Necrosis and Atherosclerosis Flashcards
what are the 2 pathways for cell death?
apoptosis (planned)
necrosis (pathological)
What are some unique features of necrosis?
swelling and karyolysis
What are some unique features of apoptosis?
shrinkage and apoptotic bodies
How can ischemia lead to necrosis?
mitochondria damage, increased glycolysis and running out of ATP
sodium pump stops working (needs ATP)
osmosis causes cell to start to swell
coagulative necrosis
architecture of cell is preserved but cell contents are condensed and hyperdense
this causes cell to stain eosinophilic
liquefactive necrosis
complete loss of cell and tissue architecture
creates pus in infection
Where does liquefactive necrosis always take place?
the brain
What type of necrosis creates abscesses?
liquefactive necrosis
What type of necrosis creates granuloma?
caseous necrosis
caseous necrosis
cannot clear pathogen so you in case it in layers of fibroblasts to wall it off
looks like cheese in gross anatomy
common cause of caseous necrosis
TB
where does saponification occur? and specifically?
fat necrosis
specifically, pancreatitis
How does fat necrosis appear? Why
appears basophilic due to accumulation of calcium lipid salts
fibrinoid necrosis
fibrin leaks into vessels
fibrin stains bright pink
often due to autoimmune disease attacking vessel walls
wet gangrene is caused by …
liquefactive necrosis
dry gangrene is caused by …
coagulative necrosis
how can you differentiate apoptotic bodies from blebs
apoptotic bodies are rounder and nicer looking
what type of cell clears apoptotic bodies?
macrophages
what is a chemotactic factor released by apoptotic cells? what do they attract?
ADP / UTP produced by connexon channels
attract macrophages
Does apoptosis produce an inflammatory response?
no, for this reason it is considered “sterile”
what serves as signal for phagocytosis in apoptosis cell?
phosphatidyl serine (PS)
What class of enzyme is the critical effector molecule for apoptosis?
Caspases
What is the active site of caspases?
cysteine
How do you active caspases?
need to cleave them
3 isoforms of caspases to know
3, 8, 9
What can caspase activation lead to?
organellar fragmentation, translational shutdown, actin depolymerization, detachment of cells from ECM and inactivation of flipases
Intrinsinc pathway of apoptosis
mitochondrial damage and formation of apoptosome
*also recognize cytochrome C as part of this
Extrinsic pathway of apoptosis
DISC (death inducing complex)
caspase 8
binding of death ligands
NK cells and cytotoxic T cells can signal extrinsic, death, pathway
What is common between intrinsinc and extrinsic apoptosis pathways?
caspase 3
What cells express the FasL ligand to trigger the extrinsic death pathway?
NK cells and activated T-cells
Caspase 9 is part of …
intrinsic (mitochrondrial) apoptosis pathway
Caspase 8 is part of …
extrinsic apoptosis pathway
Caspase 3 is part of …
both intrinsic and extrinsic apoptosis pathway
Which requires ATP, apoptosis or necrosis?
apoptosis
Difference between ischemia and infarction
infarction is irreversible injury
white infarct
not hemorrhagic
typically seen in dense tissues (heart + kidneys)
red infact
has some collateral blood flow
blood is able to re-enter the tissue to some extent
What type of vessels does atherosclerosis occur in?
arteries only
6 steps of forming an atherosclerotic plaque
1) endothelial injury
2) endothelial dysfunction leading to monocytes and platelet adhesion
3) macrophage activation and smooth muscle recruitment
4) accumulation of cholesterol in intima and foam cells
5) smooth muscle proliferation and deposition of ECM
6) formation of distinct fibrous cap and necrotic center
Where do plaques commonly form?
at turbulent flow sites
difference between pathogenesis and etiology
pathogenesis: process by which disease develops
etiology: cause of disease
How do foam cells form?
LDL is transported across endothelial barrier
LDL particles are oxidized in region of forming atheroma
Oxidized LDL are taken up by macrophages forming smooth muscle cells
Foam cells release growth factors and cytokines which recruit additional monocytes/smooth muscle cells to plaque
transcytosis
transporting LDL across endothelial barrier
What is the earliest lesion seen in formation of atherosclerotic plaque?
fatty streak
does not always form atherosclerosis
primary cellular component of fatty streak?
foam cells
where is fatty streak?
subendothelial
2 parts of atherosclerosis
1) necrotic center
2) fibrous cap
what can lead to thrombosis?
an ulcerated atherosclerotic plaque
nitroglycerin
nitrogen oxide
activates guanyl-cyclases which causes vasodilation of chest vessels
how does area of infarct stain?
stains blue on trichrome due to replacement by connective tissue in infarcted area
