Cellular pathology - stress and death - non synchronous

Question 1

State the mechanisms of cell injury.

Answer 1

Biochemical mechanisms:
- Loss of energy
- Mitochondrial damage
- Loss of calcium homeostasis
- Defects in plasma membrane permeability
- Generation of reactive oxygen species and other free radicals

Reperfusion injury

Chemical injury

Question 2

What are the three mechanisms that free radicals can damage cells?

Answer 2

1. Lipid peroxidation of membranes: double bonds in polyunsaturated membrane lipids are vulnerable to attack by oxygen free radicals
2. DNA fragmentation: free radical react with thymine in nuclear and mitochondrial DNA to produce single strands
3. Protein cross-linking: Free radicals promote protein cross-linking, resulting in increased degradation or loss of activity

Question 3

Describe the mechanism of reperfusion injury.

Answer 3

• Restoration of flow may expose compromised cells to high Ca2+
• Reperfusion increases free radical production from comprised mitochondria and circulating inflammatory cells

Question 4

What is hypertrophy?

Answer 4

• Increase in size of organs and cells due to protein accretion; a response to increased work load

Question 5

What is hyperplasia?

Answer 5

Increase in cell number and organ size; response to hormonal stimulation or compensatory to damage

Question 6

What is dysplasia?

Answer 6

Change in cellular organisation, size and organ architecture; response to irritation and damage

Question 7

What is metaplasia?

Answer 7

Substitution of one cell type for another within an organ; in response to diff. conc. or assortment of growth factors which is a response to irritation or injury

Question 8

What is atrophy and/or hypoplasia?

Answer 8

Decrease in cell size and number; response to decreased work load, hormonal or neuronal stimulation etc.

Question 9

What is sub-lethal cellular injury?

Answer 9

• Cell recovers after removal of damaging stimulus
• Characteristics: cell and/or organelle swelling, alteration in protein synthesis

Question 10

What is hydropic degeneration?

Answer 10

Disruption of ionic and fluid homeostasis; failure of energy dependant membrane pumps
- Swelling of organelles and consequent cellular enlargement
- Cytoplasm becomes pale, formation of intracellular vacuoles

Question 11

What is fatty change?

Answer 11

• Affects cells with key role in lipid metabolism
• Metabolic or hypoxic injury
• Appearance of lipid vacuoles inside cell

Question 12

What is lethal cellular injury?

Answer 12

• Severe damage stimulus
• Prolonged sub-lethal damage
• Leading to cell death: necrosis or programmed cell death

Question 13

What is necrosis?

Answer 13

• Cell death by injury; mechanical damage, exposure to toxic chemicals

Question 14

What is programmed cell death?

Answer 14

• Cell death by suicide
• internal or external cellular/biological signals

Question 15

Describe he process of necrosis

Answer 15

• Cells receive structural or chemical insult
• Cells and organelles swell up
• Activation of lysosomal enzymes
• Enzymatic digestion of cells
• Membrane digestion and leakage
• Nucleus disintegrates
• ‘Cell ghosts’
• Invasion of phagocytes and inflammation

Question 16

What is coagulative necrosis?

Answer 16

• Dead tissue appears firm and pale
• Architecture and tissue outline preserved
• Occurs in cells with fewer lysosomes
• Injury damage enzymes so blocks proteolysis

Question 17

What are the causes of coagulative necrosis?

Answer 17

• Occlusion of arterial bloody supply: kidney, heart
• Proteins released from dead cells aid diagnosis

Question 18

What is liquefactive necrosis?

Answer 18

• Dead tissue appears semi-solid
• Dissolution of tissue: hydrolytic enzymes

Question 19

What are the causes of liquefactive necrosis?

Answer 19

• Bacterial/fungal infections
• Ischaemia in central nervous system
• Liquefactive pattern: cerebral infarction
• Neurons have high lysosomal content
• Lack extracellular structural proteins,
  reticulin, collagen etc

Question 20

What is enzymatic fat necrosis?

Answer 20

• Escape of lipase
• Damage fats, producing fatty acids with Ca2+ ions appears grossly as soft chalky, white areas

Question 21

What is caseous necrosis?

Answer 21

• Bacterial liquefaction
• Coagulative and liquefactive necrosis most characteristic of granulomatous inflammation

Question 22

What is gangrenous necrosis?

Answer 22

Term for necrosis that is advanced and grossly visible

Question 23

What is dry gangrene?

Answer 23

Mostly coagulation necrosis, site dried up before bacteria could overgrow

Question 24

What is wet gangrene?

Answer 24

Mostly liquefactive necrosis

Question 25

What is autophagic cell death?

Answer 25

- Cytoplasm is actively destroyed long before nuclear changes appear

Question 26

What is apoptosis?

Answer 26

- Chromatin marginates and cell and nucleus fragment before morphological changes are seen

Question 27

In which situations does apoptosis occur?

Answer 27

- Embryonic development - Cell turnover in adult tissues - T-cell clonal deletion - Normal involutional processes - Atrophic processes - Deletion of damaged cells

Question 28

Describe the process of apoptosis.

Answer 28

- Active cell death - Requires energy and RNA and protein synthesis - Characteristic morphological features - DNA cleaved, chromatin condenses - Cells shrink - Formation of apoptotic body - Cleared by phagocytosis - No inflammation = NO TISSUE DAMAGE

Question 29

What makes a cell decide to commit suicide?

Answer 29

- Withdrawal of positive growth signals - Receipt of negative death signals - Interference in cell death pathway mechanism - Failure to replicate - Incorrect mechanistic signalling activation

Question 30

What are the two pathways that initiate apoptosis and where do they converge?

Answer 30

- Intrinsic / mitochondrial apoptosis: regulated by mitochondria - Extrinsic apoptosis: activated by ligation of death receptors - These pathways converge at the execution phase

Question 31

What morphological changed occur during apoptosis?

Answer 31

a. Normal cell b. Shrinks and then condensed chromatin collapses into crescents around nuclear envelope c. Membrane bulges and blebs d. Chromatin condenses and cell blebs into discrete packages e. Cell finally breaks into a number of apoptotic bodies f. Apoptotic bodies are phagocytosed

Question 32

Compare apoptosis and necrosis.

Answer 32

DNA: internucleosomal cleavage v random degradation Nucleus: chromosome margination v pyknosis Membrane integrity: persists until late v compromised early Mitochondria: Appear normal v swollen Inflammation: No v Yes Pattern: Individual cells v multiple cells Cell volume: decreases v increases early Cell fragmentation: yes (apoptotic bodies) v no (cell lysis)