cell injury Flashcards
what is meant by reversible cell injury?
cells adapt to changes in the environment then return to normal once stimulus is removed
what is meant by irreversible cell injury?
permanent and the consequence is cell death
what does cell injury cause?
disease
what dos cell injury give?
disease
what are factors which are involved in cell injury?
- dose intensity
- cell stress
- cell vulnerability
what is the reversiblility of the cell dependant on?
- cell type
- duration
- severity of injury
- susceptibility of the cell
- adaptability of the cell
- nutritional status
- metabolic needs (cardiac vs skeletal)
what is the aetiology (causes) of cell injury?
hypoxia (=decreased oxygen supply)
physical agents (radiation – free radicals)
chemicals/drugs
infections (bacterial toxins, viruses)
immunological reactions
nutritional imbalance
genetic defects
what is the aetiology (causes) of cell injury?
hypoxia (=decreased oxygen supply)
physical agents (radiation – free radicals)
chemicals/drugs
infections (bacterial toxins, viruses)
immunological reactions
nutritional imbalance
genetic defects
what is hypoxia?
- oxygen deficiency
- causes include anaemia and respiratory failure
- disrupts oxidative respiratory processes in the cell giving decreased ATP
- cells can still release energy via anaerobic mechanisms
what is ischaemia?
- reduction in blood supply to tissue
- caused by a blockage of arterial supply or venous drainage eg atherosclerosis
- depletion or oxygen and nutrients
- faster rate of damage than hypoxia as anaerobic energy release also stops
what are examples of physical agents which cause cell injury?
- mechanical trauma
- extreme temperatures
- ionising radiation
- electrical shock
what are examples of infectious agents which can cause cell injury?
bacteria
viruses
fungi
parasites
protons
what are examples of chemicals/drugs which can cause cell injury?
- simple chemicals (eg glucose), in excess cause osmotic disturbance
- poisons (cyanide blocks oxidative phosphorylation), environmental (insecticides)
- occupational hazards (asbestos) causes inflammation
- alcohol, smoking and recreational drug
all disrupt cell membranes and proteins
what are examples of immunological reactions which can cause cell injury?
- anaphylaxis (tp 1 hypersensitivity, IgE mediated)
- auto-immune reactions (tp 2, antibodies directed towards host antigens, tp 3 – antigen-antibody complexes)
cause damage as a result of inflammation (complement, clotting, neutrophil products, etc)
what are examples of nutritional imbalances which can cause cell injury?
- too little nutrients eg scurvy, rickets, anorexia
- too much eg hypervitaminosis A/D, obesity
what are genetic defects which can cause genetic defects?
- sickle cell anaemia
- inborn error of metabolism- lack of enzyme causes substrate build up
- cancer
what happens to the cells which undergo reversible injury?
- aerobic respiration/ATP synthesis (mitochondrial damage)
- plasma membrane integrity
- enzyme and structural protein synthesis
- DNA maintenance
- cloudy swelling/fatty change
what is cloudy swelling?
- failure of the cells energy dependant ion pumps in the cell membrane
- influx of sodium and water
- build up of intracellular metabolites
what is fatty change?
- accumulation of lipid vacuoles in the cytoplasm caused by disruption of fatty acid metabolism so that triglycerides cannot be released from the cell esp in liver
- occurs with toxic and hypoxic injury (alcohol abuse, diabetes, obesity)
- macroscopically the liver appears enlarged and pale
when is the point where a cells damage becomes irreversible?
- mitochondrial highly swollen
- voilent blebbing
what is necrosis?
- cell death
- due to pathology
- irreversible cell injury
- intracellular protein denaturation
- lysosomal digestion of cell
- cell membrane disrupted due to leakage
- inflammatory response in the surrounding tissue
- remains removed by phagocytosis
- hustopathological responses can take a while to appear
what are the microscopical changes of necrosis?
- pyknosis = nucleus shrinks; darker staining
- karyorrhexis = nucleus fragments
- karyolysis = the blue staining DNA in nucleus is digested by endonucleases and the blue staining fades away
- end result is loss of the blue staining nucleus – a useful sign that a cell is necrotic
- cytoplasm paler and pinker
what are the types of necrosis?
- coagulative
- liquefactive
- caseous
- fibrinoid
- gangrenous
- fat
what are the types of necrosis?
- coagulative
- liquefactive
- caseous
- fibrinoid
describe coagulative necrosis?
- No proteolysis of the dead cells due to denaturation of enzymes
- Architecture of tissues is preserved for some days
- No nucleus; eosinophillic cells.
