POM 03 - Cell injury and inflammation Flashcards
what are the 6 possible causes of cell stress and injury
physical injury
chemical injury
biological causes (eg viral infection)
immunological causes
genetic derangements
nutritional imbalances
what are the 3 outcomes that cell injury can lead to
no effect
adaptation
cell injury
what does it mean when the injurious agent or stress has no effect on the cell
the cell can cope with it, can function and survive in hostile environment
what does it mean when the injurious agent or stress causes adaptation in the cell
the cell can change itself in order to resist or adapt to the injury
what does it mean when the injurious agent or stress results in cell injury
there is a physical and biochemical change in the cell beyond amount of injury that can be fixed by turning on signal pathways and generating adaptation
cell injury can either be __ or __
irreversible leading to death or reversible
what is an example of cells that are no affected by injurious agents or stress
neutrophils
what is adaptation in cells a response to (2 things)
mild injurious agents
mild stress
what is an example of mild injurious agents
chronic irritant
what is an example of mild stress
altered environmental conditions
what does adaptations allow the cell to do
allows cell to continue to function without being injured despite the stress or change in environment
what are the 4 types of adaptation a cell can undergo
hypertrophy
hyperplasia
atrophy
metaplasia
what is hyperplasia
number of cells increases by stem cell dividing due to increased demand on cell
is adaptations in cell (the 4 types) active/passive processes and what drives them
active process
driven by signalling pathways
what is hypertrophy
individual cells gaining size - NOT increasing number of cells
what is atrophy
cells shrink smaller in size
what is metaplasia
stem cells reprogram themselves in order for cells to be better adapted in hostile environment
what are two broad types of signalling pathways that are activated by cell stress/injury
heat shock factors
stress enzymes
what are heat shock factors
transcription factors which induce expression of heat shock proteins which act in a circular loop that further activates heat shock factors
which two stress enzymes initiate the phosphorylation cascades
p38 MAP kinase
Jun N-terminal kinase
what does the p38 MAP kinase and Jun N-terminal kinase enzymes initiate
phosphorylation cascades
what is p53 activated by
DNA damagew
hat does p53 do to cell division and why
halts it to allow repair so they dont perpetuate damage while repairing or induces cell suicide
what does p53 sense
senses DNA damage
what is BMF a sensor for
actin cytosckeleton damage
what is Bim a sensor for
microtubule damage
what is Bad a sensor for
cell stress due to inadequate stimulation by growth factors
what are 3 stress enzymes starting with B
BMF
Bim
Bad
what is BMF, Bim and Bad examples of
stress enzymes
what are the 4 main cellular components that are due to the effect of stress/injury on cells
decreased ATP/energy
membrane damage
increased intracellular Calcium
reactive oxygen species
why does depletion of ATP occur in cell - 3 reasons
less ATP produced due to:
lack of oxygen (blood supply interrupted = less removal of CO2 = prevents oxidative phosphorylation)
damage to enzymes involved in ATP production
damage to mitochondria (decreases aerobic respiration)
why is decreased ATP in cell injury bad for the cell - 3 things
enzymes that repair damaged DNA needs ATP
ATP driven membrane pumps need ATP
protein synthesis needs ATP
what happens to when ATP driven membrane ion pumps dont have enough ATP - Na+ pumps
Na+ pump doesn’t work as well without ATP so sodium and water accumulate = cell swelling = can burst, lose function and alter tissue architecture
what happens to when ATP driven membrane ion pumps dont have enough ATP - Ca2+ pumps
Ca2+ pump doesnt work as well without ATP so Ca2+ influx into cytosol = activates destructive Ca2+ dependent enzymes (can lead to autolysis)
why is protein synthesis decreasing due to ATP dropping from cell injury bad
need protein synthesized for repairing damaged cell
what are 6 examples of membranes that are damaged in the membrane damage due to cell injury
plasma membranes
lysosomal membranes
mitochondrial membranes
nuclear membranes
endoplasmic reticular membranes
motile membranes
what does plasma membrane damage result in - 4 things
loss of cellular contents
loss of osmotic balance
influx of fluids and ions
loss of proteins, enzymes, coenzymes and ribonucleic acids
what does lysosomal membrane damage result in
leakage of enzymes into cytoplasm = digestion of cellular components (autolysis)
what does mitochondrial membrane damage result in and what are the two flow on effects of this
formation of nonselective high-conductance channels in the inner mitochondrial membrane of
- removes transmembrane potential and allows leakage of cytochrome c in wrong position for oxidative phosphorylation
- allows leakage of cytochrome c into cytosol = primes cells for apoptosis
what is cytochrome c and why is it important in mitochondrial membrane damage induced by cell stress/injury
its part of energy producing apparatus so decreases energy if damaged
also is signalling molecule that turns on apoptosis
what does increased cytosolic Ca2+ as a result of cell stress/injury do
activates enzymes that cause autolysis
what are 5 ways that free radicals can be caused by
irradiation
metabolism of chemicals or drugs
oxygen toxicity
inflammation
reperfusion (O2 reintroduced after period of blocked blood flow)
what are the 3 core changes due to free radical damage in a cell
free radicals attack the double bonds in unsat. fatty acids
oxidises amino acid side chains
react with thymine
what results when free radicals react with thymine
DNA damage
what results when free radicals oxidises amino acid side chains
causes enzyme damage and enzymes may stop functioning
