Chronic inflammation

Question 1

What are responsible for coordinating the inflammatory response?

Answer 1

Numerous inflammatory mediators

Question 2

How does the predominant inflammatory cell type differ between acute and chronic inflammation?

Answer 2

Acute= neutrophils
Chronic= macrophages, lymphocytes and plasma cells

Question 3

What are the different gross characteristics of acute vs chronic inflammation?

Answer 3

Acute: involes lots of exudate, plasma proteins and leukocytes

Chronic: fibrosis, tissue destruction and repair

Question 4

What are the causes of chronic inflammation?

Answer 4

• Persistant infections (e.g. tough microbes such as mycobacteria)
• Prolonged exposure to toxic agents (e.g. chronic hepatitis due to barbituates)
• Some foreign materials are indestructible e.g. some suture materials)
• Immune mediated inflammatory diseases (autoimmune or immunodeficient)
• Unidentified mechanisms

Question 5

What are the different morphological changes between acute and chronic inflammation?

Answer 5

In acute it is mainly oedema, vascular changes and neutrophilic inflammation. In chronic it is:

• tissue destruction (caused by the persistant stimulus)
• Attempts of healing (replace damage with CT- fibrosis and angiogenesis- and tissue proliferation)
• Infiltration of mononuclear cells (macrophages,lymphocytes and plasma cells)

Question 6

Where do kupffer cells exist?

Answer 6

Liver

Question 7

Where do sinus histiocytes exist?

Answer 7

Lymph nodes and spleen

Question 8

Where no monocytes exist?

Answer 8

In the blood

Question 9

Which mediators help activate macrophage migration?

Answer 9

• Exogenous factors: Microbial products and foreign bodies: often engage with TLRs
• Endogenous factors: cytokines (IFN-y) produced by T lymphocytes

Question 10

What is the role of an activated macrophage?

Answer 10

• Phagocytosis
• Increase lysosomal enzymes, increase ROS, Increase nitrogen species, increase proteases
• Increase cytokines (TNF, IL-1) and increase growth factors (VEGF, FGF)

**VEGF= vascular endothelial growth factor
FGF= fibroblast growth factor

Question 11

What is the role of lymphocytes in chronic inflammation?

Answer 11

Lymphocytes and macrophages interact, recruiting and activating each other. Can lead to very chronic/ severe reactions.

Question 12

What is the role of plasma proteins in chronic inflammation?

Answer 12

Activated by B lymphocytes the produce antibodies directed against persistent foreign/ self antigens.

Question 13

Why do nodular lesions form in some cases of chronic inflammation?

Answer 13

If the respnse is unable to remove the inciting agent then it is a mechanism to isolate/ sequester the lesion.
e.g. granulomas and abscesses

Question 14

What is the definition of an abscess?

Answer 14

A collection of pus surrounded by a fibrous capsule that is visible grossly
Most commonly caused by bacteria.

Question 15

What is the definition of a granuloma?

Answer 15

A nodular aggregation of macrophages which are usually surrounded by a collar of mononucelar leukocytes. It is a cellular attempt to contain an agent that is difficult to eradicate

Question 16

List some of the cells you’d usually find in a granuloma

Answer 16

• Epitheloid macrophages
• Giant multinucleated cells
• Fibroblasts
• Lymphocytes
• Macrophages

Question 17

What is a caseating granuloma?

Answer 17

A granuloma with a centre of necrotic debris

Question 18

Which agents often result in a granuloma?

Answer 18

• Many fungi, parasites, algae
• Foreign body material
• Few bacteria (mycobacteria)
• A few viruses

Question 19

What is the difference between regeneration and repair by connective tissue deposition?

Answer 19

• Regeneration is the proliferation of cells/ tissues to replace lost tissue. Results in the complete resolution of lost structures.
• Connective tissue deposition is the replacement of injured cells with connective tissue - collagen deposition and scar formation (fibrosis) or a combination of regeneration and scar tissue.

Question 20

What happens in stage one of wound healing?

Answer 20

• First 24 hours
• Activation of coagulatioin pathway
• Blood clot formation
• Neutrophils appear

Question 21

What happens in stage two of wound healing?

Answer 21

• Last 2-7 days
• Macrophages replace neutrophils (by 2-4 days)
• Proliferation of epithelial cells
• Epithelial cells and fibroblasts proliferate to form granulation tissue
• Fibroblasts develop parallel to the wound surface and perpendicular to the new capillaries (angiogenesis)

Question 22

What happens in stage three of wound healing?

Answer 22

• Lasts weeks
• Remodelling and maturation
• Leucocytes and increased vascularuty dissapear in the second week.
• granulation tissue is converted to a palce, avascular scar (made of fibroblasts and dense collagen)
• Wound contraction occurs in larger wounds.