Acute Inflammation Flashcards
Definition of acute inflammation
Immediate/early response to injury
Common causes of acute inflammation
Infection - bacterial, viral, other Physical agents - burns Chemical agents Immune responses Tissue death from any cause
Consequences of acute inflammation
May be beneficial- bacterial killing, removal of dead tissue
Potentially harmful effects - lung damage in pneumonia, kidney damage in acute pyelonephritis
May precede to chronic inflammation, healing and repair
2 main components of acute inflammation
Vascular response
Inflammatory cell infiltrate
Components of the vascular response in acute inflammation
- vasodilation –> inc blood flow (redness and warmth)
- increased permeability –> oedema (swelling
Inflammatory cell infiltrate of acute inflammation
Mainly neutrophils
Macrophages (during later stages)
Lymphocytes may also be involved
Vascular changes in acute inflammation
Vasodilation (arterioles)
- increased blood flow through the capillary bed)
Increased permeability (cap bed, venules)
- protein-rich fluid escapes into extravascular space
- inc concentration of erythrocytes (congestion)
- inc blood viscosity
- reduced blood flow (stasis)
Leukocyte margination
- loss of axial streaming
- first stage in process of leukocyte emigration
4 phases of leukocyte migration
Margination
Rolling
Adhesion
Transmigration
What occurs in the 4 phases of leukocyte migration
Margination- movement to the periphery of blood vessel
Rolling - transient weak binding to endothelium
Adhesion - firm adhesion to endothelium
Transmigration - movement into the extravascular space
What are the adhesion molecules involved in leukocyte migration
Margination - mainly linked to stasis - loss o axial streaming
Rolling - selectins - selectin receptor is on the endothelium and the ligand is on the cell
Adhesion - integrins - receptor ICAM is in the endothelium and the integrin is on the cell
Transmigration - platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31)
What is chemotaxis
Migration along chemical gradients
What are chemotactic substances
Bacterial products
Complement e.g. C5a
Leukotrienes
Chemokines
Other effects of chemotactic molecules
Leukocyte activation
Endothelial cell activation
What is phagocytosis?
Ingestion and destruction of foreign particles
Steps of phagocytosis
1) recognition and attachment of particle to leukocyte
- opsonins - IgG, C3b
2) engulfment
- pseudopods surrounds the particle
- form a phagocytic vacuole
3) killing and degradation
- production of reactive oxygen metabolites
- release of lysosomal enzymes
General aspects of chemical mediators in acute inflammation
May be locally produced or systemic
Most act on specific receptors expressed on target cells
Mediator function is tightly regulated
Others act in a non specific way
What are vasoactive amines
E.g. Histamine, serotonin
Effects arteriolar dilatation and inc permeability
What do kinins do
Arteriolar dilation
Inc permeability
E.g. Bradykinin
Action of kinins
Vasodilation Inc permeability Leukocyte adhesion Chemotaxis Opsonins for phagocytosis
Action of the clotting cascade
Leukocyte adhesion
Chemotaxis
E.g. Thrombin
Action of Arachidonic acid metabolites
Prostaglandins
Leukotrienes
Lipotoxins
Vasodilation
Inc permeability
Leukocyte response
Action of cytokines
TNF
IL-1
Endothelial activation, induction of systemic acute phage response
Action of oxygen derived radicals
Vasodilation
Bacterial killing
Nitric oxide
Action of chemokines
Migration and activation of inflammatory cells
IL8
What is suppurative (purulent) inflammation
Pus
- material composed neutrophils, necrotic cells and bacteria
- complication of infection with pus forming (pyogemic) bacteria
Abscess
- a localised collection of pus
Examples of suppurative infection
Bacterial meningitis - pus on meninges
Brain abscess - in temporal lobe - direct parsed from middle ear infection
Diseases with lymphocytes rather than neutrophils
Viral infection
- acute viral hep- A, B, C
- viral meningitis - mumps, coxsackievirus
- viral myocarditis - coxsackievirus, echovirus
Immune mediated hep - usually has a chronic cause
Sequelae of acute inflammation
Resolution - limited/short lived injury -return of tissue to normal state Scarring/fibrosis - more extensive tissue damage -tissues with little capacity for regeneration - abscess formation Progression to chronic inflammation
Clinical aspects of acute inflammation
1) classical features: Heat, redness, swelling, pain
2)raised white cell count in blood - mainly Neutrophils
- particularly high in pyogenic bacteria
- also present in non-infective causes - MI
- neutrophils rich leukocytosis in other bodily fluids
E.g. CSF fluid in bacterial meningitis
Defects in leukocyte function
- hereditary (uncommon) chronic granulatomous disease
- acquired e.g. Leukaemia
Predispose to bacterial infection , which may be lif threatening
Anti-inflammatory therapy
Broad spectrum
- NSAIDs inhibit cyclo-oxygenate enzymes involved with arachidonic acid metabolism to produce prostaglandins
Targeted treatment
- therapies blocking specific chemical mediators or receptor ligand interaction e.g. Anti-TNF antibodies, anti ICAM-1
