Arsenic Poisoning

Sources of Exposure

• Pesticides/insecticides: Paris green (copper arsenite), calcium arsenate, lead arsenate
• Contaminated groundwater (most common worldwide cause)
• Industrial exposure: smelting, semiconductor manufacturing, wood preservatives (CCA)
• Homicidal/suicidal ingestion: arsenic trioxide
• Medicinal: arsenic trioxide is used in acute promyelocytic leukemia (APL) treatment
• Arsine gas (AsH₃): occupational inhalation hazard
• Food: seafood contains organic arsenic (less toxic)

Mechanism of Toxicity

1. Sulphydryl (SH) group binding - reversibly combines with SH groups in tissue proteins and enzymes, disrupting cellular metabolism
2. Inhibition of pyruvate dehydrogenase and other enzymes essential for the Krebs cycle (arsenite binds lipoic acid)
3. Arsenate uncoupling - pentavalent arsenate substitutes for phosphate in oxidative phosphorylation, uncoupling ATP synthesis
4. Capillary toxin - dilates and damages capillaries, causing transudation of fluid, especially in the gut
5. Direct organ damage: fatty degeneration of liver, renal tubular necrosis, peripheral axonal neuropathy with myelin fragmentation

Pharmacokinetics

• Absorption: oral (main route), dermal (arsenite), inhalation (arsine gas), rectal/vaginal
• Distribution: early - highest in liver, then kidneys and spleen. Arsenic has a high affinity for keratin, accumulating in hair and nails within hours. It replaces phosphorus in bone. Does NOT cross the blood-brain barrier easily but crosses the placenta.
• Elimination: mainly renal (as methylated arsenic - monomethylarsine, dimethylarsine), also in feces, bile, sweat, milk. Urinary excretion is continuous for ~10-12 days.

Acute Arsenic Poisoning

Fatal Dose and Period

• Fatal dose: ~180 mg of arsenic trioxide (range varies with compound and tolerance)
• Fatal period: 12-48 hours (can be fatal within 2-3 hours)
• Symptoms typically begin within 30 minutes of oral ingestion

Clinical Features

Delayed Features (2-8 weeks post-acute)

• Hair loss (alopecia)
• Aldrich-Mees lines (white transverse striae on nail plates, 1-2 mm wide, appear ~5 weeks post-exposure)
• Sensorimotor peripheral neuropathy (ascending, glove-and-stocking distribution)
• Pancytopenia (within 1 week), basophilic stippling of erythrocytes

Differential Diagnosis: Arsenic vs. Cholera

Chronic Arsenic Poisoning

Skin Changes (most characteristic)

• Raindrop pigmentation: finely mottled brown hyperpigmentation on flexures, temples, eyelids, neck - persists for months
• Hyperkeratosis of palms and soles
• Dry, scaly desquamation with hyperpigmentation over trunk and extremities

Mees Lines (Aldrich-Mees Lines)

System-by-System Chronic Effects

Diagnosis

1. Urine arsenic (test of choice): Monomethylarsine and dimethylarsine appear in urine within 24 hours of ingestion
   • Urinary arsenic >200 mcg/24 hr = indicative of toxic exposure
   • Normal urine arsenic: <0.03 mcg/L
   • Acute poisoning: 24-hr excretion >100 mcg
2. Blood arsenic: only useful very early (arsenic disappears rapidly from blood); not recommended for diagnosis except in anuric patients
3. Hair and nails: arsenic appears in hair and nails within hours; >3 ppm (100 mg per 100g specimen) is diagnostic of chronic arsenic ingestion. Enables timeline reconstruction.
4. Liver arsenic at autopsy: >1 mg% is significant
5. Methods: atomic absorption spectroscopy, neutron activation analysis, colorimetry, polarography

Treatment

Acute Poisoning

1. Remove source of exposure immediately
2. Gastric lavage (if within 1-2 hours of ingestion) with water or dilute sodium bicarbonate
3. Activated charcoal (limited efficacy but can be administered)
4. IV fluids (normal saline) for dehydration and shock correction
5. Chelation therapy - the cornerstone of treatment:
   • Unithiol (DMPS): 3-5 mg/kg IV every 4-6 hours (preferred)
   • Dimercaprol (BAL): 3-5 mg/kg IM every 4-6 hours for 2 days, then 6-hourly for 1 day, then 12-hourly; total dose ~2.5-3 mg/kg body weight. Stop if side effects: nausea, vomiting, tachycardia, hypotension, throat constriction
   • Succimer (DMSA): effective but only available orally in the US; avoid in initial acute phase due to poor GI absorption from splanchnic oedema
   • D-Penicillamine: 100 mg/kg/day in 4 divided doses for 4-8 days, given after initial 12-48 hours of BAL therapy
   • Chelation is most effective when given within minutes to hours of exposure; do not wait for lab confirmation if clinical suspicion is high
   • Stop chelation when 24-hr urine arsenic falls below 50 mcg/24 hr
6. Sodium thiosulphate 10% (7.5g IV) - of doubtful value
7. Castor oil or magnesium sulphate to reduce intestinal absorption
8. Morphine for pain relief
9. Demulcents: ghee, barley water
10. Monitor ECG for QTc prolongation and arrhythmias

Arsine Gas Poisoning

• Fresh air + oxygen inhalation
• Exchange transfusion
• Haemodialysis
• Alkaline drinks
• Note: BAL is NOT effective for arsine gas poisoning

Chronic Poisoning

• Remove from source of exposure
• BAL administration
• Supportive care

Autopsy Findings

• Prolonged rigor mortis
• General shrunken appearance (dehydration)
• Shrunken eyeballs, cyanosis of hands and feet, jaundice

• Stomach: mucous membrane inflamed and ulcerated; "red velvet appearance" with lines of redness along rugae; sticky mucus covers mucosa; arsenic particles may be visible

• Intestine: flaccid, pale-violet mucosa, submucous hemorrhages along its length, large flakes of mucus
• Subendocardial petechial hemorrhages of the ventricle (characteristic and highly suggestive of arsenic poisoning)
• Liver: fatty degeneration, possibly necrosis
• Kidneys: acute tubular necrosis, glomerulonephritis
• Lungs: congestion, subpleural ecchymoses, pulmonary oedema
• Brain: oedema, patchy necrosis, hemorrhagic encephalitis; congested meninges

Medico-legal Aspects

• Arsenic poisoning is most commonly homicidal because arsenic is colourless, tasteless, and odourless when dissolved, making it easy to administer covertly
• Arsenic is also used for suicidal and accidental ingestion (pesticide workers)
• Hair and nail analysis is critical for timeline reconstruction in suspected homicide
• Segments of hair closest to the scalp represent the most recent exposure; distance of Mees lines from nail base helps estimate timing
• Arsenic is preserved in the body for years, including after putrefaction, making exhumation and toxicologic analysis valuable

Key Numbers Summary