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1

What are the 2 main types of cell death? What is the difference between the 2?

1. Apoptosis
- cell death with shrinkage
- induced by a regulated intracellular programme involving activation of enzymes that degrade own nuclear DNA and proteins

2. Oncosis
- cell death with swelling
- induced in cells injured by hypoxia or some other agents

2

What is necrosis?

The morphological changes in a living organism that occur after a cell has been dead for some time (4-24hrs).

Is an appearance and not a process.

3

Name the 2 main types, and 2 special types of necrosis.

Main types:
- coagulative
- liquefactive (colliquitive)

Special types:
- fat necrosis
- caseous

4

What molecular changes cause necrosis?

- Cell membrane (plasma and organelle) damage.
- Lyosomal enzymes are released into cytoplasm and digest the cell... cell contents leaks out of cell... inflammation.

5

What happens to necrotic tissue?

- Eventually removed by enzymatic degradation and phagocytosis by WBCs.
- Any remaining tissue may calcify - dystrophic calcification.

6

What is the difference between coagulative and liquifactive necrosis? In which tissue type do each occur?

- Coagulative: proteins are denatured and coagulate.
Occurs after ischaemia of solid organs (e.g. Kidney)

- Liquifactive: proteins are dissolved by cell's own enzymes - autolysis.
Occurs after ischaemia in loose tissues (e.g. Brain) or in presence of many neutrophils (e.g. infection)

7

How can one differentiate between coagulative and liquefactive necrosis under the microscope?

- Coagulative: cellular architecture is somewhat preserved - 'ghost outline' of cells, some karyolysis, some neutrophil presence.

- Liquefactive: complete liquefaction of tissue, inflammation causes swelling of surrounding tissue.

8

What is caseous necrosis?

- Contains amorphous (structureless) debris but not uniform ghost outline as in coagulative.
- Associated with infection, especially tuberculosis.

9

What is fat necrosis?

Break down of lipids by lipase, producing fatty acids that react with calcium - form calcium soaps.

Associated with accumulation of macrophages.

10

When/where does fat necrosis occur?

- Trauma of panceas or acute pancreatitis.
- Can also occur in the breast.

11

Define the terms infarction and infarct.

Infarction = reduction in arterial blood flow (ischaemia) causing necrosis.

Infarct = area of necrotic tissue as a result of loss of arterial blood supply - ischaemic necrosis.

12

What is gangrene and when do the different types occur?

Gangrene = necrosis visible to the naked eye.

1. Dry gangrene = necrosis modified by exposure to air (coagulative necrosis).

2. Wet/gas gangrene = necrosis modified by infection with gas-producing anaerobic bacteria (liquefactive necrosis).

13

What are the most common causes of infarction (i.e. Types of ischaemia)? How else can tissue become infarcted?

- Thrombosis (formation of blood clot in blood vessel) and embolism (bit of thrombus breaks off and blocks small vessels).

- Can also occur due to external pressure on BV, e.g. In testicular torsion or sigmoid vulvulus.

14

When would an infarct appear white?

- As a result of embolism occluding an end artery in solid organs.
- Involves coagulative necrosis.

15

When would an infarct appear red?

- When blood vessels bleed into tissue as a result of a thrombus.

- Occurs in:
1. Loose tissue (liquidative necrosis)
2. Lungs - dual blood supply
3. Tissues with numerous anastamoses (e.g. Bowel)
4. Prior congestion
5. Raised venous pressure
6. Re-perfusion

16

What is the result of potassium leakage out of injured cells? When might this occur?

- Can cause heart arrest.

- Occurs in:
1. Massive area of MI
2. Severe burns
3. Too successful chemotherapy- tumourlysis syndrome

17

Which enzyme leaking out of injured cells is used to diagnose MI?

Troponin I

18

What is rhabdomyolysis and what is the consequence of this?

- Breakdown of skeletal muscle, e.g. As a result of crush injury, strenuous exercise, heat stroke...
- Causes release of myoglobin - blocks kidney glomeruli, may lead to kidney failure.

19

What is apoptosis, how is it induced?

- Cell death with shrinkage.
- Induced by a regulated intracellular program where a cell activates enzymes that degrade it's own nuclear DNA.

20

When does apoptosis occur physiologically?

1. Maintenance of steady state (cell turnover)
2. Hormone-controlled involution (e.g. Ovaries in menopause as oestrogen no longer maintains size)
3. Digit formation in embryogenesis

21

When does apoptosis occur pathologically?

1. Cytotoxic T cell-killing of virus-infected or neoplastic cells.
2. Damaged cells, esp damaged DNA.
3. Graft vs host disease after bone marrow transplant (new leukocytes stimulate apoptosis of host cells, esp skin and bowel endothelium).

22

How is apoptosis initiated?

2 pathways: extrinsic and intrinsic.

1. Most commonly triggered by irreparable DNA damage or withdrawal of growth factors/hormones.
2. p53 protein is activated... outer mitochondrial membrane becomes leaky.
3. Release of cytochrome C from MT - activates caspases.
4. Cause cleavage of DNA and cytoskeleton proteins.
5. Cell shrinks and breaks up into apoptotic bodies.

23

What happens to apoptotic bodies?

Express specific proteins on surface which allow recognition by phagocytes or neighbouring cells - are engulfed and degraded.

24

Describe the differences between oncosis/necrosis and apoptosis.

ONCOSIS/NECROSIS. APOPTOSIS

1. Contiguous group of cells. 1. Single cells
2. Cell swelling. 2. Cell shrinking
3. Pyknosis, karyolysis or 3. Fragmentation into nucleosome
Karyorrhexis. size fragments, form clumps
beneath nuclear membrane
4. Disrupted, early lysis of PM. 4. Intact PM
5. Enzymatic digestion and 5. Intact cellular content released
leakage of cellular contents. In apoptotic bodies
6. Inflammation. 6. No inflammation
7. Invariably pathologic. 7. Often phsyiologic (elimination of
Unwanted cells), may be
pathologic after some forms of cell
Injury

25

What is the difference between pyknosis, karyorrhexis and karyolysis?

- Pyknosis = shrinking and darkening of nucleus.
- Karyorrhexis = nucleus fragmentation.
- Karyolysis = nucleus disappearance.

26

Describe the appearance of injured and dead (oncotic) cells under a light microscope.

Injured: pale and swollen due to water and sodium entering the cell.

Dead: pyknosis, karyorrhexis or karyolysis, and very pink cytoplasm (denatured proteins stained very strongly by eosin).

27

Describe the appearance of a reversibly-injured (hypoxic) cell under an electron microscope.

1. Generalised swelling
2. Membrane blebbing due to cytoskeleton breakdown
3. Clumping of nuclear chromatin
4. ER and MT swelling
5. Autophagy by lysosomes
6. Dispersion of ER ribosomes

28

Describe the appearance of an irreversibly-injured (hypoxic) cell under an electron microscope.

1. Pyknosis, karyolysis or karyorrhexis
2. Defects in cell membrane
3. Myelin figures
4. ER lysis
5. Lysosomal rupture and autolysis