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InflammationInflammation

Blagoi Marinov, MD, PhDBlagoi Marinov, MD, PhDPathophysiology Dept.Pathophysiology Dept.

Medcal University of PlovdivMedcal University of Plovdiv

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DefinitionDefinition

nn AA formform ofof nonnon--specificspecific reactivity,reactivity, evolutionallyevolutionallydevelopeddeveloped inin multicellularmulticellular organismsorganisms.. ..

nn CommonCommon pathologicpathologic processprocess developingdeveloping inin thethevascularizedvascularized tissuestissues andand associatedassociated withwithcellularcellular damagedamage..

nn AcuteAcute inflammationinflammation isis aa selfself--containingcontaining processprocessii..ee.. itit persistspersists tilltill thethe causecause isis removedremoved..

“The individuality of the cause “fades” in the uniformity of the response !

DeterminationDetermination

TheThe biologicbiologic naturenature ofof inflammationinflammation isisremovalremoval andand containmentcontainment ofof thethe pathogenicpathogenicagentsagents whichwhich causecause itit.. ItIt developsdevelops inin threethree(in)distinct(in)distinct phasesphases..

nn AlterationAlterationnn Exudation and emigrationExudation and emigrationnn ProliferationProliferation

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Inflammation Inflammation –– entity or discreet entity or discreet processprocess

Alteration

Exudation

Proliferation

Alteration

Exudation

Proliferation

Variety of etiologic factorsVariety of etiologic factors

ExogenousExogenousBiologic factorsBiologic factors

Physical factorsPhysical factors

Chemical factorsChemical factors

Mechanical factorsMechanical factors

EndogenousEndogenousHypoxiaHypoxiaSecretionsSecretions

§§ BileBile§§ UreaUrea§§ Uric acidUric acid

DepositionsDepositions§§ SaltsSalts§§ Toxic compoundsToxic compounds§§ Immune complexesImmune complexes

Immune reactionsImmune reactions

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nn AlterationAlterationnn Exudation and emigrationExudation and emigrationnn ProliferationProliferation

AlterationAlteration((damagedamage))

Forced death of cells (tissues)Forced death of cells (tissues)

Cause Reversible damage

(DYSTROPHY)

Irreversible damage

(ALTERATION)

INFLAMMATIONАpoptosisRECOVERY

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Progression of alterationProgression of alteration

nn PrimaryPrimarynn Causally determinedCausally determinednn Direct injurious action of the pathogenic agentDirect injurious action of the pathogenic agent

nn SecondarySecondarynn MediatorsMediatorsnn MetabolitesMetabolitesnn Damage of lysosomal membranesDamage of lysosomal membranesnn Free radicalsFree radicalsnn AcidosisAcidosis

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nn AlterationAlterationnn Exudation and emigrationExudation and emigrationnn ProliferationProliferation

Exudation and emigrationExudation and emigrationnn VasomotorVasomotor changeschanges

nn TransientTransient vasoconstrictionvasoconstriction ofof arteriolesarteriolesnn AcceleratedAccelerated bloodblood flowflow inin arteriolesarteriolesnn DilationDilation ofof arteriolesarteriolesnn RecruitmentRecruitment ofof newnew ((nonnon--functioning)functioning) capillariescapillariesnn ObstructedObstructed venousvenous flowflow

nn IncreasedIncreased vascularvascular permeabilitypermeability withwith formationformationofof inflammatoryinflammatory secretionssecretions -- exudateexudate

nn LeukocyteLeukocyte emigrationemigrationnn MarginalMarginal positionpositionnn ExtravasationExtravasationnn ActivationActivation

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1. Vasodilatation

2. Exudation - Edema

3. Emigration of cells

4. Chemotaxis

5. Phagocytosis

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Biologic significance of Biologic significance of exudationexudation

nn Dilutes the pathogenic agentDilutes the pathogenic agent

nn Accelerates lymphatic out flowAccelerates lymphatic out flow

nn Increases the quantity of plasma at the Increases the quantity of plasma at the site of the damagesite of the damage

nn ImmunoglobulinsImmunoglobulinsnn ComplementComplementnn Coagulation factorsCoagulation factors

Local signs of inflammationLocal signs of inflammation

Celsus Celsus презпрез 3030 г.г. пр.н. ерапр.н. ера::nnRuborRubor -- rednessrednessnnTumorTumor -- edemaedemannCalorCalor -- warmingwarmingnnDolorDolor -- painpain

Virchow Virchow презпрез 1858 :1858 :

nnFunctio laesaFunctio laesa –– loss of functionloss of function

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Heat Redness Swelling Pain Loss Of Func.

