兒科學(xué)-新生兒黃疸

NEONATALJAUNDICE新生兒黃疸1CasestudyYouareinyourfirstweekofa2-weekNICUrotation（輪轉(zhuǎn)）asanintern（實(shí)習(xí)生）Youarecalledbyanursefromthedepartmentofobstetrics（產(chǎn)科）.sheaskyoucomebytoseea3-day-oldbabywithjaundice（黃疸），whosetranscutaneousbilirubin(經(jīng)皮測膽紅素)is18mg/dl(308μmol/L)Transcutaneousbilirubinometry經(jīng)皮膽紅素測定儀CasestudyWhatiswrongwiththebaby?Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?CasestudyWhatiswrongwiththebaby?

Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?NeonatalJaundiceAyellowishpigmentation（色素沉著）oftheskinandmucousmembranes,includingtheconjunctivalmembranesoverthesclera（鞏膜）About60%oftermbabies（足月兒）andmorethan80%ofprematurebabies（早產(chǎn)兒）havejaundiceduringthefirstfewdaysorweeksoflifeNeonatalJaundiceNeonatalJaundiceCasestudyWhatiswrongwiththebaby?Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?Howdoesithappen?Itiscausedby

toomuchofbilirubin（膽紅素）buildsupinthebody.Bilirubinisayellow-colouredbilesaltswhichcandepositintissuesJaundiceisvisibleifserum

bilirubin

levels≥2mg/dlinadults,but≥5-7mg/dlinneonatesItisalsocalledhyperbilirubinemia（高膽紅素血癥）Hyperbilirubinemia

高膽紅素血癥NeonatalJaundiceWhyoccursinneonates?膽綠素結(jié)合膽紅素膽紅素(游離)未結(jié)合膽紅素腸肝循環(huán)尿膽原糞膽原肌紅蛋白血紅素加氧酶膽綠素還原酶Y蛋白Z蛋白尿苷二磷酸葡萄糖醛酸轉(zhuǎn)移酶UnconjugatedbilirubinBilirubinProduction&Metabolism紅細(xì)胞骨髓與脾臟中的巨噬細(xì)胞血紅素膽紅素結(jié)合膽紅素肝臟膽囊尿膽原糞膽原尿膽素腸肝循環(huán)IncreasedRBCsShortenedRBClifespanImmaturehepaticuptake&conjugation&excretionIncreasedenterohepaticCirculation1.Bilirubinproduction 8.8mg/Kg/dinnewborns 3.8mg/Kg/dinadultsReason:Relativepolycythemia(紅細(xì)胞增多癥)–PO2inuteroRBClifespan2.Bilirubin-albumincomplexformationa.preterminfant:albumin(白蛋白)b.acidosis

Themetaboliccharacteristicsofbilirubininnewborns

3.Bilirubinmetabolisminhepatocytea.Hepaticuptakeofbilirubin:Yprotein,Zproteinb.Bilirubinconjugation:1-5%ofadultsUDPGT(uridinediphosphateglucoronyltransferase)

尿苷二磷酸葡萄糖醛酸轉(zhuǎn)移酶

c.Defectivebilirubinexcretionabilitytobilesystem4.EnterohepaticcirculationBacteria,β-glucuronidase（葡萄糖醛酸苷酶）活性Themetaboliccharacteristicsofbilirubininnewborns

ClinicalManifestations

JaundiceappearsWhen: AtanytimeduringtheneonatalperiodWhere: Fromfacechestabdomenextremities（四肢）Evaluationofjaundice:1.Byeyes2.Bytranscutaneousmeasurement: usedforscreening3.Byserumlevels:standardClinicalManifestationsTranscutaneousbilirubinometry經(jīng)皮膽紅素測定儀ClinicalManifestationsAreaofbody

Bilirubinlevels

mg/dl

(*17.1=umol/L)

Face 5Uppertrunk 10Lowertrunk&thighs 15Armsandlowerlegs 18Palms&soles >18Visualmeasurementofbilirubinlevels

Classification:

