Cell damage and cell death

Question 1

What is necrosis?

Answer 1

cell death by accident
cell exposed to certain insults and dies
mainly due to LACK OF OXYGEN

Question 2

What kind of insults can a cell be exposed to?

Answer 2

ischaemia
trauma
chemical injury

Question 3

Which organs are most prone to necrosis?

Answer 3

the ones furthest away from the heart

Question 4

How can bacteria lead to necrosis?

Answer 4

compete for oxygen with the body or block blood vessels

Question 5

What is apoptosis?

Answer 5

programmed cell death- want to eliminate unwanted things in the body

Question 6

What is autophagic cell death?

Answer 6

a way for the cells to engulf old organelles and cellular components to renew them

Question 7

What happens as a result of necrosis (lack of oxygen to cells)?

Answer 7

oxygen is needed for ATP
so cell ATP goes
ion channels are affected
so electrolyte balance is messed up
so osmolarity cant be regulated
so water starts entering the cell
cell begins to swell

Question 8

Is necrosis reversible?

Answer 8

yes initially

if the influx of water is too high though- organelles begin to swell- cell membrane breaks down

Question 9

What happens if water influx gets too high in a cell?

Answer 9

organelles swell
cell membrane breaks down
intracellular enzymes released from lysosome- damages the cell
inflammatory response

Question 10

What is seen if a single cell undergoes necrosis under the microscope?

Answer 10

1. nucleus swells
2. DNA becomes naked and cleaved randomly
3. DNA gets destroyed eventually- cell has no DNA
4. proteins and proteolytic enzymes released into cytoplasm- leads to opacification
5. creatine kinase and lactate dehydrogenase released

Question 11

What is opacification?

Answer 11

proteolytic enzymes leade to opacification of the cytoplasm (the cells will become darker/not transparent)

Question 12

What does the muscle release during muscle dystrophy?

Answer 12

creatine kinase

lactate dehydrogenase

Question 13

What is released during a heart attack?

Answer 13

lactate dehydrogenase

Question 14

What is released during bone and liver disease?

Answer 14

damaged tissues will release alkaline phosphatase and lactate dehydrogenase

Question 15

During haemolytic anaemia, what do damaged red cells release?

Answer 15

LDH1/2

Question 16

What is astrocytoma?

Answer 16

type of necrosis
metabolically active cancer
competes with brain cells for nutrients and oxygen

Question 17

What is glomerular necrosis?

Answer 17

necrosis in the kidney

Question 18

What is coagulative necrosis?

Answer 18

seen in low oxygen areas

sometimes cell outline remains and can be observed by light microscopy

Question 19

What is liquefactive necrosis?

Answer 19

associated with complete cellular destruction
pus formation
E.G. PNEUMONIA

Question 20

What is caseous necrosis a mixture of?

Answer 20

coagulative necrosis
liquefactive necrosis
e.g. TB

Question 21

What is fatty necrosis?

Answer 21

results from action of lipases on fatty tissue

e.g. acute pancreatitis

Question 22

What is fibrinoid necrosis?

Answer 22

immune mediated vascular damage

fibrin like material in arterial walls

Question 23

What is the purpose of apoptosis?

Answer 23

• delete superfluous cells (cells not required anymore)
• delete infected cells
• delete transformed cells (cells that contain mutations and can become cancerous)
• development (good thing)- sculpt organisms
• normal tissue turnover
• endocrine tissue atrophy (when milk producing cells are not needed anymore, they will undergo apoptosis

Question 24

Give examples of apoptosis in the body:

Answer 24

• cell death in the embryonic hand to form individual fingers
• DNA damage mediated apoptosis carried out by p53 tumour suppressor gene
• cell death in tumours causing regression
• cell death in viral disease
• undergo apoptosis to prevent viral replication
• cell death induced by cytotoxic T cells

Question 25

What promotes cell survival?

Answer 25

correct growth factors correct cytokines in contact with similar cells

Question 26

What promotes apoptosis in a cell?

Answer 26

not surrounded by similar cells not correct growth factors not correct cytokines- e.g. TNF can cause apoptosis

Question 27

What does intrinsic and extrinsic apoptosis mean?

Answer 27

intrinsic- signals comes from inside the cell | extrinsic- signals come from outside the cell

Question 28

What are examples of intrinsic apoptosis (within the cell)?

