Toxicology: Arsenic and Lead Exposure

Heavy Metals

• Lead ([Pb])
  • Sources of poisoning:
    • Inorganic lead compounds are used in paints, dyes, ceramic food containers, and leaded-glazed dishes. Acidic foods like tomato juice and fruit juice can dissolve lead.
    • Lead-containing paint is a significant source of lead exposure in children due to hand-to-mouth transfer. Dust from older housing surfaces can also be a source of lead exposure.
    • Lead is used in batteries (70% of current lead use), water pipes, and as additives in gasoline.
  • Toxicokinetics:
    • Alkyl lead compounds (methyl and tetraethyl lead) are well absorbed through skin, lungs, and the gastrointestinal tract (GIT) due to their lipid solubility.
    • Initially, lead is carried in red blood cells and distributed to soft tissues (kidneys, liver), then mostly deposited in bone as a phosphate salt. High PO4 levels increase lead storage in bone.
    • Lead readily crosses the placental barrier. Breast milk from heavily exposed mothers is a potential source of lead.
  • Mechanism of toxicity:
    • Lead inhibits enzymes by reacting with thiol groups in various metabolic pathways.
    • Critically sensitive steps are in the heme pathway (6-aminolevulinic acid dehydratase (ALAD) and ferrochelatase).
    • Inhibition of ALAD results in an accumulation of δ-aminolevulinic acid (ALA), which is excreted in urine. Urine ALA levels are a biochemical indicator of lead exposure.
    • Lead inhibits ferrochelatase, which is involved in the formation of heme from iron and protoporphyrin.
    • Lead interferes with the Na+,K+-ATPase pump and various metabolic pathways, particularly in the mitochondria involved in energy production.
  • Symptoms of toxicity (CNS):
    • The nervous system is a primary target for lead in infants and children.
    • Lead can damage arterioles and capillaries, leading to cerebral edema and neuronal degeneration.
    • Lead affects virtually all neurotransmitter systems (glutamatergic, dopaminergic, and cholinergic), with symptoms potentially including headache, drowsiness, incoordination, ataxia, convulsions, and coma.
    • In children (up to 80%): permanent neurological damage, hyperactivity, decreased attention, and slight lowering of IQ scores are possible sequelae. Epilepsy, optic neuropathy, blindness, and mental retardation can also occur.
  • Symptoms of toxicity (PNS):
    • Peripheral neuropathy, a classic manifestation in adults, occurs due to demyelination and axonal degeneration, leading to motor nerve dysfunction (wrist drop and foot drop).
    • Muscle weakness is another consequence.
  • Symptoms of toxicity (GIT):
    • Nausea, vomiting, constipation, cramps, and abdominal pain are among the GIT symptoms.
  • Symptoms of toxicity (other):
    • Chronic lead exposure can lead to hypertension and anemia.
    • Renal tubular degeneration can be observed, along with bone damage (osteoporosis), dental caries, and delays in fracture repair.
    • Spontaneous abortion and oligospermia (low sperm count) are other possible consequences.
  • Biomarkers of toxicity:
    • Whole blood lead level.
    • Elevated erythrocyte protoporphyrin levels.
    • Increased urinary δ-aminolevulinic acid (ALA) levels.
  • Treatment of toxicity:
    • Decontamination methods include whole bowel irrigation (WBI) for inorganic lead compounds, activated charcoal for organolead compounds, and surgical or endoscopic removal of lead objects in the gastrointestinal tract.
    • Supportive care may involve normalizing elevated intracranial pressure, treating seizures, and referrals for physical or cognitive rehabilitation to manage neurotoxic sequelae.

