Development Of The Heart And Great Vessels

Question 1

What are the implications of increased survival to adulthood of congenital heart defects?

Answer 1

When females reach reproductive age and become pregnant, this can be the most common cause of maternal death

Medications used to manage heart disease are highly teratogenic

Question 2

When does the embryo start folding?

Answer 2

During the 4th week of development

Question 3

What are the causes of congenital heart defects?

Answer 3

– genetic

– exposure to chemicals/ drugs / infectious agents

– unexplained

• Additional complexity due to the differing circulatory needs of the fetus as compared to the newborn (mature)

Question 4

Describe the structural features of a primitive heart tube

Answer 4

A tube with:

 Aortic roots
 Truncus arteriosus
 Bulbus cordis
 Ventricle
 Atrium
 Sinus venosus

Surrounded by a pericardial sac

Question 5

What two main things must happen to the primitive heart in order to mature?

Answer 5

1) Divided (to create the 4 chambers)

2) Remodelled (the inflow and outflow vessels must be remodelled)

Question 6

What is cardiac looping and why does it happen?

Answer 6

Looping is when the primitive heart tube bends, twist and folds to fit into the space

It does this because as the tube elongates it runs out of room in the pericardial sac so it must twist and fold up on itself

This is regular and predictable

It places the inflow and outflow in the correct orientation with respect to each other.

Question 7

How does the right atria develop?

Answer 7

• RA develops from:

– most of the primitive atrium

• It is ROUGH!!

– sinus venosus - only uses a small amount of this

– receives venous drainage from the
body (venae cava) and the heart (coronary sinus)

Question 8

How does the LA develop?

Answer 8

• LA develops from:

– a small portion of the primitive atrium

• The fact that it only uses a small amount of the primitive atrium, means that it is smoother than the RA!!

– absorbs proximal parts of pulmonary
veins

– receives oxygenated blood from the
lungs

Question 9

Outline the conflicting circulatory requirements.

Answer 9

Mature Circulation
• Deoxygenated blood collected from the body

• Pumped to the lungs for
reoxygenation and removal of CO2

• Reoxygenated blood returned from
the lungs to the heart

• Pumped around the body

BUTTT!! In the foetus…

1) The lungs do not work so they are totally reliant on Mum’s circulation for gaseous exchange
2) Oxygenation and removal of CO2 occur at the placenta
3) So shunts are required to maintain fetal life
4) These must be reversible at birth because the support from the placenta is removed at birth

Question 10

What happens during fetal circulation?

Answer 10

In foetus, blood with highest partial pressure of oxygen arrives at the umbilicus from the mother travels via umbilical veins through abdomen to liver.

The liver is highly metabolically active during fetal life, and so could consume all oxygen so a shunt is needed to get the oxygen to the inferior vena cava.

The blood with the highest PO2 is in the vena cava.

Blood with high PO2 enters into right atria, so we need to find out a way of getting the blood via the left atrium and into the left ventricle to be pumped to the body.

This is because the vessel that we need to pump blood around the body, is in the left ventricle.

So it needs to be shunted as a means of getting the blood into left atrium and then ventricle and then brain and rest of body. - This is a critical shunt

There is another shunt between aorta and pulmonary trunk, which ensures we push all the oxygenated blood around the body and it doesn’t leak.

Question 11

During fetal circulation, a small amount of blood will pass from the RA to the RV. Why is this?

Answer 11

Because we need to allow the RV to work against something in order to develop during embryonic development.

If you don’t use the muscle, it doesn’t develop so small amount of blood enters the RV to ensure the right development of the right ventricle

Question 12

WHy is it important to by pass the lungs during fetal circulation?

Answer 12

To protect it as it hasn’t developed yet

Question 13

What are the fetal shunts called and where are they?

Answer 13

Ductus Venosus - between placenta and IVC

Foramen ovale - between RA and LA

Ductus Arteriosus - between aorta and Pulmonary trunk

Question 14

When are shunts used and why?