分類：

PhysiologicJaundice

生理性黃疸

PathologicJaundice

病理性黃疸ClinicalManifestations

Physiologicjaundice

1.Generalstateiswell 2.FullterminfantsPreterminfantsAppearsD2-D3(>24hofage)D3-D5PeaksD4-D5D5-D7FadesD5-D7<2weekD7-D9<4weeks3.Accumulates<85μmol/L/d(5mg/dl/d)OR<8.5μmol/L/h(0.5mg/dl/h)4.Peak?TSB<221μmol/L(12.9mg/dl)(terminfants)TSB<256μmol/L(15mg/dl)(preterminfants)

EvaluateaccordingtoageindaysorhoursandriskfactorsClinicalManifestations

美國兒科學(xué)會≥35W新生兒光療指南

PathologicJaundice 1.Appearswithinfirst24hoursoflife 2.Peak?TSB>221μmol/L(12.9mg/dl)(terminfants)TSB>257μmol/L(15mg/dl)(preterminfants)

AchievephototherapycriteriaaccordingtoageindaysorhoursandriskfactorsAccumulates>5mg/dl/dOR><0.5mg/dl/h 3.Fades>2weeks(terminfants) >4weeks(preterminfants) 4.Jaundicerecurrent(退而復(fù)現(xiàn))

5.Conjugatedbilirubin>2mg/dlClinicalManifestations

出現(xiàn)時間生后第2-3天生后24小時內(nèi)消退時間足月兒＜14天足月兒＞2周早產(chǎn)兒3-4周早產(chǎn)兒＞4周或者退而復(fù)現(xiàn)上升速度＜5mg/dl/d(85μmol/L/d)＞5mg/dl/d

＜0.5mg/dl/h(8.5μmol/L/h)＞0.5mg/dl/h

生理性黃疸病理性黃疸生理性黃疸和病理性黃疸的鑒別

黃疸程度足月兒＜12.9mg/dl

足月兒＞12.9mg/dl

(221μmol/L)

早產(chǎn)兒＜15mg/dl

早產(chǎn)兒＞15mg/dl

(256μmol/L)

較輕

達(dá)到相應(yīng)日齡和相應(yīng)危險因素下的光療干預(yù)標(biāo)準(zhǔn)結(jié)合膽紅素＜2mg/dl＞2mg/dl(34.2μmol/L)(34.2μmol/L)

生理性黃疸病理性黃疸生理性黃疸和病理性黃疸的鑒別CasestudyThisisaterminfant,gestationalage（胎齡）40W,bornbyvaginaldelivery（順產(chǎn)）Apgarscore9and10at1and5minutesafterbirthrespectivelyBW3.7Kg3-dayoldTcB18mg/dl(308μmol/L)

PhysiologicJaundiceorPathologicJaundice?SoWhat’sTheBigDeal?BilirubinEncephalopathy!!!(膽紅素腦病)Kernicterus!!!(核黃疸)BilirubinEncephalopathyNeurologicsyndromeofunconjugatedbilirubindeposition（沉積）inbrainUCBcrossblood-brainbarrier（BBB:血腦屏障）YellowstaininginbrainDamage&scarring（瘢痕）

ofbasalganglia（基底節(jié)）

&brainstemnuclei

（腦干核團(tuán)）

MRIchanges急性期雙側(cè)蒼白球?qū)ΨQ性T1加權(quán)高信號慢性期蒼白球T2加權(quán)高信號提示預(yù)后不良BilirubinEncephalopathyBeworriedifTotalserumbilirubinlevel:>25mg/dlintermbabyWITHOUThemolysis（溶血）>20mg/dlintermbabyWITHhemolysisExtremlypreterminfantmaydevelopbilirubinencephalopathyeventhoughTSB<171μmol/L(10mg/dl)DisruptionoftheBBBbydiseasesuchasasphyxia（窒息）,andotherfactorsandmaturationalchangesinBBBpermeability(通透性)increasetherisk

