Metallic Poisons: Arsenic, Lead & Mercury
Forensic Medicine · Toxicology · lean revision notes
Metallic Poisons: Arsenic, Lead & Mercury
Metallic (heavy-metal) poisons are a perennial NEET PG favourite, especially arsenic — the single most-tested metallic poison in forensic toxicology. This set hinges on classic clinical signs (Mees' lines, lead line, acrodynia), bedside chemical tests (Reinsch, Marsh), chelating antidotes, and postmortem appearances. Master the comparison tables below and you will clear almost every stem.
Classification of metallic poisons
Metallic poisons are heavy metals that disrupt cellular enzyme systems, chiefly by binding sulfhydryl (–SH) groups of enzymes, causing multi-system injury. They are broadly grouped as:
| Group | Examples | Hallmark |
|---|---|---|
| Classical "irritant" metallics | Arsenic, mercury, lead, copper, antimony | GI + neuro toxicity |
| Industrial/occupational | Thallium, cadmium, manganese, aluminium | Chronic exposure |
| Modern/medicinal | Iron, lithium | Therapeutic overdose |
In forensic medicine, arsenic, lead and mercury form the high-yield triad. Arsenic is historically called the "poison of fools / King of poisons / Poison of Kings" because it is cheap, tasteless, odourless, colourless and resembles sugar — ideal for homicide.
High-yield: The common mechanism of arsenic, mercury and many heavy metals is inhibition of sulfhydryl (–SH / thiol) containing enzymes, especially pyruvate dehydrogenase. Chelators (BAL, DMSA, penicillamine) work by donating –SH groups to compete for the metal.
ARSENIC
Forms & toxicology
- Most common toxic form: arsenic trioxide (As₂O₃, white arsenic, "Sankhya/Somalkhar") — tasteless, odourless white powder.
- Arsine gas (AsH₃) — most toxic form; produces massive intravascular haemolysis → haemoglobinuria → renal failure (a favourite distractor). Garlic odour.
- Fowler's solution = potassium arsenite (1% — old tonic).
- Trivalent (As³⁺) more toxic than pentavalent (As⁵⁺). As³⁺ binds –SH; As⁵⁺ uncouples oxidative phosphorylation by substituting phosphate ("arsenolysis").
Acute arsenic poisoning
Two clinical patterns:
- Gastrointestinal (fulminant) type — most common. Onset within ~1 hour. Burning/colicky abdominal pain, intense thirst, "rice-water stools" (mimics cholera — important differential), projectile vomiting, garlicky odour of breath/stools. Leads to dehydration, shock, oliguria.
- Narcotic type — rare; rapid CNS depression, drowsiness, coma, death without prominent GI signs.
High-yield: Acute arsenic mimics cholera ("cholera-like" rice-water stools) — but arsenic causes severe abdominal pain and is preceded by a metallic/garlicky taste, whereas cholera is painless.
Chronic arsenic poisoning (most exam-relevant)
Classic multi-system picture:
- Skin: "Rain-drop pigmentation" (hyperpigmentation), hyperkeratosis of palms and soles, arsenical keratoses → squamous cell carcinoma; Bowen's disease.
- Nails: Mees' lines (Aldrich-Mees lines) — transverse white bands across nails (also seen in thallium poisoning, chemotherapy, renal failure).
- Neuro: Symmetrical, distal sensorimotor peripheral neuropathy (glove-and-stocking, painful), the commonest chronic neuro effect.
- Eyes/face: Periorbital oedema, conjunctivitis, lacrimation.
- Haematology: Anaemia, basophilic stippling, pancytopenia.
- Carcinogen: Lung, skin, bladder, liver (angiosarcoma) cancers; arsenic is a recognised human carcinogen.
High-yield: Mees' lines appear ~6 weeks after exposure and grow out with the nail (~0.1 mm/day) — useful to date exposure. Most classically associated with arsenic (also thallium).
Diagnosis & investigations
- Reinsch test — bedside screening: copper foil/wire dipped in acidified (HCl) urine/stomach contents → silvery-grey/black coating if arsenic, antimony, mercury or bismuth present. Sensitive but not specific.
- Marsh test — classic, very sensitive confirmatory test for arsenic (forms arsine → silver-black "arsenic mirror"). Historically landmark.
- Gutzeit test — qualitative.
