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WEEK 9 SEM 4 > Cell damage and cell death > Flashcards

Cell damage and cell death Flashcards

1
Q

What is necrosis?

A

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

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2
Q

What kind of insults can a cell be exposed to?

A

ischaemia
trauma
chemical injury

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3
Q

Which organs are most prone to necrosis?

A

the ones furthest away from the heart

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4
Q

How can bacteria lead to necrosis?

A

compete for oxygen with the body or block blood vessels

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5
Q

What is apoptosis?

A

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

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6
Q

What is autophagic cell death?

A

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

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7
Q

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

A 
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
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8
Q

Is necrosis reversible?

A

yes initially

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

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9
Q

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

A

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

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10
Q

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

A
  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
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11
Q

What is opacification?

A

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

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12
Q

What does the muscle release during muscle dystrophy?

A

creatine kinase

lactate dehydrogenase

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13
Q

What is released during a heart attack?

A

lactate dehydrogenase

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14
Q

What is released during bone and liver disease?

A

damaged tissues will release alkaline phosphatase and lactate dehydrogenase

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15
Q

During haemolytic anaemia, what do damaged red cells release?

A

LDH1/2

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16
Q

What is astrocytoma?

A

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

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17
Q

What is glomerular necrosis?

A

necrosis in the kidney

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18
Q

What is coagulative necrosis?

A

seen in low oxygen areas

sometimes cell outline remains and can be observed by light microscopy

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19
Q

What is liquefactive necrosis?

A

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

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20
Q

What is caseous necrosis a mixture of?

A

coagulative necrosis
liquefactive necrosis
e.g. TB

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21
Q

What is fatty necrosis?

A

results from action of lipases on fatty tissue

e.g. acute pancreatitis

22
Q

What is fibrinoid necrosis?

A

immune mediated vascular damage

fibrin like material in arterial walls

23
Q

What is the purpose of apoptosis?

A
  • 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
24
Q

Give examples of apoptosis in the body:

A
  • 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
25
Q

What promotes cell survival?

A

correct growth factors
correct cytokines
in contact with similar cells

26
Q

What promotes apoptosis in a cell?

A

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

27
Q

What does intrinsic and extrinsic apoptosis mean?

A

intrinsic- signals comes from inside the cell

extrinsic- signals come from outside the cell

28
Q

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

A 
viral infection
DNA damage
redox state change
cell cycle interruption
interruption of protein synthesis
29
Q

How does apoptosis happen?

A
  1. capases (family of proteases)- they cleave cysteine and aspartate residues
  2. inactive capase in cells- needs to be activated
30
Q

How is a caspase activated?

A

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

31
Q

What happens when the caspase is activated?

A 
break down cytoskeleton proteins
cell shrinks
chromatin condenses
DNA fragment
membrane bulges
32
Q

What are the first caspases that get activated?

A

caspase 8 and 9

the downstream caspases are the 1, 3, 6, and 7

33
Q

Give some examples of caspases:

A

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

34
Q

What pathway is TNF apoptosis?

A

extrinsic pathway

35
Q

What are the 3 main things in the extrinsic pathway?

A

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)

36
Q

What happens when TNF comes to the cell?

A
  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
37
Q

What is the intrinsic pathway involved with?

A

CYTOCHROME C

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

38
Q

What happens when cytochrome C is in the cytoplasm?

A

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

39
Q

Where is cytochrome C found?

A

in the mitochondria

40
Q

What controls the release of cytochrome C?

A

controlled by bcl-2 proteins

41
Q

What are bcl-2 proteins made of?

A

anti apoptotic: bcl2-pro apoptotic: bax and bad

42
Q

How do bcl-2 proteins release cytochrome C?

A 
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
43
Q

When does the cell go through apoptosis?

A

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

44
Q

What happens when there is excess BAX?

A

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

45
Q

What happens when BCL2 and BAX form a dimer?

A

BCL2 puts cap on pores in mitochondria

cytochrome C remains inside

46
Q

What are Akt and PKB kinase?

A

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

47
Q

What happens if cell goes through intracellular stress?

A

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

48
Q

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

A

gel electrophoresis

49
Q

What are biochemical changes in an apoptotic cell?

A

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

50
Q

What are the cytoplasmic changes in an apoptotic cell?

A

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

51
Q

What are nuclear changes seen in necrosis?

A
  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

WEEK 9 SEM 4 (9 decks)

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