Pulmonary atresia is a birth defect (pronounced PULL-mun-airy ah-TREE-sha) of the heart where the valve that controls blood flow from the heart to the lungs doesn’t form at all. In babies with this defect, blood has trouble flowing to the lungs to pick up oxygen for the body.

What is Pulmonary Atresia?

Pulmonary atresia is a birth defect of the pulmonary valve, which is the valve that controls blood flow from the right ventricle (lower right chamber of the heart) to the main pulmonary artery (the blood vessel that carries blood from the heart to the lungs). Pulmonary atresia is when this valve didn’t form at all, and no blood can go from the right ventricle of the heart out to the lungs. Because a baby with pulmonary atresia may need surgery or other procedures soon after birth, this birth defect is considered a critical congenital heart defect (critical CHD). Congenital means present at birth.

In a baby without a congenital heart defect, the right side of the heart pumps oxygen-poor blood from the heart to the lungs through the pulmonary artery. The blood that comes back from the lungs is oxygen-rich and can then be pumped to the rest of the body. In babies with pulmonary atresia, the pulmonary valve that usually controls the blood flowing through the pulmonary artery is not formed, so blood is unable to get directly from the right ventricle to the lungs.

In pulmonary atresia, since blood cannot directly flow from the right ventricle of the heart out to the pulmonary artery, blood must use other routes to bypass the unformed pulmonary valve. The foramen ovale, a natural opening between the right and left upper chambers of the heart during pregnancy that usually closes after the baby is born, often remains open to allow blood flow to the lungs. Additionally, doctors may give medicine to the baby to keep the baby’s patent ductus arteriosus open after the baby’s birth. The patent ductus arteriosus is the blood vessel that allows blood to move around the baby’s lungs before the baby is born and it also usually closes after birth.

During prenatal development, the fetal circulatory system is integrated with the placenta via the umbilical cord so that the fetus receives both oxygen and nutrients from the placenta. However, after childbirth, the umbilical cord is severed, and the newborn’s circulatory system must be reconfigured. When the heart first forms in the embryo, it exists as two parallel tubes derived from mesoderm and lined with endothelium, which then fuse together. As the embryo develops into a fetus, the tube-shaped heart folds and further differentiates into the four chambers present in a mature heart. Unlike a mature cardiovascular system, however, the fetal cardiovascular system also includes circulatory shortcuts, or shunts. A shunt is an anatomical (or sometimes surgical) diversion that allows blood flow to bypass immature organs such as the lungs and liver until childbirth.

The placenta provides the fetus with necessary oxygen and nutrients via the umbilical vein. (Remember that veins carry blood toward the heart. In this case, the blood flowing to the fetal heart is oxygenated because it comes from the placenta. The respiratory system is immature and cannot yet oxygenate blood on its own.) From the umbilical vein, the oxygenated blood flows toward the inferior vena cava, all but bypassing the immature liver, via the ductus venosus shunt (image). The liver receives just a trickle of blood, which is all that it needs in its immature, semifunctional state. Blood flows from the inferior vena cava to the right atrium, mixing with fetal venous blood along the way.

Although the fetal liver is semifunctional, the fetal lungs are nonfunctional. The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale, a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether. Most of the rest of the blood is pumped to the right ventricle, and from there, into the pulmonary trunk, which splits into pulmonary arteries. However, a shunt within the pulmonary artery, the ductus arteriosus, diverts a portion of this blood into the aorta. This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit, which has only minor metabolic requirements. Blood vessels of uninflated lungs have high resistance to flow, a condition that encourages blood to flow to the aorta, which presents much lower resistance. The oxygenated blood moves through the foramen ovale into the left atrium, where it mixes with the now deoxygenated blood returning from the pulmonary circuit. This blood then moves into the left ventricle, where it is pumped into the aorta. Some of this blood moves through the coronary arteries into the myocardium, and some moves through the carotid arteries to the brain.

The descending aorta carries partially oxygenated and partially deoxygenated blood into the lower regions of the body. It eventually passes into the umbilical arteries through branches of the internal iliac arteries. The deoxygenated blood collects waste as it circulates through the fetal body and returns to the umbilical cord. Thus, the two umbilical arteries carry blood low in oxygen and high in carbon dioxide and fetal wastes. This blood is filtered through the placenta, where wastes diffuse into the maternal circulation. Oxygen and nutrients from the mother diffuse into the placenta and from there into the fetal blood, and the process repeats.

