CV Pathology 1 Flashcards
organization of the vasculature into tunics
- intima:
-endothelium = hemostasis regulation
-internal elastic lamina layer - media:
-smooth muscle, helically arranged
-elastic fibers - aventitia:
-connective tissues (loose/dense irregular)
-+/- vaso vasorum
vasculature classifications
- elastic:
-maintain BP
-aorta, pulmonary artery - muscular:
-distribute blood to/from organs - arterioles/venules:
-control blood into/out of capillary bed - capillaries:
-tissue gas/nutrient exchange
-types: continuous, fenestrated, sinusoidal
inflammatory markers - general
*certain proteins released into the bloodstream during inflammation
*if their concentrations increase or decrease by at least 25%, they can be used as systemic inflammatory markers
*help to identify generalized inflammatory state (NOT diagnostic for any particular condition)
*examples: C-reactive protein, erythrocyte sedimentation rate
C-reactive protein (CRP)
*a general inflammatory marker (reliable early indicator of active systemic inflammation)
*made in liver following IL6 secretion by macrophages/T cells
*helps to activate complement
*normal range: <3-10 mg/L
*infections/inflammatory conditions → several hundred-fold increase
*concentrations change rapidly in first 6-8 hours after injury, peak at 48 hours, then normalize once the issue has resolved
erythrocyte sedimentation rate (ESR; sed rate)
*a general inflammatory marker
*ESR = rate at which RBCs in anticoagulated whole blood descend in a standardized tube over a period of 1 hour
*indirect measurement of plasma protein concentrations
*normal values are specific to age and sex
*increased levels → inflammation, pregnancy, anemia, autoimmune disorders, infections, cancer
anti-neutrophilic cytoplasmic antibodies (ANCAs) - overview
*heterogenous autoantibodies directed against neutrophil primary granules and monocyte lysosomes
*directly ACTIVATE neutrophils, stimulating release of ROS and proteolytic enzymes, which in vascular beds → endothelial cell injury
*useful diagnostic markers
anti-myeloperoxidase (MPO-ANCA)
*specific type of perinuclear-ANCA (p-ANCA)
*elevated levels = EGPA (eosinophilic granulomatosis with polyangiitis)
anti-proteinase-3 (PR3-ANCA)
*specific type of cytoplasmic-ANCA (c-ANCA)
*elevated levels = GPA (granulomatosis with polyangiitis)
vasculitis - overview
*group of disorders defined by presence of vessel wall inflammation & destruction
*highly varied pathophysiology and clinical features
*any vessel in any organ may be affected
*> 20 primary forms, based on:
-vessel diameter
-role of immune complexes
-type of inflammation
-organ specificity
-population demographics
vasculitis - general clinical manifestations
*findings referable to the specific tissue(s) involved
*constitutional s/s associated with systemic inflammation: fever, myalgias, arthralgias, malaise
vasculitis - pathogenesis
- immune-mediated inflammation:
-immune complex deposition
-ANCA antibodies
-anti-endothelial cell antibodies
-autoreactive T cells - direct invasion of vascular walls by infectious pathogens:
-may generate immune complexes indirectly inducing immune-mediated process - direct physical/chemical injury (irradiation, mechanical trauma, toxins)
giant cell arteritis - overview
*chronic granulomatous disorder that principally affects LARGE-SIZED ARTERIES in the head
*most common form of vasculitis among US elderly
*arteries commonly affected: TEMPORAL ARTERY, vertebral arteries, ophthalmic arteries, aorta
note - an example of large vessel arteritides
giant cell arteritis - pathogenesis
*T cell-mediated response to as-yet uncharacterized vessel wall antigen
*pro-inflammatory cytokines (TNF) and anti-endothelial cell antibodies
*granulomatous inflammation
giant cell arteritis - pathology
*GRANULOMATOUS INFLAMMATION IN A PATCHY DISTRIBUTION
-nonnecrotizing
-multinucleated giant cells
-fragmented internal elastic membrane
-involved segments exhibit intimal thickening impinging on lumen, causing distal ischemia
Kawasaki disease - overview
*acute, febrile, self-limited arteritis of infancy/childhood
*usually medium vessels/coronary arteries are affected
note - an example medium vessel arteritides
Kawasaki disease - clinical manifestations
*frequent involvement of coronary arteries → development of coronary artery aneurysms/thromboses
*FEVER > 5 days
*CRASH syndrome:
-Conjunctival infection
