Acute Inflammation

Question 1

Definition of acute inflammation

Answer 1

Immediate/early response to injury

Question 2

Common causes of acute inflammation

Answer 2

Infection - bacterial, viral, other 
Physical agents - burns 
Chemical agents 
Immune responses 
Tissue death from any cause

Question 3

Consequences of acute inflammation

Answer 3

May be beneficial- bacterial killing, removal of dead tissue
Potentially harmful effects - lung damage in pneumonia, kidney damage in acute pyelonephritis
May precede to chronic inflammation, healing and repair

Question 4

2 main components of acute inflammation

Answer 4

Vascular response

Inflammatory cell infiltrate

Question 5

Components of the vascular response in acute inflammation

Answer 5

• vasodilation –> inc blood flow (redness and warmth)

- increased permeability –> oedema (swelling

Question 6

Inflammatory cell infiltrate of acute inflammation

Answer 6

Mainly neutrophils
Macrophages (during later stages)
Lymphocytes may also be involved

Question 7

Vascular changes in acute inflammation

Answer 7

Vasodilation (arterioles)
- increased blood flow through the capillary bed)
Increased permeability (cap bed, venules)
- protein-rich fluid escapes into extravascular space
- inc concentration of erythrocytes (congestion)
- inc blood viscosity
- reduced blood flow (stasis)
Leukocyte margination
- loss of axial streaming
- first stage in process of leukocyte emigration

Question 8

4 phases of leukocyte migration

Answer 8

Margination
Rolling
Adhesion
Transmigration

Question 9

What occurs in the 4 phases of leukocyte migration

Answer 9

Margination- movement to the periphery of blood vessel
Rolling - transient weak binding to endothelium
Adhesion - firm adhesion to endothelium
Transmigration - movement into the extravascular space

Question 10

What are the adhesion molecules involved in leukocyte migration

Answer 10

Margination - mainly linked to stasis - loss o axial streaming
Rolling - selectins - selectin receptor is on the endothelium and the ligand is on the cell
Adhesion - integrins - receptor ICAM is in the endothelium and the integrin is on the cell
Transmigration - platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31)

Question 11

What is chemotaxis

Answer 11

Migration along chemical gradients

Question 12

What are chemotactic substances

Answer 12

Bacterial products
Complement e.g. C5a
Leukotrienes
Chemokines

Question 13

Other effects of chemotactic molecules

Answer 13

Leukocyte activation

Endothelial cell activation

Question 14

What is phagocytosis?

Answer 14

Ingestion and destruction of foreign particles

Question 15

Steps of phagocytosis

Answer 15

1) recognition and attachment of particle to leukocyte
- opsonins - IgG, C3b
2) engulfment
- pseudopods surrounds the particle
- form a phagocytic vacuole
3) killing and degradation
- production of reactive oxygen metabolites
- release of lysosomal enzymes

Question 16

General aspects of chemical mediators in acute inflammation

Answer 16

May be locally produced or systemic
Most act on specific receptors expressed on target cells
Mediator function is tightly regulated
Others act in a non specific way

Question 17

What are vasoactive amines

Answer 17

E.g. Histamine, serotonin

Effects arteriolar dilatation and inc permeability

Question 18

What do kinins do

Answer 18

Arteriolar dilation
Inc permeability
E.g. Bradykinin

Question 19

Action of kinins

Answer 19

Vasodilation 
Inc permeability 
Leukocyte adhesion 
Chemotaxis 
Opsonins for phagocytosis

Question 20

Action of the clotting cascade

Answer 20

Leukocyte adhesion
Chemotaxis
E.g. Thrombin

Question 21

Action of Arachidonic acid metabolites

Answer 21

Prostaglandins
Leukotrienes
Lipotoxins

Vasodilation
Inc permeability
Leukocyte response

Question 22

Action of cytokines

Answer 22

TNF
IL-1

Endothelial activation, induction of systemic acute phage response

Question 23

Action of oxygen derived radicals

Answer 23

Vasodilation
Bacterial killing

Nitric oxide

Question 24

Action of chemokines

Answer 24

Migration and activation of inflammatory cells

IL8

Question 25

What is suppurative (purulent) inflammation

Answer 25

Pus - material composed neutrophils, necrotic cells and bacteria - complication of infection with pus forming (pyogemic) bacteria Abscess - a localised collection of pus

Question 26

Examples of suppurative infection

Answer 26

Bacterial meningitis - pus on meninges | Brain abscess - in temporal lobe - direct parsed from middle ear infection

Question 27

Diseases with lymphocytes rather than neutrophils

Answer 27

Viral infection - acute viral hep- A, B, C - viral meningitis - mumps, coxsackievirus - viral myocarditis - coxsackievirus, echovirus Immune mediated hep - usually has a chronic cause

Question 28

Sequelae of acute inflammation

Answer 28

``` Resolution - limited/short lived injury -return of tissue to normal state Scarring/fibrosis - more extensive tissue damage -tissues with little capacity for regeneration - abscess formation Progression to chronic inflammation ```

Question 29

Clinical aspects of acute inflammation

Answer 29

1) classical features: Heat, redness, swelling, pain 2)raised white cell count in blood - mainly Neutrophils - particularly high in pyogenic bacteria - also present in non-infective causes - MI - neutrophils rich leukocytosis in other bodily fluids E.g. CSF fluid in bacterial meningitis

Question 30

Defects in leukocyte function

Answer 30

- hereditary (uncommon) chronic granulatomous disease - acquired e.g. Leukaemia Predispose to bacterial infection , which may be lif threatening

Question 31

Anti-inflammatory therapy

Answer 31

Broad spectrum - NSAIDs inhibit cyclo-oxygenate enzymes involved with arachidonic acid metabolism to produce prostaglandins Targeted treatment - therapies blocking specific chemical mediators or receptor ligand interaction e.g. Anti-TNF antibodies, anti ICAM-1