The 5 Cardinal Signs of The 5 Cardinal Signs of

FurunculusFurunculus

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General signs of inflammationGeneral signs of inflammation

n Fevernn AsthenoAstheno--adinamic syndromeadinamic syndrome

loss of appetite, fatigue, somnolence, prostrationloss of appetite, fatigue, somnolence, prostrationnn BloodBlood ((biochemicalbiochemical) ) changeschanges

Leuc Leuc ↑↑, , CRPCRP ↑↑, fibrinogen, fibrinogen ↑↑,, FeFe ↓↓ ((anemiaanemia))nn Endocrine changesEndocrine changes

HypothalamoHypothalamo--pituitary axispituitary axis ↑↑Sympathetic nervous systemSympathetic nervous system ↑↑

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Cells involved in the Cells involved in the inflammatory responseinflammatory response

nn NeutrophilsNeutrophils (24 (24 hh))nn MacrophagesMacrophages (24(24--48 48 hh))nn Activated lymphocytesActivated lymphocytesnn CD8+ T CD8+ T cellscellsnn B B lymphocyteslymphocytes (PL)(PL)

Mediators of inflammationMediators of inflammationHistamine,serotonin

Calicrein-kinin system(bradikinin)

Complement system

Prostaglandins (Pg)Leucotriens (LT)

PAF

Inflammatory cytokines

(IL-1, TNFα)

Degranulation of mastocytes

Increased vascular permeability

Contraction of smooth muscle cells

Pain

Chemotaxis for Neu, Mo

minutes

hours

days

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nn AlterationAlterationnn Exudation and emigrationExudation and emigrationnn ProliferationProliferation

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ProliferationProliferation

nn Debridement phaseDebridement phase (Мо, (Мо, MacrophagesMacrophages))nn Proliferative phaseProliferative phase

Fibroblastic reactionFibroblastic reactionAngioblastic reactionAngioblastic reaction

Regeneratio ad integrumRegeneratio ad integrumCicatrixCicatrix

Starts from the peripheryStarts from the periphery

Development of inflammationDevelopment of inflammation

Localinflammation

Generalized inflammation(Sepsis or polyorgan failure)

Systemic inflammation

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Inflammation OutcomeInflammation Outcome ::

nn Restitutio ad integrumRestitutio ad integrumnn Healing wit consequencesHealing wit consequencesnn AbscessAbscess, , phlegmonphlegmonnnGeneralizationGeneralization ((diseasedisease))nn ChronificationChronificationnn DeathDeath

FactorsFactors, , determining the determining the outcome of inflammationoutcome of inflammation::

nn Nature of inflammatory agentNature of inflammatory agentØØ VirulenceVirulence, , dosedose, , entry pointentry point

nn Reactivity of the organismReactivity of the organismØØ ImmunityImmunity, , ageage, , tempertemper

n Site of the processSite of the process

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ThermoregulationThermoregulationandand

FEVERFEVER

Range of Human Body Core TemperatureRange of Human Body Core Temperature

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Processes of heat dissipationProcesses of heat dissipation

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FEVERFEVER

Common pathologic process in Common pathologic process in homoeothermic animals and manhomoeothermic animals and man

Fever Fever -- characteristicscharacteristics

nn TemporaryTemporary reorganizationreorganization inin thethethermoregulatorythermoregulatory centercenter

nn TheThe corecore temperaturetemperature isis notnot influencedinfluencedbyby thethe environmentalenvironmental temperaturetemperature butbutdiurnaldiurnal variationsvariations stillstill existexist

nn FeverFever isis causedcaused byby pyrogenspyrogens

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EtiologyEtiology

nn Exogenous pyrogensExogenous pyrogensnn BacterialBacterial

nn LipopolisacharideLipopolisacharide ((endotoxins of Grendotoxins of Gr--))nn NonNon--bacterialbacterial

nn Toxic elementsToxic elements (Pb)(Pb)nn Synthetic hormonesSynthetic hormonesnn Hypertonic salineHypertonic saline

nn Endogenous pyrogensEndogenous pyrogensnn ILIL--1, 1, αα interferoninterferonnn THF THF αα

