DR. Murali B MDR. Murali B M

INFLAMMATIONINFLAMMATION

INFLAMMATIONINFLAMMATION

DEFINITION

INFLAMMATION IS A HOST RESPONSE INFLAMMATION IS A HOST RESPONSE TO LOCAL INJURY TO LOCAL INJURY

IT IS FUNDAMENTALLY A VASCULAR IT IS FUNDAMENTALLY A VASCULAR PHENOMENON.PHENOMENON.

The suffix “itis” is added to the base word to The suffix “itis” is added to the base word to state the condition in inflammation. E.g. state the condition in inflammation. E.g. Appendix -appendicitis & Gingiva -gingivitisAppendix -appendicitis & Gingiva -gingivitis

INFLAMMATION-HISTORICAL INFLAMMATION-HISTORICAL ASPECTSASPECTS

4 ANCIENT CARDINAL SIGNS –DESCRIBED BY CELSUS IN 14 ANCIENT CARDINAL SIGNS –DESCRIBED BY CELSUS IN 1STST CENTURY A.DCENTURY A.D

RUBOR-RUBOR-REDNESSREDNESS

CALOR-CALOR-HEATHEAT

TUMOR-TUMOR-SWELLINGSWELLING

DOLOR-DOLOR-PAINPAIN

55THTH SIGN DESCRIBED BY RUDOLF VIRCHOW SIGN DESCRIBED BY RUDOLF VIRCHOW LOSS OF FUNCTION LOSS OF FUNCTION (FUNCTIO LAESA) -(FUNCTIO LAESA) -

CARDINAL SIGNS OF CARDINAL SIGNS OF INFLAMMATIONINFLAMMATION

INFLAMMATION-STIMULIINFLAMMATION-STIMULI

PHYSICAL AGENTSPHYSICAL AGENTS-Trauma, Thermal -Trauma, Thermal injury &Radiation injuryinjury &Radiation injury

CHEMICAL AGENTS- CHEMICAL AGENTS- Acids, Alkalis, Acids, Alkalis, Toxins & Poisons Toxins & Poisons

BIOLOGICAL AGENTS BIOLOGICAL AGENTS – Infections: – Infections: Bacterial, Viral, Fungal & ParasiticBacterial, Viral, Fungal & Parasitic

TISSUE NECROSISTISSUE NECROSISFOREIGN BODYFOREIGN BODY IMMUNOLOGICAL INJURIESIMMUNOLOGICAL INJURIES

Cells of inflammationCells of inflammation

CellCell ActivityActivity PhagocytosisPhagocytosis InflammationInflammation

NeutrophilNeutrophil Proteases, Proteases, oxidasesoxidases

++ AcuteAcute

EosinophilEosinophil AntihistamineAntihistamine ++ Acute, chronicAcute, chronic

Macrophage Macrophage (modified (modified monocytes)monocytes)

Antigen Antigen processing, processing, digestiondigestion

++ Late acute, Late acute, chronicchronic

LymphocyteLymphocyte LymphokinesLymphokines -- ChronicChronic

Plasma cellPlasma cell Antibody Antibody productionproduction

-- ChronicChronic

Cells of the inflammatory processCells of the inflammatory process NeutrophilsNeutrophils. These are the first inflammatory cells on the scene after . These are the first inflammatory cells on the scene after

tissue injury. They phagocytize a foreign material (e.g. bacteria) and then tissue injury. They phagocytize a foreign material (e.g. bacteria) and then attempt to oxidize and digest it through oxidase and proteasesattempt to oxidize and digest it through oxidase and proteases

Eosinophils Eosinophils are also phagocytic and possess many of the enzymes of the are also phagocytic and possess many of the enzymes of the neutrophil. In addition, they can dispense antihistamine in an area of neutrophil. In addition, they can dispense antihistamine in an area of histamine release. The histamine release. The eosinophileosinophil is also associated with allergic is also associated with allergic responses. It is seen in both acute and chronic inflammation and become responses. It is seen in both acute and chronic inflammation and become increased in parasitic infestationsincreased in parasitic infestations

MacrophagesMacrophages: Monocytes and tissue macrophages. They engulf the : Monocytes and tissue macrophages. They engulf the foreign particles at the site of entry and process their antigens and feeds foreign particles at the site of entry and process their antigens and feeds this information immune system to mount immune response through this information immune system to mount immune response through humoural (antibody) and cell mediated immune mechanismshumoural (antibody) and cell mediated immune mechanisms

