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Flashcards in MCB Lecture 57 Cell Death Deck (50)
0

What are the two modes of cell death?

Apoptosis and Necrosis

1

Describe necrosis

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

The cell did not control the death

2

What is apoptosis?

Apoptosis is the highly controlled and regulated death of a cell

3

What causes cell death by necrosis?
What causes cell death by apoptosis?

Necrosis: pathological stress

Apoptosis: physiological or pathological

4

Describe the morphology of necrotic cells

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

5

What are myelin figures, and when are they produced?

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

They are produced in irreversible cell damage

6

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

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

7

What does the appearance of necrotic tissue depend on?

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

Balance between coagulation and liquefactive

8

What are the six types of necrosis?

Coagulative
Liquefactive
Caseous
Fat necrosis
Fibrinoid
Gangrenous

9

What causes coagulative necrosis?

Severe ischemia

10

What causes liquefactive necrosis?

Bacterial or fungal infection

11

What causes caseous necrosis?

Mycobacterium tuberculosis infection

12

What causes fat necrosis?

Acute pancreatitis

13

What causes fibrinoid necrosis?

Immune vasculitis

14

What causes gangrenous necrosis?

Blood supply to a lower extremity is cut off

Bacterial infection (wet necrosis)

15

Describe the features of coagulation necrosis

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

16

Describe the features of liquefactive necrosis

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

17

Ischemia in the brain leads to which type of necrosis?
What is the morphology?

Liquefactive, a fluid filled cyst forms

18

Where does coagulative necrosis mostly occur?

Solid organs

19

What are the features of caseous necrosis?

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

20

What is happening in fibrinoid necrosis?

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

Deposition of immune complexes in the blood vessels

21

Where does fibrinoid necrosis occur?

In the tissue matrix and in the lumen of blood vessels

22

Where does gangrenous necrosis occur?

Extremities, eg. Feet

23

What is wet gangrene

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

24

What is going on in gangrene?

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

25

Describe the morphology of cells undergoing apoptosis

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

26

Which physiological stimuli cause apoptosis?

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

27

Which pathological stimuli cause apoptosis?

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

28

What are the two apoptotic pathways?

Intrinsic: Mitochondrial
Extrinsic: Death receptor

29

What are the stimuli for the intrinsic pathway?

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

30

Describe the intrinsic apoptotic pathway

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

31

Which stimuli activate the extrinsic pathway?

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

32

Describe the death receptor pathway

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

33

Where do the two apoptotic pathways converge?

At the initiator caspases

34

Can the two cell death pathways coexist?

Yes they often do

35

What is inflammation?

Response to eliminate the cause and consequence of injury

36

What happens if we don't have inflammation?

A wound or injury will never heal

37

Which suffix denotes inflammation

-itis

38

What is fat saponification, and when does it occur?

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

39

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

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

40

Describe the apoptotic pathway after the convergence of the signals

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

41

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

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

42

Compare the organelles in reversible and necrosis

Reversible: swollen
Necrosis: digested

43

Compare the cell membrane in reversible and necrosis

Reversible: blebs
Necrosis: discontinuous

44

Compare the mitochondria in reversible and irreversible

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

45

Which is the most common type of necrosis?

Coagulative

46

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

- Radiation
- UV damage
- Infection
- Hypoxia
- ROS

47

Why is cell death triggered when there is DNA damage?

To prevent propagation of the mutated DNA

48

Misfolded proteins are one of the triggers of the intrinsic apoptosis pathway.

How does this arise?

- Mutation
- Extrinsic factors

49

Compare cell size in apoptosis and necrosis

Apoptosis: shrunken
Necrosis: swollen

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