Core concept
- Lead inhibits ALA dehydratase and ferrochelatase (haem synthesis) -> impaired haem synthesis -> microcytic/normocytic anaemia
- Ferrochelatase block -> substrate (protoporphyrin) accumulates -> raised free erythrocyte protoporphyrin (FEP)
- Inhibits RNase -> RNA persists in RBCs -> basophilic stippling (coarse, aggregated ribosomes)
- Sideroblastic picture (ring sideroblasts) can occur alongside
Key detail
- Basophilic stippling is not specific - also thalassaemia, other hereditary anaemias, alcohol, arsenic
- Confirm with blood lead level, not stippling alone
- Sources: occupational (battery/smelting), old paint (pre-1970s housing), retained bullet fragments, imported cosmetics/ayurvedic remedies, moonshine
- Children more susceptible to neurotoxicity at lower levels (developing BBB, pica behaviour)
Clinical relevance
- Systemic features: abdominal pain (lead colic), wrist drop (motor radial neuropathy), encephalopathy (esp. children), Burton's line (gingival), nephropathy, saturnine gout (dec urate excretion)
- Management: remove exposure source; chelate if symptomatic or blood lead above threshold
- Severe/encephalopathy: dimercaprol (BAL) first, then EDTA
- Mild-moderate, no encephalopathy: oral succimer (DMSA)
- EDTA given before BAL in high body burden can redistribute lead into the brain and worsen encephalopathy
Correlations
- Microcytic anaemia + basophilic stippling: differentiate from thalassaemia trait via iron studies, blood lead, Hb electrophoresis
- Wrist drop differential: radial nerve palsy ("Saturday night palsy"), lead distinguished by systemic features (colic, gout, gum line)
- Sideroblastic anaemia causes: lead, alcohol, isoniazid, myelodysplasia, congenital (X-linked ALAS2)
4 of 4 sections written · drafted 2026-09-13