Cardio-Embryology Flashcards
What part of mesoderm is responsible for cardiac development?
cardiogenic mesoderm(cranial to the neural tube and the future mouth.)
What happens to the cardiogenic mesoderm at the end of week 3?
the splanchnic(?) mesoderm begins to condense into a more solid arrangement of cells that form a horse‐shoe shaped cord. The cord will hollow out, forming a horse‐shoe shaped tube that will eventually form left and right heart tubes.
The right and left cardiogenic tubes arise how?
Lateral body folding occur when the lateral margins of the disc fold ventrally, eventually meeting and fusing in the ventral midline axisthese tubes eventually fuse into a single heart tube with a common chamber
Fusion of the right and left primordial heart tubes is complete by when?
end of 4th week of development
Fusion of the right and left primordial heart tubes occurs in what manner? Caudal to cranial?
cranial to caudal (gives rise to a single embryonic heart tube in the midline with a common inner chamber)
When does head to tail folding begin?
end of 3rd week
What induces head folding?
occurs as a consequence of the rapid development of the nervous systemAs the anterior end of the neural tube develops and grows in mass, it induces the head to begin tucking in. This initiates a migration of the cardiogenic tissue, first through the cervical region and then ultimately into the thorax.
When is autonomic innervation to the developing heart tube established?
During migration of cariogenic tissue through the cervical region
What are the autonomic innervation to the heart?
parasympathetic- vagussympathetic- T1-T5
When does the heart reach its definitive position in the thorax?
end of week 4
What are the five divisions of the embryonic heart tube?
truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and sinus venosus (from cranial to caudal)
When does the heart gain contractability?
day 23. moving blood in a caudal to cranial direction in the still vertical heartThe cranial part of the tube represents the arterial outflow, while the caudal end of the tube represents the venous inflow.
How does the caudal (atrial) end of the vertical heart tube move during folding and looping?
superior, posterior, and to the right. The arterial (truncal) end of the tube will move anteriorly, inferiorly, and to the left (see image on far right). This will be complete by the end of the 4th week.
What structures does the truncus arteriosus form?
aorta & pulmonary trunk and their semilunar valves.
What structures does the bulbus cordis form?
t gives rise to the smooth walled areas (outflow tract) of the right and left ventricles (conus arteriosus & aortic vestible).
What structures does the primitive ventricle form?
the trabeculated parts of the right and left ventricles.
What structures does the primitive atrium form?
trabeculated parts of the right and left atria (i.e. the auricles)- pectinate muscles
What is the only part of the embryonic tube that consists of right and left parts?
sinus venosus
The right horn of sinus venous forms what?
the majority of the right atrium (sinus venarum).
The left horn of sinus venous forms what?
cardiac veins on the surface of the heart (coronary sinus and the oblique vein of the left atrium).
In pre‐natal development, blood from mom is being provided through the placental circulation to the fetus via what?
umbilical vein. Deoxygenated blood is returned to the placenta via a pair of umbilical arteries.The umbilical vein contains the blood with the highest oxygen content (~80 %) as it is coming directly from mom via the placenta and through the umbilical cord.
During development, what visceral structures are not doing much work?
the liver (because mom has already processed the blood) and the fetal lungs (because blood has already been oxygenated)
What is the ductus venosus?
It allows most of the blood in the umbilical vein to bypass the liver by re‐directing it into the IVCThe blood in the ductus venosus is still ~ 80% oxygenated. Notice that a small volume of blood flows through the liver, supplying those tissues with adequate oxygenation.
Is blood in the IVC more or less oxygenated than in the umbilical vein? Why?
Less. In the IVC, the high oxygen saturated blood from the ductus venosus is mixed with low oxygen saturated blood (~ 20%) returning from the fetal periphery. Nevertheless, blood flow from the IVC into the right atrium still has reasonable oxygen saturation of ~60‐70%.