- Confirmation / quantification: Atomic absorption spectrophotometry (AAS); hair and nails are the best long-term repositories — arsenic deposits in keratin (hair root concentration estimates timing; segmental hair analysis dates exposure).
- 24-hour urinary arsenic = best indicator of recent exposure (avoid seafood 48 h before — organic arsenobetaine causes false elevation).
High-yield: Arsenic is deposited in hair, nails and skin (keratin-rich tissues) and in bone; it can be detected in hair/nails long after death — exhumed bodies remain testable for months to years.
Management / antidote
- Decontamination, IV fluids, correct electrolytes.
- Chelation: Dimercaprol (BAL — British Anti-Lewisite) is the classic antidote for acute arsenic. Oral DMSA (succimer) and DMPS (unithiol) are now preferred for stable/chronic cases.
- BAL is contraindicated in arsine-induced haemolysis (no benefit) and in iron/cadmium/selenium poisoning (forms toxic complexes).
Postmortem findings (arsenic)
- "Red velvety / red velvet" appearance of gastric mucosa (sub-mucosal congestion + petechiae) — classic.
- Yellow streaky fatty change of liver, heart, kidney.
- Arsenic delays putrefaction and acts as a preservative → body well-preserved at exhumation (forensically valuable).
- Sub-pleural petechial haemorrhages.
High-yield: Arsenic, antimony and zinc chloride act as tissue preservatives and delay decomposition. So an unexpectedly well-preserved exhumed body should raise suspicion of arsenical poisoning.
LEAD (Plumbism / Saturnism)
Sources & forms
- Inorganic lead: paints (old housing), battery work, pottery glaze, ceramic, surma/sindoor/kohl (Indian eye cosmetics — important in paediatric exams), Ayurvedic preparations, lead pipes.
- Organic lead: tetraethyl lead (anti-knock petrol additive) → predominantly CNS toxicity, mania, encephalopathy.
Pathophysiology
Lead inhibits multiple enzymes of haem synthesis:
- ALA dehydratase (δ-aminolaevulinic acid dehydratase) and ferrochelatase are the key inhibited enzymes.
- Result → ↑ δ-ALA and coproporphyrin in urine, ↑ free erythrocyte protoporphyrin (FEP)/ Zinc protoporphyrin (ZPP), and microcytic hypochromic anaemia with basophilic stippling.
Clinical features (chronic plumbism)
- Lead line (Burton's line): stippled bluish-black line on gingival margin due to subepithelial deposition of lead sulphide (needs poor oral hygiene/bacterial H₂S). Distinguish from punctate basophilia.
- Lead colic — severe, paroxysmal abdominal pain, constipation (a classic "acute abdomen" mimic).
- Wrist drop / foot drop: peripheral motor neuropathy affecting extensors — radial nerve (wrist drop) classically; predominantly motor (contrast arsenic = sensory).
- Lead encephalopathy: mainly in children — irritability, ataxia, seizures, raised ICP, coma. Most dangerous manifestation.
- Anaemia with basophilic stippling (punctate basophilia) of RBCs.
- Lead lines in bones (radiology): dense metaphyseal bands at growing ends of long bones in children.
- Nephropathy (Fanconi-like), gout ("saturnine gout"), infertility.
| Feature | Lead | Arsenic |
|---|---|---|
| Neuropathy | Motor (wrist/foot drop) | Sensory (glove-and-stocking) |
| Anaemia | Microcytic + basophilic stippling | Normocytic, also stippling |
| Mucosal/skin sign | Burton's (gingival) line | Rain-drop pigmentation, Mees' lines |
| GI feature | Lead colic + constipation | Rice-water diarrhoea |
| Enzyme | Haem synthesis (ALA-D, ferrochelatase) | –SH enzymes, pyruvate DH |
Diagnosis
- Blood lead level (BLL) — definitive; CDC reference value for action in children currently ≥3.5 µg/dL (older texts: 5 / 10 µg/dL).
- ↑ Urinary δ-ALA and coproporphyrin; ↑ ZPP/FEP.
- Basophilic stippling on peripheral smear (non-specific).
Management / chelation
Stepwise approach to symptomatic/encephalopathic lead poisoning:
Remove source → supportive (control seizures, ICP) → chelate → re-check BLL
- Encephalopathy / very high BLL: BAL first, followed by calcium disodium EDTA (CaNa₂EDTA). (BAL is started first because EDTA alone can redistribute lead into the brain.)
