Dr. RoopaDr. Roopa

InflammationInflammation

Thought for todayThought for today

“ “ The investment u make in yourself The investment u make in yourself must receive “ top priority “. When u must receive “ top priority “. When u Grow your entire world expands…. Grow your entire world expands…. When u do not grow your whole When u do not grow your whole world starts to become ‘very world starts to become ‘very small’….. That smallness reflects in small’….. That smallness reflects in all areas of life including your all areas of life including your income.”income.”

What is inflammation?What is inflammation?

Vascular response to injury

Causes of inflammationCauses of inflammation

InfectionInfection TraumaTrauma Thermal sourcesThermal sources Ionizing radiationIonizing radiation Chemical sourcesChemical sources Immunologic causesImmunologic causes Tissue deathTissue death

Types of InflammationTypes of Inflammation

Acute Acute

ChronicChronic

PRINCIPAL CELL EFFECTORSPRINCIPAL CELL EFFECTORS

11stst 24 hours: NEUTROPHILS 24 hours: NEUTROPHILS Bacterial infections, infarctionBacterial infections, infarction Come from the bone marrow reserve Come from the bone marrow reserve

poolpool Band neutrophils: less mature cellsBand neutrophils: less mature cells

22ndnd-3-3rdrd day: neutrophils are replaced day: neutrophils are replaced by monocytes-macrophagesby monocytes-macrophages

Tuberculosis, salmonellosisTuberculosis, salmonellosis

EosinophilsEosinophils

Allergic reactionsAllergic reactions Parasitic infectionsParasitic infections Hodgkin lymphomaHodgkin lymphoma

Mast cells and basophilsMast cells and basophils

Chronic myelogenous leukemiaChronic myelogenous leukemia Myeloproliferative diseasesMyeloproliferative diseases histaminehistamine

Cellular response of Cellular response of leukocytesleukocytes

EmigrationEmigrationMarginationMarginationPavementingPavementingRolling/TumblingRolling/TumblingAdhesionAdhesionTransmigrationTransmigration

ChemotaxisChemotaxis PhagocytosisPhagocytosis

OpsonizationOpsonization Intracellular microbial killingIntracellular microbial killing

Oxygen-dependentOxygen-dependentOxygen-independentOxygen-independent

MARGINATION AND MARGINATION AND ROLLINGROLLING

.with increased vascular permeability, fluid .with increased vascular permeability, fluid leaves the vessel causing leukocytes to settle leaves the vessel causing leukocytes to settle out of the central column and ‘marginate’ out of the central column and ‘marginate’ along the endothelial surface.along the endothelial surface.

.endo. Cells &leukocytes have complementary .endo. Cells &leukocytes have complementary surface adhesion molecules which briefly surface adhesion molecules which briefly stick &release causing the leukocyte to roll stick &release causing the leukocyte to roll along the endothelium.along the endothelium.

DIAPEDESISDIAPEDESIS

INSINUATION OF THE INSINUATION OF THE NEUTROPHILS NEUTROPHILS THRU THE THRU THE ENDOTHELIAL CELLSENDOTHELIAL CELLS

BASEMENT MEMBRANEBASEMENT MEMBRANE

EXTRAVASCULAR TISSUESEXTRAVASCULAR TISSUES

CHEMOTAXISCHEMOTAXIS

NEUTROPHIL DIRECT ITS NEUTROPHIL DIRECT ITS MIGRATION TOWARDS THE MIGRATION TOWARDS THE CHEMOATTRACTANTCHEMOATTRACTANT

MARGINATION, CHEMOTAXIS AND MARGINATION, CHEMOTAXIS AND DIAPEDESIS CAN DELIVER HUGE DIAPEDESIS CAN DELIVER HUGE NUMBERS OF NEUTROPHILS IN A FEW NUMBERS OF NEUTROPHILS IN A FEW HOURSHOURS

PUS:CELLULAR ACUTE PUS:CELLULAR ACUTE INFLAMMATORY EXUDATE WITH PMN INFLAMMATORY EXUDATE WITH PMN CELLS AND CELLULAR DEBRISCELLS AND CELLULAR DEBRIS

PHAGOCYTOSISPHAGOCYTOSIS

FORMATION OF PHAGOSOMEFORMATION OF PHAGOSOME

LYSOSOMELYSOSOME

PHAGOLYSOSOMEPHAGOLYSOSOME

Intracellular microbial killing:Intracellular microbial killing:

Oxygen-dependent killing is the Oxygen-dependent killing is the MOST important microbial processMOST important microbial process

