兒科學教學課件：新生兒黃疸

NEONATALJAUNDICE新生兒黃疸CasestudyYouareinyourfirstweekofa2-weekNICUrotation（輪轉(zhuǎn)）asanintern（實習生）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）About85%oftermbabies（足月兒）andmostofprematurebabies（早產(chǎn)兒）havejaundiceduringthefirstfewdaysorweeksoflifeNeonatalJaundiceNeonatalJaundiceCasestudyWhatiswrongwiththebaby?Howdoesithappen?

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

toomuchofbilirubin（膽紅素）buildsupinthebody.Bilirubinisayellow-colouredbilesaltswhichcandepositintissuesJaundiceisvisible

ifserum

bilirubin

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

高膽紅素血癥NeonatalJaundiceWhyoccursinneonates?膽綠素結合膽紅素膽紅素(游離)未結合膽紅素腸肝循環(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紅細胞骨髓與脾臟中的巨噬細胞血紅素膽紅素結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(紅細胞增多癥)–PO2inuteroRBClifespan2.Bilirubin-albumincomplexformationa.preterminfant:albumin(白蛋白)b.acidosis

Themetaboliccharacteristicsofbilirubininnewborns

3.Bilirubinmetabolisminhepatocytea.Hepaticuptakeofbilirubin:Yprotein,Zproteinb.Bilirubinconjugation:1-5%ofadults

UDPGT(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

美國兒科學會≥35W新生兒光療指南

PathologicJaundice 1.Appearswithinfirst24hoursoflife 2.Peak?TSB>221μmol/L(12.9mg/dl)(terminfants)TSB>256μmol/L(15mg/dl)(preterminfants)

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

達到相應日齡和相應危險因素下的光療干預標準結合膽紅素＜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）inbrainUCBcross

blood-brainbarrier（BBB:血腦屏障）YellowstaininginbrainDamage&scarring（瘢痕）

ofbasalganglia（基底節(jié)）&brainstemnuclei（腦干核團）

MRIchanges急性期雙側(cè)蒼白球?qū)ΨQ性T1加權高信號慢性期蒼白球T2加權高信號提示預后不良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CasestudyWhatiswrongwiththebaby?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

Whatisthecauses

forPathologicJaundice?Excessiveproductionofbilirubin膽紅素生成過多Polycythemia紅細胞增多癥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

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G6PDdeficency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Biliaryatresia膽道阻塞因母嬰血型不合引起的同族免疫性溶血母嬰血型不合→胎兒RBC經(jīng)胎盤入母體→母血型抗體進入胎兒循環(huán)→RBC破壞發(fā)病率：ABO血型不合占85.3%Rh血型不合占14.6%Mn血型不合占0.1%

Hemolyticdiseaseofnewborn

ABOincompatibility

mother:typeOinfant:typeAorBRhincompatibility

mother：Rh（-）

infant:Rh（+）D,E,C,d,e,cRh血型系統(tǒng)：D、E、C、d、e、c六種抗原抗原性強弱：D>E>C>c>e，以RhD最常見，其次為RhEHemolyticdiseaseofnewborn

一般不發(fā)生在第一胎在以下情況下，第一胎可發(fā)?。狠斞篟h陰性母親輸過Rh陽性血或有流產(chǎn)史外祖母學說：極少數(shù)Rh陰性母親未接觸Rh陽性血，但其母親為Rh陽性，其母懷孕時已使孕婦致敏臨床癥狀較重Rhincompatibility

ABO Rh黃疸程度稍輕 嚴重發(fā)生時間1-2天24小時貧血稍輕嚴重，可至心衰肝脾腫大少見常見Hemolyticdiseaseofnewborn

Rh溶血的患兒比ABO溶血更易發(fā)生膽紅素腦病和胎兒水腫血型檢查：ABO和Rh血型，提示血型不合肝功能：血清總膽紅素和未結合膽紅素增加溶血的檢查RBC、Hb減少網(wǎng)織紅細胞增高：10-15%血涂片有核紅細胞增多

