DEVELOPMENT OF HEARTDEVELOPMENT OF HEARTA REVIEWA REVIEW

-DrKrishnaKanth-DrKrishnaKanth

Establishment of the Cardiogenic Field

► The vascular system appears in the middle of the third week.

► Cardiac progenitor cells lie in the epiblast.► They migrate through the streak.► Cells destined to form cranial segments of the

heart, the outflow tract, migrate first, and cells forming more caudal portions, right ventricle, left ventricle, and sinus venosus, respectively, migrate in sequential order.

► The cells proceed toward the cranium and position themselves rostral to the buccopharyngeal membrane and neural folds.

► Here they reside in the splanchnic layer of the lateral plate mesoderm

► late in the presomite stage of development, they are induced by the underlying pharyngeal endoderm to form cardiac myoblasts.

► Blood islands also appear in this mesoderm

► horseshoe-shaped “cardiogenic field”.

► pericardial cavity.► 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.

►Initially, the central portion of the cardiogenic area is anterior to the buccopharyngeal membrane and the neural plate.

Rapid development and flexion of the head, With closure of the neural tube and formation of the brain vesicles, however, the central nervous system grows cephalad so rapidly that it extends over the central cardiogenic area and the future pericardial cavity.

Two lateral extensions of cardiactissue become hollowed out toform a pair of endothelial tubes, which soon fuse to form the primitive cardiac tube.

► The developing heart tube bulges more and more into the pericardial cavity.

► Initially, however, the tube remains attached to the dorsal side of the pericardialcavity by a fold of mesodermal tissue, the dorsal mesocardium

No ventral mesocardium is ever formed

► With further development, the dorsal mesocardium disappears, creating the transverse pericardial sinus, which connects both sides of the pericardial cavity. The heart is now suspended in the cavity by blood vessels at its cranial and caudal poles

► Mesothelial cells from the region of the sinus venosus migrate over the heart to form the epicardium.

►Thus the heart tube consists of three layers: (a) the Endocardium, forming the internal endothelial lining of the heart; (b) the Myocardium, forming the muscularwall & (c) the Epicardium or visceral pericardium, covering the outside of the tube. This outer layer is responsible for formation of the coronary arteries,including their endothelial lining and smooth muscle.

The arterial trunk will divide to separate the pulmonary and systemic supply.The bulbus and the ventricle will differentiate into the right and left ventricles.

The primitive cardiac tube has five zones:

the arterial trunk

the bulbus cordis ) } some would call these two togetherthe ventricle ) the primitive ventricle, with inlet

and outlet portions

the atrium

and the sinus venosus

► The atrial portion, initially a paired structure outside the pericardial cavity, forms a common atrium and is incorporated into the pericardial cavity

► The atrioventricular junction remains narrow and forms the atrioventricular canal, which connects the common atrium and the early embryonic ventricle.

► The bulbus cordis is narrow except for its proximal third. This portion will form the trabeculated part of the right ventricle

► The midportion, the conus cordis, will form the outflow tracts of both ventricles.

► The distal part of the bulbus, the truncus arteriosus, will form the roots and proximal portion of the aorta and pulmonary artery

► The junction between the ventricle and the bulbus cordis, externally indicated by the bulboventricular sulcus , remains narrow.► It is called the primary interventricular foramen

•The fold of the loop is principally at the junction of bulbus cordis and ventricle. Note in panel C that the two end up side by side.•Left ventricle will develop from the ventricle, and the right ventricle will develop from the bulbus cordis. (And an l-loop willresult in ventricular inversion with the left ventricle on the right.)(for more, see “The Anatomy of Ventricular Looping….Jorg Manner Clinical Anatomy Jan 2009 21-35)•Note also that the arterial trunk is above the developing right ventricle.

The cardiac tube grows at a greaterlongitudinal rate then the rest of theembryo, causing it to fold. As it does thisit falls to the right. This is known asd-looping. It may fall to the left in anl-loop: this will lead to a malformed heart.

normal d-loop l-loop

►The cephalic portionof the tube bends ventrally, caudally, and to the right.

►The atrial (caudal) portion shifts dorsocranially and to the left.

►This bending, which may be due to cell shape changes, creates the cardiac loop. It is complete by day 28.

Molecular Regulation of Cardiac Development

► Signals from anterior (cranial) endoderm induce a heart-forming region in overlying splanchnic mesoderm by turning on the transcription factor NKX2.5.