Phagocytosis activates HMP shunt Phagocytosis activates HMP shunt

oxidative burstoxidative burst

suppplies electrons to NADPH oxidasesuppplies electrons to NADPH oxidase

superoxide anionsuperoxide anion

Hydrogen peroxideHydrogen peroxide

Hydrogen peroxideHydrogen peroxide

Oxides microbial proteins and Oxides microbial proteins and disrupts cell wallsdisrupts cell walls

Myeloperoxidase-halide system of Myeloperoxidase-halide system of bacterial killingbacterial killing

DEGRANULATIONDEGRANULATION THE TOXIC SUBSTANCES MAY CAUSE THE TOXIC SUBSTANCES MAY CAUSE

LOSS OF FUNCTION (FUNCTIO LAESA)LOSS OF FUNCTION (FUNCTIO LAESA)

INCREASED BLOOD FLOW DUE TO INCREASED BLOOD FLOW DUE TO RELAXATION OF THE TERMINAL RELAXATION OF THE TERMINAL ARTERIOLES ARTERIOLES

RUBOR AND CALORRUBOR AND CALOR

CONTRACTION OF CAPILLARY CONTRACTION OF CAPILLARY ENDOTHELIAL CELLSENDOTHELIAL CELLS

INCREASED VASCULAR INCREASED VASCULAR PERMEABILITYPERMEABILITY

SWELLINGSWELLING

TUMORTUMOR

MILDEST: EXTRAVASATION OF MILDEST: EXTRAVASATION OF WATER, LOW MOLECULAR WEIGHT WATER, LOW MOLECULAR WEIGHT PROTEINSPROTEINS

MODERATE: + HMW PROTEINSMODERATE: + HMW PROTEINS SEVERE: + BLOOD CELLSSEVERE: + BLOOD CELLS

Calor Rubor Tumor Dolor Functio laesa

MEDIATORS OF ACUTE MEDIATORS OF ACUTE INFLAMMATIONINFLAMMATION

Exogenous:Exogenous:microbial productsmicrobial products

Endogenous:Endogenous:1. vasoactive amines1. vasoactive amines

histaminehistamineserotoninserotonin

2. Arachidonic acid metabolites2. Arachidonic acid metabolitescyclooxygenase pathwaycyclooxygenase pathwaylipooxygenase pathwaylipooxygenase pathway

3. Cytokines3. Cytokines4. Kinin system4. Kinin system5. Complement system5. Complement system

HistamineHistamine

increase capillary permeabilityincrease capillary permeability

contracts postcapillary venulescontracts postcapillary venules Source: basophils, mast cells,plateletsSource: basophils, mast cells,platelets Stimuli:Stimuli:

binding of IgEbinding of IgE

binding of C3a and binding of C3a and C5a:”anaphylotoxins”C5a:”anaphylotoxins”

heat, coldheat, cold

Interleukin-1Interleukin-1

SerotoninSerotonin

5-hydroxytryptamine5-hydroxytryptamine Action: similar to histamineAction: similar to histamine Source: plateletsSource: platelets

Arachidonic acid Arachidonic acid metabolitesmetabolites

Cyclooxygenase Cyclooxygenase pathwaypathway

Enzymes:COX-1,COX-2Enzymes:COX-1,COX-2 Products:Products:

1.1. Platelet TxA2Platelet TxA2

--vasoconstrictor,platelevasoconstrictor,platelet aggregatort aggregator

2. Endothelial prostacyclin2. Endothelial prostacyclin

-vasodilator,inhibits -vasodilator,inhibits platelet aggregationplatelet aggregation

Lipooxygenase Lipooxygenase pathwaypathway

Products: Products: hydroperoxyeicosatetrhydroperoxyeicosatetraenoic acid (HPETE)aenoic acid (HPETE)

5-HPETE5-HPETE

-leukotrienes-leukotrienes

Important leukotrienesImportant leukotrienes

LTB4: chemotactic for neutrophilsLTB4: chemotactic for neutrophils

LTC4,LTD4,LTE4LTC4,LTD4,LTE4““slow reacting substance of slow reacting substance of anaphylaxis”anaphylaxis”vasodilatationvasodilatationbronchoconstrictionbronchoconstrictionincrease capillary permeabilityincrease capillary permeability

