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Chapters

16.0 Lear ning aims, w hat you alr eady should know, intr oduction, delving deeper

Learning aims What you already should know Introduction Delving deeper

16.1 Outer for m and position of the hear t



Introduction First signs of cardiac development The formation of the venticular loop - the U-shaped heart Development of the pericardium Descent of the heart

16.2 Fr om serial to par allel cir culation - the septation of the hear t

Introduction The transformation processes of the atria The transformation processes of the ventricles

The septation of the outflow tract

16.3 For mation of the car diac valves - the valve level

The tricuspid and mitral valves (atrioventricular valves) The aortic and pulmonary valves (semilunar valves)

16.4 Functional development of the hear t



The conduction system Innervation of the heart

16.5 Development of the vessels



Introduction The molecular basis of blood vessel development The molecular basis of lymphatic vessel development

16.6 Development of the veins



Introduction The cardinal system The umbilical system The omphalomesenteric system The pulmonary veins

16.7 Development of the ar teries



Introduction Aortic arches

Vessels of the dorsal aorta

Ventral (visceral), segmental branches of the dorsal aorta Lateral (visceral), segmental branches of the dorsal aorta Dorsolateral (parietal), intersegmental branches of the dorsal aorta Summary of the dorsal aortic vessels

Coronary arteries

16.8 Development of the lymphatic vessels



Introduction The lymphatic vessel system

16.9 Embr yo-fetal cir culation system - changes at bir th



Introduction The fetal circulation system Changes at birth

16.10 Pathologie

Introduction Right cardiac obstruction (without shunt)

Pulmonary stenosis (PS) Tricuspid stenosis

Left cardiac obstruction (without shunt) Aortic stenosis Aortic insufficiency Aortic isthmus stenosis (coarctatio aortae) Interrupted aortic arch Hypoplastic left cardiac syndrome

Heart abnormality with left-right shunt (acyanotic)

Persisting ductus arteriosus (PDA) Atrial septum defect (ASD) Ventricle septum defect (VSD) Atrioventricular septum defect

Heart abnormality with right-left shunt (cyanotic) Fallot's tetralogy Pulmonary valve atresia Tricuspid atresia

Heart abnormality with false connections of the blood vessels Transposition of the great vessels (TGA) Double inlet ventricle Complete pulmonary vein inlet errors Truncus arteriosus communis

16.11 Quiz

Test your knowledge

16.12 Brief summar y

Summarized

16.13 Bibliog r aphy

References

16.0 Lear ning aims, w hat you alr eady should know, intr oduction, delving deeper

Learning aims What you already should know Introduction Delving deeper

Learning aims
The first signs of heart development as well as the location of the cardiogenic tissues How the serial blood circulation system is converted to a parallel one during the course of embryonic development and which factors promote this development The processes that occur in the partitioning of the atria and ventricles. An enumeration of the arterial and venous systems with their various components that are near the heart The relationships of the pericardial cavity in adults, taking into account pericardial development The various nerves that are responsible for cardiac innervation

What you already should know


Embryonic disc (Module 7) Intra- and extra-embryonic spaces in the respiratory tract module (18.4)

Introduction
The cardiovascular system develops very early in the young embryo and is necessary for its survival because it supports nourishment and the exchange of gases as well as the elimination of catabolites. The heart already begins to beat in stage 10 (roughly 28 days) 10 whereby the movement of the blood is initially merely an ebb and flow. The large vessels mainly serve to transport and distribute the blood. The smaller ones are responsible for the exchange processes.
Video Heart beats (259 Kb)

Delving deeper
What controls the course of the mesoderm cell development around the cardiogenic plate? What mechanisms are involved in the formation of the cardiac loop? During its development, the heart descends. What influence could this have on cardiac development? Which forces influence cardiac septation? How does the heart build up the connection to the arterial and venous blood vessels to form the cardiovascular system? Which factors are decisive for the formation and development of arterial and venous vessels? Which development does the aortal arch go through and why does a part of the aortic arch arteries

remain while others disappear? The venous system is complex. Which influences cause some vessels to disappear while others remain as they are? Valves are necessary for a regulated blood flow. Where are such valves located? Why and how are they formed? The innervation of the heart is assured through various nerves. How do the nerves find their way to their corresponding target organs? What promotes the conversion of the circulation system at birth?

16.1 Outer for m and position of the hear t



Introduction First signs of cardiac development The formation of the venticular loop - the U-shaped heart Development of the pericardium Descent of the hearts

Introduction
In the young embryo epiblast cells wander via the primitive streak between epi- and hypoblast and form the mesoderm layer out of which various structures arise. Cells, which are destined for cardiogenesis, take up a position that is cranial to the forming neural tube. Cardiogenesis takes place via a complex series of steps: 1. 2. 3. Determination of mesoderm- and neural crest cells for heart formation Growth and differentiation processes to become cardiomyocytes Migration and transformation processes in order to form the heart

First signs of cardiac development


Quiz 01

Quiz

The cardiogenic plate is formed by a collection of mesoderm cells in the most anterior part of the embryo. In the interactive diagram, please observe how the position of the pericardial cavity changes in relation to the cardiogenic plate due to the bending of the cranial end of the embryo.

Quiz Quiz 24

Quiz Quiz 29

Up to the early stage 9 (at roughly 25 - 27 days) 9 this cardiac anlage is still located in the visceral part of the splanchnic mesoderm (splanchnopleura) above the umbilical vesicle. Out of this mainly develops the myocardium, which is responsible for the very early contractile ability 9-10 of the embryonic heart. Through the rotation following the cranial folding of the embryo the pericardial cavity comes to lie ventrally from the cardiac anlage and, as things progress, will surround it (11). The blood from the supplying vessels, the umbilical and omphalomesenteric veins, flows caudally over the inflow tract into the cardiac anlage and leaves it via the outflow tract and the aortic arches at the cranial end. Fig. 1 - Embryo at stage 9 (roughly 25 - 27 day) after the rotation of the cardiac anlage
Quiz Quiz 02

Legend

without definitions with definitions Fig. 1 Perspective side view of the embryo. The formation of the cardiac tube out of vesicles is shown in an animation.

Ingall, 1920,
modified 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Edge of the amniotic cavity (cut) Embryo (here cranial neural folds) Cardiac anlage Pericardium Anlage of the dorsal aorta Umbilical vein Umbilical artery Anlage of the (extraembryonic) arterial vessels Umbilical vesicle Anlage of the (extraembryonic) venous vessels Extraembryonic mesoderm Allantois Chorionic plate Placental villi

More info By means of various transplantation experiments on research animals, it has been shown that cell interactions play the main role in the differentiation of the mesoderm cells in the region of the subsequent cardiogenic plate. The anterior endoderm that lies ventral to the cardiogenic plate has a decisive influence by secreting inductive factors that over a short distance confer cardiogenic power to the mesoderm (5).

The cardiac tube itself consists of three layers: epicardium, myocardium andendocardium. The outermost layer and boundary of the pericardial cavity is the epicardium. Themyocardial mantle follows as the next inner layer. Together they form themyoepicardium. The considerable distance from the myocardial mantle to theendocardial tube is filled with cardiac jelly and the cardiac lumen is coated withendocardial cells.

Quiz Quiz 03

Fig. 2a - Sagittal section through an embryo in stage 10 (roughly 28th day)

Fig. 2b - Transversal section through an embryo in stage 10 (roughly 28th day)

Legend
Fig. 2a The cranial part of the embryo is shown in a medial sagittal section. The cardiac anlage is surrounded by the pericardial cavity. The heart consists of the myoepicardial mantle, the cardiac jelly and the endocardium. Fig. 2b In this transversal section the heart finds itself at the level of the rhomboencephalon, i.e., still very cranial. Note the position of the pericardium in relation to the heart, the many layers of the cardiac wall and the provisional existence of a dorsal suspension (mesocardium). (see also the development of the pericardium)

1 2 3 4 5

Pericardial cavity Cardiac jelly Endocardal tube Myoepicardium Pharyngeal pouch

6 7 8 9 10

Neural tube Mesocardium Aorta dorsalis Neural crest Notochord

More info The outer layer of the heart is formed by the epicardium that originally arises from the extracardial anlage, the proepicardial serosa cells. ntrallyThese grow over the myocardium and issue from a collection of cells in the septum transversum that lie ventrally to the liver bud near the sinus venosus. Presumably, the subepicardial mesenchymal cells also come from the epicardial layer (1).Besides the epicardial layer, it appears that the proepicardial serosal cells also form the endothelium and the smooth muscle cells of the coronary arteries. Moreover they play a modulating role in the development of the myocardium. (7)

The formation of the venticular loop the U-shaped heart


The early processes of cardiac formation, in particular the forming of the loop, are very interesting from many points of view. A long, closed tube arises out of the endocardial plexus. This tubular heart largely represents the anlage for thetrabeculated part of the future right and left ventricles (3). The outflow tract, coneand the atrium make up here only a small part. Since the curvatures of the heart take place in various planes, the following interactive diagrams show them in two views.

The loop formation in a side view should mainly illustrate how the inflow tract(pink) slips behind the embryonic ventricle (violet) and the outflow tract(yellow). Further, the beginning formation of the sulcus atrioventricularis between the atrium and ventricle can be seen well.

Overview of the illustrations

In the frontal view mainly the formation of the D-loop of the embryonic ventricle(violet) is easily seen. The inflow tract moves upwards and will be covered by a part of the ventricle. The development of the sulcus primus can be easily recognized in this view. Via the movement of the inflow tract to the right a part (later: right atrium) becomes visible besides the outflow tract (Interactive diagram) .

Quiz Quiz 04

Quiz Quiz 05

Fig. 3 - Formation of the loop, frontal view

Fig. 3 - Formation of the loop, frontal view

Legend

Fig. 3 Formation of the loop, frontal view of the embryonic heart

1 2 3 4 5 6 7

Pharyngeal pouch I Aortic arch I Foregut Myoepicardial mantle Pericardial cavity Amniotic cavity Endocardial loop

8 9 10 11 12 13 14

Midgut Septum transversum Omphalomesenteric vein Umbilical vein Sulcus primus Sulcus atrio-ventricularis later: right atrium

Video The formation of the loop and the change in position of the individual cardiac segments that are connected with it can be followed by looking at the plastillin model.

