Mechanisms of the disease two: cell death and cell damage Flashcards
What are the function of necrosis?
-removes damaged cells from an organism
-otherwise it can lead to chronic inflammation
necrosis causes acute inflammation to clear cell debris via phagocytosis.
What are the causes of necrosis?
- usually due to a lack of blood
example:
injury
infection
cancer
infarction
inflammation
What would be the mechanism of necrosis?
- An injurious agent or event - whole group of cells are affected
- The initial events are reversible unlike the later ones
- Lack of oxygen will prevent the ATP production
- Cell will swell because of the influx of water
Because ATP is required for ion pumps to work. - Lysosomes rupture: enzymes degrade other organelles and nuclear material hapzardly.
- Cellular debris released and this triggers inflammation.
Necrosis step by step process brief
- Normal
- Reversible swelling
- Irreversible swelling: mitochondrial changes,changes in the pattern conserved
- Swelling- disintegration and membrane breakdown
Microscopic appearance of necrosis:
What are the nuclear changes?
- Chromatin condensation/shrinkage
- Fragmentation of nucleus
- Dissolution of the chromatin by DNAs.
Microscopic appearance of necrosis:
What are the cytoplasmic changes?
- Opacification: protein denaturation and aggregation
2. complete digestion of cells by enzymes causing cell to liquify (liquefactive necrosis)
Microscopic appearance of necrosis:
What are the biochemical changes?
- release of enzymes such as creatine kinase or lactate dehydrogenase
- release of other protein such as myoglobin
What are the function of apoptosis?- what is it involved in
selective process for the deletion of superfluous infected and transformed cells
involved in: embryogenesis, metamorphosis, normal tissue turnover, endocrine dependent tissue atrophy, a a variety of pathological condition
What is the mechanism of apoptosis?
- programmed cell death of one or a few cells
- events are irreversible and energy (ATP) dependent
- Cells shrink as the cytoplasm is disassembled
- Orderly packaging of organelles and nuclear fragments into membrane bound vesicles.
- New molecules are expressed on the vesicle membranes that stimulate phagocytosis without an inflammatory response.
Microscopic appearance of apoptosis:
What are the cytoplasmic changes?
- shrinkage of the cell. organelles packed into membrane vesicles
- cell fragmentation. membrane bound vesicles bud off
- Phagocytosis of cell fragments by macrophages and adjacent cell.
- No leakage of cytosolic compartments
Microscopic appearance of apoptosis:
What are the nuclear changes?
- nuclear chromatin condenses on nuclear membrane
2. DNA cleavage
Microscopic appearance of apoptosis:
What are the biochemical changes?
- expression of charged sugar molecules on outer surface of cell membranes (recognised by macrophages to enhance phagocytosis)
- Protein cleavage by proteases, caspases
What are the factors which causes?
SURVIVAL: cell-cell and/or cell matrix contacts, growth factors and cytokines
APOPTOSIS: disruption of cell to cell contacts, lack of growth factors, DNA damaging agents and death domain ligands
What are the two types of apoptosis?- what are the key features of them ?
INTRINSIC:
- DNA damage - p53 dependent pathway
- interruption of the cell cycle
- inhibition of protein synthesis
- virus infection
- change in redox state
EXTRINSIC:
- withdrawal of survival factors -e.g mitogens
- extracellular signals (e.g TNF)
- T cell or NK (natural killer)
What are caspases and what do they do?
capases are cysteine pro teases.
- They are the point of convergence for the causes of apoptosis.
Intrinsic and extrinsic causes will cause the activation of the caspases and this will reuslt in apoptosis.
-caspases they will form an activation cascade where one will cleave and activate the next.