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Embryology, Heart Tube

Editor: Roman Zeltser Updated: 8/14/2023 9:21:37 PM


The heart is the first functional organ that develops in humans and all other vertebrate embryos. The heart first begins to beat by week 4 of development. During the beginning stages of development, the embryo forms a trilaminar disc that matures into the looped heart along with its 5 regions.[1][2]


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The embryo is trilaminar, which means it consists of the ectoderm, mesoderm, and endoderm. The endoderm forms the lining of the respiratory, gastrointestinal, and urogenital tract. The ectoderm forms the epidermis layer of the skin and the central nervous system from the spinal cord all the way up to the brainstem and cortex. The mesoderm forms everything in the middle. The somatic mesoderm, which is derived from somites, differentiates into the bones and muscles associated with the body walls as well as the limbs. The intermediate mesoderm forms the gonads and the kidneys. The notochord is what drives the development of the rest of the mesoderm, including the somites and the intermediate mesoderm. The lateral plate mesoderm splits during development and forms the intraembryonic space or coelom. This results in 2 sides, one with the somatic mesoderm and the ectoderm attached, and another with the visceral layer connected to the endoderm. As the embryo develops, the 2 ends of the visceral-endoderm layer are pushed together. The endoderm layer eventually becomes the primitive gut tube, while the visceral layer is where the heart begins to mature. As development continues, the visceral endoderm layer migrates medially and ventrally. Once the visceral layer comes together, the big vessels begin to form. Dorsal to the developing gut tube will be the two dorsal aortas; one on the left and one on the right. Ventral to the gut is the endocardial cells, which will become the primordial cells of the heart. Next, these parts need to come closer together to form a fused endocardial tube connected to the 2 dorsal aortas. So, the somatic mesoderm- ectoderm layer migrates down and connects, forming what will become the body wall. Between the endocardial tube and the body wall is still the intraembryonic space, which will become the pericardial space in the chest and the peritoneal space inside the abdominal and pelvic cavity. The endocardial tubes develop ventral to the foregut while the dorsal aortas develop dorsal to the foregut. They are connected so the heart can have an open connection for blood flow.

During development, the right and left dorsal aorta fuses at the inferior, or caudal, the pole of the developing embryo. The loop that connects each endocardial tube to the dorsal aorta is called the aortic arch. Humans have 6 aortic arches that mature into our functional arterial system. Around day 22 of development, the endocardial tubes fuse, which creates directionality of the blood flow. Blood comes into the heart through early embryonic veins, namely the cardinal veins, umbilical veins, and vitelline veins. Once the blood gets into the heart, it goes through an endocardial tube to the aortic arches and the dorsal aorta. For the heart to grow and continue developing, a mesenchymal tissue called cardiac jelly forms around the endocardial tube. This allows for the heart to separate from the foregut.

On day 23 of development, the heart finally begins to pump. This occurs once a layer of myocardium develops external to the cardiac jelly. Now, the cardiac jelly has become a space filler and will eventually disappear as the myocardial cells grow inward. However, the heart still requires more space. Fortunately, there is still the pericardial space that has been created by the intraembryonic coelom, which is located between the somatic and visceral mesoderm. When the brain begins to develop cranially, it pushes the coelom down inferiorly until it lies ventral to the developing heart and forms the pericardial cavity. As the myocardium pumps more effectively, it allows the endocardial tube to divide into different regions. The portion of the embryonic heart that is receiving blood is called the sinus venosus. There are 2 horns, the left and the right, that pump blood into the primordial atrium, which is then pumped into the ventricle and the bulbus cordis. From the bulbus cordis, it goes into the aortic sac which is connected to the first aortic arch. As the tubes start to develop and differentiate, it starts to move outward and invade the intraembryonic coelom, and as that happens, it loses its connection with the foregut. This allows the tube to move into the correct position to develop as the mature heart. Hence, the sinus venous and the primordial ventricle must move dorsally to end up behind the ventricles. Eventually, the tube loops so the bulbus cordis ends up on the right side of the body while the primordial ventricle moves to the left. The sinus venous, both the right and left horn mature into the right atrium, vena cava, and coronary sinus. The primordial atria eventually become the right and left auricles and the left atrium, while the primordial ventricle becomes the left ventricle. The bulbus cordis is divided into 3 sections: the proximal one-third, the conus cordis, and the truncus arteriosus. These sections become the muscular right ventricle, the smooth-walled outflow portions of the right and left ventricle, and the proximal aorta and pulmonary trunk respectively. Lastly, the aortic sac matures into the pulmonary artery and the aorta.[3][4][5]

Clinical Significance

Deviation from this normal development can cause a multitude of abnormalities in the growing heart. If there is a defect in the dynein, which guides the heart into the correct position, dextrocardia will occur. Dextrocardia occurs when the heart is located on the right side of the chest instead of the left. It is usually seen in Kartagener syndrome. If the endocardial cushion, which forms the valves and septums within the heart, does not fuse there will be an open connection between the right atrium and left atrium. This connection is called a patent foramen ovale. This will lead to shifting of oxygenated blood into the right side of the heart due to the increased pressure present on the left side, as well as paradoxical emboli. Along with a patent foramen ovale, there will also be valve absorbabilities, whether they be stenotic, regurgitant, displaced or atretic. The most common displaced valve seen in early development is Ebstein's anomaly. This is when the tricuspid valve is displaced downward into the right ventricle, which can cause right-sided heart failure and tricuspid regurgitation in the future. Lithium toxicity can cause it. The neural crest and endocardial cell migration are responsible for the twisting and fusion of the truncus arteriosus and bulbus cordis into the aorticopulmonary septum, ascending aorta, and pulmonary trunk. Failure of migration leads to the transposition of great vessels, patent truncus arteriosus, and tetralogy of Fallot. Transposition of the great vessels means that the aorta leaves from the right ventricle rather than the left and the pulmonary trunk leaves from the left ventricle. This creates a complete separation of systemic and pulmonary circulations. If not, intervention is done infants will die within months.[6][7]



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Level 3 (low-level) evidence