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Fever Fever -- stagesstages

nn Increase in body temperatureIncrease in body temperaturenn Stadium incrementiStadium incrementi

nn Increased body temperatureIncreased body temperaturenn Stadium fastigiiStadium fastigii

nn Decrease in body temperatureDecrease in body temperaturenn Stadium decrementiStadium decrementi

Fever stages

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Fever Fever -- degreesdegrees

nn SubfebrileSubfebrile –– toto 3838°° ССnn Moderately highModerately high –– toto 39 39 °° ССnn HighHigh fromfrom 3939°° С С toto 40 40 °° ССnn HyperpyreticHyperpyretic aboveabove 41 41 °° СС

Temperature curvesIntermittent

Remittent

Sustained

Recurrent

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Decrease of elevated temperatureDecrease of elevated temperature

nn LythicLythic –– slowlyslowly, , graduallygradually

nn CriticCritic –– jeopardy of acute failure of the jeopardy of acute failure of the circulationcirculation

Metabolism in feverMetabolism in fever

nn Increased glycolysisIncreased glycolysisnn Hyperlipidemia with increased Hyperlipidemia with increased ββ--oxidation oxidation

of ketone bodiesof ketone bodiesnn Lowering of Lowering of рН рН and development of and development of

acidosisacidosisnn Negative NNegative N--balancebalancenn Electrolyte disturbancesElectrolyte disturbances

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Systemic effects in feverSystemic effects in fever

nn CardioCardio--vascular systemvascular system((tachycardiatachycardia: 1: 1ооСС→→15 15 beatsbeats; ; disturbances of disturbances of

cardiac rhythm and conductancecardiac rhythm and conductance))nn Respiratory systemRespiratory system ((hyperventilationhyperventilation))nn Digestive systemDigestive system ((loss of appetite, loss of appetite,

constipationconstipation))nn CNS CNS ((insomnia, hallucinationsinsomnia, hallucinations, , deliriumdelirium, ,

seizuresseizures))nn SkinSkin ((rednessredness, , drydry →→ moistmoist))

General signs of feverGeneral signs of fevern Headachen Astheno-adynamic syndrome

БезапетитиеБезапетитие , умора, сънливост, отпадналост, умора, сънливост, отпадналостnn BloodBlood (biochemical) changes(biochemical) changes

Leuc Leuc ↑↑, , CRPCRP ↑↑, fibrinogen, fibrinogen ↑↑,, FeFe ↓↓ ((anemiaanemia))nn Endocrine changesEndocrine changes

HypotalamoHypotalamo--pituitary axispituitary axis ↑↑Sympathetic nervous systemSympathetic nervous system ↑↑ ↑↑

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Biologic significance of feverBiologic significance of feverDerangementsDerangements ofof thethe functionfunction ofof organsorgans andandtissuestissues dependdepend onon thethe degreedegree ofof elevationelevation ofofbodybody temperaturetemperature andand thethe mainmain diseasedisease..

TheThe feverfever cancan bebe regardedregarded asas::

nn Defensive and adaptive reactionDefensive and adaptive reactionnn Pathologic reactionPathologic reaction

Defensive and adaptive Defensive and adaptive reactionreaction

nn Suppression of microbial reproductionSuppression of microbial reproductionnn Synthesis of immunoglobulins by the Synthesis of immunoglobulins by the ВВ--cellscells and and ТТ--cell proliferationcell proliferation

nn Stimulation of haemopoesisStimulation of haemopoesisnn Stimulation of hypotalamoStimulation of hypotalamo--pitutary axispitutary axis

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Benefits of fever against Benefits of fever against infectioninfection

n May inhibit microbial growth (temp sensitive)

n Lymphocyte mobility and transformation (Cellular and humoral immunity)

n Ion chelating “siderophores” necessary for microbial replication is reduced in higher temp

Pathologic reactionPathologic reaction

nn Derangements in metabolismDerangements in metabolism

nn Fast exhaustion of compensationsFast exhaustion of compensations

nn High temperatures suppress immunityHigh temperatures suppress immunity

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TreatmentTreatmentnnEtiologicEtiologicnn SymptomaticSymptomaticnn NSAIDsNSAIDs ––

Caution should be applied in case of children Caution should be applied in case of children underunder 12 12 years of ageyears of age..

nn Proper feeding and hydrationProper feeding and hydrationadditional additional 500 500 mlml for everyfor every ↑↑ 11o o СС

Thank youThank you