Chronic Inflammation

Question 1

What is chronic inflammation, and what is it characterized by?

Answer 1

prolonged tissue reaction characterized by accumulation of lymphocytes and macrophages, proliferating blood vessels, and the formation of connective tissue

Question 2

What are the predominant cells in chronic inflammation?

Answer 2

macrophages, lymphocytes, plasma cells

Question 3

What precedes chronic inflammation?

Answer 3

chronic inflammation is the persistence of the stimulus of acute inflammation

Question 4

What can the lack of resolution be secondary to?

Answer 4

inability to get rid of the pathogen

pathogen resistance to antimicrobials

degradation resistant foreign body

genetic inability to mount proper response

Question 5

What is the signature cell of chronic inflammation?

Answer 5

activated macrophages

Question 6

What are macrophages associated with?

Answer 6

M1 macrophages are associated with high levels of pro-inflammatory cytokines

Question 7

What does chronic high levels of inflammatory cytokines cause?

Answer 7

increased rates of hepatic production of defense proteins

increased hepcidin production - the innate system whats to sequester Fe++ which is a growth factor for many microbes (will cause decreased Fe absorption)

Increased growth factors for platelets, monocytes, and platelets

Question 8

What will persist in the presence of microbes, IFN-gamma?

Answer 8

M1 - classically activated macrophage that will promote inflammation and microbicidal actions

Question 9

What will occur in the presence of IL13, IL4

Answer 9

alternatively activated macrophage (M2) which will promote tissue repain, anti-inflammatory effects

Question 10

What is granulomatous inflammation?

Answer 10

Distinct form of chronic inflammation associated with persistent T-cell (Th1) activation

Question 11

What kind of infection is granulomatous inflammation persistent with?

Answer 11

persistent microbial intracellular infection and with macrophage uptake of poorly degradable foreign bodies

Question 12

What diseases is granulomatous inflammation found in?

Answer 12

sarcoidosis

IBD

Question 13

What is the morphology of granulomatous inflammation?

Answer 13

central portion of necrotic debris

activated macrophages and multinucleated giant cells in the periphery

CD3/4 T cells surrounding

entire granuloma rimmed by proliferating fibroblasts

Question 14

What kind of cellular response can be expressed as granulomatous inflammation?

Answer 14

an unregulated Th-1 response when macrophages cannot kill effectively

Question 15

Discuss the sequence of events that leads to a frustrated macrophage response

Answer 15

APCs present persistent antigen/infection/defective regulation, release IL12/present to Th1 which produces INF-gamma

APC will increase TNF-alpha, IL1,6,8 and will develop into granulomatous inflammation

Question 16

What are some biochemical changes in inflammation?

Answer 16

increased hepatic production of:
fibrinogen (coagulation cascade)
Ceruloplasmin (copper metabolism)
Complement components (C3)
Hepcidin (decreased iron absorption)

decreased hepatic prodoction of:
albumin synthesis

growth factors stimulate marrow resulting in increase of leukocyte and platelet production

Question 17

What can we measure to assess inflammation status?

Answer 17

C-reactive protein (CRP)

Question 18

What is CRP?

Answer 18

CRP production is stimulated by inflammation and is linked to IL6 levels

Question 19

What is one morbidity that can cause a false elevation of CRP?

Answer 19

obesity

Question 20

What is ESR?

Answer 20

erythrocyte sedimentation rate

Question 21

How do ESR work?

Answer 21

chronic inflammation results in an increase in polyclonal IgG

IgG and fibrinogen coat erythrocytes and they will then fall more rapidly through a column of plasma

Question 22

Why is ESR becoming obsolete?

Answer 22

can have false elevations due to increase of IgG from other conditions

Question 23

What are some general trends of plasma concentrations of some proteins after an inflammatory stimulus?

Answer 23

between 0 and 7 days after an inflammatory stimulus, C-reactive protein and Serum amyloid A will peak and fall

haptoglobin, C3, and fibrinogen will rise to a lesser amount but persist for weeks

albumin and transferrin will fall but resolve after a week

Question 24

What will change in regards to plasma concentrations in chronic inflammation?

Answer 24

CRP and ESR will remain high

platelets and IgG will continuously rise

Hb and albumin will decrease

Question 25

What are the systemic protective effects of local inflammation?

Answer 25

TNF, IL1,6 will produce fever (CNS), acute phase proteins (livers), leukocyte production (marrow)

Question 26

What are the systemic pathological effects of inflammation?

Answer 26

TNF leads to low output from heart

TNF can lead to thrombus formation and increased vascular permeability

TNF, IL1 can result in insulin resistance