医学精品课件：先心双语.PPT

1、简 历 姓名姓名:庞玉生，教授，博士生导师，儿科副主任庞玉生，教授，博士生导师，儿科副主任教育经历教育经历/工作经历工作经历 19821987 广西医科大学广西医科大学 19921995 武汉大学医学院儿科学武汉大学医学院儿科学 19982001 复旦大学儿科学复旦大学儿科学 20012004 广西医科大学博士后广西医科大学博士后 20032004 Karolinska institute 2004至今至今 广西医科大学第一附属医院儿科广西医科大学第一附属医院儿科研究经历研究经历/研究方向研究方向:心血管疾病心血管疾病电话电话:13878106866 E-mail:庞玉生庞玉生授课对象：七年制

2、授课对象：七年制广西医科大学儿科广西医科大学儿科学教研室学教研室Chapter 13 循环系统疾病循环系统疾病Circulation system disease 教学目的教学目的 初步熟悉、了解先天性心脏病初步熟悉、了解先天性心脏病 掌握先天性心脏病的诊断和治疗掌握先天性心脏病的诊断和治疗教学重点教学重点 详细介绍先天性心脏病的临床表现和诊断方法详细介绍先天性心脏病的临床表现和诊断方法教学难点教学难点 先天性心脏病血液动力学改变与临床表现的关系先天性心脏病血液动力学改变与临床表现的关系Contents小儿心血管系统解剖生理特点及检查方法小儿先天性心脏病概述房间隔缺损室间隔缺损动脉导管未闭法洛

3、四联症第一节 小儿心血管系统解剖生理 特点及检查方法一一 心脏的胚胎发育心脏的胚胎发育Cardiac development during fetal period The primitive heart tube forms by 3 W Cardiac looping by 2224 days Bend ventrally and toward the right Cardiac septation第一隔第一隔原发孔原发孔心内膜垫心内膜垫静脉窦瓣静脉窦瓣膜膜第二隔第二隔继发孔继发孔第一隔第一隔室间孔室间孔第二隔第二隔继发孔继发孔第一隔第一隔卵园孔卵园孔第一隔第一隔室间孔室间孔第二隔第二隔静

4、脉窦瓣静脉窦瓣膜膜胚胎房室分隔及房室间隔发育胚胎房室分隔及房室间隔发育室间隔形成室间隔形成 心室间隔组成三个来源心室间隔组成三个来源 肌隔肌隔 心内膜垫向下生长与肌隔相合心内膜垫向下生长与肌隔相合 动脉总干及心球分化成主动脉动脉总干及心球分化成主动脉 与肺动脉时的中隔向下延伸部分与肺动脉时的中隔向下延伸部分室室间间隔隔膜膜部部Aortic arch development Right and left truncoconal ridges The aortic and pulmonary outflow tracts are fully separated The coronary sinus

5、 The semilunar valves主肺动脉由总干呈螺旋形分隔主肺动脉由总干呈螺旋形分隔AOPAPAAOPAPAAOAOPAPAPAPA大动脉位置变移系列示意图大动脉位置变移系列示意图TOFTGADORVTaussig-Bing 房室管、心房、房室管、心房、及心室的分隔及心室的分隔室间隔膜部的形成室间隔膜部的形成及室间隔的封闭及室间隔的封闭u第第2 2周原始心脏形成周原始心脏形成u第第4 4周心脏起循环作用周心脏起循环作用u第第8 8周四腔心脏形成周四腔心脏形成二二 胎儿新生儿循环转换胎儿新生儿循环转换The placenta:gas exchange,metabolic exchang

6、e The lung:constrictedThree cardiovascular structure:Ductus venosus Foramen ovale Ductus arteriosus The Fetal Circulation胎儿血循环特点胎儿血循环特点营养和气体代谢通过脐血管和胎盘与母体营养和气体代谢通过脐血管和胎盘与母体进行弥漫式交换进行弥漫式交换绝大部分为混合血绝大部分为混合血供应心脏、脑、肝及上肢血氧含量远较下供应心脏、脑、肝及上肢血氧含量远较下半身高半身高肺处于压缩状态无气体交换肺处于压缩状态无气体交换卵圆孔、动脉导管和静脉导管开放卵圆孔、动脉导管和静脉导管开放右心室

