Metal toxicity

Exposure to heavy metals such as mercury, lead, iron, and arsenic is harmful to the human body and can potentially cause both acute symptoms (e.g., local irritation, gastroenteritis, and pneumonia) and longterm effects (e.g., abnormal physical development, cancer, damage to the central nervous system, and kidney). Toxic metals have many industrial purposes and therefore represent occupational hazards for a number of professions. Industrial pollution with heavy metals can affect the wider population through the contamination of food (e.g., mercury in fish) and water (e.g., lead, arsenic).

For chronic diseases resulting from the inhalation of metal dust, see “Pneumoconiosis.”

• Sources of exposure: metal smelting; , pesticides, herbicides, contaminated water (esp. in developing countries) ^[9]
• Pathophysiology
  • Has direct toxic effects on endothelial cells
  • Induces oxidative stress, and disrupts ATP production
• Clinical features ^[2][3]
  • Acute toxicity
    • Nausea and vomiting
    • Abdominal pain, diarrhea
    • Tachycardia, QT prolongation
    • Garlic-like odor on the breath
    • CNS (coma, seizures)
  • Chronic toxicity
    • Carcinogenic
      • Lung cancer
      • Skin cancer (squamous cell carcinoma)
      • Hepatic angiosarcomas
    • Arsenical keratosis: hyperkeratosis (especially on the soles and palms) → risk of developing squamous cell carcinoma)
    • White bands across the nails (Mees lines)
    • Peripheral polyneuropathy
• Diagnostics: urinalysis
• Treatment ^[1]
  • Consider gastric lavage, activated carbon in acute toxicity
  • Dimercaprol, succimer (in children)

• Sources of exposure ^[10][11][12]
  • Battery manufacturing, metallurgy, corrosion inhibition
  • Gun ranges (lead ammunition) ^[13]
  • Tableware containing lead (e.g., ceramic crockery)
  • Drinking water (contaminated by lead plumbing) or contaminated sources
  • Lead-containing paint (common source of exposure in children) from:
    • Antique or imported toys
    • Walls of older homes
  • Consumption of illicitly distilled alcohol (moonshine)
• Pathophysiology: inhibition of aminolevulinate dehydratase and ferrochelatase → heme synthesis disruption → ↑ protoporphyrin and ↑ aminolevulinic acid in RBCs
• Clinical features
  • Nervous system ^[14][15]
    • Polyneuropathy, encephalopathy, headache, fatigue, muscle weakness, paresthesias, delirium, seizures
    • Demyelination of peripheral nerves→ peripheral neuropathy → paralysis of muscles supplied by the radial or peroneal nerve (wrist/foot drop)
    • Cognitive impairment, memory loss
    • Acute encephalopathy: persistent vomiting, ataxia, seizures, coma
  • Kidneys: nephropathy, renal cell carcinoma
  • Red blood cells: symptoms of anemia
  • Other:
    • Purple-blue line on the gums (lead line or Burton line)
    • Severe abdominal pain (lead colic)
    • Constipation
    • Hypertension
    • Miscarriages, infertility
  • Children are especially susceptible to the neurologic effects of lead poisoning
    • Many children are asymptomatic and should be assessed for blood lead levels if they have risk factors
    • “See screening in high-risk pediatric populations” below
• Diagnostics
  • Blood lead level (BLL) measurement
  • Basophilic stippling of erythrocytes on peripheral blood smear (lead inhibits RNA degeneration)
  • Microcytic, hypochromic anemia (lead inhibits heme synthesis) ^[16]
  • Ring sideroblasts in bone marrow
  • Imaging (not routinely indicated)
    • Lead flecks on abdominal x-ray
    • Lead lines on long-bone x-rays
  • Inspection of the patient's environment for lead sources to prevent further exposure
• Screening in high-risk pediatric populations ^[17][18]
  • Living in older housing with peeling paint
  • Sibling or playmate with lead poisoning
  • Recent immigrant, refugee, or foreign adoptee
  • History of pica
• Treatment ^[19]
  • Decrease exposure: professional lead paint abatement, dust reduction, minimization of contact with bare soil
  • Nutrition: calcium, iron, zinc, vitamin C, and vitamin D-rich diet ^[20]
  • Chelation therapy indications: ^[21]
    • Oral succimer with/without intravenous or intramuscular CaNa₂EDTA (calcium disodium ethylenediamine tetraacetic acid) ^[22]
      • Children with BLL ≥ 45 μg/dl ^[23]
      • Asymptomatic adults with BLL ≥ 80 μg/dl
      • Symptomatic adults with BLL ≥ 50 μg/dl
    • IM dimercaprol; (British antilewisite, BAL) with/without CaNa₂EDTA
      • Patients with lead encephalopathy
      • BLL ≥ 70 μg/dl

ABCDEFGH: Anemia, Basophilic stippling, Constipation, Demyelination, Encephalopathy, Foot drop, Gum deposition/Growth retardation/Gout, Hyperuricemia/Hypertension

“It sucks to be a child with lead poisoning!” - succimer is used to treat lead poisoning in children.

