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

Background

Heavy metal toxicity results from exposure to metals like lead, mercury, arsenic, or cadmium, which interfere with cellular function. Exposure may occur occupationally, environmentally, through ingestion, or from alternative medicines. Chronic toxicity can present insidiously, while acute toxicity may mimic sepsis or encephalopathy. Diagnosis is often delayed due to nonspecific symptoms.

Clinical Features

Symptoms depend on the metal and exposure duration but may include:

Neurologic: Peripheral neuropathy, confusion, tremor, encephalopathy

GI: Abdominal pain, nausea, vomiting, diarrhea, anorexia

Heme: Anemia (especially microcytic or hemolytic), basophilic stippling (lead)

Renal: Tubular dysfunction, proteinuria, Fanconi syndrome

Dermatologic: Mees’ lines (arsenic), hyperpigmentation, hair loss

Others: Fatigue, weight loss, hypertension (cadmium), immunosuppression

Differential Diagnosis

Sepsis or systemic inflammatory response

Drug toxicity or overdose

Metabolic disorders (e.g., porphyria, uremia)

Psychiatric illness (if symptoms are vague or bizarre)

Neurologic diseases (e.g., Guillain-Barré, MS, Parkinson’s)

Vitamin deficiencies (e.g., B12, thiamine)

Evaluation

Workup

History: Occupational exposures, home remedies, hobbies (e.g., jewelry making, battery recycling), diet, water source, imported goods

Labs:

• CBC, CMP, urinalysis
• Blood lead level, serum/urine arsenic, mercury, or cadmium (based on suspicion)
• Urine heavy metal screen (note: spot testing may require creatinine correction)

Imaging: Abdominal X-ray (radiopaque material in GI tract, especially with lead)

EKG: Evaluate for QT prolongation or arrhythmias in severe cases

Diagnosis

Confirmed by elevated blood or urine levels of the specific metal in the context of clinical findings. Hair and nail testing are unreliable for acute toxicity. Interpret results with toxicologist input if possible.

Management

Remove the source of exposure (e.g., occupational control, GI decontamination if recent ingestion)

Supportive care: IV fluids, seizure control, electrolyte repletion

Chelation therapy (in consultation with toxicology or Poison Control):

Lead: EDTA, dimercaprol (BAL), succimer

Mercury/arsenic: Dimercaprol or DMSA

Cadmium: No effective chelation—focus on supportive care

Notify local public health authorities if exposure source is environmental or occupational

Disposition

Admit if symptomatic, unstable, or requiring chelation

Discharge may be appropriate for asymptomatic patients with low-level exposure and outpatient follow-up

Arrange toxicology or environmental medicine follow-up for source control and serial testing

See Also

• 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