Trace and Toxic Elements

Jefferson Community and Technical College MLT 234: Clinical Chemistry II

Lesson 13: Trace and Toxic Elements

Instructor: Connie Savells, MPH, MLS (ASCP)

Student Learning Objectives

Upon completion of this module, students will be able to:

  • List the 4 fat-soluble vitamins and the two water-soluble vitamins.

  • Compare and contrast fat and water-soluble vitamins in terms of:

    • Absorption

    • Storage

    • Excretion

Vitamin D

  • State the chemical name for Vitamins D2 and D3:

    • Vitamin D2 is Ergocalciferol

    • Vitamin D3 is Cholecalciferol

  • State the active form of Vitamin D3:

    • 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)

  • Describe the role of ultraviolet light in the production of Vitamin D:

    • Ultraviolet light from the sun converts 7-dehydrocholesterol in the skin to Vitamin D3.

  • List the two main functions of Vitamin D:

    • Stimulates intestinal absorption of calcium and phosphate

    • Stimulates mobilization of calcium and phosphate from bone

  • Describe the clinical manifestations of Vitamin D deficiency:

    • In children: Rickets (results in bone deformities)

    • In adults: Osteomalacia (softening of the bones)

  • State the methodology used to measure Vitamin D in the laboratory:

    • Typically measured by chemiluminescent immunoassay.

Vitamin K

  • List the two main sources of Vitamin K:

    • Synthesized by gut bacteria (about 50% of total Vitamin K)

    • Dietary: cabbage, cauliflower, spinach, pork, liver, soybeans, vegetable oils

  • List three causes of Vitamin K deficiency:

    • Antibiotic use (which can disrupt gut bacteria)

    • Coumadin (warfarin) therapy

    • Infants (as they may not have enough gut bacteria initially)

  • Describe the symptoms of Vitamin K deficiency:

    • Increased bleeding tendencies due to impaired blood coagulation.

Vitamin B12

  • State the chemical name of Vitamin B12:

    • Cyanocobalamin

  • List the dietary sources of Vitamin B12:

    • Animal products: eggs, meat, poultry, shellfish, milk, and fortified grains

  • Describe the absorption of Vitamin B12:

    • Requires intrinsic factor (a glycoprotein secreted by stomach cells) for absorption in the ileum.

  • Describe the clinical manifestations of Vitamin B12 deficiency:

    • Megaloblastic anemia (characterized by the presence of large, immature red blood cells)

  • Describe the cause of pernicious anemia:

    • Autoimmune disorder leading to a deficiency of intrinsic factor, affecting Vitamin B12 absorption.

  • State the methodology used to measure Vitamin B12 in the laboratory:

    • Typically measured by immunoassay.

Folate (Vitamin B11)

  • List the dietary sources of folate:

    • Green leafy vegetables, beans, fruits, organ meats, yeast, whole grains

  • Describe the clinical manifestations of folate deficiency:

    • Similar to Vitamin B12 deficiency, causes megaloblastic anemia; in pregnant women, it can lead to neural tube defects in fetuses.

  • State the methodology used to measure Folate in the laboratory:

    • Assessed by serum measurement or red blood cell (RBC) folate measurement.

  • Differentiate between the purpose of measuring serum folate versus RBC folate:

    • Serum folate reflects recent intake, while RBC folate indicates long-term folate stores.

Vitamin C

  • List the chemical name for Vitamin C:

    • Ascorbic Acid

  • Describe the clinical manifestations of Vitamin C deficiency:

    • Causes scurvy, characterized by bleeding gums, joint pain, and anemia.

  • Describe side effects of excessive Vitamin C intake:

    • Can interfere with drug functions (anticoagulants, antidepressants) and may impact Vitamin B12 function.

Iron Distribution and Function

  • Describe the distribution of iron throughout the body:

    • Approximately 70% in red blood cells (RBC), other tissues, and muscle.

  • Describe the process of iron absorption:

    • Dietary iron is ingested, reduced to the ferrous state (Fe^2+) for absorption in intestines; typically, about 10% of dietary iron is absorbed.

  • State the molecule responsible for iron transportation:

    • Transferrin (can transport 2 iron molecules).

  • List the differentiate between the two iron storage molecules:

    • Ferritin (soluble form) and Hemosiderin (insoluble form).

  • Describe the excretion of iron:

    • Most iron is conserved; small amounts lost through epithelial cells, menstruation, and other bodily losses.

