A 4-year-old boy living in an old house with peeling paint develops abdominal colic, constipation, and irritability. Hemoglobin is 8.6 g/dL with microcytosis, and the peripheral smear shows prominent coarse basophilic stippling. Lead produces this anemia primarily by:

• A Directly lysing red cell membranes through complement activation
• B Oxidizing hemoglobin iron to the ferric state, forming methemoglobin
• C Inhibiting ALA dehydratase and ferrochelatase in the heme synthetic pathway ✓
• D Blocking ribosome assembly, causing pure red cell aplasia

Explanation

Lead blocks two enzymes of heme synthesis: ALA dehydratase (conversion of ALA to porphobilinogen) and ferrochelatase (insertion of iron into protoporphyrin). The result is a microcytic sideroblastic anemia with accumulation of ALA and zinc protoporphyrin. Basophilic stippling reflects ribosomal RNA aggregation and is a classic smear clue. Methemoglobinemia is caused by oxidant drugs and nitrates, not lead, and lead does not cause complement lysis or pure red cell aplasia.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.