医学精品课件：新生儿黄疸.ppt

1、NEONATAL JAUNDICE 新生儿黄疸,Dr. SUN YI Department of Neonatology The 2nd Affiliated Hospital of Guangzhou Medical University,Case study,You are in your first week of a 2-week NICU rotation（轮转） as an intern（实习生） You are called by a nurse from the department of obstetrics（产科）. she ask you come by to see a

2、 3-day-old baby with jaundice（黄疸），whose transcutaneous bilirubin(经 皮测胆红素) is 18mg/dl(308mol/L),Transcutaneous bilirubinometry 经皮胆红素测定仪,Case study,What is wrong with the baby? How does it happen? What will you do next? History? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory

3、 tests? Management plan?,Case study,What is wrong with the baby? How does it happen? What will you do next? History? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory tests? Management plan?,Neonatal Jaundice,A yellowish pigmentation（色素沉着） of the skin and mucous membranes, in

4、cluding the conjunctival membranes over the sclera（巩膜） About 85% of term babies（足月儿） and most of premature babies （早产儿）have jaundice during the first few days or weeks of life,Neonatal Jaundice,Neonatal Jaundice,Case study,What is wrong with the baby? How does it happen? What will you do next? Histo

5、ry? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory tests? Management plan?,How does it happen?,It is caused by too much of bilirubin（胆红素）builds up in the body. Bilirubin is a yellow-coloured bile salts which can deposit in tissues Jaundice is visible if serum bilirubin lev

6、els2mg/dl in adults, but 5-7mg/dl in neonates It is also called hyperbilirubinemia（高胆红素血症） Hyper bilirubin emia 高 胆红素 血症,Neonatal Jaundice,Why occurs in neonates?,胆绿素,结合胆红素,胆红素(游离),未结合胆红素,肠肝循环,尿胆原,粪胆原,肌红蛋白,血红素加氧酶,胆绿素还原酶,Y蛋白Z蛋白,尿苷二磷酸葡萄糖醛酸转移酶,Unconjugated bilirubin,Bilirubin Production & Metabolism,红细

7、胞,骨髓与脾脏中的巨噬细胞,血红素,胆红素,结合胆红素,肝脏,胆囊,尿胆原,粪胆原,尿胆素,肠肝循环,Increased RBCs,Shortened RBC lifespan,Immature hepatic uptake & conjugation &excretion,Increased enterohepatic Circulation,1. Bilirubin production 8.8mg/Kg/d in newborns 3.8mg/Kg/d in adults Reason: Relative polycythemia(红细胞增多症) PO2 in utero RBC lif

8、espan 2. Bilirubin-albumin complex formation a. preterm infant: albumin(白蛋白) b. acidosis,The metabolic characteristics of bilirubin in newborns,3. Bilirubin metabolism in hepatocyte a. Hepatic uptake of bilirubin: Y protein, Z protein b. Bilirubin conjugation: 1-5% of adults UDPGT (uridine diphospha

9、te glucoronyl transferase) 尿苷二磷酸葡萄糖醛酸转移酶 c. Defective bilirubin excretion ability to bile system 4. Enterohepatic circulation Bacteria , -glucuronidase（葡萄糖醛酸苷酶）活性,The metabolic characteristics of bilirubin in newborns,Clinical Manifestations,Jaundice appears When: At any time during the neonatal per

10、iod Where: From face chest abdomen extremities（四肢）,Evaluation of jaundice : 1. By eyes 2. By transcutaneous measurement : used for screening 3. By serum levels : standard,Clinical Manifestations,Transcutaneous bilirubinometry 经皮胆红素测定仪,Clinical Manifestations,Area of body Bilirubin levels mg/dl (*17.

