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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