Development of the vasculature: arterial system

Question 1

Vascular development

Answer 1

starts in the extraembryonic splanchnic mesoderm of the yolk sac at about day 17 in the form of hemangioblastic aggregates developing adjacent the endoderm;

• aggregates appear in the connecting stalk and mesoderm of the chorion; - hemangioblasts enter into the EPC lineage and differentiate into
  endothelial cells;
• organize into small capillary vessels through vasculogenesis; - capillaries lengthen and interconnect;
• by the end of the 3rd week, this network completely vascularizes the yolk sac, connecting stalk, and chorionic villi.

Question 2

Vasculogenesis

Answer 2

On day 18, blood vessels begin developing in the intraembryonic splanchnic mesoderm;

some cells of the splanchnic mesoderm differentiate into EPCs (or angioblasts) that join together to form small vesicular structures;

these coalesce into vessels;

these cords develop throughout the intraembryonic mesoderm.

Question 3

Angiogenesis

Answer 3

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.

Question 4

Angiogenesis

Answer 4

Low oxygen saturation leads to stabilization of the Hypoxia-inducible factor-1α(Hif1α);

this upregulates VegfA expression and Nitric oxide synthase expression;

nitric oxide production dilates existing blood vessels, increasing the permeability;

it leads to proliferation and migration of endothelial cells and increasing extracellular matrix turnover, which is necessary for sprouting.

Proper vascular development also involves trimming away vessels that are no longer necessary.

Question 5

Angioma

Answer 5

formed by proliferating vessels;

• either growth is not inhibited at the appropriate time or stimulated later in life;
• vessels form a tangled mass that may have clinical consequences;
• excessive growth of small capillary networks is called a capillary hemangioma or nevus vascularis;
• a proliferation of larger venous sinuses is called a cavernous hemangioma

Question 6

Hemangioma of infancy

Answer 6

chromosome region 5q31-33;

• some hemangiomas are also linked to disregulation of the Tie/Ang signaling pathway and to
  Vegfr2 mutations;
• these tumors grow rapidly;
• consist mainly of endothelial cells with or without lumens, multilayered basement membranes, and fibrous tissue;
• can be potentially life threatening if they grow in vital organs or are large enough to create a shunt of physiologic significance leading to heart failure.

In rare cases, a hemangiosarcoma (metastatic angioma) can develop.

Question 7

Von Hippel-Lindau disease

Answer 7

a rare, dominantly inherited, familial cancer syndrome (incidence 1:36,000);

• characterized by mutations in a tumor suppressor gene located at chromosome 3p25-26;
• life-threatening multiple CNS, retinal, and liver hemangioblastomas, renal cell carcinomas, and visceral cysts;
• stromal cells of these tumors produce high levels of Vegf and Hif1α.

Question 8

Hereditary hemorrhagic telangiectasia

Answer 8

revalence 1:5000 to 1:8000;

• the most common manifestations are nosebleeds and small vascular anomalies called telangiectases;
• gastrointestinal bleeding and arterial-venous malformations in the lung, brain, and liver progressively develop;
• mutations in Alk1 and Endoglin have been linked to this disease;
• these patients have endothelial cells with a disorganized, abnormal cytoskeleton.

Question 9

Aortic arches

Answer 9

4-5th weeks of development;

• each pharyngeal arch receives its own cranial nerve and artery;
• these arteries, the aortic arches (5 pairs), arise from the aortic sac;
• embedded in mesenchyme of the pharyngeal arches and terminate in dorsal aortae;
• appear in a cranial-to-caudal sequence (not all present simultaneously).

Question 10

The aortic sac:

Answer 10

forms right and left horns;

• these subsequently give rise to the brachiocephalic artery and the proximal segment of the aortic arch.

Question 11

The 1st pair of aortic arches:

Answer 11

formed between days 22-24 and by day 28, most of it has disappeared;

• a small remnants of it persists as a small portions of maxillary artery;
• may also contribute to the formation of the external carotid arteries.

Question 12

The 2nd aortic arch:

Answer 12

• disappears soon (day 29);
• its remaining portions are the
  hyoid and stapedial arteries.

Question 13

3rd aortic arch

Answer 13

formed on day 28;

• forms the common carotid;
• its distal parts join with the dorsal aortae to form the internal carotid arteries;
• the remainder of the internal carotid is formed by the cranial portion of the dorsal aorta;
• the external carotid artery is a sprout of the 3rd aortic arch

Question 14

4th aortic arch

Answer 14

persists on both sides;

• on the left, it forms part of the arch of the aorta, between the left common carotid and the left subclavian arteries;
• on the right, it forms the most proximal segment of the right subclavian artery;
• the distal part of right subclavian is formed by a portion of the right dorsal aorta and the 7th intersegmental artery.

The left subclavian artery forms from the left 7th intersegmental artery

Question 15

5th aortic arch

Answer 15

either never forms or forms incompletely and then regresses

Question 16

The 6th aortic arch (the pulmonary arch):

Answer 16

gives off a branch that grows toward the developing lung bud;

• on the right side, the proximal part becomes the proximal segment of the right pulmonary artery;
• its distal portion loses its connection with the dorsal aorta and disappears;
• on the left, the distal part persists during intrauterine life as the ductus arteriousus

Question 17

Changes from aortic arches

Answer 17

the dorsal aorta between the entrance of the 3rd and 4th arches (the carotid duct) is obliterated;

• the right dorsal aorta disappears between the origin of the 7th intersegmental artery and the junction with the left dorsal aorta;
• cephalic folding, growth of the forebrain, and elongation of the neck push the heart into the thoracic cavity;
• as a result of the caudal shift of the heart and the disappearance of various portions of the aortic arches, the course of the recurrent laryngeal nerves becomes different on the right and left sides.