LymphocytesLymphocytes are simple-appearing cells with varied and complex are simple-appearing cells with varied and complex functions. The lymphocytes are classifed into T-lymphocytes and B-functions. The lymphocytes are classifed into T-lymphocytes and B-lymphocytes. T-lymphoctyes function mediate cellular immune response lymphocytes. T-lymphoctyes function mediate cellular immune response through production various type of lymphokines, which have local effects on through production various type of lymphokines, which have local effects on other cells. B- lymphocytes medicate antibody respones through other cells. B- lymphocytes medicate antibody respones through production of Immunoglobulins or antibodies. The lymphocytes production of Immunoglobulins or antibodies. The lymphocytes characterizes chronic inflammation. Antibody production is the function of characterizes chronic inflammation. Antibody production is the function of the plasma cellthe plasma cell, a specialized B cell, which is also found in chronic , a specialized B cell, which is also found in chronic inflammation. It is especially prominent in chronic inflammation involving inflammation. It is especially prominent in chronic inflammation involving mucosal surfacesmucosal surfaces

INFLAMMATION-TYPESINFLAMMATION-TYPESACUTEACUTE

RAPID ONSETRAPID ONSET SHORT DURATIONSHORT DURATION EXUDATION OF FLUID AND PLASMA PROTEINSEXUDATION OF FLUID AND PLASMA PROTEINS NEUTROPHIL IS THE PREDOMINANT WBCNEUTROPHIL IS THE PREDOMINANT WBC StereotypicStereotypic

CHRONICCHRONIC SLOW ONSETSLOW ONSET LONGER DURATIONLONGER DURATION LYMPHOCYTES AND MACROPHAGES LYMPHOCYTES AND MACROPHAGES PROLIFERATION OF BLOOD VESSELS AND FIBROSISPROLIFERATION OF BLOOD VESSELS AND FIBROSIS Granulomatous inflammation is also regarded as Granulomatous inflammation is also regarded as

a type of chronic inflammationa type of chronic inflammation

ACUTE INFLAMMATIONACUTE INFLAMMATION

Systemic response Systemic response of Acute inflammationof Acute inflammation: : Systemically, acute inflammation may be Systemically, acute inflammation may be accompanied by fever. There may be a accompanied by fever. There may be a peripheral blood leukocytosis, especially of peripheral blood leukocytosis, especially of neutrophils, along with increased number of neutrophils, along with increased number of immature forms of neutrophils (“left shift”). immature forms of neutrophils (“left shift”). Presence of Acute phase reactants in blood eg. Presence of Acute phase reactants in blood eg. C-reactive protein.C-reactive protein.

Local response Local response of Acute inflammationof Acute inflammation: : includeinclude

VASCULAR CHANGESVASCULAR CHANGES CELLULAR EVENTSCELLULAR EVENTS

Vascular changes in Acute inflammationVascular changes in Acute inflammationLocally, it is Locally, it is the vascular responsethe vascular response to tissue injury that is to tissue injury that is

fundamental. The changes are seen in arterioles, capillaries fundamental. The changes are seen in arterioles, capillaries and venules.and venules.

The initial response to tissue injury is an episode lasting The initial response to tissue injury is an episode lasting from seconds to 5 minutes.from seconds to 5 minutes.

Transient Transient vasoconstrictionvasoconstriction, probably as a direct effect on , probably as a direct effect on the vessels. the vessels.

Followed by Followed by VasodilatationVasodilatation of the precapillary arterioles of the precapillary arterioles resulting in greater blood flow to the area. This lasts as long resulting in greater blood flow to the area. This lasts as long as the acute inflammation persists. The injured area as the acute inflammation persists. The injured area reddens from reddens from increased blood flowincreased blood flow; ;

this is accompanied by this is accompanied by increased vascular permeabilityincreased vascular permeability. . As a consequence, As a consequence, interstitial edemainterstitial edema (swelling) occurs (swelling) occurs owing to the escape of intravascular fluid, called an exudate. owing to the escape of intravascular fluid, called an exudate. This is important to bring Antibodies and leukocytes to site This is important to bring Antibodies and leukocytes to site of injury.of injury.

Then, the lymphatic vessels admit the escaped fluid into Then, the lymphatic vessels admit the escaped fluid into the lymphatic system and after several days the swelling the lymphatic system and after several days the swelling subsides.subsides.

