MCB Lecture 57 Cell Death

Question 0

Describe necrosis

Answer 0

This is the morphological features of cells after it has died due to a pathological injury

The cell did not control the death

Question 1

What are the two modes of cell death?

Answer 1

Apoptosis and Necrosis

Question 2

What is apoptosis?

Answer 2

Apoptosis is the highly controlled and regulated death of a cell

Question 3

What causes cell death by necrosis?

What causes cell death by apoptosis?

Answer 3

Necrosis: pathological stress

Apoptosis: physiological or pathological

Question 4

Describe the morphology of necrotic cells

Answer 4

Increased eosinophilia staining
Nucleus: pyknosis, karyolysis, karyorrhexia
Myelin figures
Membranes are burst
Organelles have been digested

Question 5

What are myelin figures, and when are they produced?

Answer 5

Myelin figures are whorls of phospholipid from the cell membrane that has been disrupted

They are produced in irreversible cell damage

Question 6

Describe the different morphologies of the nucleus that are seen in necrosis

Answer 6

Karyolysis: nucleic acid has been degraded (decreased basophilia)
Pyknosis: condensation of the nucleic acid (increased basophilia)
Karyorrhexia: fragmentation of the nucleic acid

Question 7

What does the appearance of necrotic tissue depend on?

Answer 7

Depends on which type of necrosis has occured, ie. coagulation or digestion of the protein in the tissues

Balance between coagulation and liquefactive

Question 8

What are the six types of necrosis?

Answer 8

Coagulative
Liquefactive
Caseous
Fat necrosis
Fibrinoid
Gangrenous

Question 9

What causes coagulative necrosis?

Answer 9

Severe ischemia

Question 10

What causes liquefactive necrosis?

Answer 10

Bacterial or fungal infection

Question 11

What causes caseous necrosis?

Answer 11

Mycobacterium tuberculosis infection

Question 12

What causes fat necrosis?

Answer 12

Acute pancreatitis

Question 13

What causes fibrinoid necrosis?

Answer 13

Immune vasculitis

Question 14

What causes gangrenous necrosis?

Answer 14

Blood supply to a lower extremity is cut off

Bacterial infection (wet necrosis)

Question 15

Describe the features of coagulation necrosis

Answer 15

Denaturant ion of the enzymes within cells
Cell architecture is maintain
Cells are dead, nucleus is gone

Question 16

Describe the features of liquefactive necrosis

Answer 16

Digestion of the proteins of cells
Cell architecture is gone
Fluid filled cysts form

Question 17

Ischemia in the brain leads to which type of necrosis?

What is the morphology?

Answer 17

Liquefactive, a fluid filled cyst forms

Question 18

Where does coagulative necrosis mostly occur?

Answer 18

Solid organs

Question 19

What are the features of caseous necrosis?

Answer 19

This is when both liquefactive and coagulative are occurring
The tissue has a crumbly texture like cheese
The tissue architecture is lost

Question 20

What is happening in fibrinoid necrosis?

Answer 20

Proteinaceious material is deposited in the tissue matrix and fibrin plugs in the blood vessels

Deposition of immune complexes in the blood vessels

Question 21

Where does fibrinoid necrosis occur?

Answer 21

In the tissue matrix and in the lumen of blood vessels

Question 22

Where does gangrenous necrosis occur?

Answer 22

Extremities, eg. Feet

Question 23

What is wet gangrene

Answer 23

This is when there is liquefactive necrosis occurring as well, in response to a bacterial infection

Question 24

What is going on in gangrene?

