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Home , Aorticopulmonary septum, Aortic sac, Blood islands, Bulbus cordis, Foramen secundum, Primitive atrium

Human

1 Anhui Medical University

Development of the

Dr. Lijie Feng Department of Histology and Embryology School of Basic Medical science School of International Education Anhui Medical University

2 Anhui Medical University Development process of an embryo

zygote blastocyst implantation

amnion amnion cavity amnion body stalk umbilical body stalk cord blastoderm amnion yolk sac exocoelom chorion 20 weeks 4 weeks 3 weeks

Question: How embryos receive oxygen and nutrients? 3 Anhui Medical University

Maternal blood diffusion Circulatory system development

4 Anhui Medical University Content

 Establishment of the primordial cardiovascular system

 * Development of the

 Fetal blood circulation and changes in the circulation after

 Congenital defects of the cardiovascular system

5 Anhui Medical University Content

 Establishment of the primordial cardiovascular system

 Development of the heart

 Fetal blood circulation and changes in the circulation after birth

 Congenital defects of the cardiovascular system

6 Anhui Medical University Establishment of the primordial cardiovascular system  Period: in the 3rd-7th weeks of

 Origin: mesoderm  Significance: provide nutrition and oxygen and remove wastes and carbon dioxide

7 Anhui Medical University Establishment of the promordial cardiovasular system

1) Extra-embryonic blood vessels  The 15th day, mesenchymal cells in the wall of yolk sac proliferate to form isolated cell clusters ----

body stalk amnion cavity ectoderm endoderm

Primordial heart

Yolk sac

extra embryonic mesoderm

Blood islands 8 Anhui Medical University Establishment of the promordial cardiovasular system  Peripheral cells endothelial cells endothelial tube  Central cells primitive blood cells (blood stem cell)  Endothelial tube approach and fuse with each other to form an endothelial tube network

Mesenchymal cell

endothelial cell

primitive blood cell 9 Anhui Medical University Establishment of the promordial cardiovasular system • Endothelial tube network appears in chorionic membrane and body stalk, and connect to vitelline circulation.

villi amnion cavity

amnion

Blood vessel Primordial heart

body stalk

Yolk sac chorionic membrane Blood islands Blood vessel

10 Anhui Medical University Establishment of the promordial cardiovasular system 2) Intra-embryonic blood vessels  The 18-20th days, blood island appears in the mesenchyma of intraembryonic splanchnic mesoderm to form intraembryonic endothelial tube network  By the end of 3rd week, intraembryonic and extra- embryonic endothelial tube networks connect to each other to form primitive cardiovascular system

Blood circulation begins at the end of 4nd week

11 Anhui Medical University Formation and variation of blood islands

D15, mesenchymal cells D18-20 intraembryonic in the wall of yolk sac mesenchymal cells

Blood island

Central cells Peripheral cells

Primitive blood cells Endothelial cells

Blood cells Endothelial tube

Primitive cardiovascular Endothelial tube network system (later of 3rd weeks) 12 Anhui Medical University Establishment of the primordial cardiovasular system  Mesenchyme near the endothelial tube differentiate into smooth muscles and CT, form the vascular medial and adventitia, evolve into artery and vein.

13 Anhui Medical University 3) Components of the primordial cardiovascular system  Primitive cardiovascular system include:

- Cardiac tubes - Artery - Vein

14 Model of primitive cardiovascular system (4th weeks) Anhui Medical University 3) Components of the primordial cardiovascular system  Cardiac tube: paired, fuse into a single cardiac tube at the 4th week.

Cardiac tube Cardiac tube Primitive heart

d20 Early of 4w Later of 4w

15 Anhui Medical University 3) Components of the primordial cardiovascular system  Arteries  At the end of 3rd weeks  Paired, the head end connect to cardiac tube  Composition:

-- Abdominal artery -- -- Aortic arch

Cardiac tube

d20 16 Anhui Medical University 3) Components of the primordial cardiovascular system  Arteries Abdominal aorta: paired, the head end connect to cardiac tube, fused to form an .

