Trace Elements and Anemia Quiz

Trace Elements

• Also known as micronutrients
• Naturally occurring, homogeneous, inorganic substance
• Humans require these in amounts less than 100 mg/day
• Have specific in vivo metabolic functions
• Cannot be effectively performed by other elements

Categories of Elements

• Classified based on their biological effects, deficiency diseases and toxicity from overdose
• Essential elements: deficiency impairs biochemical reactions that are corrected by replacement of the element
• Possibly essential elements
• Nonessential elements: primarily of medical interest because of their toxicity. Mostly metals except selenium and halogens (fluoride and iodine)

Roles of Trace Elements

• Structural signal transduction and special catalytic properties (Zn, Cu, Mg)
• Some trace elements are components of metalloenzymes and metalloproteins, acting as cofactors (Fe, Se, Mo, Cr)
• Provides electron and oxygen transport (Cu)
• Maintenance of macromolecule conformation (Zn, Cu)
• Influences vitamin or hormonal activity (Zn, Cr, Se)

Possibly Essential Elements in Animals

• Bromine
• Cadmium
• Lead
• Strontium
• Tin

Not Essential Elements

• Aluminum
• Antimony
• Bismuth
• Germanium
• Mercury
• Silver
• Thallium
• Titanium

Aluminum

• Crystalline silver-white ductile metal
• Most abundant metal in the Earth's crust
• Good conductor of heat and electricity
• Found in consumer products such as antacids, astringents, buffered aspirin, food additives, cosmetics, and antiperspirants
• Non-essential

Aluminum - Mode of Exposure and Concentration in Organs

• Mode of exposure: orally, through inhalation, and parenterally (injection)
• In plasma, aluminum is bound to carrier proteins such as transferrin
• Concentration in organs:
  • Bone: 50%
  • Lung tissues: 25%
  • Excretion: urine (95%), bile (2%)

Lab Evaluation

• Specimens: urine, serum
• Methodologies: ICP-MS, GFAAS

ICP-MS

• Inductively coupled plasma mass spectrometry
• Plasma, interface, quadrupole, carrier gas, spray chamber, sample, ion lens, detector, nebulizer

GFAAS

• Graphite furnace atomic absorption spectroscopy
• Sample injection port, atomization chamber, graphite furnace, monochromator, detector, light source

Arsenic

• Nonessential
• Food is the largest source
• Lower amounts come from drinking water and air
• Commonly found in fish and seafood
• Used as a wood preservative

Iron

• Ferrous (Fe2+) and ferric (Fe3+) irons
• Fourth most abundant element in the earth's crust and the most abundant transition metal
• No excretory system for excess iron
• Primary means of iron regulation: absorption of iron from the intestine

Iron Metabolism

• Only the Fe2+ form can be absorbed by the intestine
• Fe3+ is first reduced to Fe2+
• Present in intestinal epithelial cells
• Stored as ferritin or oxidized to Fe3+
• Exported on the basolateral side and bound to apotransferrin for distribution in the body
• Release of Fe3+ from intestinal cells is mediated by ferroportin and regulated by hepcidin

Iron - Amount in the body

• 3-5 g of iron in the body
• Approximately 2-2.5 g is in hemoglobin, mostly in RBC and its precursors
• Moderate amount of iron (130mg) is found in myoglobin
• 8mg is found in enzymes like peroxidases, cytochromes, and many of Kreb cycle's enzymes
• Stored as ferritin or hemosiderin in bone marrow, spleen or liver
• Only 3-5 mg of iron is found in plasma bound to transferrin, albumin, and free hemoglobin

Iron Deficiency

• Affects 15% of the worldwide population
• At risk: pregnant women, young children, adolescents, women of reproductive age
• Caused by increased blood loss, decreased intake, or decreased release from ferritin
• IDA (Iron Deficiency Anemia): most common anemia in the planet

Other Features of IDA

• Pagophagia (craving ice)
• Pica (craving of non-food substances: dirt, clay, laundry starch)
• Glossitis (smooth tongue)
• Restless legs
• Angular stomatitis (cracking of corners of mouth)
• Koilonychia (thin, brittle, spoon-shaped fingernails)

