Response to Injury III:

Question 1

How does chronic inflammation arise?

Answer 1

It arises as:

a progression from acute inflammation

following repeated episodes of acute inflammation

de novo if the causative agent only produces a mild acute response

Question 2

What happens in chronic inflammation?

Answer 2

The process of tissue destruction takes place alongside that of healing and repair so it’s integrated and the 2 processes should be considered together

Question 3

What are the features of chronic inflammation?

Answer 3

It’s very variable but some prevailing themes are:

• Tissue destruction & ulceration
• The inflammatory infiltrate is a mixture of macrophages, plasma cells, and lymphocytes; some polymorphs may be present
• The relative contribution of each cell type varies depending on the inflammatory stimulus
• Chronic inflammation is associated with the production of new fibrous tissue through granulation tissue formation (healing)

Question 4

What is a mechanism of chronic inflammation?

Answer 4

Proliferation of macrophages and lymphocytes:

Continued recruitment of lymphocytes an macrophages to the area
‘Activation’ of lymphocytes and macrophages
Proliferation locally at site of inflammation
Enhanced survival and immobilisation in the inflamed aea

Question 5

What signals cause chronic inflammation?

Answer 5

-Tissue derived chemical mediators
-Inflammatory cell derived chemical mediators
-Plasma enzyme systems
-Extracellular matrix components
-Extraneous products

These signals converge on target cells, lymphocytes, macrophages, plasma cells, this will cause an inflammatory response.

Question 6

give examples of Cellular mediators of inflammation:

Answer 6

Cellular mediators of inflammation: Histamine (biocative amines) Prostaglandins
Leukotrienes Cytokines/Lymphokines
Plasma derived mediators
Clotting factors
Complement cascade
Kallikrein-Kinin system
Fibrinolytic system

Question 7

give examples of Plasma derived mediators

Answer 7

Clotting factors
Complement cascade
Kallikrein-Kinin system
Fibrinolytic system

Question 8

give other examples of inflammatory mediators:

Answer 8

Bacterial products /extraneous factors
Reactive oxygen intermediates

Question 9

What pharmacological agents can you use to interfere with production of inflammatory mediators?

Answer 9

Aspirin
NSAIDs
Hydrocortisone
Antihistamines
Inhalers (various)
Other steroids

Question 10

What are the type of chronic inflammation?

Answer 10

Serous
Fibrinous
Suppurative (purulent)
Granulomatous

Question 11

What is granulomatous inflammation?

Answer 11

A form of chronic inflammation characterised by the formation of granulomas

Question 12

What is a granuloma?

Answer 12

A collection of activated macrophages

Question 13

What do granulomas look like histologically?

Answer 13

Abundant eosinophilic cytoplasm and look vaguely like epithelial cells so are termed ‘epithelioid cells’

Question 14

What can macrophages aggregate to form?

Answer 14

Giant cells

Question 15

What may solitary granulomas form in response to?

Answer 15

Persistent local inflammatory stimuli (e.g. foreign bodies)

Question 16

What are some examples of chronic granulomatous diseases?

Answer 16

TB
Leprosy
Sarcoidosis - a chronic disease of unknown cause characterized by the enlargement of lymph nodes in many parts of the body and the widespread appearance of granulomas derived from the reticuloendothelial system.
Crohn’s disease
Oro-facial granulomatosis
Chronic granulomatosis disease

Question 17

What is acid fast bacilli (AFB)?

Answer 17

A general term used to describe bacteria stained using the ‘Ziehl Neelsen’ (ZN) technique

In common usage, the term refers to M. tuberculosis

Question 18

What happens in TB?

Answer 18

Mycobacteria are ingested into the macrophages which excite a T cell response

As they are intracellular, they are protected from immunological attack & persist in the tissues.

look at slide 10

Question 19

What is a caseating granuloma?

Answer 19

It is a cheese-like necrosis ( tissue death), typically a feature of a granuloma of TB

Features include:

-dense mass of epithelioid cells
-T lymphocytes
-caseous necrosis centrally,
-Langerhans type giant cells,
- AFBs

look at slide 11

Question 20

Why can TB be considered a (Type IV) hypersensitivity reaction?

Answer 20

Because the intracellular mycobacteria drive ongoing inflammatory activity

This is characterised by a cell mediated (T cell) response

A sequel to this is tissue damage & repair

Tissue damage is caused by the hosts own cells.

IN TB AND OTHER CHRONIC INFLAMATORY CONDITIONS THERE IS A COMPLEX INTERPLAY BETWEEN HYPERSENSITIVITY AND TISSUE DAMAGE.

Question 21

What is rheumatoid arthritis?

Answer 21

A chronic, systemic inflammatory disorder that mainly affects joints

These become deformed and painful with loss of function
It may also have extra-articular features

Question 22

What makes rheumatoid arthritis a poly-arthritis?

Answer 22

Typically when >5 joints are involved

Question 23

explain the Pathogenesis of Rheumatoid Arthritis check

Answer 23

-Bone and cartilage erosion
- increased synovial fluid
- pannus formation

Question 24

What cytokines are involved in the signalling pathway for inflammatory arthritis? (check lecture recording)

Answer 24

TNF-a
Interleukin-1
Interleukin-6

Question 25

Describe the process of what happens in rheumatoid arthritis.

Answer 25

The inflammatory process causes the damage.

1. Unknown stimulus leads to chronic inflammation of the joints
2. Fibrous repair occurs in response to tissue damage
3. Fibrous tissue remodelling and contraction
4. Characteristic deformation and ankylosis of the joints (commonly symmetrical involvement of the small joints of the hand)

Question 26

Summarise chronic inflammation:

Answer 26

• Can be both protective and destructive

-Reflects a complex interrelationship between the response to damaging stimuli and hypersensitivity

-Is associated with granulation tissue formation and fibrous repair - in some instances this is helpful but in others it leads to tissue damage and loss of function.