Abdominal aorta Abdominal aorta Abdominal aorta

d20 Early of 4w Later of 4w

17 Anhui Medical University 3) Components of the primordial cardiovascular system  Arteries Abdominal aorta: paired, the head end connect to cardiac tube, fused to form a aortic sac Dorsal aorta: paired, fused to form a single vessel at the 4th week - vitelline artery: several paired, supply the yolk sac - : paired, allantoic artery, supply chorionic membrane

Dorsal aorta Dorsal aorta Dorsal aorta umbilical artery Umbilical artery

Vitelline artery vitelline artery d20 Early of 4w Later of 4w 18 Anhui Medical University 3) Components of the primordial cardiovascular system  Arteries Abdominal aorta: paired, the head end connect to cardiac tube, fused to form a aortic sac Dorsal aorta: paired, fused to form a single vessel at the 4th week Aortic arch: 6 pairs, connect dorsal aorta to aortic sac

Aortic arch Aortic arch

d20 Early of 4w Later of 4w

19 Anhui Medical University 3) Components of the primordial cardiovascular system  Veins: : paired, from upper part of the body : paired, from lower part of the body --- common cardinal vein (cardiac tube)

anterior cardinal vein posterior cardinal vein

d20

4 weeks 20 Anhui Medical University 3) Components of the primordial cardiovascular system  Veins: - common cardinal vein - vitelline vein : paired, from yolk sac sinus venosus - : paired, from chorionic membrane

21 Anhui Medical University 3) Components of the primordial cardiovascular system Three sets of blood circulation existed at the end of 3rd week

Embryonic circulation

Umbilical circulation

Vitelline circulation

22 Model of primitive cardiovascular system (4th weeks) Anhui Medical University Content

 Establishment of the promordial cardiovasular system

 * Development of the heart

 Fetal blood circulation and changes in the circulation after birth

 Congenital defects of the cardiovasular system

23 Anhui Medical University  Development of the heart

-- Formation of primitive heart

-- Establishing of the heart shape

-- Partitioning of the heart

24 Anhui Medical University  Development of the heart

1. Formation of primitive heart

2. Establishing of the heart shape

3. Partitioning of the heart

25 Anhui Medical University 1) Formation of primitive heart

The heart arises from cardiogenic area, which located in mesoderm situated cephalic of oropharyngeal membrane

brain amnion oropharyngeal membrane

body stalk

Yolk sac Allantois cloacal membrane cardiogenic area oropharyngeal membrane

Cardiogenic area

oropharyngeal membrane 26 1) Formation of primitive heart Anhui Medical University

Pericardiac coelom: space in cardiogenic area D18-19 Cardiogenic plate: mesodermal cells ventral to the pericardiac coelom aggregate and form two longitudinal, paired cell cords.

pericardiac coelom

Cardiogenic plate oropharyngeal membrane

d19 27 Anhui Medical University 1) Formation of primitive heart D20 Cardiac tubes: The cardiogenic plate become canalized to form two cardiac tubes.

pericardiac coelom

cardiac tube

28 1) Formation of primitive heart Anhui Medical University  Cephalic fold of the embryo pulls the cardiac tube and pericardiac coelom forward and located in ventral of pharynx

notochord

d20

head Tail folds folds

cardiac tube

d22 pericardiac coelom 29 Anhui Medical University 1) Formation of primitive heart

 Cephalic folds of the embryo pulls the cardiac tube and pericardiac coelom forward and located in ventral of pharynx

Cardiac tube

pericardiac coelom

d28 30 1) Formation of primitive heart Anhui Medical University

 Lateral folds of the embryo make the two cardiac tubes close together, then fused into a single layer in the midline.

