Cell death

Question 1

Define intracellular accumulations:

Answer 1

Accumulations within cells occurs when a cell is unable to metabolise a substance causing it to accumulate within the cytoplasm, organelles or nucleus of the cell.

Question 2

List the 4 reasons for intracellular accumulations:

Answer 2

1. A normal endogenous substance is produced at a normal/increased rate, but the rate of metabolism is inadequate to remove it.
2. Accumulation due to defects in folding, packaging or degradation, typically due to mutation.
3. Failure to degrade due to to enzyme deficiency
4. Deposition of an exogenous substance.

Question 3

Define necrosis:

Answer 3

Cell death that happens without the participation of the cell. Occurs when mitochondrial dysfunction can’t be reversed and when membranes lose their structural integrity.

Question 4

What is seen under a microscope when necrosis occurs?

Answer 4

• increased eosinophilic staining (due to denatured protein and loss of RNA)
• vacuolation-digested cytoplasmic organelles
• swelling of ER and mitochondria
• whorls of phospholipid from damaged membranes = myelin figures
• discontinuous plasma and organelle membranes
• nuclear change due to breakdown of DNA and chromatin

Question 5

What is the difference between coagulative necrosis and liquefactive necrosis?

Answer 5

• In coagulative necrosis, denaturation is greater than digestion, whereas in liquefactive necrosis digestion is greater.
• In coagulative necrosis tissue architecture is still preserved, as cells are just dead. In liquefactive necrosis no tissue structure remains as cells are digested.

Question 6

Where is coagulative necrosis likely?

Answer 6

Seen in solid organs: kidney, liver, heart, spleen -due to ischemia.

Question 7

Where is liquefactive necrosis likely?

Answer 7

Associated with bacterial/fungal infections as inflammatory response contributes to digestion of tissue trying to eliminate infection.

Also seen in Ischemia in brain - necrotic area becomes a fluid filled cyst.

Question 8

Where is caseous necrosis likely, and what is its morphology?

Answer 8

• Associated with centre of infection of mycobacterium tuberculosis (caseous necrosis almost diagnostic for tuberculosis)
• Fragmented lysed cells with amorphous granular appearance

Question 9

What is fat necrosis common in?

Answer 9

Acute pancreatitis

Question 10

What is fat saponification?

Answer 10

When enzymes that liquefy membranes of fat cells release FA’s which combine with calcium to cause patchy white legions.

Question 11

What is fibrinoid necrosis, and where does it occur?

Answer 11

Associated with leakage of fibrin and inflammatory cells. Occurs in blood vessels as a result of damage to blood vessels.

Question 12

What type of necrosis is gangrenous necrosis?

Answer 12

A type of coagulative necrosis - describes coagulative necrosis that occurs in a lower limb (surface of organ) which has lost its blood supply. Liquefactive necrosis may accompany a bacterial infection - wet gangrene.

Question 13

Define apoptosis:

Answer 13

Regulated form of cell death which may be both physiological and pathological.

Question 14

List the two apoptotic pathways:

Answer 14

1. Mitochondrial (intrinsic) pathway

2. Death receptor (extrinsic) pathway

Question 15

When does the mitochondrial (intrinsic) apoptotic pathway occur?

Answer 15

• Growth factor withdrawal
• DNA damage
• Protein misfolding

Question 16

Role of Bcl-2 family:

Answer 16

• Bcl-2 family sensors: sensing environment ( can identify growth factor withdrawal, DNA damage, protein misfolding)
• Regulators (Bcl-2 , Bcl-x) : determine whether we induce apoptosis or not
  Bcl-2 family effectors (Bax, Bak): Sensors and regulators interact together to determine whether or not the effector protein is going to promote apoptosis or not.

Question 17

What happens in death receptor (extrinsic) pathway?

Answer 17

The death receptors include Fas receptors, tumor necrosis factor (TNF) receptors, and TNF-related apoptosis-inducing ligand (TRAIL) receptors.

Question 18

Cell size difference in necrosis and apoptosis:

Answer 18

• In necrosis cell size = enlarged, due to swelling

- In apoptosis cell size = reduced, due to shrinkage

Question 19

What happens to the nucleus in necrosis and apoptosis?

Answer 19

Nucleus is digested in necrosis, and fragmented in apoptosis.

Question 20

Difference in plasma membrane in necrosis and apoptosis?

Answer 20

• Necrosis: plasma membrane disrupted

- Apoptosis: plasma membrane intact

Question 21

What happens to cellular contents in necrosis, and how is that different to what happens in apoptosis?

Answer 21

• Cellular contents are released (enzymatic digestion, therefore may leak out) in necrosis.
• In apoptosis, cellular content is packaged and released in apoptotic bodies.

Question 22

Does adjacent inflammation occur in apoptosis or necrosis?

Answer 22

Necrosis

Question 23

What is the difference between how the nuclear material responds in necrosis vs apoptosis:

Answer 23

In apoptosis it’s fragmentation, seen in PCR as multiple fragments.

Question 24

Define necroptosis:

Answer 24

It is a programmed form of necrosis. Has features of necrosis and apoptosis, but differs as it is initiated by ligation of receptor with ligand and is caspase independent.