CVS Embryology


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This lecture discusses about the structure, function and the differences in between the different components of the vasculature (arteries, arterioles, capillaries, venules, veins). Before delving into the details about individual components of the vasculature, an understanding about the general structure of the blood vessel will be discussed. A standard blood vessel is composed of three layers, which are discussed as following:

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  1. TUNICA INTIMA forms the innermost layer of any vessel. Tunica intima itself is composed of three component layers. Endothelium forms the innermost aspect of the tunica intima. Surrounding the endothelium is a connective tissue layer called the subendothelial layer. Subendothelial layer has a varying amount of elastic and smooth muscle fiber depending on the type of vessel. In elastic arteries the density of elastic and smooth muscle fibers is higher compared to smaller arteries. Outermost component of the tunica intima is the internal elastic lamina.
  2. TUNICA MEDIAforms the middle layer of the vessel. It is mostly composed of the elastic and smooth muscle fibers which are arranged in a circular pattern. Tunica media is surrounded by the external elastic lamina.
  3. TUNICA ADVENTITIA forms the outermost layer of any vessel. Vasa vasorum are present in the tunica adventitia layer

In various types of vessels these above mentioned layers would be either present or absent. If present, the composition and thickness of these layers can slightly vary from one vessel type to another.

ARTERIES conduct blood away from the heart towards the tissues. Arteries normally carry oxygenated blood away from the heart. However, exceptions to this rule are the pulmonary arteries and the umbilical arteries which carry deoxygenated blood away from the heart.

Elastic arteries are larger in size and have a relatively thick tunica media. Examples of elastic arteries include the pulmonary arteries and aorta plus its 3 major branches (left brachiocephalic, right common carotid & the right subclavian arteries). Tunica media is so large in the case of aorta, that it has 50 layers of alternating elastic and smooth muscle fibers present in an alternating circular pattern. Elastic arteries are also referred to as the conducting arteries. Their main function is to receive high pressure blood from the heart and distend outwards keeping the blood there before they slowly return to their normal caliber and gently push the blood forward as the heart enters diastole phase. This is called the windcastle effect and it prevents any turbulence of the high pressure blood which leaves the heart. Hence, the elastic component allows the elastic arteries to recoil appropriately and serve their function as conducting vessels.  

Endothelium is the innermost layer of the tunica intima and this is surrounded by the subendothelial layer. In case of arteries, the subendothelial layer has a lot of elastic and smooth muscle fibers. Subendothelial layer is the part of the tunica intima that is most commonly involved in atherosclerosis. Atherosclerosis is an intimal disease which results in formation of atheromatous plaques within the subendothelial layer of the tunica intima. Atherosclerosis most commonly affects the medium and large sized arteries. This plaque formation tends to decrease the luminal size of the vessels and consequently the blood which flows across them. Arteries have abundant smooth muscle and elastic fibers in their tunica media, which gives them the recoil capability. Tunica adventitia forms the outermost layer. Small vessels called the vasa vasorum are located within the tunica adventitia, and they function to vascularize the wall of the walls of the elastic arteries.

Baroreceptors and chemoreceptor are present within the walls of carotid sinus and the arch of aorta. Baroreceptors are formed by the thinning of the wall of these arteries. This allows the increased blood pressure to have a more pronounced effect in distending the arterial wall in this region where the baroreceptors are located. There are nerves located in the adventitia of the baroreceptor region which sense this stretch of the vessel and send impulses if there’s a significant rise or drop in blood pressure. Similarly there are chemical receptors that are also present within the muscular wall of the arch of aorta. These chemoreceptors are formed by Glomus type 1 cells which are situated within the walls of the arch of aorta. These Glomus type 1 cells have channels for oxygen, carbon dioxide and hydrogen ions; this allows them to act as sensory receptors for the monitoring the concentrations of oxygen & carbon dioxide plus the pH of the arterial blood. Glomus type 1 cells are supported by the satellite receptors. These receptors respond to hypoxia, hypercapnia (increased arterial CO2 levels) and the pH changes in the arterial blood. Any derangements of these above mentioned parameters result in firing of the glomus cells thereby activating the corresponding control mechanism to ensure homeostasis within the body.

Muscular arteries arise from the larger elastic arteries. They are also referred to as the conducting arteries and they supply blood to various organs of the body. These muscular arteries mainly respond to sympathetic/adrenergic control because of the presence of alpha 1and beta 2 receptors. Sympathetic stimulation is responsible for the vasoconstriction effect in these arteries. They do have an endothelial and subendothelial layer. The smooth and elastic fiber layer in the subendothelium is not that dense. Their tunica media is composed of 3 to 10 layers of smooth muscle and elastic fibers. Outermost layer is formed by the tunica adventitia. Muscular arteries are also referred to as resistance vessels. This is because they exhibit vasoconstriction upon sympathetic stimulation; hence they can change their diameter. Upon decreasing their diameter, they can decrease the forward flow hence they are called resistance vessels. The volume of blood in the muscular arteries is referred to as stressed volume, since these arteries are always compressing upon the blood inside them to help maintain the blood pressure.  

The ARTERIOLES form the terminal arterial vessels and form a connection between the arteries and the capillaries. Arterioles form the major resistance site of the systemic vasculature and therefore, they are responsible for maintaining the blood pressure. The arterioles are also referred to as the functional sphincters of the arterial system. Within the tunica intima, they do have an endothelial and subendothelial layer. Subendothelial layer is not that dense in elastic and muscle fibers. Their tunica media has 1 to 3 layers of smooth muscle and elastic fibers. This tunica media responds to sympathetic and parasympathetic stimulation. Sympathetic stimulation achieves vasoconstriction of the arterioles and results in a decreased forward flow through them. In contrast, the parasympathetic stimulation achieves vasodilatation of the arterioles, which results in an increased forward flow across the arteriole.

In the case of skin, gastrointestinal system and the renal system; the sympathetic stimulation of their arterioles is modulated via the alpha-1 receptors. The arterioles leading to the skeletal muscles are controlled by beta 2 receptors.

CAPILLARIES have the smallest caliber in terms of luminal diameter. Though the capillaries have a small diameter, but they have the greatest cross-sectional area amongst all the vasculature. The total cross-sectional area of all the capillaries in the body can add up 2/3 of a meter. Also they have the largest surface area relative to all the blood vessels in the body. The tunica intima of capillaries is only composed of an endothelium and a basement membrane. The endothelium is formed by a single layer of endothelial cells which allows them to function as sites of exchange. Tunica media and adventitia are absent in the capillaries. Capillaries function as the exchange site of the vasculature because they exhibit selective permeability of substances across their walls. This permeability allows diffusion of oxygen, nutrients, signaling molecules and water from the blood to the tissues. Carbon dioxide and waste products diffuse in the opposite direction from the tissues into the capillaries.

When the capillaries merge together they end up forming VENULES. The venules have an endothelium and a broken subendothelium but they lack tunica media and adventitia. They are normally collapsed and have a low blood pressure. Venules are also involved in exchange of metabolites with the surrounding tissue. Another important function of venules is diapedesis which involves cellular trafficking across wall of the venules. This made possible by endothelial contraction which allows gaps to appear within the endothelium of the postcapillary venules. This diapedesis allows venules to function as sites of leukocyte extraction into the tissues. Inflammatory mediators released from the inflamed tissues allow leukocyte recruitment and via diapedesis leukocyte trafficking occurs into the tissue space. This allows leukocytes to take active part at the site of inflammation.

VEINS are formed when the venules merge together. The veins function as a reservoir of the blood since 2/3rd of the total blood volume is present in the veins at any given time. Veins transport blood away from the tissues and return it to the heart. Veins normally carry deoxygenated blood, except the pulmonary veins in adults and the umbilical vein during fetal life which bring back oxygenated blood to the heart from the lungs and the placenta respectively. Veins as compared to arteries are thin walled, more compliant & distensible, have a greater luminal diameter and have valves which prevent the backward flow of blood. Veins lack the elastic and muscular component hence when the blood backflows under the influence of gravity, the valves tend to approximate and prevent the retrograde flow of blood. In contrast to venules, larger veins have more defined endothelium & subendothelium and they have a tunica media as well.


