Copper toxicity

Background

Copper piping.

Unoxidized copper wire (left) and oxidized copper wire (right)

• Widely available metal
• Obtained from various foods including nuts, fish, and 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

Copper Uses

• Pipes
• Cookware
• Electrical wire
• Medical devices (copper IUD)
• Dietary supplements
• Bordeaux solution (used as a pesticide)

Toxicokinetics

• Absorbed in the GI tract
  • Bound by ceruoplasmin
• Elimination via biliary system
  • Minimal renal elimination
• V_D : 2L/kg
• Copper sulfate
  • Most common acute poisoning
  • Lethal dose is 0.15-0.3g/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

• 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 cardiovascular collapse
  • Likely multifactorial

Chronic

• Wilson's disease
• CNS
  • Ataxia
  • Tremor
  • Parkinsonism
  • Dysphagia
  • Dystonia
• Behavioral
  • Mood changes
• Occular
  • Kayser-Fleischer rings

Differential Diagnosis

Also seen in Wilson's disease

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
• Phosphorus 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 and ceruloplasmin level
• Abdominal films to assess for foreign bodies

Copper level

No set number that establishes a prognosis

• Whole blood = 70–140 μg/dL (11–22 μmol/L)
• Total serum = 120–145 μg/dL (18.8–22.8 μmol/L)
• Free serum = 4–7 μg/dL (0.63–1.1 μmol/L)
• Ceruloplasmin = 25–50 μg/dL (3.9–7.8 μmol/L)
• Urine = 5–25 μg/24 h (.078–3.9 nmol/L)

Management

Supportive care

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

Chelation

Recommended in cases with hematologic or hepatic complications

• Most commonly used are BAL and D-penicillamine
• British anti-Lewisite (BAL)
  • Beneficial in patients with vomiting who are unable to take D-penicillamine
  • Useful in those with renal failure
• D-penicillamine
  • Should be started as soon as able to tolerate PO
  • Begin simultaneously with BAL or soon after
  • Prevents copper induced hemolysis in patients with wilson disease
  • Undergoes renal clearance
  • 1.0-1.5 g/d given PO in 4 divided doses
  • Can be used for acute and chronic copper poisoning
  • Complications
    • Worsening of neurologic findings
    • Aplastic anemia
    • Agranulocytosis
    • Renal and pulmonary disease
    • Hypersensitivity reactions in 25% of patients with pencillin allergies
    • Congenital abnormaliies in pregnenancy
• CaNa₂EDTA
  • Will reduce oxidative damage
  • Does not enhance elimination
• Succimer
  • Ineffective copper chelator
  • Does increase copper elimination in murine models
  • Dose is the same as lead dosing
• DMPS
  • Not recommended for treatment of copper poisoning
  • Can worsen copper induced hemolysis
• Trientine
  • Second line chelator for wilson disease
  • No reports in acute copper poisoning
• Tetrathiomolybdate
  • FDA chelating agent with orphan drug status
  • No human studies but showed benefits in animal models

Extracorporeal Elimination

Unlikely to benefit

• Exchange transfustion
  • Limited benefit
• Hemodialysis
  • Not recommended
  • Membranes allow copper ions to cross
  • Unlikely to be clinnicall useful
  • May also lyse erythrocytes release stored copper causing worsening toxicity
• Molecular adsorbents recirculating system (MARS) and Single Pass Albumin Dialysis (SPAD)
  • Rapidly and substantially lower serum copper concentraions
  • Risk of hemolysis
• Plasma Exchange
  • Enhanced elimination of copper by 3-12 mg
  • Unclear if benficial after large ingestions
  • Risk of hemolysis
• Peritoneal Dialysis
  • Not useful

Disposition

• Consult Toxicology or poison control

See Also

• Toxicology (main)
• Heavy Metals

References

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