Acute Inflammation 2: Mediators and Outcomes

Question 1

What are chemical mediators?

Answer 1

Chemicals involved in the communicator and transmission of information between cells. They are tightly regulated and short lived, and control the mechanisms of inflammation.

Question 2

Chemical mediators are either ____ derived In precursor form) or _____ derived (preformed in lysosomal intracellular granules or newly synthesised).

Answer 2

Plasma or Cell

Question 3

Cell derived inflammatory mediators are either pre-formed or newly synthesised. True or false?

Answer 3

True.

Question 4

Cell derived mediators include:

Answer 4

• Histamine
• Prostaglandins
• Leukotrienes
• Platelet-activating factor
• Nitric oxide
• Cytokines, including chemokines

Question 5

Plasma derived mediators include:

Answer 5

•	Factor XII activated pathways:
Factor XII (produced in the liver) is activated by contact with sub-endothelial basement membrane or interstitial collagen. When activated, it can then activate three plasma systems:
o	Fibrinolytic system 
o	Kinin system 
o	Coagulation cascade 

• Complement system
hree activation pathways:

o Classic pathway
o Alternative pathway )
o Lectin pathway

Results in the formation of many chemical mediators (such as C3a and C5a which cause vasodilation via release of histamine; and C3b which is an opsonin) and the Membrane Attack Complex (which lyses microbes).

Question 6

What is the complement system:

Answer 6

The complement system involves a cascade of proteolytic enzymes that circulate the plasma in an inactive form.
This cascade leads to the formation of a membrane attack complex, whereby the complex drills a hole in the bacterial cell walls, causing it to lyse osmotically and be destroyed.

Question 7

What is the principle mediator of arteriolar vasodilation and increased venular permeability?

Answer 7

Histamine

Question 8

____ and ____ are locally produced, short lived and do not circulate systematically. They are derivatives or arachidonic acid. _____ are responsible for Vasodilation and potentiating pain. ______ are responsible for chemotaxis, vascular permeability and smooth muscle contraction

Answer 8

Prostaglandins and Leukotrienes

Question 9

____ has been shown to:

• Increase vascular permeability
• Increase leukocyte adhesion to endothelium as well as ______ and ______
• Boosts the synthesis of ____ and _____

Answer 9

PAF
Chemotaxis
Activation
Prostaglandins and Leukotrienes

Question 10

Nitric Oxide has many pro inflammatory activities:

Answer 10

1. Killing of microbes via the creation of reactive nitrogen species
2. Potential to cause tissue damage
3. Role in septic shock (why?)

Question 11

What is an anti-inflammatory effect of NO?

Answer 11

the inhibition of leucocyte recruitment

Question 12

What are two major cytokine mediators of inflammation?

Answer 12

IL-1

TNF-a

Question 13

What are cytokines?

Answer 13

Polypeptides signalling molecules produced by activated macrophages that influence the behaviour of the cell that produces them, or nearby cells or, if entering the blood, cells through the body

Question 14

What are the local effects of cytokines?

Answer 14

Inducing adhesion molecules on endothelial cells, to help leucocytes adhere and marginate.

induce production of chemokines (chemoattractive cytokines - IL-8 attracts neutrophils to inflamed tissue) as well as prostaglandins and NO. ƒ

Activate leucocytes to produce O2 radicals and lysosomal enzymes.

Question 15

What are the systemic effects of cytokines?

Answer 15

prime mediators involved in the acute-phase response (the systemic effects of inflammation) – such as fever, appetite, neutrophilia (increase in number of neutrophils in the peripheral blood), synthesis of acute phase proteins by the liver. ƒ

They are the principal mediators of septic shock, as they can produce high amounts of NO.

Question 16

What is common complication of acute inflammation?

Answer 16

1. Tissue damage
   - The irritant itself
   - Ischemia

Question 17

What are the toxic products of inflammatory cells?

Answer 17

Superoxide radicals –
supposed to be maintained within the phagolysosomes in leucocytes, but sometimes may leak out of leucocytes and damage any cells that it comes into contact with.

Neutrophils releasing lysosomal enzymes accidentally:
ƒ Collagenase – breaks down collagenase ƒ
Plasmin – breaks down fibrin ƒ
Elastase – breaks down elastin

All of the above mediators can contribute to causing liquefactive necrosis of the host tissue (ie. Suppuration, pus – debris, exudate, dead cells)

Question 18

Toxic products of inflammatory cells released during phagocytosis include:

Answer 18

Neutrophil lysosomal enzymes- collagenase, elastase, plasmin (splits fibrin)

Superoxide radicals

Question 19

Suppuration generally occurs in the presence of pyogenic bacteria that have peptides that posses an N-formlymethionine terminal amino acid that is strongly __________

Answer 19

Chemotactic for neutrophils

Question 20

What is an abscess?

Answer 20

A localised collection of pus in an organ or tisse

Question 21

How can abscesses be caused?

Answer 21

Pyogenic (‘pus-forming’ because of their formyl cell walls being strongly chemotactic in attracting neutrophils to cause pus

Obstructed drainage of infective material

Question 22

What are some complications of abscesses?

Answer 22

• Pyaemia – when microorganisms enter the blood stream. This can cause multiple abscesses lodged by the circulation and lead to septic shock as massive amounts of IL-1 and TNF- α are produced.
• Empyema – when pus collects in a natural cavity (as opposed to the newly created cavity of an abscess).

Question 23

What is the acute inflammation time course?

Answer 23

1. Initially, there is a large burst of exudation due to the release of histamine and bradykinin, which is then sustained and then begins to decline.
2. After an initial lag, the lymphatic flow matches the rate of exudation in the tissue to prevent any further swelling of the tissue
3. Soon after this, there is the emigration of neutrophils (polymorphonucleocytes), which then die off after apoptosis.
4. After a couple of days, the monocytes (which mature into macrophages in tissue) emigrate and dominate the response – which is important for ‘cleaning up’ the debris of the inflammatory response, as well as initiating healing by repair if necessary.