Answer 14

Shunts exist during embryonic and foetal life but it changes after birth because once respiration begins, the LA pressure increases and this causes the Foraman ovale to close

The now relatively high PO2 caused by usage of lungs causes the Ductus Arteriosus to contract and the contraction forces the shunt to close down

Since the placental support has been removed, the Ductus venosus closes too

They all becomes fibrotic and are removed

Question 15

Describe how the aortic arches look like before the heart is remodelled

Answer 15

Early arterial system begins as a bilaterally symmetrical system of arched vessels

The outflow tract of the primitive heart begins in the centre of the symmetrical system

Question 16

How are the 4th and 6th arch remodelled?

Answer 16

The arches disappear and are remodelled

• 4th arch
– R = proximal part of R
subclavian A
– L = arch of aorta

• 6th arch = “pulmonary arch”
– R = R pulmonary artery
– L = L pulmonary artery & Ductus Arteriosus

Question 17

Why is the left recurrent laryngeal nerve recurrent?

Answer 17

The primitive heart starts in the neck because that is where it needs to be.

As the thorax and abdomen of the embryo elongates, it causes a caudal shift in position of heart

It ends up in chest

This creates a tangle with nerves that are associated with the heart

As the heart “descends” the nerve hooks around the 6th aortic arch and “turns back on itself”.

The left recurrent laryngeal nerve becomes hooked around the shunt between the PT & aorta

This explains why hoarse voice is one of the first symptoms of pathology of
thorax - you get impingement of nerve and because of its Innervation of the muscles of the larynx

Question 18

What is Patent Ductus Arteriosus?

Answer 18

Persistent communication between the descending aorta and the pulmonary artery

Caused by failure of physiological closure

Normally ductus arterioles undergoes a spasm and closes but sometimes that doesn’t happen, eg. In premature patients.

Question 19

In PDA which direction will the blood shunt?

Answer 19

Left to right

Question 20

How is the Foraman ovale built?

Answer 20

The foramen ovale forms in the late fourth week of gestation.

Initially the atria are separated from one another by the septum primum except for a small opening in the septum, the ostium primum.

As the septum primum grows, the ostium primum narrows and eventually closes.

Before it does so, bloodflow from the inferior vena cava wears down a portion of the septum primum, forming the ostium secundum.

(Some embryologists postulate that the ostium secundum may be formed through programmed cell death.)

The ostium secundum provides communication between the atria after the ostium primum closes completely.

Subsequently, a second wall of tissue, the septum secundum, grows over the ostium secundum in the right atrium.

Bloodflow then only passes from the right to left atrium by way of a small passageway in the septum secundum and then through the ostium secundum. This passageway is called the foramen ovale.

Question 21

What are the pressure differences between the primitive heart and mature heart in regards to the left and right atria?

Answer 21

1) Primitive heart = pressure LA < pressure RA blood flows through foramen ovale
2) Mature = pressure LA > pressure RA septum primum pushed against septum secundum

Question 22

Why is it important that the two septums are not aligned?

Answer 22

If they are aligned, you will have an atrial septum defect

Question 23

There are a variety of defects that can affect the atrial septum formation. Describe one.

Answer 23

Ostium secundum defect

– septum primum
• resorbed
• too short

– septum secundum too small

Question 24

What is Probe patent septal defect?

Answer 24

In about 25% of adults the foramen ovale does not close completely, but remains as a small patent foramen ovale (“PFO”).

It is when the atrial septum is not formed correctly. It an cause TIA (Transient Ischaemic Attack) and stroke.

Question 25

What is Hypoplastic left heart syndrome?

Answer 25

When the left ventricle isn’t developed properly

Exact cause not known BUT there is some embryological speculation…

– defect in development of mitral and aortic valves, resulting in atresia and limited flow Into the ventricle and because we don’t have blood to pump against, it won’t develop normally.

