DEVELOPMENT OF THE CARDIOVASCULAR SYSTEM

Figure 8: Successive stages in the development of blood and blood vessels. A, Lateral view of the
umbilical vesicle and part of the chorionic sac (approximately 18 days). B, Dorsal view of the
embryo exposed by removing the amnion. C to F, Sections of blood islands showing progressive
stages in the development of blood and blood vessels.
At the end of the second week, embryonic nutrition is obtained from the maternal blood by
diffusion through the extraembryonic coelom and umbilical vesicle. At the beginning of the third
week, vasculogenesis and angiogenesis (Gr. angeion, vessel + genesis, production), or blood
vessel formation, begins in the extraembryonic mesoderm of the umbilical vesicle, connecting
stalk, and chorion. Embryonic blood vessels begin to develop approximately 2 days later. The
early formation of the cardiovascular system is correlated with the urgent need for blood vessels
to bring oxygen and nourishment to the embryo from the maternal circulation through the
placenta. During the third week, a primordial uteroplacental circulation develops. Many cardiac
progenitor cells contribute to the formation of the heart. These include:
Two distinct mesodermal populations of cariac precursor cells
A primary (first) heart field and a second heart field
Neural crest cells

Vasculogenesis and Angiogenesis

The formation of the embryonic vascular system involves two processes: vasculogenesis and
angiogenesis. Vasculogenesis is the formation of new vascular channels by assembly of
individual cell precursors called angioblasts. Angiogenesis is the formation of new vessels by
budding and branching from preexisting vessels. Blood vessel formation (vasculogenesis) in the
embryo and extraembryonic membranes during the third week may be summarized as follows:

Mesenchymal cells (mesoderm derived) differentiate into endothelial cell precursors-

angioblasts (vessel-forming cells), which aggregate to form isolated angiogenic cell
clusters called blood islands, which are associated with the umbilical vesicle or
endothelial cords within the embryo.
Small cavities appear within the blood islands and endothelial cords by confluence of
intercellular clefts.
Angioblasts flatten to form endothelial cells that arrange themselves around the cavities
in the blood island to form the endothelium.
These endothelium-lined cavities soon fuse to form networks of endothelial channels
(vasculogenesis).
 Vessels sprout into adjacent areas by endothelial budding and fuse with other vessels.

Figure 9: Diagram of the primordial cardiovascular system in an embryo of approximately 21

days, viewed from the left side. Observe the transitory stage of paired symmetrical vessels. Each
heart tube continues dorsally into a dorsal aorta that passes caudally. Branches of the aortae
are (1) umbilical arteries establishing connections with vessels in the chorion, (2) vitelline
arteries to the umbilical vesicle, and (3) dorsal intersegmental arteries to the body of the
embryo. Vessels on the umbilical vesicle form a vascular plexus that is connected to the heart
tubes by vitelline veins. The cardinal veins return blood from the body of the embryo. The
umbilical vein carries oxygenated blood and nutrients from the chorion. The arteries carry
poorly oxygenated blood and waste products to the chorionic villi for transfer to the mother's
blood.
 Blood cells develop from the endothelial cells of vessels as they develop on the umbilical vesicle
and allantois at the end of the third week and later in specialized sites along the dorsal aorta.
Blood formation (hematogenesis) does not begin in the embryo until the fifth week. It occurs
first along the aorta and then in various parts of the embryonic mesenchyme, mainly, the liver,
and later in the spleen, bone marrow, and lymph nodes. Fetal and adult erythrocytes are derived
from different hematopoietic progenitor cells (hemangioblasts). The mesenchymal cells
surrounding the primordial endothelial blood vessels differentiate into the muscular and
connective tissue elements of the vessels.

The Primordial Cardiovascular System

The heart and great vessels form from mesenchymal cells in the cardiogenic area. Paired,
longitudinal endothelial-lined channels-the endocardial heart tubes-develop during the third week
and fuse to form a primordial heart tube. The tubular heart joins with blood vessels in the embryo,
connecting stalk, chorion, and umbilical vesicle to form a primordial cardiovascular system. By the
end of the third week, the blood is circulating and the heart begins to beat on the 21st or 23rd day.
The cardiovascular system is the first organ system to reach a functional state. The embryonic
heartbeat can be detected using Doppler ultrasonography during the fifth week, approximately 7
weeks after the last normal menstrual period.

DEVELOPMENT OF VEINS ASSOCIATED WITH EMBRYONIC HEART

In the fifthweek, three pairs of major veins can be distinguished: (a) the vitelline veins, or
omphalomesenteric veins, carrying blood from the yolk sac to the sinus venosus; (b) the umbilical
veins, originating in the chorionic villi and carrying oxygenated blood to the embryo; and (c) the
Common cardinal veins return poorly oxygenated blood from the body of the embryo to the heart