Hemolyticdiseaseofthenewborn致敏紅細胞和血型抗體測定：改良直接抗人球蛋白試驗（Coombs試驗）：檢測紅細胞上結合的血型抗體；若陽性，說明紅細胞已致敏，可確診

Rh溶血病陽性率高，ABO溶血病陽性率低抗體釋放試驗：陽性可確診游離抗體試驗：測定來自母體的血清抗體，非確診試驗

Hemolyticdiseaseofthenewborn產(chǎn)前診斷ABO、Rh血型檢測孕16周Rh血型抗體效價檢測孕28周監(jiān)測羊水膽紅素濃度生后診斷母子血型不合早期出現(xiàn)黃疸改良Coombs或抗體釋放試驗陽性

HemolyticdiseaseofthenewbornGlucose-6-PhosphateDehydrogenaseDeficiency葡萄糖-6-磷酸脫氫酶缺乏癥X聯(lián)鎖不完全顯性遺傳紅細胞酶缺陷病G-6-PD是葡萄糖磷酸戌糖旁路代謝上的一種重要的酶基因位于X染色體上G-6-PD缺乏NADPH減少GSH減少紅細胞膜蛋白和酶蛋白中巰基受損紅細胞完整性受破壞溶血

G-6-PDDeficiency（蠶豆?。┭趸碳ADPH減少高鐵血紅蛋白增加變性珠蛋白小體形成紅細胞膜變硬經(jīng)過脾臟時被破壞溶血感染，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)新生兒溶血黃疸：未結合膽紅素升高確診試驗：紅細胞G-6-PD活性測定對癥治療預防G-6-PDDeficiency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，萘啶酸等某些中藥：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-PDDeficiency新生兒肝炎綜合征宮內(nèi)病毒感染：乙肝病毒、巨細胞病毒、風疹病毒、單純皰疹病毒、弓形蟲、腸道病毒、EB病毒等起病緩慢而隱匿臨床表現(xiàn)生理性黃疸持續(xù)不退或退而復現(xiàn)肝脾腫大大便顏色逐漸變淺陶土色厭食、嘔吐、體重不增NeonatalHepatitis實驗室檢查結合和未結合膽紅素均升高肝功能受損，轉(zhuǎn)氨酶升高膽汁酸及谷氨酰轉(zhuǎn)肽酶、堿性磷酸酶升高病原學檢測：特異性抗原抗體測定治療：抗感染、利膽、對癥等NeonatalHepatitis

Biliaryatresia先天性膽道閉鎖黃疸出現(xiàn)在生后不久或一個月內(nèi)極期呈黃綠色大便顏色逐漸變淺，白陶土色尿呈紅茶樣肝脾腫大晚期出現(xiàn)肝硬化、腹水、食管靜脈曲張大出血結合膽紅素升高，肝功能受損影像學檢查：B超、核醫(yī)學、MRIBreastmilkjaundice病因不明確，可能與母乳中葡萄糖醛酸苷酶活性增加，膽紅素的腸肝循環(huán)增加有關分早發(fā)型和晚發(fā)型可試停母乳三天，黃疸消退，膽紅素降至原水平50%，可考慮診斷一般狀況好，生長發(fā)育正常繼續(xù)母乳喂養(yǎng)，黃疸也可逐漸消退CasestudyWhatiswrongwiththebaby?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?Laboratorytests

黃疸

測總膽紅素和結合膽紅素結合膽紅素升高未結合膽紅素升高血型鑒定Coomb’s試驗、血型抗體測定紅細胞壓積、網(wǎng)織紅細胞

G6PD活性、紅細胞形態(tài)血培養(yǎng)、C反應蛋白

Laboratorytests

黃疸

測總膽紅素和結合膽紅素結合膽紅素升高未結合膽紅素升高血型鑒定Coomb’s試驗、血型抗體測定紅細胞壓積、網(wǎng)織紅細胞

G6PD活性、紅細胞形態(tài)血培養(yǎng)、C反應蛋白

Bloodtype:“A”Hb:99g/LHct:29.1%Rct:17.48%TSB:41