– Or ostium secundum too small therefore right to left flow inadequate in utero and thus since there is not enough blood in the chamber, the use it or loose it rule applies and the muscle will be underdeveloped

• left heart is underdeveloped

Question 26

What is the most common cardiac defect?

Answer 26

Ventricular septal defects

Question 27

What are the two ventricular components?

Answer 27

Muscular

Membranous

Muscular portion forms most of the septum and grows upwards towards the fused endocardial cushions, which gives a scaffold for intraventricular and intraatrial septums.

Question 28

Why is it bad if the endocardial cushions are not formed properly?

Answer 28

If they are malaligned or not developed properly, you’re likely to have problems with both the inter ventricular and inter atrial septums formation

Question 29

How does the primary intraventricular Foramen develop?

Answer 29

Muscular portion of the heart grows upwards towards the endocardial cushions leaving a small gap, the primary interventricular foramen

Membranous portion of the interventricular septum formed by connective tissue derived from endocardial cushions “fill the gap”

Question 30

What is the common cause of ventricular septal defect?

Answer 30

In some individuals, the foramen fails to close, leading to an interventricular septal defect known as a patent interventricular foramen

Most commonly the membranous portion of interventricular septum is involved

Question 31

How do we divide the outflow tract?

Answer 31

First, ensure that the tract is routing oxygenated and deoxygenated blood appropriately

1) The endocardial cushions also appear in the Truncus Arteriosus

So we need to build a scaffold against which another septum will form

Truncus Arteriosus needs to be divided to form two discrete channels

They appear slightly offset from each other, staggered to ensure a spiral septum is formed

As they grow towards each other they twist around each other

This ensure we can route the pulmonary trunk and the aorta around each other

Question 32

What is transposition of the great arteries?

What will happen?

Answer 32

A heart defect

When the positions of the vessels are swapped over:

• The aorta arises from right ventricle
• The pulmonary trunk arises from left ventricle

The baby will have cyanosis:
- this depends on what other defects (if any) are present

Likely to relate to the development of the aortic and pulmonary values which need to be carefully positioned to ensure normal
“plumbing” - tissues need to be perfectly aligned.

Question 33

What is tetralogy of fallot?

Answer 33

Congenital heart defect present at birth

Tetralogy - refers to four separate structural defects:

1) Large ventricular septal defect - a hole between the two ventricles
2) Overriding aorta - which allows blood from both ventricles to enter the aorta
3) Right ventricular outflow tract obstruction/ pulmonary stenosis - narrowing of the exit from the right ventricle
4) Right ventricular hypertrophy - enlargement of the right ventricle (Relates to obstruction, has to work harder to gets bigger)

This may be caused by normal septation of Truncus Arteriosus - normal formation of spiral septum is bad. This is important for accurate placement of great vessels. If skewed to one side, you get obstruction.

Thus really bad if conotruncal septum formation is defective.

Question 34

Why are the neural crest cells important to embryonic development of the heart?

Answer 34

They control and contribute significantly to the formation of endocardial cushions and thus the septation of atria and ventricles and also the Conotruncal septum. So really important

Question 35

Where are the neural crest cells derived from? What substance are they sensitive to?

Answer 35

The neural ectoderm

Alcohol - it kills the cells very quickly in low concentrations so if women consume alcohol during pregnancy it can result in fetal alcohol syndrome which has a huge spectrum of defects relating to the brain, face and also the cardiovascular system because the neural crest cells make a significant contribution to all these systems

Question 36

What is the primary interventricular Foraman?

Answer 36

The primary interventricular foramen is a temporary opening between the developing ventricles of the heart.

The ventricles arise as a single cavity that is divided by the developing interventricular septum.

Before the septum closes completely, the remaining opening between the two ventricles is termed the interventricular foramen.

Question 37

What two factors influence the course of the recurrent pharyngeal nerve on the left and right sides?

Answer 37

– caudal shift of the developing heart & expansion of the developing neck region

• the need for a fetal shunt between PT & aorta