Download Development of the Heart

Pamela E. Knapp, Ph.D.
Dept. of Anatomy & Neurobiology
Embryology
DEVELOPMENT OF THE HEART
READING: Larsen, 4th Edition, Chapter 12; or, Langman, 8th Edition, pp. 208-239
OBJECTIVES: Following lecture and assigned reading, students should be able to:
• Describe formation of paired endocardial tubes that fuse to form a primitive heart tube.
• Describe the primitive heart tube, including sinus horns, sinus venosus, primitive atrium and
ventricle, bulbus cordis. Include associated arterial structures, truncus arteriosus and aortic
sac.
• Describe connections between developing heart and inflow (venous structures) and outflow
(dorsal aortae) vessels.
• Describe development of the pericardial cavity, it’s relationship to the embryonic embryonic
coelom, and positional changes driven by embryonic flexion and folding.
• Describe development of the atrioventricular canals and role of the endocardial cushions.
• Discuss the partitioning of the primitive atrium by septum primum, septum secundum.
• Describe the embryological components that contribute to the left and right atria and ventricles.
• Be able to describe the role of the foramen ovale in blood flow changes at birth.
• Explain the partitioning into right and left ventricles and the separation of both the conus cordis
and truncus arteriosus into two separate channels by the aorticopulmonary septum.
• Differentiate between the membranous and muscular interventricular septa.
• Be able to describe the path of bloodflow through the primitive heart tube, and how it changes with
septation of the heart.
• Be able to describe (in words and by diagram) the following list of congenital cardiac defects. Be
able to discuss the structural abormalities, their result, and any known etiologic factors.
1. Ventricular septal defects
2. Atrial septal defects (differentiate between probe patent foramen ovale and secundum
defects)
3. Transposition of the Great Arteries (TGA)
4. Overriding Aorta or Pulmonary Trunk (unequal division of the truncus arteriosus),
5. Tetralogy of Fallot
Useful Terminology:
Angiogenesis = blood vessel formation
Cardiogenesis = heart formation
Aortic sac = base of aortic arches
Bulbus cordis = primitive heart chamber, it’s distal portion=conus cordis
Bulboventricular loop = loop formed when early heart folds upon itself
Endocardial cushions = mesenchymal masses that contribute to partitioning of the heart
Endocardial tubes = paired tubes that fuse to form the primitive heart tube
Primitive heart = tubular structure with grooves delineating chambers, from inflow to outflow:
sinus venosus, primitive paired atria, primitive ventricle, bulbus cordus, conus cordis
Septum transversum = mesodermal mass (initially in front of pericardial cavity) that separates
thoracic and abdominal cavities
Septum primum and secundum = portions of the developing interatrial septum
Ostium primum and secundum = openings formed by the septum primum and secundum
Truncus arteriosus = arterial trunk, opening from bulbus cordis of heart
Vitelline = relating to yolk sac
Mesenchyme = tissue composed of undifferentiated, multipotential cells. Not equivalent to mesoderm
DEVELOPMENT OF THE HEART
01. Extraembryonic blood vessels form
during the early part of the third week.
Yolk sac (extraembryonic) mesodermal
cells aggregate as blood islands and
form a network of cords.
Central cells of these cords differentiate
as blood cells and peripheral cells make
up the vessel lining.
.
Embryonic blood vessels form later
during the 3rd week (about two days
after first extraembryonic vessels) in
the visceral (splanchnic) layer of
lateral plate mesoderm.
Vessel formation in the embryo is
similar to extraembryonic vessel
formation, except blood cells
do not form from central cells of
embryonic vascular cords.
02. The blood islands, labeled here, are
located in the floor of celomic cavity
(future pericardial cavity). They form
from visceral (splanchnic) mesoderm
and later will coalesce to form the heart
primordia in the form of paired
endocardial tubes.
Mesoderm that is “in front of” the
primitive pericardial cavity
(connecting mesoderm of amnion
and yolk sac) is called the
transverse septum.
03. Looking down on the embryonic disc, and
through ectoderm and somatic mesoderm,
blood islands appear as dense “patches” in a
horse-shoe shaped area to each side of the
neural plate and “in front of” (cranial to) the
prochordal plate (buccopharyngeal membrane).
