Heart Development

Question 1

describe how the heart tube develops (comes about) in embryogenesis

Answer 1

endoderm induces formation of angiogenic clusters, which are derived from splanchnic mesoderm

angiogenic clusters become dorsal aortae and 2 endocardial tubes, which merge into a single heart tube

Question 2

describe how the atrium and ventricle form from the heart tube in embryogenesis

Answer 2

the heart tube forms sections - sinus venosus, primitive atrium, primitive ventricle, bulbus cordis, and truncus arteriosus

(blood flow moving from sinus venosus towards truncus arteriosus, which matches blood flow in adult heart)

atrium and ventricle enlarge via incorporation of neighboring structures, and heart tube folds on itself into an S shape, giving the layout of the adult heart

Question 3

in the developing heart, the _____ becomes incorporated into the right atrium, becoming the _____, which makes up the smooth muscle part of the atrial wall

Answer 3

in the developing heart, the SINUS VENOSUS becomes incorporated into the right atrium, becoming the SINUS VENARUM, which makes up the smooth muscle part of the atrial wall

veins enter the right atrium through the sinus venarum (coronary sinus, SVC/IVC)

Question 4

the SVC, IVC, and coronary sinus enter the heart through which section of the right atria?

Answer 4

veins enter the sinus venarum - the smooth muscle part of the wall, which originated as the sinus venosus before becoming incorporated into the right atrium (allowing it to enlarge during development)

Question 5

describe the development of the smooth muscle portion of the left atrium - where did it come from?

Answer 5

pulmonary vein grows out of left atrium and divides into L/R branches which then subdivide again

to enlarge, the left atrium resorbs part of the pulmonary vein, and this becomes the smooth wall part of the left atrium - resorbs to the point that there are 4 veins coming into the atrium (stops at second branch point)

Question 6

in embryogenesis:
____ —> rough walled portions of right and left atria
____ —> smooth walled portion of R atrium
____ —> smooth walled portion of L atrium

Answer 6

PRIMITIVE ATRIUM —> rough walled portions of right and left atria (portion of heart tube)

SINUS VENOSUS —> smooth walled portion of R atrium (sinus venarum, where veins enter atria)

PROXIMAL PULMONARY VEIN —> smooth walled portion of L atrium (resorbed until 2nd branch point, such that 4 pulmonary veins enter atria)

Question 7

after the heart tube folds during embryogenesis, ____ enter in the back and _____ leave in the front

Answer 7

veins enter posteriorly (back wall of atria), arteries leave anteriorly (front wall of ventricles) - all due to S shape folding

think about anatomy of adult heart and this makes sense

Question 8

during what weeks of embryogenesis does septation of the heart occur?

Answer 8

septation begins late in week 4 and goes to late week 7

Question 9

describe the development of atrial septation in embryogenesis

where does the fossa ovalis come from?

Answer 9

dividing the R/L atria first in prenatal life is the septum primum, which does not extend all the way to the endocardial cushion (dividing the AV canal into 2 sides) - this leaves a space, called the foramen primum, which allows communication between the R/L atrium

however, the septum primum grows/lengthens, therefore shortening the foramen primum until it eventually fuses with the endocardial cushion

before this occurs, a second opening develops called the foramen secundum

the thicker/rigid septum secundum develops and is superimposed on the septum primum, but does not extend all the way down (allowing for foramen ovale shunt below prenatally)

the fossa ovalis is the portion of septum primum not covered by septum secondum (thinner here), and its limbus is the free edge of septum secundum (in adult heart)

Question 10

describe how the prenatal pressure gradient creates the foramen ovale, and how (why) it is closed at birth

Answer 10

in the embryo, the entire body + placenta is sending blood to right side of heart - causing it to have higher pressure than left side of heart, which isn’t really receiving blood from lungs yet

this pressure gradient pushes the flexible septum primum away from the rigid septum secundum, allowing a R to L shunt - foramen ovale

at birth, the umbilical vein closes (drop off of flow into R atrium) and breathing causes lungs to expand (reduction in vascular resistance allows more blood flow in/out of lungs to L atria) —> pressure gradient shifts and L to R gradient keeps foramen ovale closed!

Question 11

what are the 2 main causes of the change in pressure gradient from R to L in the embryo, to L to R at birth?

