Cell Injury Flashcards
what is reversible cell injury?
cells adapt to changes in environment and return to normal once stimulus is removed
what is irreversible cell injury?
permanent and cell death as consequence
if a cell fails to adapt to stress what happens?
it becomes an injured cell
what contributes to cell stress?
dose intensity and cell vulnerability
what does reversibility or irreversibility of cell injury depend on?
type, duration, severity of injury AND on the susceptibility/adaptability of the cell: nutritional status, metabolic needs
what are the causes of cell injury?
hypoxia, physical agents, chemicals/drugs, infections, immunological reactions, nutritional imbalance, genetic defects
what is hypoxia?
deficiency of oxygen
what does hypoxia cause?
anaemia and respiratory failure
what does hypoxia do?
disrupt oxidative respiratory processes in cell - decreased ATP but cells can still release energy via anaerobic mechanisms
what is ischaemia?
reduced blood supply to tissue, depletion of not just oxygen but also nutrients e.g. glucose
what is ischaemia caused by?
blockage of arterial supply or venous drainage
what is the extent of damage caused by ischaemia?
it is more rapid/severe damage than hypoxia as anaerobic energy release will also stop
what are the physical agents of cell injury?
mechanical trauma, extremes of temperate, ionising radiation, electric shock
what does mechanical trauma affect?
cell structure and membranes
what does extreme temperature affect?
proteins and chemical reactions
what does ionising radiation damage?
DNA
what are the infectious agents that contribute to cell injury?
bacteria, viruses, fungi, parasites, protons
what are the different chemicals/drugs that contribute to cell injury?
simple chemicals, poisons, environmental, occupational hazards, alcohol, smoking and recreational drug
what do chemicals/drugs do to the cell?
disrupts membranes and proteins
how does glucose damage the cell when in excess?
causes osmotic disturbance
how does cyanide cause cell injury?
blocks oxidative phosphorylation
give an example of an environmental chemical that causes cell injury
insecticides
what immunological reactions contribute to cell injury?
anaphylaxis, autoimmune reactions
how do immunological reactions cause cell injury?
they cause damage as a result of inflammation
deficiency of what nutrient causes scurvy?
vitamin C
deficiency of which nutrient causes rickets?
Vitamin D
what problems can arise from an inadequate intake of nutrients?
scurvy, rickets (specific nutrient deficiency) , anorexia (generalised)
what problems can arise from an excessive intake of nutrients?
hypervitaminosis (specific) and obesity
what genetic defects contribute to cell injury?
sickle cell anaemia, inborn error of metabolism, cancer, more subtle variations in genetic makeup an determine susceptibility too
what are the disruptions made to the cell in reversible injury?
disruptions to aerobic respiration/ATP synthesis, plasma membrane integrity, enzyme and structural protein synthesis, DNA maintenance
what do the cells appear as histologically when they are going through reversible injury?
cloudy swelling, fatty change
why do the cells take on cloudy swelling in reversible injury?
cells are incapable of maintaining iconic and fluid homeostasis, energy dependent Na pump leads to influx of Na and water, there is also a build of up intracellular metabolites
why do cells in reversible injury undergo fatty change?
accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism so triglycerides cannot be released from the cell
what type of cell injury does fatty change in cell structure in
toxic and hypoxic injury (alcohol abuse, diabetes, obesity)
what are the reversible changes of cell injury?
dilation of organelles, ribosome disaggregation, blebbing
what changes to the cell occur at the point of no return?
mitochondrial high amplitude swelling, mitochondrial matrix densities, violent blebbing
what changes occur to the cell in irreversible injury?
membrane rupture, dispersal of organelles, breakdown of lysosomes, activation of inflammatory response
what results in the digestion of cells and those that are produced from the neutrophils at inflammatory response?
breakdown of lysosomes
what is necrosis?
cell death
what causes necrosis?
pathology
what type of cell injury is necrosis?
irreversible cell injury
what happens to the cell during necrosis?
intracellular protein denaturation and lysosomal digestion of cell
what does the disrupted cell membrane during necrosis lead to?
leakage of cell contents
what happens to the surrounding tissue of necrotic tissue?
inflammatory response
how are the cell remains of a necrotic tissue removed?
by phagocytosis
what are the nuclear microscopic changes of necrosis?
nucleus shrinks, blue staining DNA in nucleus is digested by endonucleases and the blue staining fades away
what is a useful sign that a tissue is necrotic?
histologically, the end result is the loss of the blue staining nucleus showing necrotic tissue is present as endonucleases digest the blue staining DNA
what does pyknosis mean?
nucleus shrinks
what does karyorrhexis mean?
nuclear fragments
what is karyolysis?
endonucleases digesting blue staining DNA
what are the cytoplasmic changes that take place in necrosis?
appears paler, become swollen or more eosinophilic (pinker) because of denaturation of cytoplasmic structural and enzyme proteins
how long does it take the nucleus of a necrotic cell to disappear?
