Cardiovascular Embryology

Development of the CVS I

• Integration of heart tube into pericardium:
- Heart tube initially lies above the fluid filled pericardial cavity
- Heart sinks and is enveloped by the pericardium
- The two ends of the pericardium unite as it wraps around the tube, forming the dorsal mesocardium
- Dorsal mesocardium eventually disappears leaving the transverse sinus.
• Over of heart development:
- Sinus venosus: develops into the coronary sinus and smooth wall of the right atrium
- Primitive atrium: forms the right and left trabeculated auricles
- Primitive pulmonary vein: smooth wall of the left atrium
- Primitive ventricle: left and right ventricles
- Bulbus cordis: outflow tracts of both ventricles and proximal aorta and pulmonary trunk
• Sequence of events: the heart tube can be divided into 4 parts – cranial to caudal; bulbus cordis, primitive ventricle, primitive atrium and sinus venosus
- The straight tube lies on the ventral midline with a caudal inlet and cranial outlet through the bulbus cordis
- The tube forms an S shape and the primitive atrium rise dorsally while ventricles sink ventrally
- Atrium migrate further upwards passing behind the bulbus cordis carrying the sinus venosus
- Horns of the SV project laterally and attached to the common cardinal, umbilical and vitelline vein each
- Ventricle sinks so low that it forms the apex of the heart. The interventricular septum begins to form while the atrium begins to form two chambers behind the conotruncus. The horns of SV re-orientate to enter the atrium cranially and dorsally.
- Left horn of SV diminished to form the coronary sinus, and the right horn forms the smooth wall of the right atrium. The BC differentiates into the conus cordis (later forms the outflow tracts of both ventricles) and truncus arteriosus (later forms proximal aorta and pulmonary trunk)
- Spiral ridge appear running lengthwise inside the TA and CC and fuse to form a spiral partition. Left pulmonary vein sprouts from the wall of the left atrium while SVC and IVC sprouts on the right.
- In TA, apoptosis causes the spiral septum to split and aorta and pulmonary trunk become separated. Deep inside the heart, the septum does not split but forms the interventricular septum
- The heart of a full fetus with pulmonary trunk give rise to left and right pulmonary arteries and also ductus arteriosus which transfer blood from the pulmonary trunk into the aorta.
• Fate of Sinus Venosus: Left horn of the SV remains as the coronary sinus. Right horn forms the smooth walled right atrium. The pulmonary veins sprout from the walls of the left atrium and the SVC and IVC derived from parts of the right common cardinal vein and right vitelline vein
• Intussusception: the process of integration (taking up) one part into another, i.e. SV into the walls of the right atrium.
• Development of pulmonary vein: pulmonary vein after sprouting from the wall branches into two branches and then again to four. Later the stem and the two proximal branches are intussuscepted into the wall giving rise to the primitive left atrium. Four pulmonary veins are also formed this way.
• Formation of interatrial septum:
- Downwards growth of a part of the atrial roof forms the septum primum, the first interatrial septum.
- Inferiorly, cardial walls proliferate forming structures called endocardial cushion (right, left, superior, inferior). The superior and inferior cushion will fuse to form the septum intermedium marking the crux of the heart.
- The hole between the septum primum and septum intermedium is called the ostium primum (first opening), and it becomes smaller as the septum primum partition grows
- Apoptosis of the superior portion of the septum primum occurs forming a new opening called ostium secundum (second opening).
- Septum primum fuses with the septum intermedium and completely obliterates the ostium primum.
- From the roof, a second partition starts to grow downwards but does not reach the septum intermedium. This is the thick septum secundum which forms the main muscular interatrial septum in the heart and the hole is called foramen ovale.

Development of CVS II

• Atrial defects: named according to location
- Ostium secundum defect: due to excessive cell death in the septum primum or insufficient growth of the septum secundum so the septum primum is relatively smaller and unable to close the fossa ovale.
- Ostium primum defect: incomplete fusion or insufficient development of the endocardial cushions produce an incomplete septum intermedium. There is a cleft in the one of the mitral valve (more severe)
• Atrial septal defect:
- After birth, resistance to lung is low while right ventricle is thinner and more compliant
- During ventricular filing, left atrium preferentially pumps blood into the RV via the defect and less into the stiff LV.
- The end diastolic volume of RV is 2 or 3 times greater than LV (volume load)
- Pulmonary circuit blood flow is thus 2 to 3 times greater than systemic
• Ventricular septal defect: the most common congenital abnormality with heart with about 12 per 10,000 births. They usually occur in the membranous part of septum and effect depends on size. Small defect may spontaneously close.
- During ejection, LV preferentially pumps blood into the RV due to the low resistance pulmonary as opposed to the high resistant system circuit.
- Blood flow in pulmonary is against 2 to 3 times greater than systemic
• Consequences of septal defect: both defects lead on to greater blood volume in pulmonary circuit. As the pulmonary trunk is anterior to aorta, stethoscope can pick up a rush of blood to the lung
- Pulmonary vessels are tolerant of flow and after years, the arteriole thickens and lumens narrow
- Resistance to blood flow through lungs increases
- Resistance confers an pressure load of the right ventricle
- The above three steps operate in a vicious cycle leading to right ventricular hypertrophy
- Two outcomes: right ventricular hypertrophy can produce either heart failure (death) OR as a result of the incompliance and high RV pressure, the shunt is reversed and systemic blood flow exceeds that of pulmonary blood flow. This would also eventually lead to death due to cyanosis.
- Note: even though the shunt is reversed but the damage on the RV is already done so can’t be reversed.
• Development of interventricular septum
- From the primitive ventricles, the right side dilate rapidly to form the right ventricle
- The area at the “junction” of LV and RV is slow growing and as the two ventricle enlarges, the muscles remains relatively unchanged and hence forming a muscular septum to constrict and separate.
- Septum intermedium moves to the right so that the atria are aligned with the ventricles.
- The gap between septum intermedium and muscular IV septum is filled with the spiral septum that separate the pulmonary trunk from the aorta.
• Division of ventricular outflow:
- Bulbus cordis is the common outflow tract of both ventricles.
- From the walls of the TA and CC, two conotruncal ridges grow out and fuses along the midline and thus dividing the lumen into two
- The plane of fusion however varies at each level in a circular manner thus the result is the two arteries spiralling around each other.
- Spiral septum is derived from neural crest tissue as failure of neural crest cells to migrate into place give abnormalities of the outflow tracts, e.g. straight septum cause transposition of great arteries.

