Inflammation Flashcards
What is inflammation?
Reaction of living vascularized tissue to sublethal cellular injury
- Evolutionary development to protect against infections and trauma - Leukocyte and vascular response
What is the function of inflammation?
Remove cause and consequences of injury
What are the types of inflammation?
Acute: transient, early response to injury - release of chemical mediators
- Typical vascular and leukocyte response is a few hours or days
- Rapid non specific response
- Orchestrated by mediators released from injured cells
Chronic: prolonged duration - usually due to persistent injury causing agent
- Granulatomous inflammation is a special kind of chronic
What are the components of inflammatory response and healing?
- Cells: neutrophils, macrphages, eosinophils, mast cells
- ECM
- Soluble factors: antibodies, cytokines, complement, coagulation
- Vessel, immediate blood supply
What are cardinal signs of acute inflammation?
- Calor: heat due to histamine mediated vasodilation
- Tumours - swelling, odeama due to histamine mediated increase in vessel permeability
- Rubor - redness, blood flow not as fast
- Dolor - oain
- Loss of function due to swelling and pain
What are the three main components of acute inflammation
- Alteration of calibre of blood vessels increase blood flow
- Structural change in microcriculation to allow proteins, leukocytes to leave circulation
- Leukocyte Emigration, accumulation
What triggers vasodilation?
- IgE binding
- Trauma
- Heat
- Cold
- complement C3/5a
- cytokines IL-1/IL-8
What is the structure and function of histamine?
- vasoactive amine produced by mast cells
- Packaged into granules inside, when anitgen binds to IgE on surface causes degranulation
- Dysregulation is an allergy - type 1 hypersensitivity
- Leads to vasodilation and increased vascular permeability
What is exudate?
- fluid with high protein and cellular debris content
- Escaped from blood vessels and deposited in tissues as result of inflammation
What is the function of exudate?
- Dilute pathogen
- Wall off pathogen
- Spread soluble inflammatory mediators and cells
What is transudate:
- Caused by disturbances in hydrostatic and colloid pressure - not inflammation
- Low protein
- Cell poor
- Low, specific, gravity (ratio of density of substance to reference substance)
What are the types of exudate?
- Serous: fluid filled e.g blister
- Lowest protein content of all
- Fibrinous: high fibrin content e.g viral pericarditis
- Due to traumatic injury
- Purulent: pus filled
- Combination of debris, fluid, inflammatory cells
- Haemorragic
What receptors could be activated?
- Toll like receptors for e.g endotoxin
- G-protein coupled
- Opsonin
- Cytokine
What degrades pathogen during phagocytosis?
- Reactive oxygen
- Lysozyme
- Lactoferrin
- Major Basic protein
What are the key soluble mediators, their sources, and actions?
Prostaglandins: macrophages, endothelial cells
- Cause vasodilation, inhibition of platelet aggregates - Inhibited by aspirin
Chemokines: leukocyte, endothelial cells
- Activate neutrophil chemotaxis
Complement: circulating proteins released during acute inflammation
- Variety of actions e.g stimulating mast cell degranulation, neutrophil chemotaxis, opsonisation
Cytokine, interleukins, TNF: macrophages, monocytes, dendritic and endothelial cells
Variety of actions e.g fever, pro anti inflammatory signalling
see notes
How is inflammation normally resolved?
- Mediators and neutrophil have short half life
- Stimulus removed
- Mast cells, lymphocytes and macrophages release anti inflammatory products e.g lipotoxins
What is the histology of inflammation?
- Many neutrophils
- There will also be mast and eosinophils
Characteristics of chronic inflammation?
- Mononuclear cell infiltrate (macrophages, lymphocytes, plasma cells)
- Tissue destruction
- Attempts at healing replacement with connective tissue
- Active inflammation, tissue destruction and attempts at repair occur at same time
- Injury and attempts at repair coexist
- May arise as low grade shouldering inflammation
Role of macrophages?
- Phagocytosis
- Amplification of inflammation (cytokine release)
- Wound repair, fibrosis
- Anti inflammatory effect
What happens during chronic inflammation?
- Destroy offending agent, direct/indirect
- In chronic persist, don’t fade so tissue destruction
- Ongoing destruction triggers inflammatory cascade
- Cause angiogenesis
Other cell types involved in chronic inflammation?
- T lymphocytes
- Plasma cells
- Eosinophils (in response to parasites or IgE mediated inflammation
- Neutrophils
Possible causes of chronic inflammation?
- Persistent infection
- Prolonged toxin exposure
- Autoimmunity
- Foreign body e.g silica
What causes granulomatous inflammation?
- Infections - TB
- Foreign material
- Tumor
- Granulomatous diseases - Crohns sarcoidosis
What is granulation tissue?
- Many fibroblast producing granulomatous tissue formed during granulomatous inflammation
- Clusters of activated macrophages to eliminate offending agent
- Triggered by strong and specific t lymphocyte reaction