The signals require secretion of bone morphogenetic proteins (BMPs) 2 and 4 and inhibitors (crescent) of WNT genes in the endoderm and lateral plate mesoderm

► This combination later, plays a role in septation and 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 transcription factor that contains a DNA-

binding motif known as the T-box. Expressed later than NKX2.5, it plays a role in septation.

Development of the Sinus Venosus

► In the middle of the fourth week, the sinus venosus receives venous blood from the right and left sinus horns.

► Each horn receives blood from three important veins: (a) the vitelline or omphalomesenteric vein,(b) the umbilical vein, and (c) the common cardinal vein.

► At first communication between the sinus and the atrium is wide. Soon, however, the entrance of the sinus shifts to the right. This shift is caused primarily by left-to-right shunts of blood, which occur in the venous system during the fourth and fifth weeks of development.

► With obliteration of the right umbilical vein and the left vitelline vein during the fifth week, the left sinus horn rapidly loses its importance.

► When the left common cardinal vein is obliterated at 10 weeks, all that remains of the left sinus horn is the oblique vein of the left atrium and the coronary sinus

Opposite the dividing atrioventricularvalve, the posterior walls of the atriaare beginning to lateralise. The symmetrical systemic venous systembiases its growth to the right andmany of its left sided structuresdisappear or involute. Thus the systemic veins drain to the right side.

► As a result of left-to-right shunts of blood, the right sinus horn and veins enlarge greatly.

► The right horn, which now forms the only communication between the original sinus venosus and the atrium, is incorporated into the right atrium to form the smooth-walled part of the right atrium

► Its entrance, the sinuatrial orifice, is flanked on each side by a valvular fold, the right and left venous valves.

► Dorsocranially the valves fuse, forming a ridge known as the septum spurium

► when the right sinus horn is incorporated into the wall of the atrium, the left venous valve and the septum spurium fuse with the developing atrial septum. The superior portion of the right venous valve disappears entirely.

The inferior portion develops into two parts: (a) the valve of the inferior vena cava, and (b) the valve of the coronary sinus (Fig. 11.12C ).

The crista terminalis forms the dividing line between the original trabeculated part of the right atrium and the smooth-walled part (sinus venarum)

A septum is developing down themiddle of the atrium, probably in asimilar way to the ventricular septumin that it is a ridge left behind as theatrial walls grow away from it.

The to the left of the septum, the primarypulmonary vein grows and seeks outthe primitive pulmonary venous complex.As growth proceeds, the primary vein is absorbed into the atrial wallas showed here, to achieve the adultform of separate left and right lung drainage.

This is an actual looped heartNote that the ventricular mass isnow in line with the atria

By the end of the fourthweek, the two primitive ventricles begin to expand.

This is a cutaway showingthe beginnings of the ventricularseptum. The ventricles will developas outpouchings from this position,in the direction of the arrows.

► This is accomplished by continuous growth of the myocardium on the outside and continuous diverticulation and trabecula formation on the inside

► The medial walls of the expanding ventricles become apposed and gradually merge, forming the muscular interventricular septum

the “septal crest”

lumen of the original tube,here.

It forms a communication between the ventricles: persistence ofit will result in the commonestof ventricular septal defects, theperimembraneous VSD

► The interventricular foramen, above the muscular portion of the interventricular septum, shrinks on completion of the conus septum.

► During further development, outgrowth of tissue from the inferior endocardial cushion along the top of the muscular interventricular septum closes the foramen.

This tissue fuses with the abutting parts of the conus septum.

► Complete closure of the interventricular foramen forms the membranous part of the interventricular septum.

► The masses, known as endocardial cushions, develop in the atrioventricular and conotruncal regions.

► In these locations they assist in formation of the atrial and ventricular (membranous portion) septa, the atrioventricular canals and valves, and the aortic and pulmonary channels.

► Because of their key location, abnormalities in endocardial cushion formation contribute to many cardiac malformations, including atrial and ventricular septal defects and defects involving the great vessels (i.e., transposition of the great vessels and tetralogy of Fallot).

The septum primum, which is the first septum to develop, is an incomplete thin-walled partition,in which the anteroinferior free edge is above the atrioventricular canal and becomes lined by tissue derived from the superior, and inferior endocardial cushions. Before the resultant interatrial opening (ostium primum) becomes sealed by endocardial cushion tissue, programmed cell death in an area near the anterosuperior aspect of the septum primum creates small cribriform perforations. These perforations coalesce to form a large, second interatrial communication (ostium secundum) maintaining interatrial blood flow.

At this time, to the right of the first septum, an anterosuperior infolding of the atrial roof occurs and forms a second septal structure (septum secundum).