11、1=umol/L) Face 5 Upper trunk 10 Lower trunk & thighs 15 Arms and lower legs 18 Palms & soles 18,Visual measurement of bilirubin levels,Classification: 分类： Physiologic Jaundice 生理性黄疸 Pathologic Jaundice 病理性黄疸,Clinical Manifestations,Physiologic jaundice 1. General state is well 2. Full term infants P

12、reterm infants Appears D2-D3 (24h of age) D3-D5 Peaks D4-D5 D5-D7 Fades D5-D7 2 week D7-D9 4 weeks 3. Accumulates 85mol/L/d(5mg/dl/d) OR 8.5mol/L/h(0.5mg/dl/h) 4. Peak? TSB 221mol/L(12.9mg/dl) (term infants) TSB 256mol/L(15mg/dl) (preterm infants) Evaluate according to age in days or hours and risk

13、factors,Clinical Manifestations,美国儿科学会35W新生儿光疗指南,Pathologic Jaundice 1. Appears within first 24 hours of life 2. Peak? TSB 221mol/L(12.9mg/dl) (term infants) TSB 256mol/L(15mg/dl) (preterm infants) Achieve phototherapy criteria according to age in days or hours and risk factors Accumulates 5mg/dl/d

14、OR 0.5mg/dl/h 3. Fades 2 weeks (term infants) 4 weeks (preterm infants) 4. Jaundice recurrent (退而复现) 5. Conjugated bilirubin 2mg/dl,Clinical Manifestations,出现时间 生后第2-3天 生后24小时内 消退时间 足月儿14天 足月儿2周 早产儿3-4周 早产儿4周 或者退而复现 上升速度 5mg/dl/d(85mol/L/d) 5mg/dl/d 0.5mg/dl/h(8.5mol/L/h) 0.5mg/dl/h,生理性黄疸 病理性黄疸,生理性黄

15、疸和病理性黄疸的鉴别,黄疸程度 足月儿12.9mg/dl 足月儿12.9mg/dl (221mol/L) 早产儿15mg/dl 早产儿15mg/dl (256mol/L) 较轻 达到相应日龄和相应危险 因素下的光疗干预标准 结合胆红素 2mg/dl 2mg/dl (34.2mol/L) (34.2mol/L),生理性黄疸 病理性黄疸,生理性黄疸和病理性黄疸的鉴别,Case study,This is a term infant, gestational age（胎龄）40W, born by vaginal delivery（顺产） Apgar score 9 and 10 at 1 and

16、5 minutes after birth respectively BW 3.7Kg 3-day old TcB 18mg/dl(308mol/L) Physiologic Jaundice or Pathologic Jaundice?,So Whats The Big Deal?,Bilirubin Encephalopathy! (胆红素脑病) Kernicterus! (核黄疸),Bilirubin Encephalopathy,Neurologic syndrome of unconjugated bilirubin deposition（沉积） in brain UCB cros

17、s blood-brain barrier（BBB:血脑屏障） Yellow staining in brain Damage & scarring（瘢痕） of basal ganglia（基底节） & brainstem nuclei （脑干核团）,MRI changes,急性期双侧苍白球对称性T1加权高信号 慢性期苍白球T2加权高信号提示预后不良,Bilirubin Encephalopathy,Be worried if Total serum bilirubin level: 25mg/dl in term baby WITHOUT hemolysis（溶血） 20mg/dl in

18、term baby WITH hemolysis Extremly preterm infant may develop bilirubin encephalopathy even though TSB 171mol/L (10mg/dl) Disruption of the BBB by disease such as asphyxia（窒息）, and other factors and maturational changes in BBB permeability(通透性) increase the risk,Phases（分期）: Early phase（警告期） Spastic p

19、hase（痉挛期） Recovery phase（恢复期） Chronic phase（后遗症期）,Bilirubin Encephalopathy,Acute bilirubin encephalopathy,Chronic bilirubin encephalopathy,Kernicterus,Early phase（警告期） Hypotonia, lethargy, high-pitched cry, poor suck，poor feeding 肌张力低，嗜睡，脑性尖叫，吸吮力差，吃奶少 Spastic phase（痉挛期） Hypertonia: Opisthotonus, rig

20、idity, gazing，retrocollis 肌张力高：角弓反张，强直，双目凝视，颈后倾 Irritability（激惹）, fever（发热）, apnea（呼吸暂停）and seizures（惊厥） Many infants die in this phase All infants who survive this phase develop chronic bilirubin encephalopathy (clinical diagnosis of kernicterus),Bilirubin Encephalopathy,Recovery phase（恢复期）: Hypoto

