Transcription for Narration of Embryology of the Great Arteries

Transcription

1 Transcription for Narration of Embryology of the Great Arteries Slide 1: In this presentation I am going to describe for you the development of what are known as the great arteries. The great arteries are the major initial branches of the outflow tracts from the right and left ventricles. We will talk about their precursors and how they are formed and a little bit about the pattern of fetal circulation of blood. Now the great arteries are forming at the same time as heart development is going on. This makes sense of course, because in order for the heart to become a functional pump there have to be blood vessels to receive that blood. So let s begin in the 3 rd week of development. In this figure we are looking down on the developing embryonic disk and we can see the neural folds. Through the ectoderm we can see the cardiogenic area indicated in red. This area will of course be involved in the development of the heart, but also forming are something called the left and right dorsal aortae. So let s talk a little bit about how blood vessels are being formed. Slide 2: The formation of blood vessels in the embryo occurs in two major ways. The first is vasculogenesis, which entails the formation of blood vessels from clusters of mesenchymal cells called blood islands. The second is known as angiogenesis, which entails the origin of new vessels from preexisting ones. So let s talk about vasculogenesis first. In the 3 rd week of development, mesenchymal cells related to the yolk sac, to the chorion and to the connecting stalk form clusters known as blood islands. The cells forming the blood islands are called hemangioblasts. Those that are in the center of the islands form hematopoietic cells that will be the precursors of blood cells. Within the blood islands, cavities develop and the cells lining the cavities become angioblasts and will give rise to the endothelial lining of the future blood vessels. Once vasculogenesis has established a primary vascular bed, additional vessels are added by angiogenesis, which is simply the sprouting of new vessels from these previously existing ones. Through the combination then of vasculogenesis and angiogenesis a network is formed of blood vessels to allow circulation of blood. The primitive plasma and blood cells will develop from hematopoietic cells related to the yolk sac and allantois. However, blood formation will begin within the embryo itself a little later in about the 5th week of development. The first site is in the mesenchyme of the liver. Later blood cells will form in the spleen, bone marrow and lymph nodes. Slide 3: In the 3 rd week of development clusters of mesenchymal cells just dorsal to the roof of the yolk sac, which will of course be the future gut tube, form into a pair of longitudinal vessels just to the right and left of the midline. These are known as the paired dorsal aortae. Now as heart development is proceeding, by the end of the 3 rd week of development, it will be connected to these paired dorsal aortae by something known as a pair of aortic arches. Now these are not the aortic arch we know of in the adult. These are embryonic structures and they are simply the first set of several that will form in the embryo. The embryonic aortic arches will develop in the mesenchyme of what are known as branchial arches in the neck region of the embryo. Five pairs of branchial arches will develop in the human embryo, and each will contain an embryonic aortic arch. Slide 4: OK, branchial arches, aortic arches, it s kind of confusing. So let s start with just trying to figure out what these branchial arches are all about. Branchial arches are swellings that appear in the neck region of the embryo, and they will contribute to various structures in the head and neck. So if you look at the figure on the left, you can see two of these ridges indicated in the neck region and they are labeled 1 st and 2 nd branchial arch. Each consists of a core of mesenchyme and is covered externally by ectoderm and internally by endoderm. Within each of these branchial arches is going to be an artery known as an aortic arch, and they will connect the developing heart tube to the dorsal aortae. These branchial arches of course come in pairs, one on the right and one on the left side of the neck. That means that the aortic arches within them also come in pairs. So whenever I talk about embryonic aortic

