A 14 year old girl has a long history of excessive swelling after mild traumatic injury. Past 2 years she has complained of 7 episodes of intermittent abdominal pain sometimes accompanied by watery diarrhea. Lab tests show decreased c4 and normal c3 levels. C1 inhibitor levels are 20% normal
- What is the most likely diagnosis
- C1 esterase inhibitor deficiency (Hereditary angioedema)
- What pathologic changes would explain this patient’s symptoms
- A result of vasodilation and increased vascular permeability leading to Edema and diarrhoea
- What is the effect of defective C1 esterase inhibitor levels on complement system regulation
- Spontaneous activation of classical complement pathway with cleavage of C4 and C2
- C3 cleavage does not occur to any significant degree since there is no target cell surface for complement binding, C3b formed undergoes spontaneous hydrolysis
- C2a and subsequent products cause vascular permeability changes
- What other inflammatory mediator systems are affected by C1 esterase inhibitor
- Kallikrein-kinin mediator system: increased conversion of Kininogen to bradykinin by Kallikrein promoting vascular permeability changes
- Why are these patients not at significant risk for bacterial infection
- Intact alternative complement pathway
A 23 yo man complains of fever, headache, neck stiffness and fatigue of 2 days duration. Lumbar puncture shows increased pressure, cloudy CSF containing large number of neutrophils, increased proteins, decreased glucose, gram negative diplococci. Lab shows C5 levels at 18% normal and normal levels of C2, C3, and C7. The patient recovers after institution of intravenous antibiotic therapy
- Why would this patient be at increased risk of developing bacterial meningitis
- Acute bacterial meningitis secondary to C5 deficiency, Impaired formation of MAC, Encapsulated meningococci cannot be cleared
- What is the relationship among the 3 pathways of complement activation and bacterial clearance
- All 3 pathways can be activated and bacteria opsonized with C3b and its derivative
- C5 deficiency impairs the production chemotactic C5a peptide and MAC formation
- Would a defect in C2 alone place a patient at increased risk of developing bacterial meningitis
- No, Alternative pathway remains functional in C2 deficiency
- Cells can still be opsonized by C3b and MAC can be formed
