Last edited: 9/5/2021

1. DEVELOPMENT OF VASCULAR SYSTEM

Development of Vascular System Medical Editor: Dr. Sofia Suhada M. Uzir

OUTLINE (B) VASCULOGENESIS

Development of blood vessels from mesoderm of
I) BLOOD VESSELS trilaminar disc within the embryo
II) THE HEART TUBE
Developmental process:
III) CROSS SECTION OF EMBRYO
IV) SYSTEMIC CIRCULATION (1) VEGF release
V) VENOUS CIRCULATION
VI) REVIEW QUESTIONS Endodermal tissue releases vascular endothelial growth
VII) REFERENCES factor (VEGF)
→ influence splanchnic layer of lateral plate to proliferate
and differentiate into specific types of tissue
I) BLOOD VESSELS
(2) Proliferation and differentiation phase
(A) STRUCTURES OF THE TRLIMANIR DISC
(i) Endothelial cells
Mesoderm (mesenchymal cells)
o VEGF causes the cells to proliferate and differentiate
→ some areas start specializing and forming tubes
lined by angioblast
Angioblast will give rise to endothelial cells:
o Endothelium
 Lining the blood vessels
Figure 1. The structures of trilaminar disc o Endocardium
Cross section through the embryo around the third week  Line heart cavity
which shows the trilaminar disc composing of:
(ii) Formed elements
(1) Ectoderm
Some mesoderm form hemocytoblast cells inside the
Dorsal part tube which move through the tube
Amniotic cavity above it → this will develop into RBC, WBC and platelets
(2) Mesoderm (formed elements) → move through blood vessels and
heart
Parts of the mesoderm
(3) Canalization
(i) Paraxial mesoderm Tubes formed will connect (canalize between one
Which separates into blocks of cells called somites another) → make one long tube → blood vessel with
formed elements moving inside of it
(ii) Intermediate mesoderm
(C) ANGIOGENESIS
Develops into the gonads & urinary system
Blood vessels made sprout more blood vessels
(iii) Lateral plate mesoderm
Structures of the lateral plate mesoderm include: Remember:
o Intraembryonic coelom in between the two plates Vasculogenesis
o Somatic layer of lateral plate o Mesoderm developed into blood vessels
 Moves with the ectoderm and around the Angiogenesis
amniotic cavity o Blood vessels made from blood vessels
o Splanchnic layer of lateral plate
 Involves in development of cardiovascular
system
 Moves with the endoderm and around the yolk
sac
(3) Endoderm
Gives way to the gut tube: Figure 2. Vasculogenesis vs angiogenesis
o Foregut
o Midgut
o Hindgut
o Pharyngeal apparatus
Ventral part
Yolk sac below it
(4) Neural tube
In between the mesoderm
(5) Notochord
Below the neural tube

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 II) THE HEART TUBE III) CROSS SECTION OF EMBRYO

Endoderm release VEGF → lateral mesoderm At the level of aortic sac

proliferates and differentiates forming Will show structures including the:
o 2 heart tubes/blood vessels at the front o Developing arterial system
 undergo folding process → fusion of the 2 tubes o Aortic sac
o 2 dorsal aortae behind the heart tube o Dorsal aortae
 Undergo folding → fusion o Ectoderm
o Endoderm which will develop into gut tube
(A) LATERAL PLATE FOLDING  Foregut
Folding causes all the layers to come together and  Midgut
make cylindrical shape  Hindgut
o Heart tubes become 1 which also gives the blood  Primitive pharynx with the pharyngeal apparatus
vessels • The highest part of the gut tube
o Dorsal aorta comes off the heart tube and move o Neural tube
backwards into 2 dorsal aortae → fuse together as it o Notochord
moves down the embryo

Figure 5. Embryonic cut section

(A) PHARYNGEAL ARCH

Structures of the upper part of pharyngeal arch include:
o Pharyngeal pouches
 The inner part
o The arches
Figure 3. Lateral plate folding  Mesoderm around the pharyngeal pouches
(B) PARTS OF HEART TUBE o Clefts/grooves
 Ectoderm forming the outer part of the pharyngeal
From the below upwards: arch
o Sinus venosus with the inflow tracts, drain the
 Cardinal veins
 Umbilical veins
 Vitelline veins
o Primitive atria
o Primitive ventricle
o Bulbus cordis Figure 6. Structures of pharyngeal arch
o Truncus arteriosus
o Aortic sac which moves backwards into the dorsal
aortae