neural groove dorsal aorta amnion yolk sac pericardiac coelom pericardiac cardiac tube d19 coelom Cardiogenic d20 plate dorsal mesocardium neural tube

foregut pericardial cavity

cardiac tube

d21 d22 31 Anhui Medical University 1) Formation of primitive heart

 Dorsal mesocardium: cardiac tube invaginate into pericardiac coelom and connect to it by dorsal mesocardium

Pericardiac coelom turns into the pericardial cavity

dorsal mesocardium neural tube

dorsal foregut mesocardium pericardial cavity cardiac tube

cardiac tube pericardiac coelom

d22 32 1) Formation of primitive heart Anhui Medical University

 Mesenchyme adjacent to of cardiac tube proliferate and

differentiate into subendothelium of endocardium, myocardium and

epicardium.

The wall of heart is formed

section truncus artiriosus

foregut Transverse sinus

venous sinus cardiac wall

pericardial cavity

thoracic wall D28 Lateral view D28 transection 33 Anhui Medical University  Development of the heart

1. Formation of primitive heart

2. Establishing of the heart shape

3. Partitioning of the heart

34 Anhui Medical University 2) Formation of the heart shape  Single cardiac tube connected caudally to the vein; cephalically connected to the artery, two ends fixed with pericardial cavity.

D21 truncus artiriosus artery end

Transverse sinus Fused cardiac tube venous sinus

atrium

pericardial cavity Unfused cardiac tube

D28 Lateral view transversum Vein end 35 Anhui Medical University 2) Formation of the heart shape Three dilatations: Two constriction:

 bulboventricular sulcus   atrioventricular groove  atrium

Truncus arteriosus

bulbus cordis d22

cardiac ventricle

cardiac atrium

Sinus venosus transversum transversum 36 Anhui Medical University

 Sinus venosus: the 4th dilatation. Left and right horns which receives the umbilical, vitelline and .  : distal part of the bulbus cordis, connect with aortic sac cephalically.

Truncus arteriosus

bulbus cordis

d22 cardiac ventricle

cardiac atrium d23 Sinus venosus transversum transversum

37 Anhui Medical University

 Bulboventricular portion of cardiac tube grows rapidly, bends forming a “U” shaped loop---- bulboventricular loop

Truncus arteriosus bulboventricular loop Truncus arteriosus bulbus cordis bulbus cordis

cardiac ventricle cardiac ventricle cardiac atrium

cardiac atrium Sinus venosus

Sinus venosus transversum transversum

d23 d24 38 Anhui Medical University

 “S”-shaped heart: the cardiac tube continues to grow and bend, atrium leave primitive transversum, shifts in dorso-cranial direction; sinus venosus located at back and caudal portion of atrium.  Atrium expand to the left and right, located on the both sides of the truncus arteriosus.

aortic arch

Truncus arteriosus

bulbus cordis Truncus arteriosus

cardiac ventricle cardiac atrium bulbus cordis cardiac atrium Sinus venosus bulboventricular sulcus cardiac ventricle

transversum

d24 d35 39 Anhui Medical University  Atrioventricular groove  Proximal portion bulbus cordis right ventricle  Primary ventricle left ventricle  Interventricular groove

At the early of 5th week, shape of heart is formed

d35 Truncus arteriosus

Truncus arteriosus atrium Bulbus curds cardiac atrium bulbus cordis bulboventricular groove Primitive A.V canal ventricle cardiac ventricle

d23 pericardium 40 Anhui Medical University Formation of the heart shape

The first bow artery foregut The first bow artery

cardiac bulbus cordis tube Fused cardiac ventricle tube pericardiac coelom atrium fused cardiac tube midgut midgut

