HFRS合并肾病综合征的出血热.ppt

HemorrhagicFeverwithRenalSyndrome DepartmentofInfectiousDiseasesThirdAffiliatedHospitalofSunYat senUniversityLinYang 2 Definition Infectiousdiseaseswithnaturalsource Pathogen Hantanvirus Characterizedbyfever hemorrhage proteinuria shockandacuterenalfailure Fivephasesinthetypicalcases Febrilephase Hypotensive shock phase Oliguricphase Diureticphase Convalescentphase 3 EpidemicHemorrhagicFever EHF SuggestednamebyWHOin1982 HemorrhagicFeverwithRenalSyndrome HFRS 4 Hantanvirus MemberofthefamilyofBunyaviridae FeatureofvirusSingle strandnegativeRNAvirusCircularorovalinshape78 210nmindiameterEnvelopeproteins glycoprotein1 G1 glycoprotein2 G2 Viralgenome RNA LMSgene Etiology 5 ViralproteinsL PolymeraseM EnvelopeproteinG1andG2themembraneantigenG2 containneutrolizationantigen vaccineantigen S Nucleocapsidprotein strongantigenicityandimmunogenicity andcontainingcomplementbindingantigen 6 SerologictypeofHantanvirusOvertwentyserologictypeshantaanvirus typeI HTNV 汉滩病毒 seoulvirus typeII SEOV 汉城病毒 puumalavirus typeIII PUUV 普马拉病毒 prospecthillvirus typeIV PHV 希望山病毒 dobrava belgradevirus DEOV 多布拉伐病毒 7 HumanHFRS causedbyfourtypeofvirus hantaanvirus typeI HTNV seoulvirus typeII SEOV puumalavirus typeIII PUUV dobrava belgradevirus DEOV China HantaanvirusSeoulvirus hantaanvirusandDEOVshowstrongerpathogenicitythantypeIIandIIIvirus 8 ResistanceofvirusLowresistance Inactivatedbyacid pH5 0 ethanol ether chloroform heatin56 Cfor30minor100 Cfor1min Besensitivetoalcoholultravioletrays 9 Epidemiology1 Sourcesofinfection Inourcountry Apodemusagrarius 黑线姬鼠 Musnorvegicus 褐家鼠 Apodemussylvaticus 大林姬鼠 Citellusundulatus 长尾黄鼠 LaboratoryRats Otheranimals catsdogsrabbitsPatients unimportant Infectedfieldrats houserats 10 Apodemusagrarius黑线姬鼠 Musnorvegicus褐家鼠 11 2 Modesoftransmission Five1 Air bornetransmissionviainhaleaerosolcontaminatedwithvirus containingexcretionorsecretionofrats2 Food bornetransmissionviaoralandesophagealmucosa eatfoodcontaminatedwithvirus containingexcretionorsecretionofrats 12 3 InfectionviacontactBebittenbyrats woundiscontaminatedwithvirus containingexcretionsorsecretionsofrats 4 Verticaltransmission mothertobaby veryrare5 Arthropod borne ratsmite redmite harvestmitemaycarryHantanvirus Needtobeconfirmed 13 3 Epidemicfeatures1 Districtlocalization mainlyinAsia EuropeandAfrica AmericaInChina higherincidenceexceptforQinghaiandXizhangprovinces2 SeasonalityMayoccuralltheyear howeverseasonality NovembertoJanuaryandMaytoJulytransmittedbyApodemusagrarius 黑线姬鼠 MarchtoMaytransmittedbyhouserats Epidemicpeak three 14 3 Epidemicformthreekindsofepidemicform sporadic endemic seldomepidemic4 Occupationandage Residentsincountryside urbanandruralworkerMostvictimsareyoungadults 15 4 Susceptibility Susceptibilityisuniversal Lowrateofcovertinfection 3 5 4 3 StableimmunityobtainfromillnessIgGagainsttypeIvirus lastfor1 30yearsIgGagansttypeIIvirus lastless2years 16 PathogenesisPathogenesisofHFRSisnotsoclear Virusistheinitiator Immuneresponses humoralandcellularimmuneresponse bothinvolvesinthepathogenesis 17 1 