Question 18

Coarctation of aorta

Answer 18

It is characterized by an aortic constriction of varying length.

Occurs in ≈ 10% of children with congenital heart defects (CHDs);
twice as often in males as in females;
associated with a bicuspid aortic valve in 70% of cases;

most coarctations (90%) occur directly opposite the ductus arteriosis (DA) (juxtaductal coarctation).

In postductal coarctation, the constriction is just distal to the DA.

In preductal coarctation, the constriction is proximal to the DA

Question 19

Double pharyngeal arch artery

Answer 19

rare anomaly;

• characterized by a vascular ring around the trachea and esophagus;
• results from failure of the distal part of the right dorsal aorta to disappear;
• symptoms are the wheezing respirations that are aggravated by crying, feeding, and flexion of the neck;
• usually the right arch of the aorta is larger and passes posterior to the trachea and esophagus

Question 20

Right arch of aorta

Answer 20

Results from the persistence of the right dorsal aorta and involution of the left dorsal aorta.

Right arch of the aorta
without a retroesophageal component: the DA (or ligamentum arteriosum) passes from the right pulmonary artery to the right arch of the aorta (this condition is usually asymptomatic).

Right arch of the aorta with a retroesophageal component: the DA (ligamentum arteriosum) attaches to the distal part of the arch of the aorta and forms a ring, which may constrict the esophagus and trachea.

Question 21

Anomalous right subclavian artery

Answer 21

arises from the distal part of the arch of the aorta;

• passes posterior to the trachea and esophagus to supply the right upper limb;
• results from disappearance the right 4th pharyngeal arch artery and the right dorsal aorta cranial to the 7th intersegmental artery;
• differential growth shifts the origin of the right subclavian artery cranially;
• it comes to lie close to the origin of the left subclavian artery.

Question 22

An interrupted aortic arch

Answer 22

caused by obliteration of the 4th pharyngeal arch on the left side;

• the DA remains open and supplies the descending aorta and left subclavian artery;
• frequently combined with an abnormal origin of the right subclavian artery.

Question 23

Vitelline arteries

Answer 23

a number of paired vessels supplying the yolk sac;

• gradually fuse and form the arteries in the dorsal mesentery of the gut;
• in the adult, they are represented by the esophageal (about 5 pairs), celiac and superior mesenteric arteries;
• supply derivatives of the foregut and midgut.

Question 24

Umbilical arteries

Answer 24

the right and left umbilical arteries develop in the connecting stalk early in the 4th week;

• initially paired ventral branches of the dorsal aorta in the sacral region;
• course to the placenta in close association with the allantois;
• during the 4th week each artery acquires a secondary connection with the 5th pair of the lumbar intersegmental arteries, and loses its earliest origin.

Question 25

Lateral branches of descending aorta

Answer 25

The middle suprarenal arteries develop in situ.

The gonadal arteries arise initially at the 10th thoracic level.

As the gonads (especially the testes) descend, the gonadal arteries elongate and their origin becomes fixed at the 3rd-4th lumbar level.

The renal arteries are formed at the end of an upward migration of the kidneys.

As they migrate, they are vascularized by a succession of transient aortic branches.
These arteries degenerate and are replaced.

Occasionally, a more inferior pair of renal arteries persists as accessory renal arteries.

Question 26

Intersegmental branches

Answer 26

small posterolateral branches;

• arise at the end of the 3rd week by vasculogenesis between the developing somites;
• connect to the dorsal aorta;
• their dorsal branches vascularize the neural tube and the epimeres;
• ventral branches supply the developing hypomeric muscles and associated skin.

Vertebral arteries form as a longitudinal link between intersegmental arteries, loosing their secondary connections to the aorta.

The deep cervical, ascending cervical, superior intercostal, internal thoracic, and superior and inferior epigastric arteries also develop from anastomoses of intersegmental arterie

Question 27

Intersegmental branches

Answer 27

The 5th lumbar intersegmental artery:

• its branches called the internal iliac arteries;
• these vascularize pelvic organs and (initially) the lower extremity limb bud;
• later give rise to the external iliac arteries;
• proximal to these branches, the root of the 5th intersegmental artery is called the common iliac artery

Question 28

Arteries to the upper limbs

Answer 28

the 7th cervical intersegmental forms the axis artery;

• the axis artery develops into the brachial artery of the upper arm and the anterior interosseous artery of the forearm;
• in the hand, a small portion of the axis artery persists as
  the deep palmar arch;
• the other arteries of the upper limb (e.g. radial, median, and ulnar) develop partly as sprouts of the axis artery

Question 29

Arteries to the lower limbs

Answer 29

the axis artery derives from the 5th lumbar intersegmental;

• forms as the distal continuation of the internal iliac artery;
• largely degenerates;
• persists as 3 remnants: the ischiadic artery, a segment of the popliteal artery, and a section of the peroneal artery in the leg;
• the definitive supply is provided almost entirely by the external iliac artery (arises as a new branch of the 5th lumbar intersegmental artery);
• all other arteries develop as sprouts of the external iliac artery