2 arches, remember there is always going to be a right and a left one. Now the branchial arches are going to contribute to structures that are derived from the pharyngeal part of the foregut, so in many textbooks when you read about them, they will call them pharyngeal rather than branchial arches; but branchial is the traditional name and the one I prefer. In the figure on the right, there is a diagrammatic portrayal of the circulatory system at approximately the same stage of development although only one aortic arch is portrayed. The thing I wanted to point out are the branches from the paired dorsal aortae known as dorsal intersegmental arteries, or more commonly as simply the intersegmentals. As the somites develop, these arteries will travel in between individual somites to get to the developing neural tube. The primary purpose, at least initially, is to serve the developing central nervous system. The fact that they pass between somites is what gives them their name intersegmental. However, eventually most will come to primarily serve structures derived from the somites. Slide 5: On the left there is a figure of an actual embryo in which you can see the developing swellings in the neck known as branchial arches. You can also see the very prominent bulge below the neck region of the embryo that is created by the developing heart as well as the liver. The yolk sac is sort of off to one side. On the right is an illustration showing the developing circulatory system at approximately the same stage. The vessels have been highlighted in a pinkish color and blue to indicate arteries and veins. I tried to also add yellow to indicate the yolk sac and the gut tube. You can see that the heart inside the pericardial cavity is connected to the dorsal aortae via two aortic arches. Also portrayed are the vitelline veins and arteries related to the yolk sac, and an umbilical artery and vein developing within the connecting stalk. In addition, the vessels related to the placenta are also portrayed. All of the veins are going to empty into a common chamber called the sinus venosus. Slide 6: Slide 6 is a similar set of pictures just about a week later in development. The one on the left is a micrograph of an about 5 week old embryo; in this case the yolk sac has been removed to allow you to see the embryo better. You can note the prominent branchial arches, separated by what are called branchial clefts in the neck region of the embryo. On the right is a figure illustrating the developing circulatory system. You can see that there are multiple aortic arches portrayed. In fact as the 3 rd and 4 th aortic arches are added within their respective branchial arches, the 1 st and 2 nd are starting to undergo involution and will largely disappear. Humans develop five branchial arches, and they are numbered 1 through 4, and 6. The 5 th branchial doesn t really develop in humans, or if it does, its development is rather abortive and it doesn t leave any remnants behind. In the figure on the right, you ll notice that there seem to be little out-pocketings separating the individual aortic arches. These are known as pharyngeal pouches and they are the indentations between the branchial arches on the inside the pharynx. You should think of the branchial arches as sort of ridges or swelling in the neck with grooves between them. The grooves are called branchial clefts on the external surface of the embryo, and on the inside, inside the pharynx, they are called pharyngeal pouches. Slide 7: So when I said that humans develop branchial arches 1 through 4 and 6, and don t develop branchial arch 5, you are probably starting to wonder, what s with these branchial arches, and why do we have so many aortic arches if some of them are only going to disappear later? I thought maybe a little bit of an historical perspective might help to sort this all out. Branchial arches are the mesenchymal tissue bars that in fish are part of their gill apparatus. In a fish the branchial clefts establish communications with the pharyngeal pouches to form gill slits, so as water passes through the gill slits, the arteries within the gills absorb oxygen from the water. The gill apparatus in the fish consists of several gill slits and bars with their associated arteries, all of which we have inherited. So in a fish a tubular heart consisting basically of an atrium and a ventricle, pumps blood into the gill arteries where it picks up oxygen. Those arteries then feed into paired dorsal aortae to distribute that oxygenated blood to the rest of the fish body. Deoxygenated blood is collected up in veins, which is conveyed back to the

3 heart to be pumped into the gill arteries again. So this is the basic apparatus of vertebrates, and this is what we have inherited and use as building blocks to form what we call our great arteries. Slide 8: Slide 8 is a diagrammatic view of these basic building blocks in a human embryo. Now this is a very schematic view because we have all 5 pairs of aortic arches co-existing at the same time. In fact, as arches 3 and 4 are being added we already said that arches 1 and 2 are beginning to disappear. But I wanted to show you this illustration to highlight the fact that the basic building blocks are pretty much what we inherited from our vertebrate ancestors: an initially tubular heart positioned ventrally in the embryo and it pumps blood into a set of arteries that sweep to the right and left of the developing foregut to get blood to the paired dorsal aortae to be distributed out to the embryo. Now this, as I said, is just the initial stage things are going to change dramatically. There are a couple of other things I should draw your attention to. One is the orange area that indicates a common origin for each of the embryonic aortic arch arteries. This is called the