Lecture 20 – Acute inflammation

Question 1

Acute Inflammation (3)

Answer 1

• 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.

Question 2

Trigger of acute inflammation (6)

Answer 2

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

Question 3

Purpose of acute inflammation (3)

Answer 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.

Question 4

5 Rs

Answer 4

RECOGNITION of injury.
RECRUITMENT of leucocytes.
REMOVAL of injurious agent.
REGULATION (closure of inflammatory response).
RESOLUTION/REPAIR of affected tissue.

Question 5

Signs of acute inflammation

Answer 5

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

Question 6

Acute inflammation – systemic changes (6)

Answer 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).

Question 7

Acute inflammation – VASCULAR events (4)

Answer 7

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.

Question 8

Acute inflammation - CELLULAR events (3)

Answer 8

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-).

Question 9

Acute inflammation - Neutrophil recruitment (8)

Answer 9

•	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

Question 10

Acute inflammation - Neutrophil recruitment - Adhesion (5)

Answer 10

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.

Question 11

Neutrophil transmigration (3)

Answer 11

Through interendothelial spaces.
Migrate (chemotaxis) through tissue to inflammed site.
Gradient of chemoattractants guides migration in tissues.

Question 12

Neutrophil chemotaxis (3,4)

Answer 12

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

Question 13

Pathogen destruction (4)

Answer 13

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.

Question 14

Granules (6)

Answer 14

Small/Specific - Alkaline phosphorylases/lysozyme/gelatinase.
Large/Azurophil - Acid hydrolases/Proteases/lysozyme.

Question 15

Tissue repair – regeneration ability (3,2,2,2)

Answer 15

• 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.

Question 16

Factors that favour tissue resolution

Answer 16

Factors that favour tissue resolution:
• Minimal destruction.
• Minimal cell death.
• Good regeneration ability of injured tissues.
• Fats clearance of infection.
• Quick removal of dead tissue (debris).
• Removal of foreign material (sutures, bone fragments).
• Immobilisation of wound edges (sutures).

Question 17

Factors that prevent tissue healing

Answer 17

Factors that prevent tissue healing:
• Infection.
• Poor general health/nutrition (protein/Vitamin C deficiency/diabetes).
• Old age.
• Drugs: corticosteroids.
• Extensive injury.
• Poor vascular supply.
• Extensive haemorrhage.
• Foreign bodies (steel, glass, bone fragments).
• Pressure/torsion/movement on wound edges  dehiscence.