Embryology of

the heart and

the great vessels
Dr Gerrit Engelbrecht
Dept of Radiology
UFS
Steps in the embryology
of the vascular system
• ESTABLISHMENT OF THE CARDIOGENIC FIELD

• FORMATION AND POSITION OF THE HEART TUBE

• FORMATION OF THE CARDIAC LOOP

• MOLECULAR REGULATION OF CARDIAC DEVELOPMENT

• DEVELOPMENT OF THE SINUS VENOSUS

• FORMATION OF THE CARDIAC SEPTAE

• FORMATION OF THE CONDUCTING SYSTEM OF THE HEART

• VASCULAR DEVELOPMENT
ESTABLISHMENT OF
THE CARDIOGENIC
FIELD
 Dorsal view of a late presomite
embryo (approximately 18
days) after removal of the
amnion.
Prospective myoblasts and
hemangioblasts reside in the
splanchnic mesoderm in front
of the neural plate and on each
side of the embryo after
migrating up from the primitive
streak
• Transverse section through a
similar-staged embryo to show
the position of the blood islands
in the splanchnic mesoderm
layer.
• With time, the islands unite and
form a horseshoe-shaped
endothelial-lined tube
surrounded by myoblasts. This
region is known as the
cardiogenic field
• In addition to the cardiogenic
region, other blood islands
appear bilaterally, parallel and
close to the midline of the
embryonic shield. These islands
form a pair of longitudinal
vessels, the dorsal aortae.
223
Cephalocaudal section through a similar
staged embryo showing the position of the
pericardial cavity and cardiogenic field.
FORMATION AND POSITION OF
THE HEART TUBE

2 processes responsible for positioning of the heart

1. Folding of the embryo in a cephalocaudal direction

2. Simultanous folding laterally

 Cephalocaudal folding
Figures showing effects of the rapid growth of the brain on positioning
of the heart. Initially the cardiogenic area and the pericardial cavity are in front
of the buccopharyngeal membrane. A. 18 days. B. 20 days. C. 21 days. D. 22 days
Lateral folding of the embryo
Formation of the cardiac
loop
Bulbus cordis
Primitive ventricle
The primitive atrium and
sinus venosus
Abnormalities of cardiac
looping
Dextrocardia, in which the heart lies on the
right side of the thorax instead of the left, is
caused because the heart loops to the left
instead of the right.

Dextrocardia may coincide with situs

inversus
 Molecular regulation of
cardiac development

Dependent on the
activation of two
transcription factors

• NKX2.5
• Specifies
cardiogenic
field
• Septation
• Conduction
system
• TBX5
• Septation
 Development of the sinus
venosus
4th week
receives blood from
right and left sinus horns

5th week

Obliteration
R umbilical vein
left vitelline vein
Development of the sinus
venosus(2)

10th week left common cardinal vein obliterates

Development of the
venous valves
Formation of the cardiac
septae
The major septae are formed between the 27 and 37th
days of development

It is a simultanuous process if the following areas

• Septum formation in the common atrium

• Septum formation in the atrioventricular canal
• Septum formation in the truncus arteriosus and conus
cordis
• Septum formation in the ventricles
 Septum formation in the
common atria
At the end of the fourth week, a sickle-shaped crest grows from the roof of the
common atrium into the lumen. This crest is the first portion of the septum
primum

A. 30 days (6 mm).
B. Same stage as A, viewed from the right.
 Septum formation of the
common atria (2)
When the lumen of the right atrium expands as a result of incorporation of
the sinus horn, a new crescent-shaped fold appears. This new fold, the
septum secundum never forms a complete partion in the atrial cavity

C. 33 days (9 mm). D. Same stage as

C, viewed from the right
Septum formation of the
common atria(3)
When the upper part of the septum primum gradually disappears, the
remaining part becomes the valve of the oval foramen.