CVS Embryology


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  1. The fetus has a connection with the maternal blood supply at the site of placenta. This connection is formed by the two umbilical arteries and a single umbilical vein. The umbilical arteries carry deoxygenated blood from the whole body to the placenta which is the gaseous exchange site prenatally. On the other hand, the umbilical vein returns oxygenated blood from the placenta back to the fetus.
  2. The fetal heart has a right to left shunt in the form of a patent foramen ovale. This has extensively been discussed in the previous lectures. As part of interatrial septal development, the two septae (septum foramen and secundum) leave a defect in the interatrial septum which allows the shunting of the blood from the right to left atrium.
  3. The ductus arteriosus opens at the underside of the aorta and connects it with the pulmonary trunk. The role of ductus arteriosus and its situation just distal to the origin of the left subclavian artery will be discussed later into the notes.
  4. Ductus venosus connects umbilical vein to the inferior vena cava, allowing the blood to bypass the hepatic route in doing so.

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Before birth, two umbilical arteries carry deoxygenated blood from the fetus to the placenta. Placenta allows gaseous exchange via diffusion to take place between the maternal oxygenated blood and the fetal deoxygenated blood.It’s important to remember that the fetal and maternal bloods don’t come into direct contact. Prenatally the fetal lungs are collapsed; hence placenta is the site of gaseous exchange before birth. Although the placenta has maternal deoxygenated blood but still it’s able to provide fetus with its oxygen requirements. This is made possible by the higher oxygen affinity of the fetal hemoglobin, HbF. HbF has 2 alpha and two gamma globin chains, which allows it to extract oxygen from a relatively deoxygenated maternal blood.

Ductus venosus connects umbilical vein (coming from the placenta) to the inferior vena cava, thereby forming a shunt that allows half of the placental blood to bypass the hepatic route. Hence 50% of the oxygenated blood from the placenta enters the hepatic sinusoids. This blood that enters the hepatic sinusoids is returned via the hepatic veins to the inferior vena cava. All of the oxygenated blood doesn’t enter the liver and the hepatic sinusoids because the passage through the hepatic sinusoids can take a very long time for the blood to reach the heart. The oxygenated blood in the IVC (80% oxygen saturation) at this point mixes with the deoxygenated blood from the hepatic veins (26% oxygen saturation). Before entering into the right atrium, the blood in the IVC has an oxygen saturation of around 67%.  

A hallmark of fetal circulation is that, the superior vena cava returns deoxygenated blood from the head, neck and upper extremities region to the right atrium. This deoxygenated blood reaching the heart via the SVC is directed into the right ventricle and subsequently into the pulmonary trunk. The inferior vena cava on the other hand brings relatively oxygenated blood (67% Oxygen saturation) to the right atrium, which due to flow dynamics passes through the patent foramen ovale into the left atrium. As discussed in earlier lectures, foramen ovale forms a right to left shunt which allows the oxygenated blood coming from placenta to bypass the pulmonary circuit. After birth, foramen ovale becomes obliterated and forms the fossa ovalis. Once it’s in the left atrium, this relatively oxygenated blood (coming from right atrium via foramen ovale) goes into the left ventricles and subsequently leaves the heart via the aorta. Most of this blood then leaves via the three large branches of aorta (brachicephalic trunk, left common carotid and the left subclavian arteries) towards the head, neck and upper extremities region. There’s no mixing of the blood coming from SVC and IVC, though they’re both received by the right atrium.

The deoxygenated blood (25% oxygen saturation) coming from the SVC entering the right atrium, is directed into the right ventricle and subsequently into the pulmonary trunk. The ductus arteriosus opens into the underside of the aorta, and connects the pulmonary trunk to the arch of aorta. Thus, ductus arteriosus forms a right to left shunt allowing the deoxygenated blood to bypass the pulmonary circuit. This shunting across the pulmonary circuit occurs because fetal pulmonary vascular resistance is very high resulting in just 10% of the right ventricular output goes to the lungs. The rest 90% of right venticular output is shunted from the pulmonary trunk to the aorta. This deoxygenated blood from the SVC which is in the aorta, now mixes with the relatively more oxygenated blood which came from the placenta and passed through the foramen ovale.

As mentioned earlier, only 10% of the fetal right ventricular output is directed to the lungs. This blood is brought back to the left atrium by the pulmonary veins and it leaves the left side of the heart via the aorta. The blood in the aorta after the opening of ductus arteriosus is at an oxygen saturation of 60%. This blood via the descending aorta is now directed to the abdomen and lower parts of the fetus and finally reaches the internal iliac arteries. Most of the deoxygenated blood now enters the two umbilical arteries and is taken to the placenta. The umbilical arteries on their route to the placenta touch bladder as well. Later on, the proximal parts of the umbilical arteries later form the superior vesical arteries.

Levels of oxygen saturation in different fetal vessels:

  1. Umbilical Vein = 80%
  2. Ductus Venosus = 75-80%
  3. IVC            = 67%
  4. Right Atrium   = 65-67%

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Ductus Arteriosus

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Foramen Ovale

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Ductus Venosus

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Earlier there was a brief mention of the high pulmonary vascular resistance and need for a shunt across the pulmonary circuit. Let’s touch that subject now in order to gain more clarity on this concept. Before birth the fetal lungs are collapsed. Since the fetus is inside the womb surrounded by amniotic fluid, the lungs are also filled with fluid and this keeps them collapsed. Since the lungs are collapsed as a result the pulmonary arterioles are also collapsed. This is because, the alveoli are filled with fluid at this point and the surrounding arterioles tend to exhibit vasoconstriction due to this resultant hypoxia (due to absence of oxygen in the alveoli). This hypoxic pulmonary arteriolar vasoconstriction results in a very high pulmonary vascular resistance and as a consequence the lungs remain in a collapsed state before birth. Since the right ventricle has to pump against a very high pulmonary vascular resistance, it results in the right ventricle being more hypertrophied than the left ventricle before birth. Fortunately only 10% of the right ventricular output flows to the lungs (other 90% is shunted across the pulmonary circulation by DA in the aorta) so the degree of hypertrophy isn’t that pronounced at the time of birth. This situation is reversed within one month after the birth.


After birth, the 3 above mentioned shunts tend to close because of changes in pressure gradients and in oxygen tension. Immediately after birth, as the newborn breathes the lungs become expanded. As the alveoli expand, the pulmonary vasculature also tends to expands due to decreased effects of hypoxic pulmonary vascular resistance. This results in an overall decrease in pulmonary vascular resistance and blood from the right ventricle is directed via the pulmonary trunk towards the pulmonary circulation. The increased pulmonary blood flow to the lungs also results in an increased pulmonary venous return to the left atrium. Consequently left ventricular output increases and the aorta receives more blood resulting in an increase in aortic blood pressure. Hence, the increased pressure in the aorta tends to reverse the shunt across the ductus arteriosus. Overall the pressure on the left side of the heart tends to increase more than the right side of the heart. As the lungs become functional, the following changes occur:

  1. Increased bradykinin levels
  2. Increased oxygen tension (more than 50mm of Hg)
  3. Decreased PGE2 and prostacyclin levels

Overall, there’s an increased oxygen tension due to expansion of lungs and an increased released of bradykinin from the lungs. Following this, there’s an immediate drop in PGE2 and prostacyclin levels which were being produced as a result of hypoxia. Prostaglandin E actually is an inhibitor of contracting response of ductus arteriosus to an increased oxygen tension. An oxygen tension above 50 mm of Hg promotes the closure of the ductus arteriosus. Therefore, all the above mentioned changes result in the contraction of specialized smooth muscle in the walls of ductus venosus and ductus arteriosus. Consequently, DV and DA become obliterated over the next couple of hours after birth. Failure of the ductus arteriosus results in a patent ductus arteriosus after birth. The closure of ductus arteriosus is a slow event and it’s summarized below:

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Within few hours

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Within 24 hours

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Within 48 hours

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Within 96 hours

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DA starts constricting

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Obliterated in 40% of newborns

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Obliterated in 80% of newborns

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Obliterated in 100% of newborns

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The umbilcal vein also closes upon birth as the umbilcus is clipped and the connection between the placenta and the fetus is severed. Closure of umbilical vein reduces the amount of blood flowing via the inferior vena cava into the right atrium. Hence the right atrial pressure tends to further drop relative to left atrial pressure. The increased left atrial pressure results in fusion of the septum primum and secundum and the foramen ovale is subsequently closed. Closed foramen ovale is referred to as fossa ovalis. The floor of the fossa ovalis is formed by the septum prium and its margin called the limbus ovalis is derived from the septum secundum. Closure of the foramen ovale means that the right heart is connected to the pulmonary circulation and the left heart is connected to the systemic circulation.