21、nia, improving Chronic phase（后遗症期）- Kernicterus: Tetrad（四联症）： Athetosis: 手足徐动症，经常出现不自主、无目的和不协调的动作 Partial or complete sensorineural deafness: 听觉障碍 limitation of upward gaze：眼球运动障碍，不能向上转动，呈“落日眼” Dental dysplasia：牙釉质发育不良，牙呈绿色或深褐色 Others: intellectual deficits（智力落后）, cerebral palsy（脑瘫），seizures（抽搐），etc

22、.,Bilirubin Encephalopathy,Lethargy 嗜睡,Opisthotonus 角弓反张,Seizures 惊厥,Cerebral palsy 脑瘫,Case study,What is wrong with the baby? How does it happen? What will you do next? History? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory tests? Management plan?,病因分类：三大类 Excessive prod

23、uction of bilirubin 胆红素生成过多 Defective bilirubin metabolism in liver 肝脏胆红素代谢障碍 Defective bile excretion 胆汁排泄障碍,What is the causes for Pathologic Jaundice?,Excessive production of bilirubin 胆红素生成过多 Polycythemia 红细胞增多症 Hemolytic diseases: ABO/Rh incompatibility 母婴血型不合 G6PD deficency 葡萄糖6磷酸脱氢酶缺乏症 abnorm

24、al RBC morphology 红细胞形态异常 abnormal Hb 血红蛋白异常，如地中海贫血 Infection 感染,Etiology for Pathologic Jaundice,Excessive production of bilirubin 胆红素生成过多 Increased enterohepatic circulation: 肠肝循环增加 Any diseases cause delayed meconium passage such as congenital intestinal abnormality，delayed feeding 任何可引起胎粪排出延迟的疾病

25、如消化道畸形，喂养延迟等 breast milk jaundice 母乳性黄疸 Extravascular hemolysis: 血管外溶血 cephalohematoma 头颅血肿,Etiology for Pathologic Jaundice,Defective bilirubin metabolism in liver 肝脏胆红素代谢障碍 Hypoxia and infection 缺氧和感染 Crigler-Najjar syndrome 先天性UDPGT缺乏 Gilbert syndrome 先天性非溶血性UCB增高症 Lucey-Driscoll syndrome 家族性暂时性新

26、生儿黄疸 Medication 可竞争结合Y/Z蛋白的药物 Others: congenital hypothyroidism 先天性甲状腺功能低下, Trisomy-21 21-三体综合征,Etiology for Pathologic Jaundice,Defective bile excretion 胆汁排泄障碍 Neonatal hepatitis 新生儿肝炎综合征，宫内病毒感染所致 Inborn errors of metabolism 先天性代谢缺陷病 Dubin-Johnson syndrome 先天性非溶血性结合胆红素增高症 Biliary obstruction 胆道阻塞 先

27、天性胆道闭锁，先天性胆总管囊肿 胆汁粘稠综合征等,Etiology for Pathologic Jaundice,Common Causes of Pathologic Jaundice,Hemolytic disease of newborn 新生儿溶血病 G6PD deficency 葡萄糖6磷酸脱氢酶缺乏症 Breast milk jaundice 母乳性黄疸 Neonatal hepatitis 新生儿肝炎综合征 Biliary atresia 胆道阻塞,因母婴血型不合引起的同族免疫性溶血 母婴血型不合胎儿RBC经胎盘入母体母血型抗体进入胎儿循环 RBC破坏 发病率：ABO血型不合占

28、85.3% Rh血型不合占14.6% Mn血型不合占0.1%,Hemolytic disease of newborn,ABO incompatibility mother: type O infant: type A or B Rh incompatibility mother： Rh（-） infant: Rh（+）D,E,C,d,e,c Rh血型系统：D、E、C、d、e、c六种抗原 抗原性强弱：DECce，以RhD最常见，其次为RhE,Hemolytic disease of newborn,一般不发生在第一胎 在以下情况下，第一胎可发病： 输血：Rh阴性母亲输过Rh阳性血或有流产史 外