The heart folds quickly like origami and now starts beating. This begins with the formation of two tubes and beats spontaneously by week 4 of development.

Developing rapidly and early, the heart is the first organ to function in the embryo, and it takes up most of the room in the fetus's midsection in the first few weeks of its life. During its initial stages of development, the fetal heart actually resembles those of other animals. In its tubelike, two-chambered phase, the fetal heart resembles that of a fish. In its three-chambered phase, the heart looks like that of a frog. As the atria and then the ventricles start to separate, the human heart resembles that of a turtle, which has a partial septum in its ventricle. The final, four-chambered design is common to mammals and birds. The four chambers allow low-pressure circulation to the lungs and high pressure circulation to the rest of the body.

Development of the Heart

The human heart is the first functional organ to develop. It begins beating and pumping blood around day 21 or 22, a mere three weeks after fertilization. This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes both to and from the developing baby. The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo.

The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization. Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs. The heart begins to develop near the head of the embryo in a region known as the cardiogenic area. Following chemical signals called factors from the underlying endoderm (another of the three primary germ layers), the cardiogenic area begins to form two strands called the cardiogenic cords (Figure 19.36). As the cardiogenic cords develop, a lumen rapidly develops within them. At this point, they are referred to as endocardial tubes. The two tubes migrate together and fuse to form a single primitive heart tube. The primitive heart tube quickly forms five distinct regions. From head to tail, these include the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus. This is a very different pattern from that of an adult.

Development of the Human Heart This diagram outlines the embryological development of the human heart during the first eight weeks and the subsequent formation of the four heart chambers.

The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart. The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk. The bulbus cordis develops into the right ventricle. The primitive ventricle forms the left ventricle. The primitive atrium becomes the anterior portions of both the right and left atria, and the two auricles. The sinus venosus develops into the posterior portion of the right atrium, the SA node, and the coronary sinus.

As the primitive heart tube elongates, it begins to fold within the pericardium, eventually forming an S shape, which places the chambers and major vessels into an alignment similar to the adult heart. This process occurs between days 23 and 28. The remainder of the heart development pattern includes development of septa and valves, and remodeling of the actual chambers. Partitioning of the atria and ventricles by the interatrial septum, interventricular septum, and atrioventricular septum is complete by the end of the fifth week, although the fetal blood shunts remain until birth or shortly after. The atrioventricular valves form between weeks five and eight, and the semilunar valves form between weeks five and nine.

In a developing embryo, the heart has developed enough by day 21 post-fertilization to begin beating. Circulation patterns are clearly established by the fourth week of embryonic life. It is critical to the survival of the developing human that the circulatory system forms early to supply the growing tissue with nutrients and gases, and to remove waste products. Blood cells and vessel production in structures outside the embryo proper called the yolk sac, chorion, and connecting stalk begin about 15 to 16 days following fertilization. Development of these circulatory elements within the embryo itself begins approximately 2 days later. You will learn more about the formation and function of these early structures when you study the chapter on development. During those first few weeks, blood vessels begin to form from the embryonic mesoderm. The precursor cells are known as hemangioblasts. These in turn differentiate into angioblasts, which give rise to the blood vessels and pluripotent stem cells, which differentiate into the formed elements of blood. (Seek additional content for more detail on fetal development and circulation.) Together, these cells form masses known as blood islands scattered throughout the embryonic disc. Spaces appear on the blood islands that develop into vessel lumens. The endothelial lining of the vessels arise from the angioblasts within these islands. Surrounding mesenchymal cells give rise to the smooth muscle and connective tissue layers of the vessels. While the vessels are developing, the pluripotent stem cells begin to form the blood.

Vascular tubes also develop on the blood islands, and they eventually connect to one another as well as to the developing, tubular heart. Thus, the developmental pattern, rather than beginning from the formation of one central vessel and spreading outward, occurs in many regions simultaneously with vessels later joining together. This angiogenesis—the creation of new blood vessels from existing ones—continues as needed throughout life as we grow and develop.

Blood vessel development often follows the same pattern as nerve development and travels to the same target tissues and organs. This occurs because the many factors directing growth of nerves also stimulate blood vessels to follow a similar pattern. Whether a given vessel develops into an artery or a vein is dependent upon local concentrations of signaling proteins.

