Chronic Inflammation

Definition:
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 :

Chronic inflammatory cell infiltrate Macrophages Lymphocytes Plasma cells Tissue destruction

Repair Neovascularization Fibrosis

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Inflammation Comparison:
Acute inflammation
Duration: minutes to

Chronic inflammation
Duration: days to years Predominance of

days
Predominance of

neutrophils

lymphocytes and macrophages

Vascular proliferation

Fluid & plasma protein

and fibrosis

exudation
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Chronic and Acute Pneumonia

Under what circumstances does chronic Inflammation develop ?

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 6 Rheumatoid arthritis, Systemic Lupus, etc.

MACROPHAGE & LYMPHOCYTE

Macrophages & the Mononuclear Phagocytic System Macrophages:

Derived from circulating

monocytes tissue Macrophage

Scattered in tissues & act as filters

Kupffer cells (liver), Sinus histiocytes (spleen & LN) Alveolar macrophages (lung), Microglia (CNS)
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Mechanisms :
Tissue Injury Monocyte migration site of

injury MACROPHAGE activation by various cytokines : Two pathways

Classical macrophage activation important in

- host defense against ingested microbes - chronic inflammatory reactions

Alternative macrophage activation : important in

tissue repair through angiogenesis & fibroblast activation Collagen synthesis

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 Activated mainly by IFN- g secreted from T

lymphocytes,bacteria,FB.. Other cytokines from lymphocytes, eosinophilsetc

Increased cell size Epitheloid cell Increasedlysosomalenzymes,NO,ROS. More active metabolism, with greater ability

to kill ingested organisms

Result in death of macrophage or

accumulation of many macrophages at site pf injury 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

Proteases Complement and clotting factors Oxygen species and NO AA metabolites

IL-1 & TNF

Growth factors (PDGF, FGF, TGFb)

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Macrophage-lymphocyte interaction

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Other cells in chronic inflammation

Plasma

cells Eosinophils
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 metabolites

Neutrophils

with necrotic cells , persistent microbes, or

mediators Acute on Chronic Inflammation

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Granulomatous Inflammation
A distinctive form of chronic inflammation

characterized by collections of epithelioid macrophagesGRANULOMA

Granuloma, in addition to epithelioid

macrophages, may have one or more of the following:

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 tuberculosis Tuberculosis Mycobacterium Leprae Leprosy Treponema pallidum Syphilis Schistosoma Bilharziasis Histoplasma capsulatum Blastomycosis.etc Silicosis Suture material , other prosthesis, keratin Sarcoidosis, Crohn dis.
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Parasitic

Fungal

Inorganic metals Foreign body Unknown

Morphologic Appearance of Chronic Inflammation

Ulceration
Ulcer: Local defect or loss of continuity

in surface epithelia Chronic abscess cavity Induration & fibrosis Thickening of the wall of a hollow organ Caseous necrosis

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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 pyrogens synthesis of prostaglandins Exogenous from bacteria IL-1 & TNF 2- Elevated plasma level of acute phase proteins C- 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 to 15,000- 20,000cells/ ml. or more. Bacterial infections Neutrophilia Viral infections Lymphocytosis Parasitic infections & allergy Eosinophilia 4- Increasedheartrate,BP,anorexiaetc

5- Severe infections Septicshock,DIC Induced by TNF

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Consequences of Defective Inflammation

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

Allergic reactions Autoimmune disorders

Atherosclerosis
Ischemic heart disease

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