View source for 5. Development of the blood vessels. Malformations

== Learning objectives ==

* From which embryonic tissue does blood and blood vessels develop from?
* Where do the first blood cells of the foetus arise?
* Where do the definitive blood cells originate from?
* What is the first major haematopoietic organ in the foetus, and for how long does it remain as the major organ?
* What is the definite major haematopoietic organ?
* What are the two mechanisms by which blood vessels are formed?
* What is vasculogenesis, and which major vessels are formed by it?
* What is angiogenesis?
* What are the aortic arches?
* List the arteries which derive from the aortic arches
* Which embryonic artery gives rise to the coeliac trunk and superior mesenteric artery?
* Which embryonic artery gives rise to the inferior mesenteric artery?
* Which embryonic artery gives rise to the common and internal iliac arteries?
* Describe the formation of the coronary arteries
* What are the cardinal veins?
* What are the vitelline veins?
* Describe the formation of the portal vein
* Describe the formation of the hepatic sinusoids
* Describe the formation of the inferior vena cava
* Describe the formation of the superior vena cava
* Describe the formation of the azygos and hemiazygos veins
* Name some malformations of the arterial system and describe them
* Name some malformations of the venous system and describe them

== Development of blood and blood vessels ==
Both blood and blood vessels arise from mesoderm. The first blood cells arise in the wall of the yolk sac, but these cells exist only temporarily. The definitive blood cells arise from mesoderm located around the aorta in an area called the ''aorta-gonad-mesonephros'' (AGM) region. These cells will colonize the liver, which acts as the haematopoietic organ up until month 7. After that, these cells migrate to the bone marrow, which takes over as the haematopoietic organ.

Blood vessels form in two ways: by vasculogenesis or angiogenesis.

=== Vasculogenesis ===
Vasculogenesis refers to when vessels arise ''de novo'' from so-called ''blood islands''. Mesoderm cells differentiate into haemangioblasts after binding the growth factor FGF2. Haemangioblasts in the middle of the “island” differentiate into blood cells, while haemangioblasts at the periphery of the island differentiate into ''angioblasts''. The angioblasts eventually form endothelial cells. This forms a tube which will eventually become a blood vessel. VEGF (vascular endothelial growth factor) is the growth factor which induces haemangioblasts to form blood cells and vessels.

=== Angiogenesis ===
Angiogenesis refers to when new vessels sprout off from already existing vessels. After primary vascular beds have been formed by vasculogenesis, additional vessels are added by angiogenesis. This process is also stimulated by VEGF.

== Development of the arterial system ==
The arterial system develops from the dorsal aortae, which are formed by vasculogenesis. The rest of the arterial system develops from these dorsal aortae by angiogenesis. There are initially two dorsal aortae, but the right dorsal aorta will eventually obliterate.

=== Aortic arches ===
Many important arteries in the adult chest and neck develop from the so-called ''aortic arches''. During week 4 and 5 the so-called ''pharyngeal arches'' develop, each of which receive their own cranial nerve and artery, which is the aortic arch. The aortic arches develop from the ''aortic sac''.

The pharyngeal arches and their arteries appear in a cranial-to-caudal sequence, meaning that the most cranial arch is present first and the most caudal one last. This also means that not all arches are present simultaneously.

There are five pharyngeal arches and their aortic arches are numbered I, II, III, IV, and VI. Number V never forms, or it forms incompletely and then regresses. Each aortic arch terminates in the right and left dorsal aortae. Most of each aortic arch eventually obliterates, but a part of them persists to form the final artery. The table below shows which adult arteries originate from which aortic arch.
{| class="wikitable"
!Aortic arch
!Adult artery derivative
|-
|First aortic arch
|Maxillary arteries
|-
|Second aortic arch
|Hyoid and stapedial arteries
|-
|Third aortic arch
|Common carotid and part of the internal carotid
|-
|Left side of the fourth aortic arch
|The aortic arch from the left common carotid to the left subclavian
|-
|Right side of the fourth aortic arch
|Proximal portion of the right subclavian artery
|-
|Left side of the sixth aortic arch
|Left pulmonary artery and ductus arteriosus
|-
|Right side of the sixth aortic arch
|Right pulmonary artery
|}