Lateral view (1.2 Mb) Front view (1.5 Mb)

Development of the pericardium

In the early part of stage 9 (ca. 25th day) 9 the embryo is shaped like a foot soleand consists of ectoderm, mesoderm and endoderm cell layers. In the extraembryonic region the lateral plate mesoderm becomes split. The visceral layer, covering the umbilical vesicle, forms the splanchnopleura together with the adjacent endoderm. The parietal layer covers the amniotic cavity and together with the adjacent ectoderm is named somatopleura. In the lateral plate mesoderm itself, probably as a result of uneven growth, dehiscences (splits open), thereby creating small, fluid-filled cleavages. These spaces fuse in the area of the head and form the pericardial cavity that corresponds to the cranial part of the U-shaped intraembryonic coelom. During the course of stages 9 (ca. the 25th day) and 10 (ca. the 28th day) the formation of thehead fold occurs via the cranial flexion. Thereby, the future outflow tract (arterial pole), which at the start of the cardiac formation 9 lies caudally to the inflow tract (venous pole), comes to lie cranially due to this cranial flexion of the embryo through a 180 degree rotation and the relative shrinking of the umbilical vesicle. Fig. 4 - Position of the pericardium before the rotation Fig. 5 - Position of the pericardium after the rotation Legend
Fig. 4 The pericardial cavity as well as the cardiogenic plate lie cranially to the embryonic anlage. The pericardial cavity is found dorsal to the cardiogenic tissue. Further, one can distinguish the venous (inflow tract) from the arterial (outflow tract) parts of the cardiac anlage. The venous part of the later cardiac anlage is found more cranially than the arterial. Fig. 5 After the 180 degree rotation the pericardial cavity is found ventral to the cardiac anlage. Through the rotation, the venous part (inflow tract) of the cardiac anlage now lies caudal of the arterial pole (outflow tract).

1 2

Pericardial cavity Cranial end of the embryo

A V

Arterial part (outflow tract) Venous part (inflow tract)

The pericardial cavity expands on both sides of the cardiac anlage and invaginates the myocardiac mantle with the cardiac loop. This results in themesocardium 9 being transiently formed on the dorsal side of the cardiac loop.

Overview of the illustrations

More info The anatomic relationships of the adult heart can be better understood when one follows the embryonic development of the pericardium further. (Interactive diagram).

16.1 Outer for m and position of the hear t



Introduction First signs of cardiac development The formation of the venticular loop - the U-shaped heart Development of the pericardium

Descent of the heart

Descent of the heart


The first cells of the cardiac anlage are found in front of the embryonic disk in thecardiogenic plate. Due to the bending of the embryo this anlage experiences a rotation of 180o and at the same time it moves caudally. With 4 weeks the tip of the heart is already at the height of the cervical segment. In stage 16 (ca. 39th day) 16 it reaches the thoracic vertebrae. The heart sinks further until the tip of a newborn heart comes to lie at the level of the 3rd to 4th intercostal space in relation to the front side of the thorax (i.e., the level of the 8th thoracic vertebra). In the beginning of the early embryonic stages (stages 8, ca. the 23rd day 8 ), the heart forms outside the embryonic disk. It is only with the flexion of the embryo that the heart comes to lie within and ventral to the embryo. Through the growth of the brain the embryo bends forward progressively and in stage 14 (ca. the 33rd day) 14 it attains its maximum flexion. However, the heart continues to descend further and, at the end of the embryonic period, comes to lie in the thoracic region.

Fig. 6 - Descent of the heart and the diaphragm

Legend
Fig. 6 To obtain more information about embryonic stages 14, 17 or 20, click on the red triangles.

1 2

Expansion of the heart Level of the diaphragm

16.2 Fr om serial to par allel

cir culation - the septation of the hear t



Introduction The transformation processes of the atria The transformation processes of the ventricles The septation of the outflow tract

Introduction
With ca. the 28th day 10 the heart of the embryo begins to beat. Initially this only causes a back and forth movement of the blood to occur, but very soon a directional flow of the blood begins from the inflow tract over the atrium and ventricle part in the conus cordis and thepair of aortic arches. The inflow tract contains oxygen-rich blood from theumbilical veins and a contribution from the omphalomesenteric veins. Fig. 7 - Heart in stage 10 (ca. the 28th day) Legend
without definitions with definitions Fig. 7 The blood flows into the heart from the paired umbilical and omphalomesenteric veins. It leaves the heart via the pair of aortic arches in order to get into the embryo's blood circulation system.

1 2 3 4

Endocardial loop First aortic arch Foregut Cardiac jelly in the myocardiac mantle 5 Pericardial cavity 6 Amniotic cavity 7 Midgut 8 Septum transversum 9 Umbilical vein 10 Omphalomesenteric vein

More info In the embryo, the first heart contractions can be detected in stage 8 (ca. the 23rd day). In the beginning, the frequency is limited to roughly 70 contractions per minute. Up to the 7th week of pregnancy, though, the frequency increases to 170 190 beats /minute and at birth the heart beats at 160 - 180 times per minute.

The transformation processes of the atria


With the formation of the cardiac loop the inflow tract migrates with the sinus venosus and the two sinus horns up and to the rear. In addition, the vein opening that is originally located symmetrically is also shifted towards the right, together with its various branches. In the beginning, the sinus venosus contains only blood from the two umbilical veins (oxygen- and nutrient-rich from the placenta), the omphalomesenteric veins and finally the commun cardinal veins, which receive the blood from the embryonic somatic circulation proper. After various transformation processes in which the sinus venosus is incorporated into the right atrium and the left sinus horn atrophies, the blood gets directly into the right atrium through the superior and inferior vena cava. The venous openings of the left sinus horn (common cardinal vein and umbilical / left omphalo-mesenteric vein) atrophy and the remnants form the sinus coronarius. Fig. 10 - Side view of a cardiac section Fig. 11 - Ventral view of a cardiac section

Quiz Quiz 26 Quiz 27

Illustration View of the developing heart from behind

Legend
Fig. 10, 11 In stage 12 (ca. the 30th day) the blood enters through the sinu-atrial inlet into the atrium and thereby gets into the common ventricle via the atrioventricular canal, which is outwardly constricted by the sulcus atrioventricularis Fig. 10 without definitions with definitions

1 2 3

Ventricle Atrium Sinu-atrial inlet

4 5 6

Septum spurium Dorsal septum atrio-ventriculare in the atrio-ventricular canal Sulcus atrio-ventricularis

Fig. 11 without definitions with definitions

In this interactive diagram and using a front view and associated section, it is shown how the inflow tract is shifted to the right with the sinus venosus and the two sinus horns. The result is that the blood now only flows in the right part of the atrium (still common to both) through the sinu-atrial inlet. The blood flow through this opening is formed by two valves, the venous valves and their fusion forms the septum spuriumabove the opening.

Quiz Quiz 6

In the heart itself various transformation

Fig. 12 - Ventral view of a cardiac section

Legend

processes are taking place at this time so that the blood no longer flows serially through it. At the transition to the ventricle a prominent indentation named sulcus atrio-ventricularis forms between the atrium and ventricle segments. In the interior, the passage to the canalis atrioventricularis (av-canal) narrows. Theshifting of the av-canal to the right has a decisive influence on the further development (it is now in the center and no longer on the left), so that the blood that initially only flowed in the left ventricle can now empty into both ventricles. Through this shift, a connection of the two atria to theirventricles has arisen.
1 2 3 4 5 6 7 8 Right atrium Dorsal atrio-ventricular septum in the av-canal Right ventricle Interventricular septum Septum primum Left atrium Sulcus atrio-ventricularis Left ventricle

without definitions with definitions Fig. 12 In stage 13 (ca. the 32nd day) the av-canal is shifted in the middle of the heart and makes sure that each atrium is connected with its ventricle.

In the atrium itself a fold, the septum primum 12-13 , grows to the left of the septum spurium from the roof of the still common atrium towards the av-canal. Only a small opening remains above the atrio-ventricular septum, theforamen primum. Due to the septum primum, the common atrium gets divided into right and left chambers. The common ventricle is also separated by the interventricular septum into two chambers. (see transformation processes of the ventricle).

Fig. 13 - Ventral view of a cardiac section

Legend
without definitions with definitions Fig. 13 The heart in stage 15 (ca. the 36th day) exhibits incompletely separated chambers. The av-canal is divided by the dorsal (lower) and ventral (upper) cushion into left and right av-canals.

Quiz Quiz 07

1 2 3

Septum spurium Sinu-atrial inlet Dorsal atrio-ventricular septum in the av-canal 4 Sulcus atrio-ventricularis 5 Right atrium 6 Interventricular foramen 7 Interventricular septum 8 Left ventricle 9 Right ventricle 10 Left atrium 11 Septum primum 12 Foramen secundum

The flow relationships are such that the blood derived from embryonic somatic circulation, which flows into the right atrium via the common cardinal veins (later the superior vena cava), empties itself mainly via the right part of the av-canal into theright ventricle. A further septum, the septum secundum, grows subsequently on the right of theseptum primum from the front downwards and towards the lower rear. Through the newly created foramen secundum in the septum primum a connection still exists between the right and left atria. However, this connection becomes constricted and covered almost completely by the septum secundum until the end of the embryonic period. It is now called the foramen ovale and has a valve-like character in that the blood from the right side flows with a high pressure to the left side but no blood can return (more information in the interactive diagram).

Interactive diagram In this interactive diagram the septation of the atria is shown in a sagittal section through the right

In summary it can be said that for the transformation from a serial to a parallel flow both outer as well as inner transformation processes are responsible. At the atrium level these are: The relocation of the sinus venosus to the right The relocation of the av level into the middle The septation of the common atrium The septum formation at the av level

More info Today one can trace the origin of tissues using antibodies . With this method it can be shown that the tissue for the atrial septa comes from the left atrium. It appears that remaining mesenchymal cells that migrated via the mesocardium into the myocardium are decisive for the growth of the septa. One finds the corresponding gene expressing cells both there where the mesocardium atrophied as well as on the free edge of the septum primum. (8)
Quiz 08

Quiz

The transformation processes of the ventricles

Quiz Quiz 09

Quiz Quiz 10

While the common atrium is arranged

Fig. 14 - Septation of the heart side view

Legend

through septation into right and left atria the ventricle is separated into two chambers by the interventricular septum (IVS) 11-12 . In contrast with septation of the atria, which is an active process, the subdivision of the ventricles is largely passive. In fact, whereas the two ventricles increase in size, the part between them (septum portion) does not grow with the heart and forms a constriction, the sulcus interventricularis.

Fig. 14 In this illustration, the right half of the heart has been removed by a sagittal section. One is looking into the heart at the level of the septum. By the outgrowth of the septa into the atrium and ventricle the heart gets divided into its four chambers.

More info In the interactive diagram the processes that lead to septation of the heart are shown in detail.

