Chronic inflammation Flashcards
Chronic Inflammation
- prolonged duration
- accompanied by tissue destruction & repair by fibrosis (healing & repair) proceeding simultaneously
- occur after acute inflamm
- insidious w/ no acute inflamm phase
ex.
rheumatoid arthritis, atherosclerosis, tuberculosis & pulm fibrosis
neoplasia & AD
Causes
- peristen infection- Treponema pallidum or mycobacteria (delayed hypersensitivity)
- autoimmune disease- rheumatoid arthritis, MS, allergic disease
- prolonged exposure to toxic agents- silicosis & atherosclerosis (endogenous toxic lipids)
Morphology
- infiltrate w/ mononuclear cells like macrophages, lymphocytes & plasma cells
- tissue destruction, induced by the products of inflammatory cells
- repair, involving new vessel prolif (angiogenesis) & fibrosis
Comparing inflamm
Inflammation
Cells
from BM
Chronic= macrophages, lymphocytes, plasma cells (have months to years half life)
Myeloid lineage
- neutrophils in acute
- eosinophils
- mast cells/ in tissue basophils
Macrophage
Macrophages
- kupffer cells- liver
- alveolar macrophages- lung
- histiocytes- CT
- fixed & free- in spleen & LN
- microglial cells- nervous sys
- osteoclasts- bone
- langerhans’ cells- skin
- dendritic cells- lymphoid tissue
- epithelioid histiocytes- granulomas
Macrophage
abundant cytoplasm & vesicular, bean shaped nuclei
Immunity
Activate Macrophages
Plasma Cells
Clock face
Coarse chromatin
Immune Rxn Cells
IgE
eosinophils- IgE, parasitic infection
- major basic prot
- recruited by eotaxin
- allergic rxn
mast cells
- allergic condition, anaphylactic rxn via IgE
- control inflamm rxns
Mast Cells
Eosinophils
Granulomatous inflammation
- granulomas- aggregates of modified macrophages, epithelioid cells or histiocytes w/ zone of lymphocytes & fibrosis
- multinucleated giant cells
- caseous necrosis in TB
- non necrotizing in sarcoidosis
- healing granuloma’s produce fibrosis
Cascerous necrois
Epithelioid Histiocytes
Always around center of granuloma
look like a foot print
Activated macrophages resembling epithelial cells
Foreign Body Granuloma
Form giant cells
foreign body like hair, food particle, keratin, cholesterol, suture
this is cholesterol example
Foreign Body Giant Cell lung
Suture
Immune Granuloma
- macrophage engulf bac
- process & present bac infectious againt Ag w/ MHC II
- complex activates CD4+ T cells
- CD4 secrete IFN-g
- causes prolif & recruitment of modified macrophages- epithelioid histiocytic cells
Caseating Granuloa TB
Cat Scratch Disease
non caseating geographic stellate necrotizing granulomata
Non caseating Non necrotizing Granuloma sarcoid
immune disease
usually in african americans
Cannot have TB!
Specific Infections w/ granuloma
- TB
- leprosy
- brucellosis
- histoplasmosis
- parasites- schistosomiasis
- cat scratch disease
Foreign Bodies w/ granuloma
Endogenous- keratin & uric acid crystals in gout
Exogenous- silica, asbestos dust, talc, suture material, silicone, prostheses
Further issues w/ granulomas
- beryllium in body
- hepatic granuloma due to allopurinol, phenylbutazone, sulphanomides
- sarcoidosis, Crohn disease
Acute phase Response
Clinical features
- fever
- increased pulse & bp
- decreased sweating
- rigors & chills
- somnolence
- anorexia & malaise
- septic shock
Acute Phase Response
Acute phase prot
- c reactive prot
- fibrinogen
- serum amyloid A prot
Leukocytosis
- neutrophilia
- eosinophilia
- lymphocytosis
Leukopenia
Fever
- pyrogens increase hypothal PG production
- Cause by LPS
- lead to increase in IL-1 & TNF
- upreg cyclooxygenases to increase PG
- cAMP NT produce reset in temp
- help ward off infection
Increase pulse & BP, decrease sweating
ANS adrenergic effect
Rigors, chills, anorexia, malaise, somnolence
actions of cytokines on brain
Sepsis fromm organisms & LPS
increase iN TNF, IL-1
DIC, hypoglycemia, hypotensive shock
Acute Phase Proteins
- mannose binding prot- opsonization & complement activation
- c reactive prot- opsonization
- a1 antitrypsin- serine protease inhibitor
- haptoglobin- binds Hg
- ceruloplasmin- antiox, binds Cu
- fibriongen- coagulation, erythrocyte sedimentation rate ESR
- Serum amyloid A prot- apolipoprot replacement in HDL directs lipids to histiocytes
- a2 macroglobulin- antiprotease
- cysteine protease inhibitor- antiprotease
CBC
- bac infection- neutrophilia
- parasitic infection- eosinophilia
- viral- lymphocytes
leukemoid rxn: 40-100,000 ul/mL w/ neutrophila shift to immature form due to TNF & IL-1 cytokines
malaria- increase monocyte, lymphocytes
Leukopenia in infection
- decreased WBC
- typhoid fever & viral infections, rickettsia, protozoal infections
- due to sequestered lymphocyte in LN
- overwhelming infection– disseminated cancer, rampant TB & alcoholism
Defective Inflamm
- increased susceptibility to infections- innate immunity
- delayed healing of wounds
- tissue damage increase due to:
- isolating damaged area
- mobilize effector cells & molecs to site
- promoting healing & repair
