1. Types Of Cell Death

Question 1

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

Answer 1

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

Question 2

What is necrosis?

Answer 2

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.

Question 3

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

Answer 3

Main types:

• coagulative
• liquefactive (colliquitive)

Special types:

• fat necrosis
• caseous

Question 4

What molecular changes cause necrosis?

Answer 4

• Cell membrane (plasma and organelle) damage.

- Lyosomal enzymes are released into cytoplasm and digest the cell… cell contents leaks out of cell… inflammation.

Question 5

What happens to necrotic tissue?

Answer 5

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

Question 6

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

Answer 6

• 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)

Question 7

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

Answer 7

• 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.

Question 8

What is caseous necrosis?

Answer 8

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

Question 9

What is fat necrosis?

Answer 9

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

Associated with accumulation of macrophages.

Question 10

When/where does fat necrosis occur?

Answer 10

• Trauma of panceas or acute pancreatitis.

- Can also occur in the breast.

Question 11

Define the terms infarction and infarct.

Answer 11

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.

Question 12

What is gangrene and when do the different types occur?

Answer 12

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).

Question 13

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

Answer 13

• 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.

Question 14

When would an infarct appear white?

Answer 14

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

Question 15

When would an infarct appear red?

Answer 15

• 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

Question 16

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

Answer 16

• Can cause heart arrest.
• Occurs in:
  1. Massive area of MI
  2. Severe burns
  3. Too successful chemotherapy- tumourlysis syndrome

Question 17

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

Answer 17

Troponin I

Question 18

What is rhabdomyolysis and what is the consequence of this?

Answer 18

• 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.

Question 19

What is apoptosis, how is it induced?

Answer 19

• Cell death with shrinkage.

- Induced by a regulated intracellular program where a cell activates enzymes that degrade it’s own nuclear DNA.

Question 20

When does apoptosis occur physiologically?

Answer 20

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

Question 21

When does apoptosis occur pathologically?

Answer 21

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).

Question 22

How is apoptosis initiated?

Answer 22

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.

Question 23

What happens to apoptotic bodies?

Answer 23

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

Question 24

Describe the differences between oncosis/necrosis and apoptosis.

Answer 24

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

Question 25

What is the difference between pyknosis, karyorrhexis and karyolysis?

Answer 25

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

Question 26

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

Answer 26

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).

Question 27

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

Answer 27

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

Question 28

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

Answer 28

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