Cardiovascular System

Embryology
1) Formation of Heart Tube
• Lateral plate mesoderm (at the cephalic area of the embryo) will split
into a somatic layer and a splanchnic layer, thus forming the
pericardial cavity.
• Precardiac mesoderm is preferentially distributed to the splanchnic
layer and is now called heart-forming regions (HFRs).
• As lateral folding of the embryo occurs, the HFRs will fuse in the
midline to form a continuous sheet of mesoderm.
• Hypertrophied foregut endoderm secretes vascular endothelial
growth factor (VEGF), which induces the sheet of mesoderm to form
discontinuous vascular channels that eventually get remodeled into a
single endocardial tube (endocardium).
• Mesoderm around the endocardium forms the myocardium, which
secretes a layer of extracellular matrix proteins called cardiac jelly.
• Mesoderm migrating into the cardiac region from the coelomic wall
near the liver forms the epicardium.
2) Primitive Heart Tube Dilatations
• Five dilatations soon become apparent along the length of the tube: --
-Truncus arteriosus (T)
-Bulbus cordis (B)
-Primitive ventricle (PV)
-Primitive atrium (PA)
-Sinus venosus (SV)
• These five dilatations develop into the
adult structures of the heart.
***(White area: arterial portion. Shaded area: venous portion).
3) The Aorticopulmonary (AP) Septum
A. FORMATION.
• Neural crest cells migrate from the hindbrain region through pharyngeal arches 3, 4, and 6 and
invade both the truncal ridges and the bulbar ridges.
• The truncal and bulbar ridges grow and twist around each other in a spiral fashion and eventually
fuse to form the AP septum.
• The AP septum divides the truncus arteriosus and bulbus cordis into the aorta and pulmonary
trunk.
B. CLINICAL CONSIDERATIONS
• 1. Persistent truncus arteriosus (PTA) is caused by abnormal neural crest
cell migration such that there is only partial development of the AP
septum.
• PTA results in a condition in which one large
vessel leaves the heart and receives blood
from both the right and the left ventricles.
• PTA is usually accompanied by a membranous
ventricular septal defect (VSD) and is
associated clinically with marked cyanosis
(right-to-left [R → L] shunting of blood).
2. D-transposition of the great arteries (complete) is caused by abnormal neural
crest cell migration such that there is nonspiral development of the AP septum.
D-transposition results in a condition in which the aorta arises abnormally from the
right ventricle and the pulmonary trunk arises
abnormally from the left ventricle.
-The systemic and pulmonary circulations are completely
Separated from each other.
-It is incompatible with
life unless an accompanying shunt exists like a VSD,
patent foramen ovale, or patent ductus arteriosus.
-It is associated clinically with marked cyanosis
(R → L shunting of blood).
3. L-transposition of the great vessels (corrected). In L-transposition, the
aorta and pulmonary trunk are transposed and the ventricles are “inverted”
such that;
the anatomical right ventricle lies
on the left side and
the anatomical left ventricle lies
on the right side.
These two major deviations
offset one another such that
blood flow pattern is normal.
4. Tetralogy of Fallot (TF) is caused by an abnormal neural crest cell migration such that there is
skewed development of the AP septum. TF results in a condition in which the pulmonary trunk
obtains a small diameter while the aorta obtains a large diameter.
TF is characterized by four classic malformations:
-Pulmonary stenosis,
-Right ventricular hypertrophy,
-Overriding aorta,
-Ventricular septal defect
(the mnemonic PROVE).
TF is associated clinically with marked cyanosis
(R → L shunting of blood) in which the clinical
consequences depend primarily on the
severity of the pulmonary stenosis.
4) The Atrial Septum

A. FORMATION.
-The crescent-shaped septum primum forms in the roof of the primitive atrium and grows
toward the atrioventricular (AV) cushions in the AV canal.
-The foramen primum forms between the free edge of the septum primum and the AV
cushions; it is closed when the septum primum fuses with the AV cushions.
