Heart development

Heart development (also known as

cardiogenesis) refers to the prenatal
development of the human heart. This
begins with the formation of two
endocardial tubes which merge to form
the tubular heart, also called the primitive
heart tube, that loops and septates into
the four chambers and paired arterial
trunks that form the adult heart. The
heart is the first functional organ in
vertebrate embryos, and in the human,
beats spontaneously by week 4 of
development.[3]
 Heart development

Development of the human heart during the

first eight weeks (top), and the formation of
the heart chambers (bottom). In this figure,
the blue and red colors represent blood
inflow and outflow (not venous and arterial
blood). Initially, all venous blood flows from
the tail/atria to the ventricles/head, a very
different pattern from that of an adult.[1] [2]

Details

Gives rise to Heart

System Fetal circulation,

 circulatory system
Anatomical terminology

The tubular heart quickly differentiates

into the truncus arteriosus, bulbus cordis,
primitive ventricle, primitive atrium, and
the sinus venosus. The truncus
arteriosus splits into the ascending aorta
and pulmonary artery. The bulbus cordis
forms part of the ventricles. The sinus
venosus connects to the fetal circulation.

The heart tube elongates on the right

side, looping and becoming the first
visual sign of left-right asymmetry of the
body. Septa form within the atria and
ventricles to separate the left and right
sides of the heart.[4]

Early development
The heart derives from embryonic
mesodermal germ-layer cells that
differentiate after gastrulation into
mesothelium, endothelium, and
myocardium. Mesothelial pericardium
forms the outer lining of the heart. The
inner lining of the heart, lymphatic and
blood vessels, develop from
endothelium.[5] [2]

Endocardial tubes …
In the splanchnopleuric mesenchyme on
either side of the neural plate, a
horseshoe-shaped area develops as the
cardiogenic region. This has formed from
cardiac myoblasts and blood islands as
forerunners of blood cells and vessels.[6]
By day 19, an endocardial tube begins to
develop in each side of this region. These
two tubes grow and by the third week
have converged towards each other to
merge, using programmed cell death to
form a single tube, the tubular heart.[7]

From splanchnopleuric mesenchyme, the

cardiogenic region develops cranially and
laterally to the neural plate. In this area,
two separate angiogenic cell clusters
form on either side and coalesce to form
the endocardial tubes. As embryonic
folding continues, the two endocardial
tubes are pushed into the thoracic cavity,
where they begin to fuse together, and
this is completed at about 22 days.[8][2]

At around 18 to 19 days after

fertilisation, the heart begins to form.
This early development is critical for
subsequent embryonic and prenatal
development. The heart is the first
functional organ to develop and starts to
beat and pump blood at around day 22.[1]
The heart begins to develop near the
head of the embryo in the cardiogenic
area.[1] Following cell signalling, two
strands or cords begin to form in the
cardiogenic region[1] As these form, a
lumen develops within them, at which
point, they are referred to as endocardial
tubes.[1] At the same time that the tubes
are forming other major heart
components are also being formed.[7]
The two tubes migrate together and fuse
to form a single primitive heart tube, the
tubular heart which quickly forms five
distinct regions.[1] From head to tail,
these are the truncus arteriosus, bulbus
cordis, primitive ventricle, primitive
atrium, and the sinus venosus.[1] Initially,
all venous blood flows into the sinus
venosus, and contractions propel the
blood from tail to head, or from the sinus
venosus to the truncus arteriosus.[1] The
truncus arteriosus will divide to form the
aorta and pulmonary artery; the bulbus
cordis will develop into the right ventricle;
the primitive ventricle will form the left
ventricle; the primitive atrium will
become the front parts of the left and
right atria and their appendages, and the
sinus venosus will develop into the
posterior part of the right atrium, the
sinoatrial node and the coronary sinus.[1]

Heart tube position …

The central part of cardiogenic area is in

front of the oropharyngeal membrane
and the neural plate. The growth of the
brain and the cephalic folds push the
oropharyngeal membrane forward, while
the heart and the pericardial cavity move
first to the cervical region and then into
the chest. The curved portion of the
horseshoe-shaped area expands to form
the future ventricular infundibulum and
the ventricular regions, as the heart tube
continues to expand. The tube starts
receiving venous drainage in its caudal
pole and will pump blood out of the first
aortic arch and into the dorsal aorta
through its polar head. Initially the tube
remains attached to the dorsal part of
the pericardial cavity by a mesodermal
tissue fold called the dorsal mesoderm.
This mesoderm disappears to form the
two pericardial sinuses the transverse
and the oblique pericardial sinuses,
which connect both sides of the
pericardial cavity.[6]

