DEVELOPMENT OF VASCULATURE

Learning Objectives

Compare and contrast vasculogenesis and angiogenesis.

Vasculogenesis (de novo blood vessel formation) commences in the splanchnic

mesoderm of the embryonic disc and continues later in the paraxial mesoderm.
Differentiated endothelial precursor cells (EPCs), or angioblasts, organize into small
vessels that coalesce, grow, and invade other tissues to form the primary embryonic
vasculature. This primitive vasculature is expanded and remodeled by angiogenesis
(budding and sprouting of existing blood vessels). Angiogenesis is the expansion and
remodeling of the vascular system using existing endothelial cells and vessels generated
by vasculogenesis. Expansion by angiogenesis occurs by sprouting or vascular
intussusception, a splitting or fusion of existing blood vessels.

Hematopoiesis begins in the yolk sac extraembryonic mesoderm. It is later shifted to the
liver, where the embryonic hematopoietic cells are joined by a source of definitive
hematopoietic stem cells (HSCs) arising from intraembryonic splanchnic mesoderm.
Definitive HSCs are programmed from hemogenic endothelium, colonize the liver where
they are expanded, and later relocate to the bone marrow and other lymphatic organs.

By the end of the embryonic period, the yolk sac no longer serves as an erythropoietic
organ. Intraembryonic organs - specifically the liver, spleen, thymus, and bone marrow -
supply erythrocytes and other lineages of mature blood cells to the circulation.

Describe the formation of the aortic arch arteries and their derivatives.

The aortic arch arteries arise from the aortic sac, an expansion at the distal end of the
cardiac outflow tract. Dorsally, they connect to the left and right dorsal aortae. The first
two arch arteries regress as the later arches form.

1st arch pair: portion of maxillary arteries

2nd arch pair: portion of stapedial arteries

3rd arch: R and L common carotid arteries and the proximal portion of R and L internal

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carotid arteries

4th arch: L side becomes part of arch of aorta and R side becomes proximal portion of R
subclavian artery
Aortic sac connected to the R fourth artery is modified to form the branch of the
developing aorta called the brachiocephalic artery

6th arch: L sixth forms the ductus arteriosus, which later becomes the ligamentum
arteriosus and R sixth disappears
This asymmetrical development is why the R and L recurrent laryngeal arteries
run differently
Originally arise below level of sixth arch artery and cross under them to
innervate the larynx - which later moves cranially
L recurrent laryngeal nerve becomes caught under sixth arch artery on L
side and remains looped under ligamentum arteriosum
R recurrent laryngeal nerve becomes caught under fourth aortic arch
artery, which forms part of R subclavian artery

Left 7th intersegmental artery: forms the L subclavian artery

Pulmonary arteries develop as branches of the fourth aortic arch artery and then
establish a secondary connection with the sixth aortic arch arteries before losing their
connection with the fourth aortic arch arteries
Pulmonary arteries are combination of L sixth aortic arch and a portion from the
arteries growing in from the bronchial buds

The paired dorsal aortae remain separate in the region of the aortic arch arteries, but
eventually fuse to form a single median dorsal aorta, which develops three sets of
branches: (1) a series of ventral branches, which supply the gut and gut derivatives
derived from the remnants of a network of vitelline arteries - basically the celiac trunk,
superior mesenteric artery, and inferior mesenteric artery; (2) lateral branches, which
supply retroperitoneal structures such as the suprarenal glands, kidneys, and gonads -
conveyer belt of vasculature that follows kidneys as they ascend and the gonads as the
descend; and (3) dorsolateral intersegmental branches called intersegmental arteries - in
thoracic region are intercostal arteries, lumbar region are lumbar and lateral sacral
arteries.

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List the vessels that give rise to the various portions of the inferior caval vein.

Structures making up the inferior caval vein from superior to inferior:

(1) R vitelline vein gives rise to the terminal segment
(2) R subcardinal vein gives rise to segment between liver and kidneys
(3) R supracardinal vein gives rise to abdominal segment inferior to kidneys
(4) R and L posterior cardinal veins + median anastomosis connecting them
give rise to the sacral segment

Compare and contrast the circulatory systems in the fetal and neonatal periods.

Fetal circulation:
Oxygenated blood comes from the placenta and enters the body through the
umbilical vein (some of which goes through hepatic circulation - portal vein
enters liver and hepatic vein drains to IVC)
L umbilical vein has a ductus venosus which connects directly to the IVC and
bypasses the hepatic circulation
IVC brings blood to R atrium
Blood is largely shunted from R atrium to L atrium
L atrium to L ventricle
Oxygenated blood in L ventricle is them propelled into aorta for systemic
distribution
Small blood vessel connects pulmonary artery and aorta called the ductus
arteriosus - shunts blood from higher pressure pulmonary artery to lower
pressure aorta - this blood mainly originated from SVC
Blood delivered to the head, neck, and arms is more oxygenated than the
blood delivered to the trunk and lower limbs
Each internal iliac artery gives rise to an umbilical artery that brings
deoxygenated blood to the placenta

Changes when infant takes first breath:

Spontaneous constriction of the umbilical vessels cuts off the flow from the
placenta
Opening of the pulmonary circulation and the cessation of umbilical flow create
changes in pressure and flow that cause the ductus arteriosus to constrict and the
foramen ovale to close

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 Initial closing of foramen ovale is due to reduced pressure in right atrium and
increased pressure in left atrium - forces flexible septum primum against the
more rigid septum secundum
Ductus venosus also closes soon after birth

Apply your knowledge of normal vascular development to describe the embryonic basis for
common congenital vascular malformations.

Abnormal origin of R subclavian artery occurs when the R fourth aortic arch and the R
dorsal aorta superior to seventh intersegmental artery abnormally regresses. The R
subclavian artery then lies on the L side just inferior to the L subclavian artery. The R
subclavian artery must therefore cross the midline posterior to the trachea and
esophagus to supply the R arm - may cause constriction of the trachea or esophagus, but
is generally not clinically significant.

Double aortic arch occurs when an abnormal R aortic arch develops in addition to a left
aortic arch due to persistence of the distal portion of the R dorsal aorta. This forms a
vascular ring around the trachea and esophagus, which causes difficulties in breathing
and swallowing.

Right aortic arch occurs when the entire right dorsal aorta abnormally persists and part
of the L dorsal aorta regresses. The R aortic arch may pass anterior or posterior to the
esophagus and trachea. A retroesophageal R arch may cause difficulties in swallowing
and breathing.

Patent ductus arteriosus (PDA) occurs when the ductus arteriosus (a connection
between the L pulmonary artery and aorta) fails to close. The ductus arteriosus normally
undergoes functional closure within a few hours after birth via smooth muscle
contraction to ultimately form the ligamentum arteriosum. A PDA causes a left to right
shunting of oxygen-rich blood from the aorta back into the pulmonary circulation.

Double inferior vena cava occurs when the left supracardinal vein persists, forming an
additional inferior vena cava below the level of the kidneys

Left superior vena cava occurs when the left anterior cardinal vein persists, forming a
superior vena cava on the left side. The right anterior cardinal vein abnormally
regresses.

Double superior vena cava occurs when the left anterior cardinal vein persists, forming

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a superior vena cava on the left side. The right anterior cardinal vein also forms a
superior vena cava on the right side.

Absence of the haptic portion of the inferior vena cava occurs when the right vitelline
vein fails to form a segment of the inferior vena cava. Consequently, blood from the
lower part of the body reaches the right atrium via the azygos vein, hemiazygos vein,
and superior vena cava.