Once the umbilical connection to the placenta is servered after birth, the ductus venosus also begins to start closing. The closure of ductus vensosus is a slow process and it can take a month after birth to completely become obliterated. In cases where the newborn is anemic, the ductus venosus can be cannulated from the outside to initiate a blood replacement therapy. Adult remanant of the ductus venosus is referred to as the ligamentum venosum.



Postnatal changes which occur after birth result in formation of some adult remnants from the fetal circulatory system. These remnants and the changes after birth which give rise to them are summarized in the table below:

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1. Fossa Ovalis

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2. Ligamentum Arteriosum

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3. Ligamentum Venosum

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4. Medial Umbilical liagmaents

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Closure of the foramen ovale

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Closure of ductus arteriosus

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Closure of ductus venosus

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Obliteration of the distal part of the two umbilical arteries, proximal part forms superior vesical artery

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5. Ligamentum Teres hepatis/ Round ligament of liver

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Obliteration of the umbilical vein

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The ductus arteriosus is formed from the 6th pharyngeal arch artery on the left side. It connects aorta to the pulmonary trunk just distal to the origin of the left subclavian artery and forms a right to left shunt. This right to left shunt enables most of the right ventricular output to bypass the pulmonary circuit because the lungs are collapsed at this time and as a result the pulmonary vascular resistance is quite high. The ductus arteriosus is composed of specialized smooth muscle which releases PGE2 and prostacyclins in response to low oxygen tension/ relevant hypoxia. The PGE2 and prostacyclins release tends to keep the ductus arteriosus open before birth. Normally, the ductus arteriosus closes within few hours after birth due to contraction of the smooth muscle in its wall and is referred to as ligamentum arteriosum.

Congenital condition which can cause hypoxia after birth can prevent the ductus arteriosus from closing. One such condition is erythroblastosis fetalis. As mentioned earlier, the low oxygen tension due to hypoxia can cause a release of prostaglandins and prostacyclins which will prevent the ductus arteriosus from closing. Other than that, babies born with a preductal coarctation of aorta tend to have a patent ductus arteriosus which should be kept open. In case of preductal coarctation, the ductus arteriosus remains patent and provides blood flow into the descending aorta and thereby the abdomen and lower parts of the body. In situations where a left to right shunt is important for the survival of the newborn, the ductus arteriosus is necessary to be kept patent. Congenital heart defects such as transposition of great vessels requires such an intervention to keep the ductus arteriosus open. Prostaglandin E analogues such as dinoprostone, are administered in such cases which helps in keeping the ductus arteriosus patent.

In preterm babies, the lungs aren’t fully developed, therefore after birth there is a decreased arterial oxygen tension and an increased prostaglandin E2 and prostacyclins synthesis in response to this relative hypoxia. Hence, the incidence of a patent ductus arteriosus is very high in preterm/premature infants. Patent ductus arteriosus results in a left to right shunt after birth, which is non-cyanotic and the newborn has a machine-like murmur audible upon auscultation. In such cases, prostaglandin E inhibitors such as indomethicin and ibuporfen are administered in order to promote the closure of ductus arteriosus.

The situation of ductus arteriosus just distal to the origin of left subclavian artery has great significance. Most of the oxygenated blood entering the right atrium is directed towards the head and neck region via the 3 branches large branches of the arch of aorta. Just distal to the origin of subclavian artery, the aorta is connected to the pulmonary trunk via the ductus arteriosus. At this point the deoxygenated blood (coming originally from the SVC) in the pulmonary trunk is shunted into the aorta (via DA) and is allowed to mix with the oxygenated blood which originally came from the placenta. Hence, most of the oxygenated blood from the placenta directed to the head and neck region which at that that point of development has greater oxygen demands. This remaining blood in the aorta, after it has mixed with the shunted deoxygenated blood from the pulmonary trunk, has an oxygen saturation of 50% and is now directed to the rest of the body (abdomen and lower limb).


CVS Embryology


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Atrial & Ventricular septum formation process begins at the same time by the start of the 4th week and wraps up by the 8th week. Though occurring simultaneously, however, atrial septation is a little ahead of ventricular septation. Common congenital cardiac anomalies mostly occur due to defects in the formation of these septae. In this lecture and its subsequent review, we discuss the high yield topic of atrial septation and development plus relevant congenital defect which can occur during this process.


  1. It divides the primitive atria into a right and left atria.
  2. During fetal life provides it provides a patent right to left shunt and ensures the shunt is not in the opposite direction of left to right shunt. During fetal life right to left shunts are essential for the survival of the fetus. A hallmark of the fetal circulation, which differentiates it from the adult circulation, is that the right atrium receives the oxygenated blood from the placenta via the inferior vena cava. In an adult heart, the right side deals with the deoxygenated blood!
  3. After birth, when there’s no need a right to left shunt since the lungs have become functional, foramen ovale tends to close. At this point interatrial septum divides adult left and right atria into separate non-communicating chambers.

    A small Reynolds number signifies that the blood is flowing in a smooth and laminar fashion. If the Reynolds number is high, the blood flowing through the blood vessel would be turbulent.

    Murmurs and bruits point to the presence of turbulence in blood flow. These can be appreciated upon auscultation at the relevant areas. Murmurs are sounds of blood splattering on the rest of the blood due to turbulence. These disturbances result in vibrations that resonate through the walls of blood vessels or the heart itself. These are picked up as distinct sounds upon auscultation.



    Embryonic timeline of Atrial Septation: Late 4th week to the middle of the 6th week.

    Initially the right and the left atria are actually one single chamber which is referred to Primitive Atrium. Sinus Venosus provides the Inflow in this primitive atrium. The primitive atrium is divided into two separate left and right atria following the process of atrial septation. Atrial Septation is actually a series of events which involves 2 septae (Septum Primum & Septum Secundum) and 2 foraminae (Foramen Primum & Foramen Secundum) forming within the primitive atria, thereby dividing it into a right and left atrium.



