Vascular Pathology 2 Flashcards
Vasculitis
“Inflammation of Vessels”
- Clinical presentation may depend on the location of the affected vessels, but patients also frequently show NONSPECIFIC SIGNS and SYMPTOMS, including
◦ Fever
◦ Malaise, Arthralgias, Myalgias
Infection or Noninfectious Vasculitis
◦ NONINFECTIOUS VASCULITIS is mediated by IMMUNOLOGIC INJURY, such as immune complex deposition or autoantibodies
◦ INFECTIOUS VASCULITIS is mediated by PATHOGENIC ORGANISMS invading the vessel wall
◦ The distinction between the two is important, because NONINFECTIOUS VASCULITIS INDICATES IMMUNOSUPPRESSIVE THERAPY
Immune Complex Vasculitis
1) DEPOSITION of Ag-Ab Complexes in Vascular Walls
- Incites an Inflammatory Reaction WITHIN THE WALL
- Ag is often Unidentified
2) May be seen in:
- SLE
- Drug Hypersensitivity
- Secondary to exposure to infectious agent
Antineutrophil Cytoplasmic Antibodies
1) A heterogeneous group of ANTIBODIES reactant with CYTOPLASMIC ENZYMES found in Neutrophil granules, monocytes, and endothelial cells
a) Anti-proteinase-3 (previously c-ANCA)
b) Anti-myeloperoxidase (previously p-ANCA)
2) ANCA titers generally follow DISEASE SEVERITY
3) ANCAs ACTIVATE NEUTROPHILS, which then release reactive oxygen species
Giant Cell (Temporal) Arteritis
** MOST COMMON VASCULITIS AMONG OLDER PATIENTS, may present with constitutional symptoms (Greater than 50 y/o!!!!!)
1) CHRONIC (T cell mediated) INFLAMMATION of arteries in the head, especially the TEMPORAL ARTERIES:
◦ Medial GRANULOMATOUS inflammation, often with MULTINUCLEATE GIANT CELLS!!!!!!!!!!!!!!!!!!
◦ Fragmentation of the ELASTIC LAMINA
◦ Sites of involvement within an artery may be PATCHY and FOCAL
◦ Healed sites of inflammation show SCARRING OF THE MEDIA and INTIMAL THICKENING!!!!!!!!!
2) Involvement of the OPHTHALMIC ARTERY may lead to VISION LOSS!!!!
Takayasu Arteritis
1) SIMILAR HISTOLOGIC FINDINGS as those seen in GIANT CELL ARTERITIS, except:
◦ Involves the AORTIC ARCH and MAJOR Branch Vessels (“** PULSELESS DISEASE**”)
◦ PULMONARY, CORONARY and RENAL arteries may be involved
◦ YOUNGER age group (Less than 50 y/o!!!!!!!!!!!)
2) May present with WEAK PULSE and BLOOD PRESSURE in the UPPER EXTREMITIES
- *** Thickening of INTIMA!!!!
- *** Multinucleate Giant Cells
Polyarteritis Nodosa (PAN)
1) SYSTEMIC VASCULITIS, likely IMMUNE COMPLEX MEDIATED
2) Involves (decreasing order of frequency)
- Renal vessels, heart, liver, GI tract
- PULMONARY Vessels are SPARED!!!!!!
3) May affect any age group, but classically YOUNG ADULT!!!!!!
4) Almost one third of patients have CHRONIC HEPATITIS B!!!!
- HBsAg-HBsAb complexes are found in the involved vessels
5) IMMUNOSUPPRESSIVE therapy is usually EFFECTIVE
6) Transmural NECROTIZING Inflammation, containing NEUTROPHILS, EOSINOPHILS, LYMPHOCYTES and MACROPHAGES
- NO Giant Cells!!!!!!
7) FIBRINOID NECROSIS of the vessel wall!!!!!!!
8) Sites of inflammation are typically NOT CIRCUMFERENTIAL!!!!!
9) The inflamed vessel wall my become susceptible to:
◦ Thrombus formation/occlusion
◦ Aneurysm
◦ Rupture
Kawasaki Disease
1) Acute arteritis of INFANTS and SMALL CHILDREN (80% less than or equal to 4 years)
2) Often involves the CORONARY ARTERIES
- Affected sites may form ANEURYSMS → THROMBOSIS or RUPTURE → acute MI!!!!!!