It expands posteroinferiorly as a thick-walled It expands posteroinferiorly as a thick-walled muscular ridge to form an incomplete partition that muscular ridge to form an incomplete partition that overlies the ostium secundum. As atrial septation is overlies the ostium secundum. As atrial septation is

accomplished, septum secundum forms the limbus of accomplished, septum secundum forms the limbus of the fossa ovalis and septum primum forms the valve the fossa ovalis and septum primum forms the valve

of the fossa ovalisof the fossa ovalis

This diagram is a little more true. The septum secundum is not really a true intracavitary septum, but is a fold of atrial wall invaginating from the superior surface.

As atrial septation is accomplished, septum secundum formsthe limbus of the fossa ovalis and septum primum forms the valve of the fossa ovalis.

The channel for interatrial blood flow through the ostium secundum is known as the foramen ovale.

Here is someone else’s interpretation

Some authors subscribe to the feeling that the septumprimum does not actually fenestrate, but that it and the septum secundum form eccentrically overlapping flanges.

In any event, where the two cross in the middleis the oval fossa if they overlap completely, or is asecundum atrial septal defect if they leave a gap.

septum primum

septum secundum

LA

RAAo

► 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.

► Initially the atrioventricular canal gives access only to the primitive left ventricle and is separated from the bulbus cordis by the bulbo(cono)ventricular flange.

► Since the atrioventricular canal enlarges to the right, blood passing through the atrioventricular orifice now has direct

access to the primitive left as well as the primitive right ventricle.

► In addition to the superior and inferior endocardial cushions, the two lateral atrioventricular cushions appear on the right and left borders of the canal.

►The superior and inferior cushions, in the meantime,project further into the lumen and fuse, resulting in a complete division of the canal into right and left atrioventricular orifices by the end of the fifth week.

The ventricles position themselves and the great vessels spiral down to cross the circulation before the truncal septum fuses with thesuperior margin of the septal crest.

Inferior to this, the posterior part of the septal crest is heading towards the AV valve,which itself is dividing into the mitral and tricuspid valves

Four cushions (AVC) have developed at the A/V junction; the superior and inferior cushions willmeet to divide the AV orifice (AVO)into the tricuspid and mitral valves. The inferior septal crest (VS)will aim to meet the divided valve where the cushions fuse.

Atrioventricular Valves► After the atrioventricular endocardial cushions fuse, each

atrioventricular orifice is surrounded by local proliferations of mesenchymal tissue.

► When the bloodstream hollows out and thins tissue on the ventricular surface of these proliferations, valves form and remain attached to the ventricular wall by muscular cords.

► Finally, muscular tissue in the cords degenerates and is replaced by dense connective tissue. The valves then consist of connective tissue covered by endocardium.

► They are connected to thick trabeculae in thewall of the ventricle, the papillary muscles, by means of chordae tendineae

In this manner two valve leaflets, constituting the bicuspid, or mitral, valve, form in the left atrioventricular canal, and three,

constituting thetricuspid valve, form on the right side.

CLINICAL CORRELATESCLINICAL CORRELATES► Heart and vascular abnormalities make up the largest

category of human birth defects, accounting for 1% of malformations among live-born infants.The incidence among stillborns is 10 times as high.

► It is estimated that 8%of cardiac malformations are due to genetic factors, 2% are due to environmental agents, and most are due to a complex interplay between genetic andenvironmental influences (multifactorial causes).

► Classic examples of cardiovacular teratogens include rubella virus and thalidomide. Others include isotretinoin (vitamin A), alcohol, and many other compounds.

► Maternal diseases,such as insulin-dependent diabetes and hypertension, have also been linked to cardiac defects.

► 33% of children with chromosomal abnormalities have a congenital heart defect, with an incidence of nearly 100% in children with trisomy 18.

► mutations in the heart-specifying gene NKX2.5, on chromosome 5q35,produce atrial septal defects (secundum type) and atrioventricular conduction delays in an autosomal dominant fashion.

► Mutations in the TBX5 gene result in Holt-Oram syndrome, characterized by preaxial (radial) limb abnormalitiesand atrial septal defects.

► One of the most significant defects is the ostium secundum defect,characterized by a large opening between the left and right atria. It is

caused either by excessive cell death and resorption of the septum primum or by inadequate development of the septum secundum.

► The most serious abnormality in this group is complete absence of the atrial septum. This condition, known as common atrium or cor triloculare biventriculare, is always associated with serious defects elsewhere in the heart.

► premature closure of the oval foramen, leads to massive hypertrophy of

the right atrium and ventricle and underdevelopment of the left side of the heart. Death usually occurs shortly after birth.