    1. From the roof of the primitive atrium a flexible and crescenteric shaped Septum Primum grows inferiorly towards the endocardial cushions. The initial defect in between the down growing septum primum and the endocardial cushions is referred to as foramen primum. Foramen Primum functions to allow shunting of blood from the right atrium to the left atrium. Endocardial cushion itself is a derivative of neural crest cells and gives rise to the following structures in a adult heart:
    2. Foramen Primum is eventually obliterated when the inferior edge of the septum primum fuses with the endocardial cushions. Just before the foramen primum closes, multiple small secondary defects form within the upper wall of septum primum as result of apoptosis. These multiple small defects in the upper wall of septum primum coalesce into forming a single defect called the foramen secundum. Foramen secundum is formed before the foramen primum is closed, and it serves to maintain the very important function of reinforcing a right to left shunt of the oxygenated blood entering the right atrium via the inferior vena cava.
    3. While the septum primum is undergoing these changes, from the roof of the atrium and just to the right of septum primum, a second crescentic shaped septum secundum starts developing. As the septum secundum grows downwards, it extends and obliterates most of the foramen secundum. The remaining part of foramen secundum which isn’t obliterated by the septum secundum is referred to as Foramen Ovale. The function of foramen ovale is the same as that of the foraminae primum and secundum, which was to maintain a right to left shunt.
    4. It’s important to remember that septum primum is a rather flexible structure compared to septum secundum which is a relatively rigid structure. This rather flexible property of the septum primum allows its inferior flap (which isn’t covered by the septum secundum) to function as valve for foramen ovale. This valve allows the flow of blood from the right to left side thereby reinforcing the shunt, but it tends to disallow the backflow of the blood from the left atria to the right atria.
    5. Septum Primum and Septum Secundum eventually fuse to form the interatrial septum. Most of the interatrial septum is formed from two septae (primum and secundum). However, the inferior part of the interatrial septum forms from a single septum (septum primum only), and hence this part is rather thinner compared to the rest of the atrial septae. This thinner part of the interatrial septum in the adult heart is referred to as Fossa Ovalis and is a major anatomical landmark of the adult right atrium. Fossa ovalis presents as a marked crescentic ridge on the medial wall of the right atrium.
    6. Immediately after birth Foramen Ovale tends to close. After birth there’s an increase in left atrial pressure due to decreased pulmonary vascular resistance which enhances pulmonary blood flow and subsequent return of blood to the left side of the heart. Also, closure of the umbilical veins tends to decrease the right atrial pressure with respect to left atrial pressure. The above mentioned decreased right atrial and increased left atrial pressure changes result in closure of the foramen ovale after birth.



    1. PROBE PATENCY OF FORAMEN OVALE: A probe is passed from the right atrium into the left atrium to check whether the foramen ovale has closed or not. In cases where the probe can pass through into the left atrium, it means that septum secundum & septum primum have not fused completely together and hence the foramen ovale is still patent. Patent foramen ovale is present in 25% of normal adults without any symptoms. Even if it’s patent, the foramen ovale remains functionally closed due to post birth increased left atrial pressure. However, transient increase in right atrial pressure above the left atrial pressure (such as during Valsalva manoeuvre) can lead to a right to left shunt via the patent foramen ovale. This can lead to paradoxical emboli, where venous thromboemboli cross into the systemic arterial circulation and can cause various clinical complications.
    2. FORAMEN SECUNDUM DEFECT/ SECUNDUM TYPE ASD: This is the most common type of ASD, which usually presents with delayed clinical symptoms after the age of 30, before the age of 30 it’s usually asymptomatic. Secundum type ASD presents with variable sized defects in between the right and left atria. These defects are present in the central part of the interatrial septum, just above the limbus. Secundum type defects may occur due to one of the following, or both:


      Excessive resorption of the Septum Primum can result in a very large Foramen Secundum being formed which couldn’t be effectively closed by the Septum Secundum.

      Alternatively Secundum type defects can occur when there’s an underdeveloped septum secundum which has a relatively smaller size and hence cannot efficiently obliterate the foramen ovale.

      Besides Secundum type defects, although much less common but there are also Primum type atrial septal defects. These primum type atrial septal defects result due to a failure of the septum primum to fuse inferiorly with the endocardial cushions. These Primum type defects can be located in the lower aspect of interatrial septum. Fossa ovalis tends to normal in primum type defects.

      Clinical signs of atrial septal defects include:

      Wide, fixed splitting of S2.

      Systolic ejection murmur best audible in the 2nd intercostals space along the left sternal border.

      Atrial septal defects can also lead to paradoxical emboli similar to those in case of patent foramen ovale.



    It’s basically a three chambered heart with one common atrium and two ventricles, thereby highlighting the situation where interatrial septum fails to develop.

    PREMATURE CLOSURE OF THE FORAMEN OVALE: As mentioned earlier that foramen ovale is supposed to remain patent until after birth. If however, foramen ovale closes early due to premature fusion of septae primum & secundum before birth, this can result in a hypertrophied right and left ventricles plus an underdeveloped left sided chambers.



    Heart tube with its dilatations undergoes an S-shaped bending which results in an orientation where the outflow tract (truncus arteriosus) lies most anteriorly. Behind the truncus arteriosus is the primitive ventricle and still behind is the primitive atrium. On the posterior surface of the primitive atrium opens the sinus venosus along with its branches. Branches of sinus venosus are anterior cardinal vein, posterior cardinal vein and the common cardinal vein. Two vitelline and umbilical veins also drain into sinus venosus. Initially the sinus venosus drains into the middle of the posterior wall of right atrium, however due to flow and hemodynamic changes, sinus venosus starts growing towards the right side. Ultimately sinus venosus ends up opening at the posterior right end of the right atrium. Hemodynamic changes responsible for this right side shifting of sinus venosus are as following:

    An anastomosis forms between the anterior cardinal veins of either side, and the blood starts flowing from the left to the right side.

    Umbilical and vitelline veins on the left side start degenerating. This results in an increased blood flow into the right side as blood from the caudal part of the fetus is also shunted to the right side of the right atrium.

    Eventually the right umbilical vein also degenerates, and the right vitelline vein starts increasing in calibre. End result of these hemodynamic changes is that sinus venosus shifts and starts growing on the right side.

    On the left side the remaining degenerating pieces of the sinus venosus become the coronary sinus. Right vitelline vein in future becomes the inferior vena cava. The common cardinal vein becomes the future superior vena cava. All these changes contribute to an increase in the size of right atrium since sinus venosus has also shifted there as part of its development. Anterior view of the right atrium shows that it’s divided by the crista terminalis into a smooth and rough or trabeculated part. The trabeculated parts of right atrium and the right auricle are derived from the primitive atria. The smooth parts are derived from the primitive inflow tract which was sinus venosus. Crista terminalis is the landmark where parts of sinus venosus were absorbed into right atrium as parts of right atrial development. The lower part of the sinus venosus marks the valve of the inferior vena cava. Also there is an opening of coronary sinus which actually is the degenerated left sinus venosus draining into the right atrium.



    Left atrial development is relatively not as complicated. Trabeculated part and the left auricle form a very small component of left atrium and they’re derived from the primitive atrium. Majority of the left atrium is its smooth part which is derived from the primordial pulmonary trunk which gets absorbed as part of left atrial development. Primordial pulmonary trunk is actually a budding off of the left atrium. The primordial pulmonary turn initially grows and forms four branches. However, so much of the primordial pulmonary trunk is absorbed into the making of left atrium that its four branches end up opening directly into the left atrium.

    CVS Embryology


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    The aorta arises from the left ventricle as its outflow tract. Aorta forms an arch before descending downwards as the thoracic/descending aorta. This arch of aorta gives rise to three arteries; from right to left these arteries are the brachiocephaic trunk, left common carotid and the left subclavian artery. On the right side the brachiocephalic trunk gives rise to right subclavian artery and then continues as the right common carotid artery which eventually divides into internal and external carotid arteries of the right side. The left common carotid artery is a direct branch of arch of aorta and it ends up dividing into external carotid and internal carotid arteries of the left side. Finally the left subclavian artery arises from the arch of aorta prior to the ductus arteriosus, after which the arch curves downawards and continues as descending or thoracic aorta.


    Click Here To Watch Video Lecture For This Topic


    As the embryo is developing, two dorsal aortae develop on either side and give off branches to oxygenate ventral and dorsal parts of the embryo. Simultaneously the pharyngeal arches develop along with their pharyngeal arteries. There are six pharyngeal arteries that develop. The first pair of pharyngeal arteries develops by the 3rd and 4th week and the sixth pair develops by the 6th or 7th week. By the time the last pair (6th pair) of the pharyngeal arteries develops, the first and second pair of pharyngeal arteries has degenerated. It’s important to remember that all six pairs of pharyngeal arch arteries aren’t present at the same time. The 1st and 2nd pharyngeal arch arteries give rise to part of Maxillary artery and Stapedial artery respectively. Other than that the first two pharyngeal arch arteries degenerate. The 3rd pharyngeal arch artery is of importance, as it combines with the adjacent part of dorsal aorta to form common carotid and proximal part of the internal carotid arteries. The 4th pharyngeal arch artery on the right side gives rise to proximal part of right subclavian artery while the left side it gives rise to the aortic arch. The 5th pharyngeal arch artery normally doesn’t develop in humans. However, in cases where it does develop, it tends to be rudimentary and degenerates soon. The 6th pharyngeal arch artery gives rise to ductus arteriosus on the left side and it regresses on the right side.