- Grossly, firm in texture
- Cells digested by lysosomes of leukocytes
- Localised area of coagulative necrosis is called an infarct.
what is the type of necrosis in the CNS?
liquefactive as a result of hypoxia
describe liquefactive necrosis
- Digestion of dead tissues so tissue in in liquid viscous state
- Focal bacterial or fungal infections (abcess)
- Grossly, necrotic material is thick, pale yellow in colour
- CNS necrosis as a result of hypoxia often manifested as liquefactive necrosis.
describe caseous necrosis
- Grossly, friable white appearance (like cheese)
- Mostly seen in tuberculous infection
- Microscopically; granuloma-fragmented cells and granular debris ( mass apoptosis) surrounded by inflammatory cells
what type of necrosis is seen in tuberculous infection?
caseous
what is gangrenous necrosis?
coagulative necrosis with superimposed bacterial infection –liquefactive necrosis
what is fat necrosis?
focal areas of fat destruction. Fat cells may be liquefied by activated pancreatic enzymes (acute pancreatitis)
describe fibrinoid necrosis
- special type of necrosis seen in immune reactions in blood vessels
- immune (antigen –antibody) complexes are deposited in artery walls together with fibrin that leaks out of the vessels.
- bright pink and amorphous substance in H&E
what are the effects of necrosis?
- functional
- inflammation:
release of cell contents activates inflammation, cell remains are then phagocytosed, finally the necrotic area is replaced by a scar-i.e. it undergoes organisation or repair, if remains are not removed then calcium salts may be deposited in necrotic tissue
what organelle within the cell can tell you whether the cell has died?
nucleus
what organelle within the cell can tell you how the cell died?
cytoplasm
what is apoptosis and how does it differ from necrosis?
- programmed cell death
- orderly elimination of unwanted cells
- important physiological role
- can occur in pathological situations
- requires energy
- distinct pathways involved
- does not cause inflammation
- different morphology from necrosis
what are potential pathological triggers of apoptosis?
- hypoxia/ischaemia (protein misfolding)
- viral infection – cytotoxic T-lymphocytes contain - - enzymes which can induce apoptosis.
- DNA damage- if unrepairable p53 triggers apoptosis
- Caspases are activated enzymes that trigger apoptosis.
- Cell contents are degraded by enzymes activated by the cell.
what are the physiological roles of apoptosis?
- deletion of cell populations during embryogenesis
- hormone change dependent involution –uterus, breast, ovary
- cell deletion in proliferating cell populations to maintain constant number of cells - epithelium
- deletion of inflammatory cells after an inflammatory response
- deletion of self reactive lymphocytes in the thymus
what happens if there is too much apoptosis?
degenerative disease
what happens if there is too little apoptosis?
cancer
describe the morphology of apoptosis
- cell shrinkage
- chromatin condensation – packaging up of nucleus
- cell membrane remains intact, with formation of cytoplasmic blebs
- break off to form apoptotic bodies
- phagocytosed, but no widespread inflammation
intracellular accumulation
what is one of the most common materials to accumulate in the cell?
cholesterol
what happens when cholesterol accumulates in the cell (atherosclerosis)?
what is commonly accumulated in the basement membrane of cells?
amyloid
what is amyloid?
Amyloid is a fibrillar protein material that is deposited as a result of pathologic processes leading to increased production of these proteins
Deposited in extracellular location (mostly on basement membrane) in various tissues and organs.
Types:
AL -(amyloid light chain) derived from light chain immunoglobulins from plasma cells.
AA -(amyloid associated): derived from proteins synthesized in the liver
Aβ -Alzheimer’s disease
what stimuates amyloid accumulation?
- chronic inflammation
- multiple myeloma
- ageing
- drug abuse
what does amyloid look like under a microscope?
pale pink
what are common causes of endogenous pigmentation?
Lipofuscin-cellular lipid breakdown products
Melanin
Haemosiderin-localised bruising
Bilirubin
All appear brown
what are the most common causes of exogenous pigmentation?
- carbon deposition in alveoli of lungs
- black pigment from tattoos
- inhaled smoke and soot
what is pathologic calcification?
- dystrophic, valves in heart become thick
- metastatic, can compromise tissue function (BV and CT)
what are causes of hypercalcaemia?
1-increased levels of parathyroid hormone (hyperparathyroidism)
parathyroid gland tumour
2-destruction of bone tissue- leukaemia, metastasis to bone, immobilization
3- excess vitamin D
4- renal failure- causes secondary hyperparathyroidism
