Arsenic Poisoning

Introduction

Mechanism of Toxicity

• SH-group binding: Combines reversibly with sulphydryl (-SH) groups of tissue proteins and enzymes, inhibiting cellular metabolism
• Enzyme inhibition: Disrupts key enzyme systems (pyruvate dehydrogenase, lipoic acid)
• Capillary poison: Dilates and damages capillaries, causing transudation of fluid
• Organ-specific: Fatty degeneration of the liver, renal tubular necrosis, and axonal neuropathy (disintegration of the axis cylinder with myelin fragmentation)

Acute Arsenic Poisoning

Routes of exposure

Signs and Symptoms

1. Metallic/garlicky taste, xerostomia (dry mouth), dysphagia
2. Severe nausea and vomiting - projectile, dark brown/yellow, containing mucus, blood and bile
3. Profuse diarrhoea - initially dark and bloody, later colourless, odourless, rice-water stools (resembling cholera)
4. Abdominal pain - burning, colicky, worsened by pressure; tenesmus and anal irritation
5. Cardiovascular: tachycardia, hypotension, cold clammy skin, pallor - due to hypovolaemia and direct myocardial toxicity; ECG shows T-wave inversion and prolonged QT interval
6. Dehydration: sunken eyes, shrunken face, cramps in calf muscles
7. CNS: restlessness, hypoxia, convulsions and coma preceding death
8. Death is usually due to irreversible circulatory insufficiency

Secondary effects (2-4 weeks post-exposure if not fatal):

• Hair loss (alopecia)
• Mee's lines (Aldrich-Mees lines) - white transverse lines on nail plate
• Sensorimotor peripheral neuropathy
• Skin changes resembling chronic poisoning
• Possible chronic renal failure

Chronic Arsenic Poisoning

Skin (most characteristic features):

• Earliest sign: persistent erythematous flushing (capillary dilation)
• Raindrop pigmentation - finely mottled brown spots on skin flexures, temples, eyelids, neck

• Hyperkeratosis of palms and soles
• Mee's lines - transverse white streaks 1-2 mm wide on fingernails (appear ~5 weeks post-exposure; double lines if more than one exposure)
• Patchy/diffuse alopecia, brittle nails
• Bowen's disease (intraepidermal carcinoma) - a long-term complication indicating systemic neoplastic processes

Nervous system:

• Neuropathy is the hallmark - symmetrical sensorimotor polyneuropathy resembling Guillain-Barré syndrome
• Paresthesia, numbness, pain especially on soles of feet
• "Glove and stocking" distribution of sensory loss
• Distal weakness - wrist drop, inability to walk; muscle atrophy; ataxia
• Encephalopathy (severe headache, personality changes, convulsions, coma)

Other systems:

Arsine Gas Poisoning (AsH₃)

• Occurs in industrial settings (acid/water acting on arsenic-bearing metals)
• Acts as a direct haemolytic poison
• Features: cough, frothy sputum, pulmonary oedema, cyanosis, corneal ulcer, conjunctivitis, haemolysis, haemoglobinuria, renal failure
• Death can be almost instantaneous
• BAL is NOT effective for arsine gas poisoning

Diagnosis

• Blood arsenic: >1.5 mg/100 mL indicates serious poisoning (normal <4 mg/L)
• Urine arsenic: normal <0.03 mg/L; chelation can be stopped when 24-hr urine falls below 50 mg
• Hair and nails: analysed by ion emission spectroscopy / atomic absorption spectroscopy / neutron activation analysis - most useful for chronic poisoning (arsenic has predilection for keratin)
• Colorimetry, polarography for tissue levels
• X-ray abdomen: may show radio-opaque arsenic in GI tract
• Definitive diagnosis is difficult due to natural trace arsenic in the body and multi-systemic presentation

Differential Diagnosis: Arsenic Poisoning vs. Cholera

Treatment

Acute Poisoning:

1. Gastric lavage with large amounts of warm water/milk; repeated at intervals (arsenic is re-secreted into GI tract)
2. Whole bowel irrigation; nasogastric suction
3. BAL (British Anti-Lewisite / Dimercaprol): 2.5-3 mg/kg IM - given 4-hourly for 2 days, 6-hourly for 1 day, then 12-hourly; total duration depends on clinical response and urine arsenic levels
   • Stop BAL when 24-hr urine arsenic falls below 50 mg
   • Stop if side effects: nausea, tachycardia, hypotension, burning mouth
4. DMSA (Succimer) or DMPS: superior to BAL if available; can be used as alternative
5. Oral D-Penicillamine: 100 mg/kg/day in 4 divided doses for 4-8 days, after initial 12-48 hours of BAL
6. IV saline for dehydration; morphine for pain relief; castor oil/MgSO₄ to reduce intestinal absorption
7. Greasy substances (butter, ghee) help prevent arsenic absorption; alkalis should not be given (increase arsenic solubility)
8. Demulcents: ghee, barley water

Arsine Gas:

• Remove to fresh air; oxygen inhalation; exchange transfusion; haemodialysis; alkaline drinks
• BAL is ineffective

Chronic Poisoning:

• Remove from source of exposure
• BAL administration

Autopsy Findings

• Prolonged rigor mortis; generalised dehydration; shrunken eyeballs; cyanosis of hands and feet; jaundice
• Stomach: inflamed mucosa with "red velvet appearance" - lines of redness running along folds

• Mucosal vesicle formation and sloughing in small intestine; chocolate/brown discolouration of intestinal contents
• Subendocardial petechial haemorrhages of the ventricle - pathognomonic finding (also seen in phosphorus, barium, mercury poisoning and heat stroke)
• Liver, spleen, kidneys: congested, enlarged, cloudy swelling, fatty change; kidneys show acute tubular necrosis
• Lungs: congested with subpleural ecchymoses
• Brain: oedema with patchy necrosis or haemorrhagic encephalitis; congested meninges
• Arsenic values in liver and blood >1 mg% in acute arsenic poisoning death