3) Presenting picture is usually erythema of the CONJUNCTIVA, ORAL MUCOSA, PALMS and SOLES; RASH, and cervical lymph node enlargement
- “Mucocutaneous lymph node syndrome”
4) Usually SELF-LIMITED, but IVIg and ASPIRIN are indicated to lower the risk of a coronary event
Microscopic Polyangiitis
1) Necrotizing vasculitis involving ARTERIOLES, CAPILLARIES and VENUES
2) Affects vessels of many organ systems:
- RENAL GLOMERULI and LUNG CAPILLARIES MOST COMMON
3) Most cases associated with MPO-ANCA!!!!!!!!!!!!!!!!
4) SEGMENTAL NECROTIZING Inflammation with FIBRINOID NECROSIS
- Many APOPTOTIC NEUTROPHILS*** are usually seen
- “leukocytoclastic vasculitis”
Chung- Strauss Syndrome
1) Small vessel necrotizing vasculitis, associated with:
- ASTHMA, ALLERGIC RHINITIS, HYPEREOSINOPHILIA, lung infiltrates, extravascular granulomas
2) The inflammation may resemble PAN or m. polyangiitis, with the addition of EOSINOPHILS and GRANULOMAS!!!!!!!
3) Less than half show ANCA positivity
4) Many organ systems may be involved.
*** TH2 Driven PROCESS!!!!!!!
Behçet Disease
1) Vasculitis of SMALL TO MEDIUM VESSELS with the following additional findings:
- Aphthous ULVERS of the ORAL cavity
- GENITAL ULCERS
- UVEITIS
2) The vessel inflammation is NEUTROPHILIC and morphologically nonspecific, may involve visceral organ systems with subsequent ANEURYSM FORMATION
3) Associated with HLA-B51!!!!!!!!!!!!!!
Granulomatosis with Polyangiitis
1) Formerly known as WEGENER Granulomatosis
2) NECROTIZING Vasculitis featuring:
- Necrotizing GRANULOMAS of the UPPER and/or LOWER RESPIRATORY TRACT!!!!!!!
- Necrotizing or Granulomatous vasculitis, most prominently in the RESPIRATORY TRACT!!!!!
- Focal NECROTIZING, often Crescentic, GLOMERULONEPHRITIS!!!!!!!
3) Associated with PR3-ANCA (up to 95% of cases)!!!!!!!!!!
4) IMMUNOSUPPRESSIVE therapy is usually SUCCESSFUL
(UNTREATED, 80% MORTALITY in one year)
5) CLINICAL FEATURES:
- M >F
- Avg age of 40
- Most patients have PERSISTENT Pneumonitis and Sinusitis, Renal disease, and Nasopharyngeal ulceration
6) MORPHOLOGY:
- UPPER respiratory tract: sinonasal and pharyngeal inflammation with GRANULOMAS and VASCULITIS
- LOWER respiratory tract: multiple necrotizing GRANULOMAS which may COALESCE and CAVITATE
Thromboangiitis Obliterans
BERGER’S DISEASE
1) ACUTE and CHRONIC THROMBOSING VASCULITIS of small and medium vessels, especially
- Tibial arteries
- Radial arteries
2) May lead to vVASCULAR INSUFFICIENCY of the extremities
3) Patients are almost always SMOKERS, and YOUNG ADULTS
4) Inflammation may EXTEND to involve adjacent VEINS and NERVES (leading to pain)
5) CHRONIC ULCERATIONS, which may lead to GANGRENE
Raynaud Phenomenon
1) Excessive VASOSPASM of SMALL Arteries and Arterioles, especially in the fingers and toes
2) PRIMARY Raynaud phenomenon:
- Induced by COLD or EMOTION; SYMMETRIC** involvement of the digits
- Estimated 3-5% general population; YOUNG WOMEN
- BENIGN course
3) SECONDARY Raynaud phenomenon
- A component of another arterial disease such as SLE, scleroderma, or thromboangiitis obliterans; ASYMMETRIC** involvement of digits
- WORSENS with TIME!!!!
Myocardial Vessel Vasospasm
1) EXCESSIVE VASOCONSTRICTION of myocardial arteries or arterioles (“cardiac Raynaud”) may cause ischemia or infarct
2) Usually caused by CIRCULATING VASOACTIVE AGENTS, which may be Endogenous (Ex: Epinephrine) or Exogenous (Ex: Cocaine)
