Early development of the cardiovascular system

Overview

The cardiovascular system is the first functional organ system to develop in the embryo. Its development begins around day 18–19 (third week of embryogenesis), and the heart starts to beat by day 22–23.

As diffusion becomes insufficient for nutrient and gas exchange, the embryo establishes a circulatory system to ensure oxygen and nutrient transport.

1. Formation of Blood and Blood Vessels

Vasculogenesis and Angiogenesis

• Vasculogenesis is the de novo formation of blood vessels from angioblasts, derived from mesodermal cells.
• Angioblasts appear in the extraembryonic mesoderm (yolk sac, connecting stalk, chorion) and in the intraembryonic splanchnic mesoderm.
• They aggregate to form blood islands, which differentiate into endothelial cells lining primitive vascular channels.
• Hemangioblasts, present in blood islands, are common precursors of both endothelial and hematopoietic cells.
• Angiogenesis is the subsequent growth and branching of vessels from pre-existing ones by budding and sprouting.

Early Blood Formation

• The yolk sac is the first site of blood formation (3rd week).
• Later, hematopoiesis shifts to: liver (6th week), spleen, and bone marrow (6th month onward).

2. Development of the Heart

Origin and Formation

• The heart originates from splanchnic mesoderm in the cardiogenic area, located anterior to the neural plate.
• Endocardial heart tubes form via vasculogenesis.
• During lateral folding of the embryo, the paired tubes fuse in the midline to form a single primitive heart tube.

Primitive Heart Tube Structure (caudal → cranial)

1. Sinus venosus - receives venous blood from embryo, yolk sac, and placenta.
2. Primitive atrium - gives rise to right and left atria.
3. Primitive ventricle - mainly forms the left ventricle.
4. Bulbus cordis - forms the right ventricle and outflow tracts.
5. Truncus arteriosus - forms the ascending aorta and pulmonary trunk.

3. Heart Folding and Looping

Folding of the heart tube

Between day 23–28, the straight heart tube undergoes dextral (rightward) looping.

This positions the atrial region dorsally and cranially relative to the ventricles, establishing the spatial arrangement of the heart chambers.

4. Partitioning of the Heart (Weeks 4–8)

Heart - septa formation

Atrial Septation

• Septum primum grows downward toward the endocardial cushions, leaving the foramen primum.
• Before closure, foramen secundum forms in the upper part of septum primum.
• Septum secundum forms to the right, leaving the foramen ovale for fetal right-to-left shunting.

Ventricular Septation

• Muscular interventricular septum grows upward from the floor of the ventricle.
• The membranous part closes later via endocardial cushions and the aorticopulmonary septum.

Outflow Tract (Aorticopulmonary) Septation

• Aorticopulmonary (spiral) septum forms from neural crest-derived cells, dividing the truncus arteriosus into the aorta and pulmonary trunk.

5. Development of Major Blood Vessels

Aortic Arches

• Aortic sac gives rise to six paired aortic arches connecting the truncus arteriosus to the dorsal aortae.
• Remodeling forms major arteries:
  • 3rd arch → Common carotid arteries.
  • 4th arch → Aortic arch (left side), right subclavian (right side).
  • 6th arch → Pulmonary arteries and ductus arteriosus.

Venous System

• Cardinal veins drain the embryo.
• Vitelline veins form hepatic and portal veins.
• Umbilical veins carry oxygenated blood from placenta.
• Remodeling forms the systemic venous circulation (e.g. SVC, IVC).

6. Fetal Circulation and Postnatal Changes

Fetal circulatory system

Main Fetal Shunts

• Ductus venosus- bypasses hepatic circulation.
• Foramen ovale- allows right-to-left shunting.
• Ductus arteriosus- connects pulmonary artery to descending aorta.

Changes in circulation after birth

After Birth

• Lungs expand → pulmonary circulation increases.
• Foramen ovale closes (↑ left atrial pressure).
• Ductus arteriosus constricts (functional closure within hours).
• Ductus venosus closes → ligamentum venosum.

7. Summary Timeline

Week	Event
3	Cardiogenic field and blood islands form
3-4	Fusion of endocardial tubes → primitive heart tube
4	Heart begins to beat (day 22–23)
4-5	Heart looping
5-8	Septation of chambers and great vessels
6 onwards	Liver becomes main hematopoietic organ
Birth	Closure of fetal shunts

8. Clinical Correlations

• Atrial septal defect (ASD): incomplete closure of foramen ovale.
• Ventricular septal defect (VSD): failure of membranous septum to form.
• Transposition of great arteries: abnormal spiral septum formation.
• Persistent truncus arteriosus: failure of truncus to divide.
• Patent ductus arteriosus (PDA): ductus arteriosus remains open.

Sources

• Langman’s Medical Embryology, 15th edition.
• Moore, Persaud & Torchia, The Developing Human, 12th edition.
• Thieme Atlas of Embryology.
• Netter’s Atlas of Human Embryology.
• Sadler, Embryology of the Heart.