DirectdamagebyHantanvirusVirusinfection replicationininfectedcells especiallyinendotheliocytesofsmallbloodvessels damageoncells 2 Immune mediateddamageTypeIII I II andIVhypersensitivityreactions CTLreaction mediateddamage Cytokine mediatedcellsdamage 18 1 TypeIIIhypersensitivityreactionHantanvirusinfection inducespecificantibodies immunecomplex activatingcomplements accumulationofimmunecomplexinsmallbloodvessels basementofglomerulusandrenaltubule damage 19 2 OtherhypersensitivityreactionTypeI IgEmediateddamage TypeII linearIgGimmunecomplex accumulationinplateletandbasementmembranesofrenaltubuleTypeIV CD8 cellmediatedimmunedamage 20 3 Cellularimmuneresponse Hantanvirusinfection activationofCD8 Tcells CTLresponse releaselymphokines damage4 Hantanvirus lymphocyteandmacrophage cytokins suchasinterleukin1 IL 1 IFNr tumornecrosisfactor TNF damage 21 Pathophysiology1 ShockPrimaryshockandsecondaryshock2 Hemorrhage3 Acuterenalfailure 22 1 shockVirusandimmuneresponse smallbloodvesseldamage permeabilityofvessel plasmaexudation bloodvolume bloodconcentrate viscosityofblood DIC bloodflow bloodvolume hypotensionshock 23 Secondaryshock OccurindiureticphaseReasons SeverehemorrhageSecondaryinfectionImbalanceoffluid electrolytes 24 2 HemorrhagePetechia ecchymosisinskinandmucosas visceralbleedingReasons Capillarydamage Plateletdecreaseanddysfunction DIC increasedHeparin likesubstance anuria 25 3 AcuterenalfailureReasons Six1 Exudationofplasma bloodvolumebloodconcentrate bloodflowinkidneyglomerularfiltraterate GFR 2 Immune mediatedkidneydamagesmallvesselandrenaltubule3 Renalinterstitialhemorrhageandedema crushrenaltubule 26 4 Renaltissuenecrosis5 ActivationofreninangiotensinII renalarterialcontract renalcortexbloodflow GFR glomerularfiltraterate 6 Renaltubulewasblockedbyproteinsandcasts 27 Pathology1 Organofpathologicaldamage Smallbloodvesselandkidney OtherorgansSuchasheart liverandbrains soon 28 2 Pathologicalfeature pathologicalchangesEndotheliocytesofsmallbloodvesselcongestion edema hemorrhage necrosis pathognomoniclesionofHFRSinkidneys Similarpathologicalchangesinvariousorgans withoutsignificantinflammatoryreaction 29 ClinicalManifestations Incubationperiod 1 2weeks Threemajormanifestations 1 pyrexia intoxication2 hyperemiaandhemorrhage3 hypotensionandrenalmalfunction Fivetypicalphase Fiveclinictypes 30 A Fivetypicalphase1 Febrilephase2 Hypotensive shock phase3 Oliguricphase4 Diureticphase5 Convalescentphase 31 1 FebrilephasePyrexiaIntoxicationsymptomsCapillarydamagesignsKidneydamagesigns ClinicalManifestations 32 1 Febrilephase1 Pyrexiaacuteonset 39oC 40oC lasts3 7daysFeatureofpyrexia Sustainedfeverorremittentfever Formostcases goingtomoreseriouswithpyrexiagraduallydisappeared 33 2 Intoxicationsymptomsa Threeache headache lumbago orbitalpainheadachebecauseofsmallvesselexpansionlumbago orbitalpain becauseofhyperemiaandedemaintissue b Gastrointestinalsymptomshiccupvomitingabdominalpainanddiarrhea 34 3 Capillarydamagesignsa hyperemiaFlushoverface neckandchestskin threeredflush drunkennessb HemorrhageFormostcases petechia ecchymosis