Lecture 9: Heart Development

Question 1

Where and when does hematopoiesis begin?

Answer 1

Yolk sac (extra-embryonic splanchnic mesoderm): Day 17

• source of early RBC and macrophages
• forms blood islands

Question 2

How does early hematopoiesis happen?

Answer 2

Splanchnic mesoderm > Mangioblasts

Mangioblasts can either form endothelial cells or Primitive HSCs (blood)

Question 3

What happens at day 23?

Answer 3

Primitive HSCs populate the liver

Question 4

What is definitive hematopoiesis? What is the timeline?

Answer 4

AGM (Aortic Gonadal Mesonephric) region has hemogenic endothelial cells that seed at the liver at day 30. They interact with the primitive HSCs there and are programmed to be definitive (fully functional) HSCs by Day 40.

Question 5

Describe how blood vessels form. When does this start?

Answer 5

Splanchnic and paraxial mesoderm > intraembryonic vasculogenesis > endothelial cells form the blood vessels > angiogenesis (sprouting of blood vessels from existing blood vessels) and intussuseption (splitting) happens

Starts at Day 18

Question 6

What are angiomas?

Answer 6

Excessive formation of a type of blood vessel (capillary, cavernous etc.) via vasculogenesis

Question 7

How does the first heart field form?

When does this happen?

Answer 7

Cluster of endothelial cells > form cardiac crescent > splanchnic fuses to form tube (endo and myocardium) which dangles off the dorsal mesocardium > Dorsal mesocardium ruptures so tube can fold

Day 19

Question 8

What is the proepicardial organ?

Answer 8

Remnant of the dorsal mesocardium. Forms the epicardium

Question 9

What causes cardiac looping?

Answer 9

Growth of the 2nd heart field

Question 10

What is the 2nd heart field and how does it form?

Answer 10

Initially next to notochord and suppressed. Development pushes it away from notochord and starts acting like cardiogenic cells

Question 11

What factor is responsible for cardiac looping?

Answer 11

FGF8 exposure, causing addition of cells on both ends of the primitive heart and drives it to fold

Question 12

What is heterotaxia?
What is situs inversus?
What is situs ambiguous?

Answer 12

• Abnormal symmetry of positions of heart chambers
• all chamber positions reversed
• some chamber positions reversed

Question 13

What happens to the right and left sinus horns (bottom tubes of the heart tube)?

Answer 13

Right side loses elements of the left heart and becomes the right atrium (sinus venarum)
Left side loses elements of the right heart and becomes the coronary sinus

Question 14

What are the precursor structures for the IVC and SVC?

Answer 14

IVC: Right vitelline vein
SVC: common cardinal vein

Question 15

What are cushion tissues?

Answer 15

ECM formed by the myocardium of the developing heart > bulges into the lumen > fuse together > form a septum that separates the chambers

Question 16

Where do cushion tissues form, what are they derived from and what do they form there?

Answer 16

Between Atrium and ventricle (endocardial cushion tissues) > Atrioventricular septum
At conotruncal portion (endocardial cushion + NCC) > Aorticopulmonary septum

Question 17

What happens when the AV septum does not form? What causes this?

Answer 17

A and V are not separated and forms septal defects. Caused by insufficient cushion cells

Question 18

Describe the process of atrial septation

Answer 18

Cushion cells fuse and form the AV septum > Septum primum divides right and left atrium and leaves a hole called the foramen primum > septum primum closes the foramen primum > 2nd hole called the foramen secundum forms > septum secundum partially grows over the 2nd hole forming the foramen ovale

Question 19

What embryonic structures allow blood flow to bypass the lungs during development?

Answer 19

Foramen Ovale (Fossa Ovalis after birth)
Ductus arteriosus

Question 20

What are three specific causes of atrial septal defects?

Answer 20

Excessive breakdown of septum primum 
Inadequate coverage by septum secundum
Ostium primum (foramen primum not blocked)

Question 21

What is the cause and symptoms of cyanosis?

Answer 21

Low O2 saturation due to mixing of oxygenated and deoxygenated blood
Bluish color, clubbed fingers

Question 22

What happens to the AV canal?

Answer 22

Av canal is shifted midline by the spiraling
of septum formation to connect the appropriate chambers and separate the pulmonary and arterial circuits (oxygenated and oxygenated blood)

Question 23

Double outlet right ventricle
Cause
Clinical

Answer 23

• AV septum did not shift midline enough (right sided) so alignment is messed up. Now the aorta and pulmonary trunk are both connected to the right ventricle in addition to VSD
• blood mixing causing cyanosis, SOB, murmur

Question 24

What must align to properly separate the pulmonary and arterial circuits?

Answer 24

Muscular and AV septums

Question 25

What is the significance of cardiac neural crest cells?

Answer 25

Helps form the AP septum, affects the growth of heart and affects cardiac looping

Question 26

Why are ventricular septal defects problematic at birth?

Answer 26

Lungs are now inflated > increase systemic pressure in the left > shift blood from left to right causing right ventricle to work harder to get the blood to the left side since they are all spilling over to the right

Question 27

Symptoms of VSD

Answer 27

Hypertrophy of the right ventricle due to overwork (blood spills from LV to RV) and cyanosis

Question 28

What is persistence of the truncus arteriosus?
Cause
Clinical

Answer 28

Neural crest cells failed to form the AP seputm, so conotruncal ridges that divide the aorta and pulmonary arteries do not form, so no separation of outflow = mixing of blood in the trunk
-VSD, cyanosis

Question 29

What is tetralogy of Fallot?
Cause
Clinical

What can overcome this?

Answer 29

• Uneven division of conotruncal ridges, leading to VSD, small pulmonary artery and “fat” overriding aorta
• Right ventricular hypertrophy due to small outlet, cyanosis as blood “shortcuts” from RV to LV and mixes together

-Patent ductus arteriosis

Question 30

What is transposition of the great vessels? What can you do to treat this?

Answer 30

• Pulmonary artery is connected to left ventricle while aorta is connected to right ventricle, aorta is anterior to pulmonary artery instead of posterior
• due to improper spiraling of conotruncal ridges
• cyanotic

-Keep ductus arteriosis open, VSD can help as shunt

Question 31

What is pulmonary valvular atresia? What can you do to treat this?

Answer 31

• Pulmonary valve does not form

- Keep foramen ovale open, VSD can allow blood mixing

Question 32

What is aortic valvular stenosis? What does it eventually result in?

Answer 32

Aortic valve is damaged so backflow to the left ventricle isn’t stopped effectively.
Left ventricle works harder and hypertrophies

Question 33

What is aortic valvular atresia? What does it eventually result in?

Answer 33

Abnormal aortic valve, so L ventricle has no outlet. right ventricle has to work harder to compensate for defective left ventricle outlet and hypertrophies

Question 34

What is bicuspid aortic valve? What can this result in?

Answer 34

Only 2 cusps on the aortic valve compared to 3.

Causes left ventricle to work harder and hypertrophy. Can also cause aortic aneurysms

Question 35

What is tricuspid atresia?

What can you do to treat this?

Answer 35

Tricuspid valve opening is abnormal, so no blood enters the right ventricle.
Need R to L shunt (Keep foramen ovale) open and Left to Right shunt

Question 36

What is hypoplastic left ventricle?

Answer 36

Left ventricle is not developed well, along with the aortic and bicuspid valves and ascending aorta
R side of heart has to do all the work (univentricular) since left is too small and weak