Lead (Pb) Poisoning

Pathophysiology/Etiology:
- Inhibits ferrochelatase and ALA dehydratase in heme synthesis → microcytic, hypochromic anemia.
- Inhibits rRNA degradation → aggregates of ribosomes (basophilic stippling).
- Sources: Chipped paint in old houses (children), batteries, ammunition, construction.
Clinical Presentation:
- “LEAD” mnemonic:
  - Lead lines on gingiva (Burton lines) and on metaphyses of long bones on x-ray (in children).
  - Encephalopathy (irritability, developmental regression, coma) and Erythrocyte basophilic stippling.
  - Abdominal colic (constipation) and Anemia (sideroblastic).
  - Drops (wrist drop, foot drop) due to peripheral neuropathy.
- Also: Fatigue, memory loss, headache, HTN.
Diagnosis:
- ↑ blood lead level.
- Peripheral smear: Basophilic stippling.
- CBC: Microcytic anemia.
- ↑ Zinc protoporphyrin levels.
Management/Treatment:
- Chelation therapy is based on severity.
- Succimer (oral): Used for mild-moderate poisoning, especially in children.
- Dimercaprol (BAL) + EDTA: Used for severe poisoning/encephalopathy.
  - Note: Dimercaprol is given first.

Iron (Fe) Poisoning

Pathophysiology/Etiology:
- Ingestion of iron supplements (e.g., prenatal vitamins), especially in children.
- Direct corrosive effect on GI mucosa → hematemesis, bloody diarrhea.
- Systemic toxicity via Fenton reaction generates free radicals → metabolic acidosis, hepatic necrosis, shock.
Clinical Presentation:
- Acute (in stages):
  1. GI Phase (0-6 hrs): N/V, abdominal pain, hematemesis, melena.
  2. Latent Phase (6-24 hrs): Apparent improvement.
  3. Systemic Toxicity (12-72 hrs): Shock, anion gap metabolic acidosis, hepatic failure, coagulopathy.
- Chronic: Gastric scarring/pyloric stenosis.
Diagnosis:
- High serum iron level, high ferritin, low TIBC.
- Anion gap metabolic acidosis.
- Abdominal X-ray may show radiopaque pills.
Management/Treatment:
- Supportive care (ABCs), whole bowel irrigation.
- Deferoxamine (IV): Chelating agent for moderate-severe toxicity. Binds iron, forming ferrioxamine (renally excreted, gives urine a vin-rosé color).
- Oral: Deferasirox, Deferiprone.

Pathophysiology/Etiology:
- Inhibits enzymes containing sulfhydryl groups, especially pyruvate dehydrogenase.
- Sources: Contaminated groundwater (wells), pesticides, pressure-treated wood, smelting industries.
Clinical Presentation:
- Acute:
  - Severe watery, “rice-water” diarrhea, vomiting, abdominal pain.
  - Garlic breath odor.
  - Cardiovascular: QT prolongation, hypotension.
- Chronic:
  - Skin: Hyperkeratosis (palms/soles), hypo/hyperpigmentation.
  - Neuropathy: Stocking-glove sensory neuropathy.
  - Nails: Mees’ lines (transverse white lines).
  - Increased risk of skin, lung, and liver cancers.
Diagnosis:
- Urine arsenic level is the best test for recent exposure.
Management/Treatment:
- Dimercaprol (BAL).
- Succimer.

Pathophysiology/Etiology:
- Binds to sulfhydryl groups on enzymes, causing damage.
- Sources: Ingestion of contaminated fish (organic mercury - methylmercury), dental amalgams, thermometers, mining.
Clinical Presentation:
- Highly variable; depends on the form of mercury.
- Neurotoxicity is prominent: Ataxia, tremor, memory loss, irritability (“mad as a hatter”).
- Mucocutaneous: gingivitis; diaphoresis; swelling, redness, desquamation of hands/feet.
- Renal: Membranous nephropathy, acute tubular necrosis.
- GI: Gingivostomatitis.
Diagnosis:
- Blood mercury level (acute) or 24-hour urine mercury level (chronic).
Management/Treatment:
- Dimercaprol (BAL), Succimer.
- Note: Chelation is not effective for organic mercury (methylmercury).

Pathophysiology/Etiology:
- Autosomal recessive mutation in ATP7B gene on chromosome 13.
- Impaired copper transport into bile and incorporation into ceruloplasmin → copper accumulation in liver, brain (basal ganglia), cornea, kidneys.
- Excess free copper generates damaging free radicals.
Clinical Presentation:
- Presents in childhood/young adulthood (<35 yo).
- Hepatic: Asymptomatic ↑ LFTs to cirrhosis and acute liver failure.
- Neurologic: Parkinsonism-like symptoms (tremor, rigidity, dysarthria), dystonia, ataxia.
- Psychiatric: Depression, personality changes.
- Ophthalmic: Kayser-Fleischer rings (copper deposits in Descemet’s membrane of the cornea), seen on slit-lamp exam.
Diagnosis:
- ↓ Serum ceruloplasmin (key finding).
- ↑ Urinary copper excretion.
- ↑ Hepatic copper on liver biopsy (gold standard).
Management/Treatment:
- Chelating agents: D-penicillamine, Trientine.
- Oral Zinc: Interferes with dietary copper absorption.