Lecture 16: How Cells Respond to Injury Flashcards
what are the basic ways of tissue growth
- multiplicative: increase in cell number
- auxetic: increase in cell size
- accretionary: increase in extracellular tissue
labile cells
- continuously proliferate
- have a short lifespan and rapid turnover time
- eg blood cells and many epithelial cells esp. in gut
permanent cells
- have very little or no regenerative ability
- have undergone terminal differentiation
- eg keratinocytes, neurons, cardiac and skeletal muscle, red blood cells
how can a tissue adapt in response to injury
- hypertrophy
- hyperplasia
- atrophy
- metaplasia
what is hypertrophy
- increase in cell size, and more organelles within the cell
- is the only adaptive response available to permanent cells
- happens due to incrased workload, which activates the P13K/AKT and G-coupled pathways to induce hypertrophy
what are examples of physiological hypertrophy
- hypertrophy of skeletal muscle through training
- hormonal stimulation causes uterine hypertrophy
what are examples of pathological hypertrophy
- cardiac hypertrophy due to hypertension or valvular disease
- bladder hypertrophy due to prostate enlargement
what is hyperplasia
- increase in cell number
- requires cells to be able to divide, so only happens in labile or stabile cells
- controlled by growth factor activation and stem cell activation
what are examples of physiological hyperplasia
- hormonal hyperplasia of breast tissue during breastfeeding
- compensatory hyerplasia when tissue is lost, eg in liver resection or bone marrow hyperplasia in bleeding
what are examples of pathological hyperplasia
usually due to excess hormone
- excess oestrogen leads to endometrial hyperplasia
- excess androgens cause prostatic hyperplasia
- HPV induced hyperplasia in warts
what is atrophy and what is the mechanism
- reduction in cell size and numbers
- mechanism is by degradation of cellular organelles or proteins by ubiquitin-proteosome pathways
what are examples of physiological atrophy
- testicular or ovarian atrophy due to loss of hormonal stimulation in old age
- atrophy of uterus after parturition (giving birth)
- atrophy of developmental structures like the notochord / thyreoglossal duct
what are examples of pathological atrophy
- muscle wastage due to disuse
- vascular atrophy in the brain due to atherosclerosis
- malnutrition
- pressure atrophy on surrounding tissues due to benign tumours
what is metaplasia
- one differentiated cell / tissue type is replaced by another
- usually seen in epithelium but possible in mesenchyme
what are examples of physiological metaplasia
- metaplasia of cervical columnar epithelium to stratified squamous epithelium in response to vaginal acidic environment
what are examples of pathological metaplasia
- oesophageal stratified squamous epithelium to columnar epithelium in response to acid reflux, called Barrett’s oesophagus
- bronchial ciliated columnar epithelium to stratified squamous epithelium in response to smoking
- myositis ossificans within muscles after trauma
what happens in reversible cell injury
- reduced oxidative phosphorylation and depletion of ATP so ATP dependent processes stop
- change in ionic concentrations and influx of water causes swelling
- changes in intracellular organelles
- increase in eosinophils in blood
what happens in irreversible cell injury
reversible cell injury +
- lysosome rupture and autodigestion of cell
- proteins denature and membranes rupture
- nuclear changes like karyolysis, karyorrhexis and pyknosis
- cell death and cellular components leak into blood
- levels of these can determine intensity of damage, eg troponin in heart and transaminases in liver
what is necroptosis
shows features of both apoptosis and necrosis
what is pyroptosis
apoptosis with fever and IL-1 signalling
what happens during apoptosis
- cell fragments into small vesicles called apoptotic bodies
- express proteins on the surface that make them highly visible to phagocytes, which digest them
what happens during necrosis
- ATP depletion
- mitochondrial damage
- influx of calcium
- accumulation of oxygen radicals which are highly reactive and break the cell apart
- increased membrane permeability
- DNA and protein damage
- drop in pH due to lactic acid build up
- cellular constituents leak into surrounding tissues
what happens during coagulative necrosis
- ischaemia
- shape and architecture of the organ is highly preserved
what happens during liquefactive necrosis
- mainly seen in brain
- ischaemic
- liquified, viscous, soft lesion
- seen in bacterial infections