11.10: Vasculitis Flashcards
Types of immune mediated inflammation leading to vasculitis?
- Immune complex associated
- ANCA: antineutrophil cytoplasmic antibody
- Anti endothelial cell antibodies: direct vasc. attack
- Cell mediated immunity
Broad categories that can cause vasculitis?
- Immune mediated
2. Invasion by infectious pathogens
Does vasculitis occur mainly in venous or arterial system?
Arterial
Layers of vessels from inside to out?
- Intima
- Internal elastic lamina
- Media
- Adventitia
How does vasculitis move in small vessels?
From inside out
How does vasculitis move in large vessels?
Vaso vasorum in the adventitia can allows immune cells and pathogens to infiltrate
**Inside out in medium vessels as well
Is vasculitis and inside out or outside in process? Which type of cells are responsible?
- Inside to outside: in small and medium vessels where most occurs
- Normally mediated by neutrophils
How are neutrophils involved?
- Neut is traveling in blood then adheres to vessel wall
- Something causes degranulation leading to inflammation
Pathway in large vessels?
- Naive T Cells activate DCs in adventitia
- Activation cause ROS = damage of media
- Non scarring arteritis: window of opportunity?
- Scarring and fibrosis break down elastic lamina and thicken Intima
- Fibrosis = stenosis / ischemia
- Breakdown of elastic lamina = aneurysm
Difference between instigating cells in small and large vessels?
Small: Neutrophils
Large: Macrophages
Pathway in small vessel vasculitis?
- Inflammatory state is first step
- Next several things could happen:
a. IC attaches and irritates endothelium
b. Anti neutrophil Ig could active neut
c. Ig directly bind endothelium leading to neut attack - Neutrophils then degranulate causing inflammation
- Small vessel comes apart leaking blood
What happens to endothelial cell when activated?
- Procoagulant: express adhesion factors
- Proinflammatory
- Leads to turbulent flow
What are features of all vasculitides?
- Fever
- Fatigue
- Myalgia
- Weight loss
- Organ dysfunction
What is CRP?
- Biomarker for inflammation
- Produced by liver
What occurs when levels of fibrinogen rise?
- Sedimentation rate goes up
What is leukocytoclasis?
- Neutrophils are exploding like kamikazes leaving nuclear debris in wake
Characteristics of small vessel vasculitis?
- Leukocytoclasis
- Fibrinoid necrosis
- Possible Immune complex deposition
What is fibrinoid necrosis?
- Dead neutrophils with fibrin deposition
Clinical signs of small vessel vasculitis?
- Palpable purpura: bumpy and does not blanch
- Bleeding in small vessels of lungs
- Necrotizing glomerulonephritis
What is special about purpura in vasculitis?
- It is bumpy from blood vessel inflammation causing them to pop up
Features of medium vessel vasculitis?
- Muscular layer offers great protection from obliteration
1. Fibrinoid necrosis with pleomorphic infiltrate
2. Fibrinoid necrosis is focal and segmental: not entire circumference, skip along vessel
3. Aneurysms from destruction of media
Clinical findings in medium cell vasculitis?
- Skin nodules in hands
- Livedo: Ringlike rash
- Ulcers instead of palpable purpura
- Abdominal pain
- Nerve infarcts: sensory and motor loss
What causes large vessel vasculitis?
- Usually not neutrophilic like small and medium
- Can be immune complex mediated
- Usually innate cells such as macs and T cells
Characteristics of large vessel vasculitis?
- Innate cell mediated
- Outside in
- Granulomas starting in adventitia usually present
- Intima becomes hyperplastic leading to stenosis / occlusion
- Neovascularization occurs to get some blood through