18 trace elements

7/31/2019 18 Trace Elements

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TRACE ELEMENTSGeromil J. Lara, RMT, MSMT


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TRACE ELEMENTS Usually associated with an enzyme

(metalloenzyme) or another protein

(metalloprotein) as an essential component orcofactor

Deficiencies typically impair one or more

biochemical functions Excess concentrations are associated with at

least some degree of toxicity


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SAMPLE COLLECTION, PROCESSING, ANDLABORATORY DETERMINATION

Anticoagulants must be considered

Glasswares and other materials used duringprocessing of samples

Reagents and water affect analyses of these

trace elements

AAS is the most commonly used for

determinations


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IRON 35 grams

22.5 g of iron is in hemoglobin (red blood cells)

130 mg in myoglobin 8 mg bound to enzymes

35 mg is found in plasma associated with

transferrin, albumin, and free hemoglobin

Stored as ferritin and hemosiderin

Bone marrow, spleen, and liver


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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


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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 offerric iron to ferrous iron, resulting in the production

of ATP

Peroxidase and catalase are iron-containing

enzymes that convert H2O2 to water


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IRON Clinical Disorders of Iron Deficiency

IDApregnant 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 areduction in circulating iron and anemia

Decreased RBC count, MCHC, and microcytic RBCs

Decrease serum Fe, increase transferrin/TIBC

Decrease serum ferritinmore sensitive


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IRON Clinical Disorders of Iron Overload

Caused by an abnormal excess absorption of iron

from a normal dietHEMOCHROMATOSISwhether

or not tissue damage is present

HEMOSIDEROSISused to specifically designate a

condition of iron overload as demonstrated by an

increased serum iron and TIBC or transferrin, butwithout demonstrable tissue damage

Genetic Hemochromatosisgenetic defect that

causes tissue accumulation of iron, affects liver

function, and often leads to hyperpigmentation of the

skin


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IRON Role of Iron in Tissue Damage

Iron may play a role as prooxidant, by contributingto lipid peroxidation, atherosclerosis,

deoxyribonucleic acid damage, carcinogenesis, and

neurodegenerative diseases

Ferric iron, released from binding proteins, canenhance production of free radicals to cause

oxidative damage


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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 Receptorsincreases in iron

deficiency and decreases in iron overload


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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)


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IRON

Total Iron-Binding Capacity (TIBC)

Refers to the amount of iron that could be bound bysaturating transferrin and other minor iron-binding

proteins present in the serum or plasma sample

TIBC (ug/dL) = serum transferrin (mg/dL) x 1.25


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IRON

Total Iron-Binding Capacity (TIBC)

Addition of sufficient ferric iron to saturate thebinding 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 precipitatedferric iron, the supernatant containing the soluble

iron bound to proteins is analyzed for total iron

content


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IRON

Percent Saturation

Also called the transferrin saturation Is the ratio of serum iron to TIBC

%saturation = total Fe (ug/dL) / TIBC x 100%


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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


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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


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COPPER Dietary Requirements

Shellfish, liver, nuts, and legumes

Absorption, Transport, and Excretion Intestinesregulation of copper

Copper becomes bound to albumin or complexed to

histidine residues as it is transported to the liver

where it is stored in the form ofcuproproteins Small amount bound to albumin and transuprein

Mostly incorporated into ceruloplasmin


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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 inbiliary and intestinal secretions

Less than 3% is lost in urine and sweat


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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


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COPPER Deficiency

Malnutrition and malabsorption

Zinc competes with copper for absorption from theintestine

Increase zinc intake could cause copper deficiency

Causes a microcytic, hypochromic anemia

associated with low concentrations of

ceruloplasmin Neurologic symptoms

Menkes syndromerecessive X-linked genetic

defect in copper transport and storage


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COPPER Excess

Mostly by accidental ingestion of copper solutions

Use of intrauterine devices containing copper Exposure to copper-containing fungicides

Wilsons diseasehepatolenticular 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


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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 assaysmore sensitive index


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ZINC Richest Source

Meat, fish, and dairy products

Absorption, Transport, and Excretion

Mainly absorbed in the small intestine

65% = transported in the circulation by albumin

35% = alpha2-macroglobulin Major route of excretion is by the feces and 25% is

by pancreatic secretion

Relatively small amount in urine and sweat


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ZINC Biochemical Functions

Metal cofactor fro enzyme activity

Usually an integral component of the active site ofthe enzyme

ALP, Alcohol dehydrogenase, carbonic anhydrase, DNA

and RNA polymerases

For growth, wound healing, integrity of connectivetissues, reproductive function, immune system, and

protection from free radical damage


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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


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ZINC Laboratory Evaluation

Highest in the morning

Serum values are about 10% higher than plasma asa 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


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COBALT Constituent of vitamin B12, which is involved

in folate metabolism and erythropoiesis

May be absorbed by the same metabolism as

iron

Has toxic effects at high doses

AAS for measurement


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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 anessential activator of insulin

Flameless AAS


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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


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MANGANESE

Largely protein-bound

Activator of several enzymes Transported in plasma by albumin, alpha2-

macroglobulin, and transferrin

Excreted in bile and pancreatic secretions

Flameless AAS


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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 ofcopper-dependent enzymes (ceruloplasmin

and cytochrome oxidase)


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SELENIUM Cofactor in glutathione peroxidase and

iodothyronine diodinase

Antioxidant properties and is involved inmetabolism of thyroid hormones

Deficiency found in: cardiomyopathy and

skeletal weakness, osteoarthritis, and

increased incidence of cancer

AAS


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18 trace elements

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