INFLAMMATION

Composed by: Ahmad wali 3rd prof (M)

Definition:Inflammation is a protective response intended

to remove injurious stimuli as well as the necrotic cells and tissues resulting from original insert.

ORRepair process that causes the replacement of

damaged tissues by regeneration of parenchyma cells or by filling of any residual defect by firous scar tissues.

Inflammation:

ADVANTAGES:It causes destruction of microbes.

Causes detoxification of toxins.

Clears infections.

Helps in healing process.

Causes repair of damaged tissues.

DISADVANTAGES:Inflammatory responses are sometimes harmful

as they cause:Life threatening anaphylactic reactions to

insects bites, drugs and other chronic diseases like Rheumatoid arthritis, Atherosclerosis etc.

Inflammation of peritoneum leads to firous bands that causes obstruction of intestines.

Pericardial inflammation causes the formation of dense pericardium that impairs cardiac functions.

PLAYERS OF INFLAMMATION:The inflammatory responses have many players.

They include:1) CIRCULATING CELLS:I. Bone marrow derived polymorph nuclear

leukocytes e.g., Basophils, Esinophils and Neutrophils.

II. LymphocytesIII. MonocytesIV. Platelets.2) CIRCULATING PROTEINS:V. Clotting factorsVI. KininogensVII. Complement proteins

3) VASCULAR WALL CELLS:I. Connective tissue cellsII. Smooth muscle cellsIII. Epithelial cells4) EXTRA CELLULAR MATRIX:IV. Fibrous structural proteins e.g., Elastin &

FibrinogenV. Gel-forming proteoglycansVI. Adhesive glycoprotein e.g., Fibronectin,

that are cell-ECM and ECM-ECM connectors.

Inflammatory stimulus Chemical mediators

Inflammatory response until injurious stimulus is removedWhen the inflammatory stimulus is removed

these mediators are then dissipated, catabolized or removed.

TYPES OF INFLAMMATION:Acute inflammation And Chronic inflammation

PROCESS OF INFLAMMATION:

Chronic inflammation is the inflammation with prolonged duration usually from weeks to months and sometimes to years in which active inflammation, tissue injury and healing process proceed simultaneously.

DISTINGUISHING FEATURES:Infiltration of mono-nuclear cells like

lymphocytes, macrophages and plasma cells.Destruction of tissue by inflammatory cells.Proliferation of new vessels leading to repair

(angiogenesis & fibrosis).

CHRONIC INFLAMMATION:

ORIGIN AND PROCESS:Chronic inflammation arises from acute

inflammation. This transition takes place if the acute responses cannot be resolved either because of the persistence e.g., of injurious stimuli or by interference of the normal healing process e.g., peptic ulcer.

Some types of injuries engender responses with chronic inflammation initially e.g., viral infections.

SETTINGS LEADING TO CHRONIC INFLAMMATION:

I. Viral infectionsII. Persistent microbial infectionsIII. Prolonged exposure to potentially toxic materialsIV. Autoimmune diseases

The dominant cellular player in chronic inflammation is the tissue macrophage

It is joined by lymphocytes and plasma cells, however mast cells and eosinophils are as well involved in chronic allergic diseases

Blood monocytes

Tissue macrophage (RES)

migrate into tissue within 48 hours after injury

and differentiate

Kupffer cell (liver)

Microglia (CNS)

Histiocytes (spleen)

Alveolar macs (lung)

Lymphocyte Plasma cell

CHRONIC INFLAMMATORY CELLS & MEDIATORS:

1) MACROPHAGES:Macrophages are white blood cells within tissues,

produced by the division of monocytes.A majority of macrophages are stationed at strategic

points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:

In liver Kupffer cellsSpleen and lymph nodes Sinus histocytesNervous system Microglial cellsLungs Alveolar

macrophages

During chronic inflammation macrophages serve to eliminate injurious agents and initiate repair- however, they are as well responsible for much of the tissue injury that occurs

IFN-g

Activated T cell or NK cell

Tissue macrophage

Activated macrophage

Non Immune activation:Endotoxins, fibronectin, chemical mediators

Tissue injuryToxic oxygen metabolitesMetallo-proteasesCoagulation factorsAA metabolites and NO

Fibrosis (Scaring)Growth factors involved in fibroblast proliferation(PDGF,TGFb,FGF)Angiogenesis factors(FGF,VEGF)Collagen deposition (IL-13 and TGFb)

FUNCTIONS OF MACROPHAGES:They help to:Filter the particulate matterKill microbesAlert immune system of the body.Their life is 1-2 days.ACTIVATION OF MACROPHAGES:Activation of macrophages means:Increase in size Increase in lysosomal contentIncrease in metabolismIncrease in microbial killing activity

ACTIVATION SIGNALS: Different signals required to activate

macrophages are:Cytokines produced by T-lymphocytesBacterial endotoxinsDifferent mediators produced during acute

inflammationExtra cellular matrix proteins e.g., FibrinogenWhen macrophages become activated they

produce different type of biologically active substances that either cause ;

Cell injury OR Fibrosis.

Cell injury causing substances:Acid and neutral proteasesComplement proteins C1 to C5Coagulating factors V & VШAmino acids metabolitesCytokinesTumor necrosis factorFibrosis causing substances:Growth factorsFibrogenic cytokinesAngiogenesis factorsRegeneration and remodeling factors

2) LYMPHOCYTES:Both T- & B-lymphocytes are involved in chronic

inflammation. Their migration is brought about by specific adhesion molecules and cytokines. The T-lymphocytes work in reciprocal with B-lymphocytes in chronic inflammation. The already activated macrophages release TNF & IL1 and activate the inactive lymphocytes which then produce different antibodies that cause destruction of antigens at the inflammatory site.

3) ESINOPHILS:They are usually found in parasitic infections and

IgE mediated allergic reactions. Their migration is brought about by adhesion molecules produced by leukocytes and epithelial cells. Esinophils specific granules contain Major Basic Proteins which is highly cationic &toxic for parasites.

4) MAST CELLS:Mast cells are tissue cells which are like

basophils in shape. They are present in bone marrow and around blood vessels and do not enter the blood. They are specifically armed with IgE antibodies against certain antigens. When these antigens are encountered, they release histamines and amino acid metabolites. They cause initial vascular changes in acute inflammation and also cause anaphylactic reactions.

TYPES OF CHRONIC INFLAMMATION:1) AGRANULOMATOUS:Granuloma is not formed,Inflammation is characterized by all features of

chronic inflammation.Examples: Chronic viral infections e.g., Hepatitis Chronic autoimmune diseases e.g.,

Rheumatoid arthritis and Ulcerative colitis Chronic chemical intoxication e.g., Chronic

alcoholic liver disease Allergic reactions e.g., Bronchial asthma

2) GRANULOMATOUS INFLAMMATION:Characterized by aggregates of activated

macrophages that assume a squamous cell like epithelloid appearance.

GRANULOMA is defined as aggregates of macrophages formed due persistant response of T-lymphocytes to particular antigens.

This has a granular cheesy appearance called as caseous necrosis.

Examples are:Bacterial:Tuberculosis , Leprosy, Syphilis gumma etc.

Parasitic:Schistosomiasis Fungal:Histoplasma capsulatum, Blastomycosis.Inorganic metals / Dust:SilicosisForeign bodies:Suture, Vascular graft.Unknown:Sarcodiosis.

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