-Rash, desquamating
-Adenopathy (cervical)
-Strawberry tongue
-Hand/foot (edema/erythema)
Kawasaki disease - pathogenesis
*unknown
*seasonal variation in incidence (maybe a viral triggered immune response)
*?? anti-endothelial cell antibodies + delayed type IV hypersensitivity
Kawasaki disease - pathology
*TRANSMURAL, FIBRINOID NECROSIS - SUPPARATIVE
*neutrophils & lymphocytes
*fibrin
*wall damage → aneurysm
granulomatosis with polyangiitis (GPA) - diagnostic triad
- necrotizing granulomatosis vasculitis (small vessels)
- respiratory tract involvement (upper: ear, nose, sinuses, throat OR lower: lung OR both)
- renal involvement - necrotizing glomerulonephritis
note - an example of small vessel vasculitides
granulomatosis with polyangiitis (GPA) - clinical features
*bilateral pneumonitis with cavitary lesions
*CHRONIC SINUSITIS with nasopharyngeal mucosal ulcerations (SADDLE NOSE)
*renal disease
*PR3-ANCAs present (c-ANCA)
granulomatosis with polyangiitis (GPA) - respiratory tract pathology
*upper = sinusitis with ulcerating mucosal granulomas
-nose, palate, or pharynx, rimmed by granulomas with geographic patterns of central necrosis and accompanying vasculitis
*lower = NECROTIZING GRANULOMAS WITH GIANT CELLS
-leukocyte infiltrate surrounded by zone of fibroblasts
-coalesce to produce radiographically visible cavitary nodules
granulomatosis with polyangiitis (GPA) - renal pathology
*mild = focal glomerular necrosis with isolated capillary loop thrombosis
*advanced = diffuse necrosis with parietal cell proliferation
hemangioma - overview
*common BENIGN tumors composed of blood-filled vessels
*variants:
1. capillary hemangiomas (skin, SQ tissues, oral cavity, liver, spleen, kidneys)
2. juvenile hemangiomas (strawberry; skin)
3. cavernous hemangiomas (large, cystically dilated vascular channels)
4. pyogenic hemangiomas (skin of gingival or oral mucosa)
hemangiomas - pathology
*composed of OBVIOUS VASCULAR CHANNELS lined by normal-appearing endothelial cells
*lumens are filled with blood cells or lymph
*usually circumscribed
Kaposi Sarcoma - overview
*malignant vascular neoplasm caused by human herpesvirus-8 (HHV-8)
*most common in individuals with impaired T-cell function (AIDS)
Kaposi Sarcoma - 4 clinical forms
- classic Kaposi Sarcoma = older men of Ashkenazi Jews descent
-confined to skin/subcutis of lower extremities - endemic [African] Kaposi Sarcoma = HIV-negative children/young adults
-indolent or aggressive; involving lymph nodes/viscera - transplantation-associated Kaposi Sarcoma = solid-organ transplant recipients
-aggressive; involves lymph nodes, mucosa, viscera
-lesions regress with attenuation of immunosuppression - epidemic [AIDS-associated] Kaposi Sarcoma = AIDS-defining illness
-most common HIV-related malignancy worldwide
-involves lymph nodes and disseminates widely to viscera early in its course
Kaposi Sarcoma - pathogenesis
*HHV-8 latently infected endothelial cells
*encodes homologs of IL6, cyclin D, p53 inhibitors
*absent effective T cell response, proliferation persists → clonal evolution → progression to full-fledged malignancy
Kaposi Sarcoma - gross pathology
*3 sequential stages:
- patches = pink, red, or purple macules
-dilated, irregular, and angulated blood vessels associated with an infiltrate of chronic inflammatory cells - plaques = elevated lesions
-dilated dermal vascular channels lined by plump spindle cells - nodular lesions = overt tumors
-increased proliferating spindle cells with interspersed slit-like spaces
-accompanied by nodal/visceral involvement (Endemic African & Epidemic AIDS variants)
Kaposi Sarcoma - microscopic pathology
*dilated, irregular, angular blood vessels
-slit like spaces
-extravasation of RBCs/hemorrhage
*infiltrate of lymphocytes
*nuclear expression of HHV-8 (latency associated nuclear antigen-1 = LANA1)
angiosarcoma - overview
*malignant spindle cell neoplasm of ENDOTHELIAL PROLIFERATION
*more common in older adults
*affects skin, soft tissue, breast, liver
*highly aggressive tumors (invade locally & metastasize)
angiosarcoma - pathogenesis risk factors
*LYPHEDEMA
*RADIATION
angiosarcoma - pathology
*early = small, sharply demarcated, red nodules
*advanced = large with ill-defined margins
*range in differentiation:
-well differentiated = hemangioma-like
-poorly differentiated = wildly anaplastic lesions with pleomorphism, branching vascular channels, atypical mitoses