7、优势右心室优势The Fetal Circulation胎儿血液循环途径胎儿血液循环途径通过动脉导管通过动脉导管通过卵圆孔通过卵圆孔血氧含量较高血氧含量较高血氧含量较低血氧含量较低通过静脉导管通过静脉导管下腔静脉下腔静脉右心房右心房右心室右心室左心房左心房左心室左心室升主动脉升主动脉心脑及上肢心脑及上肢肺动脉肺动脉降主动脉降主动脉下半身下半身上半身静脉血上半身静脉血上腔静脉上腔静脉脐静脉动脉血脐静脉动脉血门静脉静脉血门静脉静脉血母体母体下半身静脉血下半身静脉血肺循环肺循环50%1/380%PDACirculation Changes after birth The umbilical cord

8、 clamped breathing commences Pulmonary circulation Providing gas exchange The foramen ovale and ductus arteriosus:functionally closed胎儿与出生后血液循环比较胎儿与出生后血液循环比较胎儿期出生后由母体循环完成气体交换由母体循环完成气体交换由肺循环完成气体交换由肺循环完成气体交换多为混合血，心、脑、上多为混合血，心、脑、上半身血氧含量高于下半身半身血氧含量高于下半身静脉血和动脉血分开静脉血和动脉血分开卵圆孔、动脉导管、静脉卵圆孔、动脉导管、静脉导管开放导管开放卵圆孔

9、、动脉导管、静卵圆孔、动脉导管、静脉导管闭合脉导管闭合肺动脉压与主动脉相似，肺动脉压与主动脉相似，肺循环阻力高肺循环阻力高肺动脉压下降，肺循环肺动脉压下降，肺循环阻力低阻力低右心室高负荷右心室高负荷左心室高负荷左心室高负荷AB正常血液循环途径正常血液循环途径Common symtoms Congestive heart failure Feeding difficulties/Exercise intolerance Respiratory distress Poor growth Cracked,cough Squatting Syncope Cyanosis三三 儿童心血管疾病体格检查方法

10、儿童心血管疾病体格检查方法Physical examination Commonly manifestations Evaluation for BW and BH Respiratory distress Cyanosis Clubbing digits Hepatomegaly Distended neck veins Sign of liver-jugular vein Peripheral edemaCardiovascular ExaminationInspection:Prominence of the precordium Cardiomegaly Palpation:heave

11、,thrill Percussion:size and position of the heartAuscultation:HR,rhythm (1)Normal heart sounds:S1,S2,S3,S4 (2)Abnormal heart sounds:P2 fixed splitting (3)Murmurs 小儿听诊常用听诊区小儿听诊常用听诊区二尖瓣听诊区二尖瓣听诊区肺动脉瓣听诊区肺动脉瓣听诊区主动脉瓣听诊区主动脉瓣听诊区三尖瓣听诊区三尖瓣听诊区(1)Location and radiation(2)Timing:Systolic,diastolic and continuous

12、(3)Quality:Harsh,musical,or rough;high,medium or low in pitch(4)Intensity:grade,(5)Variation with positionMurmur 周围血管征周围血管征 四肢脉搏及血压四肢脉搏及血压 主动脉缩窄：主动脉缩窄：股动脉搏动减弱或消失股动脉搏动减弱或消失 下肢血压低于上肢下肢血压低于上肢 动脉导管未闭或主动脉关闭不全：动脉导管未闭或主动脉关闭不全：脉压增宽脉压增宽 毛细血管搏动毛细血管搏动 股动脉枪击音股动脉枪击音四四 心脏的特殊检查心脏的特殊检查 (1)Chest x-ray (2)Electrocard

13、iogram (3)Echocardiogram (4)Cardiac catheterization (5)Angiocardiography (6)Radionuclide angiocardiography (7)Magnetic resonance imaging（8）Computed tomographyChest Radiographlcharacter of the pulmonary vasculaturelPosition of the cardiac apexlcardiac size(cardiothoracic ratio)lcardiac configuration,

14、heart shapelPosition of the abdominal visceraNormal cardiothoracic imaging landmarks,PA view Anterior radiographic view of cardiac anatomy X-ray你的你的X线诊线诊断分别是什断分别是什么？么？The sequence of ECG:rate,rhythm,P wave,PR interval,QRS complex(axis,amplitude,and duration),QT interval,ST segment,and T wave.Assess

