Development of the cardiovascular system
Definitions & Key takeaways
The cardiovascular system develops at the beginning of week three during prenatal life. The development of the primitive heart starts with a horseshoe-shaped structure called the primary heart field, which has a pair of tubes that fold so that the heart structures will be in the proper position. Next, septa appear, which help to partition the heart into two atria and two ventricles.
The electrical conduction system of the primitive heart initially lies in the sinus venosus. As the sinus venous becomes absorbed by the right atria, the pacemaker cells appear in the sinoatrial node in the right atrium wall. The development of blood vessels involves the endothelium, which undergoes a process called angiogenesis, which is the formation of new blood vessels from pre-existing ones. This process is driven by growth factors such as VEGF (vascular endothelial growth factor).
The cardiovascular system starts developing at the beginning of week 3 of development. At that point, the embryo is a flat little pancake made up of two layers - the epiblast on the dorsal, or back side, and the hypoblast on the ventral, or front side.
A line called the primitive streak appears on the epiblast back of this two-layered creature. Cells migrate along the primitive streak during gastrulation, giving rise to a three layered embryo pancake, with each layer containing germ cells that form organs and tissues of the body.
The heart derives from a part of the mesoderm called the visceral mesoderm. Ok, so now let’s look at this 3 week old creature from above.
Mesoderm cells go through the primitive streak and make their way up to the embryo’s head. Forming an area that’s called the primary heart field, a horseshoe-shaped area that has two limbs - one on either side of the future brain.
This region lies on a blanket of endoderm cells which secrete vascular endothelial growth factor - or VEGF, for short. VEGF signals the cells in the limbs of the horseshoe to self-organize into two heart tubes.
A primitive pericardial cavity also appears lateral to each endocardial tube. At its inferior end, each endocardial tube connects to a vitelline vein, which comes from an extraembryonic tissue called the yolk sac and through which blood enters the endocardial tube.
Blood exits each endocardial tube at its superior end through a dorsal aorta, which then continues down the embryo’s back.
During lateral folding, the flat embryo goes from a trilaminar disc to a more cylindrical shape. The lateral borders of the embryo reach out towards each other - like a self-hug - and meet anteriorly at the midline, forming a cylindrical shape.
This process makes the two endocardial tubes fuse into one - forming the primitive heart tube. The left and right vitelline veins also fuse to form the sinus venosus, which is the inflow tract of the heart tube.
Similarly, the aortae fuse to form the aortic sac, which is the outflow tract of the heart tube. The two pericardial cavities also unite around the heart tube and form the singular pericardial cavity.
The heart tube remains attached to the back wall of the pericardial cavity by a sheet of mesoderm called the dorsal mesocardium.
The heart tube itself has two layers: an endothelial lining on the inside which turns into the endocardium, and cardiac myoblasts on the outside, that give rise to the myocardium.
Some of the myocardial cells in the sinus venosus begin to produce a rhythmic electrical discharge at this early stage - however, the conduction system and working myocardium are still underdeveloped, and they can’t contract in perfect sync, so we don’t hear the familiar lub-dub at this point.
During craniocaudal folding, now cylindrical embryo curves down its length, forming more of a shrimp-like creature, and this process pushes the heart tube down towards the chest.
By the beginning of week 4, the heart tube reaches the thorax, and blood can be seen going through the heart tube. The heart tube develops sections.
First there’s the sinus venosus, which has a left and a right sinus horn that bring blood in. Above it, there’s the primitive atrium and then the primitive ventricle - which are separated from one another by the atrioventricular sulcus.
The primitive atrium gives rise to the left and right atria, and the primitive ventricle forms the left ventricle. The primitive ventricle is separated from the next region, called the bulbus cordis, by the bulboventricular sulcus.
The first part of the bulbus cordis forms the right ventricle, as well the outflow tracts for both ventricles. Finally, at the top of the heart tube, there’s the truncus arteriosus, which pumps blood through the aortic sac into an early version of the circulatory system made up of aortic arches.
This organization of structures doesn’t mirror the adult heart, so during week 4 the heart tube undergoes looping - which is a fancy way of saying the tube becomes longer, its walls become thicker and sections of the heart move around so that they end up in their right place.
The heart tube is held in place inside the pericardial cavity by blood vessels at both ends - so looping starts with the heart tube folding into a “C” shape.
The truncus arteriosus and bulbus cordis move down and to the right to form the top portion of the “C”, while the primitive ventricle bends to the right of the midline and a little to the front, forming the middle of the “C”.
Finally, the primitive atrium and sinus venosus form the bottom of the “C”, and snuggle deeper inside the pericardial cavity.
