cell injury Flashcards
what are causes of cell injury?
- oxygen deprivation
- physical damage
- microbial (like infection?)
-immunological (like autoimmune?) - chemical
How is cell harmed by
a) ionising radiation?
b) contact with strong acid?
c) carbon monoxide inhalation?
d) trauma?
a) damage to DNA
b) coagulates tissue proteins
c) prevents O2 transportation
d) mechanical disruption of tissue
how can cells be damaged? (what ways?)
- ATP depletion →multiple downstream effects
- mitochondria damage →leakage of pro-apoptotic proteins
- intra-cellular calcium →increased mitochondrial permeability & activation of multiple cellular enzymes (as calcium = cofactor)
- free radical (ROS) damage → damage to lipids, proteins, DNA (accumulation of reactive oxygen species - different from oxidative burst which is intentional release of recative oxygen species by neutrophils)
- defective membrane permeability →loss of cellular components
- protein misfolding →activation of pro-apoptotic protiens
what is hypoxia?
a state in which oxygen is not available in sufficient amounts at the tissue level to maintain adequate homeostasis
what is hypoxia caused by?
- ischaemia →most common cause & is when reduced blood flow so reduced delivery of O2 to tissues - comprimises delivery of glycogen substrates too
- Reduction in oxygen carrying capacity of the blood e.g anaemia, CO poisoning
- Inadequate blood oxygenation e.g pneumonia
what happens to cells in hypoxic injury?
=reduced intra-cellular ATP which means Na+ pump reduced so NA+ accumulates which causes iso-osmotic gain of water & acute cellular swelling
= increased anaerobic glycolysis (bc of decreased ATP) →rapid depletion in glycogen stores
= ribosomes detach from RER
= polysomes dissociate into monomers →reduced protein synthesis
what happens if hypoxia persists?
- cytoskeleton breaks down & loss of ultra structural features
-last point of return before irreversible injury or death
what can result in cell recovery?
restoration of blood flow
what is reperfusion injury?
sometimes restoration of blood flow can result in cell recovery
but sometimes reperfusion into ischaemic tissues can cause paradoxical further injury
what do high ROS levels cause?
membrane damage & promotes mitochondrial permeability damage
what is free radical induced cell injury?
it’s when free radicals damage cells by producing reactive oxygen species (ROS)
what are forms of mechanical injury? (how mechanic of cell injured)
- direct mechanical damage = cell membranes rupture, cytoplasm spills out
- Freezing = Intracellular and cell membranes perforated by ice crystals
- Osmotic imbalance = Rupture as a result of rapid change in osmotic pressure
what are forms of microbial injury?
Bacteria
= Metabolic products/secretions which then harm the host cells
= Host inflammatory response causing further damage
Viruses
= Intracellular – can cause physical rupture of host cells
= Again, host inflammatory response can cause further damage
what are forms of chemical damage to the cell?
-drugs & poisons
- systemic Vs local toxicity
- caustic substances = rapid local death from extreme alkalinity or acidity = corrosive effect on tissue (protein digestion)
what is atrophy?
shrinkage in the size of cell by the loss of cell substance
what is hypertrophy?
increase in the size of the cells and consequently an increase in the size of an organ
what is hyperplasia?
increase in number of cells in an organ or tissue
what is metaplasia?
reversible change in which one adult cell type is replaced by another adult cell type (like squamous epithelial cells?)
what are 2 forms of irreversible cell death?
apoptosis and necrosis
what is apoptosis?
pre-programmed, contained killing of cell = no surrounding damage
what is necrosis?
causes surrounding damage & leakage of cellular contents
- much less contained and more explosive than apoptosis
what is the difference in affects to the following features with necrosis & apoptosis?
a) cell size
b) nucleus
c) plasma membrane
d) nearby inflammation
e) physiological/pathological
a) necrosis = increased, swollen cell and apoptosis skrink
b) necrosis= pyknosis (going), kayohexis (going), karyolysis (gone)
apoptosis = fragmentation/condensation
c) N = disrupted, A = intact
d) N = almost always, A = never
e) N= pathological, A = physiological but may be pathological
what are types of necrosis?
- coagulative necrosis (caused by ischaemia)
- colliquative/liquefactive necrosis (liquifies -> pus)
- caseous necrosis (type of coagulative - unrecognizable chunks)
- gangrenous necrosis (wet & dry)
- fat necrosis (from lipases & trauma)
what is coagulative necrosis?
tissue with connective tissue → basic arrangement preserved
- Caused by ischemia→ results in decreased ATP, increased cytosolic Ca++, and free radical formation, which each eventually cause membrane damage
e.g. Infarct: localized area of ischemic necrosis - myocardial infarct
what is caseous necrosis?
cheese-like necrotic debris
- Distinct form of coagulative necrosis
- Coagulated tissue no longer resembles the cells, but is in chunks of unrecognizable debris
- Usually giant cell and granulomatous reaction
Example: Tuberculosis
what is colliquative necrosis?
tissue with minimal connective tissue
- Often in brain because lack of supporting stroma predisposes to total liquefaction when necrotic
- Usually caused by focal bacterial infections, because they can attract polymorphonuclear leukocytes (neutrophils)
- The enzymes in the neutrophils are released to fight the bacteria, but also dissolve the tissues nearby, causing an accumulation of pus effectively liquefying the tissue
what is gangrenous necrosis?
= Dry –sterile coagulative necrosis (doesn’t involve bacterial infection) e.g. distal limb - GI tract & bacterial
= Wet – coagulative necrosis with superimposed infection - limbs (diabetic)
- often associated with lack of blood supply
what is fat necrosis?
- Release of enzymes from pancreas or gut or traumatic
- Enzymes (lipases) release free fatty acids, which with calcium produce soapy deposits in tissues
- Histology: shadowy outlines of fat cells, calcium deposits, foam cells, surrounding inflammatory reaction
what is autolysis?
- rotting of tissue
- lysis of tissue by their own enzymes, following death of the organism
- “ no vital reaction (i.e., no inflammation)”
- Early autolysis is indistinguishable from early coagulative necrosis due to ischemia, unless the latter is focal
why is apoptosis physiologically important? (i.e what is apoptosis important for)
- Embryogenesis
- Menstrual cycle (shedding of endometrium)
- Immune system = Death of post-inflammatory neutrophils & Removal of self-reactive lymphocytes & Death of virally infected cells
a) what is healing by primary intention?
b) what is healing by secondary intention?
a) Restitution with no – or minimal – residual defect(surgical context = sewn up minimal)
b) Organisation and repair where there is tissue loss & Granulation tissue (scar) (surgical context = left open to heal itself and scar formed)
what is labile cell group?
cells that have good capacity to regenerate (like surface epithelial cells)
what is stable cell group?
cells that divide at a slow rate, but can regenerate if needed (eg hepatocytes in liver)
what is permanent cell group?
cells with no means of effective regeneration eg nerve cells, striated muscle cells