aortic sac, and it s an outgrowth of the truncus arteriosus. This figure also highlights the 7 th intersegmental arteries. That s because these vessels are going to play a prominent role in the development of the great arteries. There are of course many intersegmentals besides these. In the next two slides, I am going to give you an overview of the dramatic changes that bring about the development of our great arteries. After these slides, we will trace development in a slower, more step-by-step way. Slide 9: This is how the vessels appear a just couple of weeks later, and obviously, things have changed dramatically. Through a process called differential growth, some parts have increased in size significantly, while others have barely grown at all. In addition, some portions of the basic building blocks have been lost. So now we see something that is actually starting to resemble the adult condition: there are a couple of vessels that are heading into the head; there seems to be an arch going off to the left side; the common stem of all the aortic arches, that orange-ish-yellow area, is dividing into two different tracts; there also appear to be some vessels which are entering into the upper limb buds. Let s see how things change just a week or so later. Slide 10: The process of differential growth continues, and a week or so later we can see something that is really starting to resemble the adult condition: there is a clear aortic arch, and arising from it are three main vessels. These include a brachiocephalic trunk, which is the common stem for the right subclavian and right common carotid, and the left common carotid, and then finally the left subclavian. The ascending aorta is separate from the pulmonary trunk. One difference, however, is that the pulmonary trunk has a communication to the descending aorta. This is known as the ductus arteriosus, and is the means by which blood is pumped from the right ventricle and into the descending aorta rather than out to the lungs. Now I have purposely gone through the last two slides rather quickly to give you an overview of how you can start with something that does resemble a fish-like condition with five pairs of aortic arches, and end up with something like the modern human condition. So let s start again and take it more slowly this time. Slide 11: OK, let s begin in the 3 rd week of embryonic development. Now following longitudinal bending and lateral folding, the heart tube has come to lie in a position ventral to the newly formed foregut. As the endocardial heart tubes are fusing and the dilations and constrictions are starting to form that will eventually become the heart chambers, a pair of dorsal aortae have formed alongside the dorsal margin of the developing gut tube. The heart will be connected to those dorsal aortae via something known as aortic arches. The aortic arches are vessels that form within branchial arches in the neck region of the embryo. In the 3 rd week of development, the 1 st branchial arch has formed and the 1 st aortic arch has formed inside of it. The paired dorsal aortae send extensions into the developing head region of the embryo that will serve the developing central nervous system. They can then be identified as the future

4 internal carotid arteries. As we move into the 4 th week of development, additional pairs of branchial arches will form, each with its own aortic arch artery. Thus we will have multiple connections between the newly form heart tube and the paired dorsal aortae. In this illustration, you can see there are outpocketings from the pharynx between successive aortic arches. These are known as pharyngeal pouches, and they are the internal indentations between the bulging branchial arches in the pharynx. As multiple pairs of aortic arches form, a common stem is seen to develop as an extension of the truncus arteriosus. This common stem is known as the aortic sac. Slide 12: This is a micrograph of the developing heart and the first couple of aortic arches from a cranial perspective. You can see the developing atrium and the ventricle leading to a truncus arteriosus and an aortic sac indicated by the large white arrow. The two pairs of aortic arches sweep to the right and left, and extending from the dorsal aortae, which can t really see very well, are two vessels labeled with C s those are the developing internal carotid arteries. Slide 13: As we move through the 4 th week, more pairs of branchial arches are added, each with their own aortic arch. In the figure on the right, we can see how additional aortic arches are being added. Now as arches 3 and 4 are being added, arches 1 and 2 are beginning to diminish, and only small remnants of them will persist in the adult. Each of the aortic arches appears to be separated by a pharyngeal pouch. These mark the boundaries between successive branchial arches in the neck region of the embryo. Slide 14: We are getting into about the end of the 4 th week-beginning of the 5 th week. I mentioned earlier that vertebrates typically have 6 pairs of branchial arches, each with their own aortic arch artery. However, the 5 th pair don t actually develop