Lateral view Frontal view

Summary The change from a serial to a parallel flow of blood is accomplished during stage 13 (ca. the 32nd day) 13 . This development is mainly facilitated byhemodynamic factors in that the blood flow comes together from the two sinus horns and travels in a spiral stream to the outflow tract. The following changes occur in the heart:

1. The sinus venosus is shifted from the middle to the right side. The blood
flows thereby only via the right atrium into the heart.

2. The atrioventricular canal is shifted from the left side where it was initially to
the middle so that the right atrium can communicate directly with the right ventricle. Thus a part of the blood gets directly from the right atrium into the right ventricle. The definitive separation of atria from ventricles follows by the growing together of the dorsal and ventral av-septa. left ventricle keeps its access to the outflow tract.

3. The common atrium and ventricle become divided by septa. However, the

The septation of the outflow tract


Quiz 11

Quiz

Due to the various crease directions at various locations, each of the septa in the outflow tract receives its typical

Fig. 15 - The heart during the loop formation: view from left, stage 10 (ca. the 28th day)

Legend

localization. Here also hemodynamic factors play an important role in that the blood moves to the outflow tract in a spiral stream. In addition, the outflow tract lengthens. In stage 11 11 theconus, which lies within the pericardium, still borders directly on the aortic sacthat lies in the mesenchyma of the neck. The boundary between the aortic sac and the conus part can be recognized in that the myocardial mantle still only surrounds the conus part.

Fig. 15 The direction of the loop formation is shown by the arrows. The dashed line indicates where the reflection of the pericardium is. There the myocardial mantle of the outflow tract also ends.

1 2 3 4 5 6 7 8 9

Aortic root (aortic sac) Conus Material for the atria Material for the ventricle left horn of the sinus venosus Left umbilical vein Left omphalomesenteric vein Pericardium Sulcus interventricularis

In the course of further development of the heart the segment between the conus part and the aortic sac lengthens within the pericardium. Among other places, the material for this segment comes from neural crest cells that migrate over thepharyngeal arches III, IV and VI and are responsible for the development of the truncus arteriosus as well as the divisions of the outflow tract (9). Based on this fact, one always speaks in the following of the conotruncus. Fig. 16 - Migration of the neural crest cells via the pharyngeal arches Legend

Fig. 16 The neural crest cells migrate over the pharyngeal arches III, IV and VI along the aortic arches that have been formed to the heart. They are responsible for the lengthening of the truncus and the separation of the outflow tract.

1 2 3 4 5 6 7 8 9

Neural crest left internal carotid artery First aortic arch in the first pharyngeal arch (mandibular arch) Anlage of the eye Conotruncus Sixth aortic arch (pulmonary arch) Aorta dorsalis Aortic sac Right ventricle

More info The pax3 gene is responsible for the fine-tuning of the neural crest cell emigration from the neural tube region. In the absence of the pax3 gene (splotch embryo) or by removal of the corresponding neural crest cells it has been shown experimentally that severe cardiac abnormalities result. (9)

The lengthening of the truncus part causes a further sulcus to occur between the conus and truncus that in the later development marks the formation of the endocardial cushions for the aorta and pulmonary valves (see semilunar valves). Very important for the division of the outflow tracts is the fact that the two streams of blood thus flow around each other spirally, influencing the growth of both the conus and truncus septa. Fig. 17 - Blood flow through the heart Navigation

without definitions with definitions Fig. 17 The right ventricle is cut open. One can see the not yet completely separated conotruncus.The spiral blood flow can be identified.

1 2 3 4 5 6 7 8 9 10 11

Aorto-pulmonary septum Upper truncus septum Right conus septum Right av-canal Rear processes of the interventricular septum Aorta Pulmonary truncus Lower truncus septum Left conus septum Crista prima (almost atrophied) Interventricular septum: anterior part

Three components are responsible for forming the septa in the outflow tract (according to how the blood flows): Conus septum Truncus septum Aorto-pulmonary septum

More info In the interactive diagram the relationships of the outflow septation are shown in detail.

For the conus and truncus septa initially only the endocardial cushions, formed through the influence of immigrated neural crest cells, are involved.They grow into the lumen and join up in the middle. The aorto-pulmonary septum consists of themesenchyma between the pharyngeal arches IV and VI. (see also: development of the arteries). It grows as an unpaired relief in a direction that is against that of the blood stream. Through the spiral-shaped blood flow its right process grows onto the lower and its left process towards the upper truncus septum and unites with it. The upper truncus septum grows against the flow onto the right conus septum and the lower towards the left conus septum.Thus the outflow tract septum has completed a rotation of 180 degrees. Finally, the left conus septum joins with the free border of the septum interventriculare after the crista prima has regressed. The right conus septum joins with the dorsal avseptum

16.3 For mation of the car diac valves - the valve level

The tricuspid and mitral valves (atrioventricular valves) The aortic and pulmonary valves (semilunar valves)

The tricuspid and mitral valves (atrioventricular valves)


Very early in cardiac development the atria, which have formed in the rear upper part, are separated from the ventricles by the sulcus atrio-ventricularis. In the interior of the heart, endocardial cushions form that grow first both dorsally and ventrally into the lumen. Somewhat later, these two cushions fuse in the middle of the lumen thereby divide the av-canal into right and left openings. 18 and

Quiz Quiz 28

More info One can first rightly understand the relationships at the valve level when one takes into consideration all the septa that contribute to the separation of the cardiac chambers in this region. This is done best using a section of a ventricle.

More info In the cushion area the cardiac jelly looks like a thick basal membrane that protrudes into the lumen and thus fulfills a primitive valve-like function. In this region, induced by molecules that are given off by the myocardium cells leave the endocardium, assume a mesenchymal form and migrate into the cardiac jelly. It can be experimentally shown that only cells in the atrioventricular region and near the outflow tract can react in this way to an induction of the myocardium.

The aortic and pulmonary valves (semilunar valves)


As explained in the description of the separation in the outflow tract region, the crease between the truncus and conus has a special meaning. Here the aortic and pulmonary valves (valvulae semilunares) arise. Involved in this are primarily themesenchymal cushions that are created from immigrated neural crest cells. The septum of the outflow tract leads to a definitive separation of what was initially a common outflow tract. In the area of the conus-truncus-transition it delivers material for the pulmonary truncus and the aorta for the right and the left semilunar valves. In addition, in the ventral area, a new valve forms - the ventral semilunar valve for thetruncus pulmonalis. In the dorsal area an additional fold also forms that develops into the dorsal semilunar valve of the aorta. Fig. 18 - Outflow tract from the front right Legend
Fig. 18 On the left is the conotruncus as seen ventrally (45 from the right). In the right image (at A) the truncus is cut away so that the semilunar valve level is visible. Dorsally lies the aorta with right, left and dorsal valves and ventrally lies the truncus pulmonalis with right, left and ventral (anterior) cushions.

Animation From the common outflow tract, the conotruncus, arise two outflow vessels: the aorta and the truncus pulmonalis. Animation (671 kB)

1 2 3 4 5 6 7 8 9

Aorta Conotruncal crease Truncus pulmonalis Posterior aortic valve Left aortic valve Right aortic valve Right truncus pulmonalis valve Anterior truncus pulmonalis valve Left truncus pulmonalis valve

More info Through an additional shift of location the conus is included in the right ventricle.

Thus, the semilunar valves come to lie near the av-level with the atrioventricular valves. This is termed the valve plane. In the course of further development a rotation in an anti-clockwise direction also follows so that the aortic dorsal valve comes to the right and the right towards the front. Analogously the anterior pulmonary valve shifts to the left and the left towards the rear. Thus one obtains the nomenclature normally used with adults of a left, right and posterior cusp for the pulmonary valve and a left, right and anterior cusp for the aortic valve. Rotation of the valve planes

16.4 Functional development of the hear t



The conduction system Innervation of the heart

The conduction system


With today's technology, the first heart beats in an embryo can be detected already in stage 8 (ca. the 21rst - 22nd day) 8 . One finds thereby that the various cardiac regions have their own patterns of beating.

More info The frequencies of isolated (pacemaker) cells in the individual cardiac regions decrease as one goes from the atria to the ventricles. In the atria the frequency amounts initially to ca. 62 beats/min. and in the ventricles only to 25 beats/min. Various transplantation trials with chicken embryos have shown that the beating pattern is influenced by the extracellular matrix. If atrial tissue is transplanted into the ventricle region, it adapts to the beating pattern there.

The first morphologically visible differentiation of the conduction system in human embryos is the sinu-atrial node 14 . It is located in the wall of the right sinus horn near its opening in the right atrium, i.e., in the sulcus terminalis. Fig. 19 - Conduction system of the embryonic heart Legend

The atrioventricular conduction system,

the av-node or Aschoff-Tawara's node, becomes discernible somewhat later 15-16 . It lies at the dorsal circumference of the av-canal in the inner layer of the myocardium at the beginning of the dorsal av-septum. From it derives the His' bundle, which extends over the dorsal av-septum and forms the connection between the atrial and ventricular myocardium Here it divides into three subendocardial bundle branches. They extend into the cardiac apex region where a separation into finePurkinje's fibers occurs. In situ, this conduction system forms itself from specialized myocardial cells. Once the sinu-atrial node 14-16 as well as the av-node and His' bundle have been differentiated, the cardiac frequency increases rapidly and reaches 140 beats/min. The region with the highest frequency (sinus region) takes over thepacemaker function.
1 2 3 4 5 Sinu-atrial node in the sulcus terminalis Av-node (Aschhoff-Tawara node) Truncus (His' bundle) Right and left pedicle bundle Purkinje fibers

Fig. 19 The pacemaker for normal heart rhythm is the sinus node. The excitation spreads out over the two atria and extends to the avnode, which also possesses the pacemaker capability. From here, the excitation spreads over the His' bundle and bundle branches and finally via the Purkinje fibers into the ventricular myocardium.

nnervation of the heart


Quiz 20

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The first development of the heart takes place independently of its innervation. Later, though, three differing sources for cardiac innervation can be found. The parasympathetic innervation (cholinergic system) arises from cardiac components of the cranial neural crest cells. The neurons of the cardiac ganglia, which represent parasympathetic neurons of the second order, migrate directly from the neural crest into the heart. Somewhat later, the axons of the first order nerves obtain access to the heart via the vagus nerve. The parasympathetic innervation slows the heartbeat. The sympathetic nerve fibers (adrenergic system), which speed up the heartbeat as well as promote the positive inotropism of the cardiac musculature, arise from thethoracic sympathetic ganglia that in their turn come originally from the thoracic neural crest cells. The third component of the innervation comes directly from the vagus nerve. These are sensory nerves that arise from the ectodermal placode of the nodose ganglion. Fig. 20 - Various origins of cardiac innervation Legend

Fig. 20 In the lefthanddiagram, the source of the cardiac components of the cranial neural crest for the parasympathetic (1 + 2) and sympathetic (3) innervation of the heart are to be seen. On the right, the heart is shown isolated with the two efferent and the one afferent components involved in the cardiac innervation. This drawing also reminds us that the conotruncus is made up of derivatives of the neural crest cells (rhombencephalon) migrating through the pharyngeal arches.