What side of the heart has higher pressure during development? Why?
right.Because there is a massive volume of blood entering the right atrial chamber via the IVC and the SVC. Second, there is high pulmonary resistance because the pulmonary circulation is closed.
What does the foramen ovale do?
It sends this oxygen‐rich blood from the right atrium directly into the left atrium, bypassing the pulmonary circulation of the fetus.
Notes on mixing of blood from IVC and SVC
Within the right atrium, there are two sources of incoming blood. One is from the IVC (oxygen‐rich from mom) and the other is via the SVC (oxygen‐poor from the fetal periphery). However, the right atrium does not act like a mixing bowl for these two circulations. Rather, the respective flows remain laminar, such that the oxygen‐rich IVC flow is directed towards the foramen ovale and the left atrium, and the oxygen‐poor SVC flow is directed towards the right AV valve and the right ventricle with little mixing of the two circulations.
Oxygen rich blood from the IVC goes through what structure in the developing heart?
foramen ovale to left atrium. From there it goes to systemic circulation by passing through the left ventricle (but not before supplying the heart with oxygenated blood)- the blood that is pumped out systemic is still fairly oxygenated (~65%)
How does oxygen poor blood from the SVC move through the heart?
does not go through foramen ovale. Goes from right atrium to right ventricle, and out of the pulmonary trunk, then through the the ductus arteriosus, to enter the descending aorta distal to the arch thereby bypassing the fetal pulmonary circulation without impacting the oxygen flow to the head
When does highly and poorly oxygenated blood mix?
in the descending aorta after oxygenated blood has gotten the chance to go to the head
When do the three fetal shunts close?
foreamen ovale- almost instantly following birth and first breath due to pressure changeductus venosus and ductus arteriosus- within 24-36 hrs after birth, caused by smooth muscle contraction
The ductus venosus closes via contraction of its smooth muscle wall and forms a remnant called the?
ligamentum venosum
Foramen ovale closes in response to pressure changes in the heart, and forms a remnant called the?
fossa ovalis
The ductus arteriosus closes via contraction of its smooth muscle wall and forms a remnant called the?
ligamentum arteriosum
Where does the ligament arteriosum span?
spans between the arch of the aorta and the pulmonary trunk.
The closed umbilical vein and artery form?
the round ligament of the liver (ligamentum teres) and the medial umbilical ligaments, respectively.
neural crest cells originated from the neural folds of the neural tube and migrated into what two regions of the primitive cardiovascular system?
truncus arteriosus and the endocardial cushions
Why can’t the atria cannot be fully septated until birth?
The foramen ovale must remain open at all times during fetal life, to allow for the right‐to‐left shunting of blood.
When does atrial septation occur?
5th-8th weeks
What is the first step in atrial septation?
the downward growth of septum primum from mesoderm of the common interatrial roofThe septum primum grows toward, but initially stops just short of the endocardial cushion, leaving an opening in the developing interatrial wall called foramen primum. The right‐to‐left shunt is maintained.NOTE: Septum primum will continue its downward growth and eventually fuses with the endocardial cushion, obliterating the foramen primum
fusion of septum primum with the endocardial cushion is dependent upon what?
NC cell migration into the cushion.
What happens before the foramen primum is completely closed?
programmed cell death (apoptosis) occurs in the upper aspect of septum primum, forming a second opening higher in the interatrial wall called foramen secundum, so that the right‐to‐left shunt is maintained,
What happens after the foramen scandium is established?
a second septum (septum secundum, in green) begins to grow downward from the interatrial roof just to the right of septum primum. Septum secundum is thicker and more rigid than septum primum.
How does the foramen ovale form?
Septum secundum continues to grow, eventually overlapping foramen secundum and the lower part of septum primum with its free inferior edge. This results in the formation of an oblique passageway between the right and left atria as indicated by the curved arrow in the lowest image on the left. This passageway is the foramen ovale. Foramen ovale will remain open until birth, providing a continual right‐to‐left shunting of blood in the fetal heart. The lower half of septum primum is quite thin and flexible. It acts as a one‐way flapper valve for the foramen ovale that opens with every fetal heartbeat
The limbus of the fossa ovalis is the remnant of what structure?
the inferior free edge of septum secundum.