Answer 11

1. umbilical vein closes - drop off of blood flow into R atrium
2. breathing causes lungs to expand - reduction of vascular resistance allows more blood to flow in/out of lungs into L atrium

shift in pressure gradient (now L to R) is what keeps foramen ovale closed after birth - fusion of septum primum and septum secundum usually occurs by age 2 (~75%)

Question 12

describe the possible clinical consequences if the septum primum and septum secundum do not fuse after the change in pressure gradient at birth (now from L to R) shuts the foramen ovale

Answer 12

most of the time, the foramen ovale shuts and the septum primum/secundum fuse by age 2 (~75%)

if not, there is still no shunting as long as pressure gradient is maintained

however, if there is a reversal of pressure gradient (ex: caused by pulmonary embolism), a R to L shunt can occur

~40% of cryptogenic [read: cause unknown] stroke patients are found to have patent foramen ovale (PFO)! This allows a thrombus to get from R to L side, which travels systemically, and can reach CNS

Question 13

describe what occurs in primum type atrial septal defect, and the clinical consequence of it

Answer 13

incomplete septum primum, usually actually caused by failure of endocardial cushion to grow upwards to meet septum primum

this causes L to R shunt (*acyanotic because oxygenated blood is getting shunted into pulmonary circulation)

this can cause overloading of pulmonary circuit —> pulmonary hypertension

if pressure gets high enough, pressure gradient can cause shunt to convert to R to L shunt and becomes cyanotic !

Question 14

describe what occurs in secundum type atrial septal defect (ASD)

Answer 14

the foramen secundum (in the septum primum) forms via apoptosis, but if too much apoptosis occurs, it is larger than it should be and there is a portion not covered by the septum secundum

this causes L to R (acyanotic) shunt - oxygenated blood is shunted to pulmonary circulation

this may cause pulmonary hypertension, which could potentially cause the shunt to convert to a cyanotic R to L shunt!

same outcome as primum type ASD but different mechanism, and ~8x more common (also more likely to occur in isolation)

Question 15

which of these is LESS likely to occur in isolation and why, a primum type or secundum type atrial septic defect (ASD)?

Answer 15

primum type ASD usually does NOT occur in isolation, because it is due to defect in endocardial cushion (does not reach septum primum to close gap - creates L to R acyanotic shunt)

endocardial cushion development is related to migration of neural crest cells, so primum type ASD usually also present with other issues related to failure of neural crest cells to migrate

they ALSO often present with valve defects since the endocardial cushion is meant to separate the AV valve into channels

Question 16

primum type vs secundum type ASD

Answer 16

primum type atrial septal defect: failure of endocardial cushion to grow to reach septum primum, leaving opening —> L to R acyanotic shunt, usually not in isolation

secundum type atrial septal defect: too much apoptosis in creating foramen secundum in septum primum leaves portion not covered by septum secundum —> L to R acyanotic shunt, more often in isolation and more common overall

both can lead to overloading of pulmonary circuit and pulmonary HTN, which can cause shunt to convert to R to L cyanotic shunt (due to change of pressure gradient)

Question 17

describe how the ventricular septum develops - what are the 2 components?

Answer 17

ventricular septum is made from fusion of 2 septums:

1. embryonic ventricular septum - forms from ventricle wall, does not completely divide ventricle into 2 (cardiac muscle - muscular IV septum)
2. aorticopulmonary septum/ spiral septum - forms from invagination of neural crest cells of truncus arteriosus (fibrous CT - membranous IV septum)

Question 18

what makes up the membranous and muscular IV septum of the ventricle septum?

Answer 18

1. embryonic ventricular septum - forms from ventricle wall, does not completely divide ventricle into 2 (cardiac muscle - muscular IV septum)
2. aorticopulmonary septum/ spiral septum - forms from invagination of neural crest cells of truncus arteriosus (fibrous CT - membranous IV septum)

Question 19

describe what occurs in a tetralogy of Fallot, including the 4 key features of this defect

what kind of shunt is this?

Answer 19

usually, embryonic ventricular septum and aorticopulmonary septum fuse to create ventricular septum

in Tetralogy of Fallot, aorticopulmonary septum is displaced toward pulmonary side of circulation, causing:
1. pulmonary stenosis: pulmonary trunk is too small
2. overriding aorta: aorta straddles both L/R ventricles
3. ventricular septal defect: septums do not fuse
4. right ventricular hypertrophy: R ventricle working harder to push blood into pulmonary circuit through smaller opening

this is a R to L cyanotic shunt because a lot of deoxygenated blood from R side gets into systemic circulation

Question 20

what occurs in persistent truncus arteriosus? is this acyanotic or cyanotic and why?

Answer 20

missing an aorticopulmonary septum (which is supposed to fuse with embryonic ventricular septum to form mature ventricular septum)

—> both ventricles send blood into same outflow and blood mixes, so this is both a R to L and L to R shunt - therefore it is cyanotic due to portion of deoxygenated blood getting into systemic circulation

also presents with ventricular septal defect since the aorticopulmonary septum is meant to contribute to the ventricular septum!

Question 21

a persistent truncus arteriosus always presents with what other defect and why?

Answer 21

missing an aorticopulmonary septum (which is supposed to fuse with embryonic ventricular septum to form mature ventricular septum)

presents with ventricular septal defect since the aorticopulmonary septum is meant to contribute to the ventricular septum!