► Endocardial cushions of the atrioventricular canal not only divide this canal into a right and left orifice, but also participate in formation of the membranous portion of the interventricular septum and in closure of the ostium primum.

► Whenever the cushions fail to fuse, the result is a persistent atrioventricular canal, combined with a defect in the cardiac septum. This septal defect has an atrial and a ventricular component, separated by abnormal valve leaflets in the single atrioventricular orifice.

► Occasionally, endocardial cushions in the atrioventricular canal partially fuse. The result is a defect in the atrial septum, but the interventricular septum is closed. This defect, the ostium primum defect, is usually combined with a cleft in the anterior leaflet of the tricuspid valve.

Persistence of AV Canal & Ostium Persistence of AV Canal & Ostium PrimumPrimum

And to finish, a word on the AV valves. Looking backon this image from a few slides ago, you may havenoticed that the way the septum seals off the “VSD”space is not a simple line.

The area in question becomes the membranous septum, and is offset towards the mitral valveresulting in a portion that is interventricular (MSV) and one that is between the LV and theright atrium (MSA). You will meet this anatomy again in echocardiography and in yourunderstanding of the atrioventricular septal defects (“canal” defects). It allows thewedging of the aortic valve between the mitral and tricuspid valves described before.

Well, that’s it. I do hope it has helped. On the next slide I have classified some congenitalmalformations on the underlying embryological fault: feel free to give it a try.

► Faulty development of the endocardial cushions and of the Faulty development of the endocardial cushions and of the atrioventricular septum is thought to be responsible for the broad atrioventricular septum is thought to be responsible for the broad range of AVSDs. In partial AVSDs, incomplete fusion of the superior range of AVSDs. In partial AVSDs, incomplete fusion of the superior and inferior endocardial cushions results in a cleft in the midportion and inferior endocardial cushions results in a cleft in the midportion of the anterior mitral leaflet, often associated with mitral of the anterior mitral leaflet, often associated with mitral regurgitation. In contrast, complete AVSD is associated with lack of regurgitation. In contrast, complete AVSD is associated with lack of fusion between the superior and inferior cushions and, consequently, fusion between the superior and inferior cushions and, consequently, with the formation of separate anterior and posterior bridging leaflets with the formation of separate anterior and posterior bridging leaflets along the subjacent ventricular septumalong the subjacent ventricular septum

► Failure of the endocardial cushions to fuse creates a defect in the Failure of the endocardial cushions to fuse creates a defect in the atrioventricular septum. The primum atrial septal component of this atrioventricular septum. The primum atrial septal component of this defect is usually large. This results in downward displacement of the defect is usually large. This results in downward displacement of the anterior mitral leaflet to the level of the septal tricuspid leaflet . In anterior mitral leaflet to the level of the septal tricuspid leaflet . In AVSDs, the atrioventricular valves have the same septal insertion AVSDs, the atrioventricular valves have the same septal insertion level in contrast to the leaflet arrangement in the normal heart . The level in contrast to the leaflet arrangement in the normal heart . The distance from the cardiac crux to the left ventricular apex is distance from the cardiac crux to the left ventricular apex is foreshortened, and the distance from the apex to the aortic valve is foreshortened, and the distance from the apex to the aortic valve is

increasedincreased

Septum Formation in Truncus & Septum Formation in Truncus & ConusConus

► During the fifth week, pairs of opposing ridges appear in the truncus.

► These ridges, the truncus swellings, or cushions, lie on the right superior wall (right superior truncus swelling) and on the left inferior wall (left inferior truncus swelling)

► The right superior truncus swelling grows distally and to the left, and the left inferior truncus swelling grows distally and to the right.

► Hence, while growing toward the aortic sac, the swellings twist around each other, foreshadowing the spiral course of the future septum

► After complete fusion, the ridges form the aorticopulmonary septum, dividing the truncus into an aortic and a pulmonary channel.

► When the truncus swellings appear, similar swellings (cushions) develop along the right dorsal and left ventral walls of the conus cordis.

► The conus swellings grow toward each other and distally to unite with the truncus septum.

► When the two conus swellings have fused, the septum divides the conus into an anterolateral portion (the ouflow tract of the right ventricle) and a posteromedial portion (the outflow tract of the left ventricle).

► Neural crest cells, migrating from the edges of the neural folds in the hindbrain region, contribute to endocardial cushion formation in both the conus cordis and truncus arteriosus.

► Abnormal migration, proliferation, or differentiation of these cells results in congenital malformations in this region, such as tetralogy of Fallot , pulmonary stenoses, transposition of the great vessels and persistent truncus arteriosus.

