Trace Elements

Trace Elements

Elements found in very small amounts in body, usually 1 ug per gram of tissue.

• Excess conc. of these elements is associated with toxicity

• often function as enzyme co-factors

Trace elements significance

• An element is considered essential if:

  • deficiency impairs a biochemical or functional process and replacement of element corrects the impairment.

• Trace elements are vital to normal function and health

  • If depleted secondarily to an illness, further complications may be life-threatening.

Laboratory Marker of Iron Status on Several Disease States

Iron distribution

• Reversible interaction of Fe+ with O2 makes iron physiologically important.

• 3-5 g of iron in the body

  • 2-2.5 g in hemoglobin

  • 130 mg in myoglobin

  • 8 mg in tissues (bound to enzymes)

  • 3-5 mg found in plasma –bound to transferrin, albumin and free hemoglobin

  • Also stored as ferritin and hemosiderin in BM, liver and spleen

Trace Element Examples

zinc, copper, selenium, arsenic, cadmium, mercury, lead, iron, manganese, molybdenum and chromium

Iron intake

Dietary intake

• avg of 1 mg loss per day in adults must be replaced.

  • Menstrual cycle drains ~ 30 mg of iron

• Pregnant and pre-menopausal women, children and patients with bleeding disorders have greater requirement.

Iron absorption and transport

The process through which iron is taken up from the diet, transported in the bloodstream by proteins such as transferrin, and utilized by the body for various physiological functions, including oxygen transport.

Iron excretion

• Small amts are lost in epithelial and red cells excreted in urine and feces each day.

• Women lose 20 – 40 mg of iron with each menstrual cycle

  • 600 – 900 mg with each pregnancy.

Iron Clinical Significance Iron

• Iron (ferrous) allows hemoglobin to bind reversibly to oxygen and CO₂.

• Fe deficiency anemia

  • red. of iron stores

  • red. in circulating iron

• Labs:

  • dec. RBC, MCH, MCHC and MCV 

  • dec. serum iron and ferritin

  • inc. transferrin and TIBC (total Iron-Binding capacity)

Iron status determination

• Hemoglobin

• Serum Iron

• TIBC/TIBS

• % Saturation (transferrin saturation)

  • Ratio of serum iron to TIBC => (total iron/TIBC) * 100%

• Transferrin and Ferritin

Serum Iron

• Measures Fe3+ bound to transferrin

• Diurnal variation

• Anticoagulants: serum or heparinized plasma

TIBC / TIBS

• Amount of iron that could be bound by transferrin and other proteins

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

Normal Intervals of Iron

• Serum Iron: 50-160 ug/dL

• Transferrin: 200-400 mg/dL

• Ferritin: 20-250 ug/L

• Percent Saturation: 20%-50%

• TIBS; 250-350 ug/dL

Iron Deficiency:

• Serum Iron: Decreased

• Transferrin: Increased

• Ferritin: Decreased

• Percent Saturation: Decreased

• TIBS: Increased

Iron Overdose

• Serum Iron: Increased

• Transferrin: Decreased

• Ferritin: Increased

• Percent Saturation: Increased

• TIBS: Increased

Hematochromatosis

• Serum Iron: Increased

• Transferrin: Slightly Decreased

• Ferritin: Increased

• Percent Saturation: Increased

• TIBS: Slightly Decreased

Malnutrition

**Decreased Everything**

• Serum Iron: Decreased

• Transferrin: Decreased

• Ferritin: Decreased

• Percent Saturation: Variable

• TIBS: Slightly Decreased

Malignancy

• Serum Iron: Decreased

• Transferrin: Decreased

• Ferritin: Increased

• Percent Saturation: Decreased

• TIBS: Slightly Decreased

Chronic Infection

• Serum Iron: Decreased

• Transferrin: Decreased

• Ferritin: Increased

• Percent Saturation: Decreased

• TIBS: Slightly Decreased

Viral Hepatitis

• Serum Iron: Increased

• Transferrin: Increased

• Ferritin: Increased

• Percent Saturation: Normal/Increased

• TIBS: Increased

Acute liver disease

• Serum Iron: Increased

• Transferrin: Variable/Increased

• Ferritin: Increased

• Percent Saturation:Increased

• TIBS: Variable/Increased

Chronic Anemia

• Serum Iron: Decreased

• Transferrin: Normal/Decreased

• Ferritin: Normal/Increased

• Percent Saturation: Decreased

• TIBS: Normal/Decreased

Sideroblastic Anemia

• Serum Iron: Increased

• Transferrin: Normal/Decreased

• Ferritin: Normal/Increased

• Percent Saturation: Increased

• TIBS: Normal/Decreased

Copper

Absorbed through the intestine from dietary substances.