orstripe shapedbleedinginchestandbackskin conjunctivableeding Forapartialcases hematuria DIC 35 c Exudativeedemamainlybabularconjunctivaedema palpebraedemaandfaceedema4 KidneydamagesignsProteinuria sometimeswithcasts bloodcellsandmembrane shapedsubstanceconsistingofprotein bloodcellsandmucosalepithelia 36 SummaryinfebrilephasePyrexia threeflush threeache hemorrhageandconjunctivaedema malaise proteinuria sometimeswithcasts bloodcellsandmembrane shapedsubstance 37 38 39 40 2 Hypotensive shock phase1 Occurduringdefeverscencein4to5daysofdiseasescourse lasts1to3days 2 Mainsigns Hypotensionorshock3 nausea vomiting abdominalpain Platelet hematocritvalueproteinuria leukocytosis atypicallymphocytes 10 ClinicalManifestations 41 3 OliguricphaseOliguriaoranuriaUremiaMetabolicacidosisandimbalanceoffluidsandelectrolyte ClinicalManifestations 42 3 OliguricphaseOccurduringorsoonafterhypotensivephase in5to8daysofdiseasescourse lasts2 5days 1 OliguriaoranuriaOliguria urinevolume 500ml 24hAnuria urinevolume 50ml 24h 43 2 Uremiaa gastrointestinalsymptomshiccup vomiting abdominalpain diarrheab Aggravatinghemorrhagehemoptysis 咳血 hematemesis 咯血 hematuria 血尿 ormelenac Nervoussystemsymptoms 44 3 Metabolicacidosisandimbalanceoffluidsandelectrolyte Metabolicacidosis fatalhyperkalemia hypervolemicsyndromeedemaandrestlessnesshighbloodpressureengorgedneckveins 45 4Diureticphase Urine 3000ml 24hOccurin9to14daysofdiseasescourse lastfor1dayorseveralmonths Threephaseaccordingtourinevolumeandazotemiasigns Transitionphase Earlystageofdiureticphase Latestageofdiureticphase ClinicalManifestations 46 1 Transitionphasea Urinefrom500mlto2000ml 24hb BUNandCrpersistentlyc Stateofpatientmaychangetomoreserious moreseriousalthoughurineincrease highmortality 47 2 Earlystageofdiureticphaseurinevolume 2000ml 24hnomarkeddecreaseinazotemia 3 Latestageofdiureticphasea urinevolume 3000ml 24hinmostofcases 4000to8000 24h 15000ml 24hb azotemiaimproving BUNfallingdownc Secondaryshock dehydrationhypokalemia hyponatremia 48 5 Convalescentphaseurinereturnto1000 2000ml 24hnormalappetitetaking1 3monthsforrecovering Fivephasebenotseenineverycase hypotensionand oroliguriaphasemaybeabsentinatypicalcases ClinicalManifestations 49 B Fiveclinictypes1 Mildtype2 Moderate3 Severe4 Veryserious5 Atypicaltype 50 1 Mildtype T 39oC mildintoxicationsymptomswithoutoliguriaandshock 51 2 Moderate T 39oC severeintoxicatingsymptoms drunkenness conjunctivaedema hemorrhage hypotension oliguriaandmarkedproteinuria 52 3 Severe T 40 C moresevereintoxicatingsymptoms shock bleeding oliguriaforlessthan5daysoranuriaforlessthan2days 53 4 Veryserious Thesymptomsandsignsinseveretypewithoneoffollowingsixsigns 1 hard correctiveshock2 bleedinginmainorgan3 acuterenalfailure4 Cardiacfailurepulmonaryedema5 ComplicationinCentralnervoussystem6 Serioussecondaryinfection 54 5 AtypicalT 38 C atypicalsymptoms 55 LaboratoryFinding1 Bloodroutineleukocytosis 15 50 x109 L neutrophilsdominatedinearlystage lymphocytesinlatestage Atypicallymphocytes10 15 hematocritvalueandhemoglobinrise thrombocytopenia 56 2 