Topic 3: Cell injury and inflammation Flashcards
Reversible cell injury
- no cell death
- transient ischemic attach, bee sting, asthma, alcohol, minor contusion, tendinopathies, DOMS, compartment syndrome
Irreversible cell injury
- lethal
- stroke, acid burn, excessive alcohol, asthma, traima, muscle strains, fractures, acute tendon ruptures
What is apoptosis?
endogenosly induced cell death.
Programmed: natural
Unscheduled: SIPs, infection, inflammation
What is necrosis?
exogenously induced cell death, compromise of cell membrane integrity –> release of DAMPs
What is cell senescence?
catabolic –> anabollic phenotype
results in expression of SASPs (secretory associated secretory pattern)
How does a pro-inflammatory environment come about?
increased/sustained stress –> increase in amount of cells expressing SASPs –> pro-inflammatory cytokines –> pro-inflammatory environment
What are some SASP factors?
renal disease, type 2 diabetes, osteoporosis, CV disease, cancer, psycho-emotional stress, hypertension, sedentary disease
What are the functions of inflammation?
- degrade, eliminate, isolate source of homeostatic disturbance
- able to adapt to altered conditions
- restoration of function to normostasis
What is normostasis?
optimal cell, tissue and organ functoin
What is stress response?
- cell/tissue stress due to noxious conditions
- expression of cytokines
- reversible: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia
What is para-inflammation?
- 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
What are some examples of adaptive para-inflammation?
DOMS, post-exercise, tendinopathies, bone stress injuries
What are some examples of maladaptive para-inflammation?
CVD, CNS degeneration (Alzheimer’s), macula degeneration, type 2 diabetes, metabolic disease
What are factors leading to maladaptive para-inflammation?
cell senescence, SIPS –> SASP, lifestyle factors, increased lifespan, overweight/obesity, prolonged stress, dysregulated sleep, malnutrition/malnourishment
What is inflammation?
- activated by overt injury or infection
- stress and para-inflammation not sufficient
What are some examples of acute inflammation?
ligament sprain, muscle tear, bone fractures, contusions, burns, viral infections
What are the three components of inflammation?
increased blood flow, exudation (plasma and leucocytes out of circulation), immune cells to injury site
What is chronic inflammation?
tissue destruction and healing occurring at the same time
What are the main signs of chronic inflammation?
macrophages, fibroblast recruitment and activation, adaptive immunity activation
What are some causes of chronic inflammation?
- failure to eliminate cause of infection
- autoimmunre response
- prolonged exposure to potentially toxic agent
What is the difference between dysregulated para-inflammation and chronic inflammation?
PA: less vascular system activation –> less oedema and less non-resident immune cells
CI: vascular systems activated –> oedema and non-resident immune cells
What are the key features of acute inflammation?
increase blood flow, increase capillary permeability, neutrophil migration, diapedesis, chemo-taxis, leucocyte recruitment + activation
What are the key features of chronic inflammation?
macrophage and T and B cell circulation, tissue destruction, tissue repair
What are inducers of inflammation?
tell immune system something is wrong
What are exogenous inducers?
PAMPs, virulence factors, allergens, noxious irritants, foreign bodies
What are endogenous inducers?
produced from stressed/distressed/damaged tissue, DAMPs
What are sensors of inflammation?
- innate and drive inflammatory response
- PRRs detect PAMPs and DAMPs
- eg paranchymal cells, ECM, tissue-resident macrophages and mast cells, epithelial cells, platelets
What are mediators of inflammation?
- released by sensors to activate and drive response
- cytokines - histamine, vasoactive amines, complement, lipid mediators, chemokines, vasoactive peptides, pro-inflammatory cytokines
What are the roles of mediators?
vasodilation, vascular permeability, immune cell adhesion, chemotaxis, pain
What are effectors of inflammation?
-restore homeostasis
What are the cellular events of inflammation?
activation of endothelial cells –> gathering of immune cells –> adhesion of immune cells –> migration of immune cells –> endothelial retraction –> phagocytosis
What are the vascular events of inflammation?
vasoconstriction, vasodilation, increase vascular permeaility, hyperaemia, oedema
What is the purpose of oedema?
continuity between vascular and lymphatic systems
