Exam #1: Necrosis & Apoptosis

Question 1

What are the six different types of necrosis?

Answer 1

1) Coagulative
2) Liquefactive
3) Caseous
4) Enzymatic Fat
5) Fibrinoid
6) Gangrenous

Question 2

What is coagulative necrosis?

Answer 2

Ischemic injury where the architecture of the cell remains intact, but the cells die–>ghost-like structures without nuclei remain

*Tissues that undergo coagulative necrosis have a connective tissue framework

Question 3

Where does coagulative necrosis NOT occur?

Answer 3

Brain

Question 4

What is the body’s response to coagulative necrosis?

Answer 4

Inflammation to cellular contents that have been “spilled out”

**Will see inflammatory cells between the “ghosts” of damaged cells

Question 5

What is liquefactive necrosis? Where is this seen?

Answer 5

Death of brain tissue that usually leads to liquidation (no connective tissue framework)

E.g. response to CVA & pyogenic abscesses

Question 6

What is caseous necrosis?

Answer 6

“Cheese-like” necrosis seen with chronic inflammation

• accumulation of mononuclear cells
• LIPIDS in the walls of the organisms are NOT BROKEN DOWN
• Presence of multi-nucleated giant cells

E.g. TB & fungal infections, especially Histoplasmosis

Question 7

What is enzymatic fat necrosis?

Answer 7

• Fat is changed due to the action of lipases; these released fatty acids react with Ca++ to form a soap-like substance
• This is most often seen in Pancreatitis & sometimes, these Ca++ deposits can be seen on CXR

Question 8

Is traumatic injury that results in destruction of fat considered enzymatic fat necrosis?

Answer 8

No

Question 9

What are the two patient populations that get Pancreatitis?

Answer 9

1) Alcholism

2) Impacted Gallstones

Question 10

How can hyper parathyroidism cause enzymatic fat necrosis?

Answer 10

Increased Ca++ leads to premature activation of lipases in the pancreas–>fat necrosis

Question 11

What is fibrinoid necrosis?

Answer 11

“Looks like fibrin but isn’t”–this is an injury in blood vessels with an accumulation of plasma proteins causing the wall to stain intensely eosinophilic, like fibirin

• Remember fibrin is the end of the clotting cascade; necrosis appears to look like fibrin
• Type III Hypersensitivity leads to vasculitis by activating the alternative complement cascade

*This is seen in small and medium sized arteries

Question 12

What is gangrenous necrosis?

Answer 12

Not a specific pattern of necrosis that is usually applied to a loss of circulation
- Seen when there is a loss of blood supply to limb or bowel

*Most common cause is DM in the US

Question 13

What is the difference between dry gangrene & wet gangrene?

Answer 13

Wet gangrene= superimposed bacterial infection leading to nonspecific pattern of necrosis

Green wet gangrene–>pseudomonas

Question 14

What is ischemic reperfusion injury?

Answer 14

• Ischemia is caused by the reduction of available oxygen
• ROS are generated
• Reperfusion is when blood flow/oxygenation of the tissue is restored

Question 15

What enzymes are indicative of acute MI?

Answer 15

• Creatine kinase-MB (CK-MB)
• Troponin (I or T)

*Membrane permeability causes these things to leak out

Question 16

What is apoptosis?

Answer 16

Regulated mechanism of cell death characterized by enzymatic degradation of proteins & DNA, and removal of dead cells by phagocytes

Question 17

What is the physiologic role of apoptosis?

Answer 17

• Embryogenesis
• Hormone dependent involution
• Cell deletion in proliferation cell population
• Normal immune defense against viral infected or neoplastic transformed cells as cytotoxic T-cells clearance
• Removal of self-reactive lymphocyte clones
• Removal of cells that have served their purpose i.e. inflammatory cells

Question 18

List the different roles that apoptosis takes in pathological conditions.

Answer 18

1) Cell death in tumors–esp. cytotoxic anticancer drugs
2) DNA damage from low doses of some agents (radiation, extreme temperatures, drugs) that would cause necrosis in larger doses
3) Transplant rejection
4) Atrophy after duct obstruction
5) Viral disease

Question 19

What are the stages of apoptosis?

Answer 19

1) Signaling pathways initiate apoptosis
2) Intracellular signals commit the cell to the apoptotic pathway (initiator caspases)
3) Execution phase= execution caspases catabolize the cytoskeleton and activate endonucleases that cause DNA breakdown
4) Removal or dead cells

Question 20

What is the different between the intrinsic & extrinsic pathways of apoptosis?

Answer 20

Intrinsic= mitochondrial/ cytochrome c pathway

Extrinsic= death-receptor mediated pathway (Fas ligand/TNF activated pathway of apoptosis)

*****Both pathways converge to activate initiator caspases, which are the actual mediators of cell death

Question 21

What are Bax & Bak?

Answer 21

• Pro-apoptotic proteins that dimerize in response to activation by Bcl-2 family sensors
• Dimerized Bax & Bak insert into the mitochondrial membrane and create channels for mitochondrial proteins to leak out

*The most important of the mitochondrial proteins to leak out is Cytochrome C

Question 22

What are BCL-2 protein & BCL-x?

Answer 22

• Anti-apoptoic proteins that reside in the cytoplasm; these proteins have the ability to control mitochondrial leakage and prevent the leakage of mitochondiral proteins that have the ability to trigger apoptosis
• These block Bax & Bak

Question 23

What is the function of p53?

Answer 23

In response to DNA damage, p53 will activate the proapoptotic forms of Bcl-2, stimulating Bax & Bak (pro-apoptotic)

Question 24

What is the first thing that happens in apoptosis? How does this compare to necrosis?

Answer 24

Shrinking is the first thing that happens in apoptosis, which is in contrast to swelling that occurs in necrosis (swelling is first)

Question 25

What is the dose dependent effect of ionizing radiation on the cell?

Answer 25

The effect of ionizing radiation is dose-dependent:

• Low dose= apoptosis
• High dose= necrosis

Question 26

What dictates whether a viral infection causes a cell to undergo apoptosis or necrosis?

Answer 26

Apoptosis=

• activation of p53 that is seen with viruses that BOTH replicate in the nucleus and in the cytoplasm
• Granzyme on CD8+ T-cells leads to caspase activation and apoptosis

Necrosis=

• viral replication in the cytoplasm causes nutrient depletion that can send the cell down the pathway toward necrosis
• complement mediated clearance usually leads to necrosis

Question 27

How does acetaminophen overdose lead to death?

Answer 27

Massive liver necrosis

- Forms a metabolic product, a quinone, that reactions with protein & DNA, and causes oxygen stress

Question 28

What toxic metabolite does carbon tetrachloride form? Where is this seen?

Answer 28

Chemical in the drycleaning industiry generates a CCl3 radical that reacts with the membrane and ER

Question 29

What is the effect of heavy metal & cyanide poisoning?

Answer 29

Mitochondrial disruption & inhibition of oxidative phosphorylation pathway

Question 30

What are Phalloidin & paclitaxel?

Answer 30

Anticancer drugs that are now used to line stents: binds to the cytoskeleton & prevents cell replication

Question 31

What is the mechanism of action of chemotherapeutic alkylating agents?

Answer 31

DNA alkylating agents that directly damage DNA