As the embryo grows within the mother’s uterus, its requirements for nutrients and gas exchange also grow. The placenta—a circulatory organ unique to pregnancy—develops jointly from the embryo and uterine wall structures to fill this need. Emerging from the placenta is the umbilical vein, which carries oxygen-rich blood from the mother to the fetal inferior vena cava via the ductus venosus to the heart that pumps it into fetal circulation. Two umbilical arteries carry oxygen-depleted fetal blood, including wastes and carbon dioxide, to the placenta. Remnants of the umbilical arteries remain in the adult. (Seek additional content for more information on the role of the placenta in fetal circulation.)

There are three major shunts—alternate paths for blood flow—found in the circulatory system of the fetus. Two of these shunts divert blood from the pulmonary to the systemic circuit, whereas the third connects the umbilical vein to the inferior vena cava. The first two shunts are critical during fetal life, when the lungs are compressed, filled with amniotic fluid, and nonfunctional, and gas exchange is provided by the placenta. These shunts close shortly after birth, however, when the newborn begins to breathe. The third shunt persists a bit longer but becomes nonfunctional once the umbilical cord is severed. The three shunts are as follows (image):

• The foramen ovale is an opening in the interatrial septum that allows blood to flow from the right atrium to the left atrium. A valve associated with this opening prevents backflow of blood during the fetal period. As the newborn begins to breathe and blood pressure in the atria increases, this shunt closes. The fossa ovalis remains in the interatrial septum after birth, marking the location of the former foramen ovale.
• The ductus arteriosus is a short, muscular vessel that connects the pulmonary trunk to the aorta. Most of the blood pumped from the right ventricle into the pulmonary trunk is thereby diverted into the aorta. Only enough blood reaches the fetal lungs to maintain the developing lung tissue. When the newborn takes the first breath, pressure within the lungs drops dramatically, and both the lungs and the pulmonary vessels expand. As the amount of oxygen increases, the smooth muscles in the wall of the ductus arteriosus constrict, sealing off the passage. Eventually, the muscular and endothelial components of the ductus arteriosus degenerate, leaving only the connective tissue component of the ligamentum arteriosum.
• The ductus venosus is a temporary blood vessel that branches from the umbilical vein, allowing much of the freshly oxygenated blood from the placenta—the organ of gas exchange between the mother and fetus—to bypass the fetal liver and go directly to the fetal heart. The ductus venosus closes slowly during the first weeks of infancy and degenerates to become the ligamentum venosum.

Overview

Blood vessels begin to form from the embryonic mesoderm. The precursor hemangioblasts differentiate into angioblasts, which give rise to the blood vessels and pluripotent stem cells that differentiate into the formed elements of the blood. Together, these cells form blood islands scattered throughout the embryo. Extensions known as vascular tubes eventually connect the vascular network. As the embryo grows within the mother’s womb, the placenta develops to supply blood rich in oxygen and nutrients via the umbilical vein and to remove wastes in oxygen-depleted blood via the umbilical arteries. Three major shunts found in the fetus are the foramen ovale and ductus arteriosus, which divert blood from the pulmonary to the systemic circuit, and the ductus venosus, which carries freshly oxygenated blood high in nutrients to the fetal heart.

Heart: Heart Defects

One very common form of interatrial septum pathology is patent foramen ovale, which occurs when the septum primum does not close at birth, and the fossa ovalis is unable to fuse. The word patent is from the Latin root patens for “open.” It may be benign or asymptomatic, perhaps never being diagnosed, or in extreme cases, it may require surgical repair to close the opening permanently. As much as 20–25 percent of the general population may have a patent foramen ovale, but fortunately, most have the benign, asymptomatic version. Patent foramen ovale is normally detected by auscultation of a heart murmur (an abnormal heart sound) and confirmed by imaging with an echocardiogram. Despite its prevalence in the general population, the causes of patent ovale are unknown, and there are no known risk factors. In nonlife-threatening cases, it is better to monitor the condition than to risk heart surgery to repair and seal the opening.

Coarctation of the aorta is a congenital abnormal narrowing of the aorta that is normally located at the insertion of the ligamentum arteriosum, the remnant of the fetal shunt called the ductus arteriosus. If severe, this condition drastically restricts blood flow through the primary systemic artery, which is life threatening. In some individuals, the condition may be fairly benign and not detected until later in life. Detectable symptoms in an infant include difficulty breathing, poor appetite, trouble feeding, or failure to thrive. In older individuals, symptoms include dizziness, fainting, shortness of breath, chest pain, fatigue, headache, and nosebleeds. Treatment involves surgery to resect (remove) the affected region or angioplasty to open the abnormally narrow passageway. Studies have shown that the earlier the surgery is performed, the better the chance of survival.