1 2 3 4 5 6 7

Neural crest cells in the area of the rhombencephalon (hindbrain), parasympathetic, efferent Ectodermal placode of the nodose ganglion (parasympathetic, afferent) Neural crest cells of the trunk forming sympathetic ganglia (efferent) First order parasympathetic neurons from cranial neural crest cells (1) contained in the vagus nerve (X) Second order parasympathetic neurons from the cranial neural crest cells (1) that immigrate directly into the heart Sensory ganglia that originate from the ectodermal placode of the nodose ganglion (2) Sympathetic nerve fibers that originate from sympathetic ganglia of the trunk Note also: cardiac outflow tract with neural crest cell material (1) migrated via the pharyngeal arches

More info During the early development of the brain, sideways thickenings of the ectoderm appear, the ectodermal placodes. Such thickening of the ectoderm mainly results from induction processes between various types of tissue. In the rhombencephalon various ectodermal thickenings also form. Together with the local neural crest cells, they contribute to forming the sensory ganglia of the cranial nerves.

16.5 Development of the vessels



Introduction The molecular basis of blood vessel development The molecular basis of lymphatic vessel development

Introduction
Our body has two different vessel networks:

the blood vessels that form a circulation system for the blood the lymph system, the vessels of which transport the lymph in only one direction

The blood vessels bring oxygen, nutrients and a wide variety of immune cells to the individual organs and transport CO2 and catabolites away. The lymph system takes up fluids and immune competent cells that have left the blood vessels and conveys them back into the blood circulation system by passing them through various lymph nodes. The first signs of vessel formation are found in the region of the umbilical vesicle (extraembryonic) at stage 8 8 . Mesodermal cell masses are seen there that are also known as hemangioblasts. Within these mesodermal cell masses, those in the center become rounded and develop into the precursors of the blood cells (hemocytoblasts) while the peripheral cells come together as delimiting endothelial cells (angioblasts). Both the formation of the vessels as well as that of the cardiac tube have thus a close relationship to the endoderm that appears to have aninductive influence. Already before stage 9 9 intraembryonic vessels also form from angioblasts that have differentiated within the splanchnopleurae. Angioblast cells migrate away and settle in the various organs, attracted by angiogenetic factors that stimulate vessel formation.

The molecular basis of blood vessel development


The actual vasculogenesis, the formation of tubes by the angioblasts, takes place in that neighboring cells come to lie beside each other and thereby delimit a vessel lumen. The angioblasts further differentiate themselves into pericytes and intofibroblasts and smooth muscle cells. Ultimately, the forming of the vessel stems from a plexus of capillaries is also determined by hemodynamic factors. However, not all of the vessels arise from a capillary network; the dorsal branches of the aorta are strongly determined by the metamerism of the somites. Fig. 21 - Vasculogenesis Legend

Fig. 21 Schematic diagram of the maturation and stabilization of blood vessels. The blue arrows show that various growth factors (VEGF, Ang1, EphrinB2) and the corresponding receptors (VEGFR1/2 Tie1/2) influence vessel formation. More info The interactive diagram indicates the factors responsible for the differentiation of embryonic vessels either to lymph or to venous vessels.

More info Recently various growth factors have been found that are responsible for the formation and further development of vessels (4, 6). It is also known that these factors must work together in concert so that functional vessels can form. In theinteractive diagram (70 kB) the most important growth factors are shown that determine whether vessels differentiate further or atrophy in the course of the development.

The molecular basis of lymphatic vessel development


In both the venous and the lymphatic sections the embryonic veins form the basis for vessel formation. In an initial differentiation step in the young embryo a portion of the endothelial cells in certain regions of the cardinal vein system begins to produce special receptor molecules (Prox-1). This is the first step in the direction of lymphatic vessel determimation. Now follow further expressions of receptor patterns that are

characteristic for either blood or lymhatic vessels and which are preserved even into adulthood. Fig. 22 - Differentiation to lymphatic and blood vessels Legend
Fig. 22 Whether an embryonic vessel differentiates into a vein or a lymphatic vessel depends initially on a gene, the Prox1 Homebox gene. Depending on the direction other receptors are formed during the course of development.

More info The embryonic lymphatic vessels stem originally from blood vessels. In certain regions of the cardinal vein system of the young embryo endothelial cells express special receptor molecules (Prox-1). This is the first step in the formation in the direction of lymphatic vessel formation. What this stimulation triggers in the Prox-1 Homebox gene that forms the basis for the vessel formation is not yet known (4). (interactive diagram)

16.6 Development of the veins



Introduction The cardinal system The umbilical system The omphalomesenteric system The pulmonary veins

Introduction
The embryo's vein system develops out of a very irregular network of capillaries, from which finally individual ones transform themselves definitively into veins while others disappear again. The result of this is that the venous system is not very uniform, and in the adult far more variants of venous outflows than on the arterial side exist. One can nevertheless distinguish among three basic systems: cardinal, umbilical and omphalomesenteric. The pulmonary veins cannot be counted as belonging to these three systems and are treated separately.

The cardinal system


Quiz 18

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The cardinal veins form as the basis for the intraembryonic venous part of the circulatory system. Various venous systems appear in various stages of the embryogenesis and partially disappear again. Very early in the development two paired systems appear:

Quiz Quiz 19

The superior cardinal veins bring the blood from the head region via the left and right common cardinal vein The inferior cardinal veins drain the blood from the lower half of the body into the two common cardinal veins

From here, the blood is emptied into the sinus venosus and into the atrium via thesinus horns.

The adult venous system is much more variable as the arterial system. Through transformative processes during the development the individual sections arise from various portions of the embryonic venous system.

Overview Overview of the origin of the adult venous system Quiz Quiz 17

The umbilical system


The umbilical veins bring the nutrientand oxygen-rich blood from the placental villi via the umbilical cord to the embryo. Normally there exists only one umbilical vein in the umbilical cord: the unpaired umbilical vein. At the caudal rim of the navel, though, it becomes connected to the two intraembryonic umbilical veins, which go laterally from the umbilical coelom to the heart and empty into the two sinus horns with theomphalomesenteric veins that lie medial from them. Fig. 23 - Umbilical venous system Stage 12 (ca. the 30th day)

Legend
Fig. 23 Heart with major inand out- flowing vessels.

1 2 3 4 5 6 7 8 9 10

First aortic arch Outflow tract (distal section) Superior cardinal vein Inferior cardinal vein Upper intestinal sinus Ventricle (middle section) Sinus venosus Liver anlage Umbilical vein Omphalomesenteric vein

In the further development the umbilical veins become quickly included in the developing liver, so that they obtain a connection to the liver's capillary plexus. Now the blood from the left and right umbilical vein gets into the sinus venosus directlyon the one hand and via the anastomoses in the liver on the other. The extrahepatic part of the umbilical veins atrophies rather soon 13-14 . The blood of the umbilical veins now reaches the sinus venosus mixed with the blood of the omphalomesenteric veins passing through the liver. The posthepatic part of the left omphalomesenteric vein atrophies and the right one takes over all of the blood flowing through the liver. (compare the development of the cardinal vein system interactive diagram) In parallel a shunt, the ductus venosus, has formed within the liver. It directs a part of the nutrient- and oxygen-rich blood from the umbilical veins directly into the heart so

that it reaches organs like the brain as quickly as possible.

Development of the omphalomesenteric system


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Sinus venosus Superior cardinal vein Inferior cardinal vein Left common cardinal vein Right umbilical vein Liver Anastomose between the left and right omphalomesenteric vein Right umbilical vein (prehepatic) Left umbilical vein Right omphalomesenteric vein Umbilical vein (unpaired) Vena cava inferior Ductus venosus Portal vein Splenic vein

Navigation

Stage 13 (32nd d.)

Stage 15 (36th d.)

Stage 18 (44th d.)

Stage 20 (49th d.)

Overview of the illustrations

The prehepatic portion of the right umbilical vein later atrophies completely and all of the placental blood gets to the liver via the left umbilical vein. Following birth, the left umbilical vein is obliterated and the ductus venosus becomes the ligamentum venosum.

The omphalomesenteric system


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Below the heart and parallel to the umbilical venous system a second venous network develops, the omphalomesenteric system. It empties into the sinus venosus. The omphalomesenteric veins are closely associated with the development of the duodenum and the liver and drain the blood of the umbilical vesicle. With the development of the liver the omphalomesenteric veins form a thick hepatic plexus. They also anastomose with the umbilical veins. Through various transformative and degenerative processes the vena portae arises that brings the blood from the intestines into the liver. By this means the absorbed nutrients from the intestines can be taken up later through the liver and metabolized. On the other hand, a short-cut , the ductus venosus, is engendered from the thick network of anastomoses. Up to the time of birth, it takes the blood from the umbilical vein and the omphalomesenteric veins and directs it directly into the sinus venosus of the heart.

During the course of the early cardiac development the left sinus horn atrophies and with it the posthepatic part of the left omphalomesenteric vein. All of the blood from the liver is conveyed via the right omphalomesenteric vein to the sinus venosus. The prehepatic part of the omphalomesenteric veins also experiences various transformative processes in that individual parts around the duodenum atrophy and others become more pronounced. Development of the omphalomesenteric system Navigation

Stage 13 (32nd d.)

Stage 15 (36th d.)

Stage 18 (44th d.) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Sinus venosus Superior cardinal vein Inferior cardinal vein Left common cardinal vein Right umbilical vein Liver Anastomosis between the left and right omphalomesenteric vein Right umbilical vein (prehepatic) Left umbilical vein Right omphalomesenteric vein Umbilical vein (unpaired) Inferior vena cava Ductus venosus Portal vein Splenic vein

Stage 20 (49th d.)