► Since neural crest cells also contribute to craniofacial development, it is not uncommon to see facial and cardiac abnormalities in the same individual.

Now for the arterial trunk. This structure does truly septate, but embryologically it is a simple coronal division in its embryonic straight position.

It will end up as a spiral

The septation extends upwards fromthe valves to end just beyondthe origin of the paired sixth aortic arches, where it seals off against the posterior truncal wall. As the sixth arch vessels are destined to be the branch pulmonary arteries, the posterior channel is now the main pulmonary artery. The anterior channel is the aorta.

This is why the aorta always arches over the pulmonaryarteries from anterior to posterior, no matter whatother cardiac abnormality is present.

Because of the looping, the septating arterial trunk will be dragged to theright , and twisted as well.As a result the ascending aortacomes to lie to the right of thepulmonary artery.Note that the looping brings the trunk close to the AV canal.

The aorta is now poorly placed to attach itself to the left ventricle and some mechanism is needed todrag it to the left but still leave the PA over the rightventricle.

At this stage, as we saw before, the ventricular mass is centralising in front of the AV canal so that separate atria can serve each ventricle. If we take a view downwards onto the crest of the septum, looking from the atria, we see something like this:

See how close the outlet is to the inlet. If the gapbetween them fails to growwith the rest of the heart, inthe fully formed heart the twowill be in continuity.right

anterior

aortapulmonary artery

A surge of growth beneath the pulmonary artery pushes it up, forward and right (black arrows). The gap between the aorta and the inlet valve remains smalland fibroses (dotted line). These processes pin the aortic valve to the rim of the developing mitral valveas everything around them expands.

As a result, the aorta arises from theleft ventricle while the pulmonaryartery has risen over the right ventricle.Once the gap between the truncal septum and the septal crest obliterates, the systemic and pulmonary supplies will have been separated, andconnected to the correct ventricle.

RPA = right pulmonary arteryLPA = left pulmonary arteryAPS = aortopulmonary (truncal) septumRVO = RV outflowLVO = LV outflow

And so now you can compare the flow scheme on the left with the more lifelike imageon the right

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.

Viewing the mature anatomy form the atrial side, the two atrioventricular valveshave assumed their circular orifice shapes. The aortic valve, as we have discussed, is in continuity with the mitral annulus: the AV valves have separated slightly at the top, allowing the aortic valve to wedge between the mitral and tricuspid annuli, coming to rest very close to the tricuspid annulus. The pulmonary valve remains pushed up and forward, though still in continuity with the aortic valve.

pulmonary

aortic

tricuspid mitral

This pattern of connections between the annuli of the four cardiac valves constitutes the

fibrous “skeleton” of theheart, here viewed fromthe front.

Note that the commissures of theaortic and pulmonary valvesreflect their common origin withone commissure of each still inline with its old partner.

Thecoronary artery origins will alwaysbe from the sinuses adjacent tothe common commissure, even incongenital abnormalities of aorticposition and/or connection.

CLINICAL CORRELATES►Ventricular septal defect (VSD):

VSD is often associated with abnormalities in partitioning of the conotruncal region.

Tetralogy Of FallotTetralogy Of Fallot► Fallot's name refers to the tetrad of right ventricular outflow obstruction, Fallot's name refers to the tetrad of right ventricular outflow obstruction,

aortic override, ventricular septal defect, and right ventricular hypertrophy.aortic override, ventricular septal defect, and right ventricular hypertrophy.► It is safe to say, however, that the most characteristic and hallmark finding is It is safe to say, however, that the most characteristic and hallmark finding is

the subpulmonic stenosis created by the deviation of the outlet, or conal, the subpulmonic stenosis created by the deviation of the outlet, or conal, septum septum

► The obstruction is further exacerbated by hypertrophy of the muscular outlet The obstruction is further exacerbated by hypertrophy of the muscular outlet septum, the parietal right ventricular free wall, and components of the septum, the parietal right ventricular free wall, and components of the septomarginal trabeculations septomarginal trabeculations

► All patients with TOF demonstrate anterior and All patients with TOF demonstrate anterior and cephalad deviation of this outlet septum, and the cephalad deviation of this outlet septum, and the degree and nature of this deviation determine the degree and nature of this deviation determine the severity of subpulmonic obstructionseverity of subpulmonic obstruction

► The ventricular septal defect in TOF most frequently has fibrous continuity The ventricular septal defect in TOF most frequently has fibrous continuity between the tricuspid and aortic valve, and hence may be considered a true between the tricuspid and aortic valve, and hence may be considered a true perimembranous defectperimembranous defect

Persistent truncus arteriosus

► Results when the conotruncal ridges fail to fuse and to descend toward the ventricles

► The pulmonary artery arises some distance above the origin of the undivided truncus.► Since the ridges also participate in

formation of the interventricular septum, the persistent truncus is always

accompanied by a defective interventricular septum.