These embryonic blood islands, in visceral,
(splanchnic) mesoderm unite to form cords,
and ultimately, a plexus of vessels.
The central area of the resulting vascular plexus
(“in front of” and lateral to the prochordal plate)
represents the cardiogenic area where heart
primordia, endocardial tubes, will form.
Caudal to this region, paired dorsal aortae
will form.
04. A multi-dimensional view of the embryo with amion removed.
Transversely cut region shows the yolk sac below the developing embryo,
and relationship of the developing
blood islands to presumptive
embryonic vessels including
dorsal aortae.
Yolk sac blood islands
Recall that the space between somatic
and visceral (splanchnic) lateral plate
mesoderm is the embryonic coelomic
cavity (presumptive pericardial,
pleural and peritoneal cavities).
05. The portion of the coelomic cavity
“in front of” and lateral to the prochordal
plate (buccopharyngeal membrane) will
become the pericardial cavity.
Clusters of blood islands, formed from
splanchnic (visceral) mesodermal
mesenchyme, make up cardiogenic
tissue that later will give rise
to paired endocardial tubes.
Yolk Sac
06. A parasagittal section depicts a section
through one of the two developing endocardial
tubes located in the floor (visceral mesoderm)
of the primitive pericardial cavity.
Note the position of the presumptive pericardial
cavity and recall that cephalization ( growth in a
cephalic direction) has caused “lifting” of the
expanded neural plate (neural fold) so that it
partially overlies the prochordal plate
(buccopharyngeal membrane).
07. More rapid growth in a cephalic direction
results in expansion of neural structures and
flexion of the head region.
Flexion creates a “pocket” beneath the head
fold, the primitive mouth, or stomodeum, and
causes ventral displacement of the prochordal
plate, now more appropriately called
buccopharyngeal membrane, since it is
no longer “in front of” the notochord.
Rotation (180 degrees) of the paired
endocardial tubes, and pericardial cavity
ultimately brings them into a position ventral
to the developing foregut and caudal to the
buccopharyngeal membrane.
Vitelline veins, and later umbilical veins, form
from blood islands in the yolk sac
mesoderm and establish connections
with the endocardial tubes at the venous end
of the developing heart.
Paired endocardial tubes are continuous
with paired dorsal aortae, and with flexion,
a pair of aortic arches is created at the
arterial end of the developing heart.
At the completion of heart rotation, the
pericardial cavity has become ventral
to the endocardial tubes and the
transverse septum is positioned at the
venous end of forming heart.
08. Ventral view. Lateral body folding
brings paired endocardial tubes together
in the ventral midline as the embryo
becomes more tubular in shape.
Fusion of endocardial tubes proceeds in a
cephalic to caudal sequence.
Fused endocardial tubes will make up the lining
of the definitive heart. Later, lateral plate visceral
(splanchnic) mesoderm gives rise to myocardial
and epicardial layers.
It should be noted that future heart chambers
(stippled slashed, and cross-hatched in this illustration)
are not all contained in the pericardial cavity.
Initially, only the bulbus cordis (stippled) and
ventricle (upper slashed) are located within the
pericardial cavity.
09. The transverse section through a nearly
tubular-shaped embryo (early during the fourth week)
shows the relationships of the foregut, pericardial
cavity and fusing endocardial tubes. Formation of
the myoepicardial components is in progress at this time.
The forming heart spontaneously begins to beat
by 22 days.
(A mesentery, the dorsal mesocardium, temporarily
suspends the fused endocardial (cardiac) tube; this later
ruptures and forms the transverse and oblique coronary
sinuses of the pericardial sac.)
10. A slightly caudal transverse cut through the
same embryo (as in #09) shows portions of the
endocardial tubes that have not yet met in the
ventral midline (have not fused).
Lateral folding brings endocardial tubes
together as the gut forms by the apposition
and fusion of yolk sac (roof) endoderm.
11. Differential growth and expansion
forms four heart chambers, in linear
sequence and marked by grooves ( sulci).