Phases（分期）:Earlyphase（警告期）Spasticphase（痙攣期）Recoveryphase（恢復(fù)期）Chronicphase（后遺癥期）BilirubinEncephalopathyAcutebilirubinencephalopathyChronicbilirubinencephalopathyKernicterusEarlyphase（警告期）Hypotonia,lethargy,high-pitchedcry,poorsuck，poorfeeding

肌張力低，嗜睡，腦性尖叫，吸吮力差，吃奶少Spasticphase（痙攣期）Hypertonia:Opisthotonus,rigidity,gazing，retrocollis

肌張力高：角弓反張，強(qiáng)直，雙目凝視，頸后傾Irritability（激惹）,fever（發(fā)熱）,apnea（呼吸暫停）andseizures（驚厥）ManyinfantsdieinthisphaseAllinfantswhosurvivethisphasedevelopchronicbilirubinencephalopathy(clinicaldiagnosisofkernicterus)

BilirubinEncephalopathyRecoveryphase（恢復(fù)期）:Hypotonia,improvingChronicphase（后遺癥期）---Kernicterus:

Tetrad（四聯(lián)癥）：Athetosis:手足徐動癥，經(jīng)常出現(xiàn)不自主、無目的和不協(xié)調(diào)的動作Partialorcompletesensorineuraldeafness:聽覺障礙limitationofupwardgaze：眼球運(yùn)動障礙，不能向上轉(zhuǎn)動，呈“落日眼”Dentaldysplasia：牙釉質(zhì)發(fā)育不良，牙呈綠色或深褐色Others:intellectualdeficits（智力落后）,cerebralpalsy（腦癱），seizures（抽搐），etc.

BilirubinEncephalopathyLethargy嗜睡Opisthotonus角弓反張Seizures驚厥Cerebralpalsy腦癱ConsequencesofKernicterusDevelopmentaldelayMotordelaySensorineuraldeafnessMildmentalretardationCasestudyWhatiswrongwiththebaby?Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?病因分類：三大類Excessiveproductionofbilirubin

膽紅素生成過多Defectivebilirubinmetabolisminliver

肝臟膽紅素代謝障礙Defectivebileexcretion

膽汁排泄障礙

WhatisthecausesforPathologicJaundice?Excessiveproductionofbilirubin膽紅素生成過多Polycythemia紅細(xì)胞增多癥Hemolyticdiseases:

ABO/Rhincompatibility母嬰血型不合G6PDdeficency葡萄糖6磷酸脫氫酶缺乏癥abnormalRBCmorphology紅細(xì)胞形態(tài)異常abnormalHb血紅蛋白異常，如地中海貧血Infection感染

EtiologyforPathologicJaundiceExcessiveproductionofbilirubin膽紅素生成過多Increasedenterohepaticcirculation:腸肝循環(huán)增加Anydiseasescausedelayedmeconiumpassagesuchascongenitalintestinalabnormality，delayedfeeding任何可引起胎糞排出延遲的疾病如消化道畸形，喂養(yǎng)延遲等breastmilkjaundice母乳性黃疸Extravascularhemolysis:血管外溶血cephalohematoma頭顱血腫Intracranialhemorrhage顱內(nèi)出血pulmonaryhemorrhage肺出血

EtiologyforPathologicJaundiceDefectivebilirubinmetabolisminliver

肝臟膽紅素代謝障礙Hypoxiaandinfection缺氧和感染Crigler-Najjarsyndrome先天性UDPGT缺乏Gilbertsyndrome先天性非溶血性UCB增高癥Lucey-Driscollsyndrome家族性暫時性新生兒黃疸Medication可競爭結(jié)合Y/Z蛋白的藥物Others:congenitalhypothyroidism先天性甲狀腺功能低下,Trisomy-2121-三體綜合征

