apoptosis and necrosis Flashcards
define apoptosis
programmed cell death of a single cell through intracellular sequence of events
Removal of a targeted cell without the release of products harmful to the surrounding cells
list 3 inhibitors of apoptosis
Growth factors
Extracellular cell matrix
Sex steroids
list 4 inducers of apoptosis
Glucocorticoids
Free radicals
Ionising radiation
DNA damage
what are the 3 types of DNA damage that can cause apoptosis?
Single-strand break
Base alteration
Cross-linkage
name a disease caused by a LACK of apoptosis
cancer:
lack of apoptosis – mutated p53 gene producing faulty p53 protein so it cannot control apoptosis
name a disease caused by TOO MUCH apoptosis
HIV:
too much apoptosis – kills the antibodies in the blood so the body can’t defend itself.
define necrosis
traumatic death
death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.
There is bioenergetic failure and loss of plasma membrane integrity
give 5 clinical examples of necrosis
Toxic spider venom
Frostbite
Cerebral infarction
Avascular necrosis of bone – femur has single arterial supply through the neck of the femoral head
Pancreatitis
what are the 4 types of necrosis
- coagulative
- Liquefactive
- Caseous
4.Gangrene
what is coagulative necrosis? (where does it happen, what is its cause)
Most common type
Can occur in most organs
Cause by ischaemia
what is liquefactive necrosis? (where does it happen, what is its cause)
Occurs in the brain due to its lack of substantial supporting stroma
what is Caseous necrosis? (what is its distance pattern, which disease is characterised by this form)
Causes a ‘cheese’ pattern
TB is characterised by this form of necrosis
what is gangrene? what does it look like?
Necrosis with rotting of the tissue
Affected tissue appears black due to deposition of iron sulphide (from degraded haemoglobin)
what are the different mechanisms of apoptosis?
intrinsic - apoptosis in response to internal stimuli eg. DNA damage
extrinsic - apoptosis in response to external stimuli
what are the 2 groups of modulators involved in intrinsic apoptosis?
Bcl-2 family
Bax family
Bcl-2:Bax ratio determines the cell’s susceptibility to apoptotic stimuli
how is the extrinsic pathway of apoptosis carried out?
specific ligands binding at ‘death receptors’ on the cell surface, initiate signal transduction cascade
what is the execution phase is apoptosis?
common to both pathways (intrinsic and extrinsic)
Both pathways results in a cascade activation of caspases
initiator caspases -> executioner caspases -> degrade the cells
what happens to a cell structure when it undergoes apoptosis?
Nuclear shrinkage (pyknosis)
DNA Fragmentation (karyorrhexis)
Cell shrinks
However - Retains an intact plasma membrane
dead cells are then phagocytosed
main differences between apoptosis and necrosis:
- stimuli
apoptosis: physiological, intracellular stimulus
necrosis: pathophysiological, extracellular stimulus (injury, disease)
ie, apoptosis happens in the healthy body all the time, whereas necrosis is often due to a disease
main differences between apoptosis and necrosis:
- inflammation and tissue damage
apoptosis: no inflammation, no secondary tissue damage, integrity of cellular structures maintained
necrosis: inflammation and secondary tissue damage, swelling and disintegration of cellular structures
main differences between apoptosis and necrosis:
- ATP dependent?
apoptosis - to activate cell death pathway need ATP
necrosis - abnormal pathway, no ATP needed
give an example of necrosis
renal infarction
What is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
Activation of which family of protease enzymes can turn on apoptosis?
Caspases.
Activation of what receptor can activate caspase and therefore apoptosis?
FAS receptor