UrineroutineProteinuria sometimeswithcasts bloodcellsandmembrane shapedsubstance consistingofprotein bloodcellsandmucosalepithelia maybefoundinseconddayofdiseasescourse 57 3 BloodbiochemicalexaminationBUNandCrincreased CO2 CPdecreased hyperkalemiainoliguricphase hypokalemiaindiureticphase 58 4 Bloodcoagulatingfunctionexaminationthrombocytopenia plateletprolongatedPTFibrinogendecreasedsecondaryfibrinlysis 59 5 SerologicaltestsHantanvirusantigenandspecificantibodytestbyIFAT ELISA RIAorWB Antibodyagainstnuclearproteinisusefulfordiagnosis 1 IgMantibody 1 20positive diagnosismarker2 IgGantibody 4times weekusefulfordiagnosis Anti G2 estimateprognosis 6 MolecularbiologicaltestsViralRNAbyRT PCR 60 Complications1 VisceralbleedingIntracraniahemorrhagehemoptysis hematemesis hematuria cerebralhemorrhage 61 2 ComplicationincentralnervoussystemEncephalitisandmeningitisIntracranialhemorrhageandcerebraledema 62 3 Pneumonedemacommonlyoccurinhypotensivephaseandoliguricphase ARDS Mortality 67 Adultrespiratorydistresssyndrome Reasons increasingpermeabilityofthepulmonarycapillarries anddecreasinginalveolarsurfaceactivatingsubstances 63 4 OthersSecondaryinfectionwithbacterialsSpontaneousruptureofthekidneysHepatitis myocarditis pericarditis 64 Diagnosis Epidemiologicdata Clinicalfeature Laboratoryexaminations 65 1 Epidemiologicdataplace season historyofcontactingratsorexcretionandsecretionsofrats 66 2 Clinicalfeaturesthreemanifestationsinearlystageandthecourseoffivephaseintypicalcase Pyrexia threeaches intoxicatingsymptoms Threeflush face neckandchestskin conjunctivacongestionandedema hemorrhage Oliguria renalregionpainonpercussion Fivephaseintypicalcase Fivephaseisnotobservedineverycase hypotensionand oroliguriaphasemaybeabsentinatypicalcases 67 3 Laboratorydata1 BloodLeukocytosisatypicallymphocytes 10 thrombocytopenia 2 Urine proteinuria membrane shapedsubstanceinurine 3 VirusantigenandantibodyViralRNAbyRT PCR 68 Differentialdiagnosis1 Infebrilephasewithcommoncold influenza Septicemia 2 InHypotensivephasewithotherinfectionshock3 Pyrexia intracraniahemorrhageandcerebraledemawithmeningococcalmeningitis 69 4 Oliguriaandrenalfailurewithacutenephritis5 PyrexiaandhemorrhagewithLeptospirosis6 Markedhemorrhagewith thrombocytopenicpurpura gastrointestinalbleedingcausedbygastriculcer 70 PrognosisFatalityisrelatedtoclinicaltype whetherbeingtreatedearlier mortality1 5 majorreasonsfordeath renalfailure cerebralherniasecondarysepticemiamassivebleeding mortalityhigherininfectionwithtypeIvirus 71 Treatment Principleoftreatment Diagnosis restandtreatmentinearly Treatmentinnearhospital 72 Treatment Supportivetreatment Anti viraltherapy Symptomatictreatment 73 1 Supportivetreatmentbedresteasydigestivefoodvitaminsintravenousfluidscontainingsuitableglucose electrolytes 74 2 TreatmentinfebrilephasePrincipleoftreatmenta Anti virustherapyb Reduceexudationofplasmac Reduceintoxicatingsymptomsd PreventingfromDIC 75 1 Anti viraltherapy importantgivinganti virusdruginearlystage Ribavirin virazole 1 0givdripwith10 GSqdfor3 5days2 