8-5 CHRONIC Inflammation

Question 1

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Answer 1

A: Chronic Inflammation (CHIF) = prolonged tissue rxn with accumulated lymphocytes/macrophages/blood vessels/connective tissue formation.
A2: Chronic Inflammation is longer and has [DECREASED acute changes such as rubor/tumor/calor/dolor]

B: Chronic Inflammation (CHIF) is predominated by [Inflammatory M1 macrophages] which can cause collateral damage. Chronic Inflam occurs when an initial trigger of acute inflammation persist. This could be from many reasons:

1) Inability to eradicate pathogen or address autoantigen (like in lupus)
2) Drug resistance to abx or antiviral
3) Intracell pathogens that immune system can’t get to
4) Persistent or degradation resistant antigen (such as Silica)

Question 2

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Answer 2

A: [Inflammatory M1 macrophages] are associated with inflammatory cytokines [IL-1/6/8/TNFa].

A2: [IL8 and 17] accounts for neutrophil presence during CHIF but [IL1/6/TNFa] leads to predominance of [Inflammatory M1 macrophages] during CHIF lesions

B: Logic is that if neutrophils don’t succeed in eradicating an inflammatory stimulus, the innate system switches to a diff cell to do the job

C: [CHIF cytokines] also stimulate Liver to produce proteins associated with innate immune response (such as Hepcidin, Leukocytes and platelets) BUT this as a result leads to [DEC albumin production] = “acute phase reactants”

D: [CHIF cytokines] are elevated in plasma and can be measured using a proxy measurement like [C-reactive Protein - CRP]. Liver produces CRP in equal amounts to IL-6.
D2: CAVEOT: Obese people have more [WAT White Adipose Tissue] and thus will have more [M1 Inflammatory Macrophages]—>have the ability to produce CRP = Obese people can have a “false Positive” elevated CRP

Question 3

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Answer 3

[CHIF cytokines] also stimulate Liver to produce proteins associated with innate immune response (such as Hepcidin, Leukocytes and platelets) BUT this leads to [DEC albumin production]

A: Hepcidin is a liver peptide hormone that regulates iron absorption and iron secretion from marrow macrophages.
A2: HIGH LEVELS OF HEPCIDIN during CHIF will cause DEC iron availability in the bone and DEC gut absorption of iron—> DEC HgB/RBC production

B: INC Hepcidin will ALSO —> DEC Albumin since liver is busy making Hepcidin

C: Liver uses Hepcidin so that bacteria WON’T have iron to use for their metabolic processes. Bacteria love iron!

D: CHIF cytokines also stimulate synthetic rates of growth factors for platelets, neutrophils & monocytes

Question 4

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Answer 4

A: [Granulomatous Inflammation] = type of CHIF associated with persistent T-cell activation = (haywire TMMI process)! Caused by:
1. Typically occurs with intracell infections of macrophages with organisms resistant to intracell killing mechanisms.
A2: M. tuberculosis is the prototype infection

2. [Granulomatous Inflammation] can also be caused by macrophages eating NON-biodegradable foreign bodies
3. Persistent Antigen presentation by macrophages. (such as in Sarcoidosis or IBD)

B: TB Granuloma morphology has a [central area of necrosis = “necrotizing caseous”] that is surrounded by activated macrophages, [giant blob of frustrated multinucleated phagocytic Macrophage cells], [CD4 helper T] and [proliferating fibroblast] on the perimeter.

B2:Granulomas NOT caused by TB will NOT have a [necrotizing caseous center].

C: Purpose of Granuloma is to wall off pathogen. Granulomas do a good job of that but ALSO cause collateral damage from tissue necrosis and fibrosis :-(

Question 5

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Answer 5

A: Differences between acute and CHIF are based on intensity and duration of the stimulus. Longer stimulus—> the greater that magnitude of sx

B: [Acute Phase Reactants] = biochemical changes that occur as a result of chronic inflammation (i.e. Liver making proteins {fibrinogen/ceruloplasmin/complement C3} but DECREASING albumin) = there is a correlation between level of albumin in blood and Chronic Inflammation
[the lower the albumin in blood = the WORST the CHIF ]

C: The liver also INC Hepcidin during CHIF to keep iron away from bacteria. The INC Hepcidin INC marrow macrophage to secrete Iron and DEC iron absorption= [DEC blood iron levels] –> [DEC RBC and anemia]

Question 6

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Answer 6

A: ESR [Erythrocyte Sedimentation Rate] = Rate at which erythrocytes fall through a column of plasma. Blood with more IgG and fibrinogen (both produced heavily in CHIF) will have FASTER erythrocyte falling rates.

B: This test is becoming obsolete because ESR naturally INC with age / gender and the presence of other serum proteins NOT related to inflammation - such as myeloma proteins