Development of CVS III

• Formation of atrioventricular valves: valves are derived from the wall of the AV canals
- Endocardial cushions forms the walls of the AV canals covered with thick connected tissue and endothelium.
- In the inferior part of the canal muscles, the cardiac muscles undergo apoptosis leaving the endothelium and connective tissue in places forming the future valve leaflets
- Free ends of the leaflet are attached to ventricular walls but later removal of the inferior columns of muscle will form the tendinous cords and papillary muscles
• Formation of semilunar valve:
- Two major swellings, the conotruncal ridges, will form a spiral septum
- When the two arteries separates, minor swellings forms the leaflets of the valves
- The swelling are progressives hollowed out, i.e. muscles removed, leaving only the endothelium and connective tissue to form the cusp.
• Outflow tract abnormalities:
- Tetralogy of fallot: the caudal end of the spiral septum is displaced to the right causing stenosis of the pulmonary trunk and overriding aorta. The muscular septum also fails to contact the muscular IV septum leading to VSD. During birth, stenosis and VSD means RV have a greater load so enlarges.
- Transposition of great arteries: the spiral septum fails to spiral and the aorta is connected to RV while pulmonary trunk to LV. Consequently at birth, oxygenated blood re-circulates through the lung while de-oxygenated blood re-circulates the body. Survival is only possible with mixing, i.e. open fossa ovali.
- Persistent truncus arteriosus: absence of the spiral septum causes the TA to remain undivided as a single vessel leaving the LV and RV.
• Development of vascular system: there are three embryonic circuit
- Intraembryonic: blood is pumped into the aortic arches which feeds into the dorsal aorta and distributed throughout the body. The capillaries are then drained into anterior or posterior paired cardinals.
- Vitelline: blood from dorsal aorta feeds into the vitelline artery that supplies the walls of the empty yolk sac and is drained by vitelline veins directly into the heart.
- Umbilical: modified form of the ancient allantoic circuit. Umbilical arteries branch from dorsal aorta and carry blood to the villi of the placenta. Umbilical veins return oxygenated blood to the heart via the developing liver.
• Fetal circulation: as the lung is non-functional for the fetus, pulmonary circuit is non-existent.
- Function of foramen ovale: Blood from the RA passes directly into the LA via the foramen ovale allowing the left heart to fill and the LV pumps the blood to the systemic circuit
- Function of ductus arteriosus: blood in the RV is pumped into the pulmonary trunk and directly into the aorta via the ductus arteriosus as lung is filled with fluid (high resistant).
• Features of the fetal circulation: Blood is pumped through the left ventricle to head and arms through carotids and subclavian arteries and returned via SVC. Dorsal aorta distributes blood to the lower body and placenta and oxygenated blood returned via the IVC.
- As both the IVC and SVC empty in the RA, deoxy and oxygenated blood will mix
- The best blood is delivered to the developing brain with the supplying artery being the first branch of the aorta
• Changes at birth:
- As the infant takes the first breath the lung inflates with air and pulmonary capillaries expand. Aminiotic fluid is absorbed into the pulmonary circuit and resistance to blood flow decreases.
- Blood from RV now enters the low resistance pulmonary circuit instead of the high resistance systemic through the ductus arteriosus
- Large volume of blood returns from lung to LA and increase LA pressure
- The umbilical vein constricts and venous return from placenta decreases causing overall RA pressure to fall.
- LA pressure exceeds RA pressure and blood attempts to flow to the right causing the flap valve of the foramen ovale to close and separating the two atria.
- Smooth muscles of the ductus arteriosus contracts increase response to the oxygen tension in the blood. With the ductus closed, the pulmonary and systemic circuit are separated fully.
• Aortic co-arctation: narrowing of the descending aorta. As a result collateral vessels enlarge to bypass the obstruction by LV hypertension and heart failure may occur.
- Alternative pathway: aorta, left subclavian, internal thoracic, intercostals arteries and inferior epigastric artery to thoracic aorta and external iliac respectively.

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