Arsenic Toxicology - Comprehensive Forensic Medicine Notes

1. Introduction

• DiMaio's Forensic Pathology, 3rd Ed., p.507
• Essentials of Forensic Medicine & Toxicology, 36th Ed., p.494

2. Chemical Forms

• Essentials of FMT, p.494; P.C. Dikshit FMT, p.467

3. Mechanism of Toxicity

1. Inhibits sulfhydryl (SH) enzyme groups - particularly pyruvate oxidase and mitochondrial enzymes, blocking cellular respiration
2. Uncouples oxidative phosphorylation (arsenate specifically) - interferes with glycolysis
3. Capillary endothelial damage - increases vascular permeability → tissue edema + hemorrhage, especially in the intestine
4. Fatty degeneration of liver, heart, and kidneys
5. Renal tubular necrosis
6. Peripheral nerve damage - disintegration of the axis cylinder (axonal neuropathy) with fragmentation and resorption of myelin

• P.C. Dikshit FMT, p.467-468
• Essentials of FMT, p.494 (Essentials 36th Ed.)

4. Routes of Absorption

• Oral ingestion (most common)
• Inhalation of arsenic gas
• Dermal absorption (arsenite)
• Introduction into the rectum or vagina
• Parenteral

5. Fatal Dose and Fatal Period

6. Clinical Presentations

A. Fulminant Type

• Marked capillary dilation (especially splanchnic)
• Profound fall in blood pressure
• Peripheral vascular failure / shock
• Direct cardiotoxicity

B. Gastroenteric Type (Most Common)

• Sweetish metallic taste in the mouth
• Slight garlicky odor to breath and feces
• Xerostomia (dry mouth), dysphagia
• Intense thirst, severe projectile vomiting (contains mucus, bile, blood)
• Colicky abdominal pain
• Profuse diarrhea with rice-water stools (initially dark, bloody; later watery, odorless - resembles cholera)
• Tenesmus and anal irritation

• Cardiovascular: generalized vasodilation, hypovolemia, prolonged QT interval, non-specific ST-T changes, ventricular tachycardia/fibrillation, acute cardiomyopathy, subendocardial hemorrhages
• Renal: oliguria, proteinuria, hematuria, uremia, acute tubular necrosis
• Hepatic: fatty infiltration; hepatic failure if patient survives initial insult
• CNS: headache, vertigo, hyperthermia, tremors, convulsions, coma, hypoxic encephalopathy
• Hematologic: anemia, leukopenia, thrombocytopenia, mild eosinophilia

C. Narcotic Type

• Minimal GI symptoms
• Giddiness, formication, muscle tenderness, delirium, coma, death
• Rarely: complete paralysis of extremities
• Essentials of FMT 36th Ed., p.494-510; P.C. Dikshit FMT, p.467-469

7. Arsenic Poisoning vs. Cholera (Differential Diagnosis)

• Essentials of FMT 36th Ed., Table 27.1, p.494

8. Subacute Arsenic Poisoning

• Dysphagia
• Cough
• Foul-smelling, dry, congested tongue
• Bloody motions

9. Chronic Arsenic Poisoning

Skin (Earliest and Most Characteristic Feature):

• Persistent erythematous flushing (earliest sign - cutaneous capillary dilation)
• Raindrop type pigmentation - finely mottled brown, mostly on flexures, temples, eyelids, neck
• Hyperkeratosis of palms and soles
• Desquamation
• Irregular thickening of nails
• Aldrich-Mees lines (= Mee's lines) - transverse white bands on fingernails, seen months after exposure, persist up to 1 year
• Patchy or diffuse alopecia (hair loss)
• Periorbital/facial/ankle edema

Long-term skin complications:

• Bowen's disease (indicates systemic neoplastic processes)
• Skin cancers (arsenic is a proven carcinogen)

Neurological (Hallmark of Arsenic Poisoning):

• Symmetrical sensorimotor polyneuropathy - often resembles Guillain-Barré syndrome
• Distribution: stocking-glove pattern (asymmetric, distal)
• Predominant features: paresthesia, numbness, pain (especially soles of feet)
• Progressive: muscular atrophy → paralysis, ataxia
• Encephalopathy: severe headache, personality disturbance, convulsions, coma

Hematologic:

• Normochromic, normocytic anemia (partly from hemolysis)
• Leukopenia and thrombocytopenia
• Mild eosinophilia
• Karyorrhexis (bizarre nuclear forms on bone marrow exam)
• Megaloblastic picture (from folate metabolism interference)
• Basophilic stippling

Other features:

• Nausea, vomiting, diarrhea, irritability
• Conjunctivitis, photophobia, pharyngitis
• Chronic renal failure
• CNS: polyneuritis, anesthesias, paresthesia, encephalopathy
• P.C. Dikshit FMT, p.469-470; Essentials of FMT 36th Ed., p.510; DiMaio's Forensic Pathology, p.507

