S2: Development of the Heart

Question 1

What is the first organ to develop and function in a foetus?

Answer 1

The heart

Weeks 3-10 post conception

Question 2

What is the cardiac crescent?

Answer 2

• Crescent shaped tube of myocardium
• Derived from mesodermal cells
• Lumen of tube lined by epithelium known as endocardium

Question 3

Describe expansion of primary heart tube

Answer 3

• Medial part of cardiac crescent expands
• This becomes the left ventricle
• Endocardial tube attaches to developing aortic arches cranially (outflow) and systemic veins caudally (inflow)

Question 4

Describe the elongation of the heart tube

Answer 4

• Cells from the second heart field are added at both the outflow and inflow so the heart elongates
• The ends of the tubes are fixed so the heart bends as it elongates
• The direction of looping is genetically controlled leftward

Question 5

What is dextrocardia?

Answer 5

The heart lies on the RHS due to problem in development during elongation of heart tube.

If the looping reversal is symmetrical, the heart can still function properly.
If only parts of the heart are folded incorrectly, there is a problem.

Question 6

Describe chamber formation from the heart tube

Answer 6

• Primitive chambers formed by expansion (ballooning) of tube
• Atria start off causal and ventricles cranial, but by 28 days the atria fold up behind the ventricles so they become more cranial
• Ventricles are characterised by the presence of trabeculae

Question 7

Describe the 4 types of septation of the heart tube

Answer 7

1. Atriaventricular septation which seperates the atria from the ventricles with AV cushions.
2. Atrial septation which seperates the L and R atria with an interatrial septum
3. Ventricular septation seperates the L and R ventricles with an interventricular septum
4. Outflow tract septation which seperates the pulmonary artery from the aorta using OFT cushions

Question 8

What are the two types of septation in the heart?

What defects do they have?

Answer 8

1, Cushions

• AV and OFT cushions
• Valve formation, stenosis and atresia (vessel hasn’t opened) defects if this goes wrong

2. Muscular walls
   - A and V septation
   - Defects give rise to holes

Question 9

Describe AV septum formation (including AV cushion formation)

Answer 9

Constriction becomes the junction between the atria and ventricles. As the two septum’s (cushions) comes together they meet and fuse becoming the AV septum wall.

AV cushion formation:

• Cardiac jelly (ECM) secreted by myocardium (its in middle)
• Endocardial cells undergo epithelial-mesenchymal transition and populate the jelly becoming cushions

Question 10

Defects of AV septum

Answer 10

AVSD (atrioventricular septum defects):

• valves
• common in downs syndrome

Question 11

Describe atrial septation

Answer 11

• Primary interatrial septum grows down to fuse with the AV cushions
• The trailing edge of the primary septum breaks down to allow blood to continue to flow from right to left atrium (foramen ovale/ostium secundum –> hole forming in primary septum)
• Septum secundum grows down to form a flap valve
• Left atrial pressure increases after birth closes valve ans this eventually seals

Question 12

Defects in atrial septum (atrial septal defects -ASD)

Answer 12

• Persistent foramen ovale where flap doesn’t seal properly. Possible risk factors for stroke and in divers.
• Ostium primum defect: leading edge of primary septum hasn’t grown down far enough to fuse with AV cushions
• Ostium secundum defect: flap (secondary septum) hasn’t grown down far enough to fuse
• Left to right shunting

Question 13

Describe left to right shunting

Answer 13

• In ASD
• In VSD
• In ductus arteriosus defect

Pressure on the left is higher than the right so blood usually flows from left to right down a pressure gradient.

Defect is acyanotic (normal levels of oxyhaemoglobin in systemic circulation). Even though is less blood around the bodym the blood is still oxygenated.

Question 14

Describe interventricular septum formation

Answer 14

• The IVS grows from the wall towards the AV cushion, initially as a thickened trabeculum
• Attachment at the end of the septum tends to be membranous rather than muscular

Question 15

Defects in ventricular septum (ventricular septal defects - VSD)

Answer 15

· 75% perimembranous
· 25% muscular
· Small
	o Small L>R shunt
· Medium
	o Moderate L>R shunt
· Large
	o Large L>R shunt
Surgically repaired in childhood

Question 16

Describe septation of outflow tract

Answer 16

• A single tube is seperated into the aorta and pulmonary artery
• These must be attached to the left and right ventricles respectively
• Two outflow tract cushions spiral through the truncus arteriosus
• Complex remodelling at each end
• Spiralling cushions seperate the aorta and pulmonary artery
• Neural crest cells contribute to AP septum
• Proximal cushions fuse with IVS and AVS

Question 17

Describe remodelling of the aortic arches makes the great vessels

Answer 17

Neurocrest cells (from neuroectoderm). They delaminate from the epithelium of neural tube and undergo an epithelial-mesenchymal transition to allow them to migrate down into the pharyngeal arches (temporary buldges) and in the centre they enter into the aortic arch arteries. Arch 1, arch 2, arch 3 - when arch 1 degenerates, arch 4 forms (only 3 at a time) –> next is 6 as there is no 5 arch
- Ductus arteriosus is a derivative of aortic arch 6

Question 18

Defect in patent ductus arteriosus

Answer 18

• L to R shunting
  · Defect is acyanotic
  · Connects aorta to pulmonary artery
  · Allows foetal circulation to bypass lungs
  Normally closes after birth and becomes the ligamentum arteriosum

Question 19

OFT defects

Answer 19

· Several types of OFT defect
· Connection between pulmonary artery and aorta
· Different types that result in a common truncus
· OFT defects are associated with neural crest defects (eg 22q11 Deletion Syndrome aka DiGeorge Syndrome)
Unequal division of the OFT can lead to aortic or pulmonary stenosis

Question 20

Describe transposition of great arteries - TGA (OFT defect)

Answer 20

· Aorta connected to right ventricle
· Pulmonary trunk connected to left ventricle
· Arterial trunks usually side-by-side
· Probably caused by abnormal outflow tract cushions
· Lethal without VSD, ASD or PDA (bypasses block of blood to lungs)
Cyanotic defect (deoxygenated blood around the body)

There can be surgical correction of TGA. Atrial switch –> divert blood flows into different ventricles e.g. Pumping blood round the body from the right ventricle.

Question 21

What is Tetraogy of Fallot?

Answer 21

Four characteristic features:
o VSD (large)
o Pulmonary stenosis (narrowing of pulmonary artery)
o Right ventricular hypertrophy (usually in response to stenosis)
o Overriding aorta
· Right>Left shunt
· Cyanotic
· Complex phenotype may result from abnormal looping, leading to malalignment of segments

· Squatting increases peripheral arterial resistance and causes a left to right shunt
Increases pulmonary blood flow

Question 22

Describe R to L shunt

Answer 22

• Tetralogy of Fallot
• OFT defect (transposition of great arteries)

Right to left shunt leads to cyanosis

Question 23

Origins of conduction system in the heart

Answer 23

· Conduction tissue is specialized myocardium, not nerves (they come from neural crest cells)
· Variations in conduction properties caused by differences in ion channel and connexin (gap junctions) expression
· Conduction system differentiates by progressive, localised recruitment from heart tube myocardium
· Electrical insulation layers to prevent inappropriate signalling:
o Fibro-fatty layer at AV junction (ex cushions)
o Ventricular bundle branches wrapped in a fibrous sheath