The second bow artery

truncus artiriosus ventricle bulbus cordis

ventricle atrium atrium

venous sinus 41 Anhui Medical University

Formation of the heart shape

Truncus arteriosus

cardiac atrium

bulbus cordis

bulboventricular sulcus

cardiac ventricle

pericardium

42 Anhui Medical University Formation of the heart shape

43 Anhui Medical University  Development of the heart

1. Formation of primitive heart

2. Establishing of the heart shape

3. Partitioning of the heart (from 4th to 7th weeks)

① Partitioning of the atrioventricular canal

② Partitioning of the

③ Partitioning of the

④ Division of truncus arteriosus and bulbus cordis

44 Anhui Medical University ① Partitioning of the atrioventricular canal  Endocardial cushion: thickenings of sub-endocardial tissue in the dorsal and ventral walls of the atrioventricular canal (the 4th week)  grow toward each other and fuse, atrioventricular canal is divided into left and right atrioventricular orifice (the end of 5th week)  Mesenchyme surround each orifice form atrioventricular valve.

bulbus cordis

sinus venosus atrium Endocardiac cushion

section

ventricle

45 dorsal the heart

Truncus arteriosus ventral of the heart the of ventral atrium atrium Bulbus cordis

ventral Primitive endocardial A.V canal ventricle cushions dorsal d 23 d 26

atrium venous sinus

Fused endocardial cushions Left A.V orifice ventricle

46 d 31 d 35 Anhui Medical University ② Partitioning of the primitive atrium  Septum primum: a thin sickle-shaped membrane appearing from dorso- cranial wall of atrium (the end of 4th weeks).  Foramen primum: septum primum grows toward the endocardial cushions, leaving a temporary opening between its lower edge and the endocardial cushions

bulbus cordis

septum primum venous sinus Foramen atrium Endocardiac primum cushion

section

ventricle

47 Anhui Medical University ② Partitioning of the primitive atrium  : the upper part of the septum primum perforated and form an opening

foramen secundum

septum primum

48 Anhui Medical University ② Partitioning of the primitive atrium  Septum secundum: another thicker membrane appears in the ventro- cranial wall in the right of the septum primum (the end of 5th week)  Foramen ovale: septum secundum grows toward the endocardial cushions, leaving an opening between its lower edge and endocardial cushions  Valve of foramen ovale: the part of septum primum covers foramen ovale septum secundum

foramen secundum Valve of foramen ovale foramen ovale

membranous part of

49 Anhui Medical University

 Before birth, the pressure of left atrium is below right atrium, blood can flow from right atrium to left atrium through foramen ovale

 After birth, the pressure of left atrium increases, two septums fit closely to separate atrium completely (foramen ovale functionally closes) septum secundum

foramen secundum

foramen ovale

membranous part of interventricular septum

50 Anhui Medical University ② Partitioning of the primitive atrium

51 Anhui Medical University ③ Partitioning of the primitive ventricle  Muscular part of interventricular septum: by the end of 4th week, tissue of ventricular bottom wall grows toward endocardial cushions, but left an opening so called interventricular foramen

bulbus cordis

septum primum foramen secundum venous sinus Foramen atrium Endocardiac primum cushion interventricular foramen section muscular part of interventricular septum ventricle

52 Anhui Medical University ③ Partitioning of the primitive ventricle  Membranous part of interventricular septum: made up of left and right bulbar ridge in bulbus cordis, and endocardial cushion.

septum secundum septum secundum

foramen foramen secundum secundum

foramen ovale

interventricular foramen Membranous part of muscular part of interventricular septum interventricular septum

53 Anhui Medical University

Model of formation of membranous interventricular septum

aorta

pulmonary trunk

aortico-pulmonary Left bulbar ridge septum

right bulbar ridge

endocardial cushion interventricular foramen muscular part of interventricular membranous septum ventricular septum

54 Anhui Medical University Partitioning of the heart chambers bulbus cordis foramen septum primum sinus secundum venosus foramen atrium Endocardiac primum cushion Interventricular section muscular foramen interventricular ventricle septum

septum septum secundum secundum foramen Foramen secundum secundum Valve of foramen ovale foramen ovale Interventricular foramen membranous ventricular septum Muscular ventricular septum 55 Anhui Medical University ④ Division of truncus arteriosus and bulbus cordis

 At the 5th week, two spiral mesodermal ridges grow from the inner

walls of the truncus arteriosus and bulbus cordis are termed truncal

ridges and bulbar ridges, respectively.

