1-Cell Injury and Death Flashcards
1
Q
cell survival
depends on
A
- maintain ability to produce energy/ATP
- adapt to adverse environmental conditions
injury when stressed beyond adaptation
2
Q
cell response depends on
A
dose
duration
type of injury
3
Q
pathway of cell injury
A
- healthy cell
- stress
- adaptation
- cell injury if inability to adapt
- severe progression
- irreversible injury
- necrosis or apoptosis
4
Q
causes of cell injury
A
- lack oxygen/hypoxia
- physical agents/ trauma
- chemical agents and drugs
- infectious agents
- immunologic rxns
- genetic defects
- nutritional imbalances
5
Q
damaged cellular functions
A
- aerobic respiration mitochondrial oxidative phosphorylation and ATP
- integrity of cell membranes
- proteins synthesis
- cytoskeleton
- genetic apparatus
6
Q
injurious stimulus
A
- membrane damage
- protein/cytoskeletal damage
- DNA damage
MPD
7
Q
mitochondrial damage
results
A
-dec ATP
-inc ROS = damage to lipids, proteins, DNA
8
Q
entry/influx calcium
mechanism
A
- inc mitochondrial permeability
- binds to activate enzymes
-phospholipase breaks down phospholipids = membrane damage
-protease disrupt membrane/cytoskeletal proteins = membrane damage
-endonuclease breaks down DNA = nuclear damage
-ATPase break down ATP = dec ATP
9
Q
membrane damage
mechanism
A
-plasma membrane = loss cellular components
-lysosomal membrane = enzymes digest cellular components
10
Q
protein misfolding
mechanism
A
activates pro-apoptotic proteins
ER stress
11
Q
5 major mechanisms
A
- influx of calcium into cells, lose calcium homeostasis
- mitochondrial damage
- depletion of ATP
- acc of oxygen free radicals
- defects in membrane permeability
12
Q
sources of calcium
A
- extracellular
- mitochondria
- SER
13
Q
causes of mitochondrial injury
A
- inc Ca in cytosol
- oxidative stress
- breakdown of phospholipids by phospholipase A2 and sphingomyelin into free FA and ceramides
14
Q
mitochondrial necrosis pathway
A
- dec oxygen, toxins, radiation
- mito damage
- dec ATP + inc ROS
- cellular abnormalities
- necrosis
15
Q
mitochondrial apoptosis pathway
A
- survival signals DNA, protein damage
- inc pro-apoptotic proteins + dec anti-apop
- leakage of proteins
- apoptosis
16
Q
consequences of dec ATP
mitochondrial
A
- dec Na/K pump and Ca pump > influx of Ca, H2O, and Na, efflux of K = swelling + blebs
- inc anaerobic glycolysis > inc lactic acid > dec pH > clump nuclear chromatin
- detachment of ribosomes = dec protein synthesis
17
Q
ROS
A
O2-, OH, ONOO, lipid peroxidase radicals > membrane damage = cell injury
18
Q
lipid peroxidation
membranes
A
- unsat FA with double bonds attacked by radicals
- peroxidases formed
- unstable peroxidase react with membrane lipids to make more peroxidases
- self sustaining and great damaged until captured by vitamin E, C, A, beta carotene
19
Q
protein oxidation
A
- side chains oxidized so change function/structure
- formation of disulfide bonds = cross linking
- cross links interupt folding
20
Q
DNA damage with radicals
A
radicals interact with thymine = single stranded breaks in DNA = mutations (also shown in carcinogenesis)
21
Q
removal of free radicals
A
- SOD (superoxide dismutase) converts superoxide to hydrogen peroxide
- glutathione peroxidase converts hydroxyl radical to hydrogen peroxide
- catalase converts hydrogen peroxide to water and oxygen
22
Q
neutrophils
A
-do not divide
-multinucleated
-uses ROS to destroy bacteria
-1st line of defense
-can acc with cytokines and cell adhesion molecules
23
Q
membrane permeability damage
A
found in most forms of cell injury
damage = activation of phospholipase in cytosol
no ATP prevents reacylation of phospholipids and dec synthesis so no repair
24
Q
characteristics of necrotic cells
A
- swelling of ER and loss ribosomes