ReducepermeabilityofsmallvesselandexudationLutinandVitaminC 76 3 Reduceintoxicatingsymptomsa ForhyperpyrexiaPhysicalmeasurestodecreasetemperature Forexample puttingice bagonhead neckorbigvessellocation Avoidingusingheavyantipyreticsb CorticosteroidsforhyperpyrexiaandheavyintoxicatingsymptomsDexamethasone5 10mgiv Dripc c Anti vomiting 20mgofPaspertinimp r n 77 4 PreventionfromDICa ReducethebloodviscosityDanshensolution Dextran40b anti coagulationtherapyHeparinshouldbegivenoncetheCTislessthan3minorAPTTlessthan34seconds 78 3 TreatmentinHypotensivephasePrincipleoftreatment Supplementbloodvolume Correctmetabolicacidosis 79 1 SupplementbloodvolumeA Principle earlyrapidlyadequateB kindsoffluids CrystalloidfluidsandColloidfluidscontainingsuitableglucose electrolytesandvitamins Ringer sSolutionNormalsalinesolutionDextran 20 MannitolPlasma albumin Artificialplasma 80 2 Correctmetabolicacidosis5 sodiumbicarbonatesolution TheamountcalculatedaccordingtoCO2CPvalue 3 Bloodvesselactivatingdrugsforhypotensionandshock aramine dopamine etal 81 4 CorticosteroidsReduceseveretoxemia ReducepermeationofsmallvesselImprovingmicrocirculationoftissue 10 20mgofDexamethasoneisgivenbyintravenousdrip 82 4 TreatmentinoliguricphasePrincipleoftreatment Balanceintra environment Diuretictherapy Catharsistherapyforpreventingfromhypervolemia Dialysistherapy 83 1 Balanceintra environmenta Correctimbalanceoffluidelectrolytes acid baseCloselyobserveandrecordurinevolume Examinebloodbiochemicalparameterandrenalfunctionadjustingamountoffluidandelectrolytes 84 b Reducingproteindegradationandcontrolofazotemia Foodcontaininghighvitaminshighcarbohydrate lowprotein Fortheseriouspatient Supplementglucose200 300geverydaybyintravenousdrip20 25 GSwithinsulin 85 2 Diureticforoliguria20 Mannitolsolution givenintravenouslylasix furosemide giveninjectionintravenouslywithgrudualyincreasingdose andrepeatingevery4to6hoursaccordingtotheurineamounts 3 Catharsistherapyforhypervolemiainducingdiarrheatotakeoutfluidsbyintestinal 50 MagnesiumSulfatesolution20 Mannitolsolution 86 ReducingbloodvolumetherapyForhypervolemiawithcardiacfailureandpulmonaryedema takingout300ml 400mlbloodmaybeuseful usedrarenow 87 4 Dialysistherapyforseriousazotemia veryimportant savelife HemodialysisorPeritonealdialysis 88 MarkerofgivingDialysistherapy Oligurialastsfor4daysoranurialastsfor24hourswithoneoffollowingfivesigns a SeralBUN 28 56mmol L b BUNincreasingmorethan7 14mmol Leveryday C Bloodpotassium 6mmol L d hypervolemiaor andpulmonaryedema e beingterriblefretfulorcerebraledema 89 5 TreatmentinDiureticphasea Keepingbalanceoffluidandelectrolytes b Preventingandtreatmentsecondaryinfection antibiotics 90 6 Convalescentphasea Supplementnutritionfood b Examiningofrenalfunction bloodpressure pituitaryfunctionatregularinterval 91 7 Complicationstreatment1 HemostaticstherapyforheavybleedingsuchasgastrointestinalhemorrhagetreatmentofDIC accordingtodifferentphaseofDIC givingEACA protamine respectively 92 2 TreatmentARDSa Controlofamountofintravenousinfusion b Givingoxygen ormechanicalventilation positiveendexpiratorypr