mechanism of disease 2 Flashcards
function of necrosis
removes damaged cells from an organism
failure to do so may lead to chronic inflammation
- necrosis causes acute inflammation to clear cell debris via phagocytosis
causes of necrosis
usually lack of blood supply, e.g.:
injury infection cancer infarction inflammation
necrosis step-by-step
- result of injurious event
- initial events are reversible, later ones are not
- lack of oxygen prevents ATP production
- cells swell due to influx of water (ATP is required for ion pumps to work)
- lysosomes rupture: enzymes degrade other organelles and nuclear material haphazardly
- cellular debris released, triggering inflammation
microscopic appearance of necrosis
- nuclear changes = chromatin condenses/shrinks
- fragmentation of nucleus
- dissolution of chromatin by DNAse
cytoplasmic changes
- opacification = protein denaturation and aggregation
- complete digestion of cells by enzymes causing cell to liquify
biochemical changes:
- release of enzymes such as creatine kinase or lactate dehydrogenase
release of other proteins such as myoglobin
- these biochemical changes are useful in the clinic as ways to measure extent of tissue damage
normal vs nectrotic kidney
loss of blue stain of nuclei
functions of apoptosis
selective process for deletion of superfluous, infected or transformed cells
involved in: embryogenesis metamorphosis normal tissue turnover endocrine-dependent tissue atrophy variety of pathological conditions
apoptosis step-by-step
- programmed cell death of one or few cells
- events are irreversible and energy dependent
- cells shrink as cytoskeleton is disassembled
- orderly packaging of organelles and nuclear fragments into membrane bound vesicles
- new molecules are expressed on vesicle membranes that stimulate phagocytosis without an inflammatory response
microscopic appearance of apoptosis 1
cytoplasmic changes:
- shrinkage of cell. organelles packaged into membrane vesicles
- cell fragmentation. membrane bound vesicles bud off
- phagocytosis of cell fragments by macrophages and adjacent cells
- no leakage of cytosolic components
morphological features of apoptosis
transmission EM = cytoplasm shrinks around nucleus
slice through cell
scanning EM = 3D,
microscopic appearances of apoptosis 2
nuclear changes:
- nuclear chromatin condenses onto nuclear membrane
- DNA cleavage
biochemical changes:
- expression of charged sugar molecules on outer surface of cell membranes
- protein cleavage by protease, caspases
DNA fragmentation
normal cell = single band
apoptosis = smaller band
necrosis = entirely non specific, long band
describe survival apoptosis
growth factors cytokines cell-cell and/or matrix contacts disruption of cell-cell and cell matrix contacts ;lack of growth factors dna Damaging
two types of apoptosis
intrinsic or extrinsic
describe intrinsic apoptosis
DNA damage - p53 dependent pathway interruption of cell cycle inhibition of protein synthesis viral infection change in redox state
describe extrinsic apoptosis
withdrawal of survival factors
extracellular signals
T cell or NK