Answer 28

``` viral infection DNA damage redox state change cell cycle interruption interruption of protein synthesis ```

Question 29

How does apoptosis happen?

Answer 29

1. capases (family of proteases)- they cleave cysteine and aspartate residues 2. inactive capase in cells- needs to be activated

Question 30

How is a caspase activated?

Answer 30

caspase is activated-say there is an inactive caspase Y being activated by an active caspase X-the active caspase X will remove the N terminal from the inactive caspase Y and cut the inactive caspase Y into half-this will result in a large and a small subunit which is the active caspase Y

Question 31

What happens when the caspase is activated?

Answer 31

``` break down cytoskeleton proteins cell shrinks chromatin condenses DNA fragment membrane bulges ```

Question 32

What are the first caspases that get activated?

Answer 32

caspase 8 and 9 | the downstream caspases are the 1, 3, 6, and 7

Question 33

Give some examples of caspases:

Answer 33

lamin A and B in the nuclear envelope PARP, DNA PK which are involved in DNA repair topoisomerase II which is involved in DNA replication Raf, STAT1 which are involved in signalling Akt/PKB which is involved in cell survival eIF4 which is involved in translation

Question 34

What pathway is TNF apoptosis?

Answer 34

extrinsic pathway

Question 35

What are the 3 main things in the extrinsic pathway?

Answer 35

intracellular death receptor =which has an extracellular domain that will bind to ligands intracellular domain =called he death domain -the death domain can form a complex with death adaptor protein the death adaptor protein= can in turn form complexes with procaspase 8 (the inactive form of caspase 8)

Question 36

What happens when TNF comes to the cell?

Answer 36

1. many TNFs bind to many death receptors 2. so death receptors come close together 3. each receptor forms complex with death adaptor protein 4. forms complexes with procaspase 8 5. many procaspase 8 molecules get close to each other 6. procaspase 8 will autoproteolyse each other and activate caspase 8

Question 37

What is the intrinsic pathway involved with?

Answer 37

CYTOCHROME C | APAF protein- can bind cytochrome C and has caspase recruitment domain

Question 38

What happens when cytochrome C is in the cytoplasm?

Answer 38

2 cytochrome C bring 2 APAF molecules very close to each other SO APAF molecules will get 2 procaspase 9 molecules very close to each other then get autoproteolysis of the procaspase and the caspase will get activated

Question 39

Where is cytochrome C found?

Answer 39

in the mitochondria

Question 40

What controls the release of cytochrome C?

Answer 40

controlled by bcl-2 proteins

Question 41

What are bcl-2 proteins made of?

Answer 41

anti apoptotic: bcl2-pro apoptotic: bax and bad

Question 42

How do bcl-2 proteins release cytochrome C?

Answer 42

``` form dimers ie bcl2 can make a dimer with bcl2 bad can make a dimer with bax bcl2 can make a dimer with bad bcl2 can make a dimer with bax ```

Question 43

When does the cell go through apoptosis?

Answer 43

when there is dimerization of 2 pro-apoptotic proteins, the cell will go through apoptosis

Question 44

What happens when there is excess BAX?

Answer 44

form homodimers (BAX and BAX) and form pores in the mitochondrial membrane so cytochrome C can be released into cytoplasm

Question 45

What happens when BCL2 and BAX form a dimer?

Answer 45

BCL2 puts cap on pores in mitochondria | cytochrome C remains inside

Question 46

What are Akt and PKB kinase?

Answer 46

healthy cells get survival factors which activate Akt and PKB kinases the Akt and PKB kinases phosphorylate Bad and deactivate it

Question 47

What happens if cell goes through intracellular stress?

Answer 47

p53 (transcription factor) gets activated activates transcription of the Bax protein increases its concentration leads to cytochrome C release from mitochondria leading to caspase activation and apoptosis

Question 48

What do you use to distinguish between healthy, necrotic, and apoptotic cells?

Answer 48

gel electrophoresis

Question 49

What are biochemical changes in an apoptotic cell?

Answer 49

there will be an expression of charged sugar molecules on outer and inner surface of membranes (this will be on the exocytosed vesicles) which will enhance phagocytosis−there will be expression of caspases−there will be expression of phosphatidylserine on extracellular leaflet of apoptotic cells−there willbe protein cleavage by proteases and caspases

Question 50

What are the cytoplasmic changes in an apoptotic cell?

Answer 50

cell shrinks organelles in packaged vesicles cell fragmentation membrane bound vesicles will bud off

Question 51

What are nuclear changes seen in necrosis?

Answer 51

1. Pyknosis, this is shrinkage of the chromatin 2. karyorrhexis, which is fragmentation of the nucleus 3. karyolysis, this is dissolution of the chromatin by DNase, this eventually results in there being no DNA left in the cell