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TRACE ELEMENTS
Usually associated with an enzyme (metalloenzyme) or another protein (metalloprotein) as an essential component or cofactor Deficiencies typically impair one or more biochemical functions Excess concentrations are associated with at least some degree of toxicity
SAMPLE COLLECTION, PROCESSING, AND LABORATORY DETERMINATION Anticoagulants must be considered Glasswares and other materials used during processing of samples Reagents and water affect analyses of these trace elements AAS is the most commonly used for determinations
IRON
3 5 grams
2 2.5 g of iron is in hemoglobin (red blood cells) 130 mg in myoglobin 8 mg bound to enzymes 3 5 mg is found in plasma associated with transferrin, albumin, and free hemoglobin
IRON
Dietary Requirements
In adult male, the average loss of 1 mg iron per day must be replaced by dietary sources Pregnant or premenopausal women and children have greater iron requirements
IRON
Biochemical Functions
Essential component of hemoglobin Iron must remain in ferrous state Myoglobin facilitates diffusion of oxygen into tissue because it binds oxygen with greater affinity than hemoglobin Cytochromes are essential for electron transport in the respiratory chain, with reversible cycling of ferric iron to ferrous iron, resulting in the production of ATP Peroxidase and catalase are iron-containing enzymes that convert H2O2 to water
IRON
Clinical Disorders of Iron Deficiency
IDA pregnant women, both young children and adolescents, and women of reproductive age Increased Blood Loss Decreased iron intake Decreased release from ferritin Reduction in iron stores usually precedes both a reduction in circulating iron and anemia
Decreased RBC count, MCHC, and microcytic RBCs Decrease serum Fe, increase transferrin/TIBC Decrease serum ferritin more sensitive
IRON
Clinical Disorders of Iron Overload
Caused by an abnormal excess absorption of iron from a normal diet HEMOCHROMATOSIS whether or not tissue damage is present HEMOSIDEROSIS used to specifically designate a condition of iron overload as demonstrated by an increased serum iron and TIBC or transferrin, but without demonstrable tissue damage
Genetic Hemochromatosis genetic defect that causes tissue accumulation of iron, affects liver function, and often leads to hyperpigmentation of the skin
IRON
Role of Iron in Tissue Damage
Iron may play a role as prooxidant, by contributing to lipid peroxidation, atherosclerosis, deoxyribonucleic acid damage, carcinogenesis, and neurodegenerative diseases Ferric iron, released from binding proteins, can enhance production of free radicals to cause oxidative damage
IRON
Laboratory Evaluation of Iron Status
Packed Cell Volume (PCV) or Hematocrit Hemoglobin Red blood cell count and indices Total iron and TIBC Percent saturation Transferrin Ferritin Serum Transferrin Receptors increases in iron deficiency and decreases in iron overload
IRON
Total Iron Content (Serum Iron)
Specifically to the ferric iron bound to transferrin and not to the iron circulating as free hemoglobin in serum Serum or heparinized plasma Early morning is preferred because of the diurnal variation Hemolysis should be avoided
Fe+3 is released form binding proteins by acidification Reduced to ferrous state by ascorbate, and complexed with a color reagent (ferrozine, ferene, bathophenanthroline)
IRON
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
IRON
Total Iron-Binding Capacity (TIBC)
Addition of sufficient ferric iron to saturate the binding sites on transferrin With the excess iron removed by addition of magnesium carbonate to precipitate any ferric iron remaining in solution After centrifugation to remove the precipitated ferric iron, the supernatant containing the soluble iron bound to proteins is analyzed for total iron content
IRON
Percent Saturation
Also called the transferrin saturation Is the ratio of serum iron to TIBC
IRON
Transferrin
Measured by immunochemical methods (e.g. nephelometry)
Increased in iron deficiency and decrease in iron overload and hemochromatosis May also be decreased in chronic infection and malignancies
Primarily monitored as an indicator of nutritional status Negative acute phase protein, it will decrease in inflammatory conditions
