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Path - Cell Injury + Cell Death (i) (Adaptive cellular response to…
Path - Cell Injury + Cell Death (i)
Adaptive cellular response to stress/injury
atrophy
decrease in cell size/no. due to loss of cell substance (protein)
results in decreased organ size
can be physiological or pathological
causes
disuse (decreased workload)
loss of innervation
diminished blood supply
cachexia (undernutrition)
loss of endocrine stimulation (e.g. breast post-menopause)
ageing
foetal atrophy (e.g. thyroglossal duct)
alz (atrophic brain)
hypertrophy
increased cell + organ size
NO NEW CELLS, just larger ones
involves gene protein synthesis, organelles produced
occurs in cells incapable of division
physiological (e.g. skeletal muscle with exercise) or pathological (e.g. left ventricular hypertrophy in hypertension)
hyperplasia
increased cell no. + organ size
in cells capable of division only
can occur with hypertrophy
controlled so NOT NEOPLASTIC, but can become neoplastic
physiological causes
hormonal (oestrogen + breast + uterus in pregnancy)
compensatory (e.g. following partial hepatectomy)
can be pathological (excess hormone/gf)
metaplasia
reversible
replacement of 1 type of adult cell by another type
! cancer precursor
STEM CELL GENETIC REPROGRAMMING
smoking: resp glandular ciliated pseudo stratified epithelium replaced by squamous -> risk of squamous cell carcinoma
acid reflux: squamous epithelium replaced by intestinal (columnar/glandular, with mucin-producing goblet cells to neutralise acid) = Barrett's oesophagus -> risk of adenocarcinoma
death (necrosis/apoptosis) when injury is irreversible
mt damage
extensive membrane damage
injury to lysosomal membranes
lytic enzymes leak + digest cell (autolysis) + neighbouring cells (heterolysis)
depends on injury type, severity + duration
consequence depends on cell type, state + adaptability
causes of cell injury
O2 depletion
hypoxia (decreased delivery)
ischaemia (decreased blood flow - O2 + nutrients depleted)
shock (decreased perfusion)
physical agents
trauma
thermal injury
radiation
chemical agents
poisons
environmental pollutants
drugs
infectious agents
immunological reactions (allergies)
genetic defects
nutritional deficiency/excess (obesity)
cell components most vulnerable to injury
mt
membrane
cytoskeleton
synthetic apparatus (protein + enzymes)
genetic apparatus (DNA)
Mechanisms of injury
inhibition of aerobic resp
decreased oxidative phosphorylation in mt
ATP depleted
reversible
increased anaerobic glycolysis
decreased activity of Na+ pump
intracellular accumulation of salt + H2O
decreased activity of Ca2+ pump
intracellular Ca2+ accumulation (disrupted homeostasis)
cellular swelling
increase in enzymes
ATPase (decreased ATP)
phospholipase (decreased phospholipids)
endonuclease (nuclear chromatin damage)
protease (membrane + cytoskeleton disruption)
generation of ROS (free radicals)
extremely unstable, highly reactive chemical species with a single unpaired electron in outer orbit
physiologically generated in oxidative phosphorylation
also generated by inflamm, radiation, O2 toxicity, chemicals, drugs (e.g. paracetamol), haemochromatosis (Fe overload), copper (Wilson's disease), reperfusion injury (after ischaemia)
e.g. superoxide (O2-), H2O2, OH- (most damaging)
inactivated by enzymes + degraded by antioxidants (vit E + C)
can decay spontaneously
cause injury via...
1) lipid peroxidation of membranes (ROS + membrane lipids = highly reactive lipid peroxide)
2) oxidative phosphorylation of proteins (cross linking -> enzyme damage)
3) mutation of DNA
defects in membrane permeability