NOTICE Saturday morning & afternoon theory lesson !!! 1

Development of Cardiovascular system

Key points Development of primitive cardiovascular system Development of Heart Circulation before and after birth Congenital Malformations 3

Inner cell mass→2 layers of cell in disc (7th day) Epiblast: columnar cells Hypoblast: cuboidal cells Decidua Syncytiotrophoblast Epiblast Hypoblast Primary yolk sac Amniotic cavity Cytotrophoblast Nutritional requirements by diffusion 4

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Primitive streak 6

Yolk sac mesenchyme cells 1. Development of Early Blood Vessels(3rd) Yolk sac mesenchyme cells blood islands Central C Peripheral C Hematopoietic endothelia cell Blood C Vessels induce by FGF

Hematogenous organs Time Organ 3~6 wk Yolk sac 6~11 wk Liver 12 wk~5 month Spleen From 2 month on Bone marrow 8

Endothelial tubes expanded outgrowth from the wall and form meshwork Endothelial tubes form in same manner in stalk and chorion in 19th days. Endothelial tubes expanded outgrowth from the wall and form meshwork 3rd,intraembryo and extraembryo are conneted with each other by body stalk. 9

Blood vessel development occurs by two mechanisms: vasculogenesis ,the major vessels, including the dorsal aorta and cardinal veins, are formed by vasculogenesis. angiogenesis whereby vessels sprout from existing vessels. the remainder of the vascular system then forms by angiogenesis. 10

primitive cardiovascular system 1.1 Formation Vessels net 11

1.2 Component ① heart tube：2 tubes 1 tube  Primitive heart Heart tubes 20d 4w End of 4w ① heart tube：2 tubes 1 tube  Primitive heart ② arteries ③ veins ① heart tube：2 tubes 1 tube  Primitive heart ② arteries ③ veins 12

① heart tube ② arteries ③ veins 2 dorsal A  1 aorta，many branches Aortic arches Dorsal aorta 20d 4w End of 4w Vitelline A Umbilical A ① heart tube ② arteries ③ veins 2 dorsal A  1 aorta，many branches Few pairs of vitelline A 1 pair of umbilical A 6 pairs of aortic arches two dorsal aortae combine to become the descending aorta in later development. 13

3. Formation and modification of aortic arches 14

Formation and modification of aortic arches third —carotid arteries (internal and external artery Left fourth– arch of the aorta Right fourth-right subclavian artery Sixth(left)– pulmonary artery&ductus arteriosus sixth (right )--disappears 15

① heart tube ② arteries ③ veins Common cardinal V A cardinal V Posterior Vitelline V Common cardinal V Umbilical V 20d 4w End of 4w ① heart tube ② arteries ③ veins 1 pair of anterior cardinal V 1 pair of posterior cardinal V 1 pair of vitelline V 1 pair of umbilical V Common cardinal V 16

1.3 Three separate circulations (end of 4th week) vitelline, umbilical and embryonic circulation. 17

By the end of the 3rd week: The embryo has a system of paired vessels. The vessels forming the heart have fused. Three separate circulations vitelline, umbilical and embryonic circulation. 18

2. Development of the Heart 2.1 Development of the heart tube 2.2 Morphogenesis of the heart 2.3 Partitioning of Heart Chambers 2.4 Development of sinus venosus and differentiation of veins 19

2.1 Development of the heart tube Cardiogenic area Buccopharyngeal membrane Cardiogenic area is anterior to the buccopharyngeal membrane and the neural plate. 20

2.1 Development of the heart tube Pericardial cavity cardiac tube The 20th d C. cardiaogenic plate becomes hollow--cardiac tube 21

2.1 Development of the heart tube Pericardial coelom cardiac tube The 22nd d CNS grow cephalad so rapidily that it extends over the cardiogenic area and pericardial cavity, buccophangeal membrane is pulled forward ,the heart and percardial cavity move first the cervial region and finally to the thorax D. As the embryo folds cephalocaudally, the developing heart tube bulges more and more into the pericardial cavity. 22

2.1 Development of the heart tube Pericardial coelom cardiac tube The 28th d E. The paired heart tubes merge except at their caudalmost ends. F. The tube remains attached to the dorsal side of the pericardial cavity by the dorsal mesocardium. 23

2.1 Development of the heart tube Transverse sinus Heart tube Pericardial cavity G. The dorsal mesocardium disappears, creating the transverse pericardial sinus. H. Cephalic end  Arteries，caudal end  Veins 24