IRON
Ferritin
Measured in serum by immunochemical methods (e.g. ELISA) Decreased in iron deficiency anemia Increased in iron overload and hemochromatosis Often increased in several other conditions
COPPER
Dietary Requirements
Shellfish, liver, nuts, and legumes
COPPER
Ceruloplasmin
Synthesized in the liver and has ferroxidase activity, converting ferrous iron to ferric iron as it is incorporated into transferrin Acute phase protein
Mainly removed by fecal excretion as unabsorbed dietary copper and contained in biliary and intestinal secretions Less than 3% is lost in urine and sweat
COPPER
Biochemical Functions
Component of enzymes involved in redox reactions, with many involving reactions with oxygen
Ceruloplasmin Cytochrome c oxidase Superoxide dismutase Dopamine-beta-hydroxylase Tyrosinase Ascorbate oxidase
COPPER
Deficiency
Malnutrition and malabsorption Zinc competes with copper for absorption from the intestine
Increase zinc intake could cause copper deficiency
Causes a microcytic, hypochromic anemia associated with low concentrations of ceruloplasmin Neurologic symptoms Menkes syndrome recessive X-linked genetic defect in copper transport and storage
COPPER
Excess
Mostly by accidental ingestion of copper solutions Use of intrauterine devices containing copper Exposure to copper-containing fungicides Wilsons disease hepatolenticular degeneration
Associated with copper accumulation in the liver, brain, kidney, and cornea (Kayser-Fleischer ring) Copper is transported normally from the intestine to the liver, but cannot be transported out of the liver into the bile
COPPER
Laboratory Evaluation
Serum or plasma copper measurement
Insensitive index of overall copper status
Diurnal variation: highest in the morning Increased by inflammation and pregnancy May be decreased by steroid hormones AAS Immunochemical assays more sensitive index
ZINC
Richest Source
Meat, fish, and dairy products
ZINC
Biochemical Functions
Metal cofactor fro enzyme activity Usually an integral component of the active site of the enzyme
ALP, Alcohol dehydrogenase, carbonic anhydrase, DNA and RNA polymerases
For growth, wound healing, integrity of connective tissues, reproductive function, immune system, and protection from free radical damage
ZINC
Deficiency and Toxicity
Insufficient dietary intake Administration of steroids or metal chelating agents GI malabsorption and urinary loss Symptoms:
Growth retardation Dwarfism Sensory alterations Susceptibility to infection
ZINC
Laboratory Evaluation
Highest in the morning Serum values are about 10% higher than plasma as a result of osmotic shifts caused by anticoagulants Can decrease with inflammation Zinc in red blood cells Urinary zinc AAS, spectrophotometry, and emission spectroscopy Activities of ALP and carbonic anhydrase
COBALT
Constituent of vitamin B12, which is involved in folate metabolism and erythropoiesis
CHROMIUM
Use in metal alloys, metal plating, dyes, and leather tanning Natural or industrial waste +6 ion is far more toxic than the +3 ion Richest source is diet Transported to the tissue by transferrin Important in glucose metabolism as an essential activator of insulin Flameless AAS
FLUORIDE
Preventing dental caries Excess is associated with mottling of teeth and calcification in soft tissue May also minimize bone loss or even stimulate bone formation Readily absorbed by the gut and distributed totally to the bone and teeth Excreted in the kidney
MANGANESE
Largely protein-bound Activator of several enzymes Transported in plasma by albumin, alpha2macroglobulin, and transferrin Excreted in bile and pancreatic secretions Flameless AAS
MOLYBDENUM
Cofactors fro several oxidase enzymes Mostly absorbed in the stomach and small intestine Released and excreted either in the urine or in the bile Excess exposure may cause inhibition of copper-dependent enzymes (ceruloplasmin and cytochrome oxidase)
SELENIUM
Cofactor in glutathione peroxidase and iodothyronine diodinase Antioxidant properties and is involved in metabolism of thyroid hormones Deficiency found in: cardiomyopathy and skeletal weakness, osteoarthritis, and increased incidence of cancer AAS
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