Acute and Chronic Inflammation Flashcards
Briefly outline the process of the acute inflammatory response, including the 2 categories.
Include the mediators/proteins which are involved in each stage.
VASCULAR CHANGES:
- Vasoconstriction
- Vasodilation (histamine, NO)
- Increased vascular permeability (histamine, bradykinin, substance P)
- Vascular congestion
- Endothelial activation
CELLULAR CHANGES:
- Margination
- Rolling (selectins, L-selectin)
- Adhesion (IL1, TNF, chemokines)
- Migration/diapedesis/extravasation (chemokines)
- Chemotaxis (bacterial products, IL8, complement factors, leukotriene B)
What are the 5 cardinal signs of inflammation?
Redness Heat Swelling Pain Loss of function
Which processes cause the 5 cardinal signs of inflammation?
Redness - vasodilation
Heat - increased blood flow; fever
Swelling - accumulation of fluid in ECM
Pain - tissue stretching; activation of nociceptors
Loss of function - pain; severe swelling
What are the 4 main causes of inflammation?
Infection
Tissue necrosis
Foreign material
Immune reactions
List the 4 types of receptor involved in leukocyte activation and recognition of microbes.
Include which cell they are found on.
Toll-like receptors (leukocytes)
G-protein coupled receptors (PMNs, macrophages)
Opsonin receptors (leukocytes)
Cytokine receptors (leukocytes)
What is stimulated by activation of toll-like receptors?
Microbe killing
Cytokine production
What is stimulated by activation of G-protein coupled receptors on PMNs and macrophages?
Migration of cells
Production of respiratory burst
What is stimulated by activation of opsonin receptors?
Antibody formation
Complement activation
Phagocytosis
Briefly outline the process of phagocytosis.
- Opsonisation
- Engulfment using pseudopodia
- Formation of phagosomes
- Phagosomes fuse with lysosomes (forms phagolysosomes)
- Microbes are destroyed; removed from cell via pinocytosis
Give 4 examples of cellular derived inflammatory mediators.
- Vasoactive amines (e.g. histamine)
- Arachidonic acid metabolites (e.g. leukotrienes)
- Nitric oxide
- Cytokines (e.g. TNF, IL1/6)
Give 3 examples of plasma protein derived inflammatory mediators.
- Complement factors
- Coagulation system
- Kinin system (e.g. bradykinin)
List the 7 types of exudate.
- Serous
- Fibrinous
- Membranous
- Pseudomembranous (ulcerative)
- Haemorrhagic
- Suppurative
- Necrotising (gangrenous)
List 4 factors which might influence the development of chronic inflammation.
Site affected
Presence of infection/type of organism
Presence of indigestible material
Background disease
List the 5 things present in chronic inflammation.
Lymphocytes Plasma cells Macrophages Fibrosis Granulomas
What is a granuloma?
Clusters of epithelioid macrophages, giant cells (fused macrophages) and lymphocytes
What are the 3 causes of chronic inflammation?
Give examples of each.
- Progression from acute inflammation
(e. g. undrained abscess; foreign materials) - Repeated bouts of acute inflammation
(e. g. chronic cholecystitis) - De novo
(e. g. infections with delayed type hypersensitivity - TB; insoluble foreign materials - asbestos; autoimmune reactions - RA; unknown causes - Crohn’s disease)
List the 5 cell types involved in chronic inflammation.
What are the functions of each?
Macrophages
Function: tissue destruction; fibrosis
Lymphocytes
Function: cytokine synthesis (to attract/activate macrophages and fibroblasts); inflammatory mediators
Plasma cells
Function: produce antibodies
Neutrophils
Eosinophils
What are the 2 types of macrophage associated with chronic inflammation?
M1 - inflammatory macrophage (causes tissue destruction via TNF alpha, IL12 etc.)
M2 - fibrosis macrophage (causes wound repair/fibrosis via TGF beta, IL10 etc.)
List the 6 macrophage products which cause tissue destruction in chronic inflammation.
Toxic oxygen metabolites Proteases Neutrophil chemotactic factors Coagulation factors Arachidonic acid metabolites NO
List the 4 macrophage products which cause fibrosis in chronic inflammation.
Growth factors (PDGF, FGF) Fibrogenic cytokines (TGF beta) Angiogenesis factors Remodelling collagenases
How do you differentiate between acute and chronic inflammation?
ACUTE:
Exudative
Neutrophils most common
Terminates in resolution
CHRONIC:
Productive (i.e. cellular and fibrous tissue formed)
Macrophages, lymphocytes, plasma cells most common
Results in tissue destruction and necrosis
What is granulomatous inflammation?
A type of chronic inflammation caused by the presence of granulomas, i.e. clusters of epithelioid macrophages and giant cells
Give 2 examples of granulomatous inflammation.
TB
Crohn’s disease
List the 3 main cell types involved in granulomatous inflammation.
What are their functions?
Epithelioid macrophages
Function: secretory
Giant cells (fused macrophages) Function: dealing with material that is difficult to digest
Lymphocytes
Function: produce IFN gamma to activate macrophages