7: Mechanisms of Cell Death and Tissue Repair Flashcards
homeostasis is when a cell is at
optimal function, meeting physiological demands
reversible changes in response to cell’s environment/ stressors
adaptation
_____ happens when cells can not adapt or are at the max adaptive response to stimuli
cell injury
factors affecting cell injury include
nature/ duration/ severity + cell type/ adaptation + activation of multiple mechanisms
list the 6 mechanisms of cell injury
mitochondrial damage
abnormal calcium homeostasis
DNA damage
membrane damage
ER stress
oxidative stress
describe why mitochondrial damage causes cell injury
essential for survival by producing ATP, but is also a major source of reactive oxygen species production + activates cell death pathways (apoptosis, autophagy, etc)
describe why abnormal calcium homeostasis causes cell injury
increased Ca activates Ca dependent enzyme degradation
describe how ER stress causes cell injury
releases Ca stores, misfolded proteins
chemical injury directly targets
organelles
chemical injury requires __________ activation and often trigger an _____ response
metabolic activation
inflammatory response
chemical injury is
1. selective, not based on kinetics
2. nonselective, not based on kinetics
3. nonselective, based on kinetics
4. selective, based on kinetics
4
cellular damage occurs when __________are overwhelmed = damage to membrane, mitochondria, ER, DNA, proteins
antioxidant systems
hypoxia
tissues are starved of oxygen- 1-2% oxygen
ischemia
blood flow is cut off to tissues (no blood/ oxygen delivered but also no removal of metabolic wastes)
mild ischemic/ hypoxic injury is reversible if
tissue oxygen supply is restored
anoxia is
0% oxygen left
reversible cell injury is _______ insult or ______ duration
milder
shorter
describethe hibdernating myocardium
Delayed return to function once regional flow reestablished because muscle was hibernating to try to survive longer
loss of blood flow and oxygen results in (series after ATP drops)
↓ ATP results in
↓ ion pumps (no ATP to drive pumps Na/K levels change = cell swelling
↑ glycolysis (from ↓ oxphos)
↓pH (lactic acid production), disruption of synthesis/ storage
loss of blood flow and oxygen for too long =
membrane injury, calcium influx activates enzymes to break down cell = lysosomal breakdown of organelles/ proteins = autodigestion = protein markers released
the point at which the cell becomes unable to recover its normal morphology and function even if all processes leading to its dissolution stopped
cell death
what is programmed cell death
a active process that depends on the execution of a defined sequence of signaling events
Dependent on genetic encoded signals or activities
Not the same as apoptosis
what are the 3 distinct routes of cellular catabolism
apoptosis
autophagy
necrosis
accidental necrosis is a _________ process
passive
energy independent
give 4 characteristics of accidental necrosis
Pathological (following noxious stimuli)
Occurs synchronously in multiple cells of a tissue region
Early loss of membrane integrity
Generalized cell and nuclear swelling
Nuclear chromatin disintegration
Inflammatory reactions (triggered as membrane dies)
Energy independent (dramatic irreversible drop in ATP)
Historically regarded as unregulated cell death
4 morphological descriptions of necrosis
coagulative/ infarct
liquefactive
fatty
caseous
describe coagulative/ infarct necrosis
Infarction- necrosis caused by ischemia or anoxia (heart attack/ stroke)
Tissue shows red staining indicating clot proteins (Ex- fibrin), anoxic injury
Loss of blood supply
describe liquefactive necrosis
Death of tissue releases many lytic enzymes = degrades surrounding tissues
Fluid remains following digestion of necrotic tissue
describe fatty necrosis
Pancreas release of enzymes = lipase digests fat = produces soaps microscopically(saponification)
Loss of cellular membrane
Necrotic fat cells
Release of fatty acids combined with minerals
describe caseous necrosis
Combination of coagulative and liquefactive necrosis
Granulomas (cluster of WBCs) as a result of immune response
apoptosis is critical in the
maintenace of normal organ and tissue homeostasis
sculpting development and maintaining normal function
apoptosis is a ______ process
active
apoptosis is _____ controlled
geneticallly
which evokes less inflammatory response, necrosis or apoptosis
apoptosis
autophay is
Self digestive process to remove damaged proteins/ organelles by fusing with lysosomes for digestion
which does not display chromatin condensation
1. ncrosis
2. apoptosis
3. autophagy
3
autophagy is caspase ____ (dep/ indep)
independent
3 major categories of autophagy
macroautophagy
microautophagy
chaperone mediated autophagy
macroautophay is the
fusion of autophagosome with lysosome → degradation in lysosome → efflux of metabolites
microautophay is
specific type of organelle (may be damaged) is sequestered into lysosome for degradation
chaperone mediated autophagy is
uses specific proteins (LAMP-2A, Hsp70 chaperone) to target specific motif on proteins → translocates to lysosome → degradation → efflux
autophahy is often associated with
cell survival
autophagy is triggered by
nutrient deprivation- enables cells to restore sufficient energy levels + promotes viability
in early stages after cell death, debris is cleaned up by __________ that accumulate over ______. this process begins within ______
cleaned up by phagocytes that accumulate over few days
starts within minutes
in early tissue repair, tissue ____ begins to repair, there is new _______ to provide ________ , also known as
tissue scaffold
new blood supply
granulation tissue
when does early tissue repair start happening
several days post injury
in late tissue repair, ____ proliferate and synthesize collagen
fibroblasts
3 responses to abnormal physiologic stress
tissue adaptations
metabolic responses
growth responses