Iron Toxicity

• Hemochromatosis: collective term for iron overload with or without tissue damage
• Associated hereditary hemochromatosis (HH): leading to abnormally high iron absorption; affects liver function and often leads to hyperpigmentation of the skin
• Hemosiderosis: iron overload without demonstrable tissue damage

Lab Evaluation (Iron)

• Disorders of iron metabolism are evaluated by
  • Hematocrit & hemoglobin
  • RBC count & RBC indices
  • Total iron level
  • Percent saturation
  • Transferrin
  • Ferritin
  • TIBC (Total iron-binding capacity)

Total Iron Content (Serum Iron)

• Refers specifically to the Fe3+ bound to transferrin
• Heparinized plasma may be used
• Oxalate, citrate, EDTA binds iron and are unacceptable
• Early morning sample is preferred due to diurnal variation

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
• Direct measure of the available transferrin receptors
• All TIBC methods require addition of excess iron to saturate transferrin
• Excess iron is removed by adding magnesium carbonate to measure the bound iron
• IDA have high TIBC; other anemias have low TIBC (non-iron deficiency)

Percent Saturation

• Also known as transferrin saturation
• An index of iron storage
• Ratio of serum iron to TIBC
• Normal values are around 1/3
• IDA values significantly reduce to 1/5 or less

Lab Methodologies (various)

• COLORIMETRY: Uses HCl and ferrozine → blue color; iron dyes: bathophenanthroline, tripyridyltriazine
• ANODIC STRIPPING VOLTAMMETRY: First step in serum iron quantitation is separation from transferrin.
• Serum iron is falsely elevated by hemolysis and affected by diurnal variation. Iron is highest in the morning
• LAB METHODOLOGIES, Specimen: Whole venous blood (preferred over serum or plasma due to lead being mostly in red blood cells) Urine: useful for recent exposure or monitoring of chelation therapy
• Radiographic methods: measure amount of lead in bones
• Other methods: plasma aminolevulinic acid, whole blood Zinc protoporphyrin free erythrocyte protoporphyrin.

Lead

• Plays no known role in normal human physiology
• Lead-based household paints were banned in the US in 1972
• Recent recalls of toys from China
• Exposure primarily gastrointestinal and respiratory
• 99% of absorbed lead is taken up by erythrocytes, interfering with heme synthesis

Lead Poisoning

• Lead blocks the action of:
  • 6-aminolevulinic acid (ALA) synthetase
  • 6-ALA dehydratase (ALAD)
  • Coproporphyrinogen decarboxylase
  • Ferrochelatase
• This produces anemia

Lead Poisoning Additional Aspects

• In addition, lead blocks two other enzymes: pyrimidine-5'-nucleotidase and Na-K dependent ATPase. This leads to diminished energy supply for red blood cells and decreased cell membrane integrity.
• Because pyrimidine-5'-nucleotidase is needed to remove clumped RNA, lead inhibition results in RNA clumping observed as basophilic stippling of red blood cells.

Mercury

• Also called quicksilver
• Three naturally occurring oxidation states: Hg(0), Hg+, Hg2+
• Organic mercury: Hg2+ attached to carbon atoms
• Used in dental amalgams, electronic switches, germicides, fungicides, fluorescent light bulbs, OTC drugs, laxatives, diaper-rash ointments, eye drops, nasal sprays, and eye cosmetics (especially mascara).

Mercury - Routes of Exposure

• Inhalation (primarily elemental mercury vapor)
• Ingestion (HgCl2 and mercury-containing foods such as predatory fishes)
• Cutaneous absorption (methyl mercury through skin and even through latex gloves)
• Injection (liquid mercury and mercury-containing tattoo pigments)

Forms of Mercury

• Elemental mercury vapors: highly absorbed and toxic; harmful effects on nervous, digestive and immune systems
• Liquid elemental mercury: poorly absorbed and relatively nontoxic
• Inorganic salts: affects the skin, eyes, GIT and kidneys
• Methyl mercury: very toxic, highly selective for lipid-rich medium such as brain

Molybdenum

• An essential trace element
• Component of xanthine oxidase, aldehyde oxidase, and sulfite oxidase
• Binds molybdenum in the form of a cofactor called molybdopterin
• Grains, nuts, and legumes (peas, lentils, beans) are good sources
• Can cross the placental barrier and increase intake, increasing levels in the mother's liver