-The foramen secundum forms in the center of the septum primum.
-The crescent-shaped septum secundum forms to the right of the septum primum.
-The foramen ovale is the opening between the upper and the lower limbs of the septum
secundum.
-During embryonic life, blood is shunted from the right atrium to the left atrium via the
foramen ovale.
-Immediately after birth, functional closure of the foramen ovale is facilitated both by a
decrease in right atrial pressure from occlusion of placental circulation and by an increase
in left atrial pressure due to increased pulmonary venous return.
-Later in life, the septum primum and septum secundum anatomically fuse to complete the
formation of the atrial septum.
B. CLINICAL CONSIDERATIONS.
• Atrial septal defects (ASDs) are noted on auscultation with a loud S1 and a wide,
fixed, split S2 and are characterized by L → R shunting of blood.
1. Foramen secundum defect is caused by
excessive resorption of septum primum,
septum secundum, or both. This results
in a condition in which there is an opening
between the right and the left atria.
Some defects can be tolerated for
a long time, with clinical symptoms
Manifesting as late as age 30 years.
It is the most common clinically significant ASD.
2. Common atrium (cor triloculare biventriculare) is caused by the complete failure of septum
primum and septum secundum to develop. This results in a condition in which there is formation of
only one atrium.
3. Probe patency of the foramen ovale is caused by
incomplete anatomic fusion of septum primum and
septum secundum. It is present in approximately
25% of the population and is usually of no clinical importance.
4. Premature closure of foramen ovale is closure
of foramen ovale during prenatal life. It results in
hypertrophy of the right side of the heart
and underdevelopment of the left side of the heart.
5) The Atrioventricular (AV) Septum
A. FORMATION. The dorsal AV cushion and ventral AV cushion
approach each other and fuse to form the AV septum. The AV septum
partitions the AV canal into the right AV canal and the left AV canal.
B. CLINICAL CONSIDERATIONS
1. Persistent common AV canal is caused by failure of fusion of the dorsal and ventral AV
cushions. It results in a condition in which the common AV canal is never partitioned into
the right and left AV canals, so that a large hole can be found in the center of the heart.
Consequently, the tricuspid and bicuspid valves are represented by one valve common
to both sides of the heart. Two common
hemodynamic abnormalities are found:
a. L → R shunting of blood from the left
atrium to the right atrium, causing an
enlarged right atrium and right ventricle.
b. Mitral valve regurgitation, causing an enlarged
left atrium and left ventricle.
2. Ebstein’s anomaly is caused by the failure of the posterior and septal leaflets of
the tricuspid valve to attach normally to the annulus fibrosus; instead they are
displaced inferiorly into the right ventricle.
It results in a condition in which the right ventricle is divided
Into a large, upper, “atrialized” portion and a small,
lower, functional portion.
Due to the small, functional portion of the right
ventricle, there is reduced amount of blood available
to the pulmonary trunk. It is usually
associated with an ASD. The anteroposterior
radiograph shows massive cardiomegaly
due to enlargement of the right atrium.
3. Foramen primum defect is caused by a failure of the AV septum to
fuse with septum primum.
It results in a condition in which the foramen
primum is never closed and is
generally accompanied by an
abnormal mitral valve.
4. Tricuspid atresia (hypoplastic right heart) is caused by an insufficient amount of
AV cushion tissue available for the formation of the tricuspid valve. It results in a
condition in which there is complete agenesis of the tricuspid valve so that no
communication between the right atrium and the right ventricle exists.
It is associated clinically with marked cyanosis and is
always accompanied by the following:
-Patent foramen ovale.
-Interventricular septum defect.
-Overdeveloped left ventricle.
-Underdeveloped right ventricle.
The anteroposterior radiograph shows
a normal-sized heart with a convex left cardiac contour.
6) The Interventricular (IV) Septum
A. FORMATION.
-THE MUSCULAR IV septum develops in the midline on the floor of the
primitive ventricle and grows toward the fused AV cushions.
