Development of the Heart and Great Arteries

Question 1

Learning outcomes

Answer 1

• Describe the normal development of the chambers and valves of the heart
• Describe the formation of the foramen ovale and the changes that occur at the time of birth that lead to the formation of the fossa ovalis
• Discuss how the complex development of the heart can lead to congenital abnormalities
• Describe what is meant by patent ductus arteriosus
• Describe what is meant by patent foramen ovale
• Describe the complex organisation of the aortic arches and how it relates to the position of the recurrent laryngeal nerves
• Discuss major congenital defects in the heart (ASD, Patent FO, VSD,) and major vessels (Tetralogy of Fallot, Transposition of the great vessels, Patent ductus arteriosus Coarctation of aorta)

Question 2

Discuss the basics of heart defects

Answer 2

(8 in 1,000)
• Causes - genetic and teratogenic
• Effects depend on timing of exposure
• Defects will often be multifactorial
– Rubella virus, social drugs, thalidomide, insulin-dependant diabetes, hypertension
– Genetic syndromes such as Downs, DiGeorge, trisomy 18
– Craniofacial abnormalities are linked to cardiac malformation (neural crest cells)

Question 3

What key features/events should you be aware of in regards to the development of the heart?

Answer 3

• Formation of the 3 germ layers (trilaminar disc): ectoderm; endoderm; mesoderm
• Formation of the primitive heart tube (in the mesoderm)
• Folding and looping of the heart tube
• Septum formation in the common atrium
• Endocardial cushions and the atrioventricular canal
• Septum formation in the ventricles
• Septum formation in the truncus arteriosus
• Growth of atria and ventricles
• Valve formation

Early embryonic development can be sustained by diffusion of nutrients

Question 4

In what process does the bilaminar disc become trilaminar?

Answer 4

gastrulation

Question 5

Describe the process around gastrulation

Answer 5

The bilaminar disc becomes trilaminar (gastrulation) in the early stages of development (only 2 weeks post conception) and the 3 layers are ectoderm; endoderm; and mesoderm that are formed during the 3rd week
The embryo is 1.5 mms long!

Question 6

Discuss the formation of the heart tube

Answer 6

The Heart Tube forms in the mesoderm from angiogenetic clusters, as a horseshoe at the cephalic end of the trilaminar disc

Question 7

When and why does the cardiovascular system develop?

Answer 7

As the embryo grows diffusion is no longer sufficient to provide nutrients and development of both blood and vascular structures becomes necessary
The vascular system is the first system to develop in the embryo
By day 18 there is the beginning of heart development

Question 8

How does the cardiovascular system begin development?

Answer 8

Development begins as angiogenetic clusters coalesce to form a horseshoe in the mesoderm
As a result of folding of the disc the two limbs of the horseshoe fuse to form a single heart tube that lies in the thorax and initially consists of endothelial cells only
The tube has an inflow (venous) and an outflow (arterial) end The trilaminar disc folds in 2 directions

Question 9

In what directions does the trilaminar disc fold?

Answer 9

Ceohalo-caudal and

Lateral folding

Question 10

Describe trilaminar folding in relation to cardiovascular development

Answer 10

Starts towards the end of 3rd week i.e. at about 18 days
Head and tail folds meet 2 lateral folds at umbilicus
The lateral folding swings the 2 limbs of the horseshoe medially so that they fuse as a single heart tube

Question 11

Discuss the early development heart tube

Answer 11

Cephalo-caudal folding causes the heart tube to effectively migrate from the head end of the embryo, through the neck and in to the thorax (note nerve supply). It elongates and develops:
• Epicardium- Visceral pericardium
• Myocardium Cardiac muscle
• Endocardium Endothelial lining

Note the position of the heart tube, and its arterial and venous ends as it elongates and folds or loops (look at diagram)

Question 12

Describe the looping and folding at about 22 days (early week 4)

Answer 12

The 2 “ends” fold towards each other and to the right, pushing the “apex” of the loop to the left, and rotating slightly so that the right side of the heart tends to be more anterior

(If the “ends” fold to the left, the developing heart is pushed to the right - Dextrocardia)

Question 13

What occurs at 28 days?

Answer 13

The developing heart pushes in to the pericardial sac; the ventricles begin to trabeculate

Question 14

Describe the state of the heart at 28 days?

Answer 14

The venous end (inflow) receives blood from the cardinal, umbilical and vitelline veins; it comes to lie behind the arterial end (outflow)
(In the fully developed heart the atria and great veins are behind the ventricles and the roots of the great arteries.)
The atrium bulges out on each side of the bulbus cordis
The proximal part of the bulbus cordis will form the RV The middle part forms the outflow of the ventricles The distal part forms the PT and Aorta
Between the atrium and ventricle is a narrowing - the atrioventricular canal

Septation and Growth must occur next

Question 15

What is the purpose of endocardial cushions?

Answer 15

Bending itself causes narrowing, which is augmented by endocardial cushion growth

Question 16

What are endocardial cushions?