15、atrioventricular hypertrophy Diagnosis of dysrhythmiasElectrocardiogram,ECGNormal ECG A powerful noninvasive method:M-mode,two and three dimensional,color and Doppler Evaluate cardiac structure Estimate intracardiac pressure and gradient across stenotic valves and vessels Quantitate cardiac contract

16、ile function Determine the direction of flow across a defect Examine the integrity of the coronary arteries Evaluate endocarditis,pericardiac fluid,cardiac tumors,or chamber thrombi.EchocardiographyM-mode ECHOLong-axis view for LV2-D ECHOFour-chamber view at apex2-D ECHOShort-axis view at the great

17、artery2-D color ECHO(four-chamber view)2-D color Doppler ECHO 3-D ReconstructionSVCIVCRVCardiac Catheterization Estimate Cardiac output according to Oxygen content and saturation,pulmonary and systemic blood flow.Determine the pressures in all chambers and vessels Calculate the pulmonary and systemi

18、c vascular resistance Interventional catheterization(therapeutic procedures)20%20%1214%1214%30/30/1212121214%14%1214%1214%4 84 80 50 5100/10100/1030/530/5100/60100/60Angiocardiography选择性造影选择性造影 Selective angiocardiography数字减影造影数字减影造影(DSA)(DSA)诊断复杂先心病的主要手段诊断复杂先心病的主要手段常用成角造影常用成角造影 长轴斜位：左前斜长轴斜位：左前斜6060

19、7575向头成角向头成角202030 30 肝锁位：左前斜肝锁位：左前斜40404545向头成角向头成角40 40 坐观位：正位向头成角坐观位：正位向头成角40 40 心血管造影心血管造影心血管造影心血管造影Radionuclide angiocardiography 99m99m锝锝 iv iv 释放释放射线射线 初次循环心脏造影、平衡心脏血池造影初次循环心脏造影、平衡心脏血池造影 检测左向右分流检测左向右分流 评估心功能评估心功能Magnetic resonance imaging Noninvasive tool Follow-up Evaluate the heart and the

20、great arteries Provide the imaging of vascular structures of the thorax Paul C.Lauterbur,United States,and Sir Peter Mansfield,Britain,wined the 2003 Nobel Prize for discoveries in magnetic resonance imagingSEAOPAAOLVLARVCine MRICine-MRIMRA3-D MRIMRI is in valuable in the long term follow-up of coar

21、ctation of the aorta after angioplasty.(surgical procedure)Computed tomography Follow-up Evaluate the heart and the great arteries Provide the imaging of vascular structures of the thorax第二节第二节 小儿先天性心脏病概述小儿先天性心脏病概述 概念：概念：CHDCHD是胎儿期心脏及大血管发育异常而致是胎儿期心脏及大血管发育异常而致的心血管畸形，是小儿最常见的心脏病的心血管畸形，是小儿最常见的心脏病 发病率发病率

22、:6 688，上海上海6.876.87 我国每年出生我国每年出生1515万万CHDCHD 诊治研究取得很大进展，预后大为改观诊治研究取得很大进展，预后大为改观 病病 因因 内因：内因：与遗传有关，染色体异常或基因突变。与遗传有关，染色体异常或基因突变。外因：外因：（1 1）早期宫内感染：风疹、流感、腮腺炎、柯萨奇）早期宫内感染：风疹、流感、腮腺炎、柯萨奇病毒等。病毒等。（2 2）孕母接触大量放射线服用药物史（抗癌药、抗）孕母接触大量放射线服用药物史（抗癌药、抗癫痫药癫痫药)（3 3）代谢性疾病）代谢性疾病:糖尿病、高钙血症糖尿病、高钙血症（4 4）宫内慢性缺氧）宫内慢性缺氧（5 5）妊娠早期酗

23、酒、吸食毒品）妊娠早期酗酒、吸食毒品环境因素遗传因素环境因素遗传因素Categories of congenital heart diseaseThe left-to-right shunt lesions (ASD VSD PDA)Acyanotic early Pulmonary blood increased Systemic blood decreased Pulmonary hypertension Eisenmenger syndrome:cyanotic lately due to right-to-left shuntsThe right-to-left shunt lesio