- lysosome rupture
- myelin figures
- nuclear condensation/pyknosis > fragmentation
- swollen mitochondria
- eosinophilic and glassy cytoplasm
necrosis is always pathologic
25
necrosis
| definition
cell death from exogenous or endogenous damage leading to leaking cellular contents
not controlled so does not require signals
26
apoptosis
| definition
programmed cell death from external or internal damage, physiologic, or develop
cell fragmentation and phagocytosis
to eliminate unwanted or irreparably damaged cells thru enzymatic degradation so not trigger inflamm
| physiologic or pathologic
27
nuclear changes
| necrosis
pkynosis-condensation
karyorrhexis- break up/fragmentation
karyolysis- dissolved
28
types of necrosis
1. coagulative
2. liquefactive
3. caseous
4. enzymatic fat
5. fibrinoid
6. gangrenous
29
coagulative necrosis
due to ischemia, hypoxia, reperfusion in organs with significant CT frameworks (except brain)
basic outline of cell preserved but no nuclei
30
liquefactive necrosis
usually brain tissue bc only glial cells and not CT
in abscess with pus (enzymatic digested neutrophils)
amorphous, granular, loss of cell and tissue structure
31
caseous necrosis
acc of mononuclear/macrophage that mediate chronic inflamm response and granuloma formation
grayish, whitish, yellowish, soft, friable, cheesy appearance
32
enzymatic fat necrosis
fatty acids react with calcium to form soap like substance
white, chalky appearance in fat cells or basophilic calcium
usually pancreatitis
33
fibrinoid necrosis
injury in blood vessels with acc of plasma proteins (fibrin and debris)
very eosinophilic
34
gangrenous necrosis
loss of circulation to a limb or bowel
wet gangrene = combo with superimposed bacterial infection
35
reperfusion
blood flow/oxygen restored to ischemic tissues but leads to large amounts of ROS
clot treatment for heart attack and stroke
36
necrosis serum tests
creatine kinase or troponin levels elevated in serum after MI = necrosis
37
physiological roles apoptosis
1. embryogenesis
2. hormone dependent involution
3. cell celetion in proliferating cell pop
4. normal immune defense vs viral infections or neoplastic cells aka cytotoxic T cell clearance
5. removal self reactive lymphocyte clones
6. removal cells served purpose i.e inflamm cells
38
pathologic conditions apoptosis
1. cell death in tumors
2. DNA damage from low doses of agents that would cause necrosis in high doses
3. transplant rejection
4. atrophy after duct obstruction
5. some viral diseases
39
stages of apoptosis
1. intrinsic activated (cytochrome c released) or extrinsic (receptor activated)
2. initiation: intracell signals commit cell to apop by syn/activating initiator caspases
3. execution: execution caspases catabolize cytoskeleton, activate endonucleases for DNA break down
4. removal: removal round dead fragments of cells by macrophages
40
intrinsic apoptosis triggers
1. growth factor withdrawal
2. DNA damage via radiation, toxins, free radicals, p53 will act proapoptic Bcl-2 to stim Bax/Bak
3. protein misfolding i.e ER stress
cyt c will release thru Bak/Bax dimerized channel in mito membrane
| mitochondrial
41
extrinsic apoptosis triggers
1. receptor ligand interactions aka Fas or TNF (tumor necrosis factor) receptor > act adaptor proteins to bind caspases
42
chemicals for cell injury
1. acetaminophen: highly reactive quinone reacts with protein, DNA = oxidative stress
2. carbon tetrachloride: metabolite reacts w/ membrane and ER
3. heavy metals/cyanide: mitochondria
4. phalloidin/paclitaxel: cytoskeleton
5. chemotherapeutic alkylating agents: DNA
43
SER induction
| aka hypertrophy
adaptive response to become more efficient if metabolizing or detoxing barbituates + p-450 mixed function oxidase system
