Lecture 20 – Acute inflammation Flashcards
Acute Inflammation (3)
- Initial rapid response to tissue injury. Takes minutes/hours to develop and lasts for a short duration (hours, days).
- Acute inflammation is an innate immune response.
- Relatively non-specific: several types of injury.
Trigger of acute inflammation (6)
1) Infections
• Bacteria, viruses, parasites, fungi, toxins
2) Tissue damage due to:
• Physical agents
Frost bites, burns, radiation (ionising, UV)
• Chemical agents
Chemical burns, irritants
• Mechanical injury & ischemia
Trauma, tissue crush, reduced blood flow
3) Foreign bodies
• splinters; sutures; dirt; swallowed bones; dentures
Purpose of acute inflammation (3)
- Alert the body.
- Limit spread (of infection and/or injury).
- Protect injured site from being infected.
- Eliminate dead cells/tissue.
- Create the conditions required for healing.
- It is a beneficial response.
5 Rs
RECOGNITION of injury. RECRUITMENT of leucocytes. REMOVAL of injurious agent. REGULATION (closure of inflammatory response). RESOLUTION/REPAIR of affected tissue.
Signs of acute inflammation
Signs of acute inflammation:
• Redness (rubor)
• Increased blood flow (hyperaemia) to injured area
• Swelling (tumour)
• Fluid accumulation = Permeability of vessels
• Heat (calor)
• Increased blood flow and metabolic activity
• Pain (dolor)
• Release of pain mediators; pressure on nerve ends
• Loss of function (function laesa)
• Excessive swelling and pain
Acute inflammation – systemic changes (6)
Acute inflammation – systemic changes:
• Acute inflammation = local response
• Fever
• Neutrophilia
• Acute phase reactants
o fibrinogen stacking of RBCs (rouleaux) faster sedimentation rate (ESR).
• Rare cases: systemic inflammatory reaction sepsis. Widespread, severe manifestations. Form of Systemic Inflammatory Response Syndrome (SIRS).
Acute inflammation – VASCULAR events (4)
Vasodilation - histamines released by injured cells.
Increased blood flow to area - influx of WBCs.
Increased vessel permeability - leakage of fluid and cells into injured area.
Overall effect: leucocytes and plasma proteins exit vessels and enter inflammation site to deal with infection/damage.
Acute inflammation - CELLULAR events (3)
1) Migration and accumulation of cells
o First step – neutrophils.
o Involves a complex process of exit from blood vessels.
2) Removal of pathogens/injured/dead cells
o Neutrophils phagocytose pathogens and dead tissue.
o Neutrophils live briefly dead neutrophils = pus.
3) Migration and accumulation of monocytes
o Monocytes differentiate into macrophages.
o Phagocytosis clearance of injured site.
o Release factors that promote tissue repair (TGF-).
Acute inflammation - Neutrophil recruitment (8)
• Multistep process. • Adherence to luminal surface of endothelium. • Migration through vessel wall. 1) Margination & rolling 2) Integrin activation by chemokines 3) Firm adhesion to endothelium 4) Transmigration through endothelium into tissue 5) Chemotaxis to inflamed site
Acute inflammation - Neutrophil recruitment - Adhesion (5)
Selectins - Mediate rolling of neutrophils. Low affinity interactions –> disrupt flow of blood –> rolling slows down.
Intergrins - Activates chemokines –> Neutrophil rolling slows them down
Low affinity = No binding to ligands.
Neutrophil transmigration (3)
Through interendothelial spaces.
Migrate (chemotaxis) through tissue to inflammed site.
Gradient of chemoattractants guides migration in tissues.
Neutrophil chemotaxis (3,4)
Migrate (chemotaxis) through tissue to inflammed site.
Gradient of chemoattractants guides migration in tissues.
Produced at site of infection.
Diffuse into adjacent tissue and form gradient.
Bacterial components
Chemokines (IL-8)
Complements (C5a)
Leukotrienes LTB4
Pathogen destruction (4)
Neutrophils -> O2 in(dependent) methods.
Release granule content.
Phagocytosis.
Formation of NETS (neutrophil extracellular traps) -> Mesh of nuclear content (chromatin), traps microbes and has anti microbial molecules.
Granules (6)
Small/Specific - Alkaline phosphorylases/lysozyme/gelatinase.
Large/Azurophil - Acid hydrolases/Proteases/lysozyme.
Tissue repair – regeneration ability (3,2,2,2)
- HIGH REGENERATION ABILITY (labile tissues; divide continuously).
- Epithelial cells (e.g. skin, airways, gut; blood cells).
- Sometimes perfect regeneration, no scarring.
- INTERMEDIATE REGENERATION ABILITY (stable tissues)
- Normal state: quiescent cells (G0/G1); injury division.
- May regenerate when injured.
- e.g. liver, kidney, pancreas; endothelial cells, fibroblasts.
- If extensive injury scarring.
- NO/LITTLE REGENERATION ABILITY (permanent tissues).
- Neurons, myocardium, skeletal muscle.
- Heal with fibrosis, scarring, loss of function.