56 Anhui Medical University ④ Division of truncus arteriosus and bulbus cordis

 Truncal ridges and bulbar ridges twist around each other

and fuse to form a spiral aortico-pulmonary septum.

57 Anhui Medical University ④ Division of truncus arteriosus and bulbus cordis

 Truncus arteriosus and bulbus cordis are divides into pulmonary trunk and aorta. Pulmonary trunk connect to right ventricle, Aorta connect to left ventricle.

58 Anhui Medical University ④ Division of truncus arteriosus and bulbus cordis

aortico-pulmonary septum

right

aorta

pulmonary trunk

aortico-pulmonary septum

59 Anhui Medical University ④ Division of truncus arteriosus and bulbus cordis

60 Anhui Medical University ⑤ Changes in the sinus venosus

Study by yourself

61 Anhui Medical University Content

 Establishment of the primordial cardiovascular system

 * Development of the heart

 Fetal blood circulation and changes in the circulation after birth

 Congenital defects of the cardiovascular system

62 1) Blood circulation of Anhui Medical University

aorta

foramen ovale

left ventrical

descending aorta

63 ① umbilical V→ducts Anhui Medical University venosus or hepatic sinus → inferior vena cava → right atrium →foramen ovale →left atrium →left ventricle → aortic arch → upper region of the body/ descending aorta →umbilical A→

② head and neck region blood→superior vena cava →right atrium→right ventrical → pulmonary artery → → descending aorta →umbilical A→ placenta (lower region of 64 the body) Anhui Medical University 2) Circulatory changes after birth

 Cutting off of the placental bloodstream

 Establish of the pulmonary circulation of the function of oxygenating the blood

65 Anhui Medical University 2) Circulatory changes after birth  Closure of the umbilical vessels Umbilical vein→ round ligament of the

Distal portion → lateral umbilical ligaments Umbilical arteries Proximal portions → superior vesical arteries

66 Anhui Medical University 2) Circulatory changes after birth  Closure of the ductus arteriosus → ligamentum arteriosum

67 Anhui Medical University 2) Circulatory changes after birth  Closure of the : ligamentum venosum

68 Anhui Medical University 2) Circulatory changes after birth  Foremen ovale closed Right atrium Left atrium Pulmonary venous return increase septum secundum the pressure of left atrium. foramen secundum -- At birth, foramen ovale valve foramen ovale closely to septum secundum

(functionally closed) membranous ventricular septum -- One year following birth the septum primum fuses with the septum secundum to seal the foramen ovale (permanent closed). 69 Anhui Medical University 2) Circulatory changes after birth

70 Anhui Medical University 2) Circulatory changes after birth

71 Anhui Medical University Content

 Establishment of the primordial cardiovascular system

 * Development of the heart

 Fetal blood circulation and changes in the circulation after birth

 Congenital defects of the cardiovascular system

72 Anhui Medical University 1) (ASD): open foramen ovale is most common

 Small holes existing in the foramen ovale valve

Sinus venosus

Tricuspid valve

foramen ovale valve Perforation

Perforation of foramen ovale valve 73 Anhui Medical University 1) Atrial septal defect (ASD):

 Excessive resorption of the septum primum Foremen ovale isn’t sealed physically due to small valve of foremen ovale

Normal foramen ovale

Small septum septum primum primum

Relative small size of foramen ovale valve

74 1) Atrial septal defect (ASD): Anhui Medical University  Incomplete development of the septum secundum too large foramen ovale;

 Too large foramen ovale, and too small valve of foramen ovale

 Septum primum not fused with the endocardial cushions

large foramen ovale large foramen ovale

small septum normal septum primum primum

Incomplete development of the septum secundum 75 1) Atrial septal defect (ASD): Anhui Medical University  Permit blood to continue to flow across the septum after birth.  The higher blood pressures on the left side of the heart after birth cause left-to-right flow, overburden the right side of the heart and lead to cardiac failure and pulmonary hypertension .

