Pathology Of Vascultiis Flashcards
Vasculitis definition
Generalized term for various types and causes of vessel wall inflammation
- there are 20 primary forms of vasculitis that are recognized
Common classifications include the following characteristics:
1) vessel diameter
2) immune complexes present or not
3) presence of specific antibodies
4) granuloma formation or not
5) organs being affected
6) population demographics
Clinical manifestations of vasculitis
Very widespread but usually are associated to specific affected vascular beds
Non-specific symptoms/signs include
- myalgia
- inflammation
- fever
- arthralgia
- malaise
Main immunologic mechanisms of non infectious vasculitis
Immune complex deposition
- henloch-purpura
- cyroglobinemic
- nodosa
Anti-Neutrophil Cytoplasmic Antibodies (ANCAs)
- GPA/ wegners
- MPA
- churgg Strauss/ eosinophilc
Anti-endothelial cell antibodies
- Kawasaki’s
Auto reactive T cells
- giant cell
- takayasu
Immune complex associated vasculitis
Immunologic disorders such as SLE and is associated with autoantibody production
Anti-Neutrophil cytoplasmic antibodies (ANCAs)
Vasculitis that produces antibodies that react with neutrophil cytoplasmic antigens.
- can directly activate neutrophils stimulating the release of ROS and proteolytic enzymes
There are two main types of ANCAs
- p-ANCA
- c- ANCA
Two main types of ANCAs
1) Anti-proteinase-3 (PR3-ANCA or (c-ANCA)
- azurophilic granule constituent antibody that is associated with granulomatosis w/ polyangiitis vasculitis.
2) Anti-myeloperoxidase (MPO-ANCA) or (p-ANCA)
- lysosomal granule constituent antibody that is associated with microscopic polyangiitis and churg-Strauss syndrome
- these antibodies directly attack and activate neutrophils without reason, causing ROS to rain on endothelial cells and cause inflammation and damage-> vasculitis*
Giant Cell (temporal) arteritis
Chronic inflammatory disorder w/ granulomatous inflammation
- affects large-small arteries of the head
Diagnosis is only done via biopsy of temporal arteries, however must treat it before diagnosis w/ corticosteroids or anti-TNF therapies.
- can also induce vertebral and ophthalmic arteries
- if not treated, causes sudden and permanent blindness and possibly death*
- MOST COMMON form among >50yrs old adults in developed countries*
Pathogenesis of Giant Cell arteritis
Unknown for sure, but likely occurs as a result of T-cell-mediated immune response to an uncharacterized vessel wall antigen
- often presents with granulomas in the facial arteries and large amounts of pro-inflammatory cytokines
Morphology of Giant Cell arteritis
Involved arterial segments exhibit Nodular intima thickening and overall marked reduction of vessel diameters which causes distal ischemia
- presence of granulomas w/ inflammation within the internal elastic lamina will also be present
note these morphological are patchy in appearance, so if biopsy comes back negative, this diagnosis can not be ruled out
Signs and symptoms and to of giant cell arteritis
Can be vague and constitutional
- abrupt vision issues
- painful temporal arteries/regions
- intermittent jaw claudication
- fever
- malaise and myalgia
- thickened temporal arteries
- treatment is immediate corticosteroids (even before biopsy) when suggested diagnosis, may also use TNF- inhibtors also*
Takayasu arteritis
Granulomatous vasculitis of medium and large sized arteries characterized with ocular dysfunctions and marked weakening of the pulses in the upper extremities
- often called “Pulseless disease”
Always manifests as transudate scarring and thickening of the aorta, usually found in the aortic arch, pulmonary arteries or/and great vessels with severe luminal narrowing
Major differences between takayasu arteritis and giant cell aortitis
They all have the same symptoms however the age of the patient is the primary differential factor
- > 50yrs = giant cell
- <50yrs = takayasu
Signs and symtpoms of takayasu arteritis
Nonspecific to begin with
- fever
- weight loss
- fatigue
Specific with progression
- marked reduction in radial and branchial pulses
- neurological symptoms
- ocular defects
Polyarteritis Nodosa (PAN)
Systemic vasculitis of small-medium sized muscular arteries
- typically includes renal, cardiac and visceral/GI vessels
- almost always NO pulmonary issues
Usually transumual necrotizing inflammation when inflammation occurs
often associated with chronic Hep B infections and deposit is hepatitis B antigens into affected vessels, causing mass inflammation, but can also be idiopathic
Clinical features and Tx of PAN
Most common in young adults but can be in any age
Symptoms are EPISODIC and include
- malaise
- fever
- weight loss
- rapidly accelerating HTN seen in kidney lesions*
- abdominal pain*
- blood stools via GI lesions*
- peripheral neuritis affecting motor nerves*
TX:
- immunosuppressive via corticosteroids
- no treatment often kills, Tx = 80% survival rate
