Cell Death

Question 1

What is oncotic necrosis and what is released as a consequence of this?

Answer 1

• death of cells by swelling and rupture of membranes

Question 2

What response does necrosis elicit?

Answer 2

• elicits an inflammatory response due to release of proinflammatory material (Damage associated molecular patterns - DAMPs)

Question 3

Calcium plays an important role in cell injury - what is it associated with?

Answer 3

• associated with damage to membranes (initial release and propagation)

Question 4

How is calcium normally controlled?

Answer 4

• normally really tightly controlled

Question 5

Once calcium leaks in what can it switch on to cause a death spiral?

Answer 5

• it can switch on enzymes, ATPase, endonuclease (breaks down part of nucleus), proteases (break down proteins), membrane damage

Question 6

What is ROS and what is it involved in?

Answer 6

• Reactive oxygen species also involved in cell injury, that can lead to cell death

Question 7

What can free radicals damage and what can they be neutralised by?

Answer 7

• free radicals can damage free proteins and membranes
• free radicals can be neutralised by anti-oxidants but it can take time for these to replenish

Question 8

Necrosis can have sequential stages characterised by nuclear changes - what are they changes?

Answer 8

• pyknosis
• karyorrhexis
• karyolysis

Question 9

What is pyknosis?

Answer 9

• nucleus condenses and looks darker and smaller

Question 10

What is karyorrhexis?

Answer 10

• breaking up nucleus

Question 11

What is karyolysis?

Answer 11

• lysis of broken up nucleus

Question 12

What is coagulative necrosis a typical response to?

Answer 12

• typical response to hypoxia, infarction or toxic injury

Question 13

What does coagulative necrosis look like?

Answer 13

• preservation of cell outlines
• coagulation of proteins (eosinophilic on H&E)
• nuclear signs of necrosis

Question 14

What does a caseous necrosis look like?

Answer 14

• cheese-like, crumbling consistency
• eosinophilic cellular debris, basophilic nuclear debris (H&E)
• may become calcified (dystrophic calcification) = feels crunchy

Question 15

What is caseous necrosis like in comparison to coagulative necrosis?

Answer 15

• older lesion than coagulative necrosis with loss of cell architecture
• this can be a progression of coagulative necrosis to caseous necrosis

Question 16

What does pink stain show?

Answer 16

• cellular debris

Question 17

What does purple stain show?

Answer 17

• nuclear debris

Question 18

What is liquefactive necrosis and how does it compare to coagulative necrosis?

Answer 18

• necrotic tissue converted to fluid phase
• older lesion than coagulative necrosis, with loss of cell architecture - could be a progress for coagulative necrosis

Question 19

Liquefactive necrosis is typically the feature of necrosis in the nervous system - What is the gross appearance of liquefactive necrosis in the CNS called?

Answer 19

• called malacia

Question 20

What does liquefactive necrosis look like under the microscope?

Answer 20

• it looks like cellular and nuclear debris

Question 21

Where dies gangrenous necrosis develop?

Answer 21

• develops at the distal aspects of extremities or dependent portions of organs

Question 22

What is Wet gangrene?

Answer 22

• bacterial infection of necrotic tissue

Question 23

What is gas gangrene?

Answer 23

• gas produced by bacteria in the tissue, a progression of wet gangrene (cracking feeling (crepitant) on PM)

Question 24

What is dry gangrene?

Answer 24

• no bacteria, has a leathery appearance (like mummification)

Question 25

What types of gangrene are a type of liquefactive necrosis?

Answer 25

- wet gangrene - gas gangrene

Question 26

What is dry gangrene a form of?

Answer 26

- coagulative necrosis

Question 27

Fat necrosis can have many causes what are these?

Answer 27

- nutritional - enzymatic - traumatic - idiopathic

Question 28

Why is fat necrosis caused by nutrition and what does it look like? when can it be seen?

Answer 28

- due to highly unsaturated fats and low antioxidants - yellow brown appearance of fat - can be seen with ingestion of rancid fish

Question 29

What is enzymatic fat necrosis specific to?

Answer 29

- specific to fat in the abdomen near the pancreas

Question 30

How does enzymatic fat necrosis happen and what may occur?

Answer 30

- happens due to release of enzymes from inflamed pancreas into peri-pancreatic fat and starts to digest fat - saponification may occur (basophilic soap deposits where it mineralises

Question 31

What causes traumatic fat necrosis?

Answer 31

- blunt trauma of fat over bony prominences. - Ischaemia thought to be responsible

Question 32

What is the other form of death apart from oncotic necrosis?

Answer 32

- apoptosis

Question 33

What is Apoptosis?

Answer 33

- is a form of programmed cell death to limit injury to surrounding cells

Question 34

How does apoptosis differ from oncotic necrosis?

Answer 34

- the cells shrink and condense, rather than swell and burst - doesn't elicit an inflammatory response

Question 35

What does apoptosis happen in response to?

Answer 35

- in response to some cell injuries, but also part of development, homeostasis, and involution of hormonally stimulated organs (e.g., development of digets)

Question 36

What do tumours do to apoptosis?

Answer 36

- switch off the apoptosis machinery so they can survive

Question 37

What are some of the triggers for apoptosis?

Answer 37

- Binding of ligands (TNF) - stressors or injury from toxins or reactive oxygen species - withdrawal of growth factors - DNA damage - Immune mediated injury (cytotoxic T lymphocytes, NK cells)

Question 38

What is the extrinsic pathway for apoptosis?

Answer 38

- Binding of a ligand to death receptor which triggers caspase 3 which becomes cleaved and then causes destruction of the cells

Question 39

What is the intrinsic pathway for apoptosis?

Answer 39

- initiated by mitochondria - cells recognises and switches on caspase 9 and then goes to executioners to undergo apoptosis

Question 40

What is the microscopic appearance of apoptosis?

Answer 40

- very discrete and forms blebs (doesn't rupture) - no other cells coming in such as inflammation cells - more controlled but not necessarily good