  • Describe the functions of iron:

    • Critical for hemoglobin (binding oxygen in lungs, releasing it to tissues) and myoglobin function.

    • Plays a role in various enzymes (peroxidases, catalases, cytochromes).

  • Describe the causes and symptoms of iron deficiency and iron overload:

    • Deficiency: Anemia characterized by microcytic and hypochromic red cells.

    • Overload: Can lead to tissue damage, organ dysfunction (such as liver cirrhosis).

  • List the specimen requirements for iron testing:

    • Should not contain EDTA, citrate, or oxalate; preferred collections in the morning after fasting.

Iron Parameters

  • **Purpose of: **

    • Total Iron: Measures iron bound to transferrin in circulation.

    • Total Iron Binding Capacity (TIBC): Measures the amount of iron that could bind to transferrin if all binding sites were occupied; indirectly indicates transferrin level.

    • % Saturation: Ratio of serum iron to TIBC; calculated using the formula:
      ext{% Saturation} = \left( \frac{\text{Total Iron (g/dL)}}{\text{TIBC (g/dL)}} \right) \times 100

    • Ferritin: Reflects body iron stores; measured by immunochemical methods (e.g., ELISA).

    • Transferrin: Measures free iron transport in plasma; helpful indicator of nutritional status.

    • Soluble Transferrin: Reflects the iron requirement of erythropoietic cells; proportional to the amount of transferrin receptors expressed.

Introduction to Trace Elements

Essential Trace Elements

  • Considered essential if:

    • A deficiency impairs biochemical or functional processes and replacement corrects impairment.

  • Special associations:

    • Often part of enzymes or proteins, functioning as cofactors in enzymatic reactions.

  • Measurement:

    • Typically measured in mg/L (e.g., iron, copper, zinc).

  • Ultratrace elements:

    • Measured in µg/L (e.g., selenium, chromium, manganese).

Nonessential Trace Elements

  • Of medical interest due to toxicity:

    • Various nonessential trace elements can pose toxicity risks despite lacking known physiological functions in humans.

Laboratory Assessment of Vitamins and Trace Elements

Vitamins

  • Vitamins are organic compounds required from external sources in small amounts, essential for normal growth and health, divided into:

    • Fat-soluble: A, D, E, K; absorbed with lipids, stored in the liver, excess can be toxic.

    • Water-soluble: B-complex and C; absorbed and excreted in urine, not stored.

Trace Elements

  • Essential elements contribute to health; nonessential can be toxic:

    • Aluminum, Arsenic, Cadmium: Toxic effects on human health with no known beneficial roles.

    • Chromium, Copper, Iron, Lead, Mercury, Manganese, Selenium, Zinc: Essential nutrients with defined roles in enzyme activation, metabolism, and physiology but also present risks for toxicity.

Laboratory Techniques for Measurement

  • Various laboratory methods used include:

    • Atomic Emission Spectroscopy (AES)

    • Atomic Absorption Spectroscopy (AAS)

    • Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

Health Effects and Toxicity of Iron and Trace Elements

Iron Deficiency Anemia (IDA)

  • Common causes: Blood loss, decreased dietary intake, and decreased release from storage (ferritin).

  • Symptoms: Microcytic and hypochromic anemia; diagnosed through serum iron, ferritin, and TIBC testing.

Conditions Related to Iron and Other Trace Elements

  1. Sideroblastic Anemia:

    • Genetic or acquired inability to use iron for hemoglobin synthesis.

    • Symptoms include fatigue and breathing difficulties.

  2. Thalassemia:

    • Caused by abnormal hemoglobin production leading to iron overload from frequent blood transfusions.

  3. Toxicities associated with excess trace elements:

    • E.g., lead poisoning leading to neurological effects; mercury toxicity resulting in multiple organ system impairments.

References

  • Bishop, M. L., Fody, E. P., & Schoeff, L.E. (2024). Clinical Chemistry: Principles, Techniques, and Correlations (9th ed.). Philadelphia, PA: Wolters Kluwer.

  • Kaplan, L. A., & Pesce, A. J. (2010). Clinical Chemistry: Theory, Analysis, Correlation (5th ed.). St. Louis, MO: Mosby/Elsevier.

  • Rifai, N., Horvath, A. R., & Wittwer, C. (2019). Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics (8th ed.). St. Louis, MO: Elsevier.

  • Sunheimer, R. L., & Graves, L. (2018). Clinical Laboratory Chemistry (2nd ed.). Hoboken, NJ: Pearson.