A patent ductus arteriosus is a congenital condition in which the ductus arteriosus fails to close. The condition may range from severe to benign. Failure of the ductus arteriosus to close results in blood flowing from the higher pressure aorta into the lower pressure pulmonary trunk. This additional fluid moving toward the lungs increases pulmonary pressure and makes respiration difficult. Symptoms include shortness of breath (dyspnea), tachycardia, enlarged heart, a widened pulse pressure, and poor weight gain in infants. Treatments include surgical closure (ligation), manual closure using platinum coils or specialized mesh inserted via the femoral artery or vein, or nonsteroidal anti-inflammatory drugs to block the synthesis of prostaglandin E2, which maintains the vessel in an open position. If untreated, the condition can result in congestive heart failure.

Septal defects are not uncommon in individuals and may be congenital or caused by various disease processes. Tetralogy of Fallot is a congenital condition that may also occur from exposure to unknown environmental factors; it occurs when there is an opening in the interventricular septum caused by blockage of the pulmonary trunk, normally at the pulmonary semilunar valve. This allows blood that is relatively low in oxygen from the right ventricle to flow into the left ventricle and mix with the blood that is relatively high in oxygen. Symptoms include a distinct heart murmur, low blood oxygen percent saturation, dyspnea or difficulty in breathing, polycythemia, broadening (clubbing) of the fingers and toes, and in children, difficulty in feeding or failure to grow and develop. It is the most common cause of cyanosis following birth. The term “tetralogy” is derived from the four components of the condition, although only three may be present in an individual patient: pulmonary infundibular stenosis (rigidity of the pulmonary valve), overriding aorta (the aorta is shifted above both ventricles), ventricular septal defect (opening), and right ventricular hypertrophy (enlargement of the right ventricle). Other heart defects may also accompany this condition, which is typically confirmed by echocardiography imaging. Tetralogy of Fallot occurs in approximately 400 out of one million live births. Normal treatment involves extensive surgical repair, including the use of stents to redirect blood flow and replacement of valves and patches to repair the septal defect, but the condition has a relatively high mortality. Survival rates are currently 75 percent during the first year of life; 60 percent by 4 years of age; 30 percent by 10 years; and 5 percent by 40 years.

In the case of severe septal defects, including both tetralogy of Fallot and patent foramen ovale, failure of the heart to develop properly can lead to a condition commonly known as a “blue baby.” Regardless of normal skin pigmentation, individuals with this condition have an insufficient supply of oxygenated blood, which leads to cyanosis, a blue or purple coloration of the skin, especially when active.

Septal defects are commonly first detected through auscultation, listening to the chest using a stethoscope. In this case, instead of hearing normal heart sounds attributed to the flow of blood and closing of heart valves, unusual heart sounds may be detected. This is often followed by medical imaging to confirm or rule out a diagnosis. In many cases, treatment may not be needed. Some common congenital heart defects are illustrated in Figure.

Figure. Congenital Heart Defects (a) A patent foramen ovale defect is an abnormal opening in the interatrial septum, or more commonly, a failure of the foramen ovale to close. (b) Coarctation of the aorta is an abnormal narrowing of the aorta. (c) A patent ductus arteriosus is the failure of the ductus arteriosus to close. (d) Tetralogy of Fallot includes an abnormal opening in the interventricular septum.

There are typically two types of pulmonary atresia, according to whether or not a baby also has a ventricular septal defect (a hole in the wall that separates the two lower chambers, or ventricles, of the heart):

• Pulmonary atresia with an intact ventricular septum: In this form of pulmonary atresia, the wall, or septum, between the ventricles remains complete and intact. During pregnancy when the heart is developing, very little blood flows into or out of the right ventricle (RV), and therefore the RV doesn’t fully develop and remains very small. If the RV is under-developed, the heart can have problems pumping blood to the lungs and the body. The artery which usually carries blood out of the right ventricle, the main pulmonary artery (MPA), remains very small, since the pulmonary valve (PV) doesn’t form.
• Pulmonary atresia with a ventricular septal defect: In this form of pulmonary atresia, a ventricular septal defect (VSD) allows blood to flow into and out of the right ventricle (RV). Therefore, blood flowing into the RV can help the ventricle develop during pregnancy, so it is typically not as small as in pulmonary atresia with an intact ventricular septum. Pulmonary atresia with a VSD is similar to another condition called tetralogy of Fallot. However, in tetralogy of Fallot, the pulmonary valve (PV) does form, although it is small and blood has trouble flowing through it – this is called pulmonary valve stenosis. Thus, pulmonary atresia with a VSD is like a very severe form of tetralogy of Fallot.