The myocardium thickens and secretes a

thick layer of rich extracellular matrix
containing hyaluronic acid which
separates the endothelium. Then
mesothelial cells form the pericardium
and migrate to form most of the
epicardium. Then the heart tube is
formed by the endocardium, which is the
inner endothelial lining of the heart, and
the myocardial muscle wall which is the
epicardium that covers the outside of the
tube.[6]
Heart folding
The heart tube continues stretching and
by day 23, in a process called
morphogenesis, cardiac looping begins.
The cephalic portion curves in a frontal
clockwise direction. The atrial portion
starts moving in a cephalically and then
moves to the left from its original
position. This curved shape approaches
the heart and finishes its growth on day
28. The conduit forms the atrial and
ventricular junctions which connect the
common atrium and the common
ventricle in the early embryo. The arterial
bulb forms the trabecular portion of the
right ventricle. A cone will form the
infundibula blood of both ventricles. The
arterial trunk and the roots will form the
proximal portion of the aorta and the
pulmonary artery. The junction between
the ventricle and the arterial bulb will be
called the primary intra-ventricular hole.
The tube is divided into cardiac regions
along its craniocaudal axis: the primitive
ventricle, called primitive left ventricle,
and the trabecular proximal arterial bulb,
called the primitive right ventricle.[9] This
time no septum is present in heart.

Heart chambers

Sinus venosus …
In the middle of the fourth week, the
sinus venosus receives venous blood
from the poles of right and left sinus.
Each pole receives blood from three
major veins: the vitelline vein, the
umbilical vein and the common cardinal
vein. The sinus opening moves
clockwise. This movement is caused
mainly by the left to right shunt of blood,
which occurs in the venous system
during the fourth and fifth week of
development.[10]

When the left common cardinal vein

disappears in the tenth week only the
oblique vein of the left atrium and the
coronary sinus remain. The right pole
joins the right atrium to form the wall
portion of the right atrium. The right and
left venous valves fuse and form a peak
known as the septum spurium. At the
beginning, these valves are large, but
over time the left venous valve and the
septum spurium fuse with the developing
atrial septum. The upper right venous
valve disappears, while the bottom
venous valve evolves into the inferior
valve of the vena cava and the coronary
sinus valve.[10]

Heart wall …

The main walls of the heart are formed

between day 27 and 37 of the
development of the early embryo. The
growth consists of two tissue masses
actively growing that approach one
another until they merge and split light
into two separate conduits. Tissue
masses called endocardial cushions
develop into atrioventricular and
conotroncal regions. In these places, the
cushions will help in the formation of
auricular septum, ventricular conduits,
atrio-ventricular valves and aortic and
pulmonary channels.[11]

Atria …
The developing heart at day 30. The septum primum
(top, middle) develops downwards to separate the
initially joined primitive atrium into left and right
atria.

At the end of the fourth week, a crest

grows that leaves the cephalic part. This
crest is the first part of the septum
primum. The two ends of the septum
extend into the interior of the endocardial
cushions in the atrioventricular canal.
The opening between the bottom edge of
the septum primum and endocardial
cushions is the ostium primum (first
opening). The extensions of the upper
and lower endocardial pads grow along
the margin of the septum primum and
close the ostium primum. Coalescence
of these perforations will form the
ostium secundum (second opening),
which allows blood to flow freely from
the right atrium to the left.

When the right of the atrium expands due

to the incorporation of the pole of the
sinus, a new fold appears, called the
septum secundum. At its right side it is
fused with the left venous valve and the
septum spurium. A free opening will then
appear, called the foramen ovale. The
remains of the upper septum primum,
will become the valves of the foramen
ovale. The passage between the two
atrial chambers consists of a long
oblique slit through which blood flows
from the right atrium to the left.[11]

Ventricles …

Initially, a single pulmonary vein develops

in the form of a bulge in the back wall of
the left atrium. This vein will connect
with the veins of the developing lung
buds. As development proceeds the
pulmonary vein and its branches are
incorporated into the left atrium and they
both form the smooth wall of the atrium.
The embryonic left atrium remains as the
trabecular left atrial appendage, and the
embryonic right atrium remains as the
right atrial appendage.[12]

Septum formation of the

atrioventricular canal
…

At the end of the fourth week, two

atrioventricular endocardial cushions
appear. Initially the atrioventricular canal
gives access to the primitive left
ventricle, and is separated from arterial
bulb by the edge of the ventricular bulb.
In the fifth week, the posterior end
terminates in the center part of the upper
endocardial cushion. Because of this,
blood can access both the left primitive
ventricle and the right primitive ventricle.
As the anterior and posterior pads
project inwardly, they merge to form a
right and left atrioventricular orifice.[13]

Atrioventricular valves …

When forming intra-atrial septa, atrio-

ventricular valves will begin to grow. A
muscular interventricular septum begins
to grow from the common ventricle to
the atrio-ventricular endocardial
cushions. The division begins in the
common ventricle where a furrow in the
outer surface of the heart will appear the
interventricular foramen eventually
disappears. This closure is achieved by
further growth of the muscular
interventricular septum, a contribution of
trunk crest-conal tissue and a
membranous component.[14]

Valves and outflow tracts

Truncus septum formation and

arterial cone
…

The arterial cone is closed by the

infundibular cushions. The trunk cones
are closed by the forming of an
infundibulotroncal septum, which is
made from a straight proximal portion
and distal spiral portion. Then, the
narrowest portion of the aorta is in the
left and dorsal portion. The distal portion
of the aorta is pushed forward to the
right. The proximal pulmonary artery is
right and ventral, and the distal portion of
the pulmonary artery is in the left dorsal
portion.[11]

