Electrolytes and Water Balance
Trace Elements
Trace elements serve either physiology or pathology. Some are cofactors in metalloenzymes and metalloproteins, and their deficiency produces recognizable syndromes. Others matter chiefly because exposure poisons. Quantitative measurement depends on element-specific spectroscopic methods, and every result depends on collection that keeps environmental background out of the specimen.1
Measurement methods and specimen integrity
Flame or graphite-furnace atomic absorption spectroscopy (FAAS/GFAAS), atomic emission spectroscopy (ICP-AES), and inductively coupled plasma mass spectrometry (ICP-MS) are the principal quantitative methods. They differ in sensitivity, elemental coverage, and interference profile. ICP-MS combines high sensitivity with broad multielement coverage but generally carries higher instrument cost. FAAS has lower instrument cost and simpler operation but measures one element at a time with lower sensitivity. GFAAS increases sensitivity at the cost of throughput. Spectral overlap, such as isobaric or polyatomic interferences like 40Ca/40Ar, and matrix effects from viscosity or ionization require calibrator and control matrix-matching or an alternate isotope. The instrument engineering behind these methods belongs to the Laboratory Operations instrumentation topics.1
Specimen integrity is the dominant preanalytic issue. Trace-element concentrations approach environmental background levels, so collection requires royal-blue-top metal-free tubes, avoidance of rubber-stopper contamination from aluminum silicate, and clean-room handling. For the toxicologically important metals, arsenic, cadmium, lead, and mercury, deficiency is no concern; the toxicology module covers exposure and poisoning testing.
The essential and clinically measured elements
| Element | Key physiology | Deficiency | Toxicity | Reference interval |
|---|---|---|---|---|
| Iron (Fe) | Oxygen transport in hemoglobin and myoglobin and redox enzymes. Roughly 10% of dietary intake is absorbed. Iron requires reduction to Fe2+ for uptake and travels bound to transferrin. | Anemia, microcytic with low MCHC; affects about 15% of the world population | Hereditary hemochromatosis, autosomal recessive iron overload damaging liver, endocrine organs, and heart; secondary overload from transfusion or dietary iron | Serum Fe: males 50–150 µg/dL, females 35–145 µg/dL; TIBC 250–400 µg/dL; saturation 14–50%; ferritin: males 24–336 µg/L, females 11–307 µg/L |
| TIBC and transferrin | Estimate TIBC from transferrin only with a laboratory-validated conversion factor; normally only about one-third of transferrin binding sites are saturated | Low transferrin saturation with low ferritin indicates iron deficiency | High saturation with high ferritin indicates overload | Transferrin 270 mg/dL gives TIBC = 270 × 1.18 = 318.6 µg/dL using the example’s laboratory-validated factor 1.18; serum iron 40 µg/dL gives saturation = 40/318.6 × 100 = 12.6%, below the displayed 14% lower limit and consistent with iron deficiency |
| Copper (Cu) | Cofactor for ceruloplasmin, cytochrome-c oxidase, superoxide dismutase, tyrosinase, and lysyl oxidase. About 50 to 80% of dietary intake is absorbed; 98% is excreted in bile. | Neutropenia, hypochromic anemia, bone and connective-tissue defects, hypopigmentation; the extreme form is Menkes disease, X-linked and fatal, with kinky hair | Wilson’s disease, autosomal recessive accumulation causing neurologic disease, liver dysfunction, and corneal Kayser-Fleischer rings; ingestion or occupational exposure causes GI, hepatic, renal, and hemolytic injury | 75–145 µg/dL |
| Zinc (Zn) | Cofactor for more than 300 enzymes across all major biochemical classes; second only to iron in trace-element abundance | Growth retardation, testicular atrophy, delayed skeletal maturation, impaired taste, acrodermatitis enteropathica, the severe malabsorption form | Relatively nontoxic; high dose induces copper deficiency through competitive absorption and can cause GI upset and hyperglycemia; fume inhalation causes metal fume fever | Age >11 y: 0.66–1.10 µg/mL |
| Selenium (Se) | Component of glutathione peroxidase and thyroid deiodinase enzymes; antioxidant role | Cardiomyopathy called Keshan disease, endemic in China; osteoarthritis called Kashin-Beck disease; increased infection susceptibility | Nail and hair changes, GI upset, garlicky breath, neurologic symptoms at high dose; selenium sulfide specifically is a probable carcinogen | Age >18 y: 150–241 ng/mL |
| Chromium (Cr) | Historically classified as an essential trace element proposed to potentiate insulin action; its essentiality in humans is now questioned | No specific deficiency syndrome has been established in healthy people | Cr6+ from industrial exposure is far more toxic than Cr3+: dermatitis, respiratory irritation, carcinogenicity, and renal tubular injury with chronic low-dose exposure | <1.0 ng/mL |
| Manganese (Mn) | Cofactor for arginase, pyruvate carboxylase, and mitochondrial superoxide dismutase | Rare; associated with clotting defects, dermatitis, and growth or bone effects in children | Chronic occupational exposure causes a Parkinsonian syndrome called manganese madness | <2.4 ng/mL |
| Molybdenum (Mo) | Molybdopterin cofactor for xanthine oxidase, aldehyde oxidase, and sulfite oxidase | Very rare; inherited molybdenum cofactor deficiency causes seizures and early death | Rare; high exposure linked to hyperuricemia and gout | 0.3–2.0 ng/mL |
| Aluminum (Al) | No known essential physiologic role | No deficiency state | Encephalopathy, osteomalacia or aplastic bone disease, and microcytic anemia, classically in dialysis patients exposed to aluminum-contaminated dialysate or oral aluminum-containing phosphate binders | 0–6 ng/mL |
Reference intervals are method- and laboratory-specific; each laboratory verifies its own values for its population and instruments under CLIA. The worked TIBC conversion factor is the example’s stated laboratory-validated value, and other laboratories use their own factor. The chromium-essentiality statement and the Cr(VI) toxicity profile follow the NIH Office of Dietary Supplements and NIOSH positions.2
Iron studies in context
Serum iron, TIBC, transferrin saturation, and ferritin form a panel whose interpretation depends on inflammation, diurnal variation, and recent intake. The anemia module in Hematology covers the disease interpretation of iron studies, and the appendix contains the calculation drill for saturation and TIBC. Chronic alcohol use also raises transferrin’s carbohydrate-deficient isoforms. The alcohol biomarker CDT exploits this change, and the toxicology module covers CDT.
References
- Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023.
- National Institutes of Health Office of Dietary Supplements. Chromium: health professional fact sheet. Accessed August 31, 2026. Chromium essentiality in humans is currently questioned; Cr(VI) compounds are recognized occupational respiratory carcinogens (NIOSH, Occupational Exposure to Hexavalent Chromium).