Figure 4. The heart tube and its structures

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 (B) AORTIC ARCH

(i) Angiogenesis
Blood vessels bridging to the dorsal aorta
o Aortic sac makes blood vessels which reach the
pharyngeal arches
o Pharyngeal arches which are mesoderm make blood
vessels reaching to the dorsal aorta
This is formed at multiple levels → making a total of 6
aortic arches
The 5th doesn’t form or if it does, it regresses quickly

(ii) Arteries developed from the arches:

1 aortic arch
st

o Maxillary artery
2nd aortic arch
(C) MAJOR BLOOD VESSELS
o Hyoid artery → will developed into stapedial artery
(very rare to exist in humans, only 10%)
3rd aortic arch
o Common carotid arteries, and proximal part of
internal carotid arteries
4th aortic arch
o The right arch will form the right subclavian artery
and parts of brachiocephalic artery
o The left arch will form the aortic arch after the
brachiocephalic artery
 Which is from the left common carotid until the
left subclavian
• Subclavian arteries supply the arms Figure 8. The major blood vessels
• Aortic arch continues downwards into (i) Pulmonary trunk
descending aorta → abdomen reaching the
common iliac arteries → external iliac arteries From truncus arteriosus → splits into pulmonary
supplying the lower limbs arteries
o Right pulmonary artery
6th aortic arch
o Left pulmonary artery
o The right arch will form the right pulmonary artery
o Left arch will form the left pulmonary artery and Between pulmonary trunk and aorta is the ductus
ductus arteriosus arteriosus of the embryo

(ii) Ascending aorta

From truncus arteriosus

(iii) Aortic arch

From the left fourth arch
o Give branch to left and right subclavian and
common carotid arteries
o Goes down to descending aorta → abdomen → lower
limb

Figure 7. The aortic arch

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 IV) SYSTEMIC CIRCULATION

(A) DESCENDING AORTA

The dorsal aortae fuse downwards and supply lower
(2) Progression to an adult circulation
parts of the embryo
The general branches will develop to form the adult
circulation

(i) Dorsolateral branches

Intercostal and lumbar arteries

(ii) Lateral branches

Adrenal/suprarenal arteries supplying the adrenal
glands
o Adrenal sits on the kidneys
Renal arteries → supplying the kidneys
Gonadal arteries supplying the gonads
o Developing embryo have gonads → these later
become ovaries or testicles

(iii) Vitelline artery

Vitelline artery which goes to the yolk sac breaks into 3
Figure 9. Descending aorta of a fetus parts to supply the gut tube
o Celiac artery → supplying the foregut
(1) Beginning of fetal circulation o Superior mesenteric artery → supplying the midgut
Descending aorta goes down the length of embryo and o Inferior mesenteric artery → supplying the hindgut
gives of 4 general branches
o Dorsolateral branches (iv) Common iliac arteries
 From the back Split into internal and external iliac arteries
o Lateral branches o In the internal → have internal iliac arteries
 From the sides  Umbilical arteries descend and come off the
o Vitelline artery internal iliac arteries (Figure 10) → becomes the
 From the center adult remnant of umbilical artery which is the
 Runs into the yolk sac through the vitellin duct medial umbilical ligament
 The vitelline duct connects the embryo to the yolk o Umbilical part that persists → forms the superior
sac vesical artery → supplies the bladder
o Right and left umbilical arteries o External iliac arteries → supply lower limbs
 At the beginning point of branching of the dorsal
aorta

Figure 10. Descending aorta of a fecal development

approaching adult circulation. Note the development of iliac
arteries

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 V) VENOUS CIRCULATION (B) VITELLINE SYSTEM

Remember: (1) Embryonic life

Parts of the heart tube from the below upwards: Vitelline system consists of the right and left veins
o Sinus venosus with the inflow tracts, drain the These form plexus around the GI tract (the right and left,
 Cardinal veins respectively)
 Umbilical veins → move to the liver to give off capillaries called
 Vitelline veins sinusoids (very permeable)
o Primitive atria The blood from the sinusoids drains into hepatic veins
o Primitive ventricle → moves pass the septum transversum (future
o Bulbus cordis diaphragm)
o Truncus arteriosus → to reach sinus venosus
o Aortic sac which moves backwards into the dorsal o This is the right and left hepatocardiac channel
aortae