The floor of the fossa ovalis is comprised of?
the septum primum
Above the fossa ovalis, the interatrial wall is thicker where it is comprised of?
septum secundum
non‐cyanotic defects result from what?
Left‐to‐right shuntsThey result in continual cycling of oxygenated blood through the pulmonary circulation, producing super‐saturated oxygen levels.
cyanotic defects result from what?
Right‐to‐left shunts produce cyanotic defects. These defects push low oxygenated blood to the left side of the heart and out into the peripheral circulation. Cyanosis occurs when peripheral tissues do not receive adequate oxygenation and “bluing” of the skin and nails may occur, hence the term “blue‐ baby”. Some of these defects are so severe, that they do not permit life to continue.
What are Atrial septal defects (ASDs)?
occur when the atrial septum does not form properly.give rise to left‐to‐right shunts and are non‐cyanotic at birth
What are Secundum ASDs characterized by?
defects that are high on the interatrial wall (above the fossa ovalis).
What do Secundum ASDs result from?
excessive resorption of septum primum or underdevelopment of septum secundum, such that they no longer overlapthis type of ASD is more common in female
What is the result of Secundum ASDs?
The result is a patent foramen ovale at birth, with left‐to‐right shunting from high pressure to low pressure.aka non‐cyanotic NOTE: is NOT a neural crest cell defect.can result in atrial fibrillaton and the formation of paradoxical emboli (blood clots that can travel to the brain, producing stroke)
What are Primum ASDs characterized by?
characterized by defects that are low on the interatrial wall (below the fossa ovalis).
What do Primum ASDs result from?
result from failure of septum primum to fuse with endocardial cushion
What is the result of Primum ASDs?
patent foramen primum at birth, with left‐to‐right shunting from high pressure tolow pressure (same as scandium ASDs)aka non-cyanoticNOTE: IS a neural crest defectmore common in children with Down’s syndrome.
What are the two parts of the ventricular septum?
Inferiorly is the muscular portion of the IV septum, superiorly is the membranous part of the IV septum.
How does the muscular portion of the IV septum form?
arises from an upward growth of mesoderm from the common ventricular floor, as seen in the image on the far left. The muscular portion stops short of the endocardial cushion, temporarily leaving an interventricular foramen
How does the membranous portion of the IV septum form?
The membranous part of the IV septum is formed by a downward growth from the endocardial cushion that fuses with the superior edge of the muscular portion
Development of the membranous portion of the IV septum is dependent on what?
Neural crest cell migration into the endocardial cushion
When is the IV septum fully formed?
end of week 8
Are ventricular septal defects cyanotic?
VSDs result in left‐to‐right shunt of blood between the ventricles, and are NON‐cyanotic at birth.VSDs may be found in either the muscular portion or the membranous portion of the IV septum, however membranous VSDs are much more common. In fact, membranous VSDs are the most common of all newborn cardiac defects.
What do membranous VSDs result from?
They result from failure of the membranous portion of the IV septum to form.The result is a patent interventricular foramen at birth, with left‐to‐right shunting of bloodthrough the open interventricular foramen from high pressure to low pressure at birth
Are membranous VSDs NC cell dependent?
YES. this type of VSD is more common in males
Describe Eisenmenger Complex
In patients with VSDS:Over time, the increased volume of blood that flows through the pulmonary trunk will cause damage to the intima of the vessel and subsequent narrowing of its lumen, leading to pulmonary stenosis.Pulmonary stenosis will give rise to increasing pulmonary resistance (pulmonary hypertension) and pressure will rise on right side relative to the left. As pressure on the right exceeds pressure on the left, blood flow through the patent interventricular foramen will reverse directions, now producing a right‐to‐left shunt.This will force deoxygenated blood into the left heart and out into the peripheral circulation causing late‐onset cyanosis (or Eisenmanger complex).