Overview of the illustrations

The pulmonary veins


The pulmonary veins are not assigned to any of the three systems just mentioned because they develop independently. There is no consensus about whether the pulmonary vein as a branch from the left atrium obtains a connection to the lung plexus or the pulmonary vein forms as a solitary vessel in the dorsal mesocardium and is only secondarily incorporated into the atrium. In either case, with the further development of the heart, more and more of the pulmonary veins are incorporated into the left atrium, so that at the end of the embryonic period 4 independent pulmonary veins empty into the atrium. Fig. 24 - Formation of the pulmonary veins; Stage 12 (ca. the 30 day) Fig. 25 - Formation of the pulmonary veins; Stage 13 (ca. the 32 day) Legend

Fig. 24 Initially, only one pulmonary vein empties into the left atrium. Fig. 25 More and more of the sinus venosus and the pulmonary vein become incorporated into the atrium.

1 2 3 4 5 6

Septum spurium Inlet of the sinus venosus Dorsal septum atrio-ventriculare Sulcus atrio-ventricularis Atrium Ventricle

1 2 3

Incorporation of the sinus venosus into the right atrium Pulmonary veins Incorporation of the pulmonary veins into the left atrium

Fig. 26 - Formation of the pulmonary veins; Stage 14 (ca. the 33 day)

Fig. 27 - Formation of the pulmonary veins; Stage 15 (ca. the 36 day)

Legend
Fig. 26 With time the two pulmonary veins empty separately into the left atrium. Fig. 27 In stage 15 the 4 pulmonary veins empty into the left atrium.

1 2 3

Incorporation of the sinus venosus into the right atrium Pulmonary veins Incorporation of the pulmonary veins into the left atrium

1 2 3

Incorporation of the sinus venosus into the right atrium Pulmonary veins Incorporation of the four pulmonary veins into the left atrium

More info The latest research shows that the pulmonary veins arise as solitary vessels in the mesenchyma of the mediasatinum and canalize the blood of the pulmonary vein plexus into the heart (10). The individual pulmonary veins that have been engendered become incorporated into the left atrium and finally 4 independent pulmonary veins

empty into the heart.

16.7 Development of the ar teries



Introduction Aortic arches Vessels of the dorsal aorta

Ventral (visceral), segmental branches of the dorsal aorta Lateral (visceral), segmental branches of the dorsal aorta Dorsolateral (parietal), intersegmental branches of the dorsal aorta Summary of the dorsal aortic vessels

Coronary arteries

Introduction
Isolated vessel islands develop as the first embryonic vessels. They flow together to form plexuses, out of which forms the initially paired aorta 9 . The blood, which is pumped out of the cardiac ventricles into the embryonic circulatory system, gets into this pair of dorsal aortas 9-10 via a paired system of aortic arches. In the course of the development 6 aortic arches are engendered. Not all six, though, are present at the same time, a cranio-caudal gradient of development exists. Initially, the dorsal aortas are arranged as a pair 10 but as the development proceeds, they fuse from the C7 level to the branching of the level to the branching of the umbilical arteries.

Aortic arches
Quiz 13

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The aortic arches are vessels that connect the cardiac saccus aorticus with the paired dorsal aorta by going around the pharynx. They develop one after the other in the pharyngeal arches. Between them the pharyngeal pouches are found that represent endodermal protrusions. When the aortic arches 3-6 have appeared 14 , the first two have already more or less disappeared. It seems the neural crest cells, which migrate via the aortic arches to the heart, also have a large influence on the normal development of the aortic arches (compare separation of the outflow tract).

Quiz Quiz 14

Quiz Quiz 21

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Quiz 22

Animation Development of the aortic arches (90 kB)

This successive appearance of the aortic arches reflects the principle of morphologic adaptation of the vascular system to the various stages of embryonic development.

Fig. 28 - Connection of the aorto-pulmonary septum with the truncus septa

Legend

without definitions with definitions Fig. 28 The aorto-pulmonary septum grows upstream from material between pharyngeal arches IV and VI. It connects up with the two truncus processes. By clicking the relationships with the associated aortic arch arteries can be visualized.

1 2 3 4 5 6

Aorto-pulmonary septum Right aorto-pulmonary septum pedicle Left aorto-pulmonalry septum pedicle Upper truncus process Lower truncus process Truncus

The first 3 arches were adapted for supplying the cervical and cranial regions and, among other things, form the internal carotid artery 11 , which is responsible for the supplying the face and frontal parts of the brain. The external carotid artery independent vessel. 14 arises somewhat later as an

More info For the development of theductus arteriosusthe expression ofHoxb5 by the neural crest cells along the 6th aortic arch is probably determinant. The ductus arteriosus is a vessel of themuscular type. It is held open prenatally through the influence ofprostaglandinesth at stem from the placenta, and through the relatively low partial pressure of the oxygen (pO2). (compare adaptation at birth)

With the asymmetric development of the heart and the division of the outflow tract, the 4th aortic arch also develops asymmetrically. The left 4th aortic arch remains as the arcus aortae of the adult while the right one forms the proximal part of the right subclavian artery. 6 aortic arches have always been spoken about. The last two, however, never appear in a prominent arch-shape like the first 4. The 5th aortic arch forms only a small capillary network and the 6th appears as a prominent capillary network with the early development of the trachea and lungs. It is also called the pulmonary arch. Only its left dorsal branching from the dorsal aorta forms a proper vessel, the ductus arteriosus. The ductus arteriosus via its connection with the left ventral branching of the saccus aortae and truncus pulmonalis, forms a shunt from the lung vessels to the dorsal aorta. In this way a too forceful perfusion of the still tender pulmonary capillaries by the blood from the right ventricle is avoided. The left subclavian artery arises from the left intersegmental 6th artery in the region of the 6th -7th cervical segment. Through differing growth processes (compare descent of the heart) it appears as if the left subclavian artery arises directly from the aorta. In the literature differing opinions about the origin of the left subclavian artery can be found. Some authors describe it as a derivative of the 6th, other of the 7th intersegmenatl arteries. (14)

More info The detailed depiction of the aortic arch arteries is intended to show how the asymmetry of the vessels arise in the arcus aortae region.

Overview of the origin of the arteries that stem from the aortic arch arteries.

Vessels of the dorsal aorta


Quiz 15

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The right and left dorsal aortas (later descending aorta) develop in parallel with the heart and gain access to it via the aortic arches. In a lengthy process the paired dorsal aortic anlagen unite and finally form the unpaired descending aorta of the adult. 12-

17 Development of the dorsal aortic vessels Navigation


Stage 8 (23rd d.)

Stage 12 (30th d.)

Stage 15 (36th d.)

1 2 3 4 5 6 7

Umbilical vein Ventral, visceral branches of the aorta Dorsal intersegmental branches of the aorta Dorsal aorta Remainders of the lateral branches of the aorta for the mesonephros Dorsal branches of the dorsal intersegmental branches of the aorta Ventral branches of the dorsal intersegmental branches of the aorta (e.g., intercostal arteries) 8 Mesonephros (while atrophying) 9 Gonad anlage with paired gonad vessels from the lateral aortic segment arteries 10 Lateral segment arteries for the renal artery

One can subdivide the various branches of the dorsal aorta into three groups: 1. 2. 3. ventral (visceral), segmental branches lateral (visceral), segmental branches dorsolateral (parietal), intersegmental branches

These branchings are modified in various ways until they reach the definitive adult form.

Ventral (visceral), segmental branches of the dorsal aorta


The ventral segmental, visceral branches of the dorsal aorta, which initially appear
Quiz

paired and, in a large number, surround the intestines and the umbilical vesicle, from dorsal to ventral. With the further development of the intestines, in that the two layers of the mesenterium dorsale approach each other, the paired branches fuse in the middle and, from cranial to caudal, form the truncus coeliacus and the superior and inferior mesenteric arteries in that order. The umbilical arteries are engendered from a vessel plexus in the lower part of the still paired dorsal aorta 10 at the level of the allantois. They are segmental arteries that soon gain access, though, to the intersegmental, lumbar arteries, whereby the cranial parts atrophy. The result is that these lumbar portions become the main part of the umbilical arteries. Parallel to the development of the subclavian artery of the arms the blood supply of the leg anlagen also develops fromdorsolateral branches of the dorsal aorta. In that the umbilical arteries have incorporated the proximal portion of the dorsolateral branches, though, the leg arteries appear to spring from the umbilical artery. In adults, the superior vesical artery and the median umbilical ligament (the obliterated intracorporal part of the umbilical artery) in the lower abdominal wall form the remnants of the arterial part of the umbilical circulation system. Fig. 29 - Ventral branches (embryo) Stage 19 (ca. the 46th day) Fig. 30 - Ventral branches in adults

Quiz 16

Legend
Fig. 29 Overview of the various paired and unpaired branches of the dorsal aorta in the abdominal region. The individual sections of the embryonic vessels, which remain until adulthood, are shown in differing colors. Fig. 30 In this picture the common left iliac artery (left umbilical artery) has been cut away to provide a better overview. The colors correspond to the sections of Fig. 29.

1 2 3 4 5 6 7 8

A. dorsalis Truncus coeliacus Superior mesenteric artery Inferior mesenteric artery Umbilical artery (median umbilical ligament) Ischiadic artery Median sacral artery Femoral artery

Umbilical artery (section of the later internal iliac artery) 10 Umbilical artery (section of the later common left iliac artery) 11 External iliac artery 12 Common right iliac artery

The median sacral artery originates at the branches of the two umbilical arteries. It also comes originally from the dorsolateral parietal branches of the aorta.

Summarizing, the displacement of the umbilical artery caudally results in the following

situation: Common iliac artery: proximal part of the umbilical artery, beginning at the aortic branch. External iliac artery: proximal part of the leg artery, originally from dorsolateral branches but later from the umbilical artery. Internal iliac artery: continuation of the umbilical artery towards the navel after the branching off of the external iliac artery. Superior vesical artery: last vessel branching before the obliteration of the umbilical artery.

Lateral (visceral), segmental branches of the dorsal aorta


The second group consists of ca. 20 pairs of lateral visceral branches that are responsible for the blood supply of the mesonephros. From them paired branches come, namely the arteries for the suprarenal glands, the kidneys and the gonads.

Dorsolateral (parietal), intersegmental branches of the dorsal aorta


As the third group, the dorsolateral parietal branches form in the thoraco-lumbal part the intercostal and lumbar arteries and in the lowest part the median sacral artery which, after the various mentioned transformation processes, spring as unpaired arteries from the umbilical artery. In the cervical part, an anastomosis forms between the intersegmental cervical branches. From this long anastomosis arise on both sides the vertebral artery, which comes left and right from the subclavian artery. This is primarily a result of the transformation processes of the aortic arch arteries. The vertebral artery fuses to the basilar artery at the base of the brain and forms a blood supply source for it. The other supply sources of the head have already been treated in connection with the aortic arches and consist of the internal carotid arteryfor the anterior and lateral part of the brain and the external carotid artery for the face.

