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8/13/2019 Chronic Inflammation - Huda
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Chronic Inflammation
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Definition:
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Inflammation of prolonged duration, in
which there is :
Continuing inflammation
Tissue injury
With or without repair
Characterized by :Persistent injurious agent
Inability of the host to overcome the
injurious agent
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Chronic Inflammation Components :
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Chronic inflammatory cell infiltrateMacrophages
Lymphocytes
Plasma cells
Tissue destruction
Repair
Neovascularization
Fibrosis
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Inflammation Comparison:
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Acute inflammation
Duration: minutes to
days
Predominance of
neutrophils
Fluid & plasma protein
exudation
Chronic inflammation
Duration: days to years
Predominance of
lymphocytes and
macrophages
Vascular proliferation
and fibrosis
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Chronic and Acute Pneumonia
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Under what circumstances does chronicInflammation develop ?
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Progression from acute inflammation
Tonsillitis, osteomyelitis, etc.
Repeated exposure to toxic agent
Silicosis, asbestosis, hyperlipidemia, etc.
Persistent viral infections
Persistent microbial infections difficult to clear Mycobacteria, Treponema, Fungi, etc.
Immune mediated (Autoimmune ) disorders
Rheumatoid arthritis, Systemic Lupus, etc.
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MACROPHAGE &
LYMPHOCYTE
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Macrophages & the Mononuclear
Phagocytic System
Macrophages:
Derived from circulatingmonocytestissue MacrophageScattered in tissues & act as filters
Kupffer cells(liver),Sinus histiocytes(spleen & LN)Alveolar macrophages(lung),Microglia(CNS)
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Mechanisms :
Tissue InjuryMonocyte migrationsite ofinjury MACROPHAGE activation by variouscytokines : Two pathways Classical macrophage activation important in
- host defense against ingested microbes- chronic inflammatory reactions
Alternative macrophage activation : important intissue repair through angiogenesis fibroblastactivationCollagen synthesis
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Activated mainly by IFN- secreted from Tlymphocytes, bacteria, FB..
Other cytokines from lymphocytes,eosinophilsetc
Increased cell size Epitheloid cell Increased lysosomal enzymes, NO, ROS.More active metabolism, with greater ability
to kill ingested organisms
Result in death of macrophage oraccumulation of many macrophages at site pfinjury
MULTINUCLEATE GIANT CELLS
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Role of macrophages in defense &
inflammation :
1. Ingest & destroy microbes, FB
2. Initiate repair
3.Secrete mediators of inflammation e.g IL-1
4.Antigen presenting cells
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Products Activated macrophages
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Proteases
Complement and clotting factors
Oxygen species and NO AA metabolites
IL-1 & TNF
Growth factors (PDGF, FGF, TGF )
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Macrophage-lymphocyte interaction
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Other cells in chronic inflammation
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Plasma cellsEosinophils
Parasitic infections and allergic conditions
Recruited by Eotaxin (chemokine) and other mediators
Release Major Basic Protein
Mast cells Allergic reactions
IgE-coated
release histamine & AA metabolitesNeutrophilswith necrotic cells , persistent microbes, or
mediators Acute on Chronic Inflammation
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Granulomatous Inflammation
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A distinctive form of chronic inflammationcharacterized by collections of epithelioidmacrophages GRANULOMA
Granuloma, in addition to epithelioidmacrophages, may have one or more of thefollowing:
a surrounding rim lymphocytes & plasma cells
a surrounding rim of fibroblasts & fibrosis giant cells
central necrosis due to hypoxia & FR injury
e.g. caseous necrosis in Tuberculosis (TB)
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Histopathology of Granuloma
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Histopathology of Granuloma
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Caseating Granuloma
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AFB Stain in Caseating Granuloma
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Examples of Granulomatous
Inflammation
Bacterial
Mycobacterium tuberculosisTuberculosisMycobacterium LepraeLeprosyTreponema pallidumSyphilis
Parasitic SchistosomaBilharziasis
FungalHistoplasma capsulatumBlastomycosis.etc
Inorganic metals Silicosis
Foreign body Suture material , other prosthesis, keratin
Unknown Sarcoidosis, Crohn dis. 21
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Systemic Effects of Inflammation
(Acute phase reactions)Mainly produced by cytokines : TNF, IL-1 & IL-6 from
leukocytes:
1- Fever :
Endogenous pyrogenssynthesis of prostaglandins Exogenous from bacteriaIL-1 & TNF
2- Elevated plasma level of acute phase proteinsC- reactive protein **
Fibrinogen** correlates with level of ESR
Serum amyloid A
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3- Leukocytosis :
Due to action of cytokines & Colony Stimulating
Factors (CSFs) on BM WBC count rises to15,000- 20,000cells/ ml. or more.
Bacterial infections Neutrophilia Viral infections Lymphocytosis Parasitic infections & allergy Eosinophilia
4- Increased heart rate, BP, anorexia etc
5- Severe infections Septic shock, DICInduced by TNF
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Consequences of Defective
Inflammation
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Susceptibility to infections
Defective innate immunity
Delayed repair
Delayed clearance of debris and necrotic
tissue
Lack of stimuli for repair
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Consequences of Excessive
Inflammation
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Allergic reactions
Autoimmune disorders
Atherosclerosis Ischemic heart disease