• Travels in blood bound to albumin or histidine to the liver, brain, heart, and kidneys.

• Half is excreted in feces.

• Most is incorporated as ceruloplasmin, an acute phase reactant.

• Deficiency seen in premature infants, malnutrition, and chronic diarrhea.

  • Results in decreased hemoglobin and collagen production.

Interpretation of Copper Testing Results

Note*

• Serum copper: ↑↑↑

  • Acute copper toxicity

  • Smoking, inflammatory conditions

  • Estrogen, pregnancy

• Urine copper: ↑↑↑

  • Wilson’s Disease

Zinc

Second to iron in importance as an essential trace element.

• Absorbed through the intestine from dietary nutrients.

• Transported in blood with albumin or alpha 2 macroglobulin carriers.

• Excreted in feces or pancreatic secretions.

• Higher conc. in RBCs than in plasma or serum.

Lead

Heavy metal commonly found in the environment.

• Present in batteries, ammunition, foil, petrol, household paints, and toys.

• Exposure is primarily respiratory or gastrointestinal.

• 94% of lead is transported to RBCs (bound to hemoglobin); 6% is in plasma.

• Half-life in whole blood is 2 to 3 weeks.

• Stored in soft tissues (~5%) and bones (~95%); excreted in urine, feces, and other routes.

Lead Poisoning

• Build-up of lead in the body over months or years.

• Interferes with bodily processes, particularly heme synthesis → anemia.

• Negative effects: cognitive deficits, developmental delays in children, peripheral neuropathy, hypertension.

• Can damage organs such as the kidneys and liver.

Lead poisoning pathway

The biosynthesis of heme starts with the amino acid glycine and succinyl-CoA, leading to the formation of porphyrin, which in the presence of iron, is transformed into heme.

Specimen for Lead Testing

• Avoid contamination due to small difference between normal and elevated lead levels.

• Collect whole blood with:

  • Lead-free needle

  • Royal blue top tube (metal-free)

• EDTA is commonly used.

• Urine plastic container that is acid-washed to remove surface lead.

Capillary Blood for Lead Testing

not recommended for lead testing due to contamination risks. If capillary samples are used, results must be confirmed with venous blood for accuracy in diagnosing lead exposure.

Lead Testing - Whole Blood

Whole blood lead measurement: best for detection of lead exposure.

• Elevated lead level: >3.5 mcg/dL

• Lead level standards lowered over 20 years: from 10 mcg/dL to 5 mcg/dL, now 3.5 mcg/dL due to child development concerns.

• Significant brain development damage: >30 mcg/dL in adults.

Lead Testing Lab Tests

• Free erythrocyte protoporphyrin assay (EPP) levels

• Zinc protoporphyrin (ZPP)- considered a supplemental lead test

Arsenic

• both metallic and nonmetallic properties.

• Nonessential but can be toxic.

• Currently, main use is as a wood preservative (profession → poisoning)

• Main routes of exposure are ingestion from contaminated food, water, beverages or inhalation of contaminated air

Selenium

• Component glutathione peroxidase and tetraiodinothyronine-5’-deiodinase

• Enters food chain via plants

• Organ meats and seafood, cereals, grains, dairy products, fruits and vegetables are sources of dietary selenium

• Low Selenium content seen in parts of China resulting in Keshan disease or Kashin-Bek disease

Keshan disease or Kashin-Bek disease

A selenium deficiency-related disease characterized by cardiomyopathy and joint issues, prevalent in areas with low selenium levels. Seen in parts of China

Specimen considerations for analysis

Avoid contamination; use trace metal-free equipment and royal blue tubes for blood collection. Ensure high sensitivity and specificity in methodology. Elements must be stable; atomic absorption spectroscopy is the most precise method.