Lecture 9: Heart Development Flashcards
Where and when does hematopoiesis begin?
Yolk sac (extra-embryonic splanchnic mesoderm): Day 17
- source of early RBC and macrophages
- forms blood islands
How does early hematopoiesis happen?
Splanchnic mesoderm > Mangioblasts
Mangioblasts can either form endothelial cells or Primitive HSCs (blood)
What happens at day 23?
Primitive HSCs populate the liver
What is definitive hematopoiesis? What is the timeline?
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.
Describe how blood vessels form. When does this start?
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
What are angiomas?
Excessive formation of a type of blood vessel (capillary, cavernous etc.) via vasculogenesis
How does the first heart field form?
When does this happen?
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
What is the proepicardial organ?
Remnant of the dorsal mesocardium. Forms the epicardium
What causes cardiac looping?
Growth of the 2nd heart field
What is the 2nd heart field and how does it form?
Initially next to notochord and suppressed. Development pushes it away from notochord and starts acting like cardiogenic cells
What factor is responsible for cardiac looping?
FGF8 exposure, causing addition of cells on both ends of the primitive heart and drives it to fold
What is heterotaxia?
What is situs inversus?
What is situs ambiguous?
- Abnormal symmetry of positions of heart chambers
- all chamber positions reversed
- some chamber positions reversed
What happens to the right and left sinus horns (bottom tubes of the heart tube)?
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
What are the precursor structures for the IVC and SVC?
IVC: Right vitelline vein
SVC: common cardinal vein
What are cushion tissues?
ECM formed by the myocardium of the developing heart > bulges into the lumen > fuse together > form a septum that separates the chambers
Where do cushion tissues form, what are they derived from and what do they form there?
Between Atrium and ventricle (endocardial cushion tissues) > Atrioventricular septum
At conotruncal portion (endocardial cushion + NCC) > Aorticopulmonary septum
What happens when the AV septum does not form? What causes this?
A and V are not separated and forms septal defects. Caused by insufficient cushion cells
Describe the process of atrial septation
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
What embryonic structures allow blood flow to bypass the lungs during development?
Foramen Ovale (Fossa Ovalis after birth) Ductus arteriosus
What are three specific causes of atrial septal defects?
Excessive breakdown of septum primum Inadequate coverage by septum secundum Ostium primum (foramen primum not blocked)
What is the cause and symptoms of cyanosis?
Low O2 saturation due to mixing of oxygenated and deoxygenated blood
Bluish color, clubbed fingers
What happens to the AV canal?
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)
Double outlet right ventricle
Cause
Clinical
- 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
What must align to properly separate the pulmonary and arterial circuits?
Muscular and AV septums
What is the significance of cardiac neural crest cells?
Helps form the AP septum, affects the growth of heart and affects cardiac looping
Why are ventricular septal defects problematic at birth?
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
Symptoms of VSD
Hypertrophy of the right ventricle due to overwork (blood spills from LV to RV) and cyanosis
What is persistence of the truncus arteriosus?
Cause
Clinical
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
What is tetralogy of Fallot?
Cause
Clinical
What can overcome this?
- 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
What is transposition of the great vessels? What can you do to treat this?
- 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
What is pulmonary valvular atresia? What can you do to treat this?
- Pulmonary valve does not form
- Keep foramen ovale open, VSD can allow blood mixing
What is aortic valvular stenosis? What does it eventually result in?
Aortic valve is damaged so backflow to the left ventricle isn’t stopped effectively.
Left ventricle works harder and hypertrophies
What is aortic valvular atresia? What does it eventually result in?
Abnormal aortic valve, so L ventricle has no outlet. right ventricle has to work harder to compensate for defective left ventricle outlet and hypertrophies
What is bicuspid aortic valve? What can this result in?
Only 2 cusps on the aortic valve compared to 3.
Causes left ventricle to work harder and hypertrophy. Can also cause aortic aneurysms
What is tricuspid atresia?
What can you do to treat this?
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
What is hypoplastic left ventricle?
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