CytokinesCytokines Soluble proteinsSoluble proteins Secreted by numerous cells(monocytes-Secreted by numerous cells(monocytes-

macrophages)macrophages) Act as “effector molecules”Act as “effector molecules” IL-1 and TNF are major cytokines, that mediate IL-1 and TNF are major cytokines, that mediate

inflam..inflam.. Induce the systemic“acute phase response”Induce the systemic“acute phase response” Fever, increase WBC, loss of appetite. Fever, increase WBC, loss of appetite. Synthesis of C-reactive proteins, complement Synthesis of C-reactive proteins, complement

components, fibrinogen, prothrombincomponents, fibrinogen, prothrombin Synthesis of adhesion moleculesSynthesis of adhesion molecules Neutrophil degranulationNeutrophil degranulation

Kinin systemKinin system

Formed during active secretion in Formed during active secretion in sweat glands, salivary glands, sweat glands, salivary glands, pancreas, kidneyspancreas, kidneys

End product: bradykininEnd product: bradykinin Actions: vascular permeabilityActions: vascular permeability

arteriolar dilationarteriolar dilation

painpain

Complement systemComplement system

20 Plasma proteins20 Plasma proteins HEPATOCYTES,MACROPHAGES,HEPATOCYTES,MACROPHAGES,GIT GIT

CELLSCELLS

Action: cell lysisAction: cell lysis

COMPLEMENT CASCADECOMPLEMENT CASCADE

classical pathwayclassical pathway

alternative pathwayalternative pathway

OPSONIZE BACTERIAOPSONIZE BACTERIA ACTIVATE PMN, MACROPHAGESACTIVATE PMN, MACROPHAGES REGULATES AB RESPONSEREGULATES AB RESPONSE CLEARS AWAY IMMUNE COMPLEXESCLEARS AWAY IMMUNE COMPLEXES INFLAMMATION, TISSUE DAMAGEINFLAMMATION, TISSUE DAMAGE ANAPHYLAXISANAPHYLAXIS

MAC

Classical pathway vs Classical pathway vs alternative pathwayalternative pathway

Starts with C1 + antigen-antibodyStarts with C1 + antigen-antibody Ends with the membrane attack complexEnds with the membrane attack complex

Bacterial surface activates the pathwayBacterial surface activates the pathway Works in the absence of antibodiesWorks in the absence of antibodies Less efficient Less efficient

C3b: opsoninC3b: opsonin C3a and C5a: anaphylotoxinsC3a and C5a: anaphylotoxins C5b-C9: “MAC”C5b-C9: “MAC”

membrane attack complexmembrane attack complex

OUTCOMES OF ACUTE OUTCOMES OF ACUTE INFLAMMATIONINFLAMMATION

Resolution of tissue structure and Resolution of tissue structure and functionfunction

Tissue destruction and persistent Tissue destruction and persistent acute inflammationacute inflammation

abscessabscessulcerulcerfistulafistulascarscar

Convert to chronic inflammationConvert to chronic inflammation

ABSCESSABSCESS

Cavity filled with Cavity filled with puspus

Pus: neutrophils, Pus: neutrophils, monocytes and monocytes and cellular debriscellular debris

Fibrous wallFibrous wall Inaccessible to Inaccessible to

circulationcirculation Bacterial infections, Bacterial infections,

especially especially staphylococcistaphylococci

UlcerUlcer

Involves epithelial surfacesInvolves epithelial surfaces Loss of surface epitheliumLoss of surface epithelium

FistulaFistula

Abnormal communication between 2 Abnormal communication between 2 organs organs

or or

between an organ and a surfacebetween an organ and a surface

ScarScar

Final result of tissue destructionFinal result of tissue destruction Distortion of structureDistortion of structure Altered functionAltered function

CHRONIC INFLAMMATIONCHRONIC INFLAMMATION

Occurs when the injury is persistent Occurs when the injury is persistent or recurring; or when the or recurring; or when the inflammatory reaction is insufficient inflammatory reaction is insufficient to completely degrade the agent to completely degrade the agent which triggered the inflammatory which triggered the inflammatory reactionreaction

May also occur de novoMay also occur de novo

Patterns of chronic Patterns of chronic inflammationinflammation

Chronic nonspecific inflammationChronic nonspecific inflammation

Granulomatous inflammationGranulomatous inflammation

Chronic nonspecific Chronic nonspecific inflammationinflammation

Proliferation of fibroblasts and new Proliferation of fibroblasts and new vesselsvessels

Increased macrophages, lymphocytes, Increased macrophages, lymphocytes, plasma cellsplasma cells

Macrophage+antigen B lymphocyte Macrophage+antigen B lymphocyte activation antibody-producing activation antibody-producing plasma cellsplasma cells

Scarring and distortion of tissue Scarring and distortion of tissue architecturearchitecture

