Presentation on theme: "Embryology of the heart and the great vessels"— Presentation transcript:
1 Embryology of the heart and the great vessels Dr Gerrit EngelbrechtDept of RadiologyUFS
2 Steps in the embryology of the vascular system ESTABLISHMENT OF THE CARDIOGENIC FIELDFORMATION AND POSITION OF THE HEART TUBEFORMATION OF THE CARDIAC LOOPMOLECULAR REGULATION OF CARDIAC DEVELOPMENTDEVELOPMENT OF THE SINUS VENOSUSFORMATION OF THE CARDIAC SEPTAEFORMATION OF THE CONDUCTING SYSTEM OF THE HEARTVASCULAR DEVELOPMENT
4 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
5 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 fieldIn 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
6 Cephalocaudal section through a similar staged embryo showing the position of the pericardial cavity and cardiogenic field.
7 FORMATION AND POSITION OF THE HEART TUBE 2 processes responsible for positioning of the heartFolding of the embryo in a cephalocaudal directionSimultanous folding laterally
8 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
9 Lateral folding of the embryo the caudal regions of the paired cardiac primordia merge except at theircaudalmost ends. Simultaneously, the crescent part of the horseshoe-shapedarea expands to form the future outflow tract and ventricular regions. Thus, theheart becomes a continuous expanded tube consisting of an inner endotheliallining and an outer myocardial layer. It receives venous drainage at its caudalpole and begins to pump blood out of the first aortic arch into the dorsal aortaat its cranial pole
14 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
15 Molecular regulation of cardiac development Dependent on the activation of twotranscription factorsNKX2.5Specifies cardiogenic fieldSeptationConduction systemTBX5Signals from anterior (cranial) endoderm induce a heart-forming region in overlyingsplanchnic mesoderm by turning on the transcription factor NKX2.5. The signals require secretion of bone morphogenetic proteins (BMPs) 2 and 4 andinhibitors (crescent) of WNT genes in the endoderm and lateral plate mesoderm(Fig. 11.9). This combination is responsible for inducing expression ofNKX2.5 that specifies the cardiogenic field and, later, plays a role in septationand in development of the conduction system.NKX2.5 contains a homeodomain and is a homologue of the gene tinman,which regulates heart development in Drosophila. TBX5 is another transcriptionfactor that contains a DNA-binding motif known as the T-box. Expressed laterthan NKX2.5, it plays a role in septation.
16 Development of the sinus venosus 4th weekreceives blood fromright and left sinus horns5th weekObliterationR umbilical veinleft vitelline veinIn the middle of the fourth week, the sinus venosus receives venous bloodfrom the right and left sinus horns (Fig A). Each horn receives bloodfrom three important veins: (a) the vitelline or omphalomesenteric vein,(b) the umbilical vein, and (c) the common cardinal vein. At first communicationbetween the sinus and the atrium is wide. Soon, however, the entranceof the sinus shifts to the right (Fig B). This shift is caused primarily byleft-to-right shunts of blood, which occur in the venous system during the fourthand fifth weeks of development.With obliteration of the right umbilical vein and the left vitelline vein duringthe fifth week, the left sinus horn rapidly loses its importance (Fig B).When the left common cardinal vein is obliterated at 10 weeks, all that remainsof the left sinus horn is the oblique vein of the left atrium and the coronarysinus (Fig ).
17 Development of the sinus venosus(2) 10th week left common cardinal vein obliterates
18 Development of the venous valves As a result of left-to-right shunts of blood, the right sinus horn and veinsenlarge greatly. The right horn, which now forms the only communicationbetween the original sinus venosus and the atrium, is incorporated into theright atrium to form the smooth-walled part of the right atrium (Fig ).Its entrance, the sinuatrial orifice, is flanked on each side by a valvular fold,the right and left venous valves (Fig A). Dorsocranially the valves fuse,forming a ridge known as the septum spurium (Fig A). Initially the valvesare large, but when the right sinus horn is incorporated into the wall of theatrium, the left venous valve and the septum spurium fuse with the developingatrial septum (Fig C ). The superior portion of the right venous valvedisappears entirely. The inferior portion develops into two parts: (a) the valve ofthe inferior vena cava, and (b) the valve of the coronary sinus (Fig C ).The crista terminalis forms the dividing line between the original trabeculatedpart of the right atrium and the smooth-walled part (sinus venarum), whichoriginates from the right sinus horn (Fig C ).
19 Formation of the cardiac septae The major septae are formed between the 27 and 37th days of developmentIt is a simultanuous process if the following areasSeptum formation in the common atriumSeptum formation in the atrioventricular canalSeptum formation in the truncus arteriosus and conus cordisSeptum formation in the ventricles
20 Septum formation in the 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 septumprimumA. 30 days (6 mm).B. Same stage as A, viewed from the right.
21 Septum formation of the common atria (2) 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 cavityC. 33 days (9 mm). D. Same stage asC, viewed from the right
22 Septum formation of the common atria(3) When the upper part of the septum primum gradually disappears, theremaining 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.
23 Further differentiation of 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.
24 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.
