儿内科课件 2新生儿缺氧缺血性脑病

Hypoxic-ischemicencephalopathy(HIE)新生儿缺氧缺血性脑病Children’sHospitalof

ChongqingMedicalUniversityProf.JialinYu余加林教授OutlineNeonatalasphyxia→oxygen-poor→ischemia→braininjured

inperinatalperiodCurrentlybirthtrauma↓，O2deficiency&asphyxia↑Severeconsequence：neonataldeathorchildrendisablement,oneofreasonofcerebralpalsyinchildhood.Commoninfulltermbb,alsoinprematurecauses

mothers

fetus

antepartum

intrapartum

postpartum

20％35％35％10％hypoxiaPlacenta&umbilicalcordAnte-&intrapartumCausesofHIE

alsocausesofasphyxia:

Maternalfactors：illnesses，obstetric

deseases，smokingordrugaddiction,teenagepregnancies,olderthan35yearsIntrapartumfactors：umbilicalcore，malposition,placentalinsufficiency,placentalabruptionFetalfactors：congenitalanomalies,IUGR，

hydrops

fetalisInfantfactors：apnea,HMD,MAS,PPHN,shock.EtiopathogenesisofHIECerebralbloodflow(CBF)：1.failincompensation：2stepsofredistributionDivingreflexThefirsttime---skin

Adrenalgland

MaintainCBF

butleadtomultiorganicdamage,SecondaryredistributionAnteriorcerebralartery,ACAmiddlecerebralartery,MCAPosteriorcerebralartery,PCABranchofACABranchofMCABranchofPCAterminfant：parasagittaldamageincortex皮层矢状旁区受损preterminfant：periventricular

leukomalacia(PVL)

脑室周围的白质软化Consequenceof

secondaryredistribution脑室旁白质软化periventricular

leukomalacia,PVLBasalganglia

brainstem

cerebellumSuddenly&completelyasphyxia2.Non-compensation：ganglion-brainstemdamageCerebralbloodflow(CBF)：3.autoregulation

↓→Pressure-passivecerebralcirculation(PPCC)Cerebralischemia,HIEBrainedemacerebralhemorrhageBPCBFPPCCCerebralbloodflow(CBF)：Changeofbrainmetabolism:

1.oxygenfreeradicals→ruptureofcellmembrane

destroyBBB

(1)overproduction：

cytochrome-oxydase↓；

reperfusion：xanthine

oxidase↑

hypoxanthine----------------→urea+oxyradicals

(2)removenotenough：超氧化物歧化酶（SOD）↓Changeofbrainmetabolism:

2.imbalanceofNa&Ca：anaerobicglycolysis→lactic

acid↑,ATP↓→

pumpoutoforder→Ca++inflow→chaosofsignal

→Na++

inflow→intra-cellularedema

3.excitableneurotransmitter:

glutamicacid；

β-opioidpeptideCa++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++N-methyl-D-aspartate(NMDA)receptor

SynapticproductionofNeuroexcitatory

Aminoacidesp.GlutamateCa++reperfusioninjuryCa++Neuronalcelloxygenfreeradicalspumppumpexcitableneurotransmitterneuropathology：

脑细胞水肿(edema)脑细胞坏死(necrosisofbraincells)脑细胞凋亡(apoptosis）

commonlyoccurafter6-24

h,keepinseveraldaystowks

promptlyinterventioncould

decreasedamageCelldeathprimarilyneuronnecrosisdelayedneuroninjuretimeafterdamageduotohypoxiaideographofmitochondria

normalmitochondria

Clinicalmanifestation

history：asphyxia

nervoussystem：

basic:consciousdisturbance,tensionofmuscle,primitivereflex

severe：convulsions,bulgefontanel,irregularrespiration,pupilsdisorderCriteriaofSarnatgradesforHIEMild：alert,irritable,buthasnormaltoneandnoseizuresModerate：lethargic,hypotonic,oftenseizuresSevere：stuporousorcoma,flaccidorlimp,often