When does Eisenmenger’s Complex occur?
~9-10 months after birth. Surgical repair recommended before.NOTE: You can also get Eisenmenger’s complex with an ASD, but it occurs much more gradually over a longer period of time, since the pressures across the atria are lower than those across the ventricles.
What causes patent ductus arteriosus (PDA)?
Occasionally the ductus arteriosus will fall to close, giving rise to a PDA at birth. PDAs result in a left‐to‐right shunting of blood from the aorta to the pulmonary trunk that is non‐ cyanotic at birth
Closure of the ductus arteriosus is stimulated by what?
by a precipitous drop in the levels of prostaglandin E (PGE) and a change in oxygen tension.
When is PDA commonly seen?
in premature births or in mothers with rubella infection during pregnancy
What is the treatment for inducing closure of the ductus arteriosus?
PGE inhibitors. Sometimes surgery is required
In patients with PDA that develop Eisenmenger’s Complex, what is seen?
There is no reduction in oxygen content of the blood to the head and upper limbs because the defect and the site of the shunt are distal to those branches. The lower limbs will show cyanosis, but the upper limbs will be normal.
What is Coarctation (CoA)?
occurs when there is significant constriction or narrowing of the aorta distal to the origin of the left subclavian artery.
What causes CoA?
involve proliferation of the intimal lining of the aorta. Coarctation of the aorta occurs twice as often in males than in females, and the incidence of coarctation is increased in individuals with Down Syndrome and Turner Syndrome.
What are the clinical signs of CoA?
hypertension in the right arm concomitant with lowered blood pressure in the legs. If left untreated, the left heart must work harder than normal to try and push blood past the constriction which will eventually result in hypertrophy of the left ventricle.
Postductal coarctation occurs where?
distal to the ductus arteriosus (most common CoA= ~90%)The ductus arteriosus is closed in postductal coarctation.
How would the body supply blood to the lower limb in a post ductal coarctation?
Left subclavian arteryThoracic aortaLeft internal thoracic arteryIntercostal arteriesEven with the establishment of this collateral circulation, the head, upper body, and upper limb will be hypertensive relative to the lower limb which will be hypotensive with weak pulses.
Does the ductus arteriosus typically remain open at birth in preductal coarctation?
Yes. Thus, collateral circulation is not neededHowever, this can lead to differential cyanosis, because the upper body is perfused more adequately than the lower body, which will become cyanotic.
The truncal region is septated by the formation of?
aorticopulmonary septum, forming the pulmonary trunk and ascending aorta
T or F. NC cells migrate into the truncal region and play a critical role in the formation and spiraling of the aorticopulmonary septum.
T
Are truncal septation defects right-to-left or left-to-right?
right-to-left (i.e. produce cyanosis)
What are the three most common truncal separation defects?
tetrology of Fallot, transposition of the great vessels, and persistent truncus.
What is the most common cyanotic defect at birth?
Tetrology of Fallotnot life threatening. Cyanosis is present at birth, but it is fairly minimal. The degree of cyanosis increases with age.
What causes Tetrology of Fallot?
results when the AP septum forms and spirals as it should, but fails to align properly in the midline of the truncal lumenIt usually ends up displaced to the right resulting in unequal division of the aorta and pulmonary trunk. This results in the formation of a narrow diameter pulmonary trunk (pulmonary stenosis) and a wide diameter aorta.
What are the clinical markers of Tetrology of Fallot?
- Pulmonary stenosis (increases pressure on the right side due to pulmonary hypertension)**2. Always accompanied by a mVSD3. Large over‐riding aorta (straddles the mVSD)4. Hypertrophy of the right ventricle
Why is Tetrology of Fallot considered a right-to-left shunt?
The large, over‐riding aorta receives blood from both the left and right ventricles, so oxygen levels of the blood flowing out to the periphery is reduced
What is Tetrology of Fallot usually accompanied by?
