Cell injury, necrosis and apoptosis

Question 1

check out flow chart

Answer 1

do it

Question 2

def cell injury

Answer 2

homeostasis disruption of the cell

Question 3

3 overall causes of cell injury

Answer 3

1. adaptive failure
2. exposure to damaging stim
3. intrinsic abnormality

Question 4

2 types of possible oxygen deprivation

Answer 4

1. hypoxia - lack of O2 reducing oxidative resp

2. ischemia - def. of circulation reducing oxidative resp and metabolic processes

Question 5

7 different ways to injure a cell

Answer 5

1. O2 dep
2. physical agents - trauma, burns
3. chemical agents - cyanide, asbestos
4. infectious
5. immune reactions - autoimmine
6. genetic abnormalities - DNA damage, chromosomal
7. nutritional imbalance

Question 6

what are 4 factors that decide if injury is reversible

Answer 6

1. nature of stim
   2, target of stim
2. intensity/duration
3. capacity for cells to adapt

Question 7

3 types of irreversible injuries

Answer 7

1. incapacity to gen ATP
2. loss of menbrane function
3. damage to DNA

Question 8

6 mechanism of cell injury

Answer 8

1. no ATP
2. mitochonidrial damage - leak pro-apoptotic species
3. Ca into cell - enzyme cascade
4. ROS - damages proteins
5. membrane damage - loss of components and enzyme damage
6. protein misfolding

Question 9

3 probs with loss of ATP

Answer 9

1. Na/K pump down so get swelling of cell
2. more anaerobic glycolisis - pH drops - clumping of chrmatin
3. detached ribosomes - lipid depostition

Question 10

what is normal Ca homeostais

Answer 10

very low in cytosol and sequestered in ER and mitochondria

Question 11

3 things that happen when Ca in

Answer 11

1. activates intracellular enzymes - lipase, phosophlipase (membrane), endonuclease (nuleaus)
2. activates caspases - apop
3. mitochondrial leakage - H out and apoptosis

Question 12

what happens with ROS

Answer 12

react with other compounds to create autocatalyitc reaction

Question 13

what defines oxidative stress

Answer 13

more ROS being made than removed

Question 14

normal and patho ROS reactions

Answer 14

1. normal - inflammatory burt

2. path - reperfusion injury

Question 15

6 sources of free radicals

Answer 15

1. oxidative phosphorylation
2. radiant E
3. inflammation
4. NO conversion in endothelium
5. enzymatic transformation of drugs
6. transition metals

Question 16

2 ways to remove free radicals

Answer 16

1. enxymatic - catalase, glutathione peroxidase, superoxide dismutase
2. non-enzymatic

Question 17

2 non-enzymatic removal methods

Answer 17

1. antioxidants - viatmin A and C( membranes) or C and glutatione (cytosol)
2. seqquestrants - ferratin…

Question 18

what is important about membrane permiability

Answer 18

consistently found in all injurious processes leading to necrosis, BUT NOT APOP

Question 19

3 places where pathological processes occur in membrane leakage

Answer 19

1. mitochond - loss of ATP
2. cell membrane- osmotc loss and inflammatory trigger
3. lysosome - cell digestion and triggering of inflammatiokn

Question 20

2 options of DNA damage

Answer 20

1. isolated - apoptosis

2. complex injury - mix of necrosis and apoptosis

Question 21

2 options for accumulation of non-folding proteins

Answer 21

1. isolated - apoptosis

2. complex injury - mix of necrosis and apoptosis

Question 22

def necrosis

Answer 22

PATHOLOGICAL state of tissues resulting from IRREVERSIBLE damage with eventual breakdown of membrane leaking and induction of inflammatory response

Question 23

4 cellular features of necrosis

Answer 23

1. coagulation of cytoplasimc proteins - cytoplasmic eosinphilia
2. coag of DNA - nuclear basophilia
3. disrupted phospholipids - myelin figures
4. activates endonucleases - nuclear changes

Question 24

what is clinical utility of membrane leakage

Answer 24

can be a useful marker of disease states and timing

Question 25

3 things the tissue morphology is dependent on in necrosis

Answer 25

1. concentration of hydrolytic enzymes 2. etiology of injury 3. non-specifics

Question 26

what are 2 options based on amount of enzymes

Answer 26

1. coagulative - intact architecture, hypereosiniphilia, loss of nuc- INFARCT 2. liquefactive - rapid release of enzymes - CNS - get PUS

Question 27

what are 3 options based on the etiology of disease

Answer 27

1. caseous - TB - cheeselike with granuloma because can't break down the substance 2. fibrinoid - vasculitis - immune mediated destruction of the vessel walls 3. fat necrosis - acute pancreatitis - release of lipase breaks down fat everywhere

Question 28

2 types of gangrene

Answer 28

1. dry - limb that has lost blood supply and is coagulative | 2. wet - infected and so get bacteria and neutrophils - pussss

Question 29

def. apoptosis

Answer 29

tightly regulated form of cell death without cell breakdown and preserved membrane and no inflammatory response

Question 30

2 types of apoptosis and examples

Answer 30

1. physiologic (maintains steady state) - embryoginesis, tissue atrophy, removale of self-reactive lymphocytes 2. pathologic - severe DNA damage, misfolded proteins, viral infections

Question 31

2 pathways in apoptosis

Answer 31

1. intrinsic (mitochondrial) | 2. extrinisc

Question 32

steps in intrinsic pathways

Answer 32

lack of survivale signal on cell membrane>antagonism of BCL-2>activation of cytochrone C in mitochondria>actiaves capsases

Question 33

steps in extrinsic

Answer 33

signal from outside cell leads to direct activation of capsases

Question 34

what will be seen on PCR in necro vs. apop

Answer 34

apop - ladder pattern because fragmented endonuclease make discrete chops necrosis - smear because release of DNAases chops DNA whereever

Question 35

what happens in apop

Answer 35

cell slowly pulls pieces off and shrink and the peices are phaged

Question 36

***6 features that differentiate necrosis from apoptosis

Answer 36

1. cell size 2. nuclear morphology 3. membrane 4. cellular contents 5. nearby inflammation 6. pathologic or physiological

Question 37

* **features of apoptosis based on 1. cell size 2. nuclear morphology 3. membrane 4. cellular contents 5. nearby inflammation 6. pathologic or physiological

Answer 37

1. cell size - smaller 2. nuclear morphology - fragmented 3. membrane - intact 4. cellular contents - intact and released in vacuoles 5. nearby inflammation - no 6. pathologic or physiological - either

Question 38

* *** features of necrosis based on 1. cell size 2. nuclear morphology 3. membrane 4. cellular contents 5. nearby inflammation 6. pathologic or physiological

Answer 38

1. cell size - larger - swollen 2. nuclear morphology - karyolisis, nuclear basophilia, myelin figures 3. membrane - disruted 4. cellular contents - lyses and may spill out 5. nearby inflammation - frequent 6. pathologic or physiological - always patho