apneic,persistentseizuresPupilsnormalmydiasismiosisflaccidMuscletoneDecerebraterigidityAttentionsomedamageforHIEhappeninuterusbutnormalApgarscoreatbirthwithnotobviousmultiorganicdamagehowevernervoussymptomsandsignshouldbeappearedinseveralweeksorseveralmonthsafterbirth.investigationsElectroencephalogram(EEG):--maybenormalduringfirstfewday--poorprognosis:suppressedorfrequentseizureactivityinvestigationsImagingassessment:--cranialultrasound

hemorrhage,infarction,edema,cerebraarterybloodflowvelocityinvestigationsImagingassessment:

--brainCTscan

CTvalue<20hu

aslowdensity--

MRI：moredetailinformationsuchas:damageofparasagittalarea,

thalamencephalon,basalganglia,etal.--MRS(spectroscopy):

metabolin

ofhighenergyphosphatesoastojudgeoutcome

investigationsBloodbiochemistry

creatine

phosphokinase

isoenzyme(CPK-BB）

neuronspecific

enolase(NSE)bloodgasbloodsugar

diagnose：HistoryofasphyxiamanifestationofnervousdisorderinvestigationCriteriaofHIE

---onlyfortermbbAbnormalobstetrics,fetaldistress,

intrapartumasphyxiaPostpartumasphyxia:Apgarscore≤3at1min,≤5at5min,umbilicalbldgaspH≤7Nervousmanifestationsoonafterbirthandduration<24hExclude:electrolytedisorder,intracranalhemorrhage,

intrauterineinfections,hereditary&congenitaldiseases

objective

1.compensation

2.establishnewneuralnetwork

3.correctmistakesofconductionandarrangement

treatment发育中脑的可塑性Plasticityduringgrowthofbrain树突增长、增多

Dendronsgrowinlengthandnumber轴突延伸Axonselongation突触增加Increasesynapse

建立新的神经传导回路Rebuildloopsofnerveconduction——代偿性生长----compensationgrowthHypoxic-ischemia

necrosis

neurons

damage&apoptosis

cellbody

dendron&axon

neuralnetworksynapse

gliocytestrauma(microenvironment)

国家“九五”攻关项目简介：（治疗方案于1999.9南京全国第九届围产新生儿研究第12次会；1999.10大连第五届全国新生儿学术会上讨论并修改）

治疗原则therapeuticprinciple：早治early阶段stage综合combination足程enoughcourse信心

confidenceWithin3dof

age

(criticalperiod)4-10dAfter10dAfterneonatalperiod4stagesofHIEwithin3d：

purpose：stabilizeinternalenvionment

&controlnervoussymptom1、三项支持疗法maintenancetherapy：血气bloodgas血循环circulation血糖bloodsugarwithin3d：2、三项对症处理：symptomatictreatment

控制惊厥：phenobarbital,diazepam

降颅压：furosemide,mannitol

消除脑干症状：纳络酮naloxone指征indication：①severeHIE

②pupildisorder

③shock④frequentconvulsion3．improvemetabolismofcells：

cerebrolysin,胞二磷胆碱citicoline,复方丹参Salviamiltiorrhizahyperbaricoxygenation4-10dofage：

purpose:startimprovementin4-5doflife，obviouslyimprovementin7-9d

oflife.method:improvemetabolismofcellsAfter10d：

purpose:Consolidatetherapeuticeffect&preventsequelae

method:ifneonatalbehaviornervousassessment(NBNA)<35

1.促神经细胞代谢improvemetabolismofcells

2.新生儿期干预interventioninneonatalperiodAfterneonatalperiod:

IfNBNA<35，

developmentalquotient(DQ)<85

continuetreatmentfor3-6monthsprospectintreatment:

MagnesiumSulfate*traditionalmedicineinpregnancy-inducedhypertensionsyndrome

*↓cerebralpalsy*why？

antagonofcalciumion(Ca2+)Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++Ca++N-methyl-D-aspartate(NMDA)receptor

Synapticproductiono