Circulation system 陳建榮 http://web.nchu.edu.tw/pweb/users/chenjr/

Normal development of Heart Early Events Migration of cardiogenic mesenchyme Differentiation of mesenchyme Chamber formation Folding of the heart tube Critical Changes Vascular Changes

Migration of cardiogenic mesenchyme

血管母細胞索

Differentiation of mesenchyme 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

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

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.

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

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

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

Inflow and outflow trunks are positioned posteriorly as a result of the dorsal fold

Normal development of Heart Early Events Critical Changes Endocardial cushion（心內墊） growth and fusion Bulboventricular looping 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

Endocardial cushion 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).

Valvular atresia 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

Bulboventricular looping 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.

Looping anomalies(dextrocardia)

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

原隔 原孔 次孔 次隔

Fossa ovalis卵圓窩

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).

Formation of left atrium

Interventricular septum formation AP - aorticopulmonary; ECC - endocardial cushion; Blue arrow - direction of bulbar ridge growth; Red arrow - direction of ventricular growth  IVS Part Origin muscular ventricular wall membranous fused bulbar ridges 球狀脊 fused endocardial cushions

球狀脊

室間孔

Ventricular septal defects心室間隔缺損(VSD)

Atrioventricular septum defect房室瓣缺損

Aortico-pulmonary septum formation The aortico-pulmonary (AP) septum 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

Tetralogy of Fallot 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

Eisenmenger's syndrome Characteristics of Eisenmenger's syndrome: persistent truncus arteriosus ventricular septal defect left-right ventricular shunt right ventricle hypertrophy

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

Overview of embryonic circulatory system

Venous system development

Arterial system development

Aortic arch derivatives 動脈韌帶 動脈導管

Recurrent laryngeal n. and 6th aortic arch

Coarctation of aorta 主動脈弓緊縮

Right arch of aorta

Anomalies of right subclavian artery

Anatomical correlations

Ductus arteriosus

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

Embryologic Structure Adult 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  Left vitelline vein fuses with right vitelline vein to form portal vein  Right vitelline vein fuses with left vitelline vein to form portal vein

Development of lymphatic system