1-2 days
what are the 3 types of necrosis?
coagulative necrosis, liquefactive necrosis, caseous necrosis
what happens in coagulative necrosis?
no proteolysis of dead cells as enzymes are denatured, cells digested by lysosomes of leukocytes, there is no nucleus by instead are eosinophillic cells
what does coagulative necrotic tissue appear as?
grossly, firm in texture
what is a localised area of coagulative necrosis called?
an infarct
what happens in liquefactive necrosis?
digestion of dead tissues so tissue is in liquid viscous state
what does liquefactive necrosis appear as?
focal bacterial or fungal infections (abscess)
what does liquefactive necrosis appear as?
grossly, necrotic material is thick, pale yellow in colour (pus)
what does caseous necrosis appear as?
grossly, friable white appearance (like cheese)
what is caseous necrosis mostly seen in?
TB infection
what is caseous necrosis like microscopically?
granuloma-fragmented cells and granular debris surrounded by inflammatory cells
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
what is fibrinoid necrosis?
special type of necrosis seen in immune reactions in blood vessels
what happens in fibrinoid necrosis?
immune complexes are deposited in artery walls together with fibrin that leaks out of the vessels
what are the functional effects of necrosis dependent on?
the organ/tissue
what are the inflammatory steps of necrosis?
release of cell contents activates inflammation, cell remains are phagocytosed, necrotic area is replaced by a scar (repair or organisation)
what happens if the cell remains of a necrotic tissue are not removed?
calcium salts ma be deposited in necrotic tissue
what tells you whether the cell has died
the sate of the nuclei =, pyknosis, karyorrhexis and karyolysis = DEAD
what tells you how cells have died?
cytoplasm
what is apoptosis?
genetically programmed cell death, orderly elimination of unwanted cells
what apoptosis require?
energy
what are the pathological triggers of apoptosis?
hypoxia/ischaemia, viral infection, DNA damage, caspases
what happens in 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 depended involution, cell deletion in proliferating cell populations to maintain constant number of cells, deletion of inflammatory cells are an inflammatory response, deletion of self reactive lymphocytes in the thymus
what does too much apoptosis cause?
degenerative disease
what does too little apoptosis cause?
cancer
what is 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
what are the two types of accumulation of abnormal substances in cells?
excessive normal cellular constituent and abnormal endogenous/exogenous material
what is excessive normal cellular constituent made of?
water, lipid, glycogen
what is abnormal endogenous/exogenous material made of?
carbon, silica, metabolites, cholesterol
what is atherosclerosis?
accumulation of cholesterol in macrophages and smooth muscle cells in blood vessel walls, also found at sites of haemorrhage and necrosis
what is amyloid?
a fibrillar proteins that is deposited as a result of pathologic processes leading to increased production of these proteins
where is amyloid deposited?
in extracellular locations in various tissues and organs
whar are the 3 types of amyloid?
AL (amyloilight chain from immunoglobulins), AA (amyloid associated, from proteins in liver), Abeta (alzheimers disease)
what are the stimuli of amyloid deposition?
chronic inflammation, multiple myeloma, ageing, drug abuse
what does amyloidosis do?
prevent the degradation/removal of abnormally formed proteins
what is pathological pigmentation?
build up of pigmented substances in cytoplasm and can be either endogenous pigmentation or exogenous pigmentation
what occurs in endogenous pigmentation?
lipfuscin (cellular lipid breakdown products), melanin, haemosiderin (localised brusing), bilirubin all appear as brown
what are the types of exogenous pathological pigmentation?
carbon deposition, tattoos, heavy metal salts, pigmentation associated with intravascular drug use
how does carbon deposition occur?
it is in macrophages in alveoli of lungs, black pigment, inhaled soot/smoke, in coal workers and can be severe and lead to fibrosis = pneumoconiosis
what is dystrophic pathologic calcification?
deposits of calcium phosphate in necrotic tissue, serum calcium is normal
what is metastatic pathologic calcification?
deposits of calcium salts in normal vital tissue with raised serum calcium levels, often seen in connective tissue of blood vessels, can compromise function of tissue
what are the causes of raised calcium?
1 - increased levels of parathyroid hormone, parathyroid gland tumour , 2 - destruction of bone tissue, leukaemia, metastasis to bone, immobilisation, 3 - excess vitamin D, 4 - renal failure, causes secondary hyperparathyroidism
