Heavy Metal Screen

The heavy metal screen measures lead, mercury and arsenic (and often cadmium, thallium and others) in blood, urine, hair or nail, using inductively coupled plasma mass spectrometry (ICP-MS), atomic absorption spectrometry or anodic stripping voltammetry (point-of-care lead). The sample type depends on the metal and the time since exposure.

Lead is measured in whole blood (EDTA, trace element tube), which reflects exposure over the preceding 1 to 2 months. Mercury is measured in whole blood (recent exposure to methylmercury from fish), and in a 24-hour or spot urine (inorganic and elemental mercury).

Arsenic is measured in a 24-hour urine with speciation (inorganic arsenic and its metabolites, separate from the non-toxic arsenobetaine from seafood). Provoked (chelator challenge) urine collection is unreliable and not used.

Heavy metal exposure is a global public health problem. Lead causes an estimated 900 000 deaths a year, and over 800 million children (about one in three) have blood lead over 5 micrograms/dL, mostly in low- and middle income countries (paint, battery recycling, mining, petrol legacy, ceramics, cosmetics, traditional remedies, water pipes).

Arsenic in groundwater affects over 200 million people (Bangladesh, India, Vietnam, Argentina, Chile, parts of the United States). Mercury exposure arises from fish consumption, artisanal gold mining, dental amalgam, broken thermometers and skin lightening creams.

Components. Lead (blood). Mercury (blood and urine). Arsenic (urine, speciated). Cadmium (blood and urine). Thallium (urine) when clinically suspected. Associated tests: full blood count with film (basophilic stippling), zinc protoporphyrin, and renal function.

Indications. Children with developmental delay, abdominal pain, anaemia, pica, irritability or living in old housing, and screening at 12 and 24 months in high risk areas. Lead workers (batteries, smelting, paint, welding, plumbing, shooting ranges).

Unexplained peripheral neuropathy (motor, wrist drop), encephalopathy, abdominal colic, anaemia with basophilic stippling, hypertension, gout and renal impairment. Chronic skin lesions (hyperkeratosis, hyperpigmentation, Mees lines on nails), skin cancer, peripheral vascular disease and neuropathy with arsenic exposure.

Tremor, erethism, gingivitis, proteinuria and neurobehavioural symptoms (mercury). Alopecia, painful neuropathy and gastrointestinal illness (thallium). Occupational surveillance, contaminated food or water, and outbreaks. Pregnancy and breastfeeding with exposure.

Specimen. Whole blood 3 to 5 mL in a trace element tube (royal blue top, sodium heparin or EDTA, certified metal free), avoiding skin contamination (clean the skin with soap and water) and capillary samples contaminated by lead on fingers.

Urine in an acid washed metal free container: 24-hour collection (or spot sample corrected for creatinine); avoid seafood for 3 to 7 days before arsenic testing, and contrast media (gadolinium and iodine) and medication before testing. Hair and nails are for chronic exposure studies only and are prone to external contamination. Samples should be kept at 2 to 8 °C.

Lead (blood). Reference: under 3.5 micrograms/dL (0.17 micromol/L) in children, which is the level used to identify children with higher exposure than most; under 5 micrograms/dL in adults. There is no safe level of lead in children, and effects (lower IQ, attention problems, behaviour) occur under 5 micrograms/dL.

Adults: 5 to 9 micrograms/dL, remove from exposure source and review; 10 to 24, hypertension, renal and reproductive effects, remove from further exposure; 25 to 39, medical removal from work in many jurisdictions; 40 to 79, symptomatic risk, consider chelation if symptomatic; 80 or more (children 45 or more), chelation, and 70 or more with encephalopathy is a medical emergency.

Zinc protoporphyrin and free erythrocyte protoporphyrin rise with lead after weeks.

Mercury. Blood: under 10 micrograms/L (up to 20 with high fish consumption); methylmercury toxicity at over 20 micrograms/L, and neurological disease at over 50 to 100 micrograms/L. Urine (reflects inorganic and elemental mercury): under 10 micrograms/L, or 5 micrograms/g creatinine in the general population; occupational exposure over 20 to 35 micrograms/g creatinine; symptoms over 50 to 100 micrograms/g creatinine.

Arsenic. Urine total arsenic under 50 micrograms/L, but must be interpreted by speciation after avoiding seafood: inorganic arsenic plus monomethylarsonic acid plus dimethylarsinic acid under 20 micrograms/L; values over 50 micrograms/L indicate exposure, and over 100 micrograms/L chronic toxicity or acute poisoning.

Blood arsenic has a short half life and is of limited use except after acute ingestion. Hair arsenic over 1 microgram/g indicates exposure but is prone to external contamination.

Cadmium. Blood under 1 microgram/L in non-smokers (smokers up to 3 to 5 micrograms/L), urine under 1 microgram/g creatinine (kidney damage over 2 to 5).

