Hereditary Angioedema (HAE)

Summary

In this video, the host discusses hereditary angioedema, a genetic disorder characterized by recurrent episodes of swelling, particularly in the face, lips, eyelids, and genitalia. The condition results from a deficiency or dysfunction of the C1 inhibitor, leading to excessive bradykinin production. This causes vasodilation, increased vascular permeability, and symptoms such as pain, hypotension, and bronchoconstriction. The video explains the pathophysiology of the disorder, its types, and how it affects patients. It also highlights ACE inhibitors' role in exacerbating symptoms due to their effect on bradykinin metabolism.

Takeaways

• 😀 Hereditary angioedema (HAE) is an autosomal dominant disorder that causes swelling in various parts of the body, including the lips, face, eyelids, and genitalia.
• 😀 Bradykinin, a pro-inflammatory mediator, plays a major role in the symptoms of hereditary angioedema, such as vasodilation, increased vessel permeability, and pain.
• 😀 C1 inhibitor normally regulates bradykinin production by inhibiting plasma kallikrein, but in hereditary angioedema, this inhibition is absent or dysfunctional.
• 😀 ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, increase bradykinin levels, potentially leading to side effects like dry cough and angioedema.
• 😀 The condition is typically inherited, with a 50% chance of passing the mutant gene to offspring, leading to the disease in 50% of cases.
• 😀 There are three types of hereditary angioedema: Type 1 (C1 inhibitor deficiency), Type 2 (C1 inhibitor dysfunction), and Type 3 (normal C1 inhibitor but overactive factor XII).
• 😀 In hereditary angioedema, patients often experience abdominal pain as a common symptom due to increased vascular permeability in the gut.
• 😀 Type 1 HAE is the most common, characterized by a decreased amount of C1 inhibitor, whereas Type 2 involves a normal amount of C1 inhibitor but with decreased function.
• 😀 Type 3 HAE occurs when factor XII is abnormally overactive, leading to excessive bradykinin production despite normal C1 inhibitor levels.
• 😀 In patients with HAE, levels of prekallikrein are typically decreased, and high molecular weight kininogen levels are low due to conversion into bradykinin.
• 😀 Diagnosis and treatment for hereditary angioedema are covered in subsequent videos, with information available on Patreon for those seeking further learning materials and cases.

Q & A

What is the primary cause of hereditary angioedema (HAE)?

The primary cause of hereditary angioedema is a deficiency or dysfunction of C1 inhibitor (C1-INH), which leads to excessive production of bradykinin, a molecule responsible for inflammation and swelling.

How does bradykinin contribute to the symptoms of hereditary angioedema?

Bradykinin causes vasodilation, increases vascular permeability (leading to fluid leakage into tissues), triggers pain, and causes smooth muscle contraction, leading to bronchoconstriction and dry cough.

What is the function of C1 inhibitor in the blood coagulation system?

C1 inhibitor normally regulates the plasma kallikrein-kinin system by inhibiting the activation of kallikrein and the production of bradykinin, helping to prevent excessive inflammation and swelling.

What are the key differences between the three types of hereditary angioedema (Type 1, Type 2, and Type 3)?

Type 1 involves a deficiency of C1-INH, Type 2 involves dysfunctional C1-INH, and Type 3 is characterized by normal C1-INH levels but overactivation of factor XII, leading to excessive bradykinin production.

What role does factor XII play in Type 3 hereditary angioedema?

In Type 3 HAE, factor XII is abnormally overactivated, which leads to excessive activation of the kallikrein-kinin system and increased production of bradykinin, even though C1-INH is normal.

What are the common clinical symptoms of hereditary angioedema?

Common symptoms include angioedema (swelling), abdominal pain, pain and swelling in the limbs and genitalia, bronchoconstriction leading to dry cough, and hypotension due to vasodilation and fluid leakage.

How is hereditary angioedema inherited?

Hereditary angioedema is inherited in an autosomal dominant manner, meaning that an affected individual has a 50% chance of passing the condition on to each offspring.

What is the effect of C1 inhibitor deficiency on the production of bradykinin?

In the absence of sufficient C1 inhibitor, the kallikrein-kinin system becomes uninhibited, leading to the excessive production of bradykinin, which results in the symptoms of HAE.

What happens to the levels of prekallikrein and high-molecular-weight kininogen in hereditary angioedema?

In hereditary angioedema, both prekallikrein and high-molecular-weight kininogen levels are decreased, as these molecules are consumed in the production of bradykinin.

What is the significance of C1-INH testing in diagnosing hereditary angioedema?

C1-INH testing helps diagnose hereditary angioedema by measuring the levels and functionality of C1-INH. A deficiency or dysfunction of this inhibitor confirms the diagnosis of HAE.