chronic inflammation - huda

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

chronic inflammation - huda

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