From cranial to caudal, the primitive heart
chambers are:
Bulbus cordis (with conus cordis)
Ventricle
Paired (left and right) atria
Paired (left and right) sinus venosus
Originally, the bulbus cordis and primitive
ventricle are the only entire chambers that
occupy the pericardial cavity.
The arterial end of the primitive heart is held in
place by the aortic arches. The venous end is
also “fixed”, since paired atria and sinus horns
are temporarily embedded in the mesodermal
mesenchyme of the transverse septum.
Mesenchyme consists ofundifferentiated,
multipotential cells.)
12. The bulbus cordis delivers blood to the
truncus arteriosus, which is continuous with
paired aortic arches. These, in turn, are
continuous with paired dorsal aortae.
Later the truncus arteriosus gives rise
to an aortic sac from which additional
aortic arches arise, surround the foregut
(pharynx), and join the paired dorsal
aortae (see below).
13. The cardiac tube grows more rapidly
than its surrounding pericardial cavity.
This precocious growth gradually pulls
the paired chambers into the pericardial
cavity and causes the formation of a
bulboventricular loop.
Paired atrial components are moved together
and fuse to form a single-chambered atrium.
14. Elongation of the cardiac tube causes
it to bend and form a bulboventricular loop.
At first the loop is “U”-shaped and directed
anteriorly and to the right.
The atrial dilation is directed posteriorly
and to the left.
15. With continued growth the cardiac tube
becomes “S”-shaped and the bulboventricular
portion presents an even greater convexity
(anterior and to the right).
The atrium is moved posteriorly and toward
the head. Paired sinus horns become partially
fused, forming a transverse region of the sinus
venosus and right and left sinus horns.
16. Growth and expansion accentuates the
bulboventricular loop and forms a deep
bulboventricular sulcus (groove).
The internal ridge resulting from this
external sulcus marks the site of future
separation of definitive ventricles
(see below).
In the posterior view, illustrated here
on the right, growth and expansion have
also created a more transversely oriented
atrial dilation that has been pulled
posteriorly and cephalically.
17. In this illustration, the transversely
oriented atrial dilation (that has been pulled
posteriorly and cephalically) can be seen
from a ventral view as only small atrial portions
on each side of the conus cordis.
The distal portion of the bulbus
cordis is called the conus cordis.
The conus cordis and the truncus arteriosus
lie obliquely across the atrium to create a
depression (like an arm indenting a pillow)
that marks the future point of division of the
atrium into right and left chambers.
The transverse portion of the sinus venosus
is moved posteriorly and cephalically. It joins
the atrium at the sinu-atrial opening
and is joined by the right and left sinus horns.
The sinus horns receive, from medial to lateral,
vitelline veins from the yolk sac, umbilical veins
from the body stalk and fetal placenta, and
common cardinal veins that receive the major
veins of the body: precardinal (anterior cardinal) and
postcardinal (posterior cardinal) that drain
cranial and caudal portions of the embryo.
(see below).
18. Hemodynamic changes in the venous
channels result in most of the blood being
carried through the right sinus horn.
Because of the relationship of veins
with the forming heart they are
considered here, using dorsal
(posterior) views.
On the right:
Right precardinal and right common
cardinal veins form the superior vena
cava.
Right vitelline vein (proximal portion) forms the
proximal portion of the inferior vena cava.
Right horn of sinus venosus is incorporated into the
right atrium (forms smooth portion, the sinus venarum).
On the left:
The proximal portion of the left sinus horn and the
transverse portion of the sinus venosus form the
coronary sinus.
The distal portion of the left sinus horn, and possibly
a portion of the common cardinal vein, form the
oblique vein of the left atrium (of Marshall).
Left vitelline, umbilical and cardinal veins are obliterated.
Primitive pulmonary veins are incorporated into the
left atrium and form four pulmonary veins.
POSTERIOR VIEWS
19. Internal features of the forming heart are
observed in coronal (frontal) and sagittal sections.
Primitive trabeculae develop in both the proximal
portion of the bulbus cordis and the primitive
ventricle.
The broad junction between these two chambers is the
primary interventricular foramen. Superiorly this
junction (foramen) is marked by the bulboventricular
ridge.
The primary interventricular septum is
created, by differential growth and expansion
of both bulbus cordis and primitive ventricle,
as a progressively elongating inferior thickening.