E. 37 days (14 mm)

F. Newborn.
G. The atrial septum from the right; same
stage as F.
 Further differentiation of
the atria

Coronal sections through the heart to show development of the smoothwalled

portions of the right and left atrium. Both the wall of the right sinus horn (blue)
and the pulmonary veins (red) are incorporated into the heart to form the smooth-walled
parts of the atria.
 Septum formation of the
atrioventricular canal
At the end of the fourth week, two mesenchymal cushions, the atrioventricular
endocardial cushions, appear at the superior and inferior borders of the
atrioventricular canal, two additional lateral cushions appear at the left and
right borders.
At the end of the fifth week there is complete fusion of the superior and inferior
cushions with complete division of the canal into left and right orifices.
 Atrioventricular valves

Formation of the atrioventricular valves and chordae tendineae. The

valves are hollowed out from the ventricular side but remain attached to
the ventricular wall by the chordae tendineae.
 Clinical correlates
Heart defects
• Largest category of birth defects
• Multifactorial ( viruses, medicines, alchohol,
diabetes, hypertension.
• Genetic syndromes: DiGeorge and Downs
• TBX5 gene defect: Holt –Oram syndrome( ASD + pre
axial abnormalities.
• ASD
• Premature closure of the oval foramen
• Endocardial cushion defects AV canal( persistent
AV canal)
• Tricuspid atresia
ASD
Persistent
common
AV canal
Tricuspid atresia
 Septum formation of the truncus arteriosus
and conus cordis

Fifth week, pairs of

opposing ridges appear
in the truncus and
conus cordis
Septum formation of the truncus arteriosus
and conus cordis

Proliferations of the right and

left conus cushions, combined
with proliferation of the
inferior endocardial cushion,
close the interventricular
foramen and form the
membranous portion of the
interventricular septum.
A. 6 weeks(12 mm).

B. Beginning of the seventh

week (14.5 mm).

C. End of the seventh week

(20 mm).
 Septum formation of the
ventricles
End of the fourth week the two primitive ventricles start to expand.
The medial walls of the expanding ventricles become apposed and gradually
merge, forming the muscular interventricular septum
 Semilunar valves
When partitioning of the truncus is almost complete, primordia of the
semilunar valves become visible as small tubercles found on the main
truncus swellings.

•One of each pair is assigned to the pulmonary and aortic channels,

respectively

•A third tubercle appears in both channels opposite the fused truncus

swellings.

•Gradually the tubercles hollow out at their upper surface, forming the
semilunar valves.

•Recent evidence shows that neural crest cells contribute to formation of

these valves.
Longitudinal section through the semilunar valves

6 weeks seven weeks 9 weeks

 Clinical correlates
VSD related defects
• Isolated lesion

• Conotruncal lesions : Tetralogy of Fallot

• Persistent truncus arteriosus

• Transposition of the great vessels

• Pulmonar valvular atresia

• Aorta valvular stenosis and artresia

Isolated VSD
Tetralogy of Fallot
Persistent truncus
arteriosus
Transportation of the great vessels
Pulmonar valvular atresia
Aortic valvular stenosis
and atresia
 Formation of the conducting
system of the heart
Sinu atrial node

Initially the pacemaker for the heart lies in the caudal part of the left
cardiac tube.
Later the sinus venosus assumes this function, and as the sinus is
incorporated into the right atrium, pacemaker tissue lies near the opening
of the superior vena cava. Thus, the sinuatrial node is formed.

Atrioventricular node

The atrioventricular node and bundle (bundle of His) are derived from
two sources:
(a) cells in the left wall of the sinus venosus
(b) cells from the atrioventricular canal.

Once the sinus venosus is incorporated into the right atrium, these cells lie
in their final position at the base of the interatrial septum.
Vascular development

Arterial system

Venous system
Arterial system

• Aortic arches

• Vitelline and umbilical arteries

 Aortic arches
Key facts

• Arise from the aortic sac(truncus arteriosus ) to pharyngeal arches

( 4-5 weeks)

• Terminate in the left and right dorsal aorta

• These arches and vessels appear in a cranial to caudal sequence and

not all simultanously

• The aortic sac also forms left and right horns which give rise
to the brachiocephalic artery and proximal arch respectively
Aortic arches
Aortic
arches
 Ductus
arteriosus
 Vitelline and umbilical
arteries

Vitelline arteries fuse and form the Coeliac, SMA and IMA

Umbilical arteries

• Initially paired ventral branches of the aorta

• Fourth week acquire a secondary connection with the aorta
the common iliac artery
• After birth the proximal part persist as the internal iliac and
internal iliac and superior vesical and the distal part obliterate
to form the medial umbilical ligaments.
 Clinical correlates
Arterial system defects
• Patent ductus arteriosus

• Coarctation of the aorta ( preductal and post

ductal)

• Abnormal origin of the right subclavian artery

• Right aortic arch

• Interrupted aortic arch

Coarctation of the aorta
Abnormal origin of the
right subclavian artery
Double aortic arch
Interrupted aortic arch
 Venous system

• Vitelline veins

• Umbilical veins

• Cardinal veins

End of fourth week

 Vitelline veins
• Forms a plexus
around the
duodenum,
forms the portal
vein.

