Hereditary angioneurotic edema (HANE)

• “hereditary” comes from the fact that the people who had the disease all had family members that had it

• “edema” comes from the fact that these folks had a tendency to swell up locally for unclear reasons (bad cold leading to tracheal swelling; a blow to the arm leading to localized swelling)

• when it swells up, it freaks them out—hence, “neurotic”

• 17 yo male, hx abd swelling after trauma

• now, with unexplained abd pain

• swelling is non-painful and does not itch

• life-long history

• positive family history, both male and female

• poor history-taking by physicians—they never asked him if he had experienced this before

• successfully treated with C1INH

Characteristics of the disease

• C1INH low

• C4 low because he’s consuming it

• C3 normal

Principles you need to understand

• complement cascade: classical, MB-lectin, and alternate pathways

• inhibitory activities of C1INH ppt 5

  • inhibits blood clotting factor XII

  • inhibits plasmin, which dissolves clots

  • inhibits kallikrein

  • inhibits C1 activities

• chronic spontaneous activation of complement produces excess C2a and C4a. it potentially produces C2b and C4b, but these rapidly lose their ability to stick to membranes—with no bacteria around, C2b and C4b are inactivated in fractions of a second. this is not true for C2a and C4a. C2a and C4a these are what cause the symptoms of the disease ppt 6

• normally, C4b and C2b bind to bacteria immediately and form the C3 convertase (C3ase) called C2b4b

• instead, C2a, which persists, is cleaved by plasmin to a product that causes increased vascular permeability (C3a does this, too) and swelling

• since mast cells are not involved, no histamine is released, so there is no itching

The complement pathway

• in the classical and MB-lectin pathways, C2 and C4 get put together to form a C3 convertase

• the alternate pathway involves B and D and amplifies this pathway

Category: Pathology Notes