76 Diagram of transcatheter closure of ASD with occlusion device

Atrial septal defect occluder device

77 Anhui Medical University

78 Anhui Medical University 2) Ventricular septal defect (VSD):  Membranous ventricular septal defect (VSD): common, the endocardial cushion, bulbar ridge and muscular septal portions fail to fused with each other.  Muscular ventricular septal defect ( Muscular VSDs): occasionally occur in the trabeculated regions of the lower muscular ventricular septum.

79 2) Ventricular septal defect (VSD): Anhui Medical University  The most commonly occurring congenital heart defects.  In children with a VSD, blood usually flows through the defect from the left ventricle to the right ventricle. This causes extra blood in the pulmonary arteries and lungs, lead to left ventricle hypertrophy and pulmonary hypertension.

80 3) Defects of truncus arterious and bulbus cordis septation  Aorta or pulmonary artery stenosis: -- unequal divisions of truncus arterious and bulbus cordis leading to aorta or pulmonary artery stenosis or enlargment, usually with membranous ventricular septal defect. -- Enlarged vessel overrides a ventricular septal defect resulting in oxygenated and deoxygenated blood mixture in the outflow tract.

pulmonary aortic stenosis

pulmonary trunk aorta overriding Right Ventricular ventricular septal defect aorticopulmonary Hypertrophy septum 81 Anhui Medical University 3) Defects of truncus arterious and bulbus cordis septation

 Transposition of the aorta and pulmonary artery ：forming a straight but not spiraling aortico-pulmonary septum. Thus, the aorta is transposed to the right ventricle, and the pulmonary artery to the left.

right atrium atrial septal defect

Aorta

pulmonary trunk

ventricular septal defect

left ventricle

82 Anhui Medical University 3) Defects of truncus arterious and bulbus cordis septation

: unequal division of the truncus arterious and bulbus cordis leading to narrow right ventricular out-flow tract (pulmonary artery), overriding aorta, ventricular septal defect, and right ventricular hypertrophy

aorticopulmonary septum

pulmonary aortic stenosis aorta overriding pulmonary trunk Right ventricular Ventricular septal defect aorticopulmonary Hypertrophy septum 83 Anhui Medical University 3) Defects of truncus arterious and bulbus cordis septation  Persistent truncus arteriosus

 Aorticopulmonary septum defect or fail to form. Since pulmonary trunk Aorta and aorta fail to form, the persistent pulmonary trunk Permanent truncus truncus overrides a ventricular arteriosus ventricular septal septal defect. defect  Oxygenated and deoxygenated left ventricular hypertrophy blood mix in the outflow tract, resulting in a cyanotic defect. This defect is difficult to fix surgically.

84 Anhui Medical University 4) Patent ductus arteriosus (PDA)  The ductus arterious doesn’t close after birth to keep the aorta connection with pulmonary artery leading to being shunted from aorta to the lung, eventually causing irreversible pulmonary hypertension.

85 Anhui Medical University

Key points

1. Partitioning of the heart，especially the partitioning of primitive atrium and ventricular

2. Mechanism of atrial septal defect, ventricular septal

defect, tetralogy of Fallot form. 3. Glossary: endocardial cushion

86 Anhui Medical University Homework

1. Describe the partitioning of primitive atrium and ventricular of heart

2. Describe the mechanism of atrial septal defect, ventricular septal defect, tetralogy of Fallot formed briefly.

3. Glossary: endocardial cushion

87