Trace Elements: Week 7 Notes PDF

TRACE ELEMENTS 7 Outline INTRODUCTION CLASSIFICATION INDIVIDUAL TRACE ELEMENTS FUNCTION SOURCES BODY REQUIREMENTS NUTRITIONAL DISORDER STATES MANAGEMENT OF DISORDER LABORATORY EVALUATION TRACE ELEMENTS Naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100...

TRACE ELEMENTS 7 Outline INTRODUCTION CLASSIFICATION INDIVIDUAL TRACE ELEMENTS FUNCTION SOURCES BODY REQUIREMENTS NUTRITIONAL DISORDER STATES MANAGEMENT OF DISORDER LABORATORY EVALUATION TRACE ELEMENTS Naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100 mcg/day Constituents of living organisms, and are necessary for their growth, development, and health. Classification ESSENTIAL Iron, Zinc, Iodine, Copper, Manganese, Fluoride, Cobalt, Chromium, Molybdenum and Selenium. PROBABLE ESSENTIAL NON-ESSENTIAL Aluminium, Gold, Barium, Br, lead, Lithium, Nickel, Boron, Silicon, Tin, silver, mercury, rubidium, Cadmium & Vanadium. strontium, titanium, zirconium Essential trace elements The biological effects of deficiency state defines the essentiality of a trace element, such that, an element is considered essential when signs and symptoms induced by its deficiency is reverse by an adequate supply of the particular trace element in question. TRACE ELEMENTS ULTRA TRACE ELEMENTS Iron, zinc and copper Manganese, selenium, cobalt, chromium, fluoride, iodine, and molybdenum Reversal of clinical signs and symptoms by supplementation with either a single trace element, or micronutrient mixtures is often used as clinical evidence of preexisting deficiency. General methods & instrumentation for analyzing trace elements Specimens for the analysis of trace elements must be collected with scrupulous attention to details such as appropriate anticoagulant and specimen type (urine, serum, plasma, or blood). Because of the low concentration in biologic specimens and the ubiquitous presence in the environment, extraordinary measures are required to prevent contamination of the specimen. This includes using special sampling and collection devices, specially cleaned glassware, and water and reagents of high purity. TECHNIQUES Atomic Absorption Spectroscopy (AAS) Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Atomic Absorption Spectroscopy (AAS) Uses light absorption to identify and quantify elements. Each element absorbs specific characteristic wavelengths of light The degree of absorbance of that wavelength is directly proportional to concentration iron Most essential trace element Iron is essential for the delivery of oxygen to cells. Body content – 4 - 6g Hemoglobin Storage Iron (Ferritin, Hemosiderin) Myoglobin Labile pool – peroxidases, cytochrome, Kreb cycle enzymes Transferrin 67% 27% 3.5% 2.2% 0.08% iron-DEPENDENT ENZYMES Cytochrome oxidase xanthine oxidase peroxidase BODY REQUIREMENT Daily requirement Daily excretion 0.5 - 2 mg/day 3 - 5mg/day (pregnancy) 0.9mg/day 1.3mg/day (during menstrual cycle) DIETARY SOURCES Leafy greens, whole grains, beans , pulses, liver,spleen, mollusks METABOLISM Iron is absorbed in ferrous form, which is measurable in blood as free iron ORAL PREPARATIONS Ferrous sulfate Ferrous fumarate Ferrous gluconate Ferrous succinate Iron-Calcium complex Ferric Ammonium Citrate Adverse effects: Epigastric pain, nausea, vomiting, gastritis, metallic taste, constipation or diarrhoea and staining of teeth iron deficiency When iron is deficient, Hb cannot be produced. Insufficient Hb leads to microcytic and hypochromic red blood cells. Unable to deliver sufficient oxygen to the tissues. This is known as Iron Deficiency Anemia. Estimation : 80% of world population may be Iron deficient and 30% may suffer from Iron deficiency anemia Iron deficiency affects about 15% of the worldwide population. Those with higher than average risk of iron deficiency anemia include pregnant women, young children and adolescents, and women of reproductive age Increased blood loss, decreased dietary iron intake, or decreased release from ferritin may result in iron deficiency. Reduction in iron stores usually precedes both a reduction in circulating iron and anemia, as demonstrated by a decreased red blood cell count, mean corpuscular hemoglobin concentration, and microcytic RBCs. Symptoms Asymptomatic Weakness, headache, irritability, and varying degrees of fatigue and exercise intolerance. Treatment: 3 - 6 mg of elemental iron / kg /day iron toxicity Iron is essential for cellular metabolism, but too much can be toxic. Iron Poisoning can be life-threatening. Can damage the intestinal lining and cause abnormalities in body pH, shock and liver failure. Most common form of Iron overload is known as hemochromatosis. Can happen over time and accumulates in tissues like heart and the liver. Primary Fe overload is most frequently associated with hereditary