Lead poisoning

Summary

Lead poisoning (plumbism) is a toxic exposure to lead (Pb) that inhibits multiple enzymes in the heme synthesis pathway, producing a microcytic, hypochromic, sideroblastic anemia with characteristic basophilic stippling on peripheral smear.

• Children → exposure from old paint chips (pre-1978 housing), contaminated soil/water, pica → cognitive impairment, behavioral problems, abdominal pain.
• Adults → occupational exposure (batteries, ammunition, smelting, construction, radiator repair) → neuropathy (wrist/foot drop), abdominal colic, HTN, infertility.
• Key labs: ↑ blood lead level, microcytic anemia with normal iron studies, ↑ urine δ-ALA, ↑ zinc protoporphyrin, basophilic stippling, ring sideroblasts in marrow.
• Treatment: source removal + chelation (succimer / DMSA for moderate; dimercaprol + EDTA for severe/encephalopathy).

Etiology and Risk Factors

Sources of exposure

• Children (most common pediatric heavy-metal poisoning):
  • Lead-based paint chips/dust in homes built before 1978 (banned in US 1978).
  • Pica (ingesting non-food items), hand-to-mouth behavior.
  • Contaminated soil, water (old lead pipes), imported toys, kohl cosmetics, traditional remedies.
  • Low socioeconomic status, immigrant/international adoptee, sibling or playmate with lead poisoning.
• Adults (occupational/environmental):
  • Battery manufacturing, Ammunition (firing ranges), Radiator repair.
  • Construction/demolition, Smeltering/Soldering, Mining, pottery glazing, stained glass.
  • Moonshine (illicit alcohol distilled in lead-soldered radiators).

Pathophysiology

Lead is absorbed via GI tract (children absorb ~50%) or inhalation (adults). It is then distributed to blood (98% bound to RBCs), soft tissue, and bone (long half-life ≈ 20–30 years in bone).

Mechanism — inhibition of heme synthesis

• Blocks ALA dehydratase (in cytoplasm) → δ-aminolevulinic acid (ALA) cannot be converted to porphobilinogen → ↑ urine δ-ALA.
• Blocks ferrochelatase (in mitochondria) → iron cannot be inserted into protoporphyrin IX → iron accumulates in mitochondria around the nucleus → ring sideroblasts; protoporphyrin binds zinc instead → ↑ zinc protoporphyrin (ZPP).
• Net result → ↓ heme synthesis → microcytic, hypochromic, sideroblastic anemia.

Mechanism — basophilic stippling

• Lead inhibits RBC 5′-nucleotidase → ribosomal RNA degradation fails → coarse blue ribosomal aggregates seen on Wright–Giemsa stain.

Other toxic effects

• Nervous system: binds sulfhydryl groups, displaces Ca²⁺ → disrupts neurotransmission, impairs myelin (peripheral neuropathy), and increases vascular permeability (cerebral edema, encephalopathy).
• Kidney: proximal tubular damage → Fanconi-like syndrome, chronic interstitial nephritis, gout (saturnine gout).

Pathophysiology — Mnemonic

Clinical Features

Lead poisoning is often insidious and asymptomatic, especially with low-level chronic exposure. Symptoms reflect the four main organ systems affected: nervous system, GI tract, blood, kidney.

Classic motor finding

In adults with chronic occupational exposure → wrist drop and foot drop from a predominantly motor peripheral neuropathy (affects radial and peroneal nerves first).

Diagnosis

Step 1 — Blood lead level (BLL)

• Gold standard: venous blood lead level (capillary screen must be confirmed with venous sample).
• No safe level exists in children. CDC reference value = ≥ 3.5 µg/dL (elevated).
• Universal/targeted screening at 12 and 24 months in high-risk children (Medicaid, old housing, immigrants).

Step 2 — Supportive labs

• CBC: microcytic, hypochromic anemia.
• Peripheral smear: coarse basophilic stippling (multiple scattered blue dots = ribosomal aggregates).
• Iron studies: normal (key distinction from iron deficiency anemia and thalassemia).
• ↑ Zinc protoporphyrin (ZPP) and ↑ urine δ-ALA.
• Bone marrow: ring sideroblasts on Prussian blue (rarely needed for diagnosis).

Step 3 — Imaging (if indicated)

• Abdominal X-ray → radiopaque densities in the colon from ingested paint chips (in symptomatic children).
• Long-bone X-ray → dense metaphyseal "lead lines" (chronic exposure in growing bones — represents calcium, not lead).

For a comparison of microcytic anemias, see iron studies in microcytic anemia.

Question Idea — Lead vs Iron Deficiency

Differential Diagnosis

Lead poisoning falls under the "TAILS" microcytic anemias: Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic anemia.

Other look-alikes

• Acute intermittent porphyria (AIP): also has abdominal pain + neurologic symptoms + ↑ ALA. Differentiated by: AIP has ↑ porphobilinogen, no anemia, no stippling.
• Howell–Jolly bodies (asplenia) = single, large peripheral nuclear remnants vs. multiple scattered blue dots in lead.

Basophilic stippling vs Howell–Jolly bodies — compare smears.

Management

Step 1 — Remove the source (most important)

• Environmental investigation (home inspection, occupational source removal).
• Public health notification — reportable disease.
• Nutritional counseling: ensure adequate iron, calcium, vitamin C, zinc (deficiencies increase lead absorption).

Step 2 — Chelation (based on BLL)

Key chelation pearls

• Dimercaprol must be given BEFORE EDTA in encephalopathy — EDTA alone can mobilize lead from bone and worsen CNS toxicity.
• Dimercaprol is contraindicated in peanut allergy (vehicle = peanut oil) and G6PD deficiency.
• Adults: chelate when BLL ≥ 80 µg/dL (asymptomatic) or ≥ 50 µg/dL with symptoms.
• Avoid iron co-administration with succimer (forms toxic complex).

Complications

• Neurologic (most concerning in children):
  • Permanent cognitive impairment, ↓ IQ, learning disabilities, ADHD-like behavior.
  • Lead encephalopathy (BLL > 70–100 µg/dL) → cerebral edema, seizures, coma, death.
  • Adults → motor peripheral neuropathy (wrist drop, foot drop).
• Hematologic: chronic microcytic, hypochromic, sideroblastic anemia.
• Renal:
  • Proximal tubular dysfunction → Fanconi-like syndrome (aminoaciduria, glycosuria, phosphaturia).
  • Chronic interstitial nephritis, ↓ GFR, hypertension.
  • Impaired 1-α hydroxylation of vitamin D → ↓ active vitamin D.
  • Saturnine gout — ↓ uric acid excretion.
• Reproductive: infertility, decreased sperm count, miscarriage, prematurity; lead crosses placenta → fetal neurotoxicity.
• GI: recurrent abdominal colic, constipation.

Mnemonics