Chronic Inflammation Flashcards
What is chronic inflammation, and what is it characterized by?
prolonged tissue reaction characterized by accumulation of lymphocytes and macrophages, proliferating blood vessels, and the formation of connective tissue
What are the predominant cells in chronic inflammation?
macrophages, lymphocytes, plasma cells
What precedes chronic inflammation?
chronic inflammation is the persistence of the stimulus of acute inflammation
What can the lack of resolution be secondary to?
inability to get rid of the pathogen
pathogen resistance to antimicrobials
degradation resistant foreign body
genetic inability to mount proper response
What is the signature cell of chronic inflammation?
activated macrophages
What are macrophages associated with?
M1 macrophages are associated with high levels of pro-inflammatory cytokines
What does chronic high levels of inflammatory cytokines cause?
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
What will persist in the presence of microbes, IFN-gamma?
M1 - classically activated macrophage that will promote inflammation and microbicidal actions
What will occur in the presence of IL13, IL4
alternatively activated macrophage (M2) which will promote tissue repain, anti-inflammatory effects
What is granulomatous inflammation?
Distinct form of chronic inflammation associated with persistent T-cell (Th1) activation
What kind of infection is granulomatous inflammation persistent with?
persistent microbial intracellular infection and with macrophage uptake of poorly degradable foreign bodies
What diseases is granulomatous inflammation found in?
sarcoidosis
IBD
What is the morphology of granulomatous inflammation?
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
What kind of cellular response can be expressed as granulomatous inflammation?
an unregulated Th-1 response when macrophages cannot kill effectively
Discuss the sequence of events that leads to a frustrated macrophage response
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
What are some biochemical changes in inflammation?
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
What can we measure to assess inflammation status?
C-reactive protein (CRP)
What is CRP?
CRP production is stimulated by inflammation and is linked to IL6 levels
What is one morbidity that can cause a false elevation of CRP?
obesity
What is ESR?
erythrocyte sedimentation rate
How do ESR work?
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
Why is ESR becoming obsolete?
can have false elevations due to increase of IgG from other conditions
What are some general trends of plasma concentrations of some proteins after an inflammatory stimulus?
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
What will change in regards to plasma concentrations in chronic inflammation?
CRP and ESR will remain high
platelets and IgG will continuously rise
Hb and albumin will decrease