The causes of heart defects, such as pulmonary atresia, among most babies are unknown. Some babies have heart defects because of changes in their genes or chromosomes. Heart defects also are thought to be caused by a combination of genes and other factors, such as the things the mother comes in contact with in the environment, or what the mother eats or drinks, or certain medicines she uses.

A 2019 study using 2010-2014 data from birth defects surveillance systems across the United States, researchers estimated that each year about 550 babies in the United States are born with pulmonary atresia. In other words, about 1 in every 7,100 babies born in the United States each year are born with pulmonary atresia.

Pulmonary atresia may be diagnosed during pregnancy or soon after a baby is born.

During Pregnancy

During pregnancy, there are screening tests (also called prenatal tests) to check for birth defects and other conditions. Pulmonary atresia might be seen during an ultrasound (which creates pictures of the body). Some findings from the ultrasound may make the healthcare provider suspect a baby may have pulmonary atresia. If so, the healthcare provider can request a fetal echocardiogram to confirm the diagnosis. A fetal echocardiogram is an ultrasound specifically of the baby’s heart and major blood vessels that is performed during the pregnancy. This test can show problems with the structure of the heart and how well the heart is working.

After the Baby is Born

Babies born with pulmonary atresia will show symptoms at birth or very soon afterwards. They may have a bluish looking skin color, called cyanosis, because their blood doesn’t carry enough oxygen. Infants with pulmonary atresia can have additional symptoms such as:

• Problems breathing
• Ashen or bluish skin color
• Poor feeding
• Extreme sleepiness

During a physical examination, a doctor can see the symptoms, such as bluish skin or problems breathing. Using a stethoscope, a doctor will check for a heart murmur (an abnormal “whooshing” sound caused by blood not flowing properly). However, it is not uncommon for a heart murmur to be absent right at birth.

If a doctor suspects that there might be a problem, the doctor can request one or more tests to confirm the diagnosis of pulmonary atresia. The most common test is an echocardiogram. This test is an ultrasound of the baby’s heart that can show problems with the structure of the heart, like holes in the walls between the chambers, and any irregular blood flow. Cardiac catheterization (inserting a thin tube into a blood vessel and guiding it to the heart) also can confirm the diagnosis by looking at the inside of the heart and measuring the blood pressure and oxygen levels. An electrocardiogram (EKG), which measures the electrical activity of the heart, and other medical tests may also be used to make the diagnosis.

Pulmonary atresia is a critical congenital heart defect (critical CHD) that may be detected with newborn screening using pulse oximetry (also known as pulse ox). Pulse oximetry is a simple bedside test to estimate the amount of oxygen in a baby’s blood. Low levels of oxygen in the blood can be a sign of a critical CHD. Newborn screening using pulse oximetry can identify some infants with a critical CHD, like pulmonary atresia, before they show any symptoms.

Most babies with pulmonary atresia will need medication to keep the ductus arteriosus open after birth. Keeping this blood vessel open will help with blood flow to the lungs until the pulmonary valve can be repaired.

Treatment for pulmonary atresia depends on its severity.

• In some cases, blood flow can be improved by using cardiac catheterization (inserting a thin tube into a blood vessel and guiding it to the heart). During this procedure, doctors can expand the valve using a balloon or they may need to place a stent (a small tube) to keep the ductus arteriosus open.
• In most cases of pulmonary atresia, a baby may need surgery soon after birth. During surgery, doctors widen or replace the pulmonary valve and enlarge the passage to the pulmonary artery. If a baby has a ventricular septal defect, the doctor also will place a patch over the ventricular septal defect to close the hole between the two lower chambers of the heart. These actions will improve blood flow to the lungs and the rest of the body. If a baby with pulmonary atresia has an underdeveloped right ventricle, he or she might need staged surgical procedures, similar to surgical repairs for hypoplastic left heart syndrome.

Most babies with pulmonary atresia will need regular follow-up visits with a cardiologist (a heart doctor) to monitor their progress and check for other health conditions that might develop as they get older. As adults, they may need more surgery or medical care for other possible problems.