Lecture 2.1: Acute Inflammation Flashcards
What is Acute Inflammation?
Protective rapid response of living tissue to injury
Characteristics of Acute Inflammation
• Immediate
• Short duration
• Innate
• Stereotyped
• Initiated to limit tissue damage
Causes of Acute Inflammation
• Microbial Infections
• Hypersensitivity Reactions (acute phase)
• Physical Agents
• Chemicals
• Tissue Necrosis
• Anything which can injure tissue!
Key Features of Acute Inflammation (3)
- Vascular and cellular reactions (accumulation of fluid & neutrophils in tissues)
- Controlled by a variety of chemical mediators derived from plasma or cells
- Protective, but can lead to local complications and systemic effects
Clinical Presentations of Acute Inflammation
- Rubor (redness)
- Tumour (swelling)
- Calor (heat)
- Dolor (pain)
- Functio Laesa (loss of function)
Changes in Tissue during Acute Inflammation
- Changes in blood flow - ↑ blood flow
- Exudation of fluid into tissues
- Infiltration of inflammatory cells
1 & 2 are Vascular Phases
3 is the Cellular Phase
What Structures are involved in Blood Flow?
• Larger arteries
• Smaller arteries
• Arterioles
• Capillaries
• Venules
• Veins
• Capillaries
Vascular Phase: Changes in Blood Flow
- Transient vasoconstriction of arterioles
- Followed by vasodilatation of arterioles and then capillaries -> ↑ blood flow
- ↑ vascular permeability -> exudation of protein-rich fluid into tissues
- Slowing of circulation
- Vascular Stasis
Why does Vascular Stasis occur?
Because blood more viscous due to increased concentration of red cells in vessels from leaked fluid
Vascular Phase: Increased Vascular Permeability (3)
- Hydrostatic Pressure
• Arteriolar dilatation: hydrostatic pressure ↑
capillaries relative to pressure interstitial fluid - Osmotic Pressure
• Increased venular permeability: osmotic
pressure ↓ capillaries relative to the interstitial
fluid
1 + 2 = Net flow of protein rich fluid (exudate) into tissue spaces = Oedema
What is Starling’s Law?
Movement of fluid across vessel wall governed by balance of forces of hydrostatic and colloid osmotic pressure between intravascular and extravascular space
What is included in Plasma Proteins?
• Immunoglobulins to help destroy
microorganisms
• Coagulation factors such as fibrinogen which
deposits a fibrin
Vascular Phase: Mechanisms of Vascular Leakage (4)
1) Endothelial Cell Contraction
• Chemical mediators e.g. histamine, C5a, NO
2) Endothelial Cell Injury
• Direct e.g. trauma, chemicals, microbial toxins
• Indirect e.g. toxic oxygen species and proteolytic enzymes from neutrophils
3) Structural re-organisation of cytoskeleton
• Cytokine mediated e.g. interleukin-1, TNF
4) Transcytosis
• VEGF induces ↑ channels in endothelial cells
What is Transudate Fluid? Where is it found?
Low Protein Content
Fluid in extravascular space or serous cavity
What is Exudate Fluid? Where is it found?
High Protein Content
Fluid in extravascular space or serous cavity
Types of Exudate
• Purulent e.g. meningitis
• Haemorrhagic/Serosanguinous eg malignancies
• Serous eg: blister
• Fibrinous: eg: fibrinous pericarditis
Neutrophil Extravasation
1) Vascular stasis causes neutrophils to line up
along endothelium=Margination
2) Roll along endothelium = Rolling
3) Stick avidly to endothelium = Adhesion
4) Emigrate through the endothelium= Migration /
Diapedesis
Neutrophil Extravasation: Rolling
Selectins expressed by endothelial cells bind to carbohydrate ligands (sLex) on neutrophils
Increased by several cytokines secreted by macrophages, mast cells and endothelial cells
Examples: IL-1 and TNF
Neutrophil Extravasation: Adhesion
Integrins expressed by neutrophils bind to integrin ligands on the endothelium
C5a, leukotriene B4, IL-1 and TNF increase expression
Neutrophil Extravasation: Diapedesis
Chemotaxins stimulate neutrophils to migrate through the inter-endothelial cell junctions
Receptor ligand binding – selectins, integrins
Rearrangement of cytoskeleton
Examples of Chemotaxins: C5a, leukotriene B4, bacterial peptides
How do neutrophils escape from vessels?
• Relaxation of interendothelial cell junctions
• Digestion of vascular basement membrane
• Movement
Opsonisation
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins
Oxygen-Dependent Killing Mechanisms
• Oxygen derived free radicals are released into the phagosome
• Toxic oxygen species (Superoxide) is converted to hydrogen peroxide •
• Oxygen or respiratory burst
How is Superoxide converted to H2O2?
By myeloperoxidase from neutrophil granules
H2O2-myeloperoxidase-halide system –> hypochlorite
Oxygen-Independent Killing Mechanisms
Enzymes e.g. lysozyme, protease, nuclease, phospholipase from neutrophil granules can form holes in microbial membranes
Summary of role of Neutrophils in Acute Inflammation (5)
- Neutrophils migrate to site of injury by
chemotaxis - Phagocytose and kill microorganisms
- Eliminate foreign material and necrotic tissue
- Produce growth factors for repair
- Activated neutrophils may release toxic
metabolites and enzymes causing damage to
normal host tissue
What is the role of Chemical Mediators?
To modulate the inflammatory response
Chemical Mediator Groups
• ENDOGENOUS (Cell-derived)
• Vasoactive amines, e.g. histamine, serotonin
• Vasoactive peptides, e.g. bradykinin
• Chemokines
• Arachidonic acid metabolites from plasma
membrane phospholipids
• Nitric oxide