Wall of primitive heart tube Endocardial heart tube → endocardium Myoepicardial mentle → myocardium, epicardium Cardiac jelly → subendocardial tissue 25

2. Development of the Heart 2.1 Development of the heart tube 2.2 Morphogenesis of the heart 2.3 Partitioning of Heart Chambers 2.4 Development of sinus venosus and differentiation of veins 26

2.2 Morphogenesis of the heart The 21st d Vein end Cardiac tube Artery end A. Part of the cardiac tubes merged B. Cephalic end A Caudal end V 27

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2.2 Morphogenesis of the heart The 22nd d atrium ventricle bulbus cordis C. Heart tubes almost merged D. Three expansions bulbus cordis ventricle atrium 29

2.2 Morphogenesis of the heart The 23rd d truncus arteriosus E. The 4th expansion, sinus venosus appears ----caudal end F. truncus arteriosus appears --cephalic end G. The heart tube starts to bend bulbus cordis ventricle atrium sinus venosus 30

As the heart tube elongates and begins to loop, the blood flows into the sinus venosus, then into the primitive atria, ventricles and bulbous cordis before entering the visceral arch vessels.                                                                     31

2.2 Morphogenesis of the heart The 24th d truncus arteriosus The cephalic portion bends ventrally, caudally,and to the right. The caudal part shifts dorsocranially and to the left. Form a ‘U’ shape structure---- cardiac loop (bulboventricular loop). Bulboventricular loop Sinus venosus 32

bulbus cordis proximal third -----primitive the right ventricle. midportion( the conus cordis)----outflow tracts of both ventricles. distal bulbus(the truncus arteriosus)---roots and proximal portion of the aorta and pulmonary artery 33

2.2 Morphogenesis of the heart The 35th d Aortic arches I. The bulboventricular loop keeps turning, the atrium shifts to the cephalodorsal of the ventricle G. Two atria and two ventricles atrium ventricle The normal heart shape was established, but partitioning has not completed 34

2. Development of the Heart 2.1 Development of the heart tube 2.2 Morphogenesis of the heart 2.3 Partitioning of Heart Chambers 2.4 Development of sinus venosus and differentiation of veins 35

2.3 Partitioning of Heart Chambers 2.3.1. Division of atrioventricular canal 2.3.2. Partitiioning of the primitive atrium 2.3.3. Partitioning of the primitive ventricle 2.3.4. Division of truncus and bulbus 36

Division of atrioventricular canal Subendocardial tissue → 2 endocardial cushions → fuse → right and left canals 37

The 5th w 2.3.1 Division of atrioventricular canal Fusion of the opposing superior and inferior cushions divides the orifice into R and L aterioventricular canals. Endocardiac cushion L AV orifice R AV orifice The 5th w 38

Partitioning of primitive atrium(4th) 1) Septum primum(sickle-shaped) → endocardial cushions → ostium primum. 39

Looking into the atrial chambers, the septum primum and its union with the endocardial cushions are evident 40

2) Septum primum absorbed → ostium secundum → ostium primum closing 3) Septum secundum(crescent-shaped) → cover the ostium secundum → ovale foramen 41

Early 6th w Partitioning of the primitive atrium Septum secundum Foramen secundum H. Septum secundum extends downward to cover the foramen secundum, but leaving an opening, foramen ovale I. The septum primum covers the foramen ovale, serves as a valve. Septum primum Foramen ovale Early 6th w 42

4) Blood from right to left atrium ovale foramen 43

Partitioning of the primitive atrium From R G. Blood L atrium R L atrium K. After birth, lung circulation begin and pressure in left atrum increase,the oval foramen is pressed agaimst the septum secundum,obliterating the oval foramen-- 44

Summary Development of the heart tube Development of the heart Morphogenesis of the heart Partitioning of Heart Chambers 45

2.3.3. Partitioning of the primitive ventricle ( 4th) The muscular Interventricular septum grows up from the floor of the ventricle. EC LV RV Inter-ventricular septum The 4th w 46

                                                                             Frontal section through the heart of an embryo at the end of the seventh week. The conus septum is complete, and blood from the left ventricle enters the aorta. Note the septum in the atrial region. 47

2.3.3. Partitioning of the primitive ventricle B. The muscular interventricular septum keeps growing up, an interventricular foramen remains. EC Inter- ventricular foramen IV septum End of the 5th w 48

2.3.3. Partitioning of the primitive ventricle C. Endocardial cushion, right and left bulbar ridges → membranous interventricular septum → interventricular foramen closed EC Membranous IV septum IV septum End of the 7th w 49