The vitelline veins follow the omphaloenteric duct (yolk stalk) into the embryo. Before entering the
sinus venosus, the vitelline veins form a plexus around the duodenum and pass through the septum
transversum. The liver cords growing into the septum interrupt the course of the veins, and an
extensive vascular network, the hepatic sinusoids, forms.
With reduction of the left sinus horn, blood from the left side of the liver is rechanneled toward the
right, resulting in an enlargement of the right vitelline vein (right hepatocardiac channel). Ultimately
the right hepatocardiac channel forms the hepatocardiac portion of the inferior vena cava. The
proximal part of the left vitelline vein disappears. The anastomotic network around the duodenum
develops into a single vessel, the portal vein. The superior mesenteric vein, which drains the
primary intestinal loop, derives from the right vitelline vein. The distal portion of the left vitelline
vein also disappears.
The umbilical veins run on each side of the liver and carry well-oxygenated blood from the placenta
to the sinus venosus. As the liver develops, the umbilical veins lose their connection with the heart
and empty into the liver. The right umbilical vein disappears during the seventh week, leaving the left
umbilical vein as the only vessel carrying well-oxygenated blood from the placenta to the embryo.
Transformation of the umbilical veins may be summarized as follows:

The right umbilical vein and the cranial part of the left umbilical vein between the liver and
the sinus venosus degenerate.
The persistent caudal part of the left umbilical vein becomes the umbilical vein, which carries
all the blood from the placenta to the embryo.
A large venous shunt-the ductus venosus (DV)-develops within the liver and connects the
umbilical vein with the inferior vena cava (IVC). The DV forms a bypass through the liver,
enabling most of the blood from the placenta to pass directly to the heart without passing
through the capillary networks of the liver.

Initially the cardinal veins form the main venous drainage system of the embryo. This system
consists of the anterior cardinal veins, which drain the cephalic part of the embryo, and the
posterior cardinal veins, which drain the rest of the embryo. The anterior and posterior veins
join before entering the sinus horn and form the short common cardinal veins. During the fourth
week, the cardinal veins form a symmetrical system. During the fifth to the seventh week a
number of additional veins are formed: (a) the subcardinal veins, which mainly drain the
kidneys; (b) the sacrocardinal veins, which drain the lower extremities; and (c) the
supracardinal veins, which drain the body wall by way of the intercostal veins, taking over the
functions of the posterior cardinal veins.
Figure 2: Illustrations of the primordial veins of the trunk in the human embryo (ventral views).
Initially, three systems of veins are present: the umbilical veins from the chorion, the vitelline veins
from the umbilical vesicle (yolk sac), and the cardinal veins from the body of the embryo. Next the
subcardinal veins appear, and finally the supracardinal veins develop. A, At 6 weeks. B, At 7 weeks.
C, At 8 weeks. D, Adult. This drawing illustrates the transformations that produce the adult venous
pattern. (Modified from Arey LB: Developmental Anatomy, revised 7th ed. Philadelphia, WB
Saunders, 1974.)

Figure 3 Dorsal views of the developing heart. A, During the fourth week (approximately 24 days), showing
the primordial atrium and sinus venosus and veins draining into them. B, At 7 weeks, showing the enlarged
right sinus horn and venous circulation through the liver. The organs are not drawn to scale. C, At 8 weeks,
indicating the adult derivatives of the cardinal veins
 The supracardinal veins are the last pair of vessels to develop. They become disrupted in the
region of the kidneys. Cranial to this they become united by an anastomosis that is represented in
the adult by the azygos and hemiazygos veins. Caudal to the kidneys, the left supracardinal vein
degenerates, but the right supracardinal vein becomes the inferior part of the IVC. During the
eighth week, the anterior cardinal veins become connected by an anastomosis, which shunts
blood from the left to the right anterior cardinal vein. This anastomotic shunt becomes the left
brachiocephalic vein when the caudal part of the left anterior cardinal vein degenerates. The
superior vena cava (SVC) forms from the right anterior cardinal vein and the right common
cardinal vein.

Development of the Inferior Vena Cava

The IVC forms during a series of changes in the primordial veins of the trunk that occur as blood,
returning from the caudal part of the embryo, is shifted from the left to the right side of the body.
The IVC is composed of four main segments:

A hepatic segment derived from the hepatic vein (proximal part of right vitelline vein) and
hepatic sinusoids
A prerenal segment derived from the right subcardinal vein
A renal segment derived from the subcardinal-supracardinal anastomosis
A postrenal segment derived from the right supracardinal vein

CLINICAL ANOMALY
Venous System Defects
The complicated development of the vena cava accounts for the fact that deviations from the normal
pattern are common.
A double inferior vena cava occurs when the left sacrocardinal vein fails to lose its connection with
the left subcardinal vein. The left common iliac vein may or may not be present, but the left gonadal
vein remains as in normal conditions.
Absence of the inferior vena cava arises when the right subcardinal vein fails to make its connection
with the liver and shunts its blood directly into the right supracardinal vein. Hence the bloodstream
from the caudal part of the body reaches the heart by way of the azygos vein
and superior vena cava. The hepatic vein enters into the right atrium at the site of the inferior vena
cava. Usually this abnormality is associated with other heart malformations.
Left superior vena cava is caused by persistence of the left anterior cardinal vein and obliteration of
the common cardinal and proximal part of the anterior cardinal veins on the right. In such a case,
blood from the right is channeled toward the left by way of the brachiocephalic vein. The left superior
vena cava drains into the right atrium by way of the left sinus horn, that is, the coronary sinus.
A double superior vena cava is characterized by the persistence of the left anterior cardinal vein and
failure of the left brachiocephalic vein to form. The persistent left anterior cardinal vein, the left
superior vena cava, drains into the right atrium by way of the coronary sinus.