L1-3 Cell Injury and response Flashcards
What does cellular response depend on?
- Type of injury
- Duration of injury
- Severity of injury
What do the consequences of cell injury depend on?
- Type of cell
- State of cell
- Adaptability of cell
E.g. under the same ischemic condition, striated muscles will be ok whereas neurons will die
How does anoxia lead to cell damage?
Reduce level of ATP production, such that energy dependent sodium and calcium pump fails. This causes ionic imbalance –> cell swelling –> activation of lytic enzymes
What is reperfusion damage?
Accelerated injury due to restoration of BF after a period of ischemia
What is the speculated mechanism of reperfusion damage?
- Exposure of compromised cells to a high level of calcium
- Increased free radical production from compromised mitochondria and circulating inflammatory cells
What are the possible causes of cellular ageing?
- Reduced ability to repair damaged DNA
- Defective protein homeostasis
- Accumulation of cellular damage
- Reduced cellular capacity to divide
List the different types of necrosis
- Coagulative necrosis (heart and kidney)
- Liquefactive necrosis (brain)
- Fat necrosis (pancreas)
- Caseous necrosis (TB - lymph node)
- Fibrinoid necrosis (blood vessel)
What are the causes of apoptosis in pathological situations?
- DNA damage
- Accumulation of misfolded proteins
- Infections (mainly viral)
- Duct obstruction (atrophy in parenchymal organs)
What are the 2 activities of caspases?
- Activate caspase-activated DNAses
- Degrade components of nuclear matrix and cytoskeletons
What are the key players of extrinsic pathway of apoptosis?
- TNF-alpha + receptor
- Caspase 8
- Caspase 3
What are the key players of intrinsic pathway of apoptosis?
- Intracellular sensor (BCL-2)
- Cytochrome C from mitochondria
- Caspase 9
- Caspase 3
Activity of caspase 3 and its consequences
Activate endonuclease –> breaking down of cytoskeleton and nuclear fragmentation
How do apoptotic bodies make themselves known by phagocytes?
- Movement of phosphatidyl Serene from the inside leaflet of cell membrane to the outside
- Release of Annexin-1 protein, which binds to PS, acting as an “eat me” signal
What are the examples of cells that undergo hypertrophy as a means of cellular adaptation?
Non-dividing cells such as:
- Neurons
- Skeletal muscles
- Cardiac muscles
Characteristics of cells undergoing apoptosis
- Cell shrinks
- Blebs form on the surface
- Splitting up of cells to apoptotic bodies
- Chromatin aggregation