=== Finishing touches ===
The ''carotid ducts'', the part of the dorsal aortae which lie between the third and fourth arches, are obliterated. The right dorsal aorta, between the point where it fuses with the left dorsal aorta and the point of origin of the seventh intersegmental artery, obliterates. The left seventh intersegmental artery will form the left subclavian artery, while the right seventh intersegmental artery will form the distal portion of the right subclavian artery.

=== Arteries of the gut and the legs ===
The celiac trunk and superior mesenteric artery both form from the ''vitelline arteries'', embryonic vessels which supply the yolk sac. The inferior mesenteric artery forms from the umbilical arteries.

The umbilical arteries also give rise to the common iliac, internal iliac, and superior vesical arteries.

=== Coronary arteries ===
The coronary arteries are derived from the epicardium. Some epicardial cells undergo a transition to mesenchyme, which then form the vessels. The coronary arteries then grow into the aorta, attaching to it.

== Development of the venous system ==
The venous system develops from the cardinal veins, which are formed by vasculogenesis.

=== The cardinal veins ===
The cardinal veins are paired vessels which drain the body of the embryo into the ''sinus venosus'', the structure which will later give rise to part of the right atrium. Initially, there are two anterior and two posterior cardinal veins, one of each on each side. Each pair of anterior and posterior vein on each side join to form a common cardinal vein, which drains into the sinus venosus.

During subsequent weeks (5 – 7) additional cardinal veins are formed. The ''subcardinal veins'', which drain the kidneys, the ''sacrocardinal veins'', which drain the lower extremities, and the ''supracardinal veins'', which drain the body wall. These are also paired.

=== The vitelline veins ===
The vitelline veins drain the yolk sac into the sinus venosus. Before they reach the sinus venosus, they form a venous plexus around the duodenum. This venous plexus eventually develops into a single vessel, forming the portal vein.

As the liver grows it will grow into the vitelline veins, it fragments them to form a vascular “labyrinth”. This will form the ''hepatic sinusoids''.

=== The inferior vena cava ===
During formation of the IVC anastomoses appear between the left and right veins of the cardinal system. Blood is eventually channelled from the left side to the right side, making the right side more dominant. This paves way for the IVC, which lies on the right side.

The adult IVC is formed from many small segments of many different veins of the cardinal and vitelline systems, and anastomoses between them. From caudal to cranial, these are:

* The posterior intercardinal anastomosis
* The caudal portion of the right supracardinal vein
* The right anastomosis between the supracardinal and the subcardinal veins
* A segment of the right subcardinal vein
* The anastomosis between the right subcardinal and right vitelline veins
* The terminal portion of the right vitelline vein

=== The superior vena cava and internal jugular veins ===
The development of the SVC is simpler compared to the IVC. The SVC is formed by the right common cardinal vein and the proximal portion of the right anterior cardinal vein.

The anterior cardinal veins form the internal jugular veins.

=== The azygos and hemiazygos veins ===
The azygos vein is formed by the right supracardinal vein and a portion of the right posterior cardinal vein.

The hemiazygos vein is formed by the left supracardinal vein.

== Relevant malformations ==

=== Malformations of the arterial system ===
A ''[[patent ductus arteriosus]]'' (PDA) is one of the most frequent abnormalities of vessels. It refers to a ductus arteriosus which doesn’t close after birth. This occurs most commonly in premature infants. PDA may occur alone or together with other congenital heart defects. Due to the nature of some of these heart defects, they may actually ''require'' the ductus arteriosus to stay open for the foetus to survive. In these cases, the ductus arteriosus must be kept open by drugs to allow the foetus to survive for long enough that the heart defects can be surgically repaired.

''[[Coarctation of the aorta]]'' refers to a significant narrowing of the aorta distal to the origin of the left subclavian artery.