Mercury ([Hg])

- Mercury is the only metal that is liquid at room temperature.
- Forms:
    - Elemental mercury (HgO).
    - Inorganic: mercurous (Hg+) and mercuric (Hg2+) salts.
    - Organic: methylmercury and dimethylmercury compounds.
- Uses (Elemental Hg):
    - Thermometers, dental amalgams, electrical equipment, batteries, and paints.
- Uses (Organic Hg):
    - Antiseptics and fungicides.
- Uses (Inorganic Hg):
    - Teething powders and antibacterial agents.
    - Disinfectants.
- Mechanism of toxicity:
    - Mercury inactivates SH-enzymes, disrupting cellular function.
- Toxicokinetics:
    - Elemental mercury (vapor) readily crosses membranes and quickly moves to the CNS. 
    - Organic mercury (lipid soluble) distributes to various tissues, with elimination through the intestines.
    - Inorganic salts concentrate in the blood, plasma, and kidneys.
- Symptoms of toxicity (Elemental Mercury):
    - CNS: tremor, increased excitability, insomnia, and depression.
    - Lung corrosion and bronchitis are possible.
    - Kidney: proteinuria (protein in the urine).
    - Other symptoms: acrodynia (pain and swelling in extremities) and gingivitis
- Symptoms of toxicity (Inorganic Mercury):
    - GIT: corrosive, vomiting, hematemesis, abdominal pain, intestinal perforation, and colitis.
    - Kidney: acute renal failure.
    - CVS: cardiovascular collapse leading to death.
- Symptoms of toxicity (Organic Mercury):
    - Neurotoxicity is the primary effect and is associated with methylmercury. Severe cases include Minamata disease (neurological damage, visual loss, numbness in extremities, hearing loss, and ataxia; affecting fetuses).
    - Congenital abnormalities (micrognathia, microcephaly), mental retardation, and blindness are also possible outcomes of prenatal exposure.
- Treatment of toxicity:
    - Decontamination with a small orogastric or nasogastric tube (within two hours) for ingestion. Consider using milk and egg white in the lavage fluid to manage the exposure to inorganic and organic mercury if needed.
    - Whole bowel irrigation might be needed if mercury is visible in an abdominal radiograph. 
    - Supportive care and chelation therapy.

Arsenic ([As])

- Types:
    - Organic arsenic compounds.
    - Inorganic arsenic compounds (e.g., arsenic dioxide, arsenic trioxide, lead arsenate, arsine gas). Arsine gas is the most toxic.
- Sources of poisoning:
    - Arsenicals contamination in water, soil, and food (seafood).
    - Use in herbicides, pesticides, rodenticides, and preservatives.
    - Occupationally associated with metallurgy, glass manufacturing, and pigment production.
- Mechanism of toxicity:
    - Trivalent arsenic compounds inhibit enzymes by reacting with thiol groups.
    - Arsenic blocks the conversion of pyruvate to acetyl coenzyme A and the Krebs cycle.
    - Arsenate (pentavalent arsenic) uncouples mitochondrial oxidative phosphorylation.
    - Arsine gas is a hemolytic agent.
- Symptoms of toxicity (Acute):
    - GIT: necrosis, ulceration, esophageal and abdominal burning pain, vomiting, and bloody/watery diarrhea (rice-water stool).
    - Kidney: renal damage, oliguria, proteinuria, hematuria, and casts.
    - Skin: necrosis and sloughing.
    - CVS: hypotension, excessive bleeding, and dehydration.
    - CNS: convulsion, coma, and death.
- Symptoms of toxicity (Chronic):
    - GIT: anorexia, weight loss, ulceration, and a garlic odor in breath and stool.
    - Liver: hepatitis, necrosis, and cirrhosis.
    - Blood: anemia due to bone marrow damage.
    - Skin: hyperpigmentation, hyperkeratosis, and gangrene of extremities (black foot disease).
    - Nails: horizontal white lines (Mees lines).
    - Carcinogenesis: lung cancer. 

-Treatment of toxicity:
    - Supportive treatment
    - Chelation therapy (e.g., BAL, DMSA, EDTA).

Test your knowledge on the symptoms and treatments related to arsenic and lead toxicity. This quiz covers critical aspects of chelation therapy, biological indicators, and the harmful effects of these heavy metals on health. Understand the urgency of recognizing these toxic exposures in clinical settings.