Trans - Cellular Responses to Stress: Adaptation and Injury Flashcards
stages in the cellular response
- normal cell
- cellular adaptation
- cellular injury
homeostasis - define
process by which cells control the composition of their immediate environment and internal milieu within a narrow range of physiological parameters
adaptation - define
process by which cells reach a new steady state compatible with their new environment
cells adapt by:
altering their pattern of growth
cellular damage occurs when:
adaptive mechanisms can no longer compensate for changing environment
2 outcomes of cellular injury
- reversible
2. irreversible
reversible injury
return to normal when stress is removed
irreversible injury
severe injury leading to cell death (apoptosis and necrosis)
cellular response to injurious stimuli depends on these four factors
- type of injury
- duration of injury
- severity / intensity of injury
- vulnerability of cell
[T/F] relatively nonspecialized cells are more vulnerable to injury because they are more exposed to the environment
F, more specialized cells have high vulnerability (ex. brain)
which is lost first - symptoms of injury, or cell function?
cell function
generally, cell injury is caused by:
abnormalities on the biochemical and molecular level caused by stress
consequence of interdependence of biochemical systems in the context of injury
injury at one site typically causes secondary or tertiary injuries to other cellular processes
4 major molecular targets of cellular injury
- cell membrane
- mitochondrial function
- functional and structural proteins
- genetic integrity
5 general mechanisms of cellular injury
- ATP depletion
- loss of plasma membrane integrity
- loss of Ca2+ homeostasis
- mitochondrial damage
- oxygen deficiency
ATP depletion and decreased ATP synthesis are frequently associated with:
hypoxic and chemical injury
[T/F] cells with greater glycolytic capability are first injured in prolonged ischemia
F, cells with greater glycolytic capacity have greater capacity for anaerobic respiration
possible consequence of acidosis within the cell
damage to DNA
consequence of damage to plasma membranes
lysis due to disrupted ion balance
consequences of potassium leaking from plasma membrane
decreased ability to maintain resting membrane potential
consequences of injury to mitochondrial membrane
- impairment of energy metabolism
2. initiation of apoptosis due to release of cytochrome c
consequences of injury to lysosomal membrane
autophagy due to release of hydrolytic enzymes
consequences of injury to golgi-ER complex
impaired protein synthesis and protein transport
effect of ischemia in concentration of Ca and O2 within the cell
increase Ca
decrease O2
4 effects of increased cytosolic Ca
- phospholipid degradation due to activation of phospholipases by Ca
- degradation of the membrane due to activation of proteases by Ca
- activation of ATPase by Ca –> less ATP
- activation of endonucleases by Ca –> DNA damage
cytosolic Ca activates which two types of enzymes
- phospholipases
2. proteases
how does a decrease in ATP affect the membrane stability of a cell
a decrease in ATP causes a decrease in reacylation/synthesis of new phospholipids, which in turn allows the degradation of the membrane
high conductance channel in mitochondria that appears when the mitochondria are damaged
mitochondrial permeability transition
where in the mitochondria is the mitochondrial permeability transition located
inner mitochondrial membrane
2 main effects of mitochondrial membrane damage
- decrease in ATP
2. release of cytochrome C into the cytosol
effect of cytochrome C
facilitates apoptosis pathway
how does a cell maintain Ca homeostasis
through energy dependent pumps that keep cytosolic Ca low
free radical - define
highly reactive, unstable species with one unpaired electron, may facilitate damaging chain reactions that create other free radicals
how are free radicals generated
- from cellular metabolism (redox)
2, from enzymatic metabolism of exogenous enzymes - through ionizing radiation
- divalent metals
how are free radicals physiologically utilized in the body?
used by leukocytes in antimicrobial processes
how are free radicals neutralized
- spontaneous decay
- superoxide dismutase (for superoxide)
- glutathione (for OH)
- catalase (for H2O2)
- vitamin E, A, C, beta carotene, other antioxidants
examples of O2 determined free radicals
- superoxide O2-
- H2O2
- OH-
how do free radicals damage membranes
through lipid peroxidation –> attack on double bonds of unsaturated phospholipids
how do free radicals damage proteins
chain reactions
how do free radicals damage DNA
react with thymine in mitochondrial DNA, creating single strand breaks and abnormal cross linking
reaction wherein O2- is converted to H2O2 and then to OH
Fenton reaction
Fenton reaction is catalyzed by:
Cu 2+, Fe 2+
superoxide dismutase is used against
superoxide
catalase is used against
H2O2
glutathione is used against
OH
in general, damage to enzymes results to
very slow reactions and impaired transport mechanisms
hypoxia - define
oxygen deprivation
ischemia - define
blood deprivation
differentiate hypoxia and ischemia
hypoxia - only oxygen is gone
ischemia - oxygen and other metabolic substances gone