what results when free radicals attack the double bonds in unsat. fatty acids
lipid peroxidation and further damages membranes
free radicals propagate a chain of damage via ____ reactions
autocatalytic reactions
all together when multiple cellular components are targeted simultaneously what does it lead to for proteins and DNAs - what does it increase and decrease
increase proteins breakdown and DNA damage
decrease protein and DNA repair
when cell injury is irreversible what are the 2 options
necrotic death and apoptotic death
how do cells die via the necrotic death pathway
cells passively murdered
injury/damage is overwhelming and cells cant do anything about it so they just die
how do cells die via the apoptotic death pathway
programmed process where cells recycle themselves by wrapping up components in membrane bound coffins which are taken up by adjacent cells/macrophages
components of cell can be reused
what are the 4 main differences between necrosis and apoptosis
necrosis is passive (dont need energy) while apoptosis uses energy
necrosis is unorganised and messy, apoptosis is organised in membrane bound vesicles
components of cell can be reused in apoptosis but not in necrosis
necrosis destructive enzymes already active while apoptosis is programmed and turned on carefully
why is necrosis described as a messy process
cant see alot of structure once it happens because destructive enzymes like lysosomes chew up components = autolysis
why is apoptosis described as an organised process
cleans up dead cells and makes it easier to recover initial structure and function of tissue
how can necrosis cause inflammatory response and why
cytosolic contents can leak out causing inflammatory response
what does the cell look like after necrosis
featureless cytoplasm and faded/fragmented chromatin
on what scale does necrosis act on cells
affects large numbers of cells in a tissue
what is the characteristic appearance of a cell undergone apoptosis - 3 things
membrane blebs (vesicles), shrinkage, pyknosis
how are the membrane bound vesicles disposed of in apoptosis
phagocytosed by passing macrophages or neighbouring cells
what are the 2 pathways for apoptosis initiation
mitochondria = cells with internal derangement or insufficient energy or growth factors turn on apoptosis pathway
death receptors = cell surface receives death signals
what do the 2 pathways for apoptosis initiation cause activation of
activation of a cascade of upstream caspases
the 2 pathways for apoptosis initiation both feed down into what
feeds down into cascade of caspase enzymes (executioner enzymes)
the cascade of caspase enzymes (executioner enzymes) has what two parts
organisers = organised dismantalling of cell
executioners
what is the most potent activator of inflammation
necrosis
what is inflammation
bodys immediate response to tissue injury
what does inflammation involve in terms of cells migrating
leukocytes leaving blood vessels into tissues
what does it mean when we say inflammation is stereotyped
almost every cell does inflammation the same way irrespective of the tissue involved
but there can be a few modifications in different organs/tissues
what are 6 trigger of inflammation
infections
trauma
physical and chemical agents
tissue necrosis
foreign bodies
immune reactions
what are the 6 stages of acute inflammation
- triggering
- blood flow and permeability changes
- endothelial cell signalling and gene expression changes (incl adhesion molecule regulation)
- neutrophil signalling and gene expression changes (neutrophil adhesion to endothelial cells and migration into tissues through tight junctions betw endothelial cells)
- neutrophil activation, survival, function and death
- inflammation subsides or continues with other leukocytes entering tissue (chronic inflamm)
what are the gatekeepers of acute inflammation
endothelial cells
what does TNF alpha do in acute inflammation
binds to TNF receptor = NFkB transcription factor = other genes = neutrophil adhesion and passage into tissues
what does inflammation associated gene expression and signaling change in endothelial cells regarding the cell adhesion molecules
increase cell adhesion molecules
what does inflammation associated gene expression and signaling change in endothelial cells regarding anti-apoptosis molecules
increase anti-apoptosis molecules
what does inflammation associated gene expression and signaling change in endothelial cells regarding the cytoskeleton stabilizers
decreases cytoskeleton stabilizers
what does inflammation associated gene expression and signaling change in endothelial cells regarding the coagulation factors
increases coagulation factors
what does inflammation associated gene expression and signaling change in endothelial cells regarding the pro-angiogenesis factors
increases pro-angiogenesis factors
what happens to blood flow during inflammation
how does this relate to the physical changes
increased blood flow
hyperaemia = tissues become red and warm
what happens to fluid and protein during inflammation
why what happens
lost through exudation
tight junctions leak out fibrinogen and tissue odema occurs
what is the main leukocyte involved in acute inflammation
neutrophils
what is the first leukocyte type to enter inflammed tissues
neutrophils
what do selectin molecules do
slow down neutrophils
what does integrin do
help neutrophil firmly adhere to endothelial cells
what does diapedesis mean
process of neutrophil passing between endothelial cells
neutrophils move into tissue and become activated by what 4 things
endothelial cell surface molecules (activate neutrophils when they touch)
interlukin 1 and tumour necrosis factor alpha
bacterial products that bind to neutrophil toll-like receptors
chemotactic factors (eg C5a and IL-8)
how does neutrophils attack the cause of inflammation
generate small self contained versions of oxidative stress
the killing potential of neutrophils via oxidative stress reactions is dependent on what
dependent on oxygen