Transudate, exudate and pus..A A transudate transudate results when increased intravascular fluid results when increased intravascular fluid escapes into the interstitial tissues due to escapes into the interstitial tissues due to increased increased hydrostatic pressurehydrostatic pressure in the vessels. Vascular permeability is in the vessels. Vascular permeability is intact. A good example is the pedal (ankle) edema seen in intact. A good example is the pedal (ankle) edema seen in congestive heart failure. This fluid has low protein content congestive heart failure. This fluid has low protein content and specific gravity (< 1.020).The cells present are few and specific gravity (< 1.020).The cells present are few lymphocytes. lymphocytes.

In acute inflammation, the edema is caused by the escape of In acute inflammation, the edema is caused by the escape of fluid into the interstitial tissues due to fluid into the interstitial tissues due to increased vascular increased vascular permeability of endothelial cellspermeability of endothelial cells. This fluid is called an . This fluid is called an exudateexudate. Because more protein escapes with the fluid . Because more protein escapes with the fluid compared with that which occurs with a transudate, an compared with that which occurs with a transudate, an exudate has a higher protein content and specific gravity (> exudate has a higher protein content and specific gravity (> 1.020). More inflammatory cells (Neutrophils & Macrophages) 1.020). More inflammatory cells (Neutrophils & Macrophages)

PusPus consists mostly of neutrophils and necrotic derbis, being consists mostly of neutrophils and necrotic derbis, being

high in protein content with a specific gravity greater than high in protein content with a specific gravity greater than 1.020.1.020.

Characteristics of transudate, exudate and pusCharacteristics of transudate, exudate and pus

Characteristics of transudate, exudate and pusCharacteristics of transudate, exudate and pus

Fluid typeFluid type ConditionCondition ContentContent Specific Specific gravitygravity

TransudateTransudate Increase hydrostatic Increase hydrostatic pressure (CCF, pressure (CCF, Cirrhosis liver)Cirrhosis liver)

Low proteinLow protein < 1.020< 1.020

ExudateExudate Acute inflammationAcute inflammation High proteinHigh protein > 1.020> 1.020

PusPus Acute inflammationAcute inflammation High protein High protein plus neutrophilsplus neutrophils

> 1.020> 1.020

Cellular Events of InflammationCellular Events of Inflammation

MarginationMarginationAdhesion & rollingAdhesion & rollingPavementationPavementationEmigration & Emigration &

DiapedesisDiapedesisChemotaxisChemotaxisPhagocytosisPhagocytosis

Cellular events Cellular events in acute inflammationin acute inflammation..

Cellular events begin soon after vasodilatation. Leukocytes Cellular events begin soon after vasodilatation. Leukocytes (especially polymorphonuclear leukocytes) move from the center of (especially polymorphonuclear leukocytes) move from the center of the blood column in a vessel to the periphery the blood column in a vessel to the periphery (margination)(margination) and and they start they start rolling (tumbling)rolling (tumbling) on the endothelial surface. Later begin on the endothelial surface. Later begin to adhere to adhere (adhesion)(adhesion) to the endothelial surface with the help of to the endothelial surface with the help of adhesion molecules (Selectins and integrins) resulting in covering adhesion molecules (Selectins and integrins) resulting in covering of endothelial surface of endothelial surface (pavementing).(pavementing).

At the same time, the leukocytes move from the vessels into the At the same time, the leukocytes move from the vessels into the interstitial tissues interstitial tissues (emigration) (emigration) by forcing through endothelial by forcing through endothelial junctionsjunctions. .

Once outside the vessel they start moving towards site of injury Once outside the vessel they start moving towards site of injury with the help of chemical mediators with the help of chemical mediators (Chemotaxis).(Chemotaxis).

Once they reach the site of injury the neutrophils engulf the Once they reach the site of injury the neutrophils engulf the injurious agent injurious agent (Phagocytosis)(Phagocytosis) and tries to destroy them using and tries to destroy them using their proteolytic enzymes & oxygen derived free radicals their proteolytic enzymes & oxygen derived free radicals ( superoxides, hydrogen peroxide & hydroxyl ions)( superoxides, hydrogen peroxide & hydroxyl ions)

RECRUITMENT OF LEUCOCYTES RECRUITMENT OF LEUCOCYTES TO SITE OF INJURYTO SITE OF INJURY

INITIAL 6-24 HOURS– NEUTROPHILSINITIAL 6-24 HOURS– NEUTROPHILS LATER– MONOCYTES & LYMPHOCYTESLATER– MONOCYTES & LYMPHOCYTES Initially, it is the neutrophils that emigrate in the greatest Initially, it is the neutrophils that emigrate in the greatest

number, whereas lymphocytes, macrophages and number, whereas lymphocytes, macrophages and eosinophils also take part in this process, initially in eosinophils also take part in this process, initially in fewer numbers. As the inflammation regresses, fewer numbers. As the inflammation regresses, decreasing numbers of neutrophils emigrate, whereas decreasing numbers of neutrophils emigrate, whereas more lymphocytes and macrophages make the trip and more lymphocytes and macrophages make the trip and finally predominate when the process becomes chronic finally predominate when the process becomes chronic with the disappearance of the neutrophils.with the disappearance of the neutrophils.

