Pathology Flashcards
Increase in size of cells
hypertrophy
Increase in number of cells
hyperplasia
decrease in tissue mass due to decrease in size
atrophy
reprogramming of stem cells which results in replacement of one cell type by another that can adapt to a new stress
Metaplasia
Disordered precancerous epithelial growth
Dysplasia
Apoptosis
ATP dependent programmed cell death with intrinsic and extrinsic pathways which activate caspases (cytosolic proteases) that cause cellular breakdown –> phagocytosed
deeply eosinophilic cytoplasm and basophilic nucleus. pyknosis or nuclear shrinkage, and karyorrhexis or fragmentation caused by endonuclease mediated cleavage
cell membrane intact without significant inflammation unlike necrosis
DNA laddering is a sensitive indicator of apoptosis
Intrinsic pathway of apoptosis
mitochondrial pathway
involved in tissue remodeling in embryogenesis and after exposure to injurious stimuli. occurs when a regulating factor is withdrawn from a proliferating cell population.
The intrinsic pathway is regulated by the Bcl-2 family of proteins. BAX and BAK (proapoptotic) form pores in the mitochondrial membrane which cause release of cytochrome C from inner mitochondrial membrane into the cytoplasm which activates caspases. Bcl-2 keeps the mitochondrial membrane impermeable and thereby preventing cytochrome C release
Bcl-2 ( antiapoptotic) can decrease caspase activation and cause tumorigenesis
Extrinsic pathway
Death receptor pathway
two pathways:
1) ligand receptor interactions
- Fas-FasL interaction (important for thymic medullary negative selection) or TNF alpha binding its receptor
- defect in Fas-FasL will incrase numbers of circulating self-reacting lymphocytes due to failure of clonal deletion and thus autoimmune lymphoproliferative syndrome
2) immune cell (cytotoxic T cell release of perforin and granzymes B)
Coagulative necrosis
- due to ischemia or infarction; injury denatures enzymes and proteolysis blocked
histology: preserved cellular architecure (cell outlines seen), but nuclei disappear. Increased cytoplasmic binding of eosin stain. The increase in eosinophilia gives it a red/pink color
liquefactive necrosis
-due to neutrophils release lysosomal enzymes that digest the tissue
caseous necrosis
-In TB or fungi. Due to lymphocytes and macrophages walling off the infecting microorganism –> cellular debris. Forming a granuloma
fat necrosis
-In acute pancreatitis or trauma. Damaged cells release lipase which breaks down TGs. Liberated FA bind calcium and saponify (appears blue on H&E stain)
Fibrinoid necrosis
Due to immune complexes that combine with fibrin –> vessel wall damage (type 3 hypersensitivity rxn).
on histology the vessel walls appear thick and pink
gangrenous necrosis
Dry: ischemia. Coagulative on histology
Wet: superinfection. liquefacive superimposed on coagulative (histology)
Watershed areas
i.e. splenic flexure
Watershed areas are borderzones that receive blood supply from most distal branched of 2 arteries with limited collateral vascualrity. These areas are susceptible to ischemia fromhypoperfusion
Red infarct
Hemorrhagic
occurs in venous occlusions and tissues with multiple blood supplies
reperfusion injury that is due to damage by free radicals
Pale infarct
Anemic
occurs in solid organs with a single (end-arterial) blood supply
Inflammation
Response to eliminate initial cause of cell injury, to remove necrotic cells resulting from original insult, and to initiate tissue repair
Cardinal signs of inflammation
- Rubor/Redness and Calor/Warmth due to histamine, prostaglandins, and bradykinin
- Tumor/swelling due to endothelial contraction/disruption (leukotrienes C4,D4, E4 and histamine and serotonin). Increase in vascular permeability causes leakage of protein-rich from postcapillary venules into interstitital space (exudate) which increases oncotic pressure
- Dalor (pain) due to bradykinin and PGF2
Systemic/acute phase rxn of inflammation
Fever (pyrogens induce macrophages to release IL1 and TNF which increases COX activity in perivascular cells of hypothalamus which in turn increase PGE3 –> increases temperature set point)
Leukocytosis - elevation of WBC count.
Leukemoid reaction is a severe elevation in WBC (>40,000 cells)
Increase in plasma acute phase proteins. They are produced by the liver and notably induced by IL-6
Positive/upregulated Acute phase reactants
Ferritin - binds and sequesters iron
Fibrinogen - coagulation, ESR
Serum amyloid A- elevation leads to amyloidosis
Hepcidin - decreases iron absorption and iron release. Anemia of chronic disease
C-reactive protein(CRP)-opsonin; fixes complement and facilitates phagocytosis. Nonspecific sign of ongoing inflammation
Negative/downregulated acute phase reactants
Albumin -reduction conserves AA for positive reactants
Transferrin- internalized by macrophages to sequester iron
Erythrocyte sedimentation rate (ESR)
Products of inflammation (eg fibrinogen) coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube and thus higher ESR
Acute inflammation
- neutrophils in tissue and edema
- involves the innate immune system (first line of defense, i.e. skin etc)
- Inflammasome- cytoplasmic protein complex which recognizes cell products of dead cells, microbial products, and crystals –> activates Il-1 and inflmmatory response
- extravasation of leukocytes (mainly neutrophils) from postcapillary venules and accumulation in the focus of injury followed by leukocyte activation
- macrophages dominate in the later stages
- outcomes:
1) resolution and healing due to Il-10 and TNF beta which attenuate immune response
2) IL-8 can cause persisten acute inflammation
3) chronic inflammation due to APCs activaing CD4+ Th cells
