5.3 Cell death Flashcards
1
Q
What are intracellular accumulations?
A
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.
2
Q
When do intracellular accumulations occur?
A
- 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
3
Q
What is hydropic swelling?
A
- Water can accumulate in cells when the cell membrane permeability is increased or ion pumps fail.
- Hydropic swelling – pale vacuolated cytoplasm
4
Q
What is steatosis or fatty change?
A
- Injury to cells involved in fat metabolism (liver) can lead to accumulation of triglyceride
- Steatosis or fatty change – accumulation of lipid displaces the nucleus
5
Q
What is the accumulation of cholesterol in cells known as?
A
- 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.
6
Q
What is the accumulation of carbon in tissue known as?
A
- 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
7
Q
What accumulation is a sign of free radical injury?
A
- Endogenous pigments include lipofuscin (polymers of lipids/phopholipds/proteins) a sign of free radical injury and lipid peroxidation
8
Q
What does the accumulation of hemosiderin do to cells?
A
- Endogenous pigments include hemosiderin, a major storage form of iron that accumulates in tissue when iron is in excess.
- Accumulates as golden brown granules.
9
Q
What does the intracellular accumulation of proteins look like?
A
- 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.
10
Q
What is necrosis?
A
- Cell death that happens without the participation of the cell
- Always a pathological process, a problem, something that is not controlled by the host
11
Q
What is the morphology of cells in necrosis?
A
- 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
12
Q
What is the appearance of a necrotic lesion influenced by?
A
13
Q
What are the six types of necrosis?
A
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
- Gangrenous necrosis
- Fibrinoid necrosis
14
Q
What happens in coagulative necrosis?
A
- Denaturation > Digestion
- most common type
- nucleus lost, architecture of cells preserved
- due to severe ischaemia - occurs in solid organs
15
Q
What happens in liquefactive necrosis?
A
- 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
16
Q
What happens in caseous necrosis?
A
- 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
17
Q
What happens in fat necrosis?
A
- 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
18
Q
What happens in fibrinoid necrosis?
A
- Occurs in blood vessels in response to deposition of immune complexes
- Necrosis associated with leakage of fibrin and inflammatory cells
19
Q
What happens in gangrenous (lower limb) necrosis?
A
- 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
20
Q
What happens to the morphology of cells in apoptosis?
A
- 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
21
Q
What is the physiological induction of apoptosis?
A
- Embryogenesis
- Involution
- Cell loss in proliferating cell population
- Elimination of cells that have reached their ‘used by date’ } Self-reactive T-lymphocytes
22
Q
What leads to pathological induction of apoptosis?
A
- Growth factor deprivation
- DNA damage
- Accumulation of misfolded protein
- Cell injury in infection
- Pathologic atrophy
23
Q
What initates apoptosis in the intrinsic apoptosis pathway?
A
- Growth factor withdrawal
- DNA damage
- Protein misfolding
24
Q
How can DNA damage initate apoptosis?
A
- 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
25
How can misfolded proteins initiate apoptosis?
* Accumulation of misfolded proteins causes ER stress
* Mutations and extrinsic factors
* Degeneration in CNS
26
Which cells are activated by extrinsic apoptosis pathway?
* Cytotoxic T-cell recognition of infected cells
* Elimination of autoreactive lymphocyte
27
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
28
What happens in both intrinsic and extrinsic apoptosis pathway?
29
30
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’
31
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
32
Does necrosis/apoptosis initiate an inflammatory response?
* Necrosis-inflammatory response
* Apoptosis-no inflammatory response