24、ns Tetralogy of Fallot(TOF),transposition of the great arteries(TGA)Cyanotic early Cyanotic lesions with increased pulmonary blood flow Cyanotic lesions with decreased pulmonary blood flow The systemic circulation is hypoxemia No-shunt lesions Pulmonary stenosis(PS),Coarctation of the aorta(Coa)Acya

25、notic Hypertrophy resulting in increased pressure loadVan Praagh 顺序分段诊断方法顺序分段诊断方法 心房位置判断心房位置判断 心室位置判断心室位置判断 大血管位置判断大血管位置判断 房室连接诊断房室连接诊断 心室大动脉连接诊断心室大动脉连接诊断 心脏位置心脏位置“三层楼结构三层楼结构”“四层楼结构四层楼结构”Diagnostic process for CHD Two groups based on PE acyanotic and cyanotic lesions Further be subdivided based on X

26、-ray increased,normal or decreased pulmonary vascular markings Determine whether right,left,or biventricular hypertrophy Confirm the diagnosis by ECHO or Catheterization,or both 第三节第三节 几种常见的先天性心脏病几种常见的先天性心脏病Common congenital heart diseases一、一、Atrial Septal defect（ASD)ASD General considerations Defin

27、ition:an opening in the atrial septum permitting the shunting of blood between the atria Incidence:10%in all CHD Three major types:(1)The ostium secundum type (2)The sinus venosus type (3)The ostium primum type ASD PathophysiologyThe degree of L-R shunt(1)The size of the defect(2)The relative compli

28、ances of RV and LV(3)the relative vascular resistances in the pulmonary and systemic circulationASD Pathophysiology In neonate and early infant limiting the L R shunt Small ASD Large ASD Qp:Qs 2 4:1 PAH：R L shunt可在临床上表现出来可在临床上表现出来ASD分流分流右心室扩大右心室扩大肺动脉充血肺动脉充血肺循环充血肺循环充血肺动脉高压肺动脉高压肺静脉动脉血肺静脉动脉血左心房左心房左心室左心

29、室主动脉搏血减少主动脉搏血减少体循环缺血体循环缺血上下腔静脉上下腔静脉右心房扩大右心房扩大ASD血液循环途径血液循环途径LVRVLARAWhy the LA is not enlarged？Small ASD：Most often asymptomatic discovered during PE Large ASD（large shunt）：）：(1)Pulmonry blood：repeated URI or pneumonia(2)Systemic blood：poor growth,pale,lack of power,hidrosis,tachypnea after exercise

30、(3)Pulmonary hypertension,Eisenmengger syndrome（cyanosis）ASD Clinical manifestationASD Cardiac sign Inspection:left precordial bulge and increased cardiac activity Palpation:systolic lift,seldom with thrill Percussion:cardiomegaly Auscultation:loud S1 2,3 LSB systolic ejection murmur,grade fixed spl

31、itting of the 2nd heart sound Lower LSB diastolic murmur Early systolic click,P2 accentuated(PAH)P2P2亢进伴固定分裂，喀喇音亢进伴固定分裂，喀喇音ASD-ASD-/SM/SMASD ECG Volume overload of the RV:QRS axis:normal or right axis deviation with a clockwise loop in the frontal plane RV hypertrophy A minor right ventricular condu

32、ction delay P-R delay In the right precordial leads,a rsR patternASD ECGI AVBASD X-rayYThe pulmonary vascularity increasedYEnlargement of the RV and RAYThe pulmonary artery dilated M mode:RV volume overload2-D：sizeColor：directionDoppler：pressure3-D：ASD 3-DASD ECHOASD catheterization Oxygen content i

33、n RA:higher The catheter:RA to LA through ASD The PA pressure:usually normal pulmonary vascular resistance Qp:Qs:1.5:1 to 4:1.ASD catheterizationASD Prognosis and Complications Pneumonia Heart failure Infective endocarditis Pulmonary hypertension Atrial arrhythmia Tricuspid regurgitationASD treatmen

34、t Surgical repair:26 yrs Early surgery:Infants with CHF or significant pulmonary hypertension,“mini”sternotomy posterior thoracotomy approach Closure with device(Amplazer)ASD封堵适应证封堵适应证(Amplatzer)年龄：通常年龄：通常3 3岁岁，608kg8kg 继发孔型左向右分流继发孔型左向右分流ASDASD 直径直径 30 mm5mm5mm 房间隔的伸展径大于房缺直径房间隔的伸展径大于房缺直径14mm14mm以上以上

