Cardiac Embryology & Pathology of Congenital Heart Disease

Question 1

Where do the endocardial tubes develop from (germ layer)?

Answer 1

Cardiogenic mesoderm, which forms a horseshoe cranial to buccopharyngeal membrane.

Horseshoe of mesodermal lies within splanchnic layer of lateral mesoderm of embryonic disk

Question 2

What are the functions of the first and second heart fields?

Answer 2

First - original formation of bilateral endocardial tubes, making most of the primitive ventricle

Second - responsible for elongation of heart tube, forming outflow tract, right ventricle, and most of the atria of the heart tube

Question 3

What forms the pericardial cavity?

Answer 3

Intraembryonic coelom. As the lateral mesoderm separates, the somatic layer will surround the foregut and pericardium, and the space where the gut and heart resides comes from this coelom.

Question 4

What are the arms of the inverted Y of the heart tube? Central part? Top part?

Answer 4

The precursors of the atrial chambers (sinus venosus)

Central part is the primitive ventricle, which will mostly be the left ventricle

Top part = conotruncal segment, also known as the primitive RV + truncus arteriosus

Question 5

What are the cells which regulate the migration of the second heart field? What portions of the heart does this field play a critical role in developing?

Answer 5

Neural crest cells

Second heart field - critical role in RV + outflow tract into conus truncus

Keep in mind, heart field blood flow is currently going: Sinus venosus -> atria -> LV (primitive ventricle) -> RV -> truncus arteriosus (conotruncal segment)

Question 6

When the heat begins folding, how do the conotruncus and AV canals shift?

Answer 6

Conotruncus -> shifts leftward to be more in the center of the heart

AV canal -> shifts rightward so that when the endocardial cushions are placed, the ventricles are evenly divided

This is all with respect to the primitive ventricle bending to the right and the sinus venosus shifting upward and to with left

Question 7

What are the truncoconal cushions?

Answer 7

The neural crest derived cells which rotate to form the aorticopulmonary septum (infundibular septum) within the conotruncal segument

Question 8

How are the right and left AV canals formed?

Answer 8

When the AV cushions form on the ventral and dorsal surfaces of the large AV canal, this separates the right ventricle from the left ventricle

Question 9

What do the small endocardial cushions forming of the lateral walls of the AV canal form?

Answer 9

Form the mitral and tricuspid valves

(thus, membranous portion of IV septum, atrial septum, and mitral/triscupid valves are derived from endocardial cushions, which are derived from cardiac jelly)

Question 10

What is foramen primum?

Answer 10

The space left between septum primum and the AV cushions as it grows towards the AV cushions from the roof of the atrium

Question 11

What is foramen secundum and when does it form?

Answer 11

The perforations which coalesce into a hole in the septum primum before it completely obliterates foramen primum by attaching to the endocardial cushion

Question 12

How is foramen ovale formed? How is the valve formed?

Answer 12

When septum secundum grows to the right of the perforated septum primum, but does not quite reach the endocardial cushions. The remaining portion of the septum primum becomes the valve of foramen ovale.

Question 13

What is the most common congenital heart disease, aside from congenital bicuspid aortic valve?

Answer 13

Ventricular septal defect

Question 14

What is the most common genetic cause of CHD? What defect does it cause?

Answer 14

Down syndrome - atrioventricular septal defects (due to endocardial cushion defect)

Question 15

What is the most common cardiac defect associated with DiGeorge syndrome?

Answer 15

Tetralogy of Fallot

Question 16

What are the most common cardiac defects associated with congenital rubella, maternal diabetes, and Turner syndrome?

Answer 16

Rubella - patent ductus arteriosus

Maternal diabetes - Transposition of great vessels

Turner syndrome - Coarctation of the aorta

Question 17

What is the most common type of shunt in CHD, and how will this put stress on the heart?

Answer 17

Left-to-right shunt, associated with atrial and ventricular septal defects for the most part

-> Increases pulmonary blood flow, which increases volume and pressure in the pulmonary circulation

Question 18

What will happen as a result of left-to-right shunt within the pulmonary circulation (pathologically)?

Answer 18

Pulmonary arteries will vasoconstrict in response to increased blood flow, and media will thicken. If prolonged, can lead to intimal fibrosis, and even atherosclerosis.

Question 19

What are we trying to avoid in fixing a left-to-right shunt?

Answer 19

Irreversible changes in pulmonary arterial vasculature and RV hypertrophy whereby fixing the shunt would mean not enough blood will get to the lungs anymore

Question 20

What is it called when blood flow in a left to right shunt reverses to a right-to-left shunt because pulmonary vascular resistance has exceeded systemic vascular resistance? This can happen in ASD and VSD.

Answer 20

Eisenmenger syndrome

Question 21

What is the most common type of ASD? Where will the ASD be?

Answer 21

Ostium secundum ASD - excessive absorption of septum primum in formation of foramen secundum, or inadequate growth of septum secundum

-> ASD will be near the center of interatrial septum

Question 22

What is ostium primum ASD and who is it common in?

Answer 22

Ostium primum ASD -> failure of septum primum to fuse with AV cushions

Often has concomitant AV valve dysfunction / VSD
-> associated with trisomy 21

Question 23

Where do sinus venosus ASD defects occur?