• Pass through the

septum
transversum

• Hepatic cords
grow into the
septum and form
the hepatic
sinusoids

• Connects to the
sinus venosum
 Vitelline veins (2)
• Enlargement of
the right
vitelline vein.

• Forms the
hepatic cardiac
part of the IVC

• The SMV
derives from
the right
vitelline vein

• The left
vitelline vein
disappears.
 Umbilical veins
• Proximal and distal
right umbilical vein
disappears

• Proximal left
umbilical vein
disappears

• The left distal

umbilical vein
remains and carry
blood from the
placenta
to the liver

• The ductus venosus

form between the left
umbilical vein and
right hepatic cardiac
channel, it bypasses
the sinusoidal plexus

• Both are obliterated

after birth to form the
ligamentum teres
and venosum
respectively
 Cardinal veins
Anterior cardinal
veins, which drain
the cephalic part
of the embryo

Posterior cardinal
veins, which drain
the rest of the
embryo.

Common cardinal
veins.

During the fourth

week this forms a
symmetrical
system
From the fifth to the seventh
week additional veins are
formed:
a) Subcardinal veins,
which mainly drain the
kidneys;
b) Sacrocardinal veins,
which drain the lower
extremities
c) Supracardinal
veins, which
drain the body
wall by way of
the intercostal
veins, taking
over the
functions of the
posterior
cardinal veins
 Formation of the vena cava system is characterized by the appearance of
anastomoses between left and right in such a manner that the blood from the
left is channeled to the right side.

• Anterior cardinal
veins -> left
brachocephalic
vein

• Left posterior
cardinal vein
terminal portion
- > left superior
intercostal vein

• Right common
cardinal vein +
proximal right
anterior cardinal
vein-> SVC
• Subcardinal veins -
> left renal vein
• Left subcardinal
vein distal portion
- > left gonadal
vein
• Right subcardinal
vein - > renal
segment of the
IVC
• Sacrocardinal
veins - > left
common iliac vein
• Right sacro
cardinal vein - >
sacro cardinal
segment

When the renal segment of the inferior vena cava connects with the hepatic
segment, which is derived from the right vitelline vein, the inferior vena cava,
consisting of hepatic, renal, and sacrocardinal segments, is complete.
Right 4th to 11th intercostal veins
-> right supracardinal vein
+
post cardinal vein

- > azygos vena

Left 4th to 7th intercostal veins

-> left supracardinal vein

( hemiazygos vein )

-> Azygos vein

 Clinical correlates
Left superior vena cava: Persistence of the left anterior cardinal vein
Obliteration of the common cardinal and anterior
cardinal veins on the right

Double superior vena cava: Persistence of the left anterior cardinal vein
Failure of the right brachiocephalic vein to form
 Clinical correlates
Double inferior vena cava: Left sacrocardinal vein remain connected to the left subcardinal vein

Absence of the inferior cava : The right subcardinal vein fails to make the connection with the liver
 Conclusion
• The cardiovacular system is functionally important in development. It starts
working when the embryo is between 200 to 400 microns thick.

• The cardiovascular system is radically remodeled at least four times ( Bilateral,

central as a single pump, entire system of veins and some of the arteries regress,
splits into two pumps, at birth the placental circulation is shut down and
the pulmonary circulation opened up.

• The cardiovascular system is made up of splancnic mesoderm and neural

crest cells ( cranial skeleton, adrenals,neurons, glia, ciliary body )

• Three systems of veins empty into the sinus venosus ( vitelline, umbilical and
cardinal system)

• The heart starts out with its venous side located caudally

• The heart and arterial trunk are split into the adult compartments by six septae
Septum primum, septum secundum, AV septum, interventricular muscular
and membranous septums, Aortico pulmonary bulbae or ridges
 References 3.16

• Langman’s Medical embryology, Eight edition, p

223
• Electronic resources last accessed on 20/02/2012

 http://www.embryology.ch/
 http://www.indiana.edu/