acute inflammation Flashcards
role in pathology/physiology
Usually physiological response to tissue injury
Vascular and cellular components
Can be ACUTE or CHRONIC
Terminates in resolution, repair or continues
vascular changes
- vasodilation
-vascular congestion/stasis
-endothelial activation
-increased vascular permeability
cellular factors - margination and rolling
Margination
White cells more peripheral due to stasis
Rolling
White cells stick and detach from wall
Mediated by Selectins
Upregulated by IL-1 and TNF (from macro/PMNs)
Histamine, thrombin, PAF
Binds L-Selectin on leucocytes
cellular factors- adhesion and migration
Adhesion
Mediated by Integrins
Stimulated by IL-1 and TNF
Chemokines also facilitate binding (directly released at site of injury)
Reorganisation of cytoskeleton
Migration
Chemokines act on leucocytes to stimulate to migration across endothelium
cellular factors- chemotaxis
Travel along a chemical gradient
Bacterial products
Cytokines IL-8
Complement
Leukotriene B (from arachidonic acid)
offending agent- phagocytosis
Opsonisation
Engulfment using pseudopodia
Formation of phagosomes
Fusion with lysosomes containing enzymes to form phagolysosomes
Material destroyed and removed from cell by pinocytosis
mediators of inflammation
From cells (intracellular granules or synthesized) or plasma factors (secreted from liver in inactive state)
Cascades
Short lived
examples
- cellular derived: cytokines, vasoactive amines
- plasma protein derived: complement, coagulation and kinin systems
types of exudate
serous fluid- usually a transudate, found in pleural, pericardial and peritoneal spaces
fibrinous exudate- fluid rich in fibrin, an exudate due to high protein content
- suppurative exudate- pus forming, an exudate rich in neutrophil polymorphs
- an exudate allows delivery of nutrients, dilution of toxins, entry of antibodies and stimulates the immune response
neutrophil polymorphs
Opsonisation
Phagocytosis
Intra-cellular killing of micro-organisms
Oxygen dependent
Oxygen independent
Release lysosomal products, propagating the response
mast cells
Reside in tissues
Contain histamine and heparin in preformed granules
Stimulated to release contents by injury, complement, IgE
Role allergy/anaphylaxis
Also make eicosanoids to propagate immune response
macrophages/monocytes/histiocytes
Macrophages – tissue resident
Monocytes – circulating
Chemotaxis
Synthesize TNF, IL-1, IL-6
Phagocytosis
Antigen presenting cells, link between innate and adaptive immune response
complement cascade
classical pathway- Ag/Ab complexes
alternative pathway- bacterial products
products of dying cells in tissue necrosis
components of kini, coagulation, fibrinolytic systems can also activate
-C5a chemotactic for neutrophils, increases vascular permeability, releases histamine from mast cells
- C5,6,7,8,9- cytolytic activity
-C4b,C2a,C3b opsonisation of bacteria
plasma factors
Kinin system
Activated by coagulation factor XII
Bradykinin alters vascular permeability and mediates pain
Coagulation system
Process causing conversion of fibrinogen to fibrin
Fibrin forms part of the inflammatory exudate
Factor XII can interact with extra-cellular material to activate kinin, coagulation and fibrinolytic systems
Fibrinolytic system
Plasmin lyses fibrin into fibrin degradation products
effects of acute inflammation- beneficial
Dilution of toxins by oedema fluid
Increased entry of antibodies and drug transport
Fibrin traps micro-organisms
Delivery of nutrients
Stimulation of immune response
effects of acute inflammation- detrimental
Digestion of normal tissues
Swelling e.g. epiglottitis
Inappropriate response e.g. type I hypersensitivity response (allergic rhinitis)
outcome of acute inflammation
-resolution - complete restoration of tissue to normal
- healing by fibrosis
-progression to chronic inflammation
chronic inflammation
- persistent and lack resolutions when the inflamed tissue is unable to overcome the effects of the injurious agent
- persist for weeks, month, years with ongoing tissue damage
- infiltrates of lymphocytes, plasma cells and macrophages
acute/chronic inflammation
Acute inflammation can terminate either by
Complete resolution
Continuing chronic inflammation, then resolution
Chronic inflammation can be the initial response to certain viral infections and fungal infection
Many factors are important such as
Site affected
Type of wound
Presence of infection and the type of organism involved
Presence of indigestible material
Treatment given
Background disease
lymphocytes
T cells (Thymus derived) cell mediated immunity
T helper cells (CD4) produce cytokines
Cytotoxic T cells (CD8)
B cells (Bone marrow derived) antibody mediated immunity
Produce antibodies
activated macrophage products- tissue destruction
Toxic oxygen metabolites
Proteases
Neutrophil chemotactic factors
Coagulation factors
Arachidonic acid metabolites
Nitric oxide
activated macrophages products- fibrosis
Growth factors (PDGF, FGF)
Fibrogenic cytokines (TGF beta)
Angiogenesis factors
Remodelling collagenases
