L3: Cell death & cell damage Flashcards
What are the functions of necrosis?
→Removes damaged cells from an organism
→causes acute inflammation to clear cell debris via phagocytosis
What does lack of necrosis lead to?
→may lead to chronic inflammation
What are some examples of causes of necrosis?
Usually lack of blood supply, e.g. →injury, →infection, →cancer, →infarction, →inflammation
What can be observed in necrosing tissues as distance from blood vessels increases?
→ as distance increases
→pH and pO2 reduces
Describe the necrosis process
→Lack of oxygen prevents ATP production → increased osmolarity.
→Cells swell due to influx of water (ATP is required for ion pumps to work).
→Lysosomes rupture; enzymes degrade other organelles and nuclear material hapzardly
→Cellular debris released, triggering inflammation
What is a difference between the early and later stages of necrosis?
→first stage is reversible mitochondrial changes unlike apoptosis
What are the microscopic changes that occur during necrosis?
- Chromatin condensation/shrinkage.
- Fragmentation of nucleus.
- Dissolution of the chromatin by DNAse.
What are the cytoplasmic changes during necrosis?
- Opacification: protein denaturation & aggregation.
2. Complete digestion of cells by enzymes causing cell to liquify (liquefactive necrosis).
What are the biochemical change that during necrosis?
- Release of enzymes such as creatine kinase or lactate dehydrogenase
- Release of other proteins such as myoglobin
Why are biochemical changes useful for?
→to measure the extent of tissue damage
What is the function of apoptosis?
Selective process for the deletion of superfluous, infected or transformed cells.
What is apoptosis involved in?
→Embryogenesis
→Metamorphosis
→Normal tissue turnover
→Endocrine-dependent tissue atrophy
Describe the apoptosis process
→Events are irreversible and energy (ATP) dependent.
→Cells shrink as the 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.
What are the differences between apoptosis and necrosis?
→apoptosis involves cell death of one of a few cells, necrosis is a group of cells
→ apoptosis is irreversible, necrosis’ early stage is reversible
→ no leakage of cytosolic components
What are the cytoplasmic changes during apoptosis?
- Shrinkage of cell. Organelles packaged into membrane vesicles.
- Cell fragmentation. Membrane bound vesicles bud off.
- Phagocytosis of cell fragments by macrophage and adjacent cell.
- No leakage of cytosolic components
What are the morphological features of apoptosis?
→Cytoplasm shrinks around nucleus
→Vesicles bud from cell (“blebbing”)
What are the nuclear change during apoptosis?
- Nuclear chromatin condenses on nuclear membrane.
2. DNA cleavage.
What are the biochemical changes apoptosis?
→Expression of charged sugar molecules on outer surface of cell membranes
→Protein cleavage by proteases, caspases
Why are charged sugar molecules expressed during apoptosis?
→recognised by macrophages to enhance phagocytosis
What does DNA fragmentation show of necrosis and apoptosis?
apoptosis= bands down the gel necrosis= DNA smear, non-specific digestion
Give examples of apoptosis?
→Cell death in embryonic hand to form individual fingers.
→Apoptosis induced by growth factor deprivation (neuronal death from lack of NGF).
→If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates.
→Cell death in viral diseases (ie viral hepatitis
→Death of neutrophils during an acute inflammatory response
When does p53 trigger apoptosis?
→If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates.
→This arrests the cell cycle enabling the cell to repair the damage.
→If repair process fails, p53 triggers apoptosis.
