History
A history of exposure is the most critical aspect of diagnosing heavy metal toxicity. A complete history includes questions about potential occupational exposures, hobbies, recreational activities, and potential environmental exposure.
A complete dietary history should be taken, especially the ingestion of fish, seafood, and seaweed products since these will frequently be implicated as dietary sources of organic (and relatively nontoxic) mercury, arsenic, or both. The timing of ingestion relative to the collection of urine samples is critical to interpreting the results.
Herbal medications and dietary supplements are also potential sources of heavy metal exposure. Many Ayurvedic and Chinese patent medicines contain heavy metals.
Most acute presentations of heavy metal toxicity involve industrial exposure.
The ingestion of nonfood items such as paint chips, toys, and ballistic devices has also been implicated as the source of metal exposure in several cases.
Retained lead shot may ultimately lead to toxicity as well, although generally the shot must be bathed in relatively acidic body compartments such as the peritoneal fluid, pleural fluid, cerebrospinal fluid, or synovial fluid for significant absorption of metal ions to occur.
Physical Examination
The physical examination of patients with suspected metal toxicity should focus on the most commonly involved organ systems: the nervous, gastrointestinal, hematologic, [25] renal, and integumentary systems. See the Table in Overview for common presentations of acute and chronic exposures to specific metals.
Nausea, persistent vomiting, diarrhea, and abdominal pain are the hallmark of most acute metal ingestions. Dehydration is common. Metal salts are generally corrosive.
Encephalopathy, cardiomyopathy, dysrhythmias, acute tubular necrosis, and metabolic acidosis are also commonly seen with acute, high-dose exposures to most metals.
Patients with chronic metal toxicity tend to have more prominent involvement of the central and peripheral nervous systems. However, encephalopathy and peripheral neuropathies may occur within a few hours to days of acute high-dose exposure.
A classic presentation of chronic metal exposure includes anemia, Mees lines (horizontal hypopigmented lines across all nails), and subtle neurologic findings. These findings should prompt suspicion of heavy metal toxicity in any patient regardless of chief complaint.
Because lead toxicity is relatively common, any combination of GI complaints, neurologic dysfunction, and anemia should prompt a search for lead toxicity.
Tables
Metal |
Acute |
Chronic |
Toxic Concentration |
Treatment |
Arsenic |
Nausea, vomiting, "rice-water" diarrhea, encephalopathy, MODS, LoQTS, painful neuropathy |
Diabetes, hypopigmentation/ hyperkeratosis, cancer: lung, bladder, skin, encephalopathy |
24-h urine: ≥50 µg/L urine, or 100 µg/g creatinine |
BAL (acute, symptomatic) DMSA (succimer) DMPS (Europe) |
Bismuth |
Acute kidney injury; acute tubular necrosis |
Diffuse myoclonic encephalopathy |
No clear reference standard |
* |
Cadmium |
Pneumonitis (oxide fumes) |
Proteinuria, lung cancer, osteomalacia |
Proteinuria and/or ≥15 µg/ g creatinine |
* |
Chromium |
GI hemorrhage, hemolysis, acute renal failure (Cr6+ ingestion) |
Pulmonary fibrosis, lung cancer (inhalation) |
No clear reference standard |
NAC (experimental) |
Cobalt |
Beer drinker’s (dilated) cardiomyopathy |
Pneumoconiosis (inhaled); goiter |
Normal excretion: 0.1-1.2 µg/L (serum) 0.1-2.2 µg/L (urine) |
NAC CaNa2 EDTA |
Copper |
Blue vomitus, GI irritation/ hemorrhage, hemolysis, MODS (ingested); MFF (inhaled) |
vineyard sprayer’s lung (inhaled); Wilson disease (hepatic and basal ganglia degeneration) |
Normal excretion: 25 µg/24 h (urine) |
BAL D-Penicillamine DMSA (succimer) |
Iron |
Vomiting, GI hemorrhage, cardiac depression, metabolic acidosis |
Hepatic cirrhosis |
Nontoxic: < 300 µg/dL Severe: >500 µg/dL |
Deferoxamine |
Lead |
Nausea, vomiting, encephalopathy (headache, seizures, ataxia, obtundation) |
Encephalopathy, anemia, abdominal pain, nephropathy, foot-drop/ wrist-drop |
Pediatric: symptoms or [Pb] ≥45 µ/dL (blood); Adult: symptoms or [Pb] ≥70 µ/dL |
BAL CaNa2 EDTA DMSA (succimer) |
Manganese |
MFF (inhaled) |
Parkinson-like syndrome, respiratory, neuropsychiatric |
No clear reference standard |
* |
Mercury |
Elemental (inhaled): fever, vomiting, diarrhea, ALI; Inorganic salts (ingestion): caustic gastroenteritis |
Nausea, metallic taste, gingivo-stomatitis, tremor, neurasthenia, nephrotic syndrome; hypersensitivity (Pink disease) |
Background exposure "normal" limits: 10 µg/L (whole blood); 20 µg/L (24-h urine) |
BAL DMSA (succimer) DMPS (Europe) |
Nickel |
Dermatitis; nickel carbonyl: myocarditis, ALI, encephalopathy |
Occupational (inhaled): pulmonary fibrosis, reduced sperm count, nasopharyngeal tumors |
Excessive exposure: ≥8 µg/L (blood) Severe poisoning: ≥500 µg/L (8-h urine) |
* |
Selenium |
Caustic burns, pneumonitis, hypotension |
Brittle hair and nails, red skin, paresthesia, hemiplegia |
Mild toxicity: [Se] >1 mg/L (serum); Serious: >2 mg/L |
* |
Silver |
Very high doses: hemorrhage, bone marrow suppression, pulmonary edema, hepatorenal necrosis |
Argyria: blue-grey discoloration of skin, nails, mucosae |
Asymptomatic workers have mean [Ag] of 11 µg/L (serum) and 2.6 µg/L (spot urine) |
Selenium, vitamin E (experimental) |
Thallium |
Early: Vomiting, diarrhea, painful neuropathy, coma, autonomic instability, MODS Late: Alopecia, Mees lines, residual neurologic symptoms |
Alopecia, neuropathy |
Toxic: >3 µg/L (blood) |
MDAC Prussian blue |
Zinc |
MFF (oxide fumes); vomiting, diarrhea, abdominal pain (ingestion) |
Copper deficiency: anemia, neurologic degeneration, osteoporosis |
Normal range: 0.6-1.1 mg/L (plasma) 10-14 mg/L (red cells) |
* |
*No accepted chelation regimen; contact a medical toxicologist regarding treatment plan. MODS, multi-organ dysfunction syndrome; LoQTS, long QT syndrome; ALI, acute lung injury; ATN, acute tubular necrosis; ARF, acute renal failure; DMPS, 2,3-dimercapto-1-propane-sulfonic acid; CaNa2 EDTA, edetate calcium disodium; MDAC, multi-dose activated charcoal; NAC, N-acetylcysteine; DMSA (succimer), dimercaptosuccinic acid. |
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