cell injury and apoptosis Flashcards
Causes of cell injury
Oxygen deprivation
- hypoxia
- ischemia
key difference between hypoxia and ischemia
In ischemia there is a deficiency in metabolic processes - no energy
Time line for cell injury indicates a point of no return - what is that?
Not a clear, constant single molecular event, it is the point at which homeostasis is lost, despite possible adaptation
List the order of injury by duration
- Biochemical events first
- Ultratructural events - organelles
- Light microscopic changes
- Gross morphological changes
What are the hallmarks of irreversible cell injury?
- incapacity to generate ATP (mitochondrial damage, calcium influx, increased ROS)
- Loss of membrane function
- irreparable DNA damage
ATP needed for 2 main pumps
- Na/K+ pump -
2. Calcium pumps, sequester calcium in ER - out of the cytosol
Primary ATP generation is
from oxidative phosphorylation in mitochondria
Secondary ATP generation is
from glycolysis –> produces lactic acid as a byproduct
Intracellular calcium is sequestered in 2 places
In ER
In Mitochondria
When you have increased intracellular calcium you activate 4 enzymes and result in
- Phospholipases
- Lipases
- Endonucleases
- Caspases
mitochondrial damage results in permeability –> leads to
- Loss of hydrogen potential (ultimately less ATP generated, and necrosis)
- Leakage of cytochrome C - activates caspases -> apoptosis
6 sources of free radicals
- Oxidative phosphorylation itself - superoxides
- Radiant energy - UV
- Inflammation - Superoxides
- Nitric oxides - peroxynitrite anions
- Enzymatic transformation of CCl4
- Transition metals - iron bound by ferritin and transferrin, and Ceruloplasmin binding copper
Main enzymatic ways in which free radicals are removed
- Catalase
- Glutathione peroxidase
- SOD
2 non-enzymatic ways of removing free radicals
- Antioxidants - (vitamin A,C,E)block initiation or inactivate free radicals
- Sequestrants - ferritin, transferrin..
Free radicals can cause
- Lipid peroxidation of membranes
- Protein modification
- DNA damage
Membrane leakage is consistently found in injurious processes EXCEPT IN
Apoptosis
instead results in necrosis
DNA damage and protein damage when they are associated with complex injury cell dies by
apoptosis AND necrosis - a combination