in humans, so there is no 5 th pair of aortic arches. By the time the 6 th pair is being added, the first two pairs have essentially disappeared. So in this illustration, we can see arches 3 and 4, and the developing 6 th aortic arches. Now as the 6 th pair of aortic arches are forming, the laryngotracheal diverticulum develops from the floor of the foregut. So as the 6 th pair of arches form, each will send a branch to that developing lung bud. This pair of arteries, therefore, will become the pulmonary arteries. Meanwhile, a cranial branch develops from the 3 rd pair of aortic arches that will extend into the head region of the embryo. This pair of vessels will become the external carotid arteries. Also about this time, the truncus arteriosus is being divided into an ascending aorta and pulmonary trunk via the formation of the aorticopulmonary septum. Now intersegmental arteries form along both of the paired dorsal aortae. Although they were originally designed to serve the developing central nervous system, most will come to primarily serve structures derived from the somites. However, the first nine intersegmentals form a longitudinal anastomosis and from this develops something known as the vertebral artery. Like the original intersegmental arteries, the primary role of the vertebral artery will be to supply blood the central nervous system. Finally one other thing going on at this time is the fusion of the paired dorsal aortae into a single vessel in the region of the thorax. So at about the level of T4 and caudally, there is only a single aorta. Slide 15: So let s change our perspective a little bit and look at the developing aortic arches from a ventral perspective. In this illustration, you can see arches 3, 4 and 6 that are sweeping around to the left and right of the developing foregut here just represented as a schematic cylinder. The 6 th pair of aortic arches give rise to pulmonary arteries that are going to each of the developing lung buds. The 3 rd pair of aortic arches have given rise to vessels that will enter the developing head region of the embryo called external carotid arteries. Although the pair of dorsal aortae have fused into a single vessel in the region of the thorax, cranial to that area there are still two dorsal aortae, one on the right and one on the left, and we can see how the aortic arches are connections between what would have been the heart tube, which of course is not pictured here, and each of those paired dorsal aortae. The cranial

5 extensions of the dorsal aortae are, again, the internal carotid arteries. Also illustrated here are the first seven intersegmental arteries and their longitudinal anastomosis, which will become the vertebral artery. The 7 th intersegmentals are going to enlarge and each wil enter into the adjacent developing limb bud. The 7 th intersegmentals, therefore, will become the subclavian arteries. Finally, let me draw your attention to the fact that the division of the truncus arteriosus into the ascending aorta and pulmonary trunk has effectively separated the origin of the 6 th pair of aortic arches from the common origin of the other two. This is part of the separation into pulmonary circulation and systemic circulation. The common origin of the 3 rd and 4 th aortic arches is the aortic sac. Slide 16: As we complete the 6 th week of embryonic development, the basic building blocks of the great arteries are in place. What is going to happen from here on is a process known as differential growth. This entails several different processes. First we are going to talk about those parts of these arteries which are essentially going to involute and disappear. Then we will talk about which parts will become relatively large, and which won t keep pace and actually will become relatively small in comparison. But let s again try and do this in a step-by-step process. Slide 17: We are first going to first review those parts of these vessels that are going to disappear. First: the part of the right dorsal aorta between the 7 th intersegmental and the fused part of the aorta will disappear. That is represented by the #1 in the illustration. Second: the segment of either dorsal aorta between the 3 rd and 4 th aortic arches will disappear indicated by the #2 in this illustration. Slide 18: Third: the communicating segments between the longitudinal anastomosis of the first nine intersegmentals and either dorsal aorta will disappear. That is, all except for the 7 th intersegmental its connection to the dorsal aorta will persist. This is indicated by the #3 and the various arrows in this illustration. Fourth: the communication between the right dorsal aorta and the right 6 th aortic arch will disappear, as indicated by the #4 in this illustration. Slide 19: So this loss of segments brings us to this configuration we see here in Slide 19. Everything is still represented, but the parts that are lost are colored in a black or gray color. You can see that we still have the three pairs of aortic arches and the paired dorsal aortae fusing at about the level of T4. The bits that are lost will be: the segment of the right dorsal