Copper Poisoning

Aka: Copper Poisoning, Copper Toxicity, Copper

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II. Pathophysiology

  1. Copper (Cu) is a Heavy Metal trace element (atomic number 29, and atomic weight 63)
    1. Copper deficiency is rare (but may cause hypochromic Microcytic Anemia, Neutropenia)
    2. Copper is a key component of various Proteins (redox enzymes)
      1. Ceruloplasmin
      2. Superoxide dismutase (Erythrocuprein)
      3. Cytochrome c oxidase
      4. Tyrosinase
      5. Dopamine ß-monooxygenase (DBH)
      6. Lysyl oxidase (LOX)
      7. Peptidylglycine monooxygenase (PHM)
  2. Copper Sources
    1. Copper is primarily extracted from chalcopyrite (iron oxide ore)
    2. Commercially used, often as an alloy with zinc (brass) or tin (bronze)
      1. Wiring
      2. Plumbing
      3. Cookware
      4. Electroplating
      5. Fungicides or herbicides
      6. Fireworks
      7. Glass and paint pigments
    3. Copper is also available at low dose in foods
      1. Daily ingestion is 800 mcg/day in children, 1200 mcg/day in women, 1400 mcg/day in men
      2. Nuts
      3. Fish
      4. Legumes
      5. Drinking Water
  3. Toxic Exposure
    1. Copper Poisoning typically occurs with Copper salt ingestion (esp. >1 gram ingestion)
    2. Copper Poisoning may also occur with inhalation (Copper oxide fumes or Copper dust)
    3. Wilson Disease
      1. Autosomal Recessive defect in Copper excretion into bile
      2. Copper accumulates (first in liver, then in brain, eye, Kidney) from ceruloplasmin cleavage
  4. Copper Metabolism
    1. Actively absorbed in the Small Intestine
    2. Bound to ceruplasmin
    3. Excreted in bile
  5. Acute Toxicity Mechanism
    1. Oxidative stress
    2. Heme oxidation and red cell membrane injury
    3. Hepatocyte cell membrane injury
    4. Gastrointestinal Tract toxicity with large ingestions (caustic)
    5. Minimal CNS effects in acute toxicity (contrast with Wilson Disease)

III. Findings: Acute Poisoning

  1. See Wilson Disease for chronic effects
  2. Gastrointestinal
    1. Abdominal Pain
    2. Metallic Taste
    3. Vomiting
      1. May appear blue or green
    4. Diarrhea
      1. Less prominent than Vomiting
    5. Hepatotoxicity
      1. Excess Copper primarily deposits in liver
      2. Results in hepatic necrosis (may subsequently release stored Copper when hepatocytes are injured)
  3. Hematologic
    1. Intravascular Hemolysis within first 12 to 24 hours
    2. Methemoglobinemia
  4. Cardiovascular
    1. Hypovolemic Shock related to gastrointestinal losses
    2. Chest Pain
  5. Renal
    1. Acute Kidney Injury (due to Acute Tubular Necrosis)

IV. Labs

  1. Complete Blood Count
  2. Comprehensive Metabolic Panel
  3. Ceruplasmin
  4. Prothrombin Time (INR)
  5. Creatine Phosphokinase (CPK)
  6. Whole Blood Copper Level
    1. Level >800 mcg/dl is associated with severe Poisoning effects
  7. Hemolysis labs
    1. Total and Direct Bilirubin
    2. Haptoglobin
    3. Lactate Dehydrogenase (LDH)
  8. Methemoglobinemia labs
    1. Arterial Blood Gas (ABG
    2. Oximetry (Oxygen Saturation)
    3. Venipuncture with "Chocolate brown" appearance to blood

V. Management

  1. Intravenous Fluids
    1. Isotonic crystalloid
    2. Albumin may be considered
  2. Methemoglobinemia management
    1. Methylene Blue Indications
      1. Methemoglobin > 20-30 g/L (20-30%)
      2. Methemoglobinemia with Hypoxia or other signficant symptoms (lethargy, confusion, Dyspnea)
    2. Methylene Blue Dosing
      1. Dose: 1-2 mg/kg (1% solution) over 5 min
      2. Reduces Methemoglobin by 50% within 1 hour (by reduction back to Hemoglobin)
      3. Contraindicated in G6PD Deficiency
  3. Hepatotoxicity
    1. Consider N-Acetylcysteine IV
  4. Copper Chelation
    1. Consult poison control
    2. Indications
      1. Hepatotoxicity
      2. Hemolysis
    3. First-Line agents
      1. D-Penicillamine 250 mg orally every 6 hours
    4. Second-Line agents (if NPO, anuric or Penicillamine not available)
      1. Dimercaprol IM
    5. Third-line agents
      1. Albumin Dialysis may be considered to enhance Copper elimination in severe toxicity
    6. Other agents
      1. Dimercaptosuccinic acid orally may be used if Penicillamine not available
  5. Disposition
    1. Admit all symptomatic patients
    2. May discharge home at 6 hours if no gastrointestinal symptoms in first 6 hours after ingestion
      1. Toxicity unlikely

VI. Resources

  1. Copper Toxicity (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK557456/

VII. References

  1. Carrol and Yakey (2025) Crit Dec Emerg Med 39(1): 36
  2. Gaetke (2014) Arch Toxicol 88(11):1929-38 +PMID: 25199685 [PubMed]

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Related Studies

Ontology: Copper (C0009968)

Definition (NCI) An element with atomic symbol Cu, atomic number 29, and atomic weight 63.
Definition (MSH) A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.
Definition (CSP) reddish, malleable metal; atomic number, 29; atomic weight, 63.54; symbol Cu; with poisonous salts; copper is essential in nutrition, being a component of various proteins, including ceruloplasmin, erythrocuprein, cytochrome c oxidase, and tyrosinase; deficiency, which is rare, may result in hypochromic microcytic anemia, neutropenia, and bone changes; excessive accumulation in the body may lead to copper poisoning.
Concepts Biologically Active Substance (T123) , Element, Ion, or Isotope (T196) , Pharmacologic Substance (T121)
MSH D003300
SnomedCT 422528000, 66925006
LNC LP16814-3, MTHU003471
English Copper, Cu, Copper (product), copper, mineral supplements copper, copper (medication), COPPER, Copper [Chemical/Ingredient], coppers, copper in a drug form, copper (cu), cu, Cu element, Cu - Copper, Copper (substance), Copper, NOS
Swedish Koppar
Spanish cobre (producto), cobre (sustancia), cobre, Cobre
Czech měď
Finnish Kupari
Russian MED', МЕДЬ
Croatian BAKAR
Latvian Varš
Polish Miedź
Norwegian Kobber
French Cuivre
German Kupfer
Italian Rame
Portuguese Cobre
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Copper poisoning (C0274928)

Concepts Injury or Poisoning (T037)
SnomedCT 46655005
English poisoning by copper (diagnosis), poisoning by copper, copper poisoning, Copper poisoning, Copper poisoning (disorder)
Spanish intoxicación por cobre (trastorno), intoxicación por cobre
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Toxic effect of copper and its compounds (C0497020)

Concepts Injury or Poisoning (T037)
ICD10 T56.4 , T56.4X1, T56.4X
English Copper and its compounds, Toxic effect of copper and its compounds, Toxic effects of copper and its compounds, Toxic effects of copper and its compounds NOS
German Toxische Wirkung: Kupfer und dessen Verbindungen
Korean 구리 및 그 화합물의 중독작용
Dutch Koper en koperverbindingen
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Poisoning and Toxicology

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