1. Development of the circulation system 陳建榮 http://web.nchu.edu.tw/pweb/users/chenjr/

2. Midgut development of animals

3. Normal development of circulation system -Early Events -Migration of cardiogenic mesenchyme -Differentiation of mesenchyme -Chamber formation -Folding of the heart tube -Critical Changes -Vascular Changes

4. Migration of cardiogenic mesenchyme

5. 血管母細胞索

6. The early heart is a simple tube which commences beating during the third week (Day 21-22). Cardiogenic mesenchyme differentiates into three distinct cell populations: -Endocardium 心內膜 -Myocardium 心肌 -Epicardium 心外膜 Differentiation of mesenchyme

8. Cell Population Functions and Fates Endocardium Endothelial lining Connective tissue precursor (Valves and fibrous skeleton) Myocardium Myocytes Conduction system (Purkinje fibres) Myoendocrine cells (Atrial Natriuretic Factor production) Epicardium Coronary vessel precursors Visceral pericardial lining SA node, AV node  mesoderm

9. Early heart chambers Sinus venosus (SV) 靜脈竇 This is the collecting compartment of the heart. Oxygenated blood from the placenta and deoxygenated blood from embryonic tissues are mixed in the sinus. Primitive atrium (PA) 心房原基 This is the compartment destined for further partition to the definitive atria. Primitive ventricle (PV) 心室原基 This is the compartment destined for further partition to the definitive ventricles. Bulbus cordis (BC) 心球 This will contribute to the pulmonary trunk and aorta, along with the truncus arteriosus. Truncus arteriosus (TA) 動脈幹 This will contribute to the aortic arches. Fibrous skeleton (FS) 纖維骨架 This is the area of connective tissue proliferation, site of future valves.

10. Folding of the heart tube Apoptosis in the dorsal mesocardium will allow movement of the early heart tube within the pericardial cavity Ant. Post.

12. Normal development of Heart -Early Events -Critical Changes -Endocardial cushion （心內墊） growth and fusion -Bulboventricular looping 動脈球心室環 -Interatrial septum （心房間隔） formation -Interventricular septum （心室間隔） formation -Aortico-pulmonary septum （主肺動脈隔） formation -Vascular Changes

13. Endocardial cushion 心內墊 fusion Endocardial cushions are areas of the fibrous skeleton forming between the atrium and ventricle. Endocardial cushions serve two important functions: -form a partition in the heart tube between the atrium (PA) and ventricle (PV) (tricuspid and bicuspid valves) -provide a "scaffold" of the interatrial septae and the interventricular septum Defects in endocardial cushion fusion are associated with trisomies 18 and 21 (Down's syndrome).

15. Valvular atresia 房室瓣閉鎖 Valvular atresias arise from the uneven partition of the AV canal. Depending on the size and position of the narrowed channel, a tricuspid atresia or a biscuspid atresia results. Atresias arising from anomalous partition of the canal are referred to as congenital atresias Clinical problems

16. The folding of the heart tube brings the inflow and outflow trunks in an adjacent position at the superior aspect of the developing heart.

17. The dorsal fold forms the two pericardial sinuses and places the fibrous skeleton in a single plane

18. Inflow and outflow trunks are positioned posteriorly as a result of the dorsal fold Bulboventricular loop 動脈球心室環

19. Bulboventricular looping 動脈球心室環 BV looping is a consequence of several changes: - Dorsal folding The first dorsal fold forms an expanded primitive ventricle, referred to as the bulboventricular loop. - Ventricular growth Differential growth of the proximal ventricular tissue causes a counter-clockwise rotation of the folded heart tube. The site of ventricular growth marks the future left ventricle. Abnormal growth of the distal primitive ventricle causes clockwise rotation, an anomaly known as dextrocardia 心偏右. - AV canal 房室管 partitioning The Atrio-Ventricular (AV) canal between the primitive atrium and ventricle has now been partitioned by the fusing endocardial cushions. - Shunting of venous return The development of the venous system causes an increase in right-sided venous return to the primitive atrium. Combined with the partitioning of the AV canal, the change in blood flow volume and directions assists in the outgrowth of the left ventricle.

21. Dextrocardia 心偏右

22. Looping anomalies(dextrocardia 心偏右 ) Clinical problems

23. Bulboventricular looping 動脈球心室環 BV looping is a consequence of several changes: - Dorsal folding The first dorsal fold forms an expanded primitive ventricle, referred to as the bulboventricular loop. - Ventricular growth Differential growth of the proximal ventricular tissue causes a counter-clockwise rotation of the folded heart tube. The site of ventricular growth marks the future left ventricle. Abnormal growth of the distal primitive ventricle causes clockwise rotation, an anomaly known as dextrocardia 心偏右. - AV canal 房室管 partitioning The Atrio-Ventricular (AV) canal between the primitive atrium and ventricle has now been partitioned by the fusing endocardial cushions. - Shunting of venous return The development of the venous system causes an increase in right-sided venous return to the primitive atrium. Combined with the partitioning of the AV canal, the change in blood flow volume and directions assists in the outgrowth of the left ventricle.

25. Interatrial septum formation Blue arrows - direction of growth; Red arrow - direction of blood flow; ECC - endocardial cushion; RA - right atrium; LA - left atrium.