The proximal portion of the bulbus cordis later will
form the right ventricle, and the primitive ventricle
will become the left ventricle.
The atrioventricular canal or foramen is a broad transversely
oriented opening between the atrium and both the future right
ventricle (proximal bulbus cordis) and future left ventricle
(primitive ventricle).
Septation of the heart into right and left sides occurs from
the middle of the 4th to the end of the 5th week.
The atrioventricular canal will become partitioned by
mesenchymal masses called endocardial cushions
that divide the canal into right and left atrioventricular
canals.
Lateral endocardial cushions contribute to the
atrioventricular valves.
(Failure of fusion of endocardial cushions results in
a single A-V canal with abnormal valve leaflets, and
defective atrial and ventricular septation -uncommon.)
(Obliteration of the right A-V canal is called tricuspid
atresia. It is caused by overgrowth of endocardial cushions
or fusion of valves. It may be associated with patent foramen
ovale (see below), ventricular septal defect, underdeveloped right
ventricle and hypertrophied left ventricle).
20. Atrial septation begins with the formation
of the septum primum (weeks 5 to 6).
When the atrium is deeply grooved by the
conus cordis (distal portion of the bulbus
cordis) and truncus arteriosus, the external
depression is reflected internally
as an initially small sickle-shaped crest, the
early septum primum. It extends from the atrial
roof into the atrial lumen.
21. With growth, the sickle- shaped septum
primum extends toward the endocardial
cushion; it increases in size and thus
progressively descends (like a shade being
drawn down).
The opening beneath the free edge
of theseptum primum is called the
ostium primum. It becomes smaller
as the septum primum approaches
the endocardial cushion.
The ostium primum ultimately will close,
as the septum primum fuses with the
endocardial cushion (failure of this fusion
is rare).
Prior to closure, perforations appear in the
superior portion of the septum primum.
22. Perforations in the septum primum
coalesce to form a single opening, the
ostium secundum. Soon after the
formation of the ostium secundum,
a flange or fold, the septum secundum,
appears to the right of the septum
primum, between it and the valve of the
sinuatrial opening.
23. The septum secundum is also sickle-shaped; It progressively enlarges and descends
toward the endocardial cushion. It forms an incomplete partition and the opening beneath
its free edge is the foramen ovale.
For a time, blood flows from the right atrium through the foramen ovale, between septum
secundum and septum primum, through ostium secundum and into the left atrium.
Ultimately, the tissue superior to the
ostium secundum breaks down so
that the septum primum then acts
as a flap valve that covers the
foramen ovale.
Septum primum and secundum
together make up the interatrial
septum.
It serves as a one-way valve, allowing
blood to flow from the right atrium
to the left atrium during fetal life.
After birth, flow of blood from the umbilical
vein ceases and a large volumn of blood from
the lungs is returned to the left atrium. Pressure
in the left atrium is thus increased and the flap
valve in the interatrial septum is functionally
closed. Anatomical closure usually follows shortly thereafter.
Atrial septal defects may be due to defective endocardial cushions, excessive resorption of
septum primum (common), or inadequate development of septum secundum (uncommon).
Failure of interatrial septum formation results in a common (single) atrium, a condition referred to as
cor triloculare biventriculare (heart with 3 chambers and 2 ventricles – very rare!).
Premature closure of the foramen ovale results in massive hypertrophy of both the right atrium
and the right ventricle.
24.The right ventricle develops from the proximal
(trabeculated) part of the bulbus cordis. The left
ventricle develops from the primitive ventricle of
the early tubular heart. The opening between the
the bulbus cordis and the primitive ventricle is the
primary interventricular foramen.
Superiorly (and posteriorly), the primary
interventricular foramen is bordered
by the bulboventricular ridge. Inferiorly,
it is bordered by the primary interventricular
septum.
It should be noted that these two
bounding structures are, in fact, continuous
with each other (see below).
25. The muscular interventricular septum, due
to growth and expansion of both the bulbus
cordis (forming right ventricle) and the
primitive ventricle (forming left ventricle),
is increased in height.
As the interventricular septum approaches, but
does not yet meet the endocardial cushion,
it forms the muscular interventricular septum.
