Trace Elements

Trace Elements

Very small amounts are needed to cause a physiological reaction

Cr, Cu, Mn, Se, Zn, Fe

Chromium

Absorbed in small intestine and transported by transferrin

Excreted by feces

Found in wheat, whole grain, broccoli, spices, and green beans

Cr³⁺

Enhances the activation of insulin

Cr⁶⁺

Destructive; industrial carcinogen

Chromium Deficiency

Insulin-resistant glucose intolerance, weight loss, neurological defects

Copper

Absorbed in intestines, binds to albumin, and transported to liver

Important component of ceruloplasmin and cytochrome C oxidase

Copper Deficiency

Menkes Disease - malabsorption syndrome

Cause: infant prematurity, parenteral nutrition, CVD

Copper Excess

Wilson’s Disease - body does not properly absorb copper

• Elevated LFTS, elevated Cu, normal ceruloplasmin

Overconsumption

Can accumulate in eyes, liver, and brain

Manganese Absorption and Excretion

Absorbed in small intestine, transported to liver, protein-bound in liver, then travels to other tissue

Excreted via bile through feces

Manganese Functions

Important part of metalloenzymes - needed for enzyme activity

Needed for the formation of connective tissue, growth, reproduction, CHO + Lipid metabolism

Manganese Toxicity

Industrial exposure, severe liver disease (cent excrete Mn2+)

Causes neurological symptoms similar to Parkinson’s

Selenium

Works with vitamin E as an antioxidant

In wheat and other cereal

Absorbed in intestines and excreted in the urine

Selenium Deficiency

Severe - cardiac myopathy and severe arthritis

Mild - thyroid disease, impaired immunity, mood disorders, inflammation

Zinc

2nd most common trace element

Absorbed in intestines, transported to liver, the attached to enzymes and proteins

Excreted through feces

Zinc Deficiency

Varied and nonspecific symptoms

May have: depressed growth and stunting, diarrhea, skin lesions, alopecia

Zinc Toxicity

Abdominal pain, Diarrhea, Nausea / Vomiting

Iron

Most abundant trace element

Functions: vital compound of hemoglobin and myoglobin, attracts some enzymes

Available in iron circulating pool

Iron Absorption

Absorbed as heme (from animal meat) or nonheme (vegetables + whole grain)

• Heme iron is absorbed easier in intestine

Must be absorbed at Fe2+ (ferrous) and not Fe3+ (ferric)

Regulated by Hepcidin

Apotransferrin bind Fe3+ to form transferrin that carries iron to the liver and thru body

Iron Storage

In tissues: liver, spleen, bone marrow

Transported in bloodstream as transferrin-Fe3+ complex

Liver Ferrin synthesis rate altered by body’s iron requirements and iron reserves

Serum Iron Lab Assay

Spectrophotometry

Steps:

• Add acid to serum - releases iron from transferrin and reduces from Fe2+ → Fe3+

• Add chromogen reagent

  • mixed with bathophenanthroline or ferrozine - forms a complex with Fe3+ and induces a color change

Measured at 562nm - absorbance is proportional to [iron]

Serum Iron Reference Range - Women

50 - 150 μg/dL

Serum Iron Reference Range - Men

65 - 170 μg/dL

Total Iron Binding Capacity (TIBC)

The maximum amount of available transferrin binding sites

• indirect measurement of [transferrin]

• Measures functionality (qualitative)

Regular Transferrin Binding Percentage

25-30% saturated

TIBC Assay

Add excess Fe3+ to saturate transferrin

Remove unbound Fe3+ with MgCO3 or alumina column

Measure iron in serum iron assay after adding acid to release transferrin-bound iron