- Moderate / outpatient: oral DMSA (succimer) — drug of choice in children for moderate levels.
- Penicillamine — older oral option.
High-yield: In lead encephalopathy give BAL before CaNa₂EDTA. EDTA alone can worsen cerebral lead by mobilising it; BAL crosses into CNS and prevents this.
Postmortem (lead)
- Pale, anaemic tissues; blue lead line on gums; lead deposits demonstrable in liver, kidney, bone (>90 % body lead is in bone as triphosphate).
MERCURY (Hydrargyria / Mercurialism)
Forms (toxicity depends on form)
| Form | Example | Main toxicity |
|---|---|---|
| Elemental (metallic) | Thermometers, dental amalgam, vapour | Inhaled vapour → CNS (erethism, tremor); GI absorption negligible if swallowed |
| Inorganic salts | Mercuric chloride (corrosive sublimate, HgCl₂) | Corrosive GI + acute tubular necrosis (renal) |
| Organic | Methylmercury (fish, Minamata) | CNS, teratogen, bioaccumulates |
High-yield: Swallowed metallic mercury (e.g., broken thermometer) is virtually non-toxic because it is poorly absorbed from the gut. It is the vapour that is dangerous. Mercuric chloride, by contrast, is highly corrosive and nephrotoxic.
Acute poisoning (mercuric chloride)
- Acrid metallic taste, burning throat, "ashy-grey" coagulative burns of oral mucosa.
- Bloody vomiting/diarrhoea, intense salivation.
- Mercurial stomatitis, metallic taste, blue line on gums (resembles lead line).
- Renal failure due to acute tubular necrosis — characteristic and often fatal.
- Later: mercurial nephrosis / membranous nephropathy (nephrotic syndrome).
Chronic mercury poisoning — the classic triad
- Erethism — neuropsychiatric: shyness, irritability, insomnia, loss of confidence, depression, emotional lability ("Mad Hatter" — hat-makers used mercuric nitrate).
- Tremors — intention tremor, "hatter's shakes", "Danbury tremor"; may progress to concussio mercurialis.
- Gingivostomatitis / salivation — excessive salivation (ptyalism), gum line, loosening of teeth.
- Acrodynia (Pink disease / Feer's disease): seen in children — painful pink/red, swollen, peeling hands and feet, photophobia, irritability, hypertension, excessive sweating. Hypersensitivity reaction to mercury (e.g., teething powders).
- Minamata disease: methylmercury (industrial discharge into Minamata Bay, Japan) → ataxia, dysarthria, constriction of visual fields, sensory disturbance; congenital Minamata (transplacental) → cerebral palsy-like picture. Bioaccumulation up the food chain.
High-yield: Remember the chronic mercury triad — Erethism + Tremor + Gingivostomatitis. Mnemonic for the picture of the Mad Hatter.
Diagnosis
- 24-hour urinary mercury (inorganic/elemental exposure).
- Whole-blood mercury — better for organic/methylmercury (and recent fish exposure).
- Hair analysis for methylmercury (chronic).
Management / antidote
- Acute inorganic (mercuric chloride): Dimercaprol (BAL) is the antidote; or DMSA/DMPS. Supportive — dialysis if renal failure.
- Organic/methylmercury: oral DMSA (succimer) preferred; BAL is contraindicated (it redistributes methylmercury into the brain, worsening neurotoxicity).
- "Egg white / albumin / milk" historically given orally to precipitate mercuric chloride.
High-yield: Do NOT give BAL in methylmercury (organic) poisoning — it increases brain mercury. Use oral succimer (DMSA) instead. BAL is, however, useful for inorganic/elemental mercury.
Postmortem (mercuric chloride)
- Greyish corrosion/ulceration of mouth, oesophagus, stomach ("ashy grey").
- Necrotic, swollen kidneys, haemorrhagic colitis (mercury is excreted via colon → ulcerative colitis-like lesions, "mercurial colitis").