29、祖母学说：极少数Rh阴性母亲未接触Rh阳性血，但其母亲为Rh阳性，其母怀孕时已使孕妇致敏 临床症状较重,Rh incompatibility,ABO Rh 黄疸程度 稍轻 严重 发生时间 1-2 天 24小时 贫血 稍轻 严重，可至心衰 肝脾肿大 少见 常见,Hemolytic disease of newborn,Rh溶血的患儿比 ABO 溶血更易发生 胆红素脑病和胎儿水肿,血型检查：ABO和Rh血型，提示血型不合 肝功能：血清总胆红素和未结合胆红素增加 溶血的检查 RBC、Hb减少 网织红细胞增高：10-15% 血涂片有核红细胞增多,Hemolytic disease of the new

30、born,致敏红细胞和血型抗体测定： 改良直接抗人球蛋白试验（Coombs试验）：检测红细胞上结合的血型抗体；若阳性，说明红细胞已致敏，可确诊 Rh溶血病阳性率高，ABO溶血病阳性率低 抗体释放试验：阳性可确诊 游离抗体试验：测定来自母体的血清抗体，非确诊试验,Hemolytic disease of the newborn,产前诊断 ABO、Rh血型检测 孕16周Rh血型抗体效价检测 孕28周监测羊水胆红素浓度 生后诊断 母子血型不合 早期出现黄疸 改良Coombs或抗体释放试验阳性,Hemolytic disease of the newborn,Glucose-6-Phosphate D

31、ehydrogenase Deficiency 葡萄糖-6-磷酸脱氢酶缺乏症 X联锁不完全显性遗传 红细胞酶缺陷病 G-6-PD是葡萄糖磷酸戌糖旁路代谢上的一种重要的酶 基因位于X染色体上 G-6-PD缺乏 NADPH减少 GSH减少 红细胞膜 蛋白和酶蛋白中巯基受损 红细胞完整性受破坏 溶血,G-6-PD Deficiency（蚕豆病）,氧化刺激,NADPH减少 高铁血红蛋白增加 变性珠蛋白小体形成 红细胞膜变硬 经过脾脏时被破坏 溶血 感染，缺氧，酸中毒，母亲服用氧化剂药物，穿戴有樟脑丸气味的衣服，均可诱发新生儿溶血 黄疸：未结合胆红素升高 确诊试验：红细胞G-6-PD活性测定 对症治疗

32、预防,G-6-PD Deficiency,氧化剂药物：阿司匹林，氨基比林，VitK3，磺胺类，呋喃类，砜类，抗疟药，氯霉素，三硝基甲苯，萘啶酸等 某些中药：川莲，牛黄粉、腊梅花、熊胆、七厘散、牛黄解毒丸等 蚕豆或蚕豆制品,G-6-PD Deficiency,新生儿肝炎综合征 宫内病毒感染：乙肝病毒、巨细胞病毒、风疹病毒、单纯疱疹病毒、弓形虫、肠道病毒、EB病毒等 起病缓慢而隐匿 临床表现 生理性黄疸持续不退或退而复现 肝脾肿大 大便颜色逐渐变浅 陶土色 厌食、呕吐、体重不增,Neonatal Hepatitis,实验室检查 结合和未结合胆红素均升高 肝功能受损，转氨酶升高 胆汁酸及谷氨酰转肽酶

33、、碱性磷酸酶升高 病原学检测：特异性抗原抗体测定 治疗：抗感染、利胆、对症等,Neonatal Hepatitis,Biliary atresia,先天性胆道闭锁 黄疸出现在生后不久或一个月内 极期呈黄绿色 大便颜色逐渐变浅，白陶土色 尿呈红茶样 肝脾肿大 晚期出现肝硬化、腹水、食管静脉曲张大出血 结合胆红素升高，肝功能受损 影像学检查：B超、核医学、MRI,Breast milk jaundice,病因不明确，可能与母乳中葡萄糖醛酸苷酶活性增加，胆红素的肠肝循环增加有关 分早发型和晚发型 可试停母乳三天，黄疸消退，胆红素降至原水平50%，可考虑诊断 一般状况好，生长发育正常 继续母乳喂养，黄

34、疸也可逐渐消退,Case study,What is wrong with the baby? How does it happen? What will you do next? History? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory tests? Management plan?,Case study,History Baby boy, 3d old, TcB 18mg/dl(308umol/L) mother blood type “O”, father blood type “

35、A” No G6PD deficency patient in family Others unremarkable Physical Assessment Moderate jaundice A cephalohematoma（头颅血肿） 4cm8cm,Case study,What is wrong with the baby? How does it happen? What will you do next? History? Physical assessment? Transfer to NICU? Differential diagnosis? Laboratory tests?