aorta between the origin of the 7 th intersegmental and the fused part of the aorta - #1; the segment of either dorsal aorta between the 3 rd and 4 th aortic arches - #2 here; the communicating segments between the longitudinal anastomosis and either dorsal aorta - #3; and #4 is the loss of the communication between the right dorsal aorta and the right 6 th aortic arch. The communication between the left dorsal aorta and the left part of the 6 th aortic arch will persist as the ductus arteriosus. The connection between the 7 th intersegmentals and either dorsal aorta will not be lost and will become the stems of the subclavian arteries. Slide 20: We can see that in addition to loss of particular segments, the process of differential growth is remodeling the appearance of these vessels. The 3 rd arches are now seen as becoming the common stems for two vessels going into the head, the internal and the external carotid arteries. The 3 rd arches, therefore, will become the common carotid arteries. In comparison, the 4 th arches do not increase much in length, and serve mainly as the connections between the expanding aortic sac and the remaining portions of the dorsal aortae. The right dorsal aorta loses its connection to the 6 th arch and to the left dorsal aorta. It s going to become the stem for the right 7 th intersegmental artery, and both will contribute to forming the right subclavian artery. The left dorsal aorta enlarges dramatically as it takes over the role of becoming the descending aorta and will lead directly to that fused part of the aorta in the thorax. Although it loses its connection to the right dorsal aorta, it maintains its connection to the left 6 th aortic arch and that connection is known as the ductus arteriosus.

6 Slide 21: We are in about the 8 th week of development, and the illustration shows that things are started to look pretty much the way they do in the adult. So as a result of remodeling and loss of particular segments, we see now that the original 3 rd aortic arches have become the common carotids. Remember that the internal carotids originated as cranial extensions of the paired dorsal aortae, and external carotids were originally simply branches of the 3 rd aortic arches. The 4 th pair of aortic arches don t expand in size nearly as much as the others. They will contribute a proximal segment to the right subclavian and a small portion to the adult aortic arch. The caudal portion of the right dorsal aorta also contributes to the right subclavian. And finally, lateral expansion of the 7 th intersegmentals will become the distal part of the right subclavian and all of the left subclavian. The 6 th pair of aortic arches, with the addition of a portion of the truncus arteriosus will form the pulmonary trunk and give rise to the pulmonary arteries. The persisting connection between the 6 th aortic arch on the left and the left dorsal aorta becomes the ductus arteriosus. In the adult this duct will involute and become something known as the ligamentum arteriosum. The left dorsal aorta becomes the descending aorta, and the aortic sac contributes to the ascending aorta as well as to the brachiocephalic artery. Slide 22: I fully appreciate that this is a pretty tricky bit of development, so I thought it might be useful go through it all one more time. So let s do it again with an even more schematic set of illustrations. Here we start with the basic building blocks for the human great arteries. They include three of the five sets of aortic arches that develop in humans. There is 3, 4 and 6. These building blocks also include the distal part of the truncus arteriosus, which will be divided into an aortic outflow and pulmonary trunk, the aortic sac the common stem for the aortic arches, as well as the paired dorsal aortae and the 7 th intersegmental arteries. Slide 23: Now some of these basic building blocks will not persist. The portions that are going to be lost are indicated by dashed lines. Now these include of course the 1 st and 2 nd aortic arches, plus the 5 th pair that never really form. The segments that are lost include the segment of the right dorsal aorta between the 7 th intersegmental and the fused part of the aorta, the segments of either dorsal aorta between the 3 rd and 4 th arches, the connecting segments between the longitudinal anastomosis of the first several intersegmentals and either dorsal aorta except for the 7 th intersegmentals, and finally the communication between the right dorsal aorta and the right 6 th aortic arch is lost. The communication between the left 6 th arch and the left dorsal aorta persists as the ductus arteriosus. The ductus is an important by-pass of pulmonary circulation prior to birth. The blood pumping through the pulmonary trunk actually will mainly join systemic circulation through this by-pass the ductus arteriosus. Slide 24: In addition to loss of these particular segments, the process of differential growth will result in major remodeling of the remaining vessels. The 3 rd aortic arches will become the common stems for the carotids. The 4 th arches are just tiny segments of either the right subclavian