As development continues, the growing ventricle moves to the left, so it crosses over the midline again, covering the primitive atrium.
By the end of week 4, the cardiac loop starts to take on the general appearance of the adult heart. Also, by this point, visceral pericardium also attaches to the outside of the heart forming the epicardium.
However, on the inside, the definitive cardiac chambers have yet to partition. Taking a slice and looking at the heart from another angle, we can see the primitive atria and the primitive ventricle initially communicate through the atrioventricular canal.
On the anterior and posterior walls of the atrioventricular canal, the mesoderm proliferates and forms an anterior and a posterior endocardial cushion.
These cushions grow towards each other and fuse, which in the plane looking straight at the heart, we see this separates the heart into left and right atrioventricular canals.
On the ventricular side of both the right and left atrioventricular canals, endocardial cells proliferate to form the leaflets of the mitral and tricuspid valve, as well as the rest of the valvular apparatus.
This divides the atria from the ventricles. «Inside the atrium, a tissue called the septum primum between left and right atria grows downward, slowly creating two separate chambers by closing a gap called ostium primum, which means the “first opening”.
This septum primum then fuses with the endocardial cushion and closes the gap completely. Meanwhile, a hole appears in the upper area, called the ostium secundum, or “second opening”.
Now, we also have the septum secundum which grows downward just to the right of the septum primum, and covers the ostium secundum like a curtain, leaving a small opening called the foramen ovale, and essentially creating a makeshift valve that allows blood to go from right atrium to left atrium during fetal life.
The ventricles separate when a muscular ridge of tissue grows upward from the apex, or the tip, and then fuses with a thinner membranous region coming down from the endocardial cushions.
And voila—two separate ventricular chambers. Now, if we jump back to the outside of the heart, we see that each of these new chambers is still connected through their outflow tract to the truncus arteriosus, meaning blood just mixes from the two chambers.
The truncus arteriosus begins to divide into the aorta and the pulmonary artery when two endocardial cushions appear on the right-superior and left-inferior walls.
These grow with a spiraling trajectory - imagine a corkscrew - and they wrap around each other, forming the aorticopulmonary septum, that divides the truncus into the roots of the of the aorta and the pulmonary artery, so now blood gets routed to the right place.
and semilunar valves develop short after. The rest of the aorta and the pulmonary artery come from the aortic arches.
The aortic arches only exist briefly between weeks 4 through 6, and they sprout one after another from the aortic sac. There are 5 aortic arches on each side of the sac, and they’re numbered from 1 to 6, because the 5th arch regresses and doesn’t turn into adult structure.
The 1st and the 2nd arch disappear very quickly, but they leave behind the maxillary and the stapedial arteries, respectively, coming off the internal carotid arteries.
The 3rd arch gives rise to the two common carotid arteries and part of the internal carotid arteries. The left 4th arch forms the aortic arch and the right 4th arch forms the right subclavian artery.
The 6th arch forms the pulmonary arteries, and, on the left side, it also forms the ductus arteriosus - a fetal structure through which blood from the pulmonary artery shunts directly into the aorta, bypassing the immature lungs.
Now, rewinding just a tad, looking at our primitive inside of the heart, we can’t forget about the other, venous side of the heart—there’s the sinus venosus, which initially opens in the center of the primitive atrium.
Over time, the sinus venosus becomes asymmetric. It shifts to the right, with the right sinus horn becoming the smooth-walled part of the right atrium, as well as the openings for the superior and the inferior vena cavas.
Meanwhile, the left sinus horn shrinks and persists only as the coronary sinus and the oblique vein of the left atrium. In the wall of the sinus venosus, a special group of myocardial cells organize and synchronize their electrical discharge, forming the sinoatrial node and taking over as cardiac pacemaker near the entrance of the superior vena cava.
Soon after the sinoatrial node has developed, another group of cells located in the atrioventricular septum organizes in the atrioventricular node, the secondary pacemaker center.
At the same time, cells in the interventricular septum differentiate into specialized conducting cells that form the bundle of His.
Cells in the rest of the ventricular myocardium differentiate into conducting cells that form the Purkinje fibers. All right, as a quick recap: the cardiovascular system starts developing from the primary heart field region of the mesoderm during week 3 of prenatal life.
It begins as a horse shoe shaped structure with a pair of tubes that fold and loop around to put the primitive heart structures in the right position.
Afterwards, cardiac septa develop and partition the heart, giving rise to two ventricles and two atria. The conduction system of the heart is initially in the sinus venosus, but when the sinus is absorbed by the right atrium, pacemaker cells become the sinoatrial node in the right atrium wall.
No notes for this video yet
Try adding a note below