► The undivided truncus thus overrides both ventricles and receives blood from both sides.

Transposition of the great vessels

► occurs when the conotruncal septum fails to follow its normal spiral course and runs straight down.

► As a consequence, the aorta originates from the right ventricle, and the pulmonary artery originates from the left ventricle.

► sometimes is associated with a defect in the membranous part of the interventricular septum.► Since neural crest cells contribute to the

formation of the truncal cushions, insults to these cells

contribute to cardiac-defects involving the outflow tract.

Double Outlet VentricleDouble Outlet Ventricle

►Double Outlet Ventricle refers to Double Outlet Ventricle refers to abnormal ventriculo arterial alignment abnormal ventriculo arterial alignment in which both arteries appear to arise in which both arteries appear to arise exclusively or predominantly from exclusively or predominantly from morphological right or left ventriclemorphological right or left ventricle

Formation of the Conducting System of the Heart

► 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.

► The atrioventricular node and bundle (bundle of His) are derived from two sources: (a) cells in the left wall of the sinus venosus, and (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► When pharyngeal arches form during the fourth and fifth

weeks of development,each arch receives its own cranial nerve and its own artery.

► These arteries, the aortic arches, arise from the aortic sac, the most distal part of the truncus arteriosus.

► The aortic arches are embedded in mesenchyme of the pharyngeal arches and terminate in the right and left dorsal aortae. (In the region of the arches the dorsal aortae remain paired, but caudal to this region they fuse to form a single vessel.)

► Division of the truncus arteriosus by the aorticopulmonary septum divides the outflow channel of the heart into the ventral aorta and the pulmonary artery.

► The aortic sac then forms right and left horns, which subsequently give rise to the brachiocephalic artery and the proximal segment of the aortic arch, respectively.

first aortic arch has disappeared, although a small portion persists to form the maxillary artery.

► second aortic arch: Disappears. The remaining portions of this arch are the hyoid and stapedial arteries.

► The third aortic arch forms the common carotid artery and the first part of the internal carotid artery. The remainder of the internal carotid is formed by the cranial portion of the dorsal aorta. The external carotid artery is a sprout of the third aortic arch.

► The fourth aortic arch persists on both sides, but its ultimate fate is different on the right and left sides. On the left it forms part of the arch of the aorta, between the left common carotid and the left subclavian arteries.

► On the right it forms the most proximal segment of the right subclavian artery, the distal part of which is formed by a portion of the right dorsal aorta and the seventh intersegmental artery .

► The fifth aortic arch either never forms or forms incompletely and then regresses.

►The sixth aortic arch, also known as the pulmonary arch, gives off an important branch that grows toward the developing lung bud.

►On the right side the proximal part becomes the proximal segment of the right pulmonary artery.

►The distal portion of this arch loses its connection with the dorsal aorta and disappears. On the left the distal part persists during intrauterine life as the ductus arteriosus.

CLINICAL CORRELATESCLINICAL CORRELATES

► Ductus Arteriosus : Ductus Arteriosus : ► Under normal conditions the ductus arteriosus is functionally

closed through contraction of its muscular wall shortly after birth to form the ligamentum arteriosum.

► Anatomical closure by means of intima proliferation takes 1 to 3 months.

► coarctation of the aorta :

► aortic lumen below the origin of the left subclavian artery is significantly narrowed.

► Since the constrictionmay be above or below the entrance of the ductus arteriosus, two types, preductal and postductal, may be distinguished.

► The cause of aortic narrowing is primarily an abnormality in the media of the aorta, followed by intima proliferations.

► In the preductal type the ductus arteriosus persists, whereas in the postductal type, which is more common, this channel is usually obliterated.

What if?..............- then you get

the truncal septum fails to fuse with the septal crest?- perimembraneous VSD

the truncal septum is deviated to the PA side?- tetralogy of Fallot

the truncal septum fails to develop?- truncus arteriosus

the ventricular septum fails to reach the AV valve?- AV septal defects

the arterial trunk stays over the RV but does divide?- double outlet RV

the aortic valve pushes up and right instead of the pulmonary?- transposition of the great vessels

the ventricles fail to centralise over the AV valve- double inlet left ventricle (commonest form of single ventricle)

the loop is to the left?- ventricular inversion (RV on the left, LV on the right)

and of course, combinations exist!