Answer 23

Usually in the upper atrial septum, associated with entrance of superior vena cava

Question 24

Can you live with an ASD?

Answer 24

Yes - many go unrecognized until adulthood if small enough, but will present with pulmonary hypertension

Question 25

What are the two most common types of VSD? Where are they located?

Answer 25

Membranous VSD - usually just below the aortic valve. (area around endocardial cushions). Surgically repaired

Muscular VSD - anywhere in muscular portion of IV septum, typically heal spontaneously

Question 26

Where are inlet / outlet VSD located?

Answer 26

Inlet - close to tricuspid valve

Outlet - Close to pulmonic valve (less common than membranous VSD)

Question 27

What will happen to the left side of the heart as a result of a VSD?

Answer 27

Will have a volume overload due to more blood coming from pulmonary circulation. Since less blood is getting into systemic circulation -> decreased cardiac output -> tachycardia and RAA activation

-> eccentric hypertrophy and LA / biventricular dilatation

Question 28

Where does the ductus arteriosus normally run? What causes its closing?

Answer 28

Pulmonary artery to proximal descending aorta (just distal to left subclavian artery)

Closed by:

1. Increased arterial O2.
2. Decreased pulmonary vascular resistance (blood normally flows as right->left shunt in fetal development)
3. Decreased PGE2 levels (comes from placenta)

Question 29

What factors lead to a persistent ductus arteriosus? When might you not want to close it?

Answer 29

Opposite of what closes it:

1. Hypoxia conditions
2. Persistently high vascular resistance (i.e. prematurity, pulmonary disease)
3. Exposure to teratogens (i.e. congenital rubella)

Might not want to close it if associated with other cardiac abnormalities (i.e. transposition of great vessels).

Question 30

What do right-to-left shunts cause overall?

Answer 30

Cyanotic CHD

Question 31

Why does digital clubbing occur in the setting or right-to-left shunts? What is it?

Answer 31

Hypertrophic osteoarthropathy -> digital clubbing seen by no window between the fingers when distal phalanges are pressed together

Blood which would normally have growth factors and platelets inactivated in lungs bypasses the lungs into the systemic circulation, where it stimulates subperiosteum of digital extremity to divide

Question 32

What hematologic change occurs as a result of hypoxemia / cyanosis?

Answer 32

Polycythemia -> increased RBC count (erythrocytosis)

Question 33

What is the most common type of right-to-left shunt, and its single underlying pathophysiological mechanism?

Answer 33

Tetralogy of Fallot, anterosuperior displacement of infundibular septum during embryologic development (displaced more towards pulmonary artery)

Question 34

What are the four classic features of Tetralogy of Fallot?

Answer 34

1. Right ventricular outflow tract obstruction -> due to subpulmonic stenosis
2. Hypertrophy of RV
3. VSD
4. Over-riding aorta (overrides the VSD)

Question 35

What determines the severity of tetralogy of fallot? What is the most mild form?

Answer 35

Degree of RV outflow tract obstruction

Mildest - pink tetralogy - RVOTO is mild enough that systemic pressures > pulmonary, shunt is actually left-to-right.

Question 36

What happens in severe forms of Tetralogy?

Answer 36

RV pressures are very high due to RVOTO, right->left shunt, deoxygenated blood mixes with oxygenated blood in LV -> cyanosis

Question 37

What causes transposition of the great vessels (arteries, TGA)and who is it common in?

Answer 37

aorticopulmonary septum does not spiral correctly
-> pulmonary trunk comes from left ventricle and aorta comes from right ventricle

Most common in infants w/diabetic mothers

Question 38

How do you initially treat TGA?

Answer 38

Need to keep blood mixing. Hopefully there is a VSD, or need to keep ductus arteriosus patent with PGE until definitive corrective surgery.

Question 39

What is thought to cause coarctation of the aorta? How will the aorta appear after this segment?

Answer 39

Decreased blood flow through aortic isthmus in utero, between left subclavian artery and ductus arteriosus

Typically, poststenotic aortic dilatation -> due to jet stream from high velocity blood thru isthmus, weakening wall

Question 40

Who is coarctation of the aorta common in?

Answer 40

Most common in males, but very common in females with Turner syndrome

Question 41

What two factors are the best predictors of the severity of coarctation of the aorta?

Answer 41

1. Severity of the narrowing

2. Patency of ductus arteriosus

Question 42

What will happen in severe stenosis of the aorta before and after ductus arteriosus closes?

Answer 42

Before - some blood will move past isthmus via a right->left shunt which allows left heart to not work as hard against stenosis. Patient will be cyanotic since blood from right heart is deoxygenated

After - venous return from lungs increases, with massive increase in afterload and rapid progression to progressive heart failure + cardiogenic shock

Question 43

If aortic stenosis is mild in coarctation, how will the patient present? (include just pulse findings)

Answer 43

Later in life, patient presents with upper extremity HTN and lower extremity weak pulses.

Sometimes, if coarctation is before left subclavian artery, right arm pressure > left arm pressure.

Question 44

How will the body cope with decreased blood flow to the lower extremities in mild aortic stenosis?

Answer 44

Increased blood through thru internal thoracic artery and the intercostal arteries to descending aorta (reversal of normal flow).

Ribs can be seen as notched (pressure erosions beneath them) from increased blood pressure, and pulses in intercostal arteries will be evident.