Summary of the dorsal aortic vessels


Dorsolateral intersegmental branches Dorsolateral intersegmental branches Vertebral artery from anastomosis between the cervical intersegmental branches of the paired dorsal aorta Subclavian artery from the 6th cervical intersegmental artery dorsolateral branches (intersegmenal arteries), before the dorsal aortae fuse Intercostal arteries from the thoracic intersegmental arteries Iliac arteries partly from the lumbar intersegmenal arteries, partly through fusion with the umbilical artery

Ventral segmental branches Vessels of the umbilical vesicle Vessels of the allantois Lateral segmental branches Lateral segmental branches Medial suprarenal artery Renal artery Ovarian and testicular (spermatic) artery Truncus coeliacus Superior mesenteric artery from the omphalomesenteric artery Inferior mesenteric artery Umbilical artery

Coronar y arteries
The origin of the coronary arteries is not entirely clear. In the literature, one finds two theories. According to the first, endothelial tissue grows out of the aortic wall and connects with the subepicardial vessel plexus while the heart is developing. Other researchers are of the opinion that the vessel plexus arises in situ and finds retrogradely a connection with the aorta. Cell markings in animal trials have substantiated that their coronary arteries develop from precursor cells in situ with the formation of the epicardial layer and attain a connection with the aorta secondarily (2). The muscle layer of the coronary arteries stems from the mesoderm and not, as in the aorta, partially from immigrated neural crest cells.

16.8 Development of the lymphatic vessels



Introduction The lymphatic vessel system

Introduction
The lymphatic vessels form, like the blood vessels, from hemangioblastic stem cells which aggregate to form fine tubular vessels. The first signs of developing lymph nodes are found already in the 5th week 15 (36th day) as so-called lymph sacs near where the inferior cardinal vein and superior cardinal vein flow together and form the common cardinal vein. Bilateral evaginations of the venous system above the later subclavian vein arise as the jugular lymph sac and somewhat later below as the axillar lymph sac. In other regions of the body further such evaginations arise: mesenteric, lumbar, iliac and retroperitoneal sacs.

The lymphatic vessel system


The connections between the lymphatic sacs are formed by a fine network of lymphatic vessels. Later several of these lymphatic plexuses come together to form larger vessels. Like the venous system this is also originally arranged bilaterally and symmetric and experiences an asymmetric development. Ultimately, the thoracic duct also arises through the growing together of several local plexuses. Fig. 31 - Lymphatic plexus in stage 18 (ca. the 44th day) Fig. 32 - Lymphatic plexus at the end of the embryonic period (ca. the 56th day) Legend
Fig. 31 The development of the lymphatic systems at the 6th week. Three bilateral lymphatic sacs (jugular, axillary and lumbo-iliac) as well as the incompletely formed lymphatic vessel plexus are shown. Fig. 32 The most important lymphatic vessels arise bilaterally and form a fine network. The site where plexuses are located transform later into lymph nodes, the lymph filtering stations.

1 2 3 4 5 6 7 8

Superior cardinal vein (jugular vein) Jugular lymphatic sacs Right subclavian vein Axillary lymphatic sacs Left brachiocephalic vein Thoracic duct (bilateral) Lumbar lymphatic sacs Iliac lymphatic sacs

1 2

Right jugular vein Right jugular and axillary lymphatic plexus 3 Subclavian vein 4 Superior vena cava 5 Right thoracic duct 6 Left jugular vein 7 Left jugular and axillary lymphatic plexus 8 Left subclavian vein 9 Left thoracic duct 10 Cysterna chyli 11 Inguinal lymphatic plexus

At the end of the embryonic period 3 bilateral systems have formed: jugular-axillar lymphatic sac mesenterial lymphatic plexus lumbo-inguinal lymphatic plexus

They are connected through a very variable lymphatic vessel system. The thoracic duct drains the lymph from the lower as well as the left upper half of the body into theleft venous angle between the jugular vein and the left subclavian vein. The right arm and the right half of the head are drained by the jugular and axillary lymphatic plexus, respectively, which empties into the right venous angle. The lymph nodes develop in the early fetal period through a septation of the lymph sacs by mesenchymal cells. The spaces thus delimited become the sinus of the adult lymph nodes. Other mesenchymal cells build the connective tissue framework of the lymph node and its capsule. Fig. 33 - Lymphatic plexus in the fetal period
1 2 Right jugular vein Right jugular and axillary lymphatic duct 3 Subclavian vein 4 Superior vena cava 6 Left jugular vein 7 Left jugular and axillary lymphatic duct 8 Left subclavian vein 10 Cysterna chyli 11 Inguinal lymphatic nodes 12 Thoracic duct

Legend
Fig. 33 As in the venous system the lymphatic vessels also atrophy selectively and unilaterally. At the thoracic and abdominal level only a thoracic duct remains to drain the lymph of the entire lower part of the body and the left head and arm region. This lymph empties into the venous system at the junction of the jugular and left subclavian vein. Dashed lines indicate the atrophied portion of the lymphatic s

16.9 Embr yo-fetal cir culation system - changes at bir th



Introduction The fetal circulation system Changes at birth

Introduction
Shunts for the blood in the developing heart serve a very practical need. Initially all of

the blood returns to the right atrium. However, because the lungs develop very late, the pulmonary vessels are limited in their capacity and the resulting resistance is very high. Thus, the pulmonary circulation system cannot deal with all the blood. So the circulation system remains balanced nonetheless, there are two shunts that provide shortcuts for most of the pulmonary circulation system. First there is a direct connection between the right and left atria in that the blood from the right atrium flows directly into the left via the foramen ovale and thus goes around the pulmonary circulation system. This shunt allows a normal development of the left atrium and the left ventricle in that the cardiac musculature on this side is trained. On the other hand, the right ventricle could also not develop correctly when no blood would flow via the right side. Thus in fetal hearts blood also flows in small amounts from the right atrium via the tricuspid valve into the right ventricle but, going through the truncus pulmonalis it takes a shortcut into the aorta via the ductus arteriosus.

The fetal circulation system


The two cardiac shunts: Connection between the right and left atria via the foramen ovale Connection between the truncus pulmonalis and the aorta via the ductus arteriosus

From the parallel blood flow pathways through the heart together with the two shunts the following circulation system results: The blood from the placenta that has been enriched with oxygen and nutrients gets via the umbilical vein to the liver, part flows through it and part bypasses it via the ductus venosus and gets via the v. cava inferior into the right atrium.

More info There are indications that a functional sphincter regulates the flow of blood through the ductus venosus. The umbilical vein transports nutrient-rich blood from the placenta and a large part of it is channeled through the bed of capillaries in the liver. Due to periodic contractions of the uterus, the pressure in the umbilical veins increases and more nutrient-rich blood gets directly via the ductus venosus into the inferior vena cava. Relaxation of the uterine musculature leads to a decrease in umbilical vein pressure and blood deriving from the fetal circulation and from the hepatic vein flows into the inferior vena cava and thereby into the right atrium.

The largest part of the blood from the right atrium flows via the foramen ovale into the left atrium and via the mitral valve into the left ventricle. From there it empties into the aorta, which winds around the truncus pulmonalis (ascending aorta), glides over the bifurcation in the right and left pulmonary artery (aortic arch), and heading towards the back - goes over into the descending part of the aorta. In contrast, CO2-rich, nutrient-poor blood flows from the superior vena cava into the right atrium, is partially mixed with the O2-rich blood from the placenta and, via the tricuspidal valve, gets into the right ventricle. Via the pulmonary trunc and thepulmonary arteries a small portion of the blood passes through the pulmonary circulation and, via the pulmonary veins, reaches the left atrium and then the large circulation system. Due to the high pressure in the lungs, though, a significantly larger part flows through the ductus arteriosus and goes into the aorta descendensand thus directly into the large (systemic) circulation system.

Fig. 34 - The blood circulation system situation at the end of pregnancy

Legend
Fig. 34 In the placenta the blood becomes enriched with nutrients and oxygen and gets via the unpaired umbilical vein into the fetal blood circulation system.

More info Due to the higher pressure of the blood in the inferior vena cava, more blood flows from it directly into the left atrium via the foramen ovale. The foramen ovale opens like a valve and can direct the blood stream that comes from below directly into the left atrium. Taken together, the diameters of the inferior and superior vena cava are larger than that of the foramen ovale and therefore a small portion of the blood seeps into the right ventricle via the tricuspid valve. The heart is filled only with a mixed blood (O2 saturation).

16.9 Embr yo-fetal cir culation system - changes at bir th

Introduction

The fetal circulation system Changes at birth

Changes at birth
Quiz 30

Quiz

With birth, a change from parallel flow through the heart to a serial one gradually takes place. The following changes must occur: 1. 2. 3. The gas exchange takes place in the baby's lungs. By cutting the umbilical cord, the placental circulation system is switched off. The fetal heart shunts become closed.

With the activation of breathing the lungs becomes distended, the capillary network dilated and their resistance is reduced drastically so that a rich flow of blood can take place. As a consequence, the pressure in the right atrium sinks in comparison with that of the left one. This pressure turnaround in the atria causes the septum primum to be pressed against the septum secundum and the foramen secundum becomes functionally closed. Towards the end of the first year, it has also grown together in 99% of the babies --> The shunt between the left and right atrium is closed. On the other hand, with the cutting of the umbilical cord following birth, the placental low resistance area also disappears and the peripheral resistance increases in the systemic circulation. The pressure in the aorta is now higher than that in the truncus pulmonalis and the right-left shunt via the ductus arteriosus that is present before birth is turned around into being a left-right shunt. The pO2 pressure in the aorta increases since the blood is now oxygenated directly in the baby's lungs. This increase in pO2 triggers a contraction of the smooth musculature in the wall of the ductus arteriosus and thereby to a functional seal. After a few weeks or months this shunt via the ductus arteriosus is definitively obliterated and the remnant is known as the ligamentum arteriosus. The severing of the baby's umbilical cord leads to the obliteration of the umbilical vessels, primarily through active constriction of their muscular layer. Only the proximal part of the umbilical arteries stays open as the superior vesical artery. The distal part forms the medial umbilical ligament on both sides in the anterior abdominal wall. The umbilical vein transforms itself into the ligamentum teres hepatis. The blood circulation system situation before / following birth Navigation

Circulation system at the end of the pregnancy

Circulation system following birth

16.10 Pathologie

Introduction Right cardiac obstruction (without shunt)

Pulmonary stenosis (PS) Tricuspid stenosis

Left cardiac obstruction (without shunt) Aortic stenosis Aortic insufficiency Aortic isthmus stenosis (coarctatio aortae) Interrupted aortic arch Hypoplastic left cardiac syndrome

Heart abnormality with left-right shunt (acyanotic)

Persisting ductus arteriosus (PDA) Atrial septum defect (ASD) Ventricle septum defect (VSD) Atrioventricular septum defect

Heart abnormality with right-left shunt (cyanotic) Fallot's tetralogy Pulmonary valve atresia Tricuspid atresia

Heart abnormality with false connections of the blood vessels Transposition of the great vessels (TGA) Double inlet ventricle Complete pulmonary vein inlet errors Truncus arteriosus communis

Introduction
The formation of the heart is a very complex process - errors can occur at every step in its development. They lead to congenital disorders that, due to an incidence of 1 in 1000 newborns, belong to the most frequent birth defects. Chromosomal aberrations are also very frequently associated with heart abnormalities. In the future, it will probably be possible to trace even more congenital malformations back to genetic predispositions when the processes that lead to heart formation are better understood at the molecular level. In the clinic 4 very frequent heart abnormalities dominate. They make up more than half of the ones that are encountered. They are: VSD = ventricular septal defect (28%) ASD = atrial septal defect (11%) Pulmonary stenosis (9%) PDA= persisting ductus arteriosus (9%)
More info Compilation of some of the important diseases or syndromes that derive from heart abnormalities (etiology).

