Embryology of Embryology of the heart and the heart and

the great the great vesselsvessels

Dr Gerrit EngelbrechtDept of Radiology

UFS

• 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

Steps in the Steps in the embryology of the embryology of the vascular systemvascular system

ESTABLISHMENT OF ESTABLISHMENT OF THE CARDIOGENIC THE CARDIOGENIC

FIELDFIELD

Dorsal view of a late presomite embryo (approximately 18 days) after removal of the amnion. Prospective myoblasts and hemangioblasts reside in thesplanchnic mesoderm in front of the neural plate and on each side of the embryo after migrating up from the primitivestreak

• 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.

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Cephalocaudal section through a similar staged embryo showing the position of the pericardial cavity and cardiogenic field.

FORMATION AND POSITION OF FORMATION AND POSITION OF

THE HEART TUBETHE 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 positioningof 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 Formation of the cardiac loopcardiac loop

Bulbus cordisBulbus cordis

Primitive ventriclePrimitive ventricle

The primitive atrium The primitive atrium and sinus venosusand sinus venosus

Abnormalities of Abnormalities of cardiac loopingcardiac 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 Molecular regulation of cardiac of cardiac

developmentdevelopment

Dependent on the activation of twotranscription factors

•NKX2.5• Specifies

cardiogenic field

• Septation• Conduction

system•TBX5

• Septation

Development of the Development of the sinus venosussinus venosus

4th weekreceives blood fromright and left sinus horns

5th week

Obliteration R umbilical veinleft vitelline vein

Development of the Development of the sinus venosus(2)sinus venosus(2)

10th week left common cardinal vein obliterates

Development of the Development of the venous valvesvenous valves

Formation of the Formation of the cardiac septaecardiac 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 Septum formation in the common atriathe common atria

At the end of the fourth week, a sickle-shaped crest grows from the roof of thecommon atrium into the lumen. This crest is the first portion of the septumprimum

A. 30 days (6 mm).B. Same stage as A, viewed from the right.

Septum formation of Septum formation of the common atria (2)the common atria (2)

C. 33 days (9 mm). D. Same stage asC, viewed from the right

When the lumen of the right atrium expands as a result of incorporation ofthe sinus horn, a new crescent-shaped fold appears. This new fold, the septum secundum never forms a complete partion in the atrial cavity

Septum formation of Septum formation of the common atria(3)the common atria(3)

E. 37 days (14 mm)F. Newborn.G. The atrial septum from the right; same stage as F.

When the upper part of the septum primum gradually disappears, theremaining part becomes the valve of the oval foramen.

Further differentiation Further differentiation of the atriaof the atria

Coronal sections through the heart to show development of the smoothwalledportions 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-walledparts of the atria.

Septum formation of Septum formation of the atrioventricular the atrioventricular

canalcanalAt 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 valvesAtrioventricular valves

Formation of the atrioventricular valves and chordae tendineae. Thevalves are hollowed out from the ventricular side but remain attached to the ventricular wall by the chordae tendineae.

Clinical correlatesClinical correlatesHeart defectsHeart 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

ASDASD

PersistePersistent nt

common common AV AV

canalcanal

Tricuspid atresiaTricuspid atresia

Septum formation of the truncus Septum formation of the truncus

arteriosus and conus cordisarteriosus and conus cordis

Fifth week, pairs of opposing ridges appear in the truncus and conus cordis

Septum formation of the truncus Septum formation of the truncus

arteriosus and conus cordisarteriosus and conus cordis

Proliferations of the right and left conus cushions, combinedwith 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 Septum formation of the ventriclesthe ventricles

End of the fourth week the two primitive ventricles start to expand.The medial walls of the expanding ventricles become apposed and graduallymerge, forming the muscular interventricular septum

Semilunar valvesSemilunar valvesWhen 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 Longitudinal section through the semilunar

valvesvalves

6 weeks seven weeks 9 weeks

Clinical correlatesClinical correlatesVSD related defectsVSD 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 VSDIsolated VSD

Tetralogy of FallotTetralogy of Fallot

Persistent truncus Persistent truncus arteriosusarteriosus

Transportation of the great Transportation of the great

vesselsvessels

Pulmonar valvular atresiaPulmonar valvular atresia

Aortic valvular Aortic valvular stenosis and atresiastenosis and atresia

Formation of the conducting Formation of the conducting

system of the heartsystem of the heartSinu 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 fromtwo 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 developmentVascular development

Arterial system

Venous system

Arterial systemArterial system

• Aortic arches

• Vitelline and umbilical arteries

Aortic archesAortic archesKey factsKey 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 archesAortic arches

Aortic Aortic archesarches

Ductus Ductus

arteriosusarteriosus

Vitelline and umbilical Vitelline and umbilical arteriesarteries

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 correlatesClinical correlatesArterial system Arterial system

defectsdefects• 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 Coarctation of the aortaaorta

Abnormal origin of the Abnormal origin of the right subclavian arteryright subclavian artery

Double aortic archDouble aortic arch

Interrupted aortic Interrupted aortic archarch

Venous systemVenous system

• Vitelline veins

• Umbilical veins

• Cardinal veins

End of fourth week

Vitelline veinsVitelline 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)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 veinsUmbilical 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

Anterior cardinal veins, which drain the cephalic part of the embryo

Posterior cardinal veins, which drainthe rest of the embryo.

Common cardinal veins.

During the fourth week this forms a symmetrical system

Cardinal veins

From the fifth to the seventh week additional veins areformed: a)Subcardinal veins, which mainly drain the kidneys; b) Sacrocardinal veins, which drain the lower extremitiesc)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 ofanastomoses between left and right in such a manner that the blood from theleft 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 segmentWhen 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 correlatesClinical correlatesLeft 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 correlatesClinical correlatesDouble 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

ConclusionConclusion• 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

ReferencesReferences• Langman’s Medical embryology, Eight edition, p

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

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

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