EtiologyforPathologicJaundiceDefectivebileexcretion膽汁排泄障礙Neonatalhepatitis

新生兒肝炎綜合征，宮內(nèi)病毒感染所致Inbornerrorsofmetabolism

先天性代謝缺陷病Dubin-Johnsonsyndrome

先天性非溶血性結(jié)合膽紅素增高癥Biliaryobstruction膽道阻塞先天性膽道閉鎖，先天性膽總管囊腫膽汁粘稠綜合征等

EtiologyforPathologicJaundiceCommonCausesofPathologicJaundiceHemolyticdiseaseofnewborn新生兒溶血病G6PDdeficiency葡萄糖6磷酸脫氫酶缺乏癥Breastmilkjaundice母乳性黃疸Neonatalhepatitis新生兒肝炎綜合征Biliaryobstruction膽道阻塞Isoimmunehemolysis同族免疫性溶血Maternalandfetalbloodgroupincompatibility母嬰血型不合→fetalRBCcrosstomotherthroughplacenta胎兒RBC經(jīng)胎盤入母體→maternalBGantibodiesenteredintofetalcirculation母血型抗體進(jìn)入胎兒循環(huán)→RBCbroken破壞

Hemolyticdiseaseofnewborn

IncidenceABO85.3%Rh14.6%Mn0.1%ABOincompatibility

mother:typeOinfant:typeAorBRhincompatibility

mother：Rh（-）

infant:Rh（+）D,E,C,d,e,c

Hemolyticdiseaseofnewborn

UsuallynothappeninfirstgravidaException：MaternalinfusioninthepastGrandmatheory：MotherwassensitizedbyherRh(+)motherwhengrandmawaspregnantClinicallySevereRhincompatibility

ABO Rh1.Jaundice:mild severe 1-2day 24h2.Anemia:

mildsevere(3-6weeks)heartfailure3.Hepato-rarecommonSplenomegalyHemolyticdiseaseofnewborn

PatientswithRhhemolysisdevelopbilirubinencephalopathyandhydropsfetalis（胎兒水腫）moreoftenthanABOhemolysis1.Bloodtypeincompatibility2.Hyperbilirubinemia:Unconjugatedbilirubinlevel3.Hemolytictests1).Hemoglobinlevel:low2).Reticulocytes:10–15%3).NucleatedRBCLaboratorytests:

Antibodytest1).DirectCoombstest(+)confirm2).Antibodyreleasetest(+)confirm3).Freeantibodytest(+)judgeLaboratorytestscontinuedGlucose-6-PhosphateDehydrogenaseDeficiency

葡萄糖-6-磷酸脫氫酶缺乏癥X-linkedrecessiveinheritanceX連鎖不完全顯性遺傳MostcommonRBCenzymedefectcansehemolysisEthnicorigin11-13%ofAfricanAmericansMediterranean,MiddleEast,Arabianpeninsula,AfricaSoutheastAsia

G-6-PDDeficiency（蠶豆?。〦rythrocytesunabletogeneratesufficientNADPHtomaintainthelevelsofGSH還原型谷胱甘肽toprotectRBCagainstoxidantstressUnconjugatedhyperbilirubinemiaConfirmationtest：RBCG-6-PDlevel

G-6-PDDeficiency（蠶豆?。└腥?，缺氧，酸中毒，母親服用氧化劑藥物，穿戴有樟腦丸氣味的衣服，均可誘發(fā)新生兒溶血氧化劑藥物：阿司匹林，氨基比林，VitK3，磺胺類，呋喃類，砜類，抗瘧藥，氯霉素，三硝基甲苯，萘啶酸等中藥：川蓮，牛黃粉、臘梅花、熊膽、七厘散、牛黃解毒丸等蠶豆或蠶豆制品G-6-PDDeficiencyBreastfeedingJaundiceOccursearlyElevatedunconjugatedbilirubininthe1stweekDuetothelackofbreastmilkOftenassociatedwithpoorpassageofmeconiumTreatmentshouldbeaimedatsupportingbreastfeedingNowaterordextrosesupplementationBreastmilkJaundiceOccurslaterinlife:Day6-14Bili12-20mg/dlEtiologyunclearMayduetoSubstancesinmaternalmilk,suchasalphaglucuronidases,mayinhibitnormalbilirubinmetabolismMaypeakby2weeks,persist1-3monthsGoodweightgain,babyiswellBreastmilkJaundiceBreastfeedingmaybetemporarilyinterruptedWithformulasubstitution,thetotalserumbilirubinlevelshoulddeclinerapidlyby50%over72hours,confirmingthediagnosisBreastfeedingmaythenberesumedCasestudyWhatiswrongwiththebaby?Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?CasestudyHistoryBabyboy,3dold,TcB18mg/dl(308umol/L)motherbloodtype“O”,fatherbloodtype“A”NoG6PDdeficencypatientinfamilyOthersunremarkablePhysicalAssessmentModeratejaundiceAcephalohematoma（頭顱血腫）4cm×8cmCasestudyWhatiswrongwiththebaby?Howdoesithappen?