—> both ventricles send blood into same outflow and blood mixes, so this is both a R to L and L to R shunt - therefore it is cyanotic due to portion of deoxygenated blood getting into systemic circulation

Question 22

what embryonic defect causes transposition of the great arteries of the heart?

Answer 22

aorticopulmonary septum should develop in spiral shape, but if it forms straight instead, 2 closed loops are created —> aorta goes back to R ventricle and pulmonary trunk goes back to L ventricle

not a problem prenatally but not compatible with life after birth - however, there are usually other defects that occur that allow survival for awhile (but very cyanotic), allowing time for surgery to switch the vessels

Question 23

before birth, how does the quality of the blood supply within the IVC and SVC differ?

Answer 23

the IVC receives oxygenated blood from the umbilical cord, which mixes with the deoxygenated blood from the embryo’s body

the SVC only receives deoxygenated blood from the embryo’s upper body

so the IVC has a higher oxygen saturation than the SVC

Question 24

what is the purpose of the valve of the IVC in the embryo?

Answer 24

the IVC has some oxygenated blood in it from the umbilical cord, while the SVC does not

the valve of the IVC channels IVC blood towards the foramen ovale, taking it to the L ventricle and then out though the ascending artery

SVC blood (only deoxygenated) does not enter because it would have to make a U turn, so instead it enter R ventricle and goes out through pulmonary trunk

Question 25

how is blood from the SVC circulated before birth?

Answer 25

the SVC does not enter the foramen ovale as the more oxygenated IVC does (it would have to make a U turn to do so)

instead, it enters R ventricle and goes out through pulmonary trunk… however, high vascular resistance prevents it form entering lungs, so blood is shunted out of pulmonary circuit into aorta via ductus arteriosus…

in the aorta it mixes with IVC blood to go through systemic circulation, but this doesn’t happen until AFTER branching of the brachiocephalic trunk, L common carotid, and L subclavian

Question 26

what is the purpose of the ductus arteriosus before birth?

Answer 26

ductus arteriosus shunts blood from the SVC out of the pulmonary circuit (where vascular resistance is too higher to enter lungs) into aorta, where SVC mixed with IVC (more oxygenated) blood

however, this doesn’t occur until AFTER aortic branches of brachiocephalic trunk, L common carotid, and L subclavian (which supply brain)

Question 27

what is the significance before birth of the location where the brachiocephalic trunk, L common carotid, and L subclavian branch off the aorta?

Answer 27

the IVC has some oxygenated blood (due to umbilical cord), while SVC is all deoxygenated

IVC gets shunted by valve of the IVC through the foramen ovale, which takes it to L ventricle and out through aorta

SVC goes to pulmonary circuit but is shunted away (because of high vascular resistance) by ductus arteriosus, which dumps it into the aorta

this occurs after the branch point of these arteries off the aorta, which is important because these supply the brain

therefore, the brain gets more oxygenated blood than the rest of the body

Question 28

what do each of these become after birth?
a. ductus arteriosus
b. ductus venosus
c. umbilical vein
d. right and left umbilical arteries

Answer 28

all become fibrous and become ligaments

a. ductus arteriosus —> ligamentum arteriosum
b. ductus venosus —> ligamentum venosum
c. umbilical vein —> ligamentum teres
d. right and left umbilical arteries —: medial umbilical ligaments

Question 29

what causes the ductus arteriosus (which shunts SVC blood away from pulmonary circuit into aorta) to close after birth? (2)

Answer 29

smooth muscle of ductus arteriosus contracts until there is no lumen (but smooth muscle contracts slowly, so it takes a couple of days), due to:
1. higher oxygen and bradykinin induce smooth muscle contraction - based on conditions
2. decreased prostaglandin synthesis (which inhibits contraction and is produced in large amounts by embryo) - based on time

Question 30

why is a patent ductus arteriosus more common in pre-term babies?

Answer 30

ductus arteriosus (which shunts SVC blood away from pulmonary circuit before birth) is closed via smooth muscle contraction within a couple days of birth, due to 2 things:
1. increased O2 and bradykinin
2. decreased prostaglandin synthesis —> this is time dependent (embryos produce a lot before birth)

if baby is preterm, they have not reached the time where signaling decreases prostaglandin synthesis, so they are still production prostaglandin, which inhibits smooth muscle contraction

give prostaglandin inhibitor and O2

Question 31

preductal vs postductal coarctation of the aorta

Answer 31

coarctation = narrowing of the aorta

preductal: narrowing before ductus arteriosus - babies born without collateral circulation because ductus arteriosus is feeding into aorta, but when it closes after birth, crisis occurs

postductal: narrowing after ductus arteriosus - not symptomatic until adulthood because collateral circulation develops in utero, but later in life hypertension and other issues develop due to elevated pressure in circulation