More info In addition to pathological heart sounds obtained with a stethoscope, the following clinical signs can indicate cardiac abnormalities: In infants:

Cyanosis of the child (due to a mixture of O2 saturated with O2 unsaturated blood) Poor growth (the baby fails to gain weight) Excessive sweating, mainly when drinking (a big effort for the child

Shortness of breath Laziness at nursing (the baby often falls asleep while nursing due to the large effort it must expend) Limited somatic resilience Low stamina Tendency for infections

In older children:

One can also subdivide congenital heart abnormalities according to location and hemodynamic effects. In case of an incomplete separation of the lungs and somatic circulation systems a shunt is formed. With each cardiac contraction the blood goes over from one circulation system to the other according to the different blood pressures in the two systems. Cardiac abnormalities can thus be subdivided into the following three groupings: Anomalies without shunt Anomalies with left-right shunt (normally without cyanosis) Anomalies with right-left shunt (with cyanosis --> mixed blood)

More info In the heart various pressure relationships and O2 saturation values in the blood hold sway in a tight space (illustration)

Besides auscultation (with the stethoscope) echocardiography is the most frequently applied diagnostic method for clinical examinations. Cardiac catheterexaminations are indicated in complex cardiac abnormalities and before operations.

Right cardiac obstruction (without shunt)


Obstructions, i.e. obstructions of the passages, can occur at various levels in the right side of the heart or in the pulmonary outflow path. Pure obstructions do not result in a mixing of the blood but a massive additional strain on the cardiac muscles because they have to pump against increased resistance.

Pulmonary stenosis (PS)


Isolated PS occurs with a frequency of 9% of all congenital cardiac abnormalities and, combined with other cardiac abnormalities, with a frequency of nearly 21%. All forms lead to a hindrance of blood flow ejection from the right ventricle to the pulmonary artery. Depending on how big the stenosis is, a pressure stress and acompensatory hypertrophy of the right ventricle develop.
More info Constrictions in the region of the right ventricular outflow or of pulmonary arteries can occur at various levels. An overview, according to the clinical pictures, of the diagnostic possibilities as well as the therapy.

Tricuspid stenosis
IIt is corrected by a commissurotomy (expansion) of the valve opening rims.

Left cardiac obstruction (without shunt)


Obstructions, i.e., constrictions of the flow path at various levels can also occur on the left side of the heart. Pure obstructions result in a massive supplementary load on the cardiac muscle because it must pump against elevated resistance. Partially, there are compensatory shunts without which survival would not be possible.

Aortic stenosis
Aortic stenoses occur relatively frequently and comprise 7% of congenital cardiac abnormalities. These are obstructions of the left ventricular outflow tract, i.e., the aortic valve and the ascending aorta. In all its forms constriction of the left ventricular outflow tract gives rise topressurestress of the left ventricle with compensation by a left ventricular hypertonia.
More info Morphologically, according to the localization of the stenosis, 3 groupscan be distinguished.

More info Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Aortic insufficiency
Aortic insufficiency is seldom found in newborns and is mainly a consequence of an operative intervention, e.g., from the balloon dilatation of an aortic stenosis.

Aortic isthmus stenosis (coarctatio aortae)


The region of the distal aortic arch near the ductus arteriosus inlet is called theaortic isthmus. A coarctation is a stenosis in the aortic isthmus region and it is encountered with a frequency of ca. 6% of all congenital cardiac abnormalities. Often dispersed ductus tissue, which contracts after birth, is found in sections of a stenosized wall.

More info

Depending on the site where the stenosis is located in relation to the ductus arteriosus, one distinguishes the following forms of aortic isthmus stenoses:

preductal juxtaductal postductal

In the first two, the blood for the lower half of the body is still supplied postnatally by the ductus arteriosus. The stenosis is apparent only when the ductus closes and it comes to acute pressure stress of the left ventricle. In the third form the supply of blood for the lower half of the body comes only via collateral vessels like the intercostal or internal thoracic arteries. Accompanying abnormalities such as a bicuspid aortic valve, aortic stenosis, VSD and stenoses of the vessels that lead away from the aorta are very frequent. Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Interrupted aortic arch


While with aortic isthmus stenoses the continuity of the aortic arch is preserved, this is lost when the aortic arch is interrupted - a segment of the aortic arch is missing. This abnormality is relatively seldom, however.

Hypoplastic left cardiac syndrome


In the hypoplastic left heart syndrome, which comprises only 2% of all cardiac abnormalities, one finds a poorly developed (hypoplastic) left ventricle that is often only a few millimeters thick. The aortic and mitral valves are constricted (stenotic) or completely closed (atretic). Only the right ventricle functions normally and supplies the circulation system with blood. The arterial blood from the left atrium gets into the right atrium and ventricle via the foramen ovale that is kept open. The aorta ascendens that mostly ends blind at the valve is filled retrograde by the blood of the ductus arteriosus. In this way the coronary arteries that leave the proximal part of the aorta ascendens can also be supplied with blood. Fig. 35 - Hypoplastic left ventricle Legend
Fig. 35 The left ventricle is hypoblastic. Through an open foramen ovale the blood gets to the right side and mixes with the O2 unsaturated venous blood. This left-right shunt via the foramen ovale as well as the right-left shunt via the ductus arteriosus are necessary for survival. Such children are cyanotic.

1 2 3

Open ductus arteriosus Open foramen ovale Hypoplastic ventricle

Heart abnormality with left-right shunt (acyanotic)

With a left-right shunt an increased pulmonary perfusion to the detriment of the systemic circulation system is the result. Shunts from the oxygen-rich side to the oxygen-poor side are not usually accompanied by a cyanosis.

Persisting ductus arteriosus (PDA)


The ductus arteriosus connects the pulmonary artery with the aorta. Prenatal it is a vital structure to have. After birth, in the first days of life, though, the ductus arteriosus is closed by the active contractions of its smooth muscles, followed by an intima proliferation. The sealing of the ductus is triggered by the postnatal pO2 increasedue to the breathing of the newborn. A persisting ductus arteriosus (PDA) is spoken of when the normal, postnatal closure fails to take place (ca. 9% of all cardiac abnormalities). In hemodynamic terms, the quantity of blood flow due to a PDA depends on the diameter and length of the ductus arteriosus. In addition, the size of this left-right shunt varies with the pulmonary resistance. Since in the first 38 weeks after birth this resistance decreases continuously, a cardiac insufficiency may occur. Fig. 36 - Persisting ductus arteriosus Legend
Fig. 36 Due to the increase of the peripheral pressure in the systemic circulation system and the continuous lowering of the pulmonary resistance in the first weeks of life, a reversal of the flow through the ductus arteriosus and a flooding of the pulmonary vessels takes place.

Open ductus arteriosus

More info The symptoms of a persisting ductus arteriosus differ according to age: In infants with a large DA increasing cardiac insufficiency with tachypnea, dyspnea, and growth disorders are observed. Drinking weakness, accompanied by increased sweating occur when nursing because this represents a big effort for the newborn. In premature infants, an open DA leads to a flooding of the pulmonary circulation system. In older children an open DA is often discovered accidentally. It seldom leads to a symptom such as infection proneness.

Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Atrial septum defect (ASD)


Prenatally an ASD is of no hemodynamic importance because the foramen ovale is
More info

already open normally and directs the blood from the inferior vena cava to the left side of the heart. Only after birth does it have hemodynamic consequences in that a leftright shunt arises due to the different pressures in the two atria. Its incidence amounts to 11%.

One distinguishes according to localization among the followingdefects.

The ASD leads to a left-right shunt and to an overload for the right ventricle with recirculation through the lungs.

Fig. 37 - Blood flow with an ASD

Legend
Fig. 37 The right circulation system is overloaded because blood from the left side always recirculates through the lungs via the ASD.

Ventricle septum defect (VSD)


Ventricular septum defects are encountered relatively frequently (28% of all congenital cardiac abnormalities). They can occur by themselves but also combined with other defects.
More info One distinguishes among 4localizations.

Prenatally, even a large defect is not disadvantageous because roughly the same pressure is present in both ventricles. Postnatally, the severity of the VSD depends on its size and the resistance relationships in the pulmonary and systemic circulation systems. Small defects lead to no detriment and especially those in the muscular septum sometimes close spontaneously. Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Fig. 38 - VSD in the membranous part

Legend
Fig. 38 In the membranous part a defect is present via which, in the absence of additional abnormalities, a leftright shunt from the left ventricle to the right exists.

Defect in the membranous part of the interventricular septum

Atrioventricular septum defect


Here a part of the atrium as well as a part of the ventricular septum are missing. This probably results from an abnormal fusion of the dorsal and ventral avcushions in the early embryonic development 16-18 . The clinic adjudges according to the size of the defect. It should also be mentioned that this is the most frequently occurring cardiac abnormality in patients withDown syndrome. Fig. 39 - Atrioventricular septum defect Legend
Fig. 39 Because of the septum defects an increased volume of blood flows through the pulmonary circulation.

1 2

Defect in the atrial septum Defect in the ventricular septum

Heart abnormality with right-left shunt (cyanotic)


In cardiac abnormalities with right-left shunts oxygen-poor blood gets from the right half of the heart into the left side and thus into the systemic circulatory system. In most of the defects with right-left shunts the physiologic shunts present before birth remain functional because no reversal of pressure happens following birth.

