Copper toxicity

Background

• Widely available metal
• Obtained from various foods including nuts, fish, green vegetables
• Numerous poisonings from copper pipes
  • Occurs from storage of acidic substances (lemon/orange juice), pipes exposed to carbon dioxide from carbonation process, stagnant, and hot water which leach out copper from pipes
• Uses
  • Pipes
  • Cookware
  • Electrical wire
  • Medical devices (copper IUD)
  • Dietary supplements
  • Bordeaux solution (used as a pesticide)
• Seen in Wilson disease

Toxicokinetics

• Absorbed in the GI tract
  • Bound by ceruoplasmin
• Elimination via biliary system
  • Minimal renal elimination
• V_D : 2L/kg
• Toxicity is caused through redox reactions
  • Fenton reaction
  • Haber-Weiss cycle
  • Generates oxidative stress, inhibiting key metabolic enzymes, particularly in cell membranes and mitochondria
• Organ specific damage
  • Erythrocytes
    • Membran dysfunction resulting in hemolysis
    • Occurs within the first 24 hours
  • Hepatic
    • Excess copper not bound by metallothionein participates in redox reactions and cause lipid peroxidation
    • Centrilobular necrosis
    • After necrosis there is a release of massive amounts of copper into the blood causing a secondary hemolysis
  • Renal
    • ATN with hemoglobin casts, likely from hemolysis

Clinical Features

• Acute
  • Copper sulfate
    • Most common acute poisoning
    • Lethal dose is 0.15-0.3g/kg
  • GI irritation
    • Emesis (may be blue based on copper compound, but is not pathognomonic)
    • Abdominal pain
    • Gastroduodenal hemorrhage, ulceration, and perforation
    • Metallic taste
  • Hepatic
    • Jaundice
  • Hematologic
    • Hemolysis
    • May see methemoglobinemia
  • Renal
    • Renal failure uncommon
  • Hypotension and CV collapse
    • Likely multifactorial
• Chronic
  • Wilson disease
  • CNS
    • Ataxia
    • Tremor
    • Parkinsonism
    • Dysphagia
    • Dystonia
  • Behavioral
    • Mood changes
  • Occular
    • Kayser-Fleischer rings

Differential Diagnosis

Heavy metal toxicity

• Aluminum toxicity
• Antimony toxicity
• Arsenic toxicity
• Barium toxicity
• Bismuth toxicity
• Cadmium toxicity
• Chromium toxicity
• Cobalt toxicity
• Copper toxicity
• Gold toxicity
• Iron toxicity
• Lead toxicity
• Lithium toxicity
• Manganese toxicity
• Mercury toxicity
• Nickel toxicity
• Phosphorous toxicity
• Platinum toxicity
• Selenium toxicity
• Silver toxicity
• Thallium toxicity
• Tin toxicity
• Zinc toxicity

Evaluation

• Clinical diagnosis,as copper levels will likely take days to result
• BMP
• Hepatic function tests
• CBC
• PT/PTT/INR
• Copper level
  • No set number that establishes a prognosis
• Ceruloplasmin level
• Abdominal films to assess for foreign bodies

Management

• Supportive care
  • Antiemetics
  • Fluid and electrolyte repletion
  • GI decontamination unlikely to benefit
  • Activated charcoal contraindicated
• Chelation

Disposition

• Consult Toxicology or Poison Control Center

References

Nelson, L. Gold. In: Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill; 2011: 1256-1265