hemochromatosis (HH). HH is a single-gene homozygous recessive disorder leading to abnormally high Fe absorption, culminating in Fe overload. Secondary Fe overload may result from excessive dietary, medicinal, or transfusional Fe intake or be due to metabolic dysfunction. HH causes tissue accumulation of iron, affects liver function, and often leads to hyperpigmentation of the skin. Some conditions associated with severe hemochromatosis include diabetes mellitus, arthritis, cardiac arrhythmia or failure, cirrhosis, hypothyroidism, impotence, and liver cancer. treatment Treatment may include therapeutic phlebotomy or administration of chelators, such as deferoxamine. Transferrin can be administered in the case of atransferrinemia. laboratory evaluation Disorders of iron metabolism are evaluated primarily by packed cell volume, hemoglobin, red cell count and indices, total iron and TIBC, percent saturation, transferrin, and ferritin. 1. Total Iron Content (Serum Iron) Measurement of serum iron concentration refers specifically to the Fe3 bound to transferrin and not to the iron circulating as free hemoglobin in serum. The specimen may be collected as serum without anticoagulant or as plasma with heparin. 2. Total Iron-Binding Capacity Total iron-binding capacity (TIBC) 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. Typically, about one-third of the iron binding sites on transferrin are saturated. TIBC ranges from around 250 to 425 g/dL. 3. Percent Saturation The percent saturation, also called the transferrin saturation, is the ratio of serum iron to TIBC. The normal range for this is approximately 20% to 50%, but it varies with age and sex. transferrin Transport protein Binds to two iron molecules Transports iron to various organs and tissues Determination of transferrin gives TIBC (Total Iron Binding Capacity) Transferrin is increased in iron deficiency and decreased in iron overload and hemochromatosis, chronic infections and malignancies Transferrin can be measured by RIA, ELISA &chemiluminescence Ferritin A universal intracellular protein that stores iron & releases it in a controlled fashion. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is decreased in iron-deficiency anemia and increased in iron overload and hemochromatosis, chronic infections, malignancy, and viral hepatitis. IRMA (Immunoradiometric Assay), ELISA, Chemiluminescence zinc Second most abundant trace element. Zinc (Zn) is a bluish white, lustrous metal. Zinc and its compounds are used in a production of alloys, especially brass (with copper), in galvanizing steel, in die casting, in paints, in skin lotions, in treatment of Wilson’s disease, and in many medications. Essential for growth and development. Involved in functioning of over 300 different enzymes, including superoxide dismutase. Cofactor – DNA polymerase, Alkaline phosphatase, Carboxypeptidase regulation Growth and Reproduction Immune system, Collagen synthesis, Wound healing, Bone metabolism, Taste, smell & vision Reduce the time period of diarrhea High dose of zinc prevents dysmenorrhea Zinc required in producing testosterone For common cold body content: 2.5g 60% 30% 10% muscle bone body tissues & organs diet rich in zinc red meat, fish, sea food, pumpkin, cashews, beans, dark chocolate zinc deficiency Causes growth retardation, slows skeletal maturation, causes testicular atrophy, and reduces taste perception. Old age, pregnancy, lactation, and alcoholism are also associated with poor zinc nutrition. Leukemia, cirrhosis, hepatitis, sickle cell anemia, malnutrition treatment Zinc supplements 45 – 100 mg/day zinc toxicity Zinc is relatively nontoxic. Nevertheless, high doses (1 g) or repetitive doses of 100 mg/day for several months may lead to disorders, especially gastrointestinal tract symptoms, decrease in heme synthesis due to an induced copper deficiency, and hyperglycemia. Exposure to ZnO fumes and dust may cause “zinc fume fever.” The symptoms include chemically induced pneumonia, severe pulmonary inflammation, fever, hyperpnea, coughing, pains in legs and chest, and vomiting. REFERENCE INTERVALS: Zinc in serum Zinc in urine 70–120 g/dL 140–800 g/24 hours Copper Copper (Cu) is a relatively soft yet tough metal with excellent electrical and heat conducting properties. Copper is widely distributed in nature. 3rd most important trace element Important in helping to prevent certain types of anemia Diet rich in copper: Red meat, shellfish, nuts, chocolate, seafood, whole-grain foods. An average day’s diet may contain 10 mg or more of copper. The amount of copper absorbed from the intestine is 50%–80% of ingested copper. About half of dietary copper is excreted in feces. The exact mechanisms by which copper is absorbed and transported by the intestine are unknown 5mg/kg 34 mcg/kg