or the arch of the aorta between the left common carotid and the left subclavian. The 6 th arches will give rise to the pulmonary arteries and to the ductus arteriosus. The dorsal aorta on the right side is mainly part of the subclavian. On the left side, it is going to become a large part of the arch and the descending aorta. The ascending aorta is derived from a combination of the distal part of the truncus arteriosus and the aortic sac. The aortic sac also contributes to the stem for the right subclavian and the right common carotid known as the brachiocephalic artery. The most distal part of the right subclavian and the entire left subclavian are derived from the 7 th intersegmentals. Although not pictured here are the branches that were derived from that longitudinal anastomosis, which will become the vertebral arteries. Now at the same time, something has been going on in terms of the positioning of all these vessels. You will recall that the aortic arches develop within the branchial arches, which are in the neck region of the embryo. But as the head increases in size, these vessels are all going to essentially sink into the thorax. This is the reason why these common carotids appear to be so long because they have to reach from the arch of the aorta,

7 which is now in the thorax. At the same time, the subclavians appear to have moved to a more superior position. This is because as the arch of the aorta and the other vessels are sinking into the thorax, they are basically anchored by the limb buds and will actually have to shift cranially. Slide 25: This shift in overall position in the origin of the great arteries from the neck into the thorax has another significant impact on adult anatomy. Now while the aortic arches are developing with the branchial arches, the left and right vagus nerves are passing through the neck to get into the trunk. Their main purpose of course is to carry preganglionic parasympathetic axons to the trunk. However, as they pass through the neck, they give off their laryngeal branches to the laryngotrachial diverticulum, which is developing in the proximity of the 6 th aortic arch. Slide 26: As parts of the aortic arches disappear, these laryngeal branches pass inferior to the ductus arteriosus on the left and the 4 th aortic arch on the right. Slide 27: So as development proceeds and the heart and great arteries sink into the chest, the laryngeal nerves are essentially trapped since they pass inferior to the 6 th arch on the left and the 4 th arch on the right, and they must descend into the thorax as well. But to get back to the larynx, they have to reascend into the neck. In other words, they become recurrent. So we know these nerves (not arteries as I say in the narration) as the left and right recurrent laryngeal nerves, and the right passes inferior to the right subclavian, and the left one passes inferior to the arch of the aorta, just posterior to the remnant of the ductus arteriosus the ligamentum arteriosum. Slide 28: The next three slides contain images and text from a recent paper by Yamada et al. (2007) that appeared in the Anatomical Record (vo. 290: ). They portray 3D reconstructions of normal cardiac development, and if you are interested, you might want to look up the article yourself. I m not going to attempt to narrate these three slides, but feel free to sit and review them on your own. Slides 29, 30, 31: The non-narrated PowerPoint version of this presentation may offer better images than are available here. Slide 32: As was the case with the development of the heart, understanding the normal sequence of events in the embryological development of the great arteries can also give you some insight into the various deformations that occur in great artery development. Slide 33: As we know, the ductus arteriosus is a by-pass of pulmonary circulation during fetal life. Fullterm infants typically have functional closure of the ductus arteriosus by about 96 hours after birth. Anatomical closure is usually complete by about 3 months of age. However, if the ductus fails to involute, this can lead to a significant volume of aortic blood being diverted to the lungs. A patent ductus arteriosus is 2 to 3 times more common in female infants than males. It is the most common cardiac abnormality associated with maternal rubella infection early in pregnancy. There is some evidence that low oxygen content in the blood of an infant, for example in situations of neonatal respiratory stress, can adversely affect closure of the ductus arteriosus. A patent ductus arteriosus is one of the most common abnormalities of the great arteries, and estimated to occur in about 8 out of 10,000 births. It is especially frequently seen in premature infants. Slide 34: Coarctation of the aorta is a condition in which the lumen of the aorta is significantly narrow below the left subclavian artery. It is estimated to occur in about 3% of live births and is more common in male than female infants. It is also the most common cardiac abnormality in Turner Syndrome. There are two kinds of Coarctation of the aorta, depending on where the actual constriction may be.

