cell injury, cell death, and toxin insult Flashcards
what are the main adaptive cellular responses
hypertrophy (increase in cell size), hyperplasia (increase in # of cells), atrophy (decrease in size and metabolic activity), and metaplasia (change in phenotype)
physiological adaptation occurs under
responses to normal stimuli
pathological adaptation occurs under
responses to stress that allows cells to change structure and function
what occurs in hypertrophy
-increase in size of cells leading to increase size of organ
- adaptive response in cells with limited capacity to divide
what are the causes for hypertrophy
physiological increase hormone or pathological increase workload
what occurs in hyperplasia
- adaptive response in cell capable of replication
- increase in number of cells
what occurs in atrophy
shrinkage in size of cells
what are the etiological factors associated with atrophy
decreased workload, loss of innervation, diminished blood supply
what are the mechanisms of atrophy
decreased protein synthesis and increased protein degradation
what occurs in metaplasia
reversible changes in cell type in response to stress
what are the two types of cell death
necrosis- pathologic process
apoptosis- not necessarily associated with pathology
characteristics of necrosis
cell swelling, membrane disrupted, no ATP required
characteristics of apoptosis
cell shrinkage, requires ATP
what are the causes of cell injury
hypoxia, chemical agents, infectious agent, immunological reaction, genetic factors, nutritional imbalance, physical agents, aging
what two phenomena characterize irreversibility
inability to correct mitochondria dysfunction
profound disturbance in membrane function
two main morphological correlate of reversible cell injury are
cell swelling and fatty change
why is cell swelling first manufactured
failure of energy depended ion pumps in plasma membrane
what is seen in fatty change
appearance of lipid vacuoles in cytoplasm
occurs in hypoxic injury
necrosis is characterized by
changes in cytoplasm and nuclei of injured cells
cytoplasmic changes in necrosis is characterized by
increased eosinophilia due to increased binding of eosin to denatured protein
what are the 3 patterns that occur in nuclear changes in necrosis
karyolysis, pyknosis, karyorrhexis
karyolysis is seen by
basophils of chromatin may fade
pyknosis is seen by
nuclear shrinkage and increased basophilia
karyorrhexis is seen by
pyknotic nucleus undergoes fragmentation
dead cells may be replaced by
myelin figures that can be degraded to fatty acids
fatty acids can bind to
calcium salts that may result in dead cells calcified
what are the patterns of tissue necrosis
coagulative necrosis, liquefaction necrosis, fat necrosis, caseous necrosis, fibrinoid necrosis, gangrenous necrosis
what are the causes of coagulative necrosis
sudden cut of the blood supply (ischemic necrosis)
hypoxia is what
deficiency of oxygen
ischemia is
reduced blood flow
ultrastructure changes of reversible injury
-blabbing and loss of microvilli in plasma membrane
- modest mitochondria swelling
-dilation with detachment of polysomes of ER
ultrastructure changes of irreversible injury
- disruption of plasma membrane
- massive mitochondria swelling
- extensive disruption and fragmentation of ER
denaturation of cellular proteins in coagulative necrosis causes tissue to appear
hard, opaque white and preserve its architecture
in coagulative necrosis, it presents area of
infarcts
liquefactive necrosis is characterized by
digestion of dead cells resulting in transformation of tissue into liquid viscous mass
what organs is liquefactive necrosis typically seen
brain and spinal cord
pyogenic abscess is
the necrotic core is liquefied by proteolytic enzymes releasing pus
what mechanism is seen in liquefactive necrosis
lysosomal enzymes released by necrotic cells/neutrophils
the most clinical cause of gangrenous necrosis is
ischemia to lower extremities
caseous necrosis typical for ____ lesions
tuberculous
the tissue in caseous necrosis appears
yellowish white and cheesy
necrosis is followed by _____ in caseous necrosis
slow partial liquefaction
fat necrosis occurs due to
enzyme lipase digesting fat cells to fatty acids
combination of fatty acids with calcium leads to
calcium soaps/ opaque white patches
what is the fundamental cause of necrotic death
depletion of ATP
major causes of ATP depletion are
- decreased O2 and nutrient supply
- mitochondrial damage
- toxins
what are consequences of ATP depletion
- plasma membrane pumps decreases
- increase anaerobic glycolysis
- failure of ATP Ca2+ pumps
- disruption of protein synthesis
what are stimuli for mitochondria injury
ischemia, chemical toxins, and radiation
mitochondrial damage may result in
-failure to oxidative phosphorylation
-abnormal oxidative phosphorylation
- formation of abnormal mitochondria permeability transition pore
influx of calcium is caused by
ischemia and some toxins
what are the effects of increased cytosolic calcium
activates enzymes that can deteriorate cells
ex. phospholipase, protease, endonuclease
oxidative stress is the ….
abnormal accumulation of oxygen derived free radicals
the damage caused by free radicals is determined by
rate of production and removal of ROS
excess free radicals leads to
oxidative stress
plasma membrane can be damaged by
ischemia, microbial toxins, lytic complement components, physical agents, chemical agents
major cellular abnormality in oxygen deprived cells are
-decrease ATP generation
- mitochondria damage
- accumulation of ROS
loss of ATP leads to
- failure of ion pumps
- depletion of glycogen stores
- decreased protein synthesis
ischemia-reperfusion injury is caused when
restoration of blood flow to ischemic tissues leading to cell death
apoptosis is normal phenomena that serves to
eliminate cells that are no longer needed
apoptosis results from activation of
caspases enzymes
what are the two distinct pathways for apoptosis
mitochondria (intrinsic) pathway
death receptor (extrinsic) pathway
intrinsic pathway is triggered by…
loss of survival signals, DNA damage, and accumulation of misfolded proteins
extrinsic pathway is responsible for
elimination of self reactive lymphocytes and damage by cytotoxic T cells
autophagy refers to
lysosomal digestion of cells own components
autophagy is survival mechanism in
times of nutrient deprevation
intracellular organelles and some cytosol sequester into
a autophagic vacuole
vacuole fuses with lysosomes to form
autophagolysosome
what substances can accumulate inside cells
water, fat, mucin, glycogen, proteins, pigments
what are the 2 main pathways of abnormal intracellular accumulations
- inadequate removal of normal substances (fatty liver)
- failure to degrade a metabolite (storage disorders)
dystrophic calcification occurs when…
deposition occurs in dead or dying tissues
metastatic calcification occurs when…
- deposition of calcium salts in normal tissue
- reflects hypercalcemia
mechanism responsible for cellular aging
- DNA damage
- decreased cellular replication
- defective protein homeostasis
