Grouping III

Question 1

What are the three injurious stimulus that are reiterated constantly?

Answer 1

Membrane damage
Protein/Cytoskeletal damage
DNA damage

Question 2

What does an increase in cellular Ca2+ in result of cellular injury cause?

Answer 2

Increased cellular Ca2+ results in activation of a number of enzymes leading to membrane damage, nuclear damage and a drop in ATP (Mitochondrial permeability)
Enzymes include:
Phospholipase
Protease
Endonuclease (DNA)
ATPase

Question 3

What are the three event that occur when the mitochondria has received injury?

Answer 3

Increased Calcium in the cytosol.
Increased Oxidative stress
Breakdown of phospholipids.

Question 4

What occurs when phospholipids are broken down following mitochondrial injury?

Answer 4

Phospholipase A2 and sphingomyelin pathways break down lipids leading to toxin free fatty acids and ceramide.
This leads to even more damage

Remember:
Free FA
Ceramide = Damage

Question 5

Leakage of what specific molecule will lead to apoptosis?

Answer 5

If Cytochrome C is released from the mitochondria, the cell will undergo apoptosis.

Question 6

What occurs in the cell mitochondria following hypoxia ?

Answer 6

Less ATP meaning Na pump stops leading to an influx of Calcium and and Efflux of potassium leading to swelling.

Less oxidative phosphorylation leading to anaerobic respiration = Decreased pH = Chromatin clumping

Ribosomes become detached due to less ATP.

Question 7

Explain how lipid peroxidation occurs and its effect

Answer 7

If free radicals run rampant in the cell they will nonselectively attack lipid double bonds.
This leads to peroxide formation that continually regenerates itself damaging more lipids.

Question 8

How is cell permeability damaged in response to damaged mitochondria?

Answer 8

Damaged phospholipids (Which can come from calcium activated phospholipase) require acylation from ATP to be repaired. No mitochondria = no ATP
Thus, the cells become more permeable.

Keep in mind the cytoskelton is further damaged from protease also activated from increased Ca+

Question 9

What are the cytoplasmic changes seen in necrosis?

Answer 9

Eosinophilia, glassy appearance, and vacuolation.

Question 10

What are the nuclear changes seen in necrosis?

Answer 10

Pyknosis
Karyorrhexis
Karyolysis

Question 11

In what organs would you note coagulative necrosis?

Answer 11

In organs that have a connective tissue framework.
Thus usually seen in result of ischemia with a basic outline of the cell presereved with no nucleus looking ghost like.

NOT SEEN IN BRAIN

Question 12

Whats a classic example of coagulative necrosis?

Answer 12

Seen in the spleen, kidneys, liver and heart.

Especially HEART ATTACK.

Question 13

Describe liquefactive necrosis.

Answer 13

A classic example of this is brain tissue injury (STROKE)
often seen in organs that lack connective tissue.

Also seen in ABCESSES where the center contains pus.

Loss of cells and tissue structure.

Question 14

Describe caseous necrosis

Answer 14

Often seen as an encasing granuloma type necrosis in which the lipids in the wall of the offending organism cannot be broken down. Think Giant cells, plasma cells,etc.

Think TUBERCULOSIS or FUNGI

Question 15

Describe Enzymatic Fat Necrosis

Answer 15

Fat released from lipases interact with Ca2+ to form a soap like substance. This substance becomes engulfed and ends up in fatty cells.

THINK PANCREATITIS or FAT INFLAMMATION

Question 16

Describe fibrinoid necrosis

Answer 16

This is most often seen when blood vessels are damaged with an accumulation of plasma proteins leading to an intense eosinophilic wall stain.

Think TRANSPLANT REJECTION
VASCULITIS
AUTOIMMUNE DISEASE

Question 17

What is an ischemia/reperfusion injury?

Answer 17

This is the case when a tissue is ischemic and then all of a sudden reintroduced to oxygen and blood.

This sudden birst of material causes large ammounts of ROS

Think: Giving clot reducer (Plasmin)

Question 18

What occurs during the apoptotic execution phase?

Answer 18

Execution caspases catabolize the cytoskeleton and activate endonucleases which cause DNA breakdown.

Question 19

What action/effect does Bclx2 and Bcl-2 have on the cell?

Answer 19

These two molecules act by blocking proapoptotic Bax and Bak.

Question 20

What effect does Bak and Bax have together?

Answer 20

When activated, these two form a dimer in the mitochondria leading to the release of cytochrome C. This initiates apoptosis.

Question 21

What extrinsic factors will signal for cell apoptosis?

Answer 21

Fas and TNF biding will signal for initiator caspaces to begin.

Cytochrome-C also acts as an internal initiator caspase.
Ultimately these two will lead to endonuclease acivation.

Question 22

How do BH3 only proteins effect the cell?

Answer 22

BH3 proteins bind Bclx2 and Bcl-2 proteins leading to their dissociation from Bax and Bak allowing them to dimerize and leading to apoptosis.

Question 23

How does Acetometaphine indirectly damage cells?

Answer 23

This is a metabolite that is highly reactive with protein and DNA causing oxygen stress.

Question 24

How does Cabron tetrachloride effect the cells?

Answer 24

Carbon Tetrachloride metabolizes into CCL3 and reacts with the membrane and the ER.

Question 25

How do heavy metals and cyanide effect the cells?

Answer 25

These have an effect on the mitochondria.

Question 26

What do phalloidin and paclitaxel effect?

Answer 26

These effect the cytoskeleton.