8 Preductal is when the constriction occurs prior to the ductus arteriosus, and postductal is when it is distal to the ductus arteriosus. Slide 35: There a number of different ideas about how coarctation may come about, and it is not entirely understood which, if any, are correct. One theory suggests that coarctation is caused by abnormal involution of the left dorsal aorta opposite the normal area of involution on the right. Remember that the segment of the dorsal aorta on the right between the right subclavian and the point where the two dorsal aortae fuse is lost. This same thing may happen on the left leaving a constriction in the descending aorta. Another theory is that there is muscular tissue within the ductus arteriosus that may be incorporated into the wall of the aorta so that when the ductus contracts at birth, the same thing happens to the aorta causing a constriction. A third idea is that there is relatively little blood flowing through the area of the arch of the aorta formed by the 4 th embryonic aortic arch, so this region is fairly narrow during fetal life. It usually widens after birth and assumes that same diameter as the rest of the descending aorta. But if it doesn t and remains relatively narrow this could lead to a constriction causing coarctation. Slide 36: The more common type of coarctation is postductal, that is, when the constriction is just distal to the ductus arteriosus. The ductus normally closes, and you would think that a constriction of the descending aorta would lead to loss of blood supply to the lower part of the body. However, loss of volume of blood is what stimulates the development of anastomotic communications between vessels. Profusion of the lower body comes about through a variety of anastomoses between the subclavian and other vessels. This does however cause hypertension in the upper part of the body and left ventricular hypertrophy. This may not be detected until early childhood when a physician notices a weak femoral pulse and hypertension in the arms. If the child has a chest X-ray, this may show erosion of the lower borders of the ribs because the intercostal arteries are enlarged. Even though there is this alternative route of blood flow established, they still typically try and correct the problem to prevent permanent hypertension in the upper part of the body. Slide 37: Preductal coarctation is when the constriction occurs proximal to the ductus arteriosus. It is often associated with other abnormalities including ventricular septal defects and a patent ductus arteriosus. In fact, a patent ductus arteriosus is essential for a blood supply to reach the lower part of the body. Symptoms that are associated with a preductal coarctation include differential cyanosis to the lower part of the body. This is because blood flow is mainly derived from the pulmonary circulation through the ductus arteriosus. There is no compensation for preductal coarctation by elaboration of anastomotic communications between the subclavian and other vessels because the volume of blood flow is not affected. Slide 38: A double aortic arch is a very rare and unusual abnormality characterized by a vascular ring around the trachea and esophagus. It is interesting though, to image how this happens. If the right dorsal aorta between the right subclavian and the fused portion of the embryonic aorta fails to involute as it is supposed to, we are left with two aortic arches. Remember that the (embryonic) aortic arches are sweeping to the right and left of the developing foregut. The heart is positioned ventrally, and the aorta is positioned dorsally. The foregut, therefore, will be passing right through the center of this ring created by the right and left aortic arches. Through the process of differential growth, this large vascular ring is reduced in size, and then the descending aorta is going to shift to the left, which will end up carrying the abnormal right aorta dorsally. As the individual grows, this ring doesn t keep pace, and it can become quite small and can compress the esophagus and trachea.

