Lecture 1 - Cell Death, Insult

Question 1

What is the name of the process whereby a tissue’s blood supply is reinstated?

Answer 1

Reperfusion

Question 2

What are the outcomes of reperfusion?

Answer 2

Restoration of blood flow brings about:
• recovery of tissue

• Reperfusion injury: damage is increased

Question 3

What are the different ‘types of insult’?

Answer 3

• Hypoxia
• Chemical
• Infections
• Physical
• Immune
• Nutrition

Question 4

What are the ways that pharmaceuticals have toxic effects?

Answer 4

• directly

* effect exerted through metabolites (eg. alcohol metabolism to acetaldehyde)

Question 5

How can electrical currents be damaging?

Answer 5

Directly disrupt cell membranes

Question 6

How can changes in pressure be damaging?

Answer 6

eg. Hitting one’s thumb with a hammer; cellular disruption

Question 7

What do cytokines effect?

Answer 7

• Gene expression

* Cellular metabolism

Question 8

Describe the insult of ‘nutrition’

Answer 8

• Nutritional deficiency

* Nutritional excess

Question 9

What are free radicals?

Answer 9

Highly reactive molecules that have an unpaired valence electron, and will ‘steal’ electrons from other molecules, leading to injury

Question 10

How do free radicals arise?

Answer 10

• Irradiation
• Carcinogens
• Endogenous, normal metabolic processes
• Transition metals
• NO (a paracrine commonly found in the body)
• Toxins

Question 11

How are free radicals removed?

Answer 11

Normal decay

Antioxidants
• Vit E
• Vit A

Storage proteins

Enzymes
• SOD

Question 12

Describe the damage that free radicals cause to cellular structures

Answer 12

Lipids:
• Lipid peroxidation

Protein:
• Protein cross linking

DNA
• Single stranded breaks

Question 13

What are heat shock response genes?

Answer 13

A set of genes in our genome that are unregulated when the cell is stressed.
They serve to protect proteins in the cell

Question 14

What are the factors that determine the degree of injury?

Answer 14

• Duration of injury
• Type of injury
• Severity of injury

Question 15

Describe why time is a critical factor in reversible/irreversible cell injury

Answer 15

As time elapses, the cell function decreases.

Then once the cell is dead, it takes some time for morphological changes to be recognisable

Question 16

What changes to cells can be observed by light microscopy?

Answer 16

Nuclear changes:
• Pyknosis, Karyorrhexis, Karyolysis

Cell membrane changes

Cytoplasmic changes:
• Increased eosinophilia

Question 17

What is the cellular hallmark of irreversible injury?

Answer 17

Massive accumulation of intracellular calcium

Question 18

What are the morphological differences between reversible and irreversible cell injury?

Answer 18

Reversible:
• surface blebs
• increased eosinophilia

Irreversible:
 • necrosis
 • loss of nuclei
 • fragmentation of cells
 • leakage

Question 19

What happens during apoptosis?
Size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation
Physiologic or pathologic role

Answer 19

Size: decrease in cell size
Nucleus: condenses & fragments
Membrane: intact, but altered structure
Cellular contents: intact
Adjacent inflammation: none
Role: often physiological, but can occur in pathological situations (e.g. DNA damage)

Question 20

What happens to chromatin in apoptosis?

Answer 20

Endonucleases digest it down into nucleosome-sized fragments

Question 21

What happens during necrosis?
Size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation
Physiologic or pathologic role

Answer 21

Size: swelling
Nucleus: fragments
Membrane: disrupted
Cellular contents: enzymatic digestion
Adjacent inflammation: frequent
Role: invariably pathological

Question 22

What happens to the nucleus in necrosis?

Answer 22

Non specific breakdown of DNA:
• Pyknosis: condensation and increased eosinophilia
• Karyorrhexis: fragmentation of condensed nucleus
• Karyolysis: nucleases break down DNA

Question 23

What is necrosis?

Answer 23

Death of groups of contiguous cells in tissue or organ

Question 24

What are the various patterns of necrosis?

Answer 24

• coagulative
• liquefactive
• caseous
• fat necrosis
• (gangrene)
• (infarct)

Question 25

What is the most common cause of coagulative necrosis? Compare this with liquefactive

Answer 25

Coag.: Ischemia

Liquefactive: ischemia to brain

Question 26

What ultimately happens to cells that have undergone coagulative necrosis?

Answer 26

Removed by inflammatory cells

Question 27

What happens to the structure of tissues in coagulative necrosis? Compare this to liquefactive

Answer 27

In coagulative, the tissue structure remains intact and solid.

In liquefactive, the tissue structure is completely dissoluted

Question 28

What does ischemia in the brain often cause?

Answer 28

Liquefactive necrosis

Question 29

What is the structure of caseous necrosis?

Answer 29

Amorphous; tissue abolished

Question 30

What is the characteristic cause of caseous necrosis?

Answer 30

Tuberculosis in the lungs

Question 31

What is infarction?

Answer 31

Ischemia in a tissue or organ

Question 32

What are the types of infarction?

Answer 32

Red/haemorrhagic: venous occlusion

White: arterial occlusion

Question 33

What is the definition of apoptosis?

Answer 33

Programmed cell death

Question 34

What are the energy requirements of necrosis and apoptosis?

Answer 34

Necrosis: none
Apoptosis: expends energy

Question 35

What stimuli can trigger cell death?

Answer 35

• Withdrawal of growth stimuli
• ER stress
• Death signals
• DNA damage

Question 36

Describe what happens to the cell membrane during apoptosis

Answer 36

Blebbing, ultimately into apoptotic bodies

Question 37

Why is there no inflammation in apoptosis?

Answer 37

The contents of the cell is contained, and so there is no trigger for inflammation

Question 38

What are the mechanisms of apoptosis?

Answer 38

• Mitochondrial, intrinsic pathway

* Death receptor, extrinsic pathway

Question 39

What leads to the total digestion of tissue in liquefactive necrosis?

Answer 39

Massive infiltrate of neutrophils which release proteases