Editing Angioedema (section)

==Pathophysiology==

[[Bradykinin]] plays a critical role in all forms of hereditary angioedema.<ref>{{cite journal |vauthors=Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G |title=Nonallergic angioedema: role of bradykinin |journal=Allergy |volume=62 |issue=8 |pages=842–56 |year=2007 |pmid=17620062 |doi=10.1111/j.1398-9995.2007.01427.x|s2cid=22772933 |doi-access=free }}</ref> This [[peptide]] is a potent [[vasodilator]] and increases vascular permeability, leading to rapid accumulation of fluid in the [[interstitium]]. This is most obvious in the face, where the skin has relatively little supporting [[connective tissue]], and edema develops easily. Bradykinin is released by various cell types in response to numerous different stimuli; it is also a [[pain]] mediator.  Dampening or inhibiting bradykinin has been shown to relieve HAE symptoms.

Various mechanisms that interfere with bradykinin production or degradation can lead to angioedema. ACE inhibitors block [[Angiotensin-converting enzyme|ACE]], the [[enzyme]] that among other actions, degrades bradykinin. In [[hereditary angioedema]], bradykinin formation is caused by continuous activation of the [[complement system]] due to a deficiency in one of its prime inhibitors, C1-esterase (aka: C1-inhibitor or C1INH), and continuous production of [[kallikrein]], another process inhibited by C1INH. This [[serine protease inhibitor]] (serpin) normally inhibits the association of C1r and C1s with C1q to prevent the formation of the C1-complex, which - in turn - activates other proteins of the complement system. Additionally, it inhibits various proteins of the [[coagulation]] cascade, although effects of its deficiency on the development of [[hemorrhage]] and [[thrombosis]] appear to be limited.

The three types of hereditary angioedema are:
* Type I - decreased levels of C1INH (85%);
* Type II - normal levels, but decreased function of C1INH (15%);
* Type III - no detectable abnormality in C1INH, occurs in an [[X-linked]] dominant fashion and therefore mainly affects women; it can be exacerbated by [[pregnancy]] and use of [[hormonal contraception]] (exact frequency uncertain).<ref>{{cite journal |vauthors=Bork K, Barnstedt SE, Koch P, Traupe H |title=Hereditary angioedema with normal C1-inhibitor activity in women |journal=Lancet |volume=356 |issue=9225 |pages=213–7 |year=2000 |pmid=10963200 |doi=10.1016/S0140-6736(00)02483-1|s2cid=30105665 }}</ref> It has been linked with mutations in the [[factor XII]] gene.<ref>{{cite journal |vauthors=Cichon S, Martin L, Hennies HC |title=Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III |journal=Am. J. Hum. Genet. |volume=79 |issue=6 |pages=1098–104 |year=2006 |pmid=17186468 |doi=10.1086/509899 |pmc=1698720|display-authors=etal}}</ref>

Angioedema can be due to [[antibody]] formation against C1INH; this is an [[autoimmune disorder]]. This acquired angioedema is associated with the development of [[lymphoma]].

Consumption of foods that are themselves vasodilators, such as [[alcoholic beverage]]s or [[cinnamon]], can increase the probability of an angioedema episode in susceptible patients.  If the episode occurs at all after the consumption of these foods, its onset may be delayed overnight or by some hours, making the correlation with their consumption somewhat difficult. In contrast, consumption of [[bromelain]] in combination with [[turmeric]] may be beneficial in reducing symptoms.<ref>University of Maryland Medical Center. ''Angioedema.'' {{cite web |url=http://www.umm.edu/altmed/articles/angioedema-000011.htm |title=Page is No Longer Available |access-date=2008-01-08 |url-status=live |archive-url=https://web.archive.org/web/20071012092019/http://www.umm.edu/altmed/articles/angioedema-000011.htm |archive-date=2007-10-12 }}</ref>

The use of [[ibuprofen]] or [[aspirin]] may increase the probability of an episode in some patients. The use of [[acetaminophen]] typically has a smaller, but still present, increase in the probability of an episode.