1.03 - Inflammation

Question 1

What is Inflammation?

Answer 1

Body’s response to injury
Part of the innate immune response
Limit and then repair damage cause by an injurious agent
It is primarily a protective response, which leads to repair

Question 2

What are the macroscopic signs of inflammation?

Answer 2

Redness
Swelling
Heat
Pain
Loss of Function

Question 3

What occurs during the acute and chronic phases of inflammation?

Answer 3

Acute (Minutes, Hours, Days)
 - Leucocytes (mainly neutrophils)
 - Exudate of fluid and plasma proteins
Chronic (Weeks, Months, Years)
 - Lymphocytes and Macrophages
 - Proliferation of blood vessels, fibrosis, tissue necrosis

Question 4

What are the components of inflammation?

Answer 4

Microvasculature
Circulating blood cells (red-passive, white-active)
Tissue cells (Secretion/release of mediators)
Inflammatory mediators (numerous)

Question 5

What are the changes in the microvasculature that occur in inflammation?

Answer 5

1. Transient vasocontriction (arterioles)
2. Vasodilation of all vessels –> increase blood flow
3. Permeability of small vessels increases –> exudate
4. Blood flow becomes sluggish (stasis)
5. Leucocytes become marginated and migrate in to extravascular space

Question 6

What is exudate?

Answer 6

exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation.
Includes water, the dissolved solutes of blood, plasma proteins, white blood cells, platelets, and in the case of local vascular damage: red blood cells.

Question 7

Describe Inflammatory mediators

Answer 7

Products of circulating blood cells, local tissue and plasma proteins
End result of combined action is attraction of more leucocytes to the site of injury and facilitation of phagocytosis of injurious agent

Question 8

What are the plasma protein derived inflammatory mediators?

Answer 8

Complement system proteins

Coagulation, fibrinolytic and kinin system proteins

Question 9

What are the cell and tissue derived inflammatory mediators?

Answer 9

Cytokines
Arachidonic acid metabolites
 - Prostaglandins
 - Leukotrienes
Histamine and other biogenic amines

Question 10

What are the 5 family groups of cytokines?

Answer 10

Interferons (IFN)
Interleukins (IL)
Chemokines
Colony Stimulating Factors
Growth Factors

Question 11

What are the functional groups classification for cytokines?

Answer 11

Proinflammatory (TNF, IL-1)
Anti-inflammatory (IL-10
Immunostimulatory (IL-2)

Question 12

What are the cellular contributions to inflammation?

Answer 12

Polymorphs
Mast Cells
Monocytes & Macrophages
Platelets
Vascular Endothelial Cells
Neurons

Question 13

Describe the role of Polymorphs in inflammation

Answer 13

First to arrive

Engulf, kill (free radicals) and digest (enzymic) microbes

Question 14

Describe the role of Mast Cells in inflammation

Answer 14

When activated (such as by complement) they secrete mediators

Question 15

Describe the role of Monocytes & Macrophages in inflammation

Answer 15

Late arrivals
Secrete cytokines and chemokines
Engulf cell debris and microbes

Question 16

Describe the role of Platelets in inflammation

Answer 16

Prostaglandin/leukotriene synthesis
Free radicals
Pro-inflammatory

Question 17

Describe the role of Vascular Endothelial Cells in inflammation

Answer 17

Contract/relaxation (nitric oxide)

Also important in repair (angiogenesis)

Question 18

Describe the role of Neurons in inflammation

Answer 18

Release compounds including Substance P (pain) & Kinins

Question 19

What are the systemic sequelae of inflammation?

Answer 19

Increased temperature (Fever)
Increased blood leucocytes
Synthesis of plasma proteins
Symptoms and signs depend upon the total mass of inflammatory tissue
Site the inflammatory lesion is critical in giving rise to other symptoms and signs

Question 20

Is there a purpose behind a fever?

Answer 20

Many bacteria do not live or multiply as effectively in temperatures >38 degrees C. Therefore teleologically the “purpose” is protective and to aid clearance of infecting bacterial organisms.

Question 21

What different types of fever patterns are described? Are they useful diagnostically?

Answer 21

Many descriptive terms used. E.g. “spiking”, “nocturnal”, diurnal etc. Each gives the reader more information about “when”, “how long”, etc. The descriptions are useful clinically. E.g. in particular from of malaria, a high fever may occur every 3 to 4 days; this follows the lifecycle of that malarial parasite.

Question 22

What are some of the systemic sequelae of inflammation apart form fever?

Answer 22

Increased heart rate, increased pulse pressure, flushing, raised white cell count etc

Question 23

If you were designing pharmacological compounds to interfere with or minimise inflammation or its consequences, what sites could you target? Are there drugs which act at these sites now?

Answer 23

Decrease production of inflammatory compounds
- Decrease number of cells producing enzymes
- Immunosuppressants (Azathioprine)
- Glucocorticosteroids (Prednisolone)
- Decrease production of inflammatory cytokines
- NSAIDs (Aspirin/Paracetamol)
Decrease response to defined cytokines
- Antibodies to defined cytokines
- Anti-TNFalpha (infliximab)
- Decrease cellular response to cytokines by modification of nuclear response (mesalazine)

Question 24

Which “inflammatory” compounds cause pain? Do they act directly on receptors or via other mechanisms?

Answer 24

Some of inflammatory mediators cause pain directly by being agonists for specific receptors on pain fibres. Others “facilitate” or enhance this effect, also by acting at specific receptors on pain fibres, but in the absence of the inflammatory response, they them selves do not initiate the action potential which is subsequently “felt” as pain. See Chronic inflammation lecture.