2.3.3. Partitioning of the primitive ventricle The interventricular septum=muscular part + membranous portion

2.3.4. Division of truncus and bulbus The 5th w truncal ridge Truncus arteriosus bulbar ridge bulbus A. Two spiral truncal ridges grow from the inner walls, and bulbar ridges also form in the bulbus. 51

2.3.4. Division of truncus and bulbus Aorta pulmonary Aortico- pulmonary septum B. These ridges grow into the truncus from either side and fuse in the middle. C. Truncal ridges + Bulbar ridges → aorticopulmonary septum 52

2.3.4. Division of truncus and bulbus D. The ridges spiral neatly down the truncus until they reach the ventricles. 53

2.3.4. Division of truncus and bulbus E. Aorticopulmonary septum divides the bulbus and truncus into two channels: pulmonary trunk connecting to the right ventricle; aorta connecting to the left ventricle. 54

2.3.4. Division of truncus and bulbus F. As the same time, the division of the ventricle is completed. 55

Truncus swellings → hollowed out at upper surface → semilunar valves 5 week 6 week 7week 6 week 7 week 9 week 56

2.4 Development of sinus venosus and differentiation of veins middle of the fourth week, three important veins: (a) the vitelline (b) the umbilical vein, (c) the common cardinal vein. communication between the sinus and the atrium is wide. the entrance of the sinus shifts to the right .caused by left-to-right shunts of blood, 57

2.4 Development of sinus venosus and differentiation of veins Fifth, right umbilical vein and the left vitelline vein obliteration--the left sinus horn loses its importance 10 weeks , left common cardinal vein obliterated, left sinus horn is the oblique vein of the left atrium and the coronary sinus 58

2.4 Development of sinus venosus and differentiation of veins right sinus horn and veins enlarge greatly. The right horn,----incorporated into the right atrium to form the smooth-walled part of the right atrium , develops into two parts: (a) the valve of the inferior vena cava, and (b) the valve of the coronary sinus left venous valve and the septum spurium fuse with the developing atrial septum 59

the primitive left atrium is expanding the primitive left atrium is expanding. a single embryonic pulmonary vein During further development, the pulmonary vein and its branches are incorporated into the left atrium, forming the large smooth-walled part of the adult atrium. four pulmonary veins enter as the branches are incorporated into the expanding atrial wall. 60

Sinus-atrial orifice → right; Right horn enlarges (due to left-to-right shunts of blood in venous system) Sinus-atrial orifice → right; Receives superior and inferior vena cava; Right horn → right atrium (smooth walled part). 61

Pulmonary vein and its branches → left atrium (smooth walled part) 2) Left horn degenerates → coronary sinus, oblique vein of left atrium; Pulmonary vein and its branches → left atrium (smooth walled part) 62

4. Circulation before and after Birth before birth Placental circulation: umbilical A. & V. ductus venosus foramen ovale ductus arteriosus 63

58% 80% O2 saturation 64

Changes after birth Umbilical arteries proximal portion—superior vesical arteries distal parts—medial umbilical ligaments Umbilical vein → ligamentum teres hepatis Ductus venosus → ligament venous Ductus arteriosus → arterial ligament Foramen ovale → oval fossa 65

Congenital Malformations Atrial septal defect Excessive resorption of the septum primum; Inadequate development of the septum secundum. 66

Ventricular septal defect Defect of the membranous septum, isolated or associated with other abnormalities. 67

In the case of a VSD there is a massive left to right shunting of blood and pulmonary hypertension. The absence of the interventricular septum results in a Common Ventricle. 68

Unequal division of conus cordis; Tetralogy of Fallot Unequal division of conus cordis; 4 defects: pulmonary stenosis, overriding aorta, ventricular septal defect, hypertrophy of right ventricle; Causing cyanosis(发绀） 69

Persistent truncus arteriosus Truncoconal ridges fail to fuse and descend; Truncus overrides both ventricles; Accompanied by ventricular septal defect; Cyanosis, blood to lungs increased. 70

Absence or fusion of tricuspid valves; Tricuspid atresia Absence or fusion of tricuspid valves; Patent oval foramen & ventricular septal defect; Underdeveloped right ventricle 71

overview The cardiovascular system is derived from the mesoderm. It appears in the middle of the 3rd week. Blood circulation starts by the end of the 3rd week. Some changes take place at birth and in the 1st postnatal month. 72

Formation and division of the heart tube; SUMMARY Formation and division of the heart tube; Partitioning of atrioventricular canal, autrium, ventricle, and truncus and bulbus; Congenital heart diseases. 73