PDA, which is actually beneficial to the individual because, at least initially, it will force more blood into the lungs, increasing the oxygen saturation level.
What causes transposition of the great vessels?
This occurs when the AP septum forms in the midline, but fails to spiral. It results in the aorta arising from the right ventricle and the pulmonary trunk arising from the left ventricle. These are the most severe of the truncal defects, with the most significant cyanosis at birth (often causing death)
In closed (or pure) transposition, are there any accompanying ASDs, VSDs, or PDA?
No. This gives rise to a totally separate right and left heart, with no communication between the systemic and pulmonary circulations. Deoxygenated blood entering the right heart via the SVC and IVC, flows into the right ventricle, then back out into the peripheral circulation via the aorta without being oxygenated. On the left side of the heart, super‐saturated, oxygenated blood is cycling repeatedly from the left atrium, to the left ventricle, to the lungs via the pulmonary trunk, and then back to left atrium.
Why is open transposition less severe than closed?
There is still a right‐to‐left shunting of blood and cyanosis at birth, but the presence of other defects (ASD, VSD, or PDA) allows for some mixing of oxygenated and deoxygenated blood. Survivability is determined by the degree of oxygen saturation that can achieved for the blood flowing to the periphery via the aorta.
What causes persistent truncus arteriosus?
occurs when the AP septum fails to form, or only forms partially. The end result is a single, common outflow vessel leaving the heart. Persistent truncus is always accompanied by a mVSD, and results in a right‐to‐left shunting of blood and some degree of cyanosis at birthSome approximation of a separate aorta and pulmonary trunk usually form somewhere distal to the common outflow tract. The common truncus straddles the mVSD, and a mix of oxygenated/deoxygenated blood (purple) is sent into the peripheral circulation via the aorta. The diameter of the pulmonary trunk will determine the level of cyanosis and survivability. It the pulmonary trunk is stenotic, survival probability is low because you cannot get enough blood into the pulmonary circulation to be oxygenated. If the pulmonary trunk has a larger diameter, there is a better chance of survival..
Early in development, the embryo is drained of venous blood via three main veins. What are these veins?
cardinal veins, vitelline veins, and umbilical veins
The cardinal veins form what structures?
SVC, IVC, brachiocephalic veins, azygos veins, and other major veins of the trunk.
The vitelline veins form what structures?
form veins related to the liver (hepatic veins, hepatic portal vein, sinusoids, etc.).
The umbilical veins form what structures?
None. it carries highly oxygenated blood from mom into the fetal circulation.
What post-embryonic structures do the 1st and 2nd aortic arches form?
None
What post-embryonic structures does the 3rd aortic arches form?
gives rise to the major arterial system of the neck, the right and left common carotid arteries and most of the right and left internal carotid arteries.
What post-embryonic structures does the right side of the 4th aortic arches form?
right subclavian artery.
What post-embryonic structures does the left side of the 4th aortic arches form?
the arch of the aorta
What post-embryonic structures does 5th aortic arches form?
None
What post-embryonic structures does the right side of the 6th aortic arches form?
right pulmonary artery
What post-embryonic structures does the left side of the 6th aortic arches form?
gives rise to the left pulmonary artery and the ductus arteriosusThe presence of the ductus arteriosus maintains the connection between the left pulmonary artery and the descending aorta, while the right pulmonary artery loses any attachment to other vasculature.
Why does the left recurrent laryngeal nerve get caught under the aortic arch on the left side and is found in the superior mediastinum?
Because the left 6th arch maintains it connection to the descending aorta via the ductus arteriosusOriginally, both right and left recurrent laryngeal nerves are hooked under the developing 6th aortic arch on their respective sides.
the right recurrent laryngeal nerve can be found where?
Because the distal half of the 6th aortic arch degenerates on the right side, the right recurrent laryngeal nerve is pulled up underneath the right subclavian artery and is found in a more cranial position at the root of the neck.