Selenium

• Considered a toxic element (1930s), carcinogen (1940s), essential element (1950s) and anticarcinogen (1960s)
• Constituent of glutathione peroxidase, associated with vitamin E functions that are important in defense against oxidative stress
• Involved in the metabolism of thyroid hormones: deiodinase, thioredoxin reductase

Selenium - Deficiency & Toxicity

• Deficiency associated with cardiomyopathy, skeletal muscle weakness and osteoarthritis
  • Keshan disease: endemic cardiomyopathy affecting mostly children and child-bearing age in some areas of China
  • Kashin-Beck disease: endemic osteoarthritis occurring during adolescent and preadolescent years in certain parts of China and other regions
• Toxicity: hair loss, garlic breath, irritability, mild nerve damage, nail damage

Zinc

• Second only to iron in importance as an essential trace element
• The most common catalytic metal ion in the cytoplasm of cells
• Main biochemical role seen in its influence on the activity of more than 300 enzymes (oxidoreductases, transferases, lyases, isomerases, and lipases)

Genetic Zinc Deficiency

• Acrodermatitis enteropathica: rare autosomal recessive disorder with impaired intestinal absorption and transport of zinc
• Symptoms: hyperpigmented skin lesions, pustular and bullous dermatitis, alopecia, growth retardation, diarrhea, secondary infection, irritability, lethargy, and depression

Zinc Toxicity

• Inhalation of zinc oxide fumes is the most common cause of metal fume fever
• Chronic oral zinc supplementation interferes with copper absorption and may cause copper deficiency.

Analytical Considerations (Trace Elements)

• Assessment of trace mineral status difficult, requiring specialized analytical instruments (AAS, AES)
• Serum measurements complicated by associated diseases that affect circulating binding proteins (e.g., albumin)
• Diagnosis dependent on high degree of suspicion, careful inspection of signs and symptoms, understanding of predisposing causes, and resolution of symptoms with therapeutic trial.

Analytical Considerations - Specimen Collection

• Trace elements must be carefully analyzed using clean room techniques and ultra-pure reagents (e.g., type I water)
• Reference materials and strict quality control are requisite in each assay run to ensure analytic accuracy.
• Special collection and handling necessary; ubiquitous biological materials (needles, syringes, stoppers) can contaminate samples.
• Remedy: use trace element-free syringes, evacuated tubes with fitted siliconized needles, acid-washed glassware, use standard reference materials

Causes of Deficiency

• Decreased intake (nutritional deficiency)
• Total parenteral nutrition (inadequate supplementation)
• Increased utilization (increased catabolism)
• Interactions between trace elements (e.g., zinc, copper) or other nutrients (zinc, vitamin C)
• Increased excretion
• Disease states (insufficient intestinal absorption: acquired; malabsorption, intestinal resection; genetic; mutation resulting in lack of protein needed to absorb the element)

Lab Methodologies

• Atomic Absorption Spectrometry (AAS):
  • Most commonly used for trace and toxic metal analysis
  • Flame AAS: uses flame; used in measurement of copper, iron, zinc, LOQ (limit of quantification) - parts per million (mg/L)
  • GFAAS: uses graphite furnace; used in the measurement of selenium, cadmium, lead
• Atomic Emission Spectroscopy (AES):
  • Uses flame or inductively coupled plasma
  • Liquid sample converted into aerosol, delivered to source for atom excitation
  • Isolates specific wavelengths
  • Measures radiation intensity, photographic film (obsolete) replaced by photomultipliers and array-based detector systems.

Elemental Speciation

• Toxicity of the elements depends on their chemical form
• e.g., Arsenic:
  • Arsenobetaine: nontoxic form
  • Methylated forms: intermediate in toxicity
  • Inorganic arsenic (As(V), As(III)): highly toxic
• Hyphenated techniques: allow determination of elemental species
• Combination of two or more complementary analytical techniques.

Test your knowledge on trace minerals and their role in human health with this quiz. Covering topics from deficiencies to methods of analysis, this quiz will challenge your understanding of essential and nonessential trace elements. Perfect for students in nutrition or biomedical fields.