Chelating agents — the master table
| Chelator | Best for | Key contraindication |
|---|---|---|
| Dimercaprol (BAL) | Acute arsenic, inorganic/elemental mercury, lead (with EDTA) | Methylmercury, arsine, iron, cadmium, selenium; G6PD deficiency caution |
| DMSA (succimer, oral) | Moderate lead (children), arsenic, methylmercury | — |
| DMPS (unithiol) | Arsenic, mercury | — |
| CaNa₂EDTA | Lead | Give after BAL in encephalopathy; nephrotoxic |
| D-Penicillamine | Lead, copper (Wilson's), arsenic | Penicillin allergy |
| Desferrioxamine | Iron, aluminium | — |
| Prussian blue | Thallium, radioactive caesium | — |
High-yield: BAL is contraindicated in iron, cadmium, selenium and methylmercury poisoning — recurring NEET PG fact. Mnemonic: "I See Some Metal" is wrong for BAL → Iron, Cadmium, Selenium, Methylmercury = NO BAL.
Key differentials & quick discriminators
- Basophilic stippling → think lead (also arsenic, sideroblastic anaemia, thalassaemia, pyrimidine-5'-nucleotidase deficiency).
- Transverse white nail bands (Mees' lines) → arsenic > thallium.
- Alopecia (hair loss) + peripheral neuropathy + Mees' lines → thallium (the great mimic of arsenic; antidote = Prussian blue).
- Garlic odour of breath → arsenic (also organophosphate, phosphorus, thallium, DMSO).
- Blue gum line → lead (Burton's) or mercury — distinguish by other features.
- Rice-water stools → arsenic vs cholera (arsenic = painful).
- Nephrotoxicity prominent → mercury (ATN) and chronic lead.
| Sign | Metal |
|---|---|
| Mees' lines | Arsenic |
| Burton's line (gum) | Lead |
| Erethism / acrodynia | Mercury |
| Wrist drop | Lead |
| Rain-drop pigmentation | Arsenic |
| Alopecia + neuropathy | Thallium |
| Itai-itai (bone pain, osteomalacia) | Cadmium |
Recently asked / exam angle
- Reinsch test — what does the copper foil turning black indicate? (Arsenic/mercury/antimony/bismuth). Frequently tested as a one-liner.
- Antidote matching — BAL ↔ arsenic; CaNa₂EDTA ↔ lead; Prussian blue ↔ thallium; desferrioxamine ↔ iron. Almost guaranteed in a "match the following" stem.
- BAL contraindications (iron/cadmium/selenium/methylmercury) and BAL before EDTA in lead encephalopathy — repeatedly examined.
- Arsenic as a preservative / well-preserved exhumed body — classic forensic single-best-answer.
- Acute arsenic mimicking cholera (rice-water stools) — clinical vignette.
- Mees' lines vs Aldrich-Mees (same thing) and their association with arsenic/thallium.
- Acrodynia / Pink disease / erethism / Minamata — mercury identification questions.
- Lead = motor neuropathy (wrist drop); arsenic = sensory neuropathy — discriminator MCQ.
- Arsine gas → haemolysis & haemoglobinuria, and BAL ineffective — a tricky stem.
- Best sample for chronic arsenic exposure = hair/nails; recent = 24-h urine.
Rapid revision
- Arsenic trioxide = white, tasteless, odourless → "poison of fools / King of poisons."
- Acute arsenic → rice-water stools + abdominal pain (cholera mimic); garlicky breath.
- Chronic arsenic → Mees' lines, rain-drop pigmentation, palmar hyperkeratosis, sensory neuropathy, basophilic stippling.
- Arsenic detected best in hair & nails (keratin); delays putrefaction → preservative.
- Reinsch test = bedside screen; Marsh test = sensitive confirmatory (arsenic mirror).
- Arsine (AsH₃) = most toxic form → massive haemolysis; BAL useless.
- Lead → Burton's gum line, wrist/foot drop (motor neuropathy), lead colic, basophilic stippling, encephalopathy in children.
- Lead inhibits ALA-dehydratase & ferrochelatase; ↑ urinary δ-ALA & coproporphyrin, ↑ ZPP.
- Lead encephalopathy → BAL FIRST, then CaNa₂EDTA; moderate → oral DMSA.
- Swallowed metallic mercury is non-toxic; vapour and mercuric chloride (corrosive + ATN) are dangerous.
- Chronic mercury triad = Erethism + Tremor + Gingivostomatitis (Mad Hatter); children = acrodynia (Pink disease); fish/Minamata = methylmercury.
- BAL contraindicated in iron, cadmium, selenium, methylmercury; antidotes — arsenic→BAL, lead→EDTA, thallium→Prussian blue, iron→desferrioxamine.