Separation of the forming ventricles will not occur
until the membranous interventricular septum is
formed. The fusion of the muscular interventricular
septum with endocardial cushions and conus
cordis ridges will complete the ventricular separation .
A pair of spirally oriented, opposing conotruncal
swellings ( ridges) appear in the wall of the
conus cordis and truncus arteriosus (see below).
26. With growth, there is fusion of the pair of
spirally oriented, opposing conotruncal ridges to form
the aorticopulmonary septum. This
septum divides both conus cordis and truncus
arteriosus into an aortic trunk and a pulmonary trunk.
Fusion of the muscular interventricular septum
with both the endocardial cushions and fused ridges
of the conus cordis (proximal aorticopulmonary septum)
forms the membranous interventricular septum
(septum membranaceum) and completes the separation
of the ventricles. The membranous interventricular
septum separates the apical regions (outflow tracts)
of the right and left ventricles.
Membranous I.V. Septal defects result from failure of fusion of
the endocardial cushion and conus ridges with the muscular
interventricular septum (common).
Persistent Truncus Arteriosus is due to failure of truncal components
of the conotruncal ridges to form.
Transposition of Great Vessels: failure of conotruncal ridges to spiral.
Tetralogy of Fallot: unequal partitioning of conotruncal (bulbotruncal) region and failure of
closure by the membranous interventricular septum results in:
1.pulmonary stenosus, 2.interventricular septal defect, 3. overriding aorta (overrides
both ventricles), 4. right ventricular hypertrophy (common)
Neural crest cells contribute to the conotruncal ridges. Defective septation into pulmonary and aortic
channels is frequently observed in company with craniofacial malformations of neural crest origin.
Many thanks to Dr. Caroline Goode Jackson, Ph.D., for diagrams used in this syllabi and in lectures!!
EMBRYOLOGY - SAMPLE QUESTIONS – Development of the HEART, Dr. Knapp
1.
Which of the following are sites of vessel formation?
A.
Extraembryonic mesoderm of yolk sac.
B.
Cardiogenic tissue
C.
Visceral (splanchnic) mesoderm of embryo
D.
Embryonic blood islands
E.
All of the above
2.
Which of the following is NOT considered to be a component of the early heart tube?
A.
Bulbus cordis
D.
Primitive ventricle
B.
Dorsal aorta
E.
Primitive atrium
C.
Sinus venosus
3.
The truncus arteriosus of the primitive heart:
A.
Is later partitioned by the aorticopulmonary septum
B.
Is not a definitive structure in normal adults
C.
Gives rise to the aorta and the pulmonary trunk
D.
Is synonymous with the ductus arteriosus
E.
“A”, “B” and “C”
4.
The U-shaped bulboventricular loop of the primitive heart forms as a result of the:
A.
Growth of the bulbus cordis and primitive ventricle
B.
Fixation of the arterial end of the heart
C.
Fixation of the venous end of the heart
D.
All of the above
5.
The fetal right atrium is mainly derived from the:
A.
Primitive pulmonary veins
C.
Primitive atrium
B.
Right pulmonary vein
D.
Sinus venosus
6.
Closure of the foramen primum results from fusion of the:
A.
Septum primum and the septum secundum
B.
Septum secundum and the septum spurium
C.
Septum primum and the endocardial cushion
D.
Septum secundum and the endocardial cushion
E.
Septum primum and the right sinoatrial valve
7.
The distal portion of the bulbus cordis, called the conus cordis, of the embryonic heart:
A.
Forms the outflow tract (at base of aortic trunk) of the left ventricle.
B.
Forms the outflow tract (at base of pulmonary trunk) of the right ventricle.
C.
Becomes subdivided by the proximal portion of the aorticopulmonary septum
D.
All of the above
8.
Early during the separation of heart chambers the atrioventricular foramen is subdivided by the:
A.
Septum primum
D.
Muscular interventricular septum
B.
Septum secundum
E.
Bulboventricular ridge
C.
Endocardial cushions
ANSWERS: 1 = E; 2 = B; 3 = E; 4 = D; 5 = D; 6 = C; 7 = D; 8 = C