hormone synthesis (iodination process) o Iodine is integrated to the thyroid hormone structure Deficiency: Goiter, Cretinism, Myxedema o Deficiency in thyroid hormones Toxicity: Thyrotoxicosis • • • • • • MANGANESE • • • Function: bone and connective tissue function o Serves as active site of enzymes, cholesterol synthesis Deficiency: Skeletal defects Toxicity: Psychiatric disorders, Parkinson’s disease • • MOLYBDENUM • • • Function: DNA metabolism o Enzymes, uric acid synthesis (xanthine oxidase) Deficiency: Growth depression, Cretinism, Goiter Toxicity: Anemia, Thyrotoxicosis SELENIUM • • • • Potent antioxidant Function: prevents the oxidative damage of lipid o Important in the synthesis of glutathione peroxidase Deficiency: Keshan disease (cardiovascular myopathy) Toxicity: Hair and loss, Liver failure ZINC • • • • Function: protein synthesis o Serves as the active site of enzymes synthesis of DNA & RNA A potent cofactor/activator of alkaline phosphatase and carbonic anhydrase Important element in boosting immune system o Ascorbic acid - important in promoting WBC production to improve immunity o Zinc strengthens WBCs Component of seminal fluid to nourish sperm cells AAS: Atomic Absorption Spectroscopy/Spectrometry AES: Atomic Emission Spectroscopy FAAS: Flame Atomic Absorption Spectroscopy GFAAS: Graphite Furnace Atomic Absorption Spectroscopy ICP-AES: Inductively-Coupled Plasma - Atomic Emission Spectroscopy ICP-MS: Inductively-Coupled Plasma - Mass Spectroscopy CYSTIC FIBROSIS IODINE • Deficiency: Acrodermatitis enteropathica, Growth retardation, Immune deficiency, Infertility, Delayed wound healing, Osteoporosis Toxicity: Gastrointestinal irritation • • • • Aka Mucoviscidosis An inherited disorder of the exocrine gland Manifestation: o Glands produce abnormally thick secretions o Sweat electrolytes are elevated o In saliva, increased organic and enzymatic constituents o Overactivity of the automatic nervous system Caused by defective gene and protein (cystic fibrosis transmembranous conductance regulator gene & protein) o Defective gene is found on chromosome 7 Usually recognized in infancy or early childhood Affected organs: with exocrine glands o Pancreas, Respiratory system, Sweat glands Signs: o Chronic cough o Frequent foul-smelling stool o Persistent Upper Respiratory Tract (URT) infection Test requirements o 48 hrs of age; without rashes, cuts, or skin inflammation o Sweat inducer: Pilocarpine Diagnostic test: Sweat test o Measure sweat electrolytes (Na & Cl using coulometric principle) o Requires >50 mg of sweat sample Reference method: Gibson and Cooke Pilocarpine Iontophoresis (+) result: > 65 mmol/L of sweat electrolytes (5 -40 mmol/l)