9 Slide 39: Another rare abnormality is a right aortic arch. This is a situation that arises when the right dorsal aorta persists, and the distal segment of the left dorsal aorta is the one that involutes. There are said to be two different kinds of right aortic arch with a retroesophageal component and without a retroesophageal component. Without a retroesophageal component is probably the situation where genuinely it is the right dorsal aorta that takes over. The ductus arteriosus passes from the right pulmonary artery to the aortic arch, and this could be completely asymptomatic, however, it is often associated with other defects. Slide 40: A right aortic arch with a retroesophageal component probably started out as a double aortic arch. So rather than having an abnormal area of involution on the left side, neither side underwent any involution. As development proceeds and a ring is formed around the trachea and esophagus, for some reason the left arch disappears leaving the right arch posterior to the esophagus. Now the ductus arteriosus in this situation would have formed normally from the left side of the pulmonary arteries. It s positioning may therefore, constrict the esophagus and trachea. Slide 41: This is an illustration of the fetal pattern of blood circulation. In this illustration, the degree of oxygen content is indicated by the different colors so red means high oxygen content, blue means low, and purple is intermediate. In the fetus, the oxygen supply is renewed in the placenta rather than the lungs, so the umbilical vein carrying blood from the placenta has the highest oxygen content. After passing through the umbilicus, the umbilical vein enters the liver. Although some of that blood is diverted to the liver cells themselves, mostly the blood flows through something called the ductus venosus to by-pass the liver and enter the inferior vena cava. From there, the blood enters the right atrium. But we saw in cardiac development that the positioning of the inferior vena cava is immediately opposite the foramen ovale, so the blood entering the right atrium from the inferior vena cava preferentially passes through the foramen ovale into the left atrium. From there it will be pumped out the left ventricle and into the arch of the aorta where it can enter the carotid arteries and get to the developing brain. The blood that doesn t enter into the carotids or subclavians continues into the descending aorta. There it will be joined by blood that has been pumped from the right side of the heart through the ductus arteriosus. So the blood that is entering the descending aorta has only an intermediate level of oxygen content, but this is sufficient for the rest of the embryo because only the brain needs the highest level of oxygen content. So where is the blood coming from that is being pumped by the right side of the heart? Well, there are jugular veins and subclavian veins which are emptying into the superior vena cava and into the right atrium. Inside the right atrium there is a little mixing of blood from the superior vena cava and the inferior vena cava, so the blood that flows out the right ventricle and into the pulmonary trunk has an intermediate level of oxygen content. Very little blood actually enters into the lungs; most of it is going to pass through the ductus arteriosus and into the descending aorta. The aorta of course has many branches that serve the fetus. Among those branches are the umbilical arteries. These vessels will pass through the umbilicus and into the umbilical cord back out to the placenta to renew the oxygen supply. What about the blood flowing in the inferior vena cava toward the liver from the fetus? This is low oxygen content blood. It will join with the blood flowing through the ductus venosus, which is very high in oxygen content. The resulting mix is actually only slightly less than what was in the umbilical vein and ductus venosus, so still the blood entering through the inferior vena cava, and then flowing through the foramen ovale into the left side of the heart is probably the highest that is going to be found anywhere in the fetus. Slide 42: This final slide has an illustration of the adult pattern of circulation. However, we can identify the remnants of the fetal pattern of circulation. Of course, the umbilicus is where the umbilical vessels entered and left the fetus. Among those vessels are the umbilical vein and the umbilical arteries. The umbilical vein is known as the ligamentum teres in the adult. It is a fibrous cord that is located in the

10 inferior margin of something called the falciform ligament. The ligamentum teres will lead again to the liver, and the old ductus venosus is represented by a similarly involuted tube known as the ligamentum venosum. Inside the heart, the remnant of the foramen ovale is an oval-shaped depression in the right wall of the interatrial septum. It is called the fossa ovalis. The remnant of the ductus arteriosus between the pulmonary trunk and the inner arch of the aorta is called the ligamentum arteriosum. Finally, the umbilical arteries persist in the adult and continue to carry blood. However, there is a point in which they lose their lumen as they pass toward the umbilicus. After they lose their lumen, they are known as the obliterated umbilical arteries.