DEVELOPMENT OF THE CARDIOVASCULAR SYSTEM
Read: Langman's Medical Embryology chapter 12
The development of the cardiovascular system is an early embryological event. From fertilization, it takes eight weeks for the human heart to develop into its definitive fetal structure. During this period the system develops so it can 1) supply nutrients and oxygen to the fetus, and 2) immediately function after birth. To understand the development of the heart, you must begin with a thorough understanding of the anatomy of the adult heart and the great vessels. Next, as you consider each stage of development you must keep in mind what the fetus is like at that particular stage of development, and what are the demands placed on the cardiovascular system.
II. Early Development of the Circulatory System
A. Blood Islands
During the third week of gestation angioblastic blood islands of mesoderm (angiogenic clusters) appear in the yolk sac, chorion and body stalk. The innermost cells of these blood islands are hematopoietic cells that give rise to the blood cell lines. The outermost cells give rise to the endothelial cell layer of blood vessels. A series of blood islands eventually coalesce to form blood vessels.
B. Heart Tube
By the middle of the third week of gestation angioblastic blood islands from the splanchnic mesoderm appear and form a plexus of vessels lying deep to the horseshoe-shaped prospective pericardial cavity. These small vessels develop into paired endocardial heart tubes. The splanchnic mesoderm proliferates and develops into the myocardial mantle which gives rise to the myocardium. The epicardium develops from cells that migrate over the myocardial mantle from areas adjacent to the developing heart.
The bilateral endocardial heart tubes continue to develop and connect with a pair of vessels, the dorsal aortae, located on either side of the midline. As the embryo develops, the lateral folding and cephalic growth of the embryo shift the endocardial heart tubes medially, ventrally and caudally. They fuse in the midline as a single endocardial heart tube. The endocardial heart tube is surrounded by the myocardial mantle and between these two layers is the cardiac jelly. The resulting heart tube is suspended in the pericardial cavity by the dorsal mesocardium. When the single heart tube is formed, the embryo is in the fourth week of gestation, is about 3 mm in length, has 4 - 12 somites, and the neural tube is beginning to form. The heart now begins to beat.
C. Vascular Circuits
As the heart begins to beat three sets of blood islands coalesce to form three vascular circuits. Within the embryo an embryonic circuit forms. It consists of paired dorsal aortae that arise from the endocardial heart tube and break up into capillary networds that supply blood to the developing embryonic tissues. Blood is drained from these tissues by anterior and posterior cardinal veins that drain into common cardinal veins, which in turn drain into the endocardial heart tube.
Two extraembryonic circuits also form. The first is the vitelline (omphalomesenteric, yolk sac) circuit. In this circuit blood from the dorsal aortae drain into vitelline arteries that in turn supply the yolk sac. The blood drains back to the heart tube via paired vitelline veins. The second circuit is the umbilical (allantoic, placental) extraembryonic circuit. In this instance, the dorsal aortae supply blood to umbilical arteries that in turn bring this now unoxygenated blood back to the placenta. Blood from the placenta is carried to the heart tube via umbilical veins.
III. Formation of the Primitive Four Chambered Heart.
As the endocardial heart tubes fuse, several bulges and sulci appear. From the cephalic end, the bulges are the bulbus cordis (truncus arteriosus and the conus arteriosus), the primitive ventricle, the primitive atrium and the sinus venosus. The veins connect to the heart tube via the sinus venosus, while the paired dorsal aortae arise from aortic arches that in turn arise from the aortic sac. The aortic sac is at the most cephalic end of the bulbus cordis. The sulci present are the bulboventricular sulcus, between the bulbus cordis and the ventricle, and the atrioventricular sulcus, between the atrium and the ventricle.
There now occurs a rapid growth of the heart tube and the heart begins to convolute (to view an animation of the convolution of the heart tube, go to the heart animation page). With this convolution the dorsal mesocardium begins to degenerate. During the process of convolution, the first flexure seen is between the bulbus cordis and the ventricle. The bulboventricular loop that is formed shifts this region of the heart to the right and ventrally. The second flexure, atrioventricular loop, is between the atrium and the ventricle and this region of the heart is shifted to the left and dorsally. As growth continues the atria shift cephalically.
The sinus venosus gradually shifts to the right to empty into the right atrium. The bulboventricular sulcus is represented inside the heart as the bulboventricular flange. The bulboventricular flange and the muscular interventricular septum begin to separate the primitive ventricle (which will become the left ventricle) from the proximal bulbus cordis (which will become the definitive right ventricle). The atria continue to grow, and bulge forward on either side of the bulbus cordis, and shifts the bulbus medially. With increased blood flow the bulboventricular flange regresses. Thus, the primitive four-chambered heart is formed and blood flows from the veins to sinus venosus, to atria, to ventricles, to conus, to truncus, to aortic sac, to dorsal aorta.