    On the right side, the 1st, 2nd, 5th and 6th pharyngeal arch ateries tend to regress (completely or partially) whereas, the 3rd and 4th are of importance in terms of giving rise to adult structures. On the left side 1st, 2nd and 5th pharyngeal arch arteries tend to regress (completely or partially), whereas the 3rd, 4th and 6th give rise to arterial structures. This above information is summarized in the table overleaf:

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    Aortic arch derivative

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    Arterial structure formed on the right side

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    Arterial structure formed on the left side

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    1st (Maxillary artery)*

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    2nd (Stapedial artery)*

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    3rd pharyngeal arch artery

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    Common carotid & proximal part of the internal carotid arteries

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    4th pharyngeal arch artery

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    Proximal part of the right subclavian artery

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    Aortic arch, rest of it degenerates

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    5th pharyngeal arch artery

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    6th pharyngeal arch artery

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    proximal parts of pulmonary arteries of both sides, rest of it degenerates

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    Ductus arteriosus

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    So what happens is, that the first two pharyngeal arch arteries degenerate and the third one ,as mentioned earlier, is directly connected to the dorsal aortae on either side. The parts of dorsal aortae connected to the 4th and 6th pharyngeal arches tend to degenerate as well. As a result the 3rd pharyngeal arch arteries on either side get directly connected in the middle to the aortic sac. Inferiorly, the aortic sac is connected to the truncus arteriosus which at this point is undergoing septation to form aorta and the pulmonary trunk.  So, the initial part of the pulmonary trunk is formed by the truncus arteriosus whereas the point where the pulmonary trunk bifurcates into two pulmonary arteries (proximal parts of pulmonary arteries) is formed by the 6th pharyngeal arch artery.

    Eventually, the 3rd pharyngeal arch (which is directly connected to the aortic sac) starts dividing along with the aortic sac. This division eventually results in the brachiocephalic trunk developing on the right side. On the left side, part of the 3rd pharyngeal arch forms the aortic arch. Common carotid and internal carotid arteries on both sides are formed by the 3rd pharyngeal arch artery as well. However, distal part of internal carotid is formed by the dorsal aorta.

    The fate of dorsal aorta is different on either side. On the right side, the dorsal aorta ends up forming the right subclavian artery. On the left side however, the dorsal aorta forms a part of the descending aorta and the arch of aorta. Aorta primarily forms from the aortic sac. Although, part of aorta that is proximal to the commencement of the common carotid artery on the left side, is formed by the artery of the 4th pharyngeal arch. On the right side as well, the part just before the commencement of the common carotid artery from the brachiocephalic trunk is formed by the 4th pharyngeal arch artery. Right Subclavian artery forms from the dorsal aorta, whereas the left subclavian artery forms from existing vasculature as part of angiogenesis.

    On the right side, the right vagus nerve gives rise to right recurrent laryngeal nerve which passes under the the right subclavian artery to ascend towards the larynx region. On the left side, the left vagus nerve gives rise to left recurrent laryngeal nerve which hooks around the ligamentum arteriosum and further curves under the aortic arch to ascend and reach the larynx. On the right side, part of the 6th pharyngeal artery tends to degenerate hence the right recurrent laryngeal nerve has to pass behind the right subclavian artery on, as it courses upward.

    An important clinical correlate to remember is that, as the left recurrent laryngeal nerve curves under the arch of aorta, it can get damaged by aortic arch aneurysm or a malignancy. Left recurrent laryngeal nerve damage can result in paralysis of the left vocal cords. On the right side, since right recurrent laryngeal is unaffected by any aortic arch pathologies because it arises from the right vagus nerve in the root of the neck and subsequently passes under the subclavian artery (and not under the arch of aorta).

    Ligamentum arteriosum is the embryologic remanant of the ductus arteriosus. Ductus arteriosus itself arises from the left 6th pharyngeal arch artery. Ductus arteriosus opens into underside of the arch of aorta (distal to origin of the left subclavian artery) and it functions to form a shunt which allows the flow of deoxygenated blood from the pulmonary trunk to the aorta (right to left shunt). This right to left shunting allows the deoxygenated blood to complete bypass the pulmonary circuit.



    Coarctation of aorta is a constriction of the aorta just after it has given rise to subclavian artery. Post the coarctation site, the aorta becomes significantly narrowed and the blood supply to the lower limb and the abdomen is diminished which results in weak pulses of the lower limb. As compensation, over time collaterals develop around the chest wall and the abdomen to supply the lower body. Coarctation of aorta also affects the heart, which now has to pump against greater peripheral resistance and hence at a higher pressure in order to maintain peripheral circulation, thus it may lead to cardiac failure in severe cases.

    It’s important to understand the underlying cause for this coarctation of aorta. During development, the ductus arteriosus is composed of a specialized smooth muscular contractile tissue. This specialized contractile tissue at times makes its way into the arch of aorta. Hence, after birth when this migrated contractile tissue conracts and tends to narrow the aortic lumen (similar to obliteration of ductus arteriosus in response to increased oxygen and decreased PGE levels), there’s a resultant coarctation of the aorta. Alternatively, developmental alteration can also result in the coarctation of aorta.

    Clinically, coarctation of aorta manifests with the following:

    1. Brachial-femoral pulse delay.
    2. Blood pressure discrepancies between upper and lower extremities. These discrepancies normally present as hypertension in the upper extremities but feeble and delayed pulses in the lower limb.
    3. Associated with bicuspid aortic valve.

    Coarctation of aorta is divided into two types based on the location of the narrowing of aorta with respect to the position of ductus arteriosus:


      is also referred to as the infantile type, and it occurs prior to the site of ductus arteriosus. In this case the ductus arteriosus tends to remain patent. As part of compensation, the patent ductus arteriosus provides blood to the descending aorta and hence the lower parts of the body. Prostaglandin E analogues tend to keep the ductus arteriosus patent and they are administered to newborns in cases where DA patency is required. An important high yield point to remember is that preductal coarctation has a strong association with Turner’s syndrome.


      is the more common type and tends to occur in the adults. The narrowing of aorta in this case is distal to the origin of ductus arteriosus and hence DA tends to obliterate according to its normal timeline (immediately after birth). The compensatory collateral circulation in this case is provided by the intercostal arteries which link the internal thoracic artery (branch of the left subclavian artery) and the thoracic aorta to provide circulation to lower limb extremites. Over time, the collateral intercostal arteries enlarge resulting in erosion of the lower border of ribs which presents as notched appearance of ribs on the chest x-ray. This notched appearance of ribs on CXR is referred to as costal notching.


    CVS Embryology


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    Sinus venosus forms the inflow tract of the primitive heart tube. On each side of the sinus venosus, the common cardinal veins open into it. Anterior and posterior cardinal veins combine to form the common cardinal vein on each side of the sinus venosus. The common cardinal vein on the right side forms part of the superior vena cava. Besides the common cardinal veins, the umbilical and the vitelline veins also drain into the sinus venosus. On the left side, these veins undergo specific remodelling. This results in formation of specific anastamosis on the left side, giving rise to left to right shunts thereby causing most of the blood to be received by the right side of the sinus venosus. Consequently, the veins of the right side start maturing and increase in size relative to their left side counterparts. As the sinus venosus also grows and matures, it becomes incorporated into the right side of the primitive atrium. Eventually the vitelline, common cardinal and the umbilical veins of the left side degenerate. The blood received by the left side of sinus venosus is greatly reduced and as a result the left side of the sinus venosus shrinks.  Inferiorly the posterior cardinal veins anastamose together and form the iliac veins.


