ICL 4.7: Cardiac Development

Question 1

what are the steps of cardiogenesis?

Answer 1

1. bilateral heart primordia
2. primitive heart tube
3. heart looping
4. atrial and ventricular septation
5. outflow tract septation (aorta and pulmonary trunk division)

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Question 2

what is the first organ to form?

Answer 2

the heart! it forms by 8 weeks!

Question 3

what is the highly sensitive period of development for the heart during embryogenesis?

Answer 3

3-6 weeks

Question 4

what are the cellular origins of the heart?

Answer 4

cardiogenesis involves cellular determination, migration, and differentiation along with a series of critical morphogenetic events

cells from the anterior lateral plate mesoderm give rise to the precardiogenic mesoderm, which is fated to form the heart well before cardiac morphogenesis begins

the precardiac mesoderm constitutes a horse-shoe-shaped region of the mesoderm extending back on either side along the foregut – an inductive influence from the neighboring endoderm has been postulated to stimulate the early formation of the heart (slide 6)

Question 5

how many types of cells are generated from the cariogenic mesoderm?

Answer 5

every single cardiac cell type is established by lineage
diversification of embryonic cells which arise from the
cardiogenic mesoderm!! so all the different types of heart cells come from the cardiogenic mesoderm!

so the endocardial endothelial cells, atrial myocytes and ventricular myocytes all comes from the cariogenic mesoderm!!

then the endocardial endothelial cells differentiate into cushion cells and the ventricular myocytes differentiate into purkinje fibers

Question 6

what are the stages of development of the mesoderm?

Answer 6

1. embryonic mesoderm
2. paraxial, intermediate and lateral mesoderm
3. lateral mesoderm divides into splanchnic (organs) and somatic (skin) mesoderm

so the heart will be developed from the lateral mesoderm, specially the splanchnic mesoderm!

Question 7

which part of the mesoderm is the heart developed from?

Answer 7

splanchnic mesoderm!

the heart is derived from the splanchnic mesoderm as bilateral tubular primordia located ventrolateral to the early pharynx

the splanchnic mesoderm develops from the lateral mesoderm along with the somatic mesoderm

Question 8

what is the cardiogenic plate?

Answer 8

an area of the splanchnic mesoderm anterior to the head process of the early mammalian embryo that subsequently gives rise to the heart

as the mesoderm begins to split into the splanchnic mesoderm
and somatic layers, a cardiogenic plate is recognizable in the
splanchnic mesoderm rostral to the oropharyngeal membrane

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Question 9

what is the cardiac jelly?

Answer 9

thecardiac jellyis an acellular gelatinous matrix secreted by the myocardium which separates it from the endocardium in early heart development

the cardiac jelly surrounds the two bilateral primordial tubes which later fuse and they form the primitive cardiac tube – all of this is surrounded by the myocardium and epicardium

it permits shape changes needed for twisting and folding of the heart but as the heart tube matures, cardiac jelly gradually diminishes until the myocardium is adjacent to the endocardium

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Question 10

what are the 4 layers that contribute to the wall of the heart tube?

Answer 10

1. epicardium
2. myocardium
3. cardiac jelly
4. endocardium

at this point the heart starts beating once the primitive heart tube is formed!

Question 11

what are the parts of the primitive heart tube and what do they turn into?

Answer 11

1. aortic sac
2. truncus
3. conus

truncus + conus = bulbus cordis –> right ventricle

this makes sense because the conus arteriosus is in the right ventricle!

4. primitive ventricle –> expands to become left ventricle
5. primitive atria –. fuse together to form common atrium
6. sinus venosus –> right atrium

right now the right ventricle is separated from the right atrium by the left ventricle which is why the heart has to loop!

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Question 12

what happens during looping of the heart?

Answer 12

The atrium and sinus venosus come to lie dorsal to the bulbus cordis, truncus arteriosus
and ventricles

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Question 13

how does the heart wall form?

Answer 13

splanchnic mesoderm proliferates to form the
myocardial primordium

between the myocardial primordium and endoderm of the primitive gut, isolated mesodermal vesicles appear and fuse to form the endocardial primordium

cardiac jelly separates the myoepicardium from the endocardium – this layer gives rise to subendocardial tissue

slide 22/23

Question 14

what happens during early partitioning of the heart? late?

Answer 14

EARLY PARTITIONING
1. formation of the atrial-ventricular canal

2. formation of the endocardial cushions (valves)
3. separation of the atrium from ventricles

LATE PARTITIONING
1. partitioning of the atria

2. repositioning of the sinus venosus
3. partitioning of the ventricles (L/R)
4. partitioning of the outflow tract (aortic/pulmonary trunks)

Question 15

what is the endocardial cushion?