Now the enlarging liver encroaches upon the developing vitelline and umbilical veins and gradually all the blood will drain to the proximal right vitelline vein. The distal vitelline veins will give rise to the portal system. The left umbilical vein remains and drains into the ductus venosus, a shunt which allows blood to bypass the developing liver.
IV. Septation of the Heart
During the second month, the heart begins to septate into two atria, two ventricles, the ascending aorta and the pulmonary trunk.
A. Atrial Septation.
Endocardial cushions develop in the dorsal (inferior) and ventral (superior) walls of the heart. These grow toward each other as the cardiac jelly mesenchyme proliferates deep to the endocardium. These cushions fuse and divide the common AV canal into the left and right AV canals.
At the same time there is a developing septum from the dorsocranial atrial wall that grows toward the cushions. This is the septum primum, and the intervening space is called the foramen primum. As the septum reaches the endocardial cushions closing foramen primum, a second opening, foramen secundum appears in septum primum. As foramen secundum enlarges, a second septum, septum secundum forms to the right of septum primum. Septum secundum forms an incomplete partition (lying to the right of foramen secundum) which leaves an opening, the foramen ovale. The remaining portions of septum primum become the valve of foramen ovale.
Concurrently, the sinus venosus has shifted to the right as the proximal portions of the left vitelline and umbilical veins are obliterated by the liver. The right sinus venosus becomes incorporated into the right atrium forming the smooth portion of the right atrium. The primitive right atrium is seen in the adult as the rough portion (auricle) of the right atrium. The remainder of the left sinus horn is the coronary sinus and the oblique vein (of Marshall) in the adult heart.
On the left side, the primitive atrium is enlarged by the incorporation of tissue from the original, single pulmonary vein and its proximal branches. This incorporated tissue is the adult smooth left atrial wall through which four pulmonary veins empty independently. The trabeculated left atrial appendage originated from the primitive left atrium.
B. Ventricular Septation
The muscular interventricular (I.V.) septum grows as a ridge of tissue from the caudal heart wall toward the fused endocardial cushions. The remaining opening is the interventricular foramen. The IV foramen is closed by the conal ridges, outgrowth of the inferior endocardial cushion, the right tubercle, and connective tissue from the muscular interventricular septum. This portion of the I.V. septum is called the membranous part of the interventricular septum.
C. Septation of the Bulbus Cordis.
Truncal swellings (ridges) appear first as bulges in the truncus on the right superior and the left inferior walls. They enlarge and fuse in the midline to form the truncal (aorticopulmonary) septum. This septum spirals as it develops distally separating the distal pulmonary artery from the aorta. At the same time right dorsal and left ventral conal ridges form and fuse in the midline. The conal septum helps divide the proximal aorta from the pulmonary artery and contributes to the membranous IV septum. The truncal and conal septa fuse to form a 180o spiral and together definitively form the aorta and the pulmonary artery. Cells that contribute to the conal and the truncal septa are in part derived from neural crest cells that migrate into these regions.
D. Cardiac Valve Fromation
Semilunar valves develop in the aorta and pulmonary artery as localized swellings of endocardial tissue. The atrioventricular valves develop as subendocardial and endocardial tissues and project into the AV canal. These bulges are excavated from the ventricular side and invaded by muscle. Eventually, all the muscle, except that remaining as papillary muscle disappear and three cusps of the right AV (tricuspid) valve, and two cusps of the left AV (mitral) valve remain as fibrous structures.
V. Development of the Major Arteries
The six pairs of aortic arches, develop in a cephalocaudal direction and interconnect the ventral aortic roots and the dorsal aorta. They are never all present in the developing human heart. Of the six pairs of aortic arches, most of the first, second and fifth arches disappear. The fate of the arches, ventral roots and the dorsal aorta are listed on the right by clicking here.
V. Development of the Veins
The veins develop from the three major vascular circuits. As with the arteries they develop in a cephalocaudal direction and as a consequence the precursors to the veins are never all present at the same time. In addition, as new structures develop the course of veins changes.
In considering the development of the veins, the veins to the head are derived from the anterior cardinal veins. New channels also develop such as the thymicothyroid anastomises and the external jugular veins and give rise to veins of the head and neck.
In the trunk, one set of veins develops from the posterior cardinal veins and veins that develop from it later in development such as the subcardinal, supracardinal, and sacrocardinal veins. These veins will give rise to the inferior vena cava, the renal, adrenal and gonadal veins as well as the azygos and hemiazygos viens.
The superior mesenteric vein (and perhaps the splenic vien) as well as the veins to the liver develop from the vitelline (omphlomesenteric) veins. The ductus venosus develops as a new structure that connects the left umbilical vein with the inferior vena cava.