Answer 24

Blood supply to the extremity is lost, and the cells undergo coagulative necrosis (and sometimes liquefactive)

Question 25

Describe the morphology of cells undergoing apoptosis

Answer 25

``` Cell shrinks in size Nucleus condenses and fragments Apoptotic bodies form Organelles are digested Cytoplasmic is intensely eosinophilic ```

Question 26

Which physiological stimuli cause apoptosis?

Answer 26

a. Embryogenesis: eg. Developing digits b. Involution: shrinking of an organ, eg. Uterus after pregnancy c. Removing cells at their use by date d. Autoreactive T lymphocytes e. CD8+ killing

Question 27

Which pathological stimuli cause apoptosis?

Answer 27

a. Growth factor deprivation b. DNA damage c. Accumulation of misfolded protein d. Infection e. Atrophy

Question 28

What are the two apoptotic pathways?

Answer 28

Intrinsic: Mitochondrial Extrinsic: Death receptor

Question 29

What are the stimuli for the intrinsic pathway?

Answer 29

a. DNA damage b. Misfolded protein c. GF withdrawal

Question 30

Describe the intrinsic apoptotic pathway

Answer 30

1. Stimulus detected by Bcl-2 family receptor 2. Activation of Bcl family effectors (Bax, Bak) 3. Signalling to mitochondria to 4a. Release cytochrome c 4b. Release pro-apoptotic proteins 5. Initiator caspases Regulation: Bcl-2 and Bcl-x

Question 31

Which stimuli activate the extrinsic pathway?

Answer 31

Cytotixic T cell killing (Fas, Fas-l) | Removal of autoreactive lymphocytes

Question 32

Describe the death receptor pathway

Answer 32

``` 1. Ligand - receptor interaction Fas & Fas-L TNF & TNF-Receptor 2. Adaptor proteins 3. Initiator caspases ```

Question 33

Where do the two apoptotic pathways converge?

Answer 33

At the initiator caspases

Question 34

Can the two cell death pathways coexist?

Answer 34

Yes they often do

Question 35

What is inflammation?

Answer 35

Response to eliminate the cause and consequence of injury

Question 36

What happens if we don't have inflammation?

Answer 36

A wound or injury will never heal

Question 37

Which suffix denotes inflammation

Answer 37

-itis

Question 38

What is fat saponification, and when does it occur?

Answer 38

Fat saponification is the break down of the membranes of fat cells, releasing fatty acids The fatty acids combine with extracellular calcium to form the patchy white lesions

Question 39

What is Bcl-2, Bax, Bak and Bcl-x?

Answer 39

Bcl-2: B-cell lymphoma receptor, receptor in the intrinsic pathway of apoptosis Bax: Bcl-2 associated X protein Bak: Bcl-2 homologous antagonist killer These are effector proteins of apoptosis Bcl-x negative inhibitor

Question 40

Describe the apoptotic pathway after the convergence of the signals

Answer 40

1. Initiator caspases 2. Executioner caspases 3. Degredation of protein (nuclear, cytosolic, membrane, cytoskeleton) 4. Formation of apoptotic bodies 5. Phagocytosis of the apoptotic bodies

Question 41

What stimulation do phagocytes get to come and eat the apoptotic bodies?

Answer 41

1. Dying cells release factors that attract phagocytes | 2. Phosphatidyl serine flip detected

Question 42

Compare the organelles in reversible and necrosis

Answer 42

Reversible: swollen Necrosis: digested

Question 43

Compare the cell membrane in reversible and necrosis

Answer 43

Reversible: blebs Necrosis: discontinuous

Question 44

Compare the mitochondria in reversible and irreversible

Answer 44

Reversible: swollen Irreversible: lost the membrane potential & cytochrome c

Question 45

Which is the most common type of necrosis?

Answer 45

Coagulative

Question 46

DNA damage is one of the stimuli for the intrinsic pathway of apoptosis. Describe how this may occur

Answer 46

- Radiation - UV damage - Infection - Hypoxia - ROS

Question 47

Why is cell death triggered when there is DNA damage?

Answer 47

To prevent propagation of the mutated DNA

Question 48

Misfolded proteins are one of the triggers of the intrinsic apoptosis pathway. How does this arise?

Answer 48

- Mutation | - Extrinsic factors

Question 49

Compare cell size in apoptosis and necrosis

Answer 49

Apoptosis: shrunken Necrosis: swollen