Lead poisoning

Overview & Pathophysiology

Lead poisoning (plumbism) is toxic exposure to lead (Pb) that inhibits several enzymes of the heme synthesis pathway, producing a microcytic, hypochromic, sideroblastic anemia with coarse basophilic stippling on the peripheral smear. It is the most common heavy-metal poisoning in children and a classic occupational toxin in adults.

Top exposure scenarios (risk factors)

• Lead-based paint & dust — children (#1 source): chips/dust in homes built before 1978, amplified by pica and hand-to-mouth behavior; low socioeconomic status and immigrant/international-adoptee status raise risk.
• Occupational exposure — adults: battery manufacturing, ammunition/firing ranges, smelting, soldering, construction/demolition, radiator repair, and pottery/stained-glass glazing.
• Contaminated water & soil: old lead pipes/solder and leaded soil; also imported toys, kohl cosmetics, traditional remedies, and moonshine distilled in lead-soldered stills.

Core mechanism — inhibition of heme synthesis

Lead is absorbed via the GI tract (children absorb ~50%) or by inhalation (adults), then distributed to blood (98% bound to RBCs), soft tissue, and bone (half-life ≈ 20–30 years). The hallmark toxicity is two enzyme blocks:

• ↓ ALA dehydratase (cytoplasm) → δ-aminolevulinic acid cannot become porphobilinogen → ↑ urine δ-ALA.
• ↓ Ferrochelatase (mitochondria) → iron cannot be inserted into protoporphyrin IX → mitochondrial iron accumulates around the nucleus (ring sideroblasts) and protoporphyrin binds zinc instead → ↑ zinc protoporphyrin (ZPP).
• Net effect → ↓ heme → microcytic, hypochromic sideroblastic anemia.
• Inhibition of RBC 5′-nucleotidase → undegraded ribosomal RNA aggregates → coarse basophilic stippling.

Lead also binds sulfhydryl groups and displaces Ca²⁺, driving peripheral motor demyelination (wrist/foot drop), cerebral edema/encephalopathy, and proximal tubular injury (Fanconi-like syndrome, saturnine gout).

Clinical Presentation & Complications

Lead toxicity is often insidious or asymptomatic, especially with low-level chronic exposure. Manifestations track four organ systems — nervous system, GI tract, blood, kidney — with a different emphasis in children versus adults.

High-yield buzzwords to lock in: wrist drop and foot drop (adult motor neuropathy, radial and peroneal nerves first), Burton lines (blue-grey gingival lead lines), and lead colic (crampy, recurrent abdominal pain).

Serious complications, by system

• Neurologic (most concerning in children): permanent ↓ IQ, learning disability, ADHD-like behavior; lead encephalopathy (BLL > 70–100 µg/dL) → cerebral edema, seizures, coma, death. Adults → persistent motor neuropathy (wrist/foot drop).
• Renal: proximal tubular dysfunction → Fanconi-like syndrome (aminoaciduria, glycosuria, phosphaturia); chronic interstitial nephritis, ↓ GFR, hypertension; impaired vitamin-D 1-α-hydroxylation; saturnine gout (↓ urate excretion).
• Hematologic: chronic microcytic, hypochromic, sideroblastic anemia.
• Reproductive: infertility, ↓ sperm count, miscarriage, prematurity; lead crosses the placenta → fetal neurotoxicity.

Diagnostic Approach

Step 1 — Confirm with a blood lead level (BLL)

• First-line & gold standard: venous blood lead level (a capillary screen that is elevated must be confirmed venously).
• No safe level exists in children; the CDC blood lead reference value = ≥ 3.5 µg/dL (elevated).
• Targeted screening at 12 and 24 months in high-risk children (Medicaid, pre-1978 housing, immigrant/adoptee, affected sibling/playmate).

Step 2 — Supportive labs & imaging

• CBC / smear: microcytic, hypochromic anemia with coarse basophilic stippling.
• Iron studies: normal serum iron, ferritin, and TIBC — the pivotal distinction from iron deficiency.
• Zinc protoporphyrin (ZPP): ↑.
• Urine δ-aminolevulinic acid (ALA): ↑.
• Bone marrow (rarely needed): ring sideroblasts on Prussian blue.
• Imaging: abdominal X-ray → radiopaque paint chips in the colon (symptomatic children); long-bone X-ray → dense metaphyseal "lead lines" (represents calcium, not lead).

Differential diagnosis — the microcytic anemias (TAILS)

Lead poisoning is one of the "TAILS" microcytic anemias: Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic anemia. The single master table below separates them by iron studies and smear:

Other look-alikes

• Acute intermittent porphyria: abdominal pain + neuro symptoms + ↑ ALA, but ↑ porphobilinogen, NO anemia, and NO basophilic stippling.
• Howell–Jolly bodies (asplenia): a single, large nuclear remnant — versus the multiple scattered blue dots of basophilic stippling.

Management

Step 1 — Remove the source (most important)

• Environmental investigation + lead abatement (home inspection, occupational source control).
• Public-health notification — lead poisoning is a reportable disease.
• Nutritional counseling: replete iron, calcium, vitamin C, and zinc (deficiencies increase lead absorption).

Step 2 — Chelation, stratified by BLL

See the Treatment of Asymptomatic Lead Toxicity by Blood Lead Level for the exact chelator and threshold at each band.

Key chelation pearls

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

High-Yield Exam Pearls

The highest-yield, board-tested facts about plumbism, consolidated for rapid review.

• Buzzword smear: coarse basophilic stippling + microcytic anemia with normal iron studies (ferritin normal).
• First diagnostic step: venous blood lead level (gold standard).
• Encephalopathy rule: give BAL before EDTA.
• Child clue: pre-1978 housing + pica → ↓ IQ + abdominal pain. Adult clue: occupational exposure → wrist/foot drop, lead colic, HTN.