(A) SINUS VENOSUS Remember:

o Vitelline system connects the yolk sac to the heart

(2) Development to adult life

(i) Left vitelline vein digression

The left vitelline system will start to digress
The right vitelline system will dominate
o More blood goes to the right vein, which then
enlarges in size → capillaries network formed,
taking blood from the spleen and gastrointestinal tract
Figure 11. Cut section of sinus venosus → draining it into the liver feeding both sinusoids
Cut section of the sinus venosus and the inflow tracts  Splenic veins
(Figure 11) will show: • From the spleen
 Superior mesenteric vein
(1) The right side • Upper part of the gut
Right horn gives rise to  Inferior mesenteric vein
o Right posterior cardinal vein • Lower part of gut tube
 Drain blood from the bottom The hepatic portal vein, which combines all the three
o Right anterior cardinal vein veins above → drains the blood into the sinusoids of the
 Drain blood from the top liver
o Right common cardinal vein
 Connecting the two cardinal veins (ii) Hepatic veins formation
→ blood will empty into the right horn → which When the left vitelline vein digresses, the right
empties into the sinus venosus hepatocardiac channel receives blood from the left and
(2) The left side right sinusoids
o This forms the right and left hepatic veins
Left horn gives rise to:
o Left post cardinal vein (iii) Inferior vena cava formation
 from the bottom
When the two hepatic veins combine together → it will
o Left anterior cardinal vein
become the inferior vena cava → this empty into the
 from the top
right horn → sinus venosus → primitive atria which
o Left common cardinal vein
becomes the right atrium
 Connecting the two cardinal veins → blood will
empty into the left horn → which empties into the
sinus venosus
(3) The middle
Umbilical veins
o Medial to the right and left horns respectively
Vitelline system (right and left vitelline veins)
o The most medial portion

Remember:
The right side is dominant in the venous system
o The left sided veins will either shift their supply to the
right side or degenerate

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 (C) UMBILICUS SYSTEM LOWER PART OF VENOUS CIRCULATION
(1) Embryonic life After the degeneration of the posterior cardinal veins,
Placenta gives off right and left umbilical veins three systems will develop
o The right vein will digress From the top to the bottom:
o Supracardinal veins
(i) Ductus venosus o Subcardinal veins
Left umbilical vein reaches the bottom portion of o Sacro-cardinal veins
inferior vena cava, near the liver → this is called the These will drain blood from abdominal cavity and lower
ductus venosus limbs
o It also gives branches to the liver along the way
(1) Supracardinal veins
It is the bridging vein between the left umbilical vein and
the inferior vena cava (i) Intercostal veins
o Ductus venosus have a lot of smooth muscle
Supracardinal veins have branches:
 This enables it to control the blood flow that
o Branches of left supracardinal veins
comes into the circulation
 4,5,6,7
 All the blood that flows to the heart via the
 Which forms the left intercostal veins
umbilical venous circulation, need to go
o Branches of the right supracardinal veins
through ductus venosus before draining into
 4,5,6,7,8,9,10,11
inferior vena cava
 Which form the right intercostal vein
(2) Adult:
(ii) Azygos and hemiazygos
(i) Ligamentum teres Anastomosis happen between the left and right
When the yolk sac degenerate → the whole system supracardinal veins
regress, cutting the umbilical cord o The blood will primarily flow from left to the right
The umbilical vein will become ligamentum teres which draining the respective intercostals → empty into
is an adult remnant that connects around the liver superior vena cava
The right supracardinal vein will become the azygos
(ii) Ligamentum venosum vein
Ductus venosus → becomes fibrotic adult remnant → The left supracardinal vein which shunts the blood to
ligamentum venosum the right will become the hemiazygos