    Click Here To Watch Video Lecture For This Topic

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    The formation of the inferior vena cava is contributed by three set of veins:

    1. Anterior & posterior cardinal veins
    2. Subcardinal veins
    3. Supracardinal veins (develop a little latter)

    The anterior cardinal and the common cardinal veins on the left side give rise to brachicephalic and the left subclavian vein which drain into the SVC.  It is important to remember that, the umbilical vein on both sides and the vitelline vein on the left side, all tend to degenerate.  The vitelline vein on the right side along with the common cardinal vein of the right side together form parts of the SVC.

    The subcardinal veins have an anastomosis in the middle which is referred to as subcardinal venous anastomosis. These subcardinal veins are also connected to the posterior cardinal vein and form another anastomosis which is referred to as the mesonephric shunt. Later on the inferior part of posterior cardinal vein on the left side starts degenerating, however, it’s still connected to the subcardinal vein via the mesonephric shunt. Also, there are tiny buds arising from the subcardinal veins, these form parts of the future ovarian and spermatic veins.

    Subcardinal veins on the right side separate from the posterior cardinal veins and are joined in by the hepatic veins. This will later form the initial parts of the IVC. At this point it’s important to understand that an anastomosis forms between the supracardinal and the subcardinal veins, which is referred to as the supra-subcardinal anastomosis. This anastamosis becomes part of the IVC and later gives rise to the renal vein and parts of the spermatic veins. Over time the posterior cardinal vein on the right side also degenerates.

    As the IVC is formed, it is composed of the following parts:

    1. HEPATIC PART comes from the liver sinusoids and the hepatic vein. It also has a contribution from the sinus veonsus.
    2. PRERENAL PART of the IVC is contributed by the subcardinal veins. Primarily the right subcardinal vein has a greater contribution in forming this part.
    3. RIGHT AND LEFT SUPRARENAL VEINSare also parts of the IVC. They also develop from the subcardinal veins.
    4. RENAL SEGMENT OF THE IVC arises from the mesonephric shunt of the right side. The mesonephric shunt itself forms as a result of the anastamosis between the subcardinal and the posterior cardinal veins. Right renal vein also arises from this renal segment of the IVC. On the left side the mesonephric shunt becomes incorporated into the IVC and gives rise to the left renal vein. The spermatic/ovarian vein on the left side drains into the left renal vein which then opens into the IVC. However, on the right side, the right spermatic/ovarian vein opens directly into the IVC.
    5. POSTRENAL SEGMENT OF THE IVC is the region below the renal segment of IVC. Supracardinal veins contribute to the formation of the postrenal segment of the IVC.
    6. ILIAC VEINS form the most inferior parts of the IVC. The inferior anastomosis between the posterior cardinal veins is responsible for the formation of iliac veins.

    CVS Embryology

    Lecture # 3 – Ventricles And Aorticopulmonary Septum


    Embryonic time line of Interventricular septum begins in the late 4th week and commences by the end of 7th week.

    By the end of 4th week, the primitive ventricle is one single chamber which receives blood from the atria via the divided atrioventricular canal. Then there’s also a single aorticopulmonary trunk opening into primitive ventricles which forms the outflow tract. At this point aorticopulmonary trunk is formed of bulbus cordis and truncus arteriosus and it provides the outflow tract for the primitive ventricles. During later parts of the development the bulbus cordis gets incorporated into the right and left ventricles. Upon incorporation, on the right side the bulbus cordis forms the infundibulum of the right ventricle, and on the left side it forms the vestibule of the left ventricle. Hence, bulbus cordis forms the smooth outflow tracts of the ventricles on either side. Truncus arteriosus on the other hand develops into forming aorta and the pulmonary trunk on the left and the right sides respectively.

    Adult IV septum consists of two parts, a muscular part (derived from the myocardial cells) which forms the majority of the septum, and a relatively thin membranous part which forms the superior aspect of the IV septum which is part of the outflow tract.

    By the early 5th week, the muscular IV septum develops as an IV septal ridge from the floor of the primitive ventricle near the apex of the heart. This interventricular septal ridge ascends towards the atrioventricular canal, and thereby partially divides the primitive ventricle into left and right ventricles. The IV septal ridge extends towards the atrioventricular canal but it does not reach it, hence giving rise to a gap or defect which is referred to as interventricular foramen (IV Foramen). Thus the IV foramen is formed by the concave upper edge of the IV septum which gives rise to a gap through which shunting of blood between the right and left ventricles occurs.The membranous IV septum descends downward from the AV canal and fuses with the muscular IV septum thereby completely obliterating the IV foramen.

    The membranous part of IV septum is contributed by the following:

    • Endocardial cushions (Neural crest cells derivative)
    • Aorticopulmonary trunk septum (Mesenchymal derivative)
    • Muscular IV septum (Myocardial cells derivative)


    • COR TRILOCULARE BIATRIUM: It’s a three chambered heart with a single/common primitive ventricle and two atria. It occurs due to failure of development of the interventricular septum.
    • MUSCULAR IV SEPTAL DEFECTS: During its development the muscular IV septum can present with defects or holes allowing left to right shunts. Severity of these defects depends upon the size of these gaps. The resultant shunting caused by these defects can lead to right ventricular hypertrophy.
    • MEMBRANOUS IV SEPTAL DEFECTS:This is the most common of the IV septal defects. Part of the membranous IV septum is derived from the endocardial cushions which themselves are neural crest cells derivatives. Neural crest cells are also involved in the craniofacial development, therefore, abnormal migration of neural crest cells will result in concurrent facial and cardiac defects (mostly septal defects & atrioventricular valve problems). As mentioned earlier that it’s the membranous IV septum which is responsible for filling the gap formed by the IV foramen. If there is any defect in the formation of the membranous part of IV septum, the IV foramen will remain patent and left to right shunting of blood will occur. The severity of the left to right shunting due to IV septal defects depends upon the size of the defect.

    Clinically IV septal defects manifest themselves as following:

    • A harsh holosystolic murmur, best audible at the left lower sternal border.
    • Excessive fatigability upon exertion.
    • EISENMENGER COMPLEX: Initially the left to right shunting of the blood via the VSD is noncyanotic because it’s the oxygenated left ventricular blood mixing with the deoxygenated right ventricular blood. However, if this left to right shunt is left uncorrected, the increased blood flow into the right side of the heart can lead to pulmonary hypertension due to increased blood flow to the lungs. With time, this pulmonary hypertension can cause pathologic remodeling of pulmonary vasculature. This remodeling involves marked proliferation of tunica intima & media of the muscular pulmonary arteries and arterioles. Ultimately, pulmonary vascular resistance and the compensatory right ventricular hypertrophy together reverse the initial direction of the shunt from “left to right” to “right to left”. After birth, a right to left shunt is cyanotic, because the blood via the shunt is bypassing pulmonary gaseous exchange process and hence remains deoxygenated. Eisenmenger complex presents with late cyanosis, clubbing and polycythemia. Other then,with ventricular septal defects, Eisenmenger complex can also present along with atrial septal defects and patent ductus arteriosus. It’s important to remember that post birth, right to left shunts result in early cyanosis. Whereas, “left to right” shunts result in late cyanosis. Children suffering from late cyanosis are referred to as blue kids in contrast to the newborns which present with cyanosis at birth and are referred to as blue babies.


    Aorticopulmonary trunk arises from the primitive ventricles and serves as an outflow tract for the primitive ventricle. An aorticopulmonary septum forms within the aorticopulmonary trunk, thereby subsequently dividing it into the aorta & pulmonary trunk. Aorticopulmonary septum is formed by the migration of neural crest cells into the conotrunal and bulbar ridges of the truncus arteriosus. These neural crest cells grow in a spiral fashion and fuse to form aorticopulmonary septum. As the aorticopulmonary septum descends as part of its growth, it spirals in such a fashion that aorta becomes the left ventricular outflow tract and the pulmonary trunk becomes the right ventricular outflow tract. As mentioned earlier, as part of its descent the aorticopulmonary septum contributes to the development of the membranous part of interventricular septum and therefore helps fill in the opening formed by the interventricular foramen.