35、 不合并必须外科手术的其他心脏畸形不合并必须外科手术的其他心脏畸形 外科术后残余分流外科术后残余分流 ASD封堵禁忌症封堵禁忌症 明显紫绀，肺动脉高压，右向左分流；明显紫绀，肺动脉高压，右向左分流；部分或完全肺静脉畸形引流；部分或完全肺静脉畸形引流；筛网状、冠状窦型及多发筛网状、冠状窦型及多发ASDASD；左心房发育不良；左心房发育不良；复杂型先天性心脏病；复杂型先天性心脏病；全身感染，出凝血功能障碍，阿司匹林禁忌。全身感染，出凝血功能障碍，阿司匹林禁忌。自膨胀双伞镍钛合自膨胀双伞镍钛合金网结构；金网结构；左房侧比右房侧大左房侧比右房侧大4mm4mm；腰部为腰部为3 3层膜结构，层膜结构，直径

36、即封堵器大小，直径即封堵器大小，腰长腰长34mm。ASD封堵器封堵器Closure procedureBefore and after ASD closure定义：胚胎期室间隔（流入道、小定义：胚胎期室间隔（流入道、小梁部和流出道）发育不全所致。梁部和流出道）发育不全所致。发病率：最常见的先心病发病率：最常见的先心病 占先天性心脏病占先天性心脏病2525 单独室缺单独室缺 其它合并室缺者其它合并室缺者二、室间隔缺损二、室间隔缺损（VSD)（Ventricular Septal defect）Types due to the position(1)Membranous(2)Supracrista

37、l(3)Muscular Ventricular Septal defect,VSDVSD Pathophysiology(1)Small VSD,restrictive VSD,diameter 1.0cm,RVP=LVP 小型室缺小型室缺（Roger病）病）中型室缺中型室缺大型室缺大型室缺缺损直径缺损直径(mm)10分流大小分流大小少少较多较多Qp/Qs 23大非限制性大非限制性Qp/Qs 35症状症状无或轻微无或轻微有有明显明显肺血管肺血管可无影响可无影响有影响有影响肺高压肺高压EisenmengerVSD按缺损大小分类按缺损大小分类VSD血液循环途径血液循环途径VSD分流分流肺循环充血

38、肺循环充血肺动脉充血肺动脉充血右心室右心室右心房右心房上下腔静脉上下腔静脉肺静脉回流增多肺静脉回流增多左心房扩大左心房扩大左心室扩大左心室扩大主动脉搏血减少主动脉搏血减少体循环缺血体循环缺血Why the LA is enlarged？LVRVLARA Small VSD：Most often asymptomatic discovered during PE Large VSD（large shunt）：）：(1)Pulmonry blood：repeated URI or pneumonia(2)Systemic blood：poor growth,pale,lack of power,h

39、idrosis,tachypnea after exercise,feed difficulty(3)Hoarse voice(4)Cyanosis early,Eisenmenger syndrome VSD Clinical manifestationVSD Cardiac sign Inspection:apical impulse widespread Palpation:systolic lift,with thrill Percussion:cardiomegaly Auscultation:3,4 LSB pansystolic rough murmur,diastolic mu

40、rmur at apex P2 accentuated(PAH)Cyanosis(Eisenmenger)VSD /级全收缩期杂音级全收缩期杂音VSD ECG Normal:small L-R shunts.Left ventricular hypertrophy(LVH):large L-R shunts Combined ventricular hypertrophy(both right and left):PAH caused by increased flow,increased resistance,or both.Pure RVH:PAH secondary to pulmona

41、ry vascular obstruction(Eisenmenger syndrome)VSD心电图心电图小缺损：小缺损：正常或轻度左室肥大正常或轻度左室肥大中型缺损：中型缺损：RV5RV5、V6V6升高伴深升高伴深Q Q，T T波直立高尖对称波直立高尖对称大型缺损：大型缺损：左右心室肥厚，伴心肌劳损。左右心室肥厚，伴心肌劳损。VSD X-ray Normal:small shunts Significant cardiac enlargement:large shunts The aorta:small to normal in size MPA segment:dilated The p

