《传染病学教学课件》7、流行性出血热.pptx

Hemorrhagic Fever with Renal Syndrome Zhang Dazhi,M.DDepartment of Infectious DiseaseThe second hospital of CMUOverviewPathogen:Hantaviruses Clinical features:fever；renal failure；shock;hemorrhagic manifestationsHemorrhagic fever with renal syndrome(HFRS)includes a group of clinically similar illnesses nEpidemic hemorrhagic fever(China)nKorean hemorrhagic fever(Korean)nNephropathis epidemica(PuumalaVirology of HantaviruseBelong to the family Bun-yaviridaeSpherical enveloped viruses about 80-120 nm in diameterGenome consists of three single-stranded,negative sense RNA segments-S,M,Ln S(small):encodes neucleocapsid proteinn M(medium):encodes envelope glycoproteinn L(large):encodes polymeraseThe viruses that cause hemorrhagic fever with renal syndrome include:nHantaannDobrava-BelgradenSeouln PuumalaSin Nombre virus can cause hantavirus pulmonary syndrome(America)Virology of HantaviruseEpidemiology Sources of transmission:rodent reservoirs Virus speciesReservoirEpidemic&endemic areasHantaan Striped field mouse(Apodemus agrarius)Korea,China,Eastern Russia SeoulNorway rat(Rattus norvegicus)WorldwidePuumalaBank voles(Clethrionomys glareolus)Western Europe Dobrava-BelgradeYellow-necked field mouse(Apodemus flavicollis)BalkansStriped field mouse Norway rat Bank voles Yellow-necked field mouse pOccurs mainly in Europe and Asia Striped field mouseApodemus agrarius Norway rat Rattus norvegicus,Bank volesClethrionomys glareolusYellow-necked field mouseA.flavicollisEpidemiology Route of transmissionnExposure to aerosolized urine,droppings,or saliva of infected rodentsnDirect introduction of infectious material through broken skin or onto mucous membranes nThrough rodent bites from infected animalsnFrom mother to childnTransmission from human to human is extremely rare.Epizootic CycleRodent breedingEpidemiologySusceptibility of populationnPeople are generally susceptiblenCommonly reported in male adultnSubclinical infection rate is 2.54.3%nStable and persistent immunity PathogenesisImmune mechanisms may play an major pathogenic rolenViremia is only present in early stage of infection No cytopathic effectnAt the time that severe symptoms begin Viremia is absentSpecific antibodies and T cells are detectedmarked cytokine production,kallikrein-kinin activation,complement pathway activationPathogenesisBasic pathological changes Systemic microvascular endothelial edema,degeneration and necrosisThe most dramatic damage is seen in the kidneysImmune mediated vascular endothelial injury Increased capillary permeabilityPlasma extravasationInsufficient blood volumePrimary shockoccurs before oliguric stageMassive hemorrhageorSecondary infectionorInsufficient water-electrolyte supply during polyuric stageInsufficient blood volumeSecondary shock:occurs after oliguric stagePathogenesis:shockPathogenesis:hemorrhage tendencyDamage of the blood vessel wallThrombocytopenia Uremic bleeding defectsIncrease of heparinlike substances DIC Decreased blood flow Direct injury to the kidneyPathogenesis:acute renal failure Histopathologic changes in kidney(cortex)Small arrow:interstitial edema with mild infiltration of mononuclear cellsLarge arrow:degeneration of renal tubules Arrow head:proteinaceous casts and exudate Histopathologic changes in kidney(medulla)Most prominent change in the medulla is welldefined necrotic lesion(asterisk)*Intracranial hemorrhage in HFRS patientClinical Manifestations:overviewIncubation period:usually 1 to 2 weeksA triad of fever,hemorrhage,and renal insufficiency5 progressive stages:Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stageSkipping of phase is common in atypical and mild individuals.The individual phases may overlap in severe cases.Clinical Manifestations:Febrile stageAbrupt onset of fever lasting 3-7 daysGastrointestinal discomfort Anorexia,nausea,vomiting and abdominal pain Systemic toxic symptoms Myalgia,triad of pains(Headache,lumbago and retroorbital pain)Clinical Manifestations:Febrile stageSigns of Capillary injuryn Congestionn Hemorrhagic tendencyn Exudation and edemaClinical Manifestations:Febrile stageCongestionnDermathemia:triad of flushings Flushing over Face,the V area of the neck(drunken face),and the backnMucosal hyperemia Conjunctival suffusion,pharyngeal injectionDrunken faceClinical Manifestations:Febrile stageHemorrhagic tendencynDermatorrhagia Petechiae often develop in areas of pressure,axilla Ecchymosis in severe case nMucosal bleeding Petechiae in the conjunctivae,soft palatenVisceral bleeding Epistaxis,bloody stool,hemoptysis,cerebral bleedingPetechiae on axillaEcchymosis in severe caseSubconjunctival hemorrhagePetechiae on the soft palateClinical Manifestations:Febrile stageExudation and edema cause painnPeriorbital edema,chemosis nRetroperitoneal edemanAscitespAbdominal pain:Differential diagnosis?chemosisClinical Manifestations:Hypotensive stageLasts approximately a few hours to 2 daysExacerbation of the disease after