Acute Inflammation

Question 1

What are the triggers of acute inflammation?

Answer 1

Infection - by infectious agents
Physical agents - frost bites, burns and radiation
Chemical agents - chemical burns and irritants
Mechanical injury and ischaemia - trauma, reduced blood flow
Foreign bodies - splinters, dust, sutures

Question 2

What is the purpose of acute inflammation?

Answer 2

Awareness - make the body alert that there is an infection
Limit - limit the spread of infection
Protect - protect the site of infection
Eliminate - kill invading pathogens and clear dead cells/tissues
Healing - produce conditions for healing

Question 3

What are the 5 Rs for acute inflammation?

Answer 3

Recogition - injury
Recruitment - leukocytes
Removal - pathogen and dead cells
Regulation - closure of inflammatory response 
Resolution/repair - of tissue

Question 4

What are the symptoms of an acute infection?

Answer 4

Redness (rubor) - increased blood flow to area (vasodilation)
Pain (dolor) - pressure from swelling on nerve fibres, activating pain mediators
Swelling (tumor) - increased vessel permeability = fluid leakage = oedema
Heat (calor) - increased blood flow and metabolic activity
Loss of function - excessive swelling and pain

Question 5

What are the systemic changes that occur?

Answer 5

Fever - caused by exogenous (pathogens) and endogenous (cytokines) pyrogens
Neutrophilia - increased recruitment of neutrophils, immature ready to replace dead/dying ones
Acute phase reactants - CRP, fibrinogen (increased = rouleaux), complement, serum amyloid A protein (induced by IL6, IL1 and TNFa)

Question 6

What are the vascular changes that occur?

Answer 6

Vasodilation - increased blood flow to area, brings WBCs, oxygen, fluid and nutrients (due to histamine)
Permeability - increased permeability + contraction of endothelial cells = fluid exudate into site of infection (contains water, salt, plasma proteins, inflammatory cells and RBCs)

Question 7

What are the cellular changes that occur?

Answer 7

Migration and accumulation of neutrophils to site from blood vessels
Removal of dead cells/pathogens by neutrophils (have a short life span)
Migration and accumulation of monocytes - differentiate into macrophages (phagocytosis), survive longer and release tissue repair factors e.g. TGF-b
Recruitment of neutrophils - multi-step process of them attaching to vessel wall and entering

Question 8

List the steps of neutrophil recruitment

Answer 8

1. Migration and rolling (selectins)
2. Integrin activation by chemokines
3. Adhesion to endothelium
4. Transmigration through endothelium
5. Chemotaxis

Question 9

Describe the migration and rolling stage of neutrophil recruitment

*leukocytes are a broad term for inflammatory cells (white blood cells)

Answer 9

Blood vessel dilates = blood flow to area (brings nutrients, WBC and oxygen)

Leukocytes move towards lumen wall from centre

Inflammation activates endothelium = expression of selectins (induced by IL1 and TNFa)

Selectins on surface of endothelial cells are P-selectins (already there) and E-selectins
Selection on surface of leukocyte is L-selectin

P and E selectins bind to ligands on leukocytes and L selectins bind to ligand on endothelial cell

The bonds are low affinity = due to blood continously flowing, the bonds are breaking/forming to allow leukocyte to roll

Question 10

Describe how integrins are activated by chemokines in neutrophil recruitment

Answer 10

Rolling neutrophils express low-affinity integrins = no firm binding to endothelial cells

Activated endothelium (due to infection) produce chemokines

Chemokines bind to receptors on leukocyte = activation of integrins = high-affinity configuration

Question 11

Describe how firm adhesion of integrins to endothelial cells is achieved

Answer 11

High-affinity integrins form bonds with ligands on endothelium (via ICAM-1 and VCAM-1) = firm adhesion

Question 12

Describe the process of transmigration of leukocytes through the endothelium wall

Answer 12

Leukocytes migrate through the inter-endothelial space, through the vessel wall into the tissue

Question 13

What is the role of chemotaxis in neutrophil recruitment?

Answer 13

Chemoattractant molecules involved: IL8, C5a, LTB4 and bacterial components
- These are released by microbes and macrophages

Formation of a chemoattractant gradient towards site of infection

Neutrophils bind to these molecules and move down the gradient to site

Question 14

What do neutrophils contain that can destroy pathogens?

Answer 14

Granules containing toxic enzymes

e.g. azurophil (lysozymes, acid hydroxylase), specific (collaginase, lactoferrin) and secretory granules

Question 15

What methods can neutrophils use to kill pathogens?

Answer 15

Phagocytosis
Oxygen-independent killing e.g. enzymes from granules
Oxygen-dependent killing e.g. reactive oxygen species (ROS and NOS)

Question 16

What are the 3 main outcomes of acute inflammation?

Answer 16

1. Complete resolution - damaging agent removed, injured tissue replaced, no change in tissue structure or function
2. Repair - injured tissue repaired using connective tissue, formation of scar so altered structure/function (fibrosis triggered by TGF-b)
3. Chronic inflammation - if acute inflammation cannot be drained, a mass of necrotic tissue can be produced by pyrogenic bacteria (carry on for longer)