26. 原隔 原孔 次孔 次隔

28. Fossa ovalis 卵圓窩

29. Atrial septal defects 心房間隔缺損 (ASD) Atrial septal defects (ASD) are fairly common, present in 10-15% of patients with congenital cardiac anomalies. It is more commonly observed in females than males (2-3:1). Clinical problems

30. Atrium septum defects (ASD)

31. Formation of left atrium

32. IVS PartOrigin muscular ventricular wall membranous fused bulbar ridges 球狀脊 fused endocardial cushions AP - aorticopulmonary 主肺動脈幹 ; ECC - endocardial cushion 心肉墊 ; Blue arrow - direction of bulbar ridge growth; Red arrow - direction of ventricular growth Interventricular septum formation 球狀脊

35. 室間孔

36. Ventricular septal defects 心室間隔缺損 (VSD) Clinical problems

37. Atrioventricular septum defect 房室瓣缺損

38. Aortico-pulmonary septum formation The aortico-pulmonary (AP) septum 主肺動脈間隔 arises within the truncus arteriosus. The septum results from the downwards growth and fusion of bulbar ridges, induced by invasion of neural crest cells. The AP septum serves to divide the ventricular outflow between the pulmonary artery and the ascending aorta 球狀脊

42. Semilunar valve 半月瓣

43. Aortic stenosis and atresia 動脈瓣膜狹窄、閉鎖 Clinical problems

44. Tetralogy of Fallot ( 法樂氏四重畸形 ) The tetralogy of Fallot results from the asymmetric division of the AP septum. The result is a stenosed pulmonary artery and a VSD. Tetralogy of fallot: -Pulmonary valve stenosis -Ventricular septal defect -Overriding aorta -Hypertrophy of right ventricle

46. Eisenmenger's syndrome( 森曼格綜合症 ) Characteristics of Eisenmenger's syndrome: -persistent truncus arteriosus -ventricular septal defect -left-right ventricular shunt -right ventricle hypertrophy

47. Normal development of Heart -Early Events -Critical Changes -Vascular Changes -Overview of embryonic circulatory system -Venous development -Arterial development -Anatomical correlations

48. Overview of embryonic circulatory system

51. Venous system development

55. Persistent left superior vena cava Clinical problems

57. Arterial system development

60. Aortic arch derivation: -1st pair of aortic arches: maxillary a. -2nd pair of aortic arches: stapedial a. -3rd pair of aortic arches: common carotid a. and int. carotid a. -4th pair of aortic arches: -Left  aortic arch -Right  subclavian a. -5th pair of aortic arches: -6th pair of aortic arches: -Left  left pulmonary a., ductus arteriosus -Right  right pulmonary a.

61. Aortic arch derivatives 動脈導管 動脈韌帶

62. Aortic arch derivatives 動脈導管 動脈韌帶

63. Recurrent laryngeal n. and 6th aortic arch

64. Anomalies of aortic arch Double aortic archRight arch of aorta Anomalies of right subclavian artery Normal Clinical problems

65. Right arch of aorta Clinical problems

66. Double aortic arch 雙主動脈弓

67. Anomalies of right subclavian artery

68. Anatomical correlations

70. Portacaval shunt 門脈分流 = portasystemic shunt

71. Porto-systemic (porta-cava) shunt Intrahepatic porto-systemic shunt Extrahepatic porto-systemic shunt Clinical problems

72. Ductus arteriosus 動脈導管

73. Persistent Ductus arteriosus

74. Patent ductus arteriosus Blue-pulmonary trunk; Red-aorta and tributaries; Green-patent ductus arteriosus

75. PDA Closure Device Surgery

80. Embryologic StructureAdult Equivalent Left anterior cardinal vein disappears proximally distal portion contributes to Left superior intercostal vein anastomoses with Right anterior cardinal vein distally to form Left brachiocephalic vein Left common cardinal vein oblique vein of left atrium Left posterior cardinal vein disappears Left horn of sinus venosus coronary sinus Right anterior cardinal vein superior vena cava Right common cardinal vein superior vena cava Right posterior cardinal vein azygous vein Primitive atrium right auricle Foramen ovale fossa ovalis and limbus First aortic arch maxillary artery contribution to external carotid artery Second aortic arch persists dorsally as stapedial artery Third aortic arch proximal portions form common carotid artery distal portions form internal carotid artery Fourth aortic arch left arch (with aortic sac) forms ascending aorta and arch right arch contributes to right subclavian artery Fifth aortic arch does not persist Sixth aortic arch proximal left arch - left pulmonary artery distal left arch - ligamentum arteriosum proximal right arch - right pulmonary artery distal right arch - does not persist Ductus venosus ligamentum venosum Left umbilical vein ligamentum teres distally degenerates proximally portion within septum transversum contributes to hepatic portal system Right umbilical vein degenerates proximally and distally portion within septum transversum contributes to hepatic portal system Left vitelline vein fuses with right vitelline vein to form portal vein Right vitelline vein fuses with left vitelline vein to form portal vein

81. Development of lymphatic system Lymph sac 淋巴囊 -2 jugular lymph sac 頸淋巴囊 -1 retroperitoneal lymph sac 腹膜後淋巴囊 -1 cisterna chyli 乳糜池 -2 iliac lymph sac 髂淋巴囊