Chronic Inflammation Flashcards
Define chronic inflammation.
- longer duration
- slower process
- angiogenesis
- connective tissue deposits (fibrosis and scarring)
- accumulation of lymphocytes and macrophages
Characterize chronic inflammation.
- M1 macrophages, leukocytes, plasma cells
- collateral tissue damage/angiogenesis
- repair processes going on in parallel
- scar formation
List potential causes of chronic inflammation.
- acute inflammation was not resolved
- autoimmune disease
- genetic inability to destroy pathogen
- chronic infections
- persistent injury
List potential causes of lack of resolution of acute inflammation
- inability to eradicate microbial pathogen
- drug resistance
- intracellular pathogen
- persistent or resistant antigen (ex: foreign antigens, sutures)
What is the signature cell of chronic inflammation?
macrophages
Presence and persistence of activated M1 macrophages is associated with…
high levels of pro-inflammatory cytokines (IL-1, -6, -8, TNF-a)
Chronic high levels of pro-inflammatory cytokines causes increased production of…
- innate immune proteins => decrease in albumin
- hepcidin
- growth factors for platelets, neutrophils, and monocytes
Define hepcidin.
- master regulating peptide for iron metabolism
- regulates rate of absorption in the gut with the release from bone marrow macrophages
What does increased hepcidin cause?
increased hepcidin => decreased iron availability in the bone marrow and availability for it to be used by bacteria as a growth factor
Define granulomatous inflammation.
- type of chronic inflammation
- associated with persistent T cell activation
- characteristic of intracellular microbial infection that is resistant to the body’s killing mechanisms
What disorders present with granulomas?
- TB
- sarcoidosis
- IBD
==> many with unknown etiology
==> many that present antigen on macrophages
Describe granuloma morphology/histology.
- center = caseous necrosis; mainly neutrophils
- surrounded by activated macrophages, giant cells
- peripheral cuff of T helper lymphocytes
- rim of proliferating fibroblasts
Define multinucleated giant cells.
- fusion of activated macrophages
- functions as a huge phagocytic cell
What is the logic behind granuloma formation?
- to wall off the infection
- but consequently, constant necrosis and fibrosis is damaging
Clinical differences between acute and chronic inflammation are based on….
duration and intensity of stimulus
- the longer it lasts, the more systemic effects you will see (fever, leukopenia, etc)
Define the acute phase reactants.
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
How is CRP used clinically to measure inflammation?
- 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
Why would you get a false positive CRP?
obese patients have higher number of M1 macrophages in adipose tissue => higher baseline
Describe the use of the erythrocyte sedimentation rate (ESR).
- 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
List clinical tests done to diagnose chronic inflammation.
- CRP
- ESR
- anemia (hepcidin)
- low albumin
- leukocytosis/thrombocytosis (growth factors)
________ is characteristic of acute, _____________ is characteristic with chronic (growth factors).
acute = leukocytosis chronic = thrombocytosis
