Topic 3: Cell injury and inflammation

Question 1

Reversible cell injury

Answer 1

• no cell death

- transient ischemic attach, bee sting, asthma, alcohol, minor contusion, tendinopathies, DOMS, compartment syndrome

Question 2

Irreversible cell injury

Answer 2

• lethal

- stroke, acid burn, excessive alcohol, asthma, traima, muscle strains, fractures, acute tendon ruptures

Question 3

What is apoptosis?

Answer 3

endogenosly induced cell death.
Programmed: natural
Unscheduled: SIPs, infection, inflammation

Question 4

What is necrosis?

Answer 4

exogenously induced cell death, compromise of cell membrane integrity –> release of DAMPs

Question 5

What is cell senescence?

Answer 5

catabolic –> anabollic phenotype

results in expression of SASPs (secretory associated secretory pattern)

Question 6

How does a pro-inflammatory environment come about?

Answer 6

increased/sustained stress –> increase in amount of cells expressing SASPs –> pro-inflammatory cytokines –> pro-inflammatory environment

Question 7

What are some SASP factors?

Answer 7

renal disease, type 2 diabetes, osteoporosis, CV disease, cancer, psycho-emotional stress, hypertension, sedentary disease

Question 8

What are the functions of inflammation?

Answer 8

• degrade, eliminate, isolate source of homeostatic disturbance
• able to adapt to altered conditions
• restoration of function to normostasis

Question 9

What is normostasis?

Answer 9

optimal cell, tissue and organ functoin

Question 10

What is stress response?

Answer 10

• cell/tissue stress due to noxious conditions
• expression of cytokines
• reversible: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia

Question 11

What is para-inflammation?

Answer 11

• cell/tissue stress due to prolonged/heightened noxious conditions
• exudate formation and recruitment of non-resident immune cells (NOT seen in stress response)
• allows tissue to adapt to conditions (short term), restore homeostasis (long-term)
• adaptive; localised or systemic

Question 12

What are some examples of adaptive para-inflammation?

Answer 12

DOMS, post-exercise, tendinopathies, bone stress injuries

Question 13

What are some examples of maladaptive para-inflammation?

Answer 13

CVD, CNS degeneration (Alzheimer’s), macula degeneration, type 2 diabetes, metabolic disease

Question 14

What are factors leading to maladaptive para-inflammation?

Answer 14

cell senescence, SIPS –> SASP, lifestyle factors, increased lifespan, overweight/obesity, prolonged stress, dysregulated sleep, malnutrition/malnourishment

Question 15

What is inflammation?

Answer 15

• activated by overt injury or infection

- stress and para-inflammation not sufficient

Question 16

What are some examples of acute inflammation?

Answer 16

ligament sprain, muscle tear, bone fractures, contusions, burns, viral infections

Question 17

What are the three components of inflammation?

Answer 17

increased blood flow, exudation (plasma and leucocytes out of circulation), immune cells to injury site

Question 18

What is chronic inflammation?

Answer 18

tissue destruction and healing occurring at the same time

Question 19

What are the main signs of chronic inflammation?

Answer 19

macrophages, fibroblast recruitment and activation, adaptive immunity activation

Question 20

What are some causes of chronic inflammation?

Answer 20

• failure to eliminate cause of infection
• autoimmunre response
• prolonged exposure to potentially toxic agent

Question 21

What is the difference between dysregulated para-inflammation and chronic inflammation?

Answer 21

PA: less vascular system activation –> less oedema and less non-resident immune cells
CI: vascular systems activated –> oedema and non-resident immune cells

Question 22

What are the key features of acute inflammation?

Answer 22

increase blood flow, increase capillary permeability, neutrophil migration, diapedesis, chemo-taxis, leucocyte recruitment + activation

Question 23

What are the key features of chronic inflammation?

Answer 23

macrophage and T and B cell circulation, tissue destruction, tissue repair

Question 24

What are inducers of inflammation?

Answer 24

tell immune system something is wrong

Question 25

What are exogenous inducers?

Answer 25

PAMPs, virulence factors, allergens, noxious irritants, foreign bodies

Question 26

What are endogenous inducers?

Answer 26

produced from stressed/distressed/damaged tissue, DAMPs

Question 27

What are sensors of inflammation?

Answer 27

• innate and drive inflammatory response
• PRRs detect PAMPs and DAMPs
• eg paranchymal cells, ECM, tissue-resident macrophages and mast cells, epithelial cells, platelets

Question 28

What are mediators of inflammation?

Answer 28

• released by sensors to activate and drive response
• cytokines - histamine, vasoactive amines, complement, lipid mediators, chemokines, vasoactive peptides, pro-inflammatory cytokines

Question 29

What are the roles of mediators?

Answer 29

vasodilation, vascular permeability, immune cell adhesion, chemotaxis, pain

Question 30

What are effectors of inflammation?

Answer 30

-restore homeostasis

Question 31

What are the cellular events of inflammation?

Answer 31

activation of endothelial cells –> gathering of immune cells –> adhesion of immune cells –> migration of immune cells –> endothelial retraction –> phagocytosis

Question 32

What are the vascular events of inflammation?

Answer 32

vasoconstriction, vasodilation, increase vascular permeaility, hyperaemia, oedema

Question 33

What is the purpose of oedema?

Answer 33

continuity between vascular and lymphatic systems