Hageman factor (factor XII) activation at sites of injury triggers which inflammatory mediator system that is primarily responsible for the increased vascular permeability seen in hereditary angioedema (C1 inhibitor deficiency)?

• A C5a via alternative complement pathway
• B Prostaglandin E2 via COX pathway
• C Bradykinin generated from kallikrein-kinin system ✓
• D Histamine from mast cell degranulation

Explanation

Activated Hageman factor (XIIa) activates the kallikrein-kinin system: XIIa converts prekallikrein to kallikrein, which cleaves high-molecular-weight kininogen (HMWK) to release bradykinin. Bradykinin causes vasodilation, increased vascular permeability, pain, and bronchoconstriction via B2 receptors. C1 inhibitor (C1-INH) normally inhibits both C1r/C1s AND plasma kallikrein; its deficiency leads to bradykinin accumulation and angioedema. Treatment is icatibant (B2 receptor antagonist), C1-INH concentrate, or lanadelumab (anti-kallikrein). This is not histamine-mediated, explaining why antihistamines are ineffective.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.