Fallot's tetralogy
Fallot's tetralogy, described in 1888, is met with in roughly 8% of all congenital cardiac abnormalities. It comprises the following defects: Pulmonary stenosis (PS) Ventricle septum defect (VSD) Overriding aorta Right ventricular hypertrophy Fig. 40 - Fallot's tetralogy Legend
Fig. 40 The pulmonary stenosis (PS) determines the degree of severity of this defect. Pulmonary perfusion depends on the size of the PS.

1 2 3 4

Pulmonary stenosis Ventricle septum defect Hypertrophy of the right ventricle Aorta riding over the septum defect

More info The hemodynamic is determined by the size of the pulmonary stenosis. With increasing degree of the pulmonary stenosis the severity of the right-left shunt via the ventricular septum defect, facilitated by the overriding of the aorta, increases. The origin of this cardiac abnormality is not known in detail, but a correlation with a chromosome aberration has been found (22q11, compare catch syndrome, 12). Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Pulmonary valve atresia


This cardiac abnormality is very rare and accounts for only 1-3%. In this affliction the pulmonary valve is atretic and there is no exit from the right ventricle. Thus all of the blood regurgitates into the left atrium via the foramen ovale and the lungs get perfused retrogradely via a very wide ductus arteriosus.
More info One distinguishes several forms.

Tricuspid atresia
With an incidence of 3% tricuspidal atresia also belongs to the rare cardiac abnormalities. Through atresia of the tricuspidal valve a connection between the right atrium and the right ventricle is missing. Since this abnormality is mostly combined with a VSD, its effects depend on the size of the VSD.

Heart abnormality with false connections of the blood vessels


All of these abnormalities are very rare. One distinguishes between purely abnormal inlets and such that result from an absent or abnormal separation of the outflow tract.

Transposition of the great vessels (TGA)


While the cause of TGA (5%) is unknown, an increased risk is associated with maternal diabetes mellitus. In a TGA, the aorta arises completely out of the right ventricle and the pulmonary arteries from the left one. From an embryologic point of view, the rotation of the aorto-pulmonary septum of 180o did not take place. The hemodynamic of the TGA is characterized by the parallel connection of the two circulatory systems that permit no oxygen intake or release. Such a circulation situation can only be survived when in addition to the TGA a mixing of O2 enriched pulmonary venous blood with the systemic venous blood via a crossed shunt can take place. Such shunt connections at the atrium level are an open foramen ovale or an atrium septum defect, at the ventricle level a VSD, and at the vessel level an open ductus arteriosus.
More info Overview, according to the clinical picture, of the diagnostic possibilities as well as the therapy.

Fig. 41 - Pure TGA

Fig. 42 - TGA with VSD

Legend
Fig. 41 This defect cannot be survived because there are two complete, separated and parallel circulatory systems. The left heart receives oxygenated blood from the lung and send it back to the lung through the pulmonary trunk. Fig. 42 A TGA can only be survived when at the same time at the atrial or ventricular level a septum defect exists.

Transposition of the great vessels

1 2

Transposition of the great vessels VSD

Double inlet ventricle


With an incidence of 2% this is a rare malformation of the heart. In this cardiac abnormality one or both av-valves empty into a common ventricle (see name). In addition, a rudimentary outflow tract mostly still exists that is connected with the main chamber via a VSD. This rudimentary cardiac chamber has no connection to the avvalve and thus cannot form an inflow tract or a cavum during cardiac development. The great arteries can diverge from the associated ventricle in either a normal way or transposed. The cause of this defect is probably an atrophy of the crista prima that occurs too late and thus the right conus septum cannot fuse with the dorsal av-septum.

Complete pulmonary vein inlet errors


In an early stage of development connections exist between the pulmonary vein and somatic vein systems. When the junctions of the pulmonary veins with the left atrium are unsuccessful, the pulmonary veins thereby empty into the somatic circulation system. This abnormality is also rare (2%).
More info One distinguishes various typesaccordin g to the inlet locations.

Truncus arteriosus communis


In this cardiac abnormality only one arterial vessel, the truncus arteriosus communis, emerges from the heart and the two ventricles are connected with each other via a large VSD. Most often the truncus arteriosus straddles it, so that it receives blood from both ventricles. The pulmonary artery emerges dorsally and the aorta ventrally, since here the formation of the conus septum failed to take place. The outflow tract is divided by the truncus septum only in the upper part. In this cardiac abnormality only a common valve, the truncus valve, has formed. This also is a very rare cardiac abnormality.

16.11 Quiz

Easy learning: Test your knowledge with various questions to the individual chapters. With the quiz you can review important details and possibly thereby detect gaps in what you think you know. The "Associated theory" links lead directly to the corresponding pages of the theoretical sections, where you find the right answers. We would like to point out, though, that the quiz does not replace a serious working through of the theory sections of this module ;-)

Note In order to take the quiz, you must have the Flash 6 plugin installed on your computer (see "Downloads" in the Help menu)

Quiz 01: First signs of cardiac development Quiz 02: Heart position following the rotation in stage 10 Quiz 03: Formation of the cardiac loop I Quiz 04: Formation of the cardiac loop II Quiz 05: Formation of the cardiac loop III Quiz 06: Restructuring of the atrium (stage 12) Quiz 07: Openings in the heart Quiz 08: Septation of the heart: atrium Quiz 09: Septation of the heart: ventricle Quiz 10: Septation of the heart Quiz 11: Septation of the outflow tract Quiz 12: Outer form of the heart Quiz 13: Development of the aortic arches I Quiz 14: Development of the aortic arches II Quiz 15: Vessels of the dorsal aorta (stage 12)

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Quiz 16: Development of the aortic arches Quiz 17: Development of the umbilical and omphalomesenteric vein system Quiz 18: Development of the vein system I Quiz 19: Development of the vein system II Quiz 20: Innervation of the heart Quiz 21: Aortic arches Quiz 22: Ductus arteriosus Quiz 23: Ductus venosus Quiz 24: Cardiac anlage Quiz 25: Cardiac tube Quiz 26: Septa formation Quiz 27: Veins near the heart Quiz 28: Valves Quiz 29: Cardiac blastema Quiz 30: Changes in the circulation at birth

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16.12 Brief summar y

The first sign of cardiac development is the cardiogenic plate that is still to be found cranially outside the embryo. The development of the heart then goes rapidly through 3 main phases: plexiform phase tubular phase loop phase

The flexion of the embryo causes the tissue of the original cardiogenic plate, which is enveloped by the

pericardial cavity, to move into a ventral position. It consists ofepicardium, myocardim and endocardium. A gelatinous mass, the cardiac jelly, temporarily forms between the myo- and endocardium and this is of decisive importance for the subsequent tube formation. On the inside, diverse differentiation processes also take place whereby the blood is pumped through the heart, initially serially, and later in parallel. The following restructuring processes occur: Shifting of the inflow tract to the right Shifting the atrio-ventricular plane into the middle Dividing the atria and ventricles by septa Dividing of the outflow tracts by septa

The vessels near the heart are influenced in their development by the right-left determination of the heart. Certain portions of the venous and arterial systems atrophy and others develop further for this reason. At birth large pressure changes take place. On the one hand, the low pressure area of the placenta falls away while, on the other hand, the pressure in the pulmonary circulation system decreases due to the distention of the lungs following thebeginning of breathing. These two events cause the pressure in the left part of the heart to increase and in the right part of the heart to sink. The foramen ovale between the right and left atria closes thereby and the ductus arteriosus obliterates at the same time. Now the pulmonary circulation system is completely separated from the systemic one and they now operate in series. The cardiac pacemaker and signal conduction system is important for a coordinated sequence of cardiac contractions. The sinus node is already delimited relatively early. The AV node and the bundle of His follow afterwards. Thanks to the sympathetic,parasympathetic and sensory innervation the heart can adequately deal with loads. In cardiac pathologies cardiac vitia (defects) without shunts and those with shuntsare distinguished. With the latter, there are right-left shunts that lead to a cyanosis as well as left-right shunts that are acyanotic. In addition, inlet abnormalities of the large vessels can be observed.

16.13 Bibliog r aphy

1. The origin, formation and developmental significance of the epicardium: a

review. Manner J, Perez-Pomares JM, Macias D, Munoz-Chapuli R.: Cells Tissues Organs 2001;169(2):89-103.

2. Does the subepicardial mesenchyme contribute myocardioblasts to the

myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium. Manner J. Anat Rec 1999 Jun 1;255(2):212-26.

3. Cardiac looping in the chick embryo: a morphological review with special


reference to terminological and biomechanical aspects of the looping process. Manner J. Anat Rec. 2000 Jul 1;259(3):248-62. Review.

4. Blood vessel maturation: vascular development comes of age. Darland DC,


D'Amore PA. J Clin Invest 1999 Jan;103(2):157-8.

5. Cell-cell interactions in vascular development. Darland DC, D'Amore PA. Curr


Top Dev Biol 2001;52:107-49.

6. TGF beta is required for the formation of capillary-like structures in threedimensional cocultures of 10T1/2 and endothelial cells. Darland DC, D'Amore

PA. Angiogenesis 2001;4(1):11-20.

7. Sequential programs of retinoic acid synthesis in the myocardial and

epicardial layers of the developing avian heart. Xavier-Neto J, Shapiro MD, Houghton L, Rosenthal N. Dev Biol 2000 Mar 1;219(1):129-41.

8. Atrial development in the human heart: an immunohistochemical study with


emphasis on the role of mesenchymal tissues. Wessels A., et al. Anat Rec 2000 Jul 1; 259(3):288-300

9. Migration of cardiac neural crest cells in Splotch embryos. Epstein J. A. et al.


Development 127, 1869-1878, 2000.

10. Development of the human pulmonary vein and its incorporation in the
morphologically left atrium. Webb S et al., Cardiol Young 2001 Nov;11(6):63242

11. Serrate and Notch specify cell fates in the heart field by suppressing
cardiomyogenesis. Rones MS et al., Development 2000 Sep;127(17):3865-76.

12. Can we predict 22q11 status of fetuses with tetralogy of Fallot? Boudjemline Y
et al. Prenat Diagn 2002 Mar;22(3):231-4.

13. Chamber Formation and Morphogenensis in the Developing Mammalian


Heart. Christoffels VM et al., Dev Biol 2000 Jul 15;223(2):266-78. 14. O'Rahilly R.und Mller F.; Human embryology und teratology, Wiley-Lyss; 2001, p. 210.