W1_06 Cell Injury, Necrosis, Apoptosis

Question 1

How is high intracellular calcium damaging to the cell?

Answer 1

Activation of intracellular enzymes (phospholipases, lipases, endonucleases, DNAases)
Activation of caspases
Mitochondrial permeability for loss of H potential and triggering of apoptosis

Question 2

What are effects of mitochondrial damage?

Answer 2

Mitochondrial permeability transition pore is more permeable. Loss of hydrogen potential. Leakage of cytochrome C, which activates caspases.

Question 3

Which 3 enzymes are most important in removing free radicals?

Answer 3

Catalase, glutathione peroxidase, superoxide dismutase

Question 4

Name some non-enzymatic substances in removing free radicals

Answer 4

Antioxidants (Vit A and E in the membrane, Vit C and glutathione in the cytosol)
Sequestrants (transferrin, ferritin, lactoferring, ceruloplasmin)

Question 5

How does the membrane become damaged when oxygen isn’t present?

Answer 5

Lack of ATP prevents phospholipid synthesis, and the net loss causes structural detriments.
Increase in calcium activates more phospholipases.

Question 6

How does the cell respond to misfolded proteins?

Answer 6

Increased chaperone protein synthesis to repair
Decrease translation of proteins
Activate ubiquitin pathway
Activate caspases and apoptosis

Question 7

Define necrosis

Answer 7

Pathologic state of tissues resulting from irreversible cell injury, leakage of intracellular material via membrane breakdown, and induction of an inflammatory response

Question 8

Define infarct

Answer 8

Localized area of coagulative necrosis

Question 9

Define pus

Answer 9

Localized collection of cellular debris and neutrophils

Question 10

What causes caseous necrosis?

Answer 10

Indigestible stimuli that the macrophages can’t digest (e.g. mycobacterium)

Question 11

Define granuloma

Answer 11

Collection of activated macrophages with rim of chronic inflammation

Question 12

Define fibrinoid necrosis

Answer 12

Immune-mediated destruction of vessel walls via deposition of immune complexes and fibrin in vessel wall

Question 13

Define fat necrosis

Answer 13

(not “true” necrosis…really just fat deposition)
Lipases release fatty acids. (e.g. acute pancreatitis that breaks down abdominal triglycerides)
Free fatty acids combine with calcium (saponification)

Question 14

Define gangrenous necrosis

Answer 14

Occurs in a limb that’s lost blood supply and undergoes something similar to coagulative necrosis

Question 15

What’s the difference between wet and dry gangrene?

Answer 15

Wet gangrene involves degradative enzyme digestion by bacteria or neutrophils (liquefactive necrosis)

Question 16

Name an anti-apoptotic protein

Answer 16

Bcl-2 (or Bcl-x). This prevents leakage of cytochrome c through the Bax/Bak channels

Question 17

Which organelle is involved in the intrinsic apoptotic pathway?

Answer 17

Mitochondria

Question 18

What is involved in the extrinsic apoptotic pathway?

Answer 18

Death receptor, Fas, FasL

Question 19

What is the significance of phosphatydylserine in apoptosis?

Answer 19

On cell membrane – when flipped from inside to outside, it triggers apoptosis and being eaten by a phagocyte. (apoptotic body)