42、ulmonary vascular markings:increased in large shuntsVSD X-ray1.Pulmonary vascular markings increased and pulmonary edema2.Gross cardiomegaly with prominence of both ventricles,the left atrium 3.Prominence of PA4.Aortic nob:small5.Eisenmenger患儿，男，患儿，男，3y3yVSDVSD伴肺动脉高压伴肺动脉高压胸片示全心扩大，肺动脉胸片示全心扩大，肺动脉段突出，肺

43、纹理增粗段突出，肺纹理增粗ECGECG示左房大，双室大，示左房大，双室大，I IAVBAVB。VSD ECHO 2-D ECHO:the position and size of the VSD.In small defects,difficult to image visualized by color Doppler examination Pulsed Doppler:the pressure gradient across the defect Estimation of RV pressure Determine the presence of aortic valve insuff

44、iciency or leaflet prolapse in the case of supracristal VSDsVSD ECHO-DopplerCatheterization and angiocardiography Severe PAH Multi-VSD aortic valve insufficiency or leaflet prolapse Complicated CHD An increase in oxygen content in the right ventricleCatheterization and angiocardiographyPrognosis and

45、 complication of VSD Spontaneous closure Aneurysm of membranous septum Congestive heart failure Infective endocarditisMedical managementCHF:Digitalis,Diuretics,vasodilator agentSurgery:infant with progressive PAH Large VSD ineffective to medicine Qp:Qs2:1 Supracristal VSDThanscatheter closure of mus

46、cular or perimembranous VSDs with the devices(Amplatzer)Amplatzer封堵膜部封堵膜部VSDVSD适应证适应证年龄年龄3 3岁，岁，605kg5kg有血流动力学意义的单纯有血流动力学意义的单纯VSDVSD膜周部膜周部VSDVSD直径直径3mm3mm，最窄直径，最窄直径14mm16mm16mm 合并其他心脏畸形而不能进行介入者合并其他心脏畸形而不能进行介入者VSD封堵器封堵器（1 1）包括输送系统和封堵双）包括输送系统和封堵双面伞；面伞；（2 2）双面伞是自膨胀镍钛合）双面伞是自膨胀镍钛合金网结构；金网结构；（3 3）左室侧伞不对称，一

47、端）左室侧伞不对称，一端仅仅0.5mm0.5mm的边缘，另一端的边缘，另一端5mm5mm边边缘；缘；（4 4）右室侧伞为均匀有）右室侧伞为均匀有5mm5mm边缘；边缘；（5 5）腰的直径代表封堵器规格）腰的直径代表封堵器规格：4mm、6mm、8mm、10mm、12mm、14mm、16mm。VSD封堵前后封堵前后ECHOPatent ductus arteriosus（PDA)Definition:PDA is the persistence of the normal fetal vessel that joins the pulmonary artery to the aorta Incid

48、ence:15%in CHD In preterm infants (1)Duct type (2)Tundish type (3)Window typeClassification of PDA PDA血液动力学血液动力学 左向右分流的大小取决于左向右分流的大小取决于导管的粗细及主、肺动脉导管的粗细及主、肺动脉压差压差 左向右连续分流左向右连续分流 充血性心力衰竭充血性心力衰竭 动力性肺动脉高压动力性肺动脉高压 梗阻性肺动脉高压梗阻性肺动脉高压 差异性紫绀差异性紫绀PDA血液循环途径血液循环途径PDA分流分流右心室右心室肺动脉充血肺动脉充血肺循环充血肺循环充血肺动脉高压肺动脉高压肺静脉回流增

49、多肺静脉回流增多左心房扩大左心房扩大左心室扩大左心室扩大主动脉主动脉体循环缺血体循环缺血脉压差增宽脉压差增宽上下腔静脉上下腔静脉右心房右心房LVRVLARAWhy LA is enlarged in PDA？PDA Clinical Manifestationsymptom A small PDA:Most often asymptomatic A large PDA:heart failure similar to that encountered in infants with a large VSD cough,tachypnea,feeding difficulty,poor grow

50、th Differential cyanosisPDA Cardiac sign Inspection:apical impulse prominent,heaving Palpation:lift,with thrill Percussion:cardiomegaly Auscultation:continuous murmur,like machinery or rolling thunder Diastolic murmur at apex P2 accentuated Peripheral vessel sign:water hammer pulse-/continuous murmu