At the beginning of 4th week of development, heart is a continuous and valveless linear tube that resembles a chicken hung upside-down. It consists of 5 embryonic dilatation, that are destined to be the inflow and outflow tract and compartments of the hear without septum and valves.
From cranial to caudal, these dilations are:
- Truncus arteriosus (arteries)
- Ascending aorta
- Pulmonary trunk
- Distal end dilates to form aortic sac which divides into right and left limbs. Each limb is connected to corresponding dorsal aorta through 6 aortic arches.
- Bulbus cordis
- Smooth part of left (conus arterious) antd right ventricles (aortic vestibule)
- Primitive ventricle
- Trabeculated part of left and right ventricles
- Primitive atrium
- Trabeculated part of left and right atrium
- Sinus venosus
- Right – smooth part of right atrium (sinus venarum)
- Left – coronary sinus
- Oblique vein of left atrium
Smooth part of left atrium is formed by primitive pulmonary veins.
Crista terminalis: Junction of the trabeculated and smooth parts of the right atrium
- The heart tube grows and starts to bend to the right at day 22 and is completed by the end of 4th week (day 28)
- Retinoic acid is thought to act as a signal for antero-posterior values in heart development.
- Looping depends on the laterality inducing genes.
- Looping aligns the future atria, ventricles, inflow and outflow tract.
- During this process, the proepicardial cells invest the outer layer of heart tube and eventually form epicardium and coronary vasculature.
- Here, we will use the analogy of inverted sit ups to imagine how the looping occurs and how it positions the embryonic dilations of heart tube.
Timeline of Other Important Events
|Normal Time||Developmental Events||Malformations arising during period|
|Mid 3rd week||Horseshoe-shaped cardiac primordium appears.|
2 Endocardial tubes form on either side of neural plate.
|20 days||Bilateral Endocardial tubes fuse to form a single heart tube.||Cardiac bifida (experimental)|
|Cardiac jelly appears.|
|Aortic arch is forming.|
|22 days||Heart is looping into S shape.||Dextrocardia|
|Heart begins to beat.|
|Dorsal mesocardium is breaking down.|
|Aortic arches I and II are forming.|
|24 days||Atria are beginning to bulge.|
|Right and left ventricles are likely to pump in series.|
|Outflow tract is distinguished from right ventricle.|
|Late week 4||Sinus venosus is being incorporated into right atrium. Sinus venosus receives 3 sets of veins on either horns:||Venous inflow malformations|
|Endocardial cushions appear. Endocardial cushions are derived from:|
Once, EMT has occured, both types of cells proliferate and invade the Cardiac Jelly, to form the endocardial cushions.
Sox9 plays an important role in endocardial cushion formation.
|Persistent common atrioventricular canal|
|Septum primum appears from primitive atrial roof between right and left atria.||Common atrium (Cor triloculare biventriculare):|
|Muscular interventricular septum is forming from the floor of primitive ventricle.||Common ventricle|
|Truncoconal ridges are forming.||Persistent trucus arteriosus|
|Aortic arch I is regressing.|
|Aortic arch III is forming.|
|Aortic arch IV is forming.|
|Early week 5||Endocardial cushions are coming together, forming right and left atrioventricular canals.||Persistent atrioventricular canal.|
|Sinoatrial orifice shifts to right:|
|Further growth of interatrial septum primum and muscular interventricular septum occurs.||Muscular ventricular septal defects|
|Truncus arteriosus is dividing into aorta and pulmonary artery.||Transposition of great vessels:|
Tetralogy of Fallot:
|Atrioventricular bundle is forming; there is possible neurogenic control of heartbeat.|
|Pulmonary veins are being incorporated into the left atrium.||Aberrant pulmonary drainage|
|Aortic arches I and II have regressed.|
|Aortic arches III and IV have formed.|
| Aortic arch VI is forming.|
|Late week 5 to Early week 6||Endocardial cushions fuse.|| Persistent common AV canal:|
|Interatrial foramen secundum is forming in septum primum.|
|Interatrial septum primum is almost contacting endocardial cushions (for closure of foramen primum).||Low atrial septal defects|
|Membranous part of interventricular septum starts to form.||Membranous ventricular septal defect|
|Semilunar valves begin to form.||Aortic and pulmonary vascular stenosis|
|Late week 6||Interatrial foramen secundum is large.||High atrial septal defects|
|Interatrial septum secundum starts to form.||Foramen secundum defect: Excessive resorption of septum primum or secundum or both. It may be tolerated for a long time.|
|Atrioventricular valves and papillary muscles are forming.||Ebstein’s anomaly:|
Tricuspid atresia (hypoplastic right heart):
|Interventricular septum is almost complete.||Membranous ventricular septal defects|
|Coronary circulation is being established.|
|8-9 weeks||Membranous part of interventricular septum is complete.||Membranous ventricular septal defects|