Inflammation

Question 1

List the cell derived inflammatory mediators

Answer 1

Vasoactive amines
Arachidonic acid derivatives
PAF
Cytokines
Lysosomal contents

Question 2

Give an example of a vasoactive amine, and explain how it functions

Answer 2

Histamine binds to receptors on nearby capillaries and venules, causing vasodilation and increased permeability

Question 3

Give examples of inflammatory mediators derived from arachidonic acid

Answer 3

Leukotrienes B4, C4, D4, and E4

Prostaglandins D2, F2-alpha and Thromboxane A2

Question 4

Describe the effects of the inflammatory mediators derived from arachidonic acid by the leukotriene pathway

Answer 4

Leukotriene B4 - Neutrophil chemotaxis and activation, augmentation of vascular permeability

Leukotrienes C4 and D4 - Potent bronchoconstrictors, increase vascular permeability, and cause arteriolar constriction

Leukotriene E4 - Enhances bronchial responsiveness and increases vascular permeability

N.B. Leukotrienes C4, D4, and E4 - Comprise what was previously known as the slow-reacting substance of anaphylaxis

Question 5

Describe the effects of the inflammatory mediators derived from arachidonic acid by the COX pathway

Answer 5

Prostaglandin D2 – bronchoconstrictor, peripheral vasodilator, coronary and pulmonary artery vasoconstrictor, platelet aggregation inhibitor, neutrophil chemoattractant, and enhancer of histamine release from basophils

Prostaglandin F2-alpha - Bronchoconstrictor, peripheral vasodilator, coronary vasoconstrictor, and platelet aggregation inhibitor

Thromboxane A2 - Causes vasoconstriction, platelet aggregation, and bronchoconstriction

Question 6

How is platelet activating factor (PAF) synthesized?

Answer 6

PAF is synthesized from membrane phospholipids via a different pathway from arachidonic acid.

Question 7

What is the function of PAF?

Answer 7

It aggregates platelets but is also a very potent mediator in allergic reactions.

It increases vascular permeability, causes bronchoconstriction, and causes chemotaxis and degranulation of eosinophils and neutrophils.

100 to 1,000 times more potent than histamine in inducing vasodilatation and vascular permeability

Question 8

What are cytokines?

Answer 8

Polypeptides, secreted by cells, that act to regulate cell behaviour

Question 9

What effects do cytokines have?

Answer 9

Autocrine, paracrine or endocrine effects

Question 10

What is the function of TNF-alpha?

Answer 10

Activates neutrophils, increases monocyte chemotaxis, and enhances production of other cytokines by T cells

Question 11

List the plasma derived inflammatory mediators

Answer 11

Kinin system
Clotting & fibrinolytic system
Complement

Question 12

What is the function of bradykinins?

Answer 12

An important group of inflammatory mediators, small peptides called kinins, are normally present in blood plasma in an inactive form.

Tissue injury activates these peptides.

Bradykinin, also stimulates pain receptors in the skin.
This effect probably serves a protective role, because pain normally causes an individual to protect the injured area.

Question 13

How are bradykinins formed?

Answer 13

Kininogenase released from the mast cell can act on plasma kininogens to produce bradykinin

Question 14

What effect do bradykinins have?

Answer 14

Bradykinin increases vasopermeability, vasodilation, hypotension, smooth muscle contraction, pain, and activation of arachidonic acid metabolites.

Question 15

What purpose does the clotting cascade have in inflammation?

Answer 15

Vasodilatation and the increase in capillary permeability in an injured tissue also enable enzymes of the blood-clotting system to enter the tissue.

These enzymes activate an enzyme cascade that results in the deposition of insoluble strands of fibrin, which is the main component of a blood clot.

The fibrin strands wall off the injured area from the rest of the body and serve to prevent the spread of infection.

Question 16

What is the role of complement (C3a and C5a) in inflammation?

Answer 16

Vascular effects
Increase vascular permeability and vasodilation
Similar to Histamine
Activates lipoxygenase pathway of arachidonic acid metabolism (c5a)
Complement system
Leukocyte activation, adhesion and chemotaxis (c5a)
Phagocytosis
C3b acts as opsonin and promotes phagocytosis by cells bearing receptors for C3b

Question 17

What are the normal patient reference values?

Answer 17

Temp - 37C
RR - 12-18
HR - 60-100
BP - 120/80

Question 18

What is inflammation?

Answer 18

A protective response intended to eliminate the initial cause of cell injury and the necrotic cells and tissues arising from the injury

Inflammation is intimately associated with the repair process which includes cell regeneration and scarring

Question 19

What can trigger inflammation?

Answer 19

A molecular component of a microbe, such as LPS, may trigger an inflammatory response via interaction with cell surface receptors(Toll -Like Receptors)

Question 20

Describe the differences between acute and chronic inflammation

Answer 20

Acute - minutes to days
Characterized by fluid and protein
Polymorphonuclear cells (neutrophils)

Chronic - weeks to years
Mononuclear cells (Lymphocytes and macrophages)

Question 21

What are the major components of acute inflammation?

Answer 21

Vasodilation
Endothelial injury
Extravasation of polymorphonuclear cells

Question 22

What are the 5 local signs of acute inflammation?

Answer 22

Heat - vasodilation
Redness - vasodilation
Swelling - vascular permeability
Pain - mediator release
Loss of function - mediator release

Question 23

Describe the mechanism behind influx of phagocytes

Answer 23

Influx of phagocytes from the capillaries into the tissues is facilitated by the increased permeability of the capillaries.

The emigration of phagocytes is a multistep process that includes adherence of the cells to the endothelial wall of the blood vessels (margination), followed by their emigration between the capillary-endothelial cells into the tissue (diapedesis or extravasation), and, finally, their migration through the tissue to the site of the invasion (chemotaxis).

As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms a substance called pus.

Question 24

What are the possible outcomes of acute inflammation?

Answer 24

Resolution
Fibrosis (Scarring)
Abscess Formation (A walled off collection of pus)
Progression to Chronic Inflammation

Question 25

Define chronic inflammation

Answer 25

Inflammation that may have a rapid or slow onset but is characterized primarily by its persistence and lack of clear resolution; it occurs when the tissues are unable to overcome the effects of the injuring agent.

Question 26

What are the consequences of inflammation?

Answer 26

Once the inflammatory response has subsided and most of the debris has been cleared away by phagocytic cells, tissue repair and regeneration of new tissue begins.

Capillaries grow into the fibrin of a blood clot. New connective tissue cells, called fibroblasts, replace the fibrin as the clot dissolves.

As fibroblasts and capillaries accumulate, scar tissue forms.