Chronic inflammation

Question 1

Three characteristics of chronic inflammation

Answer 1

• Accumulation of lymphocytes and macrophages
• Proliferating blood vessels
• Formation of connective tissues

Question 2

What things can qualify as injurious and are most likely to form acute inflammation?

Answer 2

Infarction
Bacterial infections
Toxins
Trauma

Question 3

What things can qualify as injurious and are most likely to form chronic inflammation?

Answer 3

Viral infections
Chronic infections
Persistant injury
Autoimmune diseases

Question 4

Why may there be lack of resolution occurring with chronic inflammation? (5)

Answer 4

• Inability to get rid of the pathogen
• Pathogen resistance to antimicrobials
• Degradation resistant foreign body
• Persistant exposure to an autoantigen
• Genetic inability of the host to mount the appropriate response to the pathogen

Question 5

M1 macrophages

Answer 5

“Signature cell” of inflammation. Associated with high levels of pro-inflammatory cytokines

Question 6

What three things do chronic high levels of inflammatory cytokines cause?

Answer 6

• Increased rates of hepatic production of defense proteins
• Increased hepcidin production, which sequesters iron
• Increased growth factors for platelets and monocytes

Question 7

M1 vs M2

Answer 7

M1: microbicidal actions and inflammation
M2: tissue repair, fibrosis, and anti-inflammatory effects

Question 8

Granulomatous inflammation

Answer 8

Distinct form of inflammation associated with persistent, unregulated Th1 cell activation

Question 9

Where are granulomatous inflammation sites commonly found?

Answer 9

Persistent microbial intracellular infection or when macrophages uptake poorly degradable foreign bodies

Question 10

Examples of diseases with granuloma formation

Answer 10

TB
Sarcoidosis
IBD

Question 11

What types of cells are found in granulomas?

Answer 11

Activated macrophages, CD4+ T cells, proliferating fibroblasts, and multinucleated giant cells

Question 12

Describe the layout of a granulomatous formation.

Answer 12

There is a central area of caseous necrosis, lined by activated epithelioid macrophages and giant cells, and peripheral accumulation of lymphocytes.

Question 13

What is the benefit of granuloma formation?

Answer 13

The infectious organism is “walled off”

Question 14

What is the negative side of granuloma formation?

Answer 14

Collateral damage caused by progressive tissue necrosis and fibrosis can be extensive

Question 15

Clinical differences in inflammation are based on . . .

Answer 15

Intensity and duration of the injurious stimulus

Question 16

Three things from liver that increase production during inflammation

Answer 16

Fibrinogen
Ceruloplasmin
Complement proteins (C3 in particular)

Question 17

Rough estimate of inflammatory process duration

Answer 17

Based on albumin levels: rough correlation between decrease in albumin synthesis and duration of inflammatory process

Question 18

What other clinical disorder is noted after chronic inflammation? Why?

Answer 18

Anemia; increased hepatic production of hepcidin, which blocks iron uptake, as iron is a common growth factor among microbes

Question 19

What do growth factors do to blood levels?

Answer 19

Stimulate marrow to increase leukocyte and platelet production

Question 20

CRP

Answer 20

C-reactive protein: stimulated by inflammation and is tightly linked to IL-6 levels. Measures inflammation levels reliably

Question 21

What causes false elevation of CRP?

Answer 21

Obesity

Question 22

What is the most useful measure of CRP?

Answer 22

When it is normal, it rules out acute inflammation. Very non-specific positive result

Question 23

ESR

Answer 23

Erythrocyte sedimentation rate; chronic inflammation causes clinically detectable antibody synthesis expressed as polyclonal increase in IgG and increased fibrinogen that coat and “weigh down” the red blood cells

Question 24

Why is ESR being phased out?

Answer 24

“False elevations” can occur when there is IgG increase for non-inflammatory reasons, including myeloma, age

Question 25

Granulation

Answer 25

Reactive tissue; a lot of fibrosis and a lot of vessels in it; phase in the process of scar formation. NOT to be confused with granuloma