25 Atrioventricular 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.
26 Clinical correlates Heart defects Largest category of birth defectsMultifactorial ( viruses, medicines, alchohol, diabetes, hypertension.Genetic syndromes: DiGeorge and DownsTBX5 gene defect: Holt –Oram syndrome( ASD + pre axial abnormalities.ASDPremature closure of the oval foramenEndocardial cushion defects AV canal( persistent AV canal)Tricuspid atresia
30 Septum formation of the truncus arteriosus and conus cordis Fifth week, pairs of opposing ridges appear in the truncus and conus cordis
31 Septum formation of the truncus arteriosus 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.6 weeks(12 mm).B. Beginning of the seventh week (14.5 mm).C. End of the seventh week(20 mm).
32 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 graduallymerge, forming the muscular interventricular septum
33 Semilunar 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.
34 Longitudinal section through the semilunar valves 6 weeks seven weeks weeks
35 Clinical correlates VSD related defects Isolated lesionConotruncal lesions : Tetralogy of FallotPersistent truncus arteriosusTransposition of the great vesselsPulmonar valvular atresiaAorta valvular stenosis and artresia
41 Formation of the conducting system of the heart Sinu atrial nodeInitially 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 nodeThe atrioventricular node and bundle (bundle of His) are derived fromtwo sources: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.
42 Vascular developmentArterial systemVenous system
43 Arterial systemAortic archesVitelline and umbilical arteries
44 Aortic arches Key facts Arise from the aortic sac(truncus arteriosus ) to pharyngeal arches( 4-5 weeks)Terminate in the left and right dorsal aortaThese arches and vessels appear in a cranial to caudal sequence andnot all simultanouslyThe aortic sac also forms left and right horns which give riseto the brachiocephalic artery and proximal arch respectively
48 Vitelline and umbilical arteries Vitelline arteries fuse and form the Coeliac, SMA and IMAUmbilical arteriesInitially paired ventral branches of the aortaFourth week acquire a secondary connection with the aortathe common iliac arteryAfter birth the proximal part persist as the internal iliac andinternal iliac and superior vesical and the distal part obliterateto form the medial umbilical ligaments.
49 Clinical correlates Arterial system defects Patent ductus arteriosusCoarctation of the aorta ( preductal and post ductal)Abnormal origin of the right subclavian arteryRight aortic archInterrupted aortic arch
54 Venous system Vitelline veins Umbilical veins Cardinal veins End of fourth week
55 Vitelline veinsForms a plexus around the duodenum, forms the portal vein.Pass through the septum transversumHepatic cords grow into the septum and form the hepatic sinusoidsConnects to the sinus venosum
56 Vitelline veins (2) Enlargement of the right vitelline vein. Forms the hepatic cardiac part of the IVCThe SMV derives from the right vitelline veinThe left vitelline vein disappears.
57 Umbilical veins Proximal and distal right umbilical vein disappears Proximal left umbilical vein disappearsThe left distal umbilical vein remains and carry blood from the placentato the liverThe ductus venosus form between the left umbilical vein andright hepatic cardiacchannel, it bypassesthe sinusoidal plexusBoth are obliterated after birth to form the ligamentum teres and venosum respectively
58 Cardinal veinsAnterior cardinal veins, which drain the cephalic part of the embryoPosterior cardinal veins, which drainthe rest of the embryo.Common cardinal veins.During the fourth week this forms a symmetrical system
59 From the fifth to the seventh week additional veins are formed:Subcardinal veins, which mainly drain the kidneys;Sacrocardinal veins, which drain the lower extremitiesSupracardinalveins, whichdrain the bodywall by way ofthe intercostalveins, takingover thefunctions of theposteriorcardinal veins
60 left is channeled to the right side. 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 veinLeft posterior cardinal vein terminal portion - > left superior intercostal veinRight common cardinal vein + proximal right anterior cardinal vein-> SVC
61 Subcardinal veins - > left renal vein Left subcardinal vein distal portion - > left gonadal veinRight subcardinal vein - > renal segment of the IVCSacrocardinal veins - > left common iliac veinRight 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.
62 Right 4th to 11th intercostal veins -> right supracardinal vein+post cardinal vein- > azygos venaLeft 4th to 7th intercostal veins-> left supracardinal vein( hemiazygos vein )-> Azygos vein
63 Clinical correlatesLeft superior vena cava: Persistence of the left anterior cardinal veinObliteration of the common cardinal and anteriorcardinal veins on the rightDouble superior vena cava: Persistence of the left anterior cardinal veinFailure of the right brachiocephalic vein to form
64 Clinical correlatesDouble inferior vena cava: Left sacrocardinal vein remain connected to the left subcardinal veinAbsence of the inferior cava : The right subcardinal vein fails to make the connection with the liver
65 ConclusionThe cardiovacular system is functionally important in development. It startsworking 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 andthe pulmonary circulation opened up.The cardiovascular system is made up of splancnic mesoderm and neuralcrest cells ( cranial skeleton, adrenals,neurons, glia, ciliary body )Three systems of veins empty into the sinus venosus ( vitelline, umbilical andcardinal system)The heart starts out with its venous side located caudallyThe heart and arterial trunk are split into the adult compartments by six septaeSeptum primum, septum secundum, AV septum, interventricular muscularand membranous septums, Aortico pulmonary bulbae or ridges
66 References Langman’s Medical embryology, Eight edition, p 223 3.16Langman’s Medical embryology, Eight edition, p 223Electronic resources last accessed on 20/02/2012