CELLULAR EVENTS

CHEMOTAXIS Definition: Definition: Process of directed cell Process of directed cell

migration along a chemical gradientmigration along a chemical gradient

OrOrMovement of leukocytes along the Movement of leukocytes along the

chemical gradient.chemical gradient. It is responsible for the movement of It is responsible for the movement of

leukocytes towards the site of injuryleukocytes towards the site of injury

CHEMOTACTIC-AGENTS

EXOGENOUSEXOGENOUS (from bacteria) (from bacteria)BACTERIAL PRODUCTS-COMMONESTBACTERIAL PRODUCTS-COMMONESTPEPTIDES OR LIPIDSPEPTIDES OR LIPIDS

ENDOGENOUS ENDOGENOUS ( from cells and plasma)( from cells and plasma)COMPLEMENT COMPONENTS-C5aCOMPLEMENT COMPONENTS-C5aLEUKOTRIENE B4LEUKOTRIENE B4CYTOKINES-IL-8CYTOKINES-IL-8

PhagocytosisPhagocytosis

DefinitionDefinition: : Engulfment of Engulfment of particulate matter or particulate matter or

bacteria by the WBCsbacteria by the WBCs..

Stages of PhagocytosisStages of Phagocytosis

1. Chemotaxis1. Chemotaxis: Phagocytes are chemically : Phagocytes are chemically attracted to site of infection ( C5a).attracted to site of infection ( C5a).

2. Recognition & Adherence:2. Recognition & Adherence: Phagocyte Phagocyte plasma membrane attaches to surface of plasma membrane attaches to surface of pathogen or foreign material. pathogen or foreign material. Adherence can be inhibited by capsules (Adherence can be inhibited by capsules (S. S.

pneumoniaepneumoniae) or M protein () or M protein (S. pyogenesS. pyogenes).).

OpsonizationOpsonization: Coating process with opsonins : Coating process with opsonins

that facilitates attachment. that facilitates attachment. OpsoninsOpsonins include include

antibodies (IgG) and complement proteins antibodies (IgG) and complement proteins

(C3b).(C3b).

Stages of PhagocytosisStages of Phagocytosis

3. Ingestion3. Ingestion: Plasma membrane of : Plasma membrane of phagocytes extends projections phagocytes extends projections (pseudopods) which engulf the microbe. (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called Microbe is enclosed in a sac called phagosomephagosome..

4. Digestion4. Digestion: Inside the cell, phagosome : Inside the cell, phagosome fuses with lysosome to form a fuses with lysosome to form a phagolysosomephagolysosome. .

Lysosomal enzymes kill most bacteria Lysosomal enzymes kill most bacteria within 30 minutes and include:within 30 minutes and include:Lysozyme: Destroys cell wall peptidoglycanLysozyme: Destroys cell wall peptidoglycanLipases and ProteasesLipases and ProteasesRNAses and DNAsesRNAses and DNAses

After digestion, After digestion, resresmaterial is material is dischargeddischargedidual bodyidual body with undigestable. with undigestable.

Process of killingProcess of killing

Oxygen dependentOxygen dependent Myeloperoxidase-Myeloperoxidase-

Halide systemHalide system Free radicalsFree radicals

SuperoxidesSuperoxides Hydroxyl ionsHydroxyl ions

Oxygen independentOxygen independent Lysosomal EnzymesLysosomal Enzymes Cat ionic proteinsCat ionic proteins

OUTCOMEOUTCOME

1. COMPLETE RESOLUTION1. COMPLETE RESOLUTION

RESTORATION OF SITE TO NORMALRESTORATION OF SITE TO NORMAL

LIMITED AND SHORT LIVED INJURYLIMITED AND SHORT LIVED INJURY

MINIMAL TISSUE DAMAGEMINIMAL TISSUE DAMAGE

REGENERATION OF PARENCHYMAL CELLSREGENERATION OF PARENCHYMAL CELLS

MACROPHAGES PLAYS AN IMPORTENT ROLE MACROPHAGES PLAYS AN IMPORTENT ROLE

OUTCOMEOUTCOME2. FIBROSIS2. FIBROSIS EXTENSIVE TISSUE DAMAGEEXTENSIVE TISSUE DAMAGE TISSUES INCAPABLE OF REGENERATIONTISSUES INCAPABLE OF REGENERATION ABUNDANT FIBRIN-Eg SEROUS CAVITY-ABUNDANT FIBRIN-Eg SEROUS CAVITY-

