GP 06 - Acute Inflammation

Question 1

What are the two major phases of acute inflammation?

Answer 1

1. Vascular changes
2. Cellular events

Question 2

What are the major vascular changes that take place during acute inflammation? What is the purpose of these changes?

Answer 2

• Changes in vascular diameter
• Changes in blood flow
• Changes in vascular permeability

These changes are designed to maximize the movement of plasma proteins and leukocytes out of circulation and into the site of infection or injury

Question 3

What is exudate?

Answer 3

Fluid that has entered the tissues from the circulation during acute inflammation

Question 4

How does vascular diameter change during acute inflammation? What causes this? What is the result? When does this occur?

Answer 4

Vasodilation begins early after injury and is induced by the activation of several mediators, notably histamine, on vascular smooth muscle. The result is increased blood flow.

Question 5

What causes the heat and erythema (redness) at the site of inflammation?

Answer 5

The increased blood flow

Question 6

How does vascular permeability change during acute inflammation? What causes this? When does it happen? What is the result?

Answer 6

Increased vascular permeability occurs shortly after vasodilation occurs. This happens by one of four mechanisms:

• Endothelial cell contraction in the postcapillary venule
• Direct endothelial injury by the injurious agent
• Endothelial injury by adherent leukocytes
• Increased transcytosis

The increased permeability and vasodilation lead to a loss of fluid, slower more turbulent blood flow, and increased viscosity, causing stasis. This allows for leukocytes to accumulate on and adhere to the epithelium, helping them to migrate through the vascular wall.

Question 7

What changes occur with the lymph vasculature during acute inflammation?

Answer 7

Since lymph vessels are found in the interstitial spaces near sites of injury they may become dilated or inflammed (lymphangitis). If microorganism makes its way into the lymph vessel, it could travel all the way to a lymph node and cause an inflammation reaction known as lymphadenitis.

Question 8

What are the two major cellular events that occur during acute inflammation?

Answer 8

• Leukocyte recruitment
• Leukocyte activation

Question 9

What are the phases involved in leukocyte recruitment? What is the predominant leukocyte recruited during acute inflammation?

Answer 9

1. Margination, Rolling, and Adhesion
2. Migration across the endothelium and vessel wall
3. Migration into the tissues toward a chemotactic stimulus

Neutrophils

Question 10

What is and what causes margination?

Answer 10

Margination is movement of leukocytes towards the endothelial surface of a blood vessel, caused by blood flow stasis.

Question 11

What causes leukocyte rolling?

Answer 11

Selectins expressed on leukocytes (L-selectin) and the vessel endothelium (E-selectin) transiently bind to each other, detach, and bind again. This causes the leukocyte to roll along the vessel wall.

Question 12

What causes the expression of selectins?

Answer 12

Cytokines

Question 13

When and how does leukocyte adhesion occur?

Answer 13

Leukocyte rolling interactions slow the leukocyte down so that integrins expressed by the leukocyte can firmly bind to the following ligands expressed on the endothelial surface:

• Vascular Cell Adhesion Molecule 1 (VCAM-1)
• Intercellular Adhesion Molecule 1 (ICAM-1)

Question 14

Where and how do leukocytes migrate across the endothelium and vessel wall?

Answer 14

After adhesion, platelet endothelial cell adhesion molecule 1 (PECAM-1) aids the leukocyte in squeezing between endothelial cells. When the leukocyte reaches the basement membrane, it pierces it by secreting collagenases, and then enters the extravascular tissues.

Question 15

Once in the extravascular tissue, how do leukocytes make their way to the injurious agent?

Answer 15

By chemotaxis

The chemotactic gradients they follow are to the following factors:

• Bacterial products
• Cytokines, IL-8
• C5a
• Leukotriene B4 (LTB4)

Question 16

What activates leukocytes and what does leukocyte activation even mean?

Answer 16

Leukocyte activation means that the leukocyte can now perform the following functions:

• Phagocytosis
• Intracellular killing of engulfed pathogens
• Production of mediators that amplify the inflammatory reaction

Leukocytes become activated when bind to a microbe or dead cell

Question 17

What are the primary ways leukocytes carry out intracellular killing?

Answer 17

• With ROSs
• Directly with enzymes

Question 18

How do leukocytes sometimes damage the surrounding tissue during an inflammatory response?

Answer 18

• Accidental leakage of lysosomal contents to the extracellular space
  
  • Phagosome leakage (regurgitation during feeding)
  • Futile phagocytosis (molecule too large for phagocytosis)
  • Engulfment of a cytotoxic material that results in phagocyte disintegration

Question 19

What are the beneficial effects of inflammation derived from the cellular infiltrates and fluid exudate?

Answer 19

• Cellular Infiltrates - phagocytosis, microbial killing, release of mediators
• Exudate - toxin diultion, delivery of protective antibodies, firbin formation (fibrinogen), activation of plasma mediator system, cell nutrition, general promotion of immunity

Question 20

What is serous inflammation? Give some common examples of serous inflammation

Answer 20

Exudation of cell poor fluid into spaces created by cell injury or into body cavities.

Examples:

• Blisters following burns or viral infections
• Pleural an pericardial effusions
• Ascites

Question 21

What is fibrinous inflammation and where is it usually seen?

Answer 21

When vascular leakage during inflammation leaks fibrinogen as well, leading to the formation and deposition of fibrin in the extracellular space.

Typically seen when body cavity linings like the meninges, pericardium, or pleura becom inflammed

Question 22

What is suppurative (purulent) inflammation and when does it usually occur? Give major examples of this

Answer 22

When the exudate contains large numbers of neutrophils, liquefied debris or necrotic cells, and edema fluid. Typically seen in inflammations caused by pyogenic bacteria that cause liquefactive tissue necrosis, such as staphylococci

Major examples are boils, furuncles, and abscesses

Question 23

What is and what causes an ulcer? Do they usually occur with acute or chronic inflammations?

Answer 23

• An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing of inflamed necrotic tissue
• Can be seen with both acute and chronic inflammations

Question 24

What are the primary outcomes of acute inflammation?

Answer 24

• Complete resolution
• Progression to chronic inflammation
• Abscess formation
• Scarring (fibrosis)

Question 25

What happens to the inflammation products after the insult has been resolved?

Answer 25

• The blood vessel heals itself
• Neutrophils undergoe apoptosis and get phagocytosed by macrophages
• Everything else gets absorbed by the lymphatics

Question 26

What are the primary chemical mediators of inflammation and where do they come from?

Answer 26

• Plasma derived mediators are produced by the liver
• Cell derived mediators are produced at the site of inflammation by:
  
  • endothelial cells at the site of inflammation
  • tissue macrophages
  • mast cells
  • recruited leukocytes

Question 27

How are the chemical mediators of inflammation deactivated?

Answer 27

1. Spontaneous decay
2. Enzymatic degradation
3. Elimination
4. Inhibition

Question 28

List the major cell-derived and plasma-derived mediators?

Answer 28

• Cell-derived Mediators - vasoactive amines, arachidonic acid metabolites (e.g. - prostaglandins, leukotrienes, etc.), cytokines, ROSs, lysosomal enzymes
• Plasma-derived Mediators - complement system, coagulation & fibrinolytic systems, kinin system

Question 29

Which mediator is responsible for the pain felt during inflammation?

Answer 29

Bradykinin

Question 30

What is this an image of?

Answer 30

A blister