5.3 Cell death Flashcards
What are intracellular accumulations?
Accumulations within cells occur when a cell is unable to metabolise a substance causing it to accumulate within the cytoplasm, organelles or nucleus of the cell.
When do intracellular accumulations occur?
- A normal endogenous substance is produced at a normal or increased rate, but the rate of metabolism is inadequate to remove it.
- Accumulation due to defects in folding, packaging or degradation, typically due to mutation.
- Failure to degrade due to enzyme deficiency (mutation)
- Deposition of exogenous substance
What is hydropic swelling?
- Water can accumulate in cells when the cell membrane permeability is increased or ion pumps fail.
- Hydropic swelling – pale vacuolated cytoplasm
What is steatosis or fatty change?
- Injury to cells involved in fat metabolism (liver) can lead to accumulation of triglyceride
- Steatosis or fatty change – accumulation of lipid displaces the nucleus
What is the accumulation of cholesterol in cells known as?
- The accumulation of cholesterol and cholesterol esters in macrophages and smooth muscle cells in the intimal layer of blood vessels give these cells a foamy appearance – foam cells
- Aggregates of foam cells form atherosclerotic plaques.
What is the accumulation of carbon in tissue known as?
- Exogenous pigments such as carbon found in air pollution are taken up by alveolar macrophages.
- The accumulation of carbon in tissue is known as anthracosis
What accumulation is a sign of free radical injury?
- Endogenous pigments include lipofuscin (polymers of lipids/phopholipds/proteins) a sign of free radical injury and lipid peroxidation
What does the accumulation of hemosiderin do to cells?
- Endogenous pigments include hemosiderin, a major storage form of iron that accumulates in tissue when iron is in excess.
- Accumulates as golden brown granules.
What does the intracellular accumulation of proteins look like?
- Intracellular accumulation of proteins gives a homogeneous, glassy pink appearance under H&E stain described as hyaline change.
- Aggregation of specific proteins is associated with specific diseases and called proteinopathies of protein- aggregation diseases.
What is necrosis?
- Cell death that happens without the participation of the cell
- Always a pathological process, a problem, something that is not controlled by the host
What is the morphology of cells in necrosis?
- Increased eosinophilic staining-denatured protein and loss of RNA
- Vacuolation-digested cytoplasmic organelles
- Swelling of ER and mitochondria
- Myelin figures-whorls of phospholipid from damaged membranes
- Discontinuous plasma and organelle membranes
- Nuclear change due to breakdown of DNA and chromatin
- Karyolysis-decreased basophilia from DNA breakdown
- Pyknosis-nuclear shrinkage and increased basophilia (condensed)
- Karyorrhexia-nuclear fragmentation
What is the appearance of a necrotic lesion influenced by?
What are the six types of necrosis?
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
- Gangrenous necrosis
- Fibrinoid necrosis
What happens in coagulative necrosis?
- Denaturation > Digestion
- most common type
- nucleus lost, architecture of cells preserved
- due to severe ischaemia - occurs in solid organs
What happens in liquefactive necrosis?
- Denaturation < Digestion
- Complete digestion of dead cells
- Associated with infection (bacterial and fungal)
- Inflammatory response contributes to digestion of tissue
- Ischaemia in brain - necrotic area becomes fluid-filled cyst
What happens in caseous necrosis?
- Digestion and denaturation
- Fragmented lysed cells with amorphous granular appearance
- Tissue architecture obliterated
- Associated with centre of infection of mycobacterium tuberculosis
- Large numbers of organisms and degenerating tissue
What happens in fat necrosis?
- Refers to focal areas of fat destruction
- Enzymes liquefy membranes of fat cells
- Release fatty acids which combine with calcium to cause
- patchy white lesions (fat saponification).
- Most common in acute pancreatitis
What happens in fibrinoid necrosis?
- Occurs in blood vessels in response to deposition of immune complexes
- Necrosis associated with leakage of fibrin and inflammatory cells
What happens in gangrenous (lower limb) necrosis?
- Usually describes coagulative necrosis that occurs in a lower limb which has lost its blood supply
- Liquefactive necrosis may accompany a bacterial infection – wet gangrene
What happens to the morphology of cells in apoptosis?
- Cells shrink
- Intensely eosinophillic cytoplasm
- Nuclear chromatin condensation and fragmentation
- Formation of apoptotic bodies (nuclei and cytoplasm) membrane bound vesicles of cytosol and organelles
- Quickly phagocytosed
- No inflammatory response
What is the physiological induction of apoptosis?
- Embryogenesis
- Involution
- Cell loss in proliferating cell population
- Elimination of cells that have reached their ‘used by date’ } Self-reactive T-lymphocytes
What leads to pathological induction of apoptosis?
- Growth factor deprivation
- DNA damage
- Accumulation of misfolded protein
- Cell injury in infection
- Pathologic atrophy
What initates apoptosis in the intrinsic apoptosis pathway?
- Growth factor withdrawal
- DNA damage
- Protein misfolding
How can DNA damage initate apoptosis?
- Caused by:
- Radiation, cytotoxic drugs, extreme temperature and hypoxia
- Direct or indirect through ROS
- If the injury cannot be repaired the cell triggers intrinsic apoptosis –’programmed cell death’ or ‘suicide’
- To prevent the risk of propagating a mutation
How can misfolded proteins initiate apoptosis?
- Accumulation of misfolded proteins causes ER stress
- Mutations and extrinsic factors
- Degeneration in CNS
Which cells are activated by extrinsic apoptosis pathway?
- Cytotoxic T-cell recognition of infected cells
- Elimination of autoreactive lymphocyte
How can cell death due to infection trigger apoptosis?
- Often in response to viral infection
- Direct affect of the virus or response of the host to eliminate infected cell
What happens in both intrinsic and extrinsic apoptosis pathway?
How does the DNA fragmentation of a cell compare in apoptosis and necrosis?
- A. Normal
- B. Apoptosis: DNA broken down into large fragments and appear as ‘ladder’
- C. Necrosis: appear as ‘smear’
How does necroptosis show features of both necrosis and apoptosis?
- Features of necrosis
- Loss of ATP
- Cell and organelle swelling
- Generation of ROS
- Rupture of cell membrane
- Features of apoptosis
- Genetically programmed signal transduction events
- But different
- Initiated by ligation of receptor with ligand
- Caspase independent
Does necrosis/apoptosis initiate an inflammatory response?
- Necrosis-inflammatory response
- Apoptosis-no inflammatory response
