Case Study: Hereditary Angioedema
1. Translate “angioedema”. [Translate the term, don’t provide a description of the disease]
Angio refers to blood vessels and edema refers to swelling. Overall, the term means “swelling of
blood vessels” (Previous Knowledge)
2. Describe hereditary angioedema. (Provide a brief description of the disease)
Hereditary angioedema is a disorder that has significant recurring swelling affecting extremities,
skin, GI tract and tissue/mucus surfaces. The disease is caused by a lack or deficiency of C1-INH,
which is a major inhibitor and regulator of the complement system; C1-INH also plays a
significant role in regulating the contact pathway of coagulation. This disease is split into 2
different types. Type 1 is due to a decrease in C1-INH production and Type 2 which is when C1-
INH levels are normal, but function is impaired. Each type will help determine what mechanism
of action of C1-INH is affected; however, both types are caused by an autosomal dominant gene
which either codes for a dysfunctional C1-INH or limits the production of C1-INH. (Case Study,
Textbook)
3. The complement system is described as a ‘cascade system’. How does the system fit this
description?
The complement system involves complement proteins that bind to the surface of different cells
or organisms. Complement proteins bind to a cell surface in a particular and specific sequence.
Each complement protein bound will cause a structural change or cleavage which will then allow
a successive complement protein to attach. It is called a “cascade system” as each complement
protein allows a successive protein to attach thus a cascade or domino effect occurs. (Textbook,
Case Study, Prior Knowledge)
4. Is complement involved in the innate or the adaptive immune system, or both? Explain your
answer.
Complement is typically used as an innate immune response but can also work with the
adaptive immune system. For this reason, complement can be involved with both. Complement
proteins are floating throughout an individual’s circulation and can act as a nonspecific defense
mechanism against foreign antigens that appear. Likewise, in the adaptive immune response,
antibodies that are produced may also activate complement in which complement proteins help
with opsonization or destruction of the foreign antigen-containing cell. (Case Study, Textbook)
5. What role does C1INH play in the complement system? Why is it so important?
C1-INH is a protease inhibitor that solely inhibits the function of C1 complement protein. It is
important as it regulates proteases of the clotting and kinin system which is significant as it is
activated by blood vessel and toxin injury. Moreover, C1-INH will inhibit the first stage of the
complement pathway by preventing C1r a C1s from binding to an antigen. C1INH presents a bait
site where C1r and C1s will covalently bind to and dissociate from C1q. As this reaction occurs,
C1INH limits the antibody bound C1 resulting in less cleavage of C4 and C2 and thus less
generation of C4b2a. (Case Study)
6. What was the physiologic cause of Richard’s abdominal pain?
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Due to Richard having deficient C1INH, activation of Factor XII will lead to the eventual
production of bradykinin. Bradykinin may cause Hereditary Angioedema by causing vasodilation,
increased permeability of postcapillary venules through contraction of endothelial cells and
creating gaps in blood vessel walls. These specific physiologic mechanisms will cause edema or
swelling to occur as fluid from a vascular region of the body moves into another compartment of
the body. This movement of fluid from the intestines to the abdominal cavity causes a great deal
of pain which explains the abdominal pain that Richard was experiencing. Additionally, swelling
of the intestine may also be so severe that it obstructs the intestine, thus causing vomiting to
occur. (Case Study)
7. How can one distinguish the swelling of HAE from the swelling of allergic angioedema?
HAE can bee distinguished from allergic angioedema as HAE attacks do not typically involve signs
or symptomology related to allergic reactions such as itching or hives. Additionally, the
mechanism of action for which HAE occurs is different from allergic angioedema. A significant
factor that plays a role in allergic angioedema is histamine; however, HAE attacks are not
mediated through histamine but rather through the activation of certain serine proteases that
are unable to be inhibited by C1INH. (Case Study)
8. What is bradykinin’s role in HAE?
Deficient or non-functional C1INH will allow the uninhibited activation of Factor XII will
eventually lead to the production of bradykinin. Bradykinin may cause Hereditary Angioedema
by causing vasodilation, increased permeability of postcapillary venules through contraction of
endothelial cells and creating gaps in blood vessel walls. These specific physiologic mechanisms
will cause edema or swelling to occur as fluid from a vascular region of the body moves into
another compartment of the body. (Case Study)
9. What is used to treat attacks of HAE?
Purified or recombinant C1INH can be infused/given to the patient to restore the role of C1INH’s
inhibitory and regulatory properties on the complement cascade. This recombinant C1INH will
be given and used as a substitute for those that are deficient or have non-functioning C1INH.
Additionally, a kallikrein inhibitor and bradykinin receptor antagonist may also assist to combat
symptomology. Kallikrein enzymes help catalyze the formation of bradykinin which causes
swelling to occur, so naturally, inhibition of such will help lessen the formation of bradykinin.
Furthermore, bradykinin plays a significant role in the causation of swelling and pain so a
bradykinin receptor antagonist will assist in decreasing bradykinin activity and functionality so
that swelling is reduced thus helping symptomology for the patient. (Case Study)
10. Swelling in the extremities is not dangerous. What other areas of the body are subject to
swelling? What is the most dangerous location for swelling to occur and why is it the most
dangerous?
Other areas of the body that are subject to swelling are the skin, intestines, and subcutaneous
or mucosal linings, the face, trunk, genitals, lips, tongue, larynx, and colon. The most dangerous
location for swelling to occur would be the larynx as it directly affects airway patency. A swollen
larynx will cause obstruction to the airway and thus result in a patient choking to death. (Case
Study)
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