10. Post-Mortem Findings

External:

• Sunken eyeballs
• Cyanosed skin
• Shrunken body (due to dehydration)

Internal (Acute Poisoning):

• Mucosa swollen, edematous, red velvet appearance (characteristic)
• Lines of redness along the walls
• Curved lines of submucous hemorrhages
• Petechiae scattered over mucosa
• Large submucosal and subperitoneal hemorrhages
• Small acute ulcerations/large erosions (especially at pyloric end)
• Sticky mucus covering mucosa - arsenic particles may be visible

• Entire small intestine may be reddened (if individual lives 1-2 days)
• Pseudomembrane formation may occur
• Dilated, thickened mucosa

• Subendocardial petechial hemorrhages of the ventricle - typical of arsenic poisoning (pathognomonic; also seen in phosphorus, barium, mercury poisoning, heat stroke)
• Fatty deposits (after a few days)

• Congested, enlarged, cloudy swelling
• Fatty infiltration → severe necrosis over days
• Jaundice

• Congested, enlarged
• Acute tubular necrosis

• Congested with subpleural ecchymoses

• Edema with patchy necrosis
• Hemorrhagic encephalitis
• Congested meninges

• Essentials of FMT 36th Ed., p.510-511; P.C. Dikshit FMT, p.469; DiMaio's Forensic Pathology, p.507

11. Diagnosis

Urine:

• Normal: < 0.2 mg/L
• Poisoning: > 0.1-1 mg/L
• Proteinuria, casts, albuminuria present

Blood:

• Normal level: ~100 mcg/L
• Fatal blood levels: 0.2-10 mg/L
• Moderate anemia and leukopenia (2000-5000/mm³)
• Exception: Arsine causes leukocytosis and mild eosinophilia

Hair and Nails:

• Normal: < 0.05 mg/100 g hair; < 1 mg/100 g nails
• Diagnostic: > 3 ppm or > 100 mg/100 g of specimen = arsenic poisoning
• Analysis of hair can be performed years after death (useful in exhumed bodies)
• Arsenic is incorporated into growing hair at ~1 cm/month - allows timing of exposure

Liver function tests:

• Raised bilirubin and alkaline phosphatase
• Decreased protein metabolism
• Urobilinogen in urine

CSF: Normal

Definitive Diagnosis (important caveat):

• P.C. Dikshit FMT, p.469-470; Henry's Clinical Diagnosis & Management by Laboratory Methods

12. Treatment

Immediate:

1. Empty stomach - emetics (NOT tartar emetic; NOT copper sulphate as it forms copper arsenite)
2. Gastric lavage with:
   • Freshly prepared hydrated ferric oxide (forms insoluble ferric arsenite)
   • Or 1% sodium thiosulphate in water
   • Dialyzed iron as substitute
3. Whole bowel irrigation
4. Nasogastric suction (arsenic is re-secreted into GI tract)
5. Alkalis should NOT be given (increase arsenic solubility)
6. Butter/greasy substances to prevent absorption (demulcents)
7. Castor oil or magnesium sulfate (prevent intestinal absorption)

Chelation Therapy (most important):

• BAL (British Anti-Lewisite / Dimercaprol) - chelator of choice for acute arsenic poisoning
  • IM injection: 400-800 mg on day 1; 200-400 mg on days 2-3 (q4h); 100-200 mg in divided doses for 7-10 days
  • Stop when 24-hr urine arsenic < 50 mg
  • BAL is ineffective in arsine gas poisoning
• DMSA (Succimer) or DMPS - oral alternatives; superior to BAL if available
• Penicillamine - may be used with BAL; 100 mg/kg/day up to 1-2 g in 4 divided doses for 5 days
• Chelation should start as early as possible WITHOUT waiting for lab confirmation (Rosen's EM)

Supportive:

• Glucose-saline with sodium bicarbonate (combat shock, improve alkali reserve)
• Hemodialysis or exchange transfusion for renal failure
• Demulcents (lessen irritation)
• Essentials of FMT 36th Ed., p.511; P.C. Dikshit FMT, p.470; Rosen's Emergency Medicine, p.3977

13. Medico-Legal Importance

• Most common mode: homicidal (historically called "inheritance powder") - given in repeated small doses due to tasteless and odorless nature
• Also: accidental (insecticides, pesticides) and suicidal
• The body is well-preserved after death - arsenic acts as a natural preservative (inhibits putrefaction)
• Arsenic from contaminated soil may enter a buried body (Reinsch test for exhumed bodies)
• Hair analysis can detect arsenic exposure many years after death
• Napoleon Bonaparte's death is attributed partly to chronic arsenic poisoning (high arsenic in preserved hair samples)
• Arsenic is a Group 1 carcinogen - associated with skin, lung, bladder, liver, and kidney cancers

14. Key Points Summary