Cell injury, necrosis and apoptosis Flashcards
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def cell injury
homeostasis disruption of the cell
3 overall causes of cell injury
- adaptive failure
- exposure to damaging stim
- intrinsic abnormality
2 types of possible oxygen deprivation
- hypoxia - lack of O2 reducing oxidative resp
2. ischemia - def. of circulation reducing oxidative resp and metabolic processes
7 different ways to injure a cell
- O2 dep
- physical agents - trauma, burns
- chemical agents - cyanide, asbestos
- infectious
- immune reactions - autoimmine
- genetic abnormalities - DNA damage, chromosomal
- nutritional imbalance
what are 4 factors that decide if injury is reversible
- nature of stim
2, target of stim - intensity/duration
- capacity for cells to adapt
3 types of irreversible injuries
- incapacity to gen ATP
- loss of menbrane function
- damage to DNA
6 mechanism of cell injury
- no ATP
- mitochonidrial damage - leak pro-apoptotic species
- Ca into cell - enzyme cascade
- ROS - damages proteins
- membrane damage - loss of components and enzyme damage
- protein misfolding
3 probs with loss of ATP
- Na/K pump down so get swelling of cell
- more anaerobic glycolisis - pH drops - clumping of chrmatin
- detached ribosomes - lipid depostition
what is normal Ca homeostais
very low in cytosol and sequestered in ER and mitochondria
3 things that happen when Ca in
- activates intracellular enzymes - lipase, phosophlipase (membrane), endonuclease (nuleaus)
- activates caspases - apop
- mitochondrial leakage - H out and apoptosis
what happens with ROS
react with other compounds to create autocatalyitc reaction
what defines oxidative stress
more ROS being made than removed
normal and patho ROS reactions
- normal - inflammatory burt
2. path - reperfusion injury
6 sources of free radicals
- oxidative phosphorylation
- radiant E
- inflammation
- NO conversion in endothelium
- enzymatic transformation of drugs
- transition metals
2 ways to remove free radicals
- enxymatic - catalase, glutathione peroxidase, superoxide dismutase
- non-enzymatic
2 non-enzymatic removal methods
- antioxidants - viatmin A and C( membranes) or C and glutatione (cytosol)
- seqquestrants - ferratin…
what is important about membrane permiability
consistently found in all injurious processes leading to necrosis, BUT NOT APOP
3 places where pathological processes occur in membrane leakage
- mitochond - loss of ATP
- cell membrane- osmotc loss and inflammatory trigger
- lysosome - cell digestion and triggering of inflammatiokn
2 options of DNA damage
- isolated - apoptosis
2. complex injury - mix of necrosis and apoptosis
2 options for accumulation of non-folding proteins
- isolated - apoptosis
2. complex injury - mix of necrosis and apoptosis
def necrosis
PATHOLOGICAL state of tissues resulting from IRREVERSIBLE damage with eventual breakdown of membrane leaking and induction of inflammatory response
4 cellular features of necrosis
- coagulation of cytoplasimc proteins - cytoplasmic eosinphilia
- coag of DNA - nuclear basophilia
- disrupted phospholipids - myelin figures
- activates endonucleases - nuclear changes
what is clinical utility of membrane leakage
can be a useful marker of disease states and timing
3 things the tissue morphology is dependent on in necrosis
- concentration of hydrolytic enzymes
- etiology of injury
- non-specifics
what are 2 options based on amount of enzymes
- coagulative - intact architecture, hypereosiniphilia, loss of nuc- INFARCT
- liquefactive - rapid release of enzymes - CNS - get PUS
what are 3 options based on the etiology of disease
- caseous - TB - cheeselike with granuloma because can’t break down the substance
- fibrinoid - vasculitis - immune mediated destruction of the vessel walls
- fat necrosis - acute pancreatitis - release of lipase breaks down fat everywhere
2 types of gangrene
- dry - limb that has lost blood supply and is coagulative
2. wet - infected and so get bacteria and neutrophils - pussss
def. apoptosis
tightly regulated form of cell death without cell breakdown and preserved membrane and no inflammatory response
2 types of apoptosis and examples
- physiologic (maintains steady state) - embryoginesis, tissue atrophy, removale of self-reactive lymphocytes
- pathologic - severe DNA damage, misfolded proteins, viral infections
2 pathways in apoptosis
- intrinsic (mitochondrial)
2. extrinisc
steps in intrinsic pathways
lack of survivale signal on cell membrane>antagonism of BCL-2>activation of cytochrone C in mitochondria>actiaves capsases
steps in extrinsic
signal from outside cell leads to direct activation of capsases
what will be seen on PCR in necro vs. apop
apop - ladder pattern because fragmented endonuclease make discrete chops
necrosis - smear because release of DNAases chops DNA whereever
what happens in apop
cell slowly pulls pieces off and shrink and the peices are phaged
***6 features that differentiate necrosis from apoptosis
- cell size
- nuclear morphology
- membrane
- cellular contents
- nearby inflammation
- pathologic or physiological
- **features of apoptosis based on
1. cell size
2. nuclear morphology
3. membrane
4. cellular contents
5. nearby inflammation
6. pathologic or physiological
- cell size - smaller
- nuclear morphology - fragmented
- membrane - intact
- cellular contents - intact and released in vacuoles
- nearby inflammation - no
- pathologic or physiological - either
- *** features of necrosis based on
1. cell size
2. nuclear morphology
3. membrane
4. cellular contents
5. nearby inflammation
6. pathologic or physiological
- cell size - larger - swollen
- nuclear morphology - karyolisis, nuclear basophilia, myelin figures
- membrane - disruted
- cellular contents - lyses and may spill out
- nearby inflammation - frequent
- pathologic or physiological - always patho
