Acute inflammation Flashcards
What is acute inflammation?
- Initial response to tissue injury
- Relatively non-specific
What are triggers of acute inflammation?
- Pathogens/infection: bacteria, viruses, parasites
- Physical: frost bites, burns, radiation
- Chemical: chemical burns, irritants
- Mechanical: trauma, tissue crush
- Foreign: silica, swallowed bones, dentures, sutures
What is the purpose of acute inflammation?
- Alert the body
- Limit spread (of infection/injury)
- Protect injured site from becoming infected
- Eliminate dead cells + tissue
- Create conditions required for healing
What are the signs of inflammation?
- Redness (rubor): inc BF to injured area
- Swelling (tumor): fluid accumulation due to inc vasc perm
- Heat (calor): inc BF + metabolic activity
- Pain (dolor): release of pain mediators; inc pressure on nerve ends
- Loss of function (functio laesa): xs swelling + pain
What agents cause fever?
Pyrogens: IL-1, TNF-a
What causes neutrophilia?
- G-CSF stimulation of bone marrow
- Replenish dead neutrophils
- Release of immature neutrophils
What are the acute phase reactants?
- CRP, fibrinogen, complement, SAP
- prod in liver
- induced by IL-6, IL-1, TNF-a
- Inc fibrinogen -> roleaux -> higher ESR
What are the 4 vascular events of acute inflammation?
- Vasodilation: due to histamine, 5HT release from injured cells
- Inc BF to injured area: results in influx of WBC, O2, nutrients
- Inc vessel perm: endothelial cells contract, results in leakage of fluid + cells in injured tissue
- Walling off of injured area: due to formation of fibrinogen clots
What does inflammatory exudate consist of?
- Water
- Salts
- Small plasma proteins (fibrinogen)
- Inflammatory cells
What are the 4 different types of inflammatory exudate?
- Purulent
- Fibrinous
- Serous
- Haemorrhagic
What are the cellular events of acute inflammation?
-
Migration + accumulation of cells
- > first step - neutrophils
- > involves a complex process of exit from blood vessels -
Removal of pathogens/injured/dead cells
- > neutrophils phagocytose pathogens + dead tissue
- > neutrophils live briefly -> dead neutrophils = pus -
Migration + accumulation of monocytes
- > monocytes diferentiate into macrophages
- > phagocytosis -> clearance of injured site
- > release factors that promote tissue repair (TGF-B)
RIFTC
What are the 5 steps of neutrophil recruitment?
- Rolling
- Integrin activation by chemokines
- Firm adhesion
- Transmigration through endothelium into tissue
- Chemotaxis to inflammed site
Which molecules are involved in neutrophil recruitment?
- Selectins
- Integrins
- Immunoglobulin superfamily cell adhesion molecules (CAMs)
What is the role of selectins?
- Mediate rolling of neutrophils
- Expressed by activated endothelium
- Selectins bind to ligands on neutrophils
- Ligands - carbohydrates
- Low affinity interaction -> disrupted by flowing blood -> repetetive binding + detaching -> rolling; slow down
What are the two types of selectins?
- P-selectin - preformed granules
- E-selectin - induced by IL-1 and TNF-a
How does integrin play into neutrophil recruitment?
- Rolling neutrophils express integrins (LFA-1)
- Integrins in low affinity configuration; no binding to ligands
- Activated endothelial cells produce chemokines
- Chemokines bind to receptors on neutrophils
- -> integrin activation -> high affinity configuration
- Binding of integrins to ligands on endothelium
- -> firm adhesion of neutrophils to endothelium
- Integrin ligands: ICAM-1, VCAM-1
Describe neutrophil transmigration
- Neutrophils migrate through interendothelial spaces
- Neutrophils pass through vessel wall + enter tissue
- Migrate (chemotaxis) through tissue towards inflammed site
Describe neutrophil chemotaxis including examples
- Movement of cells into inflammed sites
- Guided by chemoattratants:
- Chemokines (IL-8)
- Complement components (C5a)
- Bacterial components (formyl-methionyl petides)
*Note that monocytes use similar mechanisms to leave blood vessels and enter sites of inflammation
At the inflammation site, neutrophils clear pathogens. How do they do this?
- Release of granule content
- Phagocytosis
- Generation of reactive oxygen species
- Formation of Neutrophil Extracellular Traps (NETs)
What can be phagocytosed?
- Pathogens
- Damaged cells
- Dead cells
- Nutrients
What are the roles of phagocytosis?
- Protection from pathogens
- Disposal of damaged/dying cells
- Processing + presentation of antigens
- activation of adaptive immune system
- links innate + adaptive immunity
Name some mediators of acute inflammation
- Inflammatory cytokines: IL-1, TNF-a
- Histamine, prostaglandins, leukotrienes
- Chemokines: IL-8
- Complement (C5a)
What are the 3 possible outcomes of acute inflammation?
- Resolution
- Repair
- Chronic inflammation
What is regeneration?
- Damaging agent removed
- Injured tissue replaced by cells of same type
- No change in tissue structure/function
What is repair by replacement?
- Injured tissue replaced with connective tissue
- Scarring -> can alter tissue function
What is an abscess?
- Mass of necrotic (dead) tissue
- Caused by pyogenic (pus-forming) bacteria
- Can become chronic if not reabsorbed/drained
Which tissues have high regeneration ability?
- Epithelial cells
- Blood cells
Sometimes perfect regeneration, no scarring
Which tissues have an intermediate regeneration ability?
- May regenerate when injured
- Eg. liver, kidney, pancreas
- If extensive injury -> scarring
Which tissues have no/limited regeneration ability?
- Neurons
- Skeletal muscle
- Myocardium
Heal with fibrosis, scarring, loss of function
What are factors that favour resolution?
- minimal destruction
- minimal cell death
- good regenration ability of injured tissue
- fast clearance of infection
- quick removal of dead tissue (debris)
What factors prevent healing?
- extensive injury
- poor vascular supply
- haemorrhage
- infection
- poor general health/nutrition; diabetes
- old age
- drugs: corticosteroids
What is chronic inflammation?
- damaging/infective agent persists
- persistent inflammation
- tissue destruction