(D) CARDINAL SYSTEM

(2) Subcardinal veins
Remember:
On both sides, left and right: Right and left subcardinal vein have three branches
o Anterior cardinal vein and the posterior cardinal vein which drains the following organs on both sides
connect → forming common cardinal vein which respectively
drains into right/left horn respectively → into sinus o Adrenal glands
venosus o Kidneys
o Gonads
UPPER PART OF VENOUS CIRCULATION
(i) Renal portion of inferior vena cava
(i) Digression of posterior cardinal vein The left subcardinal vein → degenerates
Left anterior cardinal vein → forms shunt connection at The blood from the left side drains into the right
the top to the right anterior cardinal veins subcardinal vein → this forms the renal portion of the
Anything above the shunt will remain intact inferior vena cava
o This drains the head The renal portion of inferior vena cava drains the right
and left adrenal glands, kidneys and gonads
Anything below the shunt → digress
o The blood then drains into the inferior vena cava →
(ii) Superior vena cava right atrium

Right common cardinal vein below the level of (3) Sacro-cardinal veins
anastomosis becomes the superior vena cava In the embryonic life, the sacro-cardinal veins drain the
(iii) Brachiocephalic veins blood from the lower limbs separately (right and left side)

The right anterior cardinal vein at the level and above (i) Lumbosacral portion of the inferior vena cava
the shunt/anastomosis will become the right Development into the adult life, the blood from the left
brachiocephalic vein sacro-cardinal vein will shift to right
The shunt/anastomosis which is form the left side is o Left sacro-cardinal vein will degenerate, at the
now the left brachiocephalic vein portion just above the drainage of the lower limb →
(iv) Internal jugular and subclavian veins shunt into right sacro-cardinal vein
o Right sacro-cardinal which is now the lumbosacral
On the right side, the right brachiocephalic vein is portion of the inferior vena cava receives blood
formed by the confluence of the right subclavian and from the right and left lower limb
internal jugular veins
On the left side, above the shunt (left brachiocephalic
vein) → the left internal jugular and subclavian veins
also drains into the brachiocephalic vein

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 (E) SUMMARY VI) REVIEW QUESTIONS
Hepatic inferior vena cava is derived from the right
1) Which mesodermal layer gives rise to the
vitelline vein
endocardial heart tubes?
Renal portion of inferior vena cava is derived right
a) Paraxial mesoderm
subcardinal vein
b) Somatic mesoderm
Sacral portion/post renal portion of inferior vena cava is
c) Intermediate mesoderm
derived from the right sacro-cardinal vein
d) Splanchnic mesoderm
2) Which heart chamber does the right horn of the
sinus venosus contribute to during development of
the fetal heart?
a) Left atrium
b) Right atrium
c) Right ventricle
d) Common ventricle
3) Which part of the primitive heart tube gives rise to
the pulmonary artery and the aorta?
a) Bulbus cordis
b) Primitive atrium
c) Primitive ventricle
d) Sinus venosus
e) Truncus arteriosus
4) During vascular development, the hepatic portal
venous system arises from:
a) umbilical veins
b) vitelline veins
c) subcardinal veins
d) supracardinal veins
5) The supracardinal veins give rise to
a) Azygos veins
b) Common iliac veins
c) Hepatic veins
d) Suprarenal veins

6) The right brachiocephalic vein is formed from the

a) Supracardinal vein
b) Right common cardinal vein
c) Right anterior cardinal vein
d) Left anterior cardinal vein
7) Regarding ligamentum teres, which is true?
a) It is the adult remnant of ductus venosus
b) It is the bridging vein of left umbilical to inferior vena
cava
c) It is the adult remnant of umbilical vein
d) The persistence into adult life causes death
8) Regarding aortic arch, which is false?
a) There are a total of 6 arches formed
b) 1st arch give rise to mandibular artery
c) 5th arch regresses quickly
d) 4th arch give rise to subclavian artery
9) All of the following are structures forming the heart
tube except
a) Primitive atria
b) Primitive ventricle
c) Bulbus cortical
d) Truncus arteriosus
Figure 12. The venous system
10) Regarding inferior vena cava, which is true?
a) It is the combination of two hepatic portal veins
b) It is the combination of two portal veins
c) It empties into the left horn
d) It is formed from the umbilical system

CHECK YOUR ANSWERS

VII) REFERENCES
Sadler TW. Langman's Medical Embryology. Philadelphia: Wolters Kluwer; 2019.
Le T. First Aid for the USMLE Step 1 2020. 30th anniversary edition: McGraw Hill; 2020.
Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: Pearson; 2020.
Boron WF, Boulpaep EL. Medical Physiology.; 2017.

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