36、 Management plan?,Laboratory tests,黄疸 测总胆红素和结合胆红素 结合胆红素升高 未结合胆红素升高 血型鉴定 Coombs 试验、血型抗体测定 红细胞压积、网织红细胞 G6PD活性、红细胞形态 血培养、C反应蛋白,Laboratory tests,黄疸 测总胆红素和结合胆红素 结合胆红素升高 未结合胆红素升高 血型鉴定 Coombs 试验、血型抗体测定 红细胞压积、网织红细胞 G6PD活性、红细胞形态 血培养、C反应蛋白,Blood type: “A” Hb: 99g/L Hct:29.1% Rct: 17.48% TSB: 410mol/L, UCB: 34

37、8.7mol/L Coombs test: negative Antibody release test (+) Free antibody test (+) Diagnosis? ABO incompability,Laboratory tests,Treatment,Why do we treat? Prevent bilirubin encephalopathy 预防胆红素脑病 How do we treat? Phototherapy 光照疗法 Exchange transfusion 换血疗法 Medication 药物,原理：UCB在光的作用下转变成水溶性的异构体，经胆汁和尿液排出

38、 波长420至 500nm，蓝光和绿光效果好 方法：单、双面蓝光灯、蓝光毯 持续或间歇光疗,Phototherapy 光疗,Phototherapy 光疗,Phototherapy 光疗,光疗指征,任何原因的高未结合胆红素血症 血清总胆红素达指标 预防性光疗：有胆红素脑病高危因素放宽指征 高结合胆红素血症者不光疗,美国儿科学会35W新生儿光疗指南,光疗注意事项及副作用,眼的保护 温度、湿度、水分 可出现发热、腹泻、皮疹、青铜症,Exchange Transfusion 换血疗法,治疗新生儿重症高未结合胆红素血症最迅速而有效的方法 作用 换出血中游离的抗体和致敏的红细胞，减轻溶血 换出血中大量胆

39、红素，防止胆红素脑病 纠正贫血，防止心衰,换血指征： 确诊溶血病，出生时脐血总胆红素68mol/L（4mg/dl），Hb120g/L，伴水肿、肝脾大、心衰 生后12小时内胆红素上升12mol/L/h 血清总胆红素342mol/L 有早期胆红素脑病症状者，不论胆红素高低 早产儿、合并缺氧、酸中毒者、上一胎溶血严重者，放宽指征,Exchange Transfusion 换血疗法,美国儿科学会35W新生儿换血指南,血源选择 ABO溶血病：O型红细胞+AB型血浆 Rh溶血病：Rh血型同母亲, ABO血型同患儿的血液 换血途径 经脐静脉插管 经外周动静脉同步换血 换血量 用双倍于新生儿个体的血量（150

40、-180ml/kg ),Exchange Transfusion 换血疗法,Exchange Transfusion 换血疗法,肝酶诱导剂：苯巴比妥，5mg/kg/d 静脉用丙种球蛋白：阻断Fc受体而抑制溶血，1g/kg，68小时内持续静滴。 预防胆红素脑病：白蛋白：1g/kg 肠道微生态制剂：妈咪爱 锡原卟啉、锌原卟啉：血红素加氧酶抑制剂,Medication 药物疗法,Case study,Phototherapy Albumin Exchange transfusion IVIG After exchange transfusion, TSB 184mol/L, Hb 105g/L Plt 73109/L 7 days later, baby discharged,思考题,生理性黄疸与病理性黄疸的鉴别要点 新生儿高胆红素血症的治疗方法有哪些 几种常见的引起新生儿黄疸的疾病的临床特点,谢 谢！,