Pathology Flashcards
Pathologic findings of apoptosis
Deeply eosinophilc cytoplasm Cell and nuclear shrinkage Basophilia Membrane blebbing and nuclear karyorrhexis Apoptotic bodies
DNA laddering
Sensitive indicators of apoptosis. Endonucleases cleave nucleosomes leaving 180bp multiples.
MOA of radiation therapy
Causes apoptosis of tumors and surrounding tissues by causing free radical formation and dsDNA breakage. Rapidly dividing cells most susceptible
Intrinsic vs extrinsic pathway of apoptosis
Intrinsic
- used in tissue remodeling in embryogenesis as well as after exposure to injrious stimuli
- inccreased pro/decreased anti apoptotic factors increases mitochondrial permeability and increases cytochrome c release
- BAX and BAK are proapoptotic; bcl-2 is antiapoptotic
Extrinsic
- occurs due to Fas-FasL interactions in thymic medulla negative selection
- also can occur by immune cell release of perforin and granzyme B
- defective Fas-FasL interactions a cause of autoimmune disease
Bcl-2
Anti-apoptotic factor that prevents cytochrome c release. Bcl-2 overexpression leads to decreased caspase activation and tumorigenesis
Coagulative necrosis
- seen in ischemia/infarcts in most tissues
- proteins denature, enzymatic degradation
- cell outlines preserved
- increased cytoplasmic binding of acidophilic dyes
Liquefactive necrosis
- seen in bacterial abscesses and brain infarcts
- neutrophils release lysosomal enzymes that digest tissue
- early findings are cellular debris and macrophages
- late findings are cystic spaces and cavitation
Caseous necrosis
- seen in TB, systemic fungi infection, Novardia
- macrophages wal off organism resulting in granular debris
- pathology: fragmented cells and debris surrounded by lymphocytes and macrophage
Fat necrosis
- seen in acute panreatitis (enzymatic) and breast trauma (non-enzymatic)
- damaged cells release lipase which breaks down fatty acids of membranes
- pathology: outline of dead fat cells, saponification of fat is dark blue on H%E
Fibrinoid necrosis
- caused by immune reactions in vessels when immune complexes combine with fibrin, causing vessel wall damage
- vessel walls thick and pink
Irreversible forms of cell damage
- nuclear changes of apoptosis
- plasma membrane damage
- lysosomal rupture
- mitochondrial permeability/vacuolization
Ischemic-prone area of kidney
Straight segment of proximal tubule
Thick ascending limb
Rep vs white infarct
Red
- occurs in venous occlusion in tissues with multiple blood supplies (liver, lung, intestine)
- reperfusion injury
White
- occurs in solid organs with single end-arterial blood supply
- heart, kidney, spleen
Chromatolysis
- seen in neuronal cell body following axonal injury
- increased protein synthesis to repair damaged axon
- round cellular swelling, displacement of nucleus to periphery, dispersion of Nissl substance
Dystrophic vs metastatic calcification
Dystrophic
- Ca++ deposition in abnormal tissues secondary to injury or necrosis
- seen in TB, liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis
Metastatic
- widespread deposition in normal tissue secondary to hypercalcemia
- deposits predoinantly in interstitial tissues of kidney, lung, gastric mucosa
Steps and deficiencies of leukocyte extravasation
- Margination and rolling; defective in LAD type 2
- Tight binding; defective in LAD type 1 due to decreased CD18
- Diapedesis in which WBC travels between endothelial cells and exits BV
- Migration in which WBC travels through interstitium to site of injury or infection
Retinopathy of prematurity
Abnormal vascularization of retina due to free radical injury
Platelet derived growth factor
Secreted by platelets and macrophages
Induces vascular remodeling and smooth muscle migration
Stimulates fibroblast growth
fibroblast growth factor
stimulates angiogenesis
endothelial growth factor
stimulates cell growth via tyrosine kinases such as EGFR
TGF-beta1
stimulates angiogenesis, fibrosis, cell cycle arrest
Stages of wound healing
Inflammatory: first three days, clot formation, increased vessel permeability and neutrophil migration
Proliferative: day 3- weeks after; deposition of granulation tissue and collagen, angiogenesis, clot dissolution
Remodeling: 1 wk - 6 mos, fibroblasts replace type III collagen with type I collagen
Pathogenesis of granulomas
Th1 cells secrete IFN-gamma activating macrophages
TNFalpha from macrophages induces and maintains granuloma formation
Erythrocyte sedimentation rate
Inflammatory products coat RBCs causing aggregation. Denser RBC aggregates fall at faster rate causing elevated ESR.
Increased in anemia, cancer, pregnancy, anything causing inflammation
Decreased in sickle cell anemia due to altered shape, polycythemia due to dilution of aggregation factors by increased number of red cells, HF, microcytosis, hyperfibrinogenemia
Amyloidosis- general
abnormal aggregation of proteins into beta pleated sheets leading to damage and apoptosis
Primary amyloidosis
Deposits of Ig light chains. Occurs as a plasma cell disorder or in association with multiple myeloma. Often affects multiple organ systems
Secondary amyloidosis
Seen in chronic inflammatory conditions. Composed of serum alyloid A. OFten multi system
Dialysis related amyloidosis
Composed of beta2 microglobulin. Can present as carpal tunnel
Age-related systemic amyloidosis
deposition of transthyretin in myocardium, cardiac dysfunction progresses slower than in primary amyloidosis
Organ specific amyloidosis
Alzhemeris, islet cell amyloidosis in DM2
