A 30-year-old woman presents with hemolytic anemia, thrombocytopenia, and renal failure following a diarrheal illness caused by Shiga toxin-producing E. coli. The peripheral smear shows schistocytes and reduced platelets, but clotting studies are normal. What is the pathomechanism by which Shiga toxin causes glomerular injury?

• A Toxin activates complement via lectin pathway, depositing C3d on red cells and causing intravascular hemolysis
• B Toxin directly inhibits ADAMTS13 enzyme, permitting large vWF multimers to cause platelet aggregation
• C Toxin induces IgG autoantibodies against factor H, leading to complement dysregulation on endothelium
• D Toxin binds GB3/Gb3 (globotriaosylceramide) on renal glomerular endothelial cells, causing endothelial cell death and thrombotic microangiopathy ✓

Explanation

Shiga toxin (Stx1, Stx2) binds with high affinity to globotriaosylceramide (Gb3), a glycolipid receptor highly expressed on renal glomerular endothelial cells. Internalized toxin inhibits ribosomal protein synthesis (N-glycosidase activity on 28S rRNA), killing endothelial cells and triggering thrombotic microangiopathy — the pathological hallmark of HUS. Gb3 is also expressed on neurons, explaining the CNS complications. ADAMTS13 inhibition characterizes TTP; factor H autoantibodies occur in complement-mediated (atypical) HUS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.