cell injury and apoptosis

Question 1

Causes of cell injury

Answer 1

Oxygen deprivation

• hypoxia
• ischemia

Question 2

key difference between hypoxia and ischemia

Answer 2

In ischemia there is a deficiency in metabolic processes - no energy

Question 3

Time line for cell injury indicates a point of no return - what is that?

Answer 3

Not a clear, constant single molecular event, it is the point at which homeostasis is lost, despite possible adaptation

Question 4

List the order of injury by duration

Answer 4

1. Biochemical events first
2. Ultratructural events - organelles
3. Light microscopic changes
4. Gross morphological changes

Question 5

What are the hallmarks of irreversible cell injury?

Answer 5

• incapacity to generate ATP (mitochondrial damage, calcium influx, increased ROS)
• Loss of membrane function
• irreparable DNA damage

Question 6

ATP needed for 2 main pumps

Answer 6

1. Na/K+ pump -

2. Calcium pumps, sequester calcium in ER - out of the cytosol

Question 7

Primary ATP generation is

Answer 7

from oxidative phosphorylation in mitochondria

Question 8

Secondary ATP generation is

Answer 8

from glycolysis –> produces lactic acid as a byproduct

Question 9

Intracellular calcium is sequestered in 2 places

Answer 9

In ER

In Mitochondria

Question 10

When you have increased intracellular calcium you activate 4 enzymes and result in

Answer 10

1. Phospholipases
2. Lipases
3. Endonucleases
4. Caspases

Question 11

mitochondrial damage results in permeability –> leads to

Answer 11

1. Loss of hydrogen potential (ultimately less ATP generated, and necrosis)
2. Leakage of cytochrome C - activates caspases -> apoptosis

Question 12

6 sources of free radicals

Answer 12

1. Oxidative phosphorylation itself - superoxides
2. Radiant energy - UV
3. Inflammation - Superoxides
4. Nitric oxides - peroxynitrite anions
5. Enzymatic transformation of CCl4
6. Transition metals - iron bound by ferritin and transferrin, and Ceruloplasmin binding copper

Question 13

Main enzymatic ways in which free radicals are removed

Answer 13

1. Catalase
2. Glutathione peroxidase
3. SOD

Question 14

2 non-enzymatic ways of removing free radicals

Answer 14

1. Antioxidants - (vitamin A,C,E)block initiation or inactivate free radicals
2. Sequestrants - ferritin, transferrin..

Question 15

Free radicals can cause

Answer 15

1. Lipid peroxidation of membranes
2. Protein modification
3. DNA damage

Question 16

Membrane leakage is consistently found in injurious processes EXCEPT IN

Answer 16

Apoptosis

instead results in necrosis

Question 17

DNA damage and protein damage when they are associated with complex injury cell dies by

Answer 17

apoptosis AND necrosis - a combination