Pacemaker and conduction

system
The rhythmic electrical depolarization
waves that trigger myocardial
contraction is myogenic, which means
that they begin in the heart muscle
spontaneously and are then responsible
for transmitting signals from cell to cell.
Myocytes that were obtained in the
primitive heart tube, start beating as they
connect together by their walls in a
syncytium. Myocytes initiate rhythmic
electrical activity, before the fusion of the
endocardial tubes. The heartbeat begins
in the region of the pacemaker which has
a spontaneous depolarization time faster
than the rest of myocardium.[15]

The primitive ventricle acts as initial

pacemaker. But this pacemaker activity
is actually made by a group of cells that
derive from the sinoatrial right venous
sinus. These cells form an ovoid
sinoatrial node (SAN), on the left venous
valve. After the development of the SAN,
the superior endocardial cushions begin
to form a pacemaker as known as the
atrioventricular node. With the
development of the SAN, a band of
specialized conducting cells start to form
creating the bundle of His that sends a
branch to the right ventricle and one to
the left ventricle. Most conduction
pathways originate from the cardiogenic
mesoderm but the sinus node may be
derived from the neural crest.[15]

The human embryonic heart begins

beating approximately 21 days after
fertilization, or five weeks after the last
normal menstrual period (LMP), which is
the date normally used to date pregnancy
in the medical community. The electrical
depolarizations that trigger cardiac
myocytes to contract arise
spontaneously within the myocyte itself.
The heartbeat is initiated in the
pacemaker regions and spreads to the
rest of the heart through a conduction
pathway. Pacemaker cells develop in the
primitive atrium and the sinus venosus to
form the sinoatrial node and the
atrioventricular node respectively.
Conductive cells develop the bundle of
His and carry the depolarization into the
lower heart. Cardiac activity is visible
beginning at approximately 5 weeks of
pregnancy.
The human heart begins beating at a rate
near the mother’s, about 75-80 beats per
minute (BPM). The embryonic heart rate
(EHR) then accelerates linearly for the
first month of beating, peaking at 165-
185 BPM during the early 7th week, (early
9th week after the LMP). This
acceleration is approximately 3.3 BPM
per day, or about 10 BPM every three
days, an increase of 100 BPM in the first
month.[16]

After peaking at about 9.2 weeks after

the LMP, it decelerates to about 150 BPM
(+/-25 BPM) during the 15th week after
the LMP. After the 15th week the
deceleration slows reaching an average
rate of about 145 (+/-25 BPM) BPM at
term.

Imaging

Device for obstetric ultrasonography including

usage in 1st trimester.

Transvaginal ultrasonography of an embryo at 5

weeks and 5 days of gestational age with
discernible cardiac activity

In the first trimester, heartbeat can be

visualized and the heart rate quantified
by obstetric ultrasonography. A study of
32 normal pregnancies came to the
result a fetal heartbeat was visible at a
mean human chorionic gonadotropin
(hCG) level of 10,000 UI/l (range 8650-
12,200).[17] Obstetric ultrasonography
can also use doppler technique on key
vessels such as the umbilical artery can
detect abnormal flow.
Doppler fetal monitor

In later stages of pregnancy, a simple

Doppler fetal monitor can quantify the
fetal heart rate.

During childbirth, the parameter is part of

cardiotocography, which is where the
fetal heartbeat and uterine contractions
are continuously recorded.

Heart rates …
Starting at week 5 the embryonic heart
rate accelerates by 3.3 bpm per day for
the next month. Before this, the embryo
possesses a tubular heart.

The embryonic heart begins to beat at

approximately the same rate as the
mother's, which is typically 80 to 85 bpm.
The approximate fetal heart rate for
weeks 5 to 9 (assuming a starting rate of
80):

Week 5 starts at 80 and ends at 103

bpm
Week 6 starts at 103 and ends at 126
bpm
 Week 7 starts at 126 and ends at 149
bpm
Week 8 starts at 149 and ends at 172
bpm
At week 9 the embryonic heart tends to
beat within a range of 155 to 195 bpm.

By the end of week 9, the embryonic

heart has developed septa and valves,
and has all four chambers.

At this point, the fetal heart rate begins to

decrease, and generally falls within the
range of 120 to 160 bpm by week 12.[18]
Obstetric ultrasonography of an embryo of 8 weeks
with visible heartbeat.

Additional images
M-mode sonography measuring
embryonic heart rate.

Blood flow in a neonate

 Human embryo, 38 mm, 8–9 weeks–
anterior view, heart is visible.

References
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1938168130. Retrieved 11 August
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2. Hosseini, Hadi S.; Garcia, Kara E.;
Taber, Larry A. (1 July 2017). "A new
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This article incorporates text from the CC-

BY book: OpenStax College, Anatomy &
Physiology. OpenStax CNX. 30 Jul 2014.
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