    DEFECTS IN THE DEVELOPMENT OF AORTICOPULMONARY SEPTUM result due to defects in migration of neural crest cells into the truncus arteriosus. At birth these aorticopulmonary septal defects always present with some cyanosis due to right to left shunting of the blood. Following are the congenital abnormalities associated with development of AP septum:

    • PERSISTENT TRUNCUS ARTERIOSUS occurs when there’s complete failure of the development of the AP septum due to abnormal migration of neural crest cells. As a result the separation of left ventricular and right ventricular outflow tracts never occurs. Therefore, the aorta and pulmonary trunk form a single outflow vessel (persistent truncus arteriosus) which receives blood from both the right and left ventricles. The common outflow tract allows mixing of oxygenated and deoxygenated blood, resulting in cyanosis of varying degree. Even though the two outflow tracts separate downstream, but by that time the mixing of oxygenated and deoxygenated blood has already occurred, hence it’s a cyanotic defect. Persistent truncus arteriosus is always accompanied by a membranous VSD (AP septum contributes to the formation of membranous part of IV septum, only muscular IV septum forms)and therefore this further allows right to left shunting of the blood.
    • TRANSPOSITION OF GREAT ARTERIES occurs when there’s a failure of the AP septum to develop in a spiral fashion secondary to a defective migration of the neural crest cells. This results in a transposition of the outflow tracts, as a result of which, the left ventricle is connected to the pulmonary trunk and the right ventricle is connected to the aorta. Consequently, two completely closed non-communicating circuits are formed which involve the systemic and pulmonary circulations. The systemic circuit forms a closed loop carrying completely deoxygenated blood involving the right side of the heart and the aorta. The pulmonary circuit forms another closed loop carrying oxygenated blood, and involves the left side of the heart and the pulmonary trunk. As expected, transposition and resultant complete separation of pulmonary and systemic circulations lead to a situation which is incompatible with life in the absence of an accompanying shunt or mixing defects. Therefore, infants born alive with this defect tend to have other defects as well, which allow shunting and therefore mixing of oxygenated and deoxygenated bloods in between two otherwise closed circuits. As a result, for these newborns, accompanying shunting disorders (ASD, VSD, PDA, PFO)* are rather protective. Absence of a mixing defect requires an atrial septoplasty surgery to create a shunt so that mixing of could occur and thereby sustain life. Transposition of outflow tracts is the most common cause of severe cyanosis, which occurs and persists immediately after birth. Without any surgical intervention or maintenance of PDA (Prostaglandin E analogue administration), most infants don’t survive past the first few months. It’s important to remember that upon imaging, in case of great vessels transposition, the echocardiogram shows an aorta which lies anteriorly and to the right of the pulmonary artery.
    • TETRALOGY OF FALLOT (ToF): It is the most common of cyanotic congenital heart defect. This is caused by a misalignment of the aorticopulmonary septum, where it fails to divide the aorticopulmonary trunk in the mid line. In case of ToF the AP septum is displaced anteriorly and towards the right or pulmonary side. This results in forming two unequal sized outflow vessels, with a very stenosed pulmonary artery and larger than normal aorta. As the name suggests, Tetralogy of Fallot has 4 component defects which coexist simultaneously. These 4 defects which as following (best remembered with mnemonic PROVe):


    • Pulmonary Stenosisit’s a direct manifestation of the defective rightward misalignment of the AP septum.
    • Overriding/Straddling Aortalarger than normal calibre aorta which receives blood from both the left and right ventricles.
    • Ventricular Septal defectfailure of AP septum to form the membranous part of the IV septum and subsequently fuse with the muscular IV septum, hence the IV foramen isn’t closed which gives rise to a VSD.
    • Right Ventricular Hypertrophydevelops secondary to pulmonary stenosis, because right ventricle has to pump against a greater resistance of a stenosed outflow tract thereby resulting in compensatory hypertrophy of the right ventricle

    Due to the presence of a ventricular septal defect, and a stenosed pulmonary outflow tract which presents with greater resistance to blood flow, there’s a right to left shunting of the blood. This right to left shunting results in cyanosis because the blood leaving the heart via the aorta is mixed with deoxygenated blood from the right ventricle.

    A very important point to remember and which is highly tested as well is that, squatting tends to improve this cyanosis. This is because squatting tends to increase systemic vascular resistance or after load, which tends to decrease right to left shunting of the blood via the VSD and thereby helps improve the cyanosis.

    Clinically, ToF presents with a harsh systolic ejection murmur which can be auscultated at middle to left sternal border. This murmur occurs due to presence of right ventricular outflow tract obstruction.

    light bulbDrbeen Study Tip: Tetralogy of Fallot is an extremely important topic, frequently tested in USMLE.


    ASD = Atrial septal defect

    VSD = Ventricular septal defect

    PDA = Patent ductus arteriosus

    PFO = Persistent foramen ovale

    AP = Aorticopulmonary

    IV = Interventricular


    CVS Embryology


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    SAN which is present near the opening of the superior vena cava. SA nodal cells have the highest intrinsic rhythm of spontaneous depolarization (roughly 60- 100/min) which makes them the automatic choice for the pacemaker of the heart.


    Click Here To Watch Video Lecture For This Topic


    The AVN is present behind the endocardial cushions and infront of the coronary sinus. It’s important to remember that the coronary sinus is actually the attritioned left horn of the sinus venosus. AV nodal cells have the second highest intrinsic rhythm (40-60/min). This automatically makes AVN the as the pacemaker of heart in case there’s a damage to the SA nodal cells.

    Bundle of HIS originates from the AV node and subsequently branches into two within interventricular septum. These two branches are the right and left bundle branches which ends up froming the HIS Purkinje system that supplies the papillary muscles and the rest of the ventricular myocardium. Papillary muscles are part of the trabeculated region of the ventricles which are derived from the primordial ventricle. Although, Purkinje cells are specialized for conduction only, they still possess an intrinsic rhythm of 35/min which gives them the property of automaticity. Hence, Purkinje system is third in line to take over as the pacemaker of the heart if anything goes wrong with both the SA and AV nodal cells.

    The SA and the AV node develop from the sinus venosus. Before the sinus venosus gets incorporated into the right atrium and forms the conducting system of the heart, the primitive atrium serves as the function of the pacemaker. Atrial myocytes around the sinus venosus develop a faster intrinsic rhythm thereby naturally taking over as the pacemaker cells. This means that as the myocardial cells are developing to form atria, they develop this ability to depolarize spontaneously. This allows the primitive heart to start beating by the 22nd day and that too without a true pacemaker, hence the primitive atria starts depolarizing even before the pacemaker is formed. Since sinus venosus is at the caudal end of the heart tube and serves as the inflow region. The initial pulsations are in coherence with the direction of the blood flow i.e., from caudal to the cranial side of the developing heart tube.  Eventually as the sinus venosus is incorporated into the right atrium, the SA node develops from the sinus venosus near the entry of the superior vena cava.

    The AV node also develops from the SA node near the opening of the coronary sinus. As the AV node develops, bundle of HIS also develops along with it from the sinus venosus. The bundle of HIS develops within the interventricular septum and divides into right and left bundle branches. The cells around the AV node which become consolidated into forming the Bundle of HIS exhibit the MSX-2 homeobox gene. Purkinje fibers are actually modified contractile myocytes which start to function as conducting fibers when they become connected with Bundle of HIS cells.

    Another important structure is the fibrous septum which insulates the ventricles from the depolarization of the atria and vice versa. This fibrous skeleton of the heart develops from the epicardium which is the visceral pericardium of the heart. The cells of the epicardium are derived from the local mesodermal cells around the sinus venosus as well.