TIBC Assay Calculations

TIBC = UIBC + Serum Iron

OR TIBC (μg/dL) = Serum Transferrin (mg/dL) x 1.43

TIBC Reference Range

250 - 400μg/dL

TIBC and Serum Iron Relationship

Low TIBC = High Serum Iron = Low Transferrin

High TIBC = Low Serum Iron = High Transferrin

Low TIBC

Less available transferrin to bind to; Less free iron - all bound to transferrin

Iron Overload - 80-90% transferrin saturation

Liver Cirrhosis - elevated Transferrin Saturation %

Chronic Inflammatory Disease

Protein-Losing States (nephrotic syndrome)

High TIBC

More available transferrin to bind to; Iron isn’t available to bind

Iron Deficiency

Pregnancy

Oral Contraceptives

Unsaturated Iron Binding Capacity (UIBC)

Measures the amount of open / unused binding sites on transferrin that do not contain iron

UBIC Assay

Direct measurement; quantitative

Process:

• add a known [iron] to serum at neutral pH

• Iron binds to free transferrin binding sites

• Measure remaining iron in the serum that did not bind using iron-binding chromogen

  • DO NOT acidify sample to release transferrin-bound iron

    • Only measures unbound iron

UBIC Calculation

UIBC (μg/dL) = TIBC (μg/dL) - Serum Iron (μg/dL)

Transferrin Reference Range

170-370 md/dL

Transferrin Saturation Percentage Range

20-50%

Transferrin Percentage Calculation

(Serum Iron / TIBC) x 100

Transferrin and Transferrin Saturation Purpose

Screening for chronic overload disease

Transferrin Measured by immunoturbidity, immunonephelometry, or by calculation

Transferrin Calculation

TIBC x 0.007 (estimation)

High Transferrin Saturation %

Iron Overload - 80-90%

Liver cirrhosis - Low TIBC

Protein-Losing States - Low TIBC

Low Transferrin Saturation %

Iron Deficiency - <10% transferrin saturation

Normal iron levels but unable to release iron

• hypoplastic anemia

• liver cirrhosis

• protein-losing states

Ferritin

Measured to determine the body’s iron stores

Measured by: ELISA, immunoluminescence, immunoturbidimetry

Ferritin Reference Range - Women

22-336 ng/mL

Ferritin Reference Range - Men

11-306 ng/mL

Ferritin Indicated

Sensitive indicator of iron deficiency

[Ferritin] lowers before changes in hemoglobin, RBC size, or serum changes

Ferritin Reactant Type

Acute Phase Reactant

Under normal condition, reflects iron stores

Levels increase in inflammatory conditions

• acute liver disease

• neoplasms

• acute/chronic liver infections

• hemolysis

Iron Deficiency Anemia

Insufficient iron to support RBC production

Cause: insufficient dietary intake, pregnancy, excessive loss (menorrhagia, GI bleeding, intestinal parasites)

Lab Diagnosis:

• Low iron, High TIBC, Low Ferratin, Low Transferrin Saturation %

• Hypochromic Microcytic Anemia

Hyperchromic Microcytic Anemia

Indicator of iron deficiency anemia

RBC that lack color - large white hole in pink

RBC Prescence of immature RBC - stain purple, look like WBC but similar size to RBC

Iron Overload Absorption

Increased iron absorption

• hemochromatosis (hereditary or secondary)

• Increased RBC turnover (chronic hemolytic anemia)

  • rapid breakdown of RBC releases Fe

• Increased dietary intake (absorption regulated by hepcidin)

  • overdose on multivitamins

Multiple blood transfusions

Sickle Cell Anemia - mis-formed RBC cant bind iron properly

Hereditary Hemochromatosis

Genetic iron overload due to increased iron absorption

Symptoms: bronze skin, cirrhosis, diabetes

Lab Diagnosis:

• High iron, Low TIBC, High Ferritin, High Transferrin Saturation %

• Genetic and Abnormal Liver Function testing

Hemosiderosis

Iron overload due to increased iron exposure

No localized tissue injury

Can be systemic or localized (hemorrhage)

Hemosiderin

An aggregate of lipid, protein, carbs, and iron

Mostly found in macrophages

Formed from the partial degradation of ferratin

Stains bright blue with Prussian Blue Dye