• Definition: chemical element often used as a supplement in pediatrics and prenatal care and in the management of anemia
• Epidemiology: toxicity is common in pediatric care (ingestion of red iron tablets mistaken for candy)
• Pathophysiology: Iron mediated toxicity and cell death is caused by
  • Free radical formation
  • Lipid peroxidation
  • Disruption of oxidative phosphorylation and mitochondrial function
• Clinical features
  • Initially hemorrhagic gastroenteritis, possibly symptoms of shock
  • Abdominal pain, vomiting (most common symptoms in children)
  • Causes dark-colored stools
  • Later: risk of renal and liver failure, unconsciousness, and respiratory depression
  • Complication: GI scarring and stricture formation → intestinal obstruction
• Diagnostics
  • Anion gap metabolic acidosis
  • Abdominal x-ray: radiopaque iron tablets may be visible
• Management
  • Deferoxamine
  • Gastric lavage or whole bowel irrigation

• Sources of exposure
  • Organometallic methylmercury in fish ^[24]
  • Inorganic, metallic mercury in thermometers, amalgam (dental fillings), pyrotechnics, and metalworking
• Clinical features
  • Acute toxicity
    • Gastroenteritis (bloody diarrhea)
    • Kidney failure
    • Inflammation of the airways (from inhalation exposure)
  • Chronic toxicity (Minamata disease) ^[25]
    • Glomerulonephritis (albuminuria)
    • CNS disorders: ataxia, erethism mercuralis (abnormal irritability); , and tremor
    • Polyneuropathy
    • Gingival and/or buccal inflammation with bluish‑violet discoloration of the margins of the gums ^[26]
    • Teratogenicity
• Diagnostics ^[27]
  • Inorganic mercury in urine
  • Organic mercury in blood
• Treatment ^[27][28]
  • Dimercaprol (BAL)
  • Succimer (dimercaptosuccinic acid; DMSA)
  • 2,3 dimercaptopropane-1-sulfonate (DMPS)
  • D‑penicillamine

• Sources of exposure: food, batteries, metallurgy, plastics and paint manufacturing, cigarette smoke
• Clinical features ^[29][30]
  • Acute toxicity: irritation of the airways (pulmonary edema, interstitial pneumonia)
  • Chronic toxicity
    • Kidney damage (tubulointerstitial nephritis), renal cell carcinoma
    • Lung disease (emphysema, carcinoma)
    • Anosmia
    • Osteoporosis/osteomalacia
    • Itai‑itai disease: chronic cadmium toxicity with kidney failure and osteomalacia (with aching joints and bones)
• Diagnostics
  • Acute toxicity: increased blood cadmium
  • Chronic toxicity
    • Increased urine cadmium
    • β2 microglobulin in urine
• Treatment: not known ^[31]

• Sources of exposure: galvanization (chrome plating), paint and glass manufacturing, tanning leather, building materials (potassium dichromate in cement → “cement eczema” is an occupational hazard among construction workers)
• Clinical features
  • Acute toxicity
    • Ulceration of the nasal septum from contact with contaminated fingers → risk of perforation
    • Contact dermatitis
  • Chronic toxicity
    • Welder's lung
    • Lung cancer
• Diagnostics: urine or blood

• Sources of exposure
  • Glass industry
  • Rat poison
• Clinical features
  • Hair loss
  • Polyneuropathy
  • Memory disorders ^[32]
  • White bands across the nails (Mees lines)
• Diagnostics: present in blood and/or urine

• Sources of exposure: metallurgy, alloys
• Clinical features
  • Acute
    • Mucous membrane irritation
    • Bronchitis
    • Bronchopneumonia
  • Chronic
    • Welder's lung
    • Pulmonary fibrosis
    • Black‑green discoloration of the tongue
• Diagnostics: present in blood and/or urine

• Sources of exposure: metallurgy, welding
• Clinical features ^[33]
  • Manganese pneumonia: a form of fibrinous pneumonia
  • Manganism: a form of parkinsonism (see “Secondary parkinsonism”)
  • Decreased fertility
  • Fetal toxicity
• Treatment ^[33]
  • Chelation therapy with EDTA
  • Levodopa for manganism

• Sources of exposure: alloys (e.g., in coins, jewelry)
• Clinical features
  • Acute toxicity: contact dermatitis
  • Chronic toxicity
    • Squamous‑cell carcinoma of the nose or paranasal sinuses
    • Lung cancer

• Sources of exposure
  • Jewelry
  • Catalytic converters
• Clinical features
  • Obstructive lung diseases (immediate reaction allergy)
  • Nephrotoxicity

• Source of exposure ^[34][35][36]
  • Chrysotherapy
  • Gold nanoparticles for diagnosis (e.g., antibody sensing) and therapy (e.g., cancer treatment)
• Clinical features
  • Typical
    • Pruritus
    • Dermatitis
    • Stomatitis
    • Metallic taste
  • Severe cases
    • Vasomotor reaction: nausea, flushing, hypotension including syncope, sweating, and weakness
    • Renal: proteinuria
    • Hematological: thrombocytopenia, neutropenia, and aplastic anemia
    • Gastrointestinal: diarrhea and enterocolitis
• Diagnostics: laboratory studies
  • CBC: decreased WBCs, decreased platelet count
  • LFTs: decreased transaminases
  • Renal function tests: increased creatinine, increased urea, increased uric acid
  • Urinalysis: proteinuria, hematuria
• Treatment: discontinuation of gold therapy
• Complications
  • Renal: membranous glomerulonephritis
  • Cardiovascular: myocardial infarction, stroke

• Source of exposure ^[7]
  • Genetic: Wilson disease
  • External
    • Uncoated copper cookware heated with acidic food
    • Contaminated water
    • Copper-containing creams for burn healing
    • Suicide attempts (via i.v. copper sulfate injection)
• Clinical features
  • Gastrointestinal: abdominal pain, diarrhea, or vomiting (early symptoms)
  • Hepatic: jaundice
  • Altered mental status: encephalopathy, coma
• Diagnostics ^[37]
  • Laboratory studies: increased serum copper, ceruloplasmin
  • Urinalysis: increased copper excretion
• Treatment ^[7]
  • Early stage: zinc
  • Chelating agents: penicillamine, trientine
• Complications
  • Liver failure
  • Heart failure
  • Kidney failure
  • Intravascular hemolysis
  • Death

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