Thallium. Urine under 1 microgram/L; over 20 micrograms/L indicates poisoning.

Interpretation.

• Lead: abdominal colic, constipation, anaemia with basophilic stippling, motor neuropathy, encephalopathy (children), hypertension and chronic kidney disease. Gum lead lines and microcytic anaemia mimic iron deficiency, and iron deficiency increases lead absorption.
• Arsenic acute poisoning: vomiting, rice water diarrhoea, hypotension, QT prolongation, then neuropathy, Mees lines and pancytopenia. Chronic: skin lesions, cancers (skin, lung, bladder), diabetes and cardiovascular disease.
• Mercury: elemental vapour causes tremor, gingivostomatitis, erethism and nephrotic syndrome; methylmercury causes ataxia, visual field loss, paraesthesiae and foetal brain damage; organic compounds and mercuric salts cause renal injury.
• Cadmium: proximal tubular dysfunction, low-molecular-weight proteinuria, osteomalacia and lung disease.
• Thallium: painful ascending neuropathy followed by alopecia after 2 to 3 weeks.
• Concentrations are interpreted with exposure history, symptoms and creatinine, and repeated after removal from the exposure source.

Critical values and findings needing immediate action.

• Blood lead 70 micrograms/dL or more, or any level with encephalopathy (seizures, coma, vomiting, ataxia) or severe abdominal colic: emergency admission, chelation (calcium disodium edetate with dimercaprol in encephalopathy, or succimer orally for lower levels), and removal from source.
• Acute arsenic poisoning: fluids, monitoring of QT and electrolytes, and chelation with dimercaprol or dimercaptosuccinic acid (succimer) for symptomatic patients.
• Elemental mercury inhalation with respiratory symptoms: oxygen, supportive care, chelation, and removal of exposure; acute mercuric salt ingestion needs gastrointestinal protection and chelation.
• Thallium poisoning: Prussian blue and haemodialysis for severe cases.
• Child with blood lead over 45 micrograms/dL: chelation and an urgent investigation of the home, parents' occupation, and siblings.
• Pregnant woman with high lead: nutritional support, calcium, removal from exposure, and obstetric advice; chelation only for severe poisoning.
• Public health notification and environmental investigation of lead, mercury or arsenic sources in clusters.

Interferences and pitfalls.

• Contamination (non-certified tubes, unwashed skin, dust, hair dyes, metal needles) causes false elevations; trace element tubes and rigorous skin cleaning are required.
• Seafood contains non-toxic organic arsenic (arsenobetaine) that raises total urine arsenic to several hundred micrograms/L; speciation or a seafood free period avoids false alarm.
• Gadolinium and iodinated contrast, and some medications (especially in the 48 to 96 hours before testing), interfere with ICP-MS measurements.
• Blood lead reflects recent exposure and falls as bone stores (half life 20 to 30 years) release; bone lead (X-ray fluorescence) reflects cumulative exposure but is a research tool.
• Chelator provoked urine testing, hair analysis for chronic fatigue or "detox" and unvalidated commercial screens produce misleading results and unjustified treatment.
• Urine spot samples need creatinine correction, and results vary with hydration and renal function.
• Chelation lowers blood levels and can mobilise metals into the brain; it is reserved for symptomatic patients or high levels, with monitoring of renal function and essential minerals.
• Iron, calcium and zinc deficiencies increase lead absorption, and nutrition is part of management.
• Other causes of neuropathy, anaemia and abdominal pain remain in the differential.
• Reporting, legal notification and source control (not chelation alone) determine outcome.

Special groups.

• Children: mouthing behaviour, pica, higher absorption (40 to 50% of ingested lead, against 10% in adults), and developing brain; screening at 12 and 24 months in high risk groups.
• Pregnancy and breastfeeding: lead mobilises from bone and crosses the placenta; methylmercury damages the foetal brain.
• Occupational groups: battery, smelter, scrap metal, painters, plumbers, glass and ceramic makers, miners, gold panners, and dental staff.
• Users of traditional remedies, cosmetics and spices: Ayurvedic and other medicines (lead, mercury, arsenic), kohl, skin lightening creams, and some imported spices.
• Regions: lead from battery recycling in low income cities, arsenic in groundwater in South Asia, and mercury from artisanal gold mining in Africa, South America and Asia.

Follow up tests. Full blood count and film, zinc protoporphyrin, iron studies, urea, creatinine and eGFR, urinalysis with low-molecular-weight proteins (beta-2 microglobulin), liver function, nerve conduction studies, abdominal radiograph (radio opaque material in children), long bone radiographs (lead lines), developmental assessment,

repeat levels after removal from source (every 1 to 3 months), tests on household members, environmental sampling (paint, water, soil), thyroid function (mercury), ECG (arsenic), skin examination and cancer screening (arsenic), and nutrition review.