cell injury + cell death Flashcards
(38 cards)
what are the different ways a cell responds to injury?
- cell adapts
- cell remains injured then returns to normal
- cell dies
what are the different causes of cell injury?
environmental:
* hypoxia
* toxins
* immune mediated
* physical agents
* infection
* nutritional/dietary
non-environmental:
* genetic
* ageing
how does hypoxia cause cell injury?
cells undergo oxygen deprivation
what are the different types of hypoxia?
- hypoxaemic hypoxia: arterial content of oxygen is low
- anaemic hypoxia: decreased ability of haemoglobin to carry oxygen
- ischaemic hypoxia: interruption to blood supply
- histotoxic hypoxia: inability to utilise oxygen due to diabled oxidative phosphorylation enzymes
how are different cells/tissue affected by hypoxia?
different tissues are affected in different ways by hypoxia:
* brain can only go a few mins vs skeletal muscle can go a few hours
cause of hypoxia needs to be adressed
what are immune mediated causes of cell injury?
Hypersensitivity reactions:
* injury secondary to excessive immune reaction to “non-self” antigen
Autoimmune reactions:
* immune system reacts to self antigens
how do physical agents cause cell injury?
trauma
extreme temps
electric currents
radiotherapy
how do infections cause cell injury?
bacterial
fungi
virus
parasites
how do genetics/ageing cause cell injury?
inborn errors in metabolism
non functional enzymes
cells are more prone to injury as they age
what are the different mechanisms of cell injury?
- depletion of ATP
- direct mitochondrial damage
- direct membrane damage
- disruption to calcium homeostasis
- oxidative stress
- direct damage to DNA and proteins
how does ATP depletion cause cell injury?
(varying causes reduce ATP prodction, whats important is the issues which arise from low ATP levels)
* anaerobic glycolysis - increase lactic acid production which lowers pH and denatures cellular enzymes
* affects energy dependent Na+/K+ pump - Na+ and water enter cell, cell swells, Ca2+ enters cell
* causes ribosomes to detach from ER - altered protein synthesis, proteins cant function
why does calcium influx cause irreversible cell injury?
activates following:
1. ATPases - increases ATP consumption
2. phospholipases - break down cell and organelle membranes
3. proteases - breaks down proteins
4. enodnucleases - breakdown DNA in cell
how does production of free radicals cause cell injury?
free radical formation can be pathological or physiological
free radicals damage the following:
1. lipids - target unsaturated fatty acids, cell membrane and organelles damaged, resulting in Ca2+ influx
2. proteins - promotes protein-protein cross-links and protein fragmentations form
3. DNA - nuclear DNA and mitochondrial DNA is broken down
how does the body control free radicals?
free radicals are unstable and decay spontaneously
body removes free radicals by:
1. anti-oxidants
2. transport proteins
3. enzymes
what are examples of anti-oxidants which control free radicals?
- lipid soluble vitamins
- ascorbic acid
- glutathione
what are examples of transport proteins which control free radicals?
metals produce free radicals so its dangerous for them to just exist in body
* iron binds to transferrin
* copper binds to ceruloplasmin
what are examples of vitamins which control free radicals?
- superoxide dismutases
- glutathione peroxidase
what are mechanisms which repair free radical damage?
heat shock proteins (ubiquitin):
* repair and re-fold damage proteins
* if they can’t repair proteins they label them for degradation
* in times of stress cells reduce normal protein synthesis and increase heat shock protein synthesis
what does an injured cell look like?
reversible changes:
* swelling - due to damage to Na+/K+ pump
* clumped chromatin - due to reduced pH
* ribosome dispersion- lack of ATP which normally holds them together
* cytoplasmic blebs - symptomatic of cell swelling
irreversible changes:
* nuclear changes -
* lysosome ruptures
* membrane defects - reflects membrane damage
* lysis of ER - due to membrane defects
what is the difference between apoptosis + necrosis?
apoptosis:
* individual cells death
* programmed cell death
* cell shrinks
* plasma membrane is preserved
* organelles contract
* DNA is cleaved between nucelosomes
* dead cells taken up by phagocytosis
necrosis:
* grouped cell death
* cells swell
* plasma membrane destroyed
* organelles swell and break down
* DNA is degraded randomly
* dead cells start inflammatory process
what happens in apoptosis?
individual programmed cell death
* cells shrink
* no inflammation
* physiological or pathological
what are physiological causes of apoptosis?
- embryogenesis
- involution of hormone dependent tissue
what are pathological causes of apoptosis?
- cell death in viral infection
- cells with damaged DNA
what are the 2 pathways for apoptosis?
intrinsic pathway (mitochondrial):
* mitochondria release cytochrome C which activate caspases which induce apoptosis
Extrinsic pathway (death receptor):
* death receptors are released by T killer cells and attach to the cell membrane which then activate caspases which leads to cell death