''Double aortic arch'' occurs when the distal portion of the right dorsal aorta doesn’t obliterate, causing there to be two aortic arches. The second aortic arch, unlike the normal one, travels behind the trachea and oesophagus, compressing these structures.

== Malformations of the venous system ==
''Duplicated inferior vena cava'' refers to the presence of two IVCs. This occurs due to the left sacrocardinal vein not obliterating.

''Absent inferior vena cava'' occurs due to the right subcardinal vein failing to connect to the liver. Instead, the lower body is drained by the azygos vein.

== Summary ==

* From which embryonic tissue does blood and blood vessels develop from?
** From mesoderm
* Where do the first blood cells of the foetus arise?
** In the wall of the yolk sac
* Where do the definitive blood cells originate from?
** From mesoderm in the AGM region
* What is the first major haematopoietic organ in the foetus, and for how long does it remain as the major organ?
** The liver, which is the major haematopoietic organ up until month 7
* What is the definite major haematopoietic organ?
** The bone marrow
* What are the two mechanisms by which blood vessels are formed?
** Vasculogenesis and angiogenesis
* What is vasculogenesis, and which major vessels are formed by it?
** Vasculogenesis is the formation of blood vessels ''de novo'' from blood islands
** Mesoderm differentiate into haemangioblasts, which form blood cells and endothelial cells
** The dorsal aortae and the cardinal veins are formed by vasculogenesis
* What is angiogenesis?
** Angiogenesis is the formation of new vessels from already existing vessels
* What are the aortic arches?
** The aortic arches are arteries of the pharyngeal arches
* List the arteries which derive from the aortic arches
** First aortic arch – Maxillary arteries
** Second aortic arch – Hyoid and stapedial arteries
** Third aortic arch – Common carotid and part of the internal carotid
** Left side of the fourth aortic arch – The aortic arch from the left common carotid to the left subclavian
** Right side of the fourth aortic arch – Proximal portion of the right subclavian artery
** Left side of the sixth aortic arch – Left pulmonary artery and ductus arteriosus
** Right side of the sixth aortic arch – Right pulmonary artery
* Which embryonic artery gives rise to the coeliac trunk and superior mesenteric artery?
** The vitelline arteries
* Which embryonic artery gives rise to the inferior mesenteric artery?
** The umbilical arteries
* Which embryonic artery gives rise to the common and internal iliac arteries?
** The umbilical arteries
* Describe the formation of the coronary arteries
** Cells of the epicardium undergo a transition to mesenchyme, which forms vessels which will grow into the aorta
* What are the cardinal veins?
** The cardinal veins are paired vessels which drain the embryo into the sinus venosus
* What are the vitelline veins?
** The vitelline veins drain the yolk sac into the sinus venosus
* Describe the formation of the portal vein
** The portal vein is formed from a venous plexus which originates from the vitelline veins and lies around the duodenum
* Describe the formation of the hepatic sinusoids
** The hepatic sinusoids are formed as the liver grows into the vitelline veins, fragmenting them into sinusoids
* Describe the formation of the inferior vena cava
** The IVC is formed from many small segments of veins of the cardinal and vitelline systems and anastomoses between them
* Describe the formation of the superior vena cava
** The SVC is formed by the right common cardinal vein and the proximal portion of the right anterior cardinal vein
* Describe the formation of the azygos and hemiazygos veins
** Azygos is formed by the right supracardinal vein and a portion of the right posterior cardinal vein
** Hemiazygos is formed by the left supracardinal vein
* Name some malformations of the arterial system and describe them
** Patent ductus arteriosus refers to a ductus arteriosus which doesn’t close after birth
** Coarctation of the aorta refers to a significant narrowing of the aorta distal to the origin of the left subclavian artery
** Double aortic arch occurs when the distal portion of the right dorsal aorta doesn’t obliterate, causing there to be two aortic arches
* Name some malformations of the venous system
** Duplicated IVC
** Absent IVC

[[Category:Embryology]]