defervescenceFalling blood pressure and Tachycardia In severe case shock(primary shock)Clinical Manifestations:Oliguric stagePersists for 2-5 days Oliguria:urine output 400 ml/d Anuria:urine out put2000ml;stabilization of the azotemianLate polyuric stage:Daily urine volume 3000ml;recover of the azotemiaFluid replacement is inadequate secondary shockClinical Manifestations:Convalescent stagelast for as long as 1-3 monthsDaily urine volume returns to normalClinical ManifestationsWhat are five progressive stages of HFRS?Febrile stage;Hypotensive stage;Oliguric stage;Polyuric stage;Convalescent stageLaboratory findingsBlood routine testnLeukocytosis with a left shiftnElevated hematocrit levernThrombocytopenianAtypical lymphocytes Q:Viral infections causing leukocytosisuHFRSuInfectious mononucleosisuJapanese encephalitisuRabiesLaboratory findingsUrine routine testnHeavy proteinurianHematurianCastuMassive protein and shedded epithelial cells in urine form Membrane-like substanceLaboratory findingsBiochemical testsnElevated levels of liver enzymes,BUN,and serum creatinine n Electrolyte disturbancesn Altered coagulation profileLaboratory findingsEtiological diagnosisnEnzyme-linked immunosorbent assay(ELISA)Antihantaviral-specific IgM1:20(+)Early diagnostic value Antihantaviral-specific IgG1:40(+)Fourfold or greater rise in IgG titer can also confirm suspected casesnIsolation of virus nRT-PCR:identify viral RNASummary of the clinical featuresA triad of fever,hemorrhage,and renal insufficiency5 progressive stages:Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stageLaboratory finding:n Leukocytosis and thrombocytopenian Proteinurian Elevated levels of BUN,and serum creatinine ComplicationDigestive tract bleedingIntracranial hemorrhagesMyocardial damagePulmonary edema:ARDS,heart failure Secondary Infections Spontaneous kidney ruptureTreatment:overviewEarly recognition and hospitalization,bed restTreatment is supportivePrevent for secondary infectionPrevent the GI bleedingTreatment:Febrile stageAnti-viral therapy:IV ribavirin Preferably begun within the first 4 days of illnessReduce exudate:Rutosids and vitamin CManagement of the fever and toxic symptomsnPhysical cooling nShort course dexamethasone Prevent DICTreatment:Hypotensive stageSupplement of blood volumenModest crystalloid infusionnHuman serum albuminnPlasmaVasoactive agentsnDopamine,norepinephrineCorrection of acidosisn 5%Sodium Bicarbonate InjectionTreatment:Oliguric stageMaintenance of internal environment homeostasis nRestrict the volume of infusion Daily urine volume+500-700mlnControl the azotemia Supply sufficient carbohydrate to reduce the protein degradationnMaintaining electrolyte balance Treatment of HyperkalemianCorrection of acidosis 5%Sodium Bicarbonate InjectionTreatment of hyperkalemiaStop further potassium accumulationProtect the cardiac membrane Calcium gluconate 10%Shift the potassium from the blood into the cell InsulinRemoval of potassium from the body Haemodialysis,FurosemideTreatment:Oliguric stageDiuretics:furosemideCatharsis:rheum officinaleConsider Dialysis in following conditionsnSevere azotemia nFluid overload that cannot be managed with diureticsnHyperkalemia refractory to medical therapynSevere acid-base disturbances TreatmentPolyuric stageMaintain fluid and electrolyte balancePrevent secondary infection Antibiotics with nephrotoxic potential should be avoidedConvalescent stageMonitored in rest homePrognosisFatality rate ranges from 5 to 15%with Hantaan virus to less than 1%for Puumala virus infectionFor survivors,convalescence can take several months but recovery is often completePreventionRodent controlAvoid contact with rodent urine,droppings,saliva,and nesting materialsVaccinationHome work1.Hantaan virus is mainly transmitted byA.Patients B.Carriers C.Swine D.Mosquitoes E.Rodents（E）Home work2.The most cardinal reason of bleeding in febrile period of EHF is A.DICB.Heparin-like substance increasingC.Thrombocytopenia and vascular injuryD.AzotemiaE.Coagulation factor decreasing（C）Home work3.The main reason for early shock in EHF isA.Infection.B.Blood plasma-losing C.Hypervolemia D.Hemorrhage E.Vomiting.(B)Home work4.The patient had fever,lumbago,headache for three days.Physical examination:drunken face,petechiae in axillary folds,chemosis.Blood routine test:WBC 19109，N 83%,PLT 20109.Urine protein(+),RBC 3-5/HP.The diagnosis may be A.Typhoid fever B.Typhus C.Acute glumerulonephritisD.Epidemic hemorrhagic fever E.Leptospirosis(D)Home work5.Which is not proper in management of hemorrhagic fever with renal syndrome when hyperkalemia occurs A.Insulin and dextrose solutions B.10%calcium gluconateC.5%sodium bicarbonate D.Hemodialysis E.Whole blood transfusion(E)Home work6.Canonical hemorrhagic fever with renal syndrome caused by Hantaan virus evolve in five identifiable stages:_,_,_,_ and _.7.Give a introduction about the management principle of the oliguric phase of the hemorrhagic fever with renal syndrome