Answer 16

(derived from neural crest cells)
Enlargement of these masses forms the
• interatrial septum
• the membranous part of the interventricular septum
• AV valves (tricuspid and mitral)
• formation of the PT and Aorta from the truncus arteriosus

The tissue in the narrowing between the single atrium and the single ventricle swells to form endocardial cushions
that grow to meet in the middle and divide the atrioventricular canal into right (tricuspid) and left (mitral) channels

Question 17

Go and watch the part of the lecture on atrial separation + take some notes man

Answer 17

+ remember to consider the path of blood flow in the foetal atria and why
(+ so purpose of osmium primum et secundum)

Question 18

Describe a summary of the formation of the interatrial septum

Answer 18

• Septum primum grows down towards the endocardial, atrio- ventricular cushions. Blood passes from RA to LA via the foramen (ostium) primum
• Before the foramen primum closes, perforations appear in the upper part of the septum - develop into the foramen (ostium) secundum
• Septum secundum (stiff, muscular and to the right of S. Primum) grows down, but does not fuse with Endocardial Cushion and forms foramen ovale
• Blood passes from RA to LA thro 2 openings: foramen ovale and foramen secundum
• Formed between weeks 5 and 6, embryo grows from 5 mm to17mm
• At post mortem 10 % of people have a probe patency of the fossa or foramen ovale i.e. anatomically patent but functionally sealed

Question 19

Describe a common atrial septal defect (ASD) as found in infants

Answer 19

• More common in female infants

Patent Foramen Ovale (PFO) (20%) may be asymptomatic
Foramen secundum defect or Foramen primum Probably caused by excessive cell death or resorption of
septum primum
A large opening between the RA and LA leads to significant shunting from left to right
(Sometimes, the interatrial septum is totally absent)

Question 20

Describe the formation of the inter ventricular septum

Answer 20

(complete by end of 7th week)

There are 4 elements (making defects more possible)
Endocardial cushions form left and right ridges in the conus
An extension of the inf. atrio-ventricular cushion will contribute to the membranous portion of the interventricular septum

Proliferation of, and ventricular growth around, forms the muscular portion of the IVS

The left and right truncal ridges spiral and fuse to form the conotruncal septum
(In the adult, the Ao and PT tend to spiral around each other)

The ridges (i.e. septum) advance inferiorly towards the muscular IVS, making the temporary interventricular foramen smaller and smaller; ventricular growth makes the muscular septum effectively advance towards the truncal septum too

Truncal septum formed from left and right spiralling ridges

Truncal septum formed from left and right spiralling ridges
The interventricular foramen is closed by the membranous part of the interventricular septum, derived from the truncal ridges and the inferior atrio-ventricular cushion

Question 21

Describe some common ventriculo-septal defects (VSD)

Answer 21

Most common congenital cardiac malformation
More common in males

1. Persistent trunkus arteriosus (no trunkal ridges)
2. Transposition of the vessels (no spiral to the ridges)
3. Fallot’s tetralogy

Question 22

What is Fallot’s tetralogy?

Answer 22

Where the truncal septum deviates right and does not meet the interventricular septum

Classically there are four resulting defects:

pulmonary stenosis, narrowing of the exit from the right ventricle

a ventricular septal defect, a hole between the two ventricles

right ventricular hypertrophy, thickening of the right ventricular muscle

an overriding aorta, which allows blood from both ventricles to enter the aorta

Question 23

Describe atrial growth

Answer 23

The atria grow, but also need to incorporate the adjacent veins (sinus venosus).
In the right atrium, the crista terminalis marks the change and the original atrium shows muscular ridges (musculi pectinati) while the atrium derived from foetal vein (sinus venosus) is smooth

Question 24

Describe ventricular growth

Answer 24

The two ventricles “balloon” to grow around and away from the muscular septum dividing them

Question 25

Describe the formation of the valves

Answer 25

Mitral and Tricuspid, endocardial cushion growth and cavitation to form papillary muscles and chordae tendineae

Question 26

Formation of the great vessels

Answer 26

Arterial development is intimately associated with the sequential formation of the pharyngeal or gill arches (weeks 4 and 5) that have their own cranial nerve and arterial supplies
Arches give rise to structures in the head and neck
As each pharyngeal arch develops an artery arises from the aortic sac (the part of the truncus arteriosus that will become the Ao), grows through the gill arch and joins the dorsal aorta

1st arch forms maxillary arteries
3rd arch (with dorsal aorta) forms the common carotid arteries
Left 4th arch forms the Sac aortic arch
Right 4th arch forms the right subclavian artery

Development is sequential (earlier arches progressing or resorbing as later ones arise).
The 2nd and 5th arches hardly develop, giving rise to nothing particularly notable
Left 6th arch forms the pulmonary trunk and ductus arteriosus Right 6th arch also contributes to the pulmonary trunk.

Complex system, therefore variation and abnormality

Question 27

Describe a patent ductus arteriosus

Answer 27

Remember from last lecture Postnatally the aortic pressure is greater than PT. Blood will flow back into the pulmonary circulation (continuous “machinery” murmur”)

Question 28

Describe coarctation of the aorta

Answer 28

Aortic narrowing after the origin of the left subclavian due to an abnormality in the aortic media and intimal proliferation
May be proximal or distal to the ductus arteriosus
Postductal is more common and blood travels in the subclavian to internal thoracic to intercostal vessels and back to the thoracic aorta; femoral pulses will be weak

Question 29

Describe recurrent laryngeal nerves

Answer 29

The nerves branch from the vagus nerves and hook around the 6th arch, before “recurring” up to the larynx
On the left, the arch persists as the ductus and ligamentum arteriosus(um), so the RLN is carried in to the thorax
On the right, the 5th and 6th arches regress and the RLN hooks around the 4th arch, i.e. the subclavian artery at the root of the neck, NOT in the thorax

Further illustrations of the left 6th arch remaining as the ductus arteriosus and ligamentum arteriosum, “holding” the left recurrent laryngeal nerve in the thorax
While on the right, both the 5th and 6th arches regress so that the left recurrent laryngeal nerves passes inferior to the 4th arch – right subclavian artery

Question 30

Formative questions lol:

The foetal circulation differs from the post natal circulation. Which embryonic structure is NOT correctly matched with its postnatal derivative?

a. umbilical artery - medial umbilical ligament
b. ductus venosus - ligamentum venosum c. ductus arteriosus - ligamentum teres
d. foramen ovale - fossa ovalis
e. sinus venosus – right atrium

Answer 30

c. ductus arteriosus - ligamentum teres