Answer 15

endocardial cells lining the AV canal after the heart has looped undergo epithelial mesenchymal transformation and migrate into the cardiac jelly within the walls of the AV canal and the outflow tract

these transformed cells are now called cushion cells; they proliferate and differentiate into mesenchymal-filled bulges called cushion tissue or endocardial cushion

neural crest cells also migrate into the cardiac jelly of the outflow tract so the cushion cells and tissue in the outflow tract is formed from both endothelial-derived cells and from neural crest cells

3 pairs of endocardial cushions are formed: anterior, right/left, right/left conotruncal

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the endocardial cushions are what form the left atrioventricular canal!!!

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Question 16

what happens during partitioning of the atria?***

Answer 16

this is part of late partitioning of the heart

the septum premum decends from the roof of the common atria and starts to form a divide between what’s going to be the two atria

it doesn’t extend all the way down though so the opening at the bottom still connecting the two atria is called the osmium premium

eventually the septum premum reaches the endocardial cushion at the bottom and closes off the atria but at the same time, the top part of it dissolves to allow flow of blood from the right to left atria and this opening is called the ostium secundum – there’s also 2 little flaps that forms to sorta cover this opening called the septum secundum and the hole in-between the flaps is called the foramen ovale!

Question 17

during the partitioning of the atria, why is the pressure in the right atrium higher than the left?

Answer 17

because you don’t have lungs yet so there’s nothing being pumped into the left atrium!

when the baby is born, the lungs will open and blood will start flowing in the LA and the pressure will rise and surpass the RA and push /wedge the wall of the septum premum into the foramen ovale to close it which results in the fossa ovale which is what we have in our adult hearts!

Question 18

what happens to the sinus venosus?

Answer 18

after all the partitioning, the sinus venosus disappears!

unlike the atria, the sinus venosus
remains a paired structure with
right and left horns; each horn
receives venous blood from three
vessels: vitelline, umbilical and common cardinal veins

externally, gradually the sinoatrial orifice shifts to the right, until the
sinus venosus communicates with only the right atrium

1. the right sinus horn becomes smooth part of RA
2. the right anterior cardinal vein becomes superior vena cava
3. the right vitelline vein becomes upper
   part of inferior vena cava
4. the right umbilical vein is obliterated
5. left sinus horn becomes the coronary sinus

internally, the sinoatrial office is flanked by two valves, the right and left venous valves –> superiorly the two valves meet to form the septum spurium

Question 19

what happens during partitioning of the ventricles?

Answer 19

partitioning of the ventricles is first indicated by the formation of a muscular ridge (the interventricular septum) in the floor of the ventricle near the apex –> instead of descending down like in the atria, it rises up

as the ventricles dilate on both sides of the septum the interventricular grooves appears on the surface of the heart

by the end of the eight week the interventricular foramen is closed and the septum completed

Question 20

what happens during partitioning of the outflow tract?

Answer 20

the outflow tract is a single tube (bulbus cordis) in the early stages

the bulbus elongates and divides into a proximal conus arteriosus and a distal truncus arteriosus

appearance of two spiral truncoconal ridges, the outflow tract is partitioned into aortic and pulmonary channels

these ridges, (derived from neural crest mesenchyme), bulge into the lumen and finally meet, separating it into two channels

this partitioning starts near the ventral aortic root and extends to the ventricles, spiraling as it goes

before and during the partitioning process, neural crest-derived cells of the outflow tract begin to produce elastic fibers, which provides the resiliency required of the aorta and pulmonary vessels!

two new sets of semilunar valves, which each have three leaflets, form at the base of the conus

slide 44

Question 21

what is the role of neural crest during outflow tract partitioning?

Answer 21

before and during the partitioning process, neural crest-derived cells of the outflow tract begin to produce elastic fibers, which provides the resiliency required of the aorta and pulmonary vessels!

so basically the neural crest cells come in and split the outflow tract into 2 tubes because it influences the endocardial cushions to form the aorta and the pulmonary trunk!

Question 22

what is the conduction system of the embryological heart?

Answer 22

in very early heart development the location of
the pacemaker shifts from the caudalmost end of
the left tube of the unfused heart to the sinus venosus

as the sinus venosus is incorporated into the right
atrium, the pacemaker, now called sinoatrial node,
becomes situated high in the right atrium

there’s speculation that the coronary arteries have something to do with providing signals for the conduction system to develop but who knows

Question 23

what is the route of fetal circulation?

Answer 23

blood goes out the aorta to the iliac arteries and to the umbilical artery bringing deoxygenated blood into the placenta

in the placenta, it’s oxygenated, then goes through the umbilical veins through the ductus venosus in the liver which feeds into the IVC which then will continue to the right atrium

in the right atrium the blood will go to both the left atrium and the right ventricle –> the blood that went to the left atrium gets there by passing through the foramen ovale and then goes to the LV and back out the aorta while the blood in the right ventricle will continue through the ductus arteriosus and then straight back into the aorta because the lungs aren’t developed and you don’t get oxygen from them

Question 24

what is the mechanism of closure of the ductus arteriosus?

Answer 24

it remains open with prostaglandins and low oxygen content

but when you get oxygen when you’re born, bradykinin and high concentrations of O2 constrict the ductus arteriosus