HAE Range menu
printThe role of bradykinin
The special role played by bradykinin in the development of hereditary angioedema
Bradykinin is part of a blood coagulation subsystem known as the contact system, which is regulated by C1-INH.
In the contact system, an external stimulus, such as a fresh wound, initiates a whole cascade of reactions, each of which triggers the next. This process starts with a protein circulating in the blood called factor XII, which converts itself into its active form, factor XIIa, in the event of an injury. This in turn converts prekallikrein into kallikrein, which then releases bradykinin from HMW kininogen.
In the contact system, an external stimulus, such as a fresh wound, initiates a whole cascade of reactions, each of which triggers the next. This process starts with a protein circulating in the blood called factor XII, which converts itself into its active form, factor XIIa, in the event of an injury. This in turn converts prekallikrein into kallikrein, which then releases bradykinin from HMW kininogen.
- Chart: Drugs showing an effect on the kallikrein-kinin system. Bradykinin is the key mediator in hereditary angioedema.
Finally, after binding to the bradykinin receptor, bradykinin triggers a series of reactions in the tissues:
- Bradykinin increases the permeability of the vessels (vascular permeability), which allows liquid to pass into the tissues and therefore causes edema.
- Bradykinin widens the blood vessels (vasodilation), which turns the skin red and lowers blood pressure.
- Bradykinin causes the smooth muscle in the tissues to contract, producing cramps and pain.
C1-INH can normally inhibit the reaction cascade at two points: by preventing self-activation of factor XII and by inhibiting the release of bradykinin from HMW kininogen. If there is a C1-INH deficiency, these processes are not controlled and local bradykinin concentration may increase to a critical level if additional triggers are present. As a result edema develops.
Besides the contact system, a system known as the complement system of immune defence also contributes to the development of edema. As in the contact system, an external stimulus, in this case a foreign body or microbe, triggers a reaction cascade which aims to eliminate the alien.
The cascade starts with the protein C1, whose direct counterpart is C1-INH. C1 is activated as soon as the immune system detects a foreign body, although the process is also self-activating to a lesser extent. Activated C1 triggers a series of other factors in the complement system. These either attack the alien directly or, like factor C4, an important factor for diagnosis of HAE, lead to a bradykinin mediated increase in vascular permeability and therefore the development of oedema. If there is a C1-INH deficiency, C1 activation cannot be regulated, which encourages the development of swelling.
Frequently inquired
|
Author: Jerini AG |