This is just a rough summary, but I hope you get the idea. Can you see now whydouble outlet RV is common and double outlet LV is very rare? Similarly double inlet LVis common, double inlet RV rare? And why a VSD so commonly accompanies problems of connection of the ventricles to the great vessels.

Septal DefectsSeptal DefectsAtrial Septal DefectsAtrial Septal Defects

► Any opening in the atrial septum, other than a Any opening in the atrial septum, other than a competent foramen ovale, is an atrial septal defect competent foramen ovale, is an atrial septal defect (ASD).(ASD).

► Atrial septal defects are classified according to their

location relative to the fossa ovalis 1) Interatrial communications in the region of the 1) Interatrial communications in the region of the

fossa ovalis may represent either a true secundum fossa ovalis may represent either a true secundum

ASD or a valvular incompetent patent foramen ovaleASD or a valvular incompetent patent foramen ovale 2) Defects anterior to the fossa ovalis (primum 2) Defects anterior to the fossa ovalis (primum

defects) (often are associated with a cleft in the defects) (often are associated with a cleft in the

anterior leaflet of the mitral valveanterior leaflet of the mitral valve ))

► 3) Those posterior and superior to the fossa ovalis, the sinus 3) Those posterior and superior to the fossa ovalis, the sinus venosus defects, usually occur in conjunction with anomalous venosus defects, usually occur in conjunction with anomalous connection of the right pulmonary veins.connection of the right pulmonary veins.

► 4)4) Finally, interatrial communications at the expected site of Finally, interatrial communications at the expected site of the coronary sinus ostium are often associated with an the coronary sinus ostium are often associated with an unroofed coronary sinus and left atrial connection of a unroofed coronary sinus and left atrial connection of a persistent left superior vena cava.persistent left superior vena cava.

►

Ventricular Septal DefectsVentricular Septal Defects

► Defects involving the membranous septum with extension into the Defects involving the membranous septum with extension into the adjacent inlet, outlet, or muscular septum are termed adjacent inlet, outlet, or muscular septum are termed perimembranous defects. A perimembranous defect lies in the perimembranous defects. A perimembranous defect lies in the outflow tract of the left ventricle immediately beneath the aortic outflow tract of the left ventricle immediately beneath the aortic valve. Synonyms include membranous defect and infracristal defect. valve. Synonyms include membranous defect and infracristal defect. When viewed from the right side of the heart, the defect is beneath When viewed from the right side of the heart, the defect is beneath the crista supraventricularis and posterior to the papillary muscle of the crista supraventricularis and posterior to the papillary muscle of the conus (Fig. 32.1B). This is the location for approximately 80% of the conus (Fig. 32.1B). This is the location for approximately 80% of

defects seen at surgery or at autopsydefects seen at surgery or at autopsy

► These defects may involve varying amounts of muscular tissue These defects may involve varying amounts of muscular tissue adjacent to the membranous septum and have been variously adjacent to the membranous septum and have been variously subclassified as perimembranous inlet, perimembranous muscular, subclassified as perimembranous inlet, perimembranous muscular, or perimembranous outlet VSD, depending on the extension of the or perimembranous outlet VSD, depending on the extension of the defect. Minor anomalies of the tricuspid valve, which may be defect. Minor anomalies of the tricuspid valve, which may be acquired secondary to left-to-right shunting, frequently are acquired secondary to left-to-right shunting, frequently are

associated with perimembranous defectsassociated with perimembranous defects

► These anomalies take the form of extra septal leaflet tissue or These anomalies take the form of extra septal leaflet tissue or pouches that can partially or completely occlude the defect. These pouches that can partially or completely occlude the defect. These pouches have been called aneurysms of the ventricular septum and pouches have been called aneurysms of the ventricular septum and

can be associated with spontaneous closure of the VSD.can be associated with spontaneous closure of the VSD.