GROWTH OF FIBROUS TISSUE LEADS TO GROWTH OF FIBROUS TISSUE LEADS TO ORGANIZATIONORGANIZATION

3. PROGRESSION TO CHRONIC 3. PROGRESSION TO CHRONIC INFLAMMATIONINFLAMMATION

MORPHOLOGICAL PATTERNS MORPHOLOGICAL PATTERNS OF ACUTE INFLAMMATIONOF ACUTE INFLAMMATION

Acute and chronic inflammation conform Acute and chronic inflammation conform themselves into several appearances. themselves into several appearances.

An effusion of thin fluid An effusion of thin fluid under acute under acute inflammatory inflammatory conditions from a conditions from a surface (often surface (often mesothelial) is called mesothelial) is called serous inflammation. serous inflammation.

Eg. Blisters of skinEg. Blisters of skin

Bullous pemphigoidBullous pemphigoid

Dermis

SEROUSSEROUS Inflammation Inflammation

Blister fluid

Serous Exudate

Fibrinous Exudate

FIBRINOUSFIBRINOUS Inflammation Inflammation

•Fibrinous inflammation consists of neutrophils admixed with fibrin (e.g., fibrinous pericarditis).•The fibrin in this fluid can form a fibrinous exudate on the surfaces. •Bread & Butter appearance Here, the pericardial cavity has been opened to reveal a fibrinous pericarditis with strands of stringy pale fibrin between visceral and parietal pericardium

CatarrhalCatarrhal inflammation inflammation

Mucosa-lined surfaces may exhibit Mucosa-lined surfaces may exhibit catarrhal inflammationcatarrhal inflammation with the with the outpouring of outpouring of watery mucuswatery mucus. .

Eg. Common coldEg. Common cold

SuppurativeSuppurative Inflammation Inflammation Suppurative Suppurative

inflammation (Purulent) inflammation (Purulent) exudes pus, a mixture of exudes pus, a mixture of neutrophils and necrotic neutrophils and necrotic debris.eg.pyogenic debris.eg.pyogenic bacterial infection. bacterial infection.

Exuded yellowish fluid fluid in this opened pericardial cavity also contains a large number of acute inflammatory cells. So it is a purulent exudate

SUPPURATIVE INFLAMMATIONSUPPURATIVE INFLAMMATION

A A purulent exudate is seen beneath the meninges in the A purulent exudate is seen beneath the meninges in the brain of this patient with acute meningitis from brain of this patient with acute meningitis from Streptococcus pneumoniae infection. The exudate Streptococcus pneumoniae infection. The exudate obscures the sulci.obscures the sulci.

B The abdominal cavity is opened at autopsy here to reveal The abdominal cavity is opened at autopsy here to reveal an extensive purulent peritonitis that resulted from rupture an extensive purulent peritonitis that resulted from rupture of the colon. of the colon.

A B

ABSCESSABSCESS

A localised (enclosed) A localised (enclosed) collection of pus is called collection of pus is called an an abscess.abscess.

Extensive acute Extensive acute inflammation may lead to inflammation may lead to abscess formation, as abscess formation, as seen here with rounded seen here with rounded abscesses (the purulent abscesses (the purulent material has drained out material has drained out after sectioning to leave a after sectioning to leave a cavity) in the lungcavity) in the lung..

Diverticulitis of Colon Diverticulitis of Colon with abscess with abscess formationformation

AbscessAbscess

ABSCESSABSCESS

Sulfur granules of Sulfur granules of actinomycosesactinomycoses

Lots of neutrophilsLots of neutrophils

ULCERULCER UlcerUlcer is a focal defect usually on is a focal defect usually on

an epithelial surface where the an epithelial surface where the epithelium is entirely lacking;epithelium is entirely lacking;

the exposed tissue is covered by the exposed tissue is covered by a fibrinopurulent exudate a fibrinopurulent exudate (mixture of fibrin and (mixture of fibrin and neutrophils).neutrophils).

Eg. Peptic ulcer, Ophthus ulcerEg. Peptic ulcer, Ophthus ulcer

CellulitisCellulitis

cellulitiscellulitis denotes a denotes a spreading acute spreading acute inflammation inflammation through interstitial through interstitial tissuestissues