Whatwillyoudonext?History?Physicalassessment?TransfertoNICU?Differentialdiagnosis?Laboratorytests?Managementplan?PathologicJaundiceworkupTSB+conjugated&unconjugatedbilirubinCBCwithdiffReticulocytecountBloodtypeRhcompatabilityCoomb’stestPeripheralbloodsmearPathologicJaundiceworkupG6PDscreen(ifapplicable)BloodcultureUA,urinecultureTSHforhypothyroidism(onstatescreen)CholestaticJaundice(needtor/obiliaryatresiaiflightcoloredstool,darkurine,urinewithbilirubin,persistentjaundice>3wks)Laboratorytests

黃疸Jaundice

測總膽紅素和結(jié)合膽紅素TSB&Bc

結(jié)合膽紅素Bc升高未結(jié)合膽紅素Bu升高血型鑒定bloodtypeCoomb’stest、血型抗體測定紅細(xì)胞壓積Hct、網(wǎng)織紅細(xì)胞RecG6PD活性、紅細(xì)胞形態(tài)bloodsmear

血培養(yǎng)bloodculture、C反應(yīng)蛋白CRP

Laboratorytests

黃疸Jaundice

測總膽紅素和結(jié)合膽紅素TSB&Bc

結(jié)合膽紅素Bc升高未結(jié)合膽紅素Bu升高

血型鑒定bloodtypeCoomb’stest、血型抗體測定

紅細(xì)胞壓積Hct、網(wǎng)織紅細(xì)胞Rec

G6PD活性、紅細(xì)胞形態(tài)morphology

血培養(yǎng)bloodculture、C反應(yīng)蛋白CRP

Bloodtype:“A”Hb:99g/LHct:29.1%Rct:17.48%TSB:410μmol/L,UCB:348.7μmol/LCoomb’stest:negativeAntibodyreleasetest(+)Freeantibodytest(+)Diagnosis?ABOincompabilityLaboratorytests

TreatmentWhydowetreat?Preventbilirubinencephalopathy預(yù)防膽紅素腦病Howdowetreat?Phototherapy光照療法Exchangetransfusion換血療法Medication藥物Unconjugatedbilirubinintheskincanbeconvertedtolesstoxicwater-solublephotoisomersbycertainwavelengthsoflightandexcretedinthebileandurinewithoutconjugationUCB下轉(zhuǎn)變成水溶性的異構(gòu)體，經(jīng)膽汁和尿液排出在光的作用Wavelength420to500nm，betteruseblueandgreenlightSinglesideordoublesides,continuousorintermittent,bluelight

藍(lán)光燈orfiberopticblanket藍(lán)光毯

Phototherapy光療

Phototherapy光療

Phototherapy光療

Phototherapy光療

IndicationsforphototherapyUnconjugatedhyperbilirubinemiawithaTSBlevelmorethanacertainlevel高未結(jié)合膽紅素血癥其血清總膽紅素達(dá)指標(biāo)Prophylacticphototherapy預(yù)防性光療：

newbornswithriskfactorsforbilirubinencephalopathy

有膽紅素腦病高危因素放寬指征Nophototherapyforbabieswithconjugatedhyperb