Granulomatous Granulomatous inflammationinflammation

Granuloma: nodular collection of Granuloma: nodular collection of macrophages called “epitheloid cells”macrophages called “epitheloid cells”

Surrounded by rim of lymphocytesSurrounded by rim of lymphocytes Macrophage+antigen presented Macrophage+antigen presented

to CD4+lymphocytes release of to CD4+lymphocytes release of cytokines cytokines monocytes/macrophages transform monocytes/macrophages transform epitheloid cells and giant cells epitheloid cells and giant cells

Most characteristic: CASEOUS NECROSISMost characteristic: CASEOUS NECROSIS Multinucleated giant cellsMultinucleated giant cells

Langhans giant cellsLanghans giant cells

foreign body giant cellforeign body giant cell TB, fungal infections, Syphyllis, cat-scratch TB, fungal infections, Syphyllis, cat-scratch

fever, foreign bodiesfever, foreign bodies

HEALINGHEALING

REPAIR + REGENERATIONREPAIR + REGENERATION

NEW EPITHELIUM GROWTHNEW EPITHELIUM GROWTH

WOUND HEALINGWOUND HEALING

PRIMARY INTENTIONPRIMARY INTENTION SECONDARY INTENTIONSECONDARY INTENTION THIRD INTENTIONTHIRD INTENTION

STEPS IN WOUND HEALINGSTEPS IN WOUND HEALING

COAGULATIONCOAGULATION

HEMORRHAGEHEMORRHAGE

CLOT FORMATIONCLOT FORMATION

FIBRIN, PLATELETSFIBRIN, PLATELETS

HEMOSTASISHEMOSTASIS

INFLAMMATIONINFLAMMATION

LOCAL VASOCONSTRICTIONLOCAL VASOCONSTRICTION

VASODILATATIONVASODILATATION

INCREASED CAPILLARY INCREASED CAPILLARY PERMEABILITYPERMEABILITY

PAINPAIN

NEUTROPHILS 24-48 HRSNEUTROPHILS 24-48 HRS

MACROPHAGES 48 HRS-72 HOURSMACROPHAGES 48 HRS-72 HOURS

FIBROBLASTS 5 -7DAYSFIBROBLASTS 5 -7DAYS

FIBROBLASTS MIGRATEFIBROBLASTS MIGRATE SECRETE FIBRIN, PROTEOGLYCANSSECRETE FIBRIN, PROTEOGLYCANS UNITES WOUND EDGESUNITES WOUND EDGES

ANGIOGENESISANGIOGENESIS

EPITHELIALIZATION IN 24-48 HOURSEPITHELIALIZATION IN 24-48 HOURS THICKENING OF THE BASAL CELL THICKENING OF THE BASAL CELL

LAYER-1LAYER-1STST SIGN SIGN

COLLAGEN SYNTHESIS 3-5 DAYS COLLAGEN SYNTHESIS 3-5 DAYS POST INJURYPOST INJURY

WOUND CONTRACTION IN A WOUND CONTRACTION IN A CENTRIPETALCENTRIPETAL FASHIONFASHION

6 WEEKS, 80-90% WOUND 6 WEEKS, 80-90% WOUND STRENGTHSTRENGTH

HYPERTROPHIC SCARHYPERTROPHIC SCAR

RAISED, ERYTHEMATOUS, RAISED, ERYTHEMATOUS, PRURITIC LESIONSPRURITIC LESIONS

LIMITED MARGINS LIMITED MARGINS 6 WKS TO 6 MONTHS6 WKS TO 6 MONTHS

CAUSES OF HYPERTROPHIC CAUSES OF HYPERTROPHIC SCARSCAR

FOREIGN BODY IN THE WOUNDFOREIGN BODY IN THE WOUND SCRATCHINGSCRATCHING HEMATOMAHEMATOMA SECONDARY INTENTIONSECONDARY INTENTION EXCESSIVE TENSIONEXCESSIVE TENSION INADEQUATE WOUND CLOSUREINADEQUATE WOUND CLOSURE

KELOIDSKELOIDS

ERYTHEMATOUS, PRURITIC LESIONS ERYTHEMATOUS, PRURITIC LESIONS SPREAD INTO THE DERMIS AND SPREAD INTO THE DERMIS AND

SUBCUTANEOUS TISSUESSUBCUTANEOUS TISSUES LOCALLY INVASIVE BENIGN LOCALLY INVASIVE BENIGN

NEOPLASTIC TISSUENEOPLASTIC TISSUE RARELY REGRESSRARELY REGRESS