    CVS Embryology


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    Link to the video lecture:


    The cardiovascular system is the first organ system to start developing and reach a functional state; which is even before its own development is complete. Cardiovascular development occurs during the 3rd to 5th week of intraembryonic life. Up until the second week, diffusion is enough for the embryo to receive the oxygen, nutrition and to get rid of the waste products. The lacunae of maternal blood-filled spaces and embryonic villi of the syncytiotrophoblast are involved in an intimate relationship, which allows gaseous exchange via diffusion in between the developing embryo and the maternal blood. However, into the third week, diffusion alone is not sufficient to match the needs of the growing embryo and it needs a circulatory system, hence heart has to develop.

    Click Here To Watch Video Lecture For This Topic



    Gastrula is a stage of development of the embryo, when it is in the form of tri-laminar germ disc including ectoderm, mesoderm, and endoderm. Endoderm is associated with umbilical vesicle; ectoderm is associated with Amniotic cavity. Cytotrophoblast around the gastrula develops multiple cavities. The cavities merge to form one big cavity called extraembryonic coelom. The cytotrophoblast is connected to the embryo through the connecting stalk. The cellular layer from cytotrophoblast which covers the gastrula is called extraembryonic mesoderm


    Around 15th day of intraembryonic life, multiple cavitations start appearing in the lateral plate mesoderm which later merges together to form a Horseshoe-shaped Intraembryonic Coelom. The Horseshoe shaped Coelom divides lateral plate mesoderm into two layers which are called Splanchnopleure (connected to underlying Endoderm) and Somatopleure (connected to overlying Ectoderm). It’s the splanchnic layer of mesoderm which mainly forms the cardiogenic area in the latter half of the 3rd week. In addition to this, Neural crest cells also contribute to heart formation especially the Aorticopulmonary septum and the Endocardial Cushion regions.

    Around 17the day of intraembryonic life, the Endoderm layer of the Gastrula secretes VEGF, which causes Ectodermal cells to migrate into the cranial end of the underlying mesoderm and form Blood islands. A horseshoe-shaped area forms on either side of the neural plate. The blood islands formed above the Prechordial plate (Cranial side) are called Cardiogenic or Heart-forming regions.


    Cephalic-caudal Body folding ensures that the cardiogenic area and septum transversum (future diaphragm) come to lie under and below the prechordal plate and in front of the foregut. Lateral body folding approximates the intraembryonic coelom in the midline, folds of which give rise to adult pericardial sacs which envelope the cardiogenic area in the midline.


    The ectodermal cells migrate into the mesoderm as cardiogenic cells which condense to form a pair of primordial Heart tubes. The pharyngeal area mesoderm contributes further cells which form a secondary heart forming region around the primordial heart tubes. Further cells are contributed to the Splanchnic Mesoderm which forms the myocardium around the primordial heart tubes. This newly formed Myocardium will start secreting Hyaluronic acid and other connective tissue components which are termed together and called as Cardiac Jelly. Cardiac jelly in the future becomes the connective tissue of the heart. These newly formed primordial heart tubes are surrounded by a pericardial cavity which provides the outer Parietal layer of the Pericardium which is adherent to the Fibrous pericardium in the adult heart. The Caudal or Inflow part of the Heart tube that is Sinus Venosus provides the cells which form the visceral or inner layer of the pericardium, also called EPICARDIUM. By the 21st day, the two primordial heart tubes fuse under the influence of VEGF into a single endocardial or Heart tube. On the 22nd day the embryonic heart starts beating.


    The Primordial heart tube now orients itself into a cephalic INFLOW (Venous region) and a cranial OUTFLOW (Arterial Region) ends. At this point the primitive heart tube has five dilatations which are as follows:

    1.  Truncus Arteriosus (Arterial Outflow region): Forms Adult Aorta, Pulmonary trunk, and their respective semilunar valves.
    2.  Bulbus Cordis: Forms Smooth parts of the Adult right ventricle (conus arteriosus) and left ventricle (aortic vestibule).
    3.  Primitive Ventricle: Forms trabeculated/rough parts of right and left ventricles.
    4.  Primitive Atrium: Forms trabeculated/rough parts of right and left atriums i.e., the pectinate muscles.
    5. Sinus Venosus: On the right side it forms Sinus Venarum (smooth part of right Atrium), Superior vena cava and the inferior vena cava. On the left side, it forms Coronary sinus and oblique vein of the left atrium.

    Note: (a) The vascular parts when incorporated into the adult heart form the smooth regions of the heart whereas the primitive chambers form the rough or trabeculated parts of the respective adult heart chambers.

    (b) Incorporation of parts of the Pulmonary veins forms the smooth-walled part of the left Atrium. On the right side, incorporation of right sinus venosus forms the smooth-walled part of the right atrium.


    The heart tube at this point undergoes Right-sided bending or rotation which referred to as Dextral looping. The Truncus Arteriosus or the ventricular end of the heart tube grows more rapidly and tends to fold downwards, forwards and to the right side. Subsequently, the lower parts of the tube i.e., the primitive atria and sinus venosus tend to fold upwards, backward and to the left side. This dextral looping tends to place the chambers of the heart in their adult anatomic positions where the right ventricle forms most of the right border plus the anterior surface of the heart and the left atrium is the posterior-most chamber of the heart. Also, the ventricles are rather more anteriorly placed relative to atria in an adult heart.


    Levo-Dynein is a protein involved in the formation of Cilia. However, Levo-Dynein also functions to create symmetry within the human body. An abnormality of Levo-dynein can lead to symmetry problems such as, Situs Inversus whereas the viscera tend to be present on the opposite sides of their normal anatomical location. It can also lead to Dextrocardia, which is a rare clinical condition in which the Apex of the heart is located on the right side of the body. The above two abnormalities often present as part of Kartagener Syndrome (Primary Ciliary Dyskinesia). Kartagener Syndrome results due to a defect in the dynein arm of the cilia which renders cilia immotile. It is a cause of infertility in both males and females due to immotile sperm and dysfunctional fallopian tube cilia respectively. In females, there’s an additional risk of ectopic pregnancies. Besides Dextrocardia on CXR and infertility in both sexes, Kartegener Syndrome can also lead to Bronchiectasis and recurrent sinusitis due to ineffectiveness of the mucociliary escalator.


    Post the cranial-caudal body folding, the embryonic heart tubes come to lie in front of the foregut. This is before the fusion of the primordial heart tubes into a single Heart tube. At this point, the primordial heart tubes are connected to the foregut via the Mesocordium. The Mesocordium itself is a derivative of the peritoneum. Subsequently, a gap appears within the Mesocordium which is called transverse sinus and this eventually results in degeneration of Mesocardium, following which the Pericardial cavity is thus separated from the Foregut.


    Teratogens are substances (normally drugs) which can either cause birth defects or they can accelerate other embryonic deformities that are present. Developing embryo is most susceptible to teratogens exposure during its embryonic period which is from 3rd to 8th week (first 2 months). This is because the embryonic period is the time when most organ systems are developing; hence teratogen exposure at this point can be disastrous. Teratogens frequently tested by the USMLE are given below:

    1.  ACE Inhibitors: Cause Renal damage
    2.  Aminoglycosides: Cranial nerve 8, Vestibulocochlear Nerve Abnormalities.
    3.  Carbamazepine: Facial dysmorphism, developmental delay, and neural tube defects.
    4.  Lithium (used to treat the manic phase of Bipolar disorder): Ebstein Anomaly in which the tricuspid valve leaflets are displaced inferiorly into the right ventricle. It presents with widely split S2 and Tricuspid Regurgitation.
    5.  Phenytoin: Can cause fetal Hydantoin syndrome i.e., cleft palate, cardiac defects, and phalanx or fingernail hypoplasia.
    6.  Tetracyclines: Discoloration of teeth.
    7.  Thalidomide: Limb defects.


    The increased retinoic acid concentration in an area of blood vessel formation leads to the formation of a venous channel. However, a decrease in retinoic acid concentration favors the formation of an arterial channel.


    Vasculogenesis is defined as the formation of a new blood vessel literally from nothing or scratch. Angiogenesis, on the other hand, is defined as, the formation of a new blood vessel from an existing vascular channel by branching. Regions of an existing blood vessel bud of as part of angiogenesis to form independent new vessels.