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Mechanism of Human Disease > Chronic Inflammation > Flashcards

Chronic Inflammation Flashcards

1
Q

Define chronic inflammation.

A
  • longer duration
  • slower process
  • angiogenesis
  • connective tissue deposits (fibrosis and scarring)
  • accumulation of lymphocytes and macrophages
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2
Q

Characterize chronic inflammation.

A
  • M1 macrophages, leukocytes, plasma cells
  • collateral tissue damage/angiogenesis
  • repair processes going on in parallel
  • scar formation
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3
Q

List potential causes of chronic inflammation.

A
  • acute inflammation was not resolved
  • autoimmune disease
  • genetic inability to destroy pathogen
  • chronic infections
  • persistent injury
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4
Q

List potential causes of lack of resolution of acute inflammation

A
  • inability to eradicate microbial pathogen
  • drug resistance
  • intracellular pathogen
  • persistent or resistant antigen (ex: foreign antigens, sutures)
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5
Q

What is the signature cell of chronic inflammation?

A

macrophages

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6
Q

Presence and persistence of activated M1 macrophages is associated with…

A

high levels of pro-inflammatory cytokines (IL-1, -6, -8, TNF-a)

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7
Q

Chronic high levels of pro-inflammatory cytokines causes increased production of…

A
  • innate immune proteins => decrease in albumin
  • hepcidin
  • growth factors for platelets, neutrophils, and monocytes
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8
Q

Define hepcidin.

A
  • master regulating peptide for iron metabolism

- regulates rate of absorption in the gut with the release from bone marrow macrophages

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9
Q

What does increased hepcidin cause?

A

increased hepcidin => decreased iron availability in the bone marrow and availability for it to be used by bacteria as a growth factor

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10
Q

Define granulomatous inflammation.

A
  • type of chronic inflammation
  • associated with persistent T cell activation
  • characteristic of intracellular microbial infection that is resistant to the body’s killing mechanisms
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11
Q

What disorders present with granulomas?

A
  • TB
  • sarcoidosis
  • IBD
    ==> many with unknown etiology
    ==> many that present antigen on macrophages
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12
Q

Describe granuloma morphology/histology.

A
  • center = caseous necrosis; mainly neutrophils
  • surrounded by activated macrophages, giant cells
  • peripheral cuff of T helper lymphocytes
  • rim of proliferating fibroblasts
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13
Q

Define multinucleated giant cells.

A
  • fusion of activated macrophages

- functions as a huge phagocytic cell

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14
Q

What is the logic behind granuloma formation?

A
  • to wall off the infection

- but consequently, constant necrosis and fibrosis is damaging

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15
Q

Clinical differences between acute and chronic inflammation are based on….

A

duration and intensity of stimulus

- the longer it lasts, the more systemic effects you will see (fever, leukopenia, etc)

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16
Q

Define the acute phase reactants.

A

biochemical changes during chronic inflammation

  • energy devoted to making innate immune proteins by the liver ==> fibrinogen, ceruloplasmin, complement proteins
  • reciprocal decrease in albumin (correlation between decrease and intensity of stimulus)
  • increased hepcidin => anemia b/c bone marrow cannot utilize iron trapped in macrophages
17
Q

How is CRP used clinically to measure inflammation?

A
  • elevated CRP epresents elevated levels of IL-6
  • reliable and low cost
  • best used to rule out inflammation, b/c if positive hard to tell if its chronic or during healing stage
18
Q

Why would you get a false positive CRP?

A

obese patients have higher number of M1 macrophages in adipose tissue => higher baseline

19
Q

Describe the use of the erythrocyte sedimentation rate (ESR).

A
  • chronic inflammation leads to antibody production (increased IgG and fibrinogen)
  • with more proteins in the blood, it becomes heavier, and will fall at a faster rate when placed in a tube
  • now obsolete because many factors affect ESR (age, gender, irrelevant serum protein
20
Q

List clinical tests done to diagnose chronic inflammation.

A
  • CRP
  • ESR
  • anemia (hepcidin)
  • low albumin
  • leukocytosis/thrombocytosis (growth factors)
21
Q

________ is characteristic of acute, _____________ is characteristic with chronic (growth factors).

A 
acute = leukocytosis
chronic = thrombocytosis

Mechanism of Human Disease (18 decks)

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