-The IV foramen is located between the free edge of the muscular IV
septum and the fused AV cushions.
-This foramen is closed by the membranous IV septum, which forms by
the proliferation and fusion of tissue from three sources: the right
bulbar ridge, the left bulbar ridge, and the AV cushions.
B. CLINICAL CONSIDERATIONS. IV SEPTAL
DEFECTS (VSDS)
-Membranous VSD is caused by faulty fusion of the right bulbar ridge,
the left bulbar ridge, and the AV cushions.
-It results in a condition in which an opening between the right and left
ventricles allows free flow of blood.
-A large VSD is initially associated with L →R shunting of blood,
increased pulmonary blood flow, and pulmonary hypertension.
-Patients with L → R shunting of blood complain of excessive fatigue on
exertion.
-The anteroposterior radiograph demonstrates cardiomegaly and a
marked enlargement of the main pulmonary artery.
2. Eisenmenger syndrome (uncorrected VSD, ASD, or PDA). Initially, a VSD,
ASD, or PDA is associated with L → R shunting of blood, increased pulmonary
blood flow, and pulmonary hypertension.
-Later, the pulmonary hypertension causes marked proliferation of the tunica
intima and tunica media of pulmonary muscular arteries and arterioles,
resulting in a narrowing of their lumen.
-Ultimately, pulmonary resistance may become higher than systemic
resistance and cause R → L shunting of blood and cyanosis.
3. Muscular VSD is caused by single or multiple perforations in the muscular
IV septum.
4. Common ventricle (cor triloculare biatriatum) is caused by failure of the
membranous and muscular IV septa to form.
7) Development of the Arterial System
A. FORMATION. In the head and neck region, the arterial pattern
develops mainly from six pairs of arteries (called aortic arches) that
course through the pharyngeal arches.
-The aortic arch arteries undergo a complex remodeling process that
results in the adult arterial pattern.
-In the rest of the body, the arterial patterns develop mainly from the
right and left dorsal aortae.
-The right and left dorsal aortae fuse to form the dorsal aorta, which
then sprouts posterolateral arteries, lateral arteries, and ventral
arteries (vitelline and umbilical).
8) Development of the Venous System.
• The venous system develops from the vitelline, umbilical, and
cardinal veins that empty into the sinus venosus.
• These veins undergo remodeling due to a redirection of venous blood
from the left side of the body to the right side in order to empty into
the right atrium.
B. CLINICAL CONSIDERATIONS
1. Postductal coarctation of the aorta occurs when the aorta is abnormally constricted.
-A postductal coarctation is found distal to the origin of the left subclavian artery and
inferior to the ductus arteriosus.
-It is clinically associated with increased blood pressure in the upper extremities, lack of
pulse in femoral artery, high risk of both cerebral hemorrhage, and bacterial
endocarditis.
-Collateral circulation around the constriction involves the internal thoracic, intercostal,
superior epigastric, inferior epigastric, and external iliac arteries.
-Dilation of the intercostal arteries causes erosion of the lower border of the ribs (called
“rib notching”), which can be seen on X-ray.
-Less commonly, a preductal coarctation may occur where the constriction is located
superior to the ductus arteriosus.
-Turner syndrome (45,XO) is associated with a preductal coarctation.
2. Patent ductus arteriosus (PDA) occurs when the ductus arteriosus—a
connection between the left pulmonary artery and aorta—fails to close.
-Normally the ductus arteriosus functionally closes within a few hours after
birth via smooth muscle contraction to ultimately form the ligamentum
arteriosum.
-A PDA causes L → R shunting of oxygen-rich blood from the aorta back into
the pulmonary circulation.
-A PDA can be treated with prostaglandin-synthesis inhibitors (such as
indomethacin), acetylcholine, histamine, and catecholamines, all of which
promote closure of the ductus arteriosus.
-Prostaglandin E (PGE1), intrauterine asphyxia, and neonatal asphyxia sustain
patency of the ductus arteriosus.
-A PDA is very common in premature infants and maternal rubella infection.