► With the perimembranous defect, there can be a variable degree of With the perimembranous defect, there can be a variable degree of anterior malalignment between the infundibular septum and the anterior malalignment between the infundibular septum and the anterior ventricular septum such that the aortic valve appears to anterior ventricular septum such that the aortic valve appears to override the defect (9). Posterior or leftward malalignment also override the defect (9). Posterior or leftward malalignment also occurs, producing subaortic stenosisoccurs, producing subaortic stenosis

► When the septal commissure of the tricuspid valve is deficient at its When the septal commissure of the tricuspid valve is deficient at its attachment to the atrioventricular membranous septum, a left attachment to the atrioventricular membranous septum, a left ventricular–to–right atrial shunt can occur (10). Such defects ventricular–to–right atrial shunt can occur (10). Such defects

normally are associatednormally are associated with both left ventricular–to–right with both left ventricular–to–right ventricular and left ventricular–to–right atrial shuntingventricular and left ventricular–to–right atrial shunting

► Rarely, a defect can occur in the atrioventricular septum (Gerbode's Rarely, a defect can occur in the atrioventricular septum (Gerbode's defect) that produces an isolated left ventricular–to–right atrial defect) that produces an isolated left ventricular–to–right atrial shuntshunt

► Defects in the outflow tract of the right ventricle beneath the Defects in the outflow tract of the right ventricle beneath the pulmonary valve have been called supracristal, infundibular, conal, pulmonary valve have been called supracristal, infundibular, conal,

subpulmonary, or doubly committed subarterial defectssubpulmonary, or doubly committed subarterial defects ► Outlet VSDs constitute approximately 5% to 7% of defects Outlet VSDs constitute approximately 5% to 7% of defects

seen at surgery or autopsy, except in Japan and other Far seen at surgery or autopsy, except in Japan and other Far Eastern countries, where the incidence is approximately 30%Eastern countries, where the incidence is approximately 30%

► Inlet defects that are posterior and inferior to the membranous Inlet defects that are posterior and inferior to the membranous defect, beneath the septal leaflet of the tricuspid valve, and inferior defect, beneath the septal leaflet of the tricuspid valve, and inferior to the papillary muscle of the conus have been called atrioventricular to the papillary muscle of the conus have been called atrioventricular septal defectsseptal defects

► Defects in the muscular septum are frequently multiple and make Defects in the muscular septum are frequently multiple and make

up 5% to 20% of defects found at surgery or autopsyup 5% to 20% of defects found at surgery or autopsy ► Apical defects are the most common and frequently are difficult to Apical defects are the most common and frequently are difficult to

visualize from the right ventricle because they are usually multiple visualize from the right ventricle because they are usually multiple

with bordering and overlying trabeculae and tortuous channelswith bordering and overlying trabeculae and tortuous channels ► Apical defects are the most common and frequently are difficult to Apical defects are the most common and frequently are difficult to

visualize from the right ventricle because they are usually multiple visualize from the right ventricle because they are usually multiple

with bordering and overlying trabeculae and tortuous channelswith bordering and overlying trabeculae and tortuous channels

► Another type of muscular defect is the central defect (Fig. 32.1B), Another type of muscular defect is the central defect (Fig. 32.1B), which is posterior to the trabecula septomarginalis (septal band of which is posterior to the trabecula septomarginalis (septal band of the crista) and in the midportion of the septum. Commonly, it is the crista) and in the midportion of the septum. Commonly, it is partially hidden by overlying trabeculae when viewed from the right partially hidden by overlying trabeculae when viewed from the right ventricle and can give the impression of multiple defectsventricle and can give the impression of multiple defects

►

► Small muscular defects near the septal–free wall margins have Small muscular defects near the septal–free wall margins have been termed marginal or anterior defects. These defects are usually been termed marginal or anterior defects. These defects are usually multiple, small, tortuous, and distributed along the ventricular multiple, small, tortuous, and distributed along the ventricular septal–free wall marginsseptal–free wall margins

► Prolapse of one of the aortic valve cusps may occur with outlet or Prolapse of one of the aortic valve cusps may occur with outlet or

perimembranous VSDsperimembranous VSDs

Anyway, the relocation of the aorta to the left requires an appreciation of the modelling power of differential growth.All this is happening as the embryo is rapidly growing, even though it is only millimetres long.

day 9

day 13

► Concurrently with atrial septation, the left horn Concurrently with atrial septation, the left horn of the sinus venosus forms the coronary sinus, of the sinus venosus forms the coronary sinus, and the right sinus horn becomes a part of the and the right sinus horn becomes a part of the right atrium. right atrium.

► Infolding at the sinoatrial junction forms the Infolding at the sinoatrial junction forms the right and left venous valves. Whereas the right right and left venous valves. Whereas the right venous valve is maintained and forms the venous valve is maintained and forms the rudimentary valves of the inferior vena cava rudimentary valves of the inferior vena cava (eustachian valve) and the coronary sinus (eustachian valve) and the coronary sinus (thebesian valve), the left venous valve (thebesian valve), the left venous valve becomes fused to the superior, posterior, and becomes fused to the superior, posterior, and inferior margins of the fossa ovalis.inferior margins of the fossa ovalis.