Heart tube formation

•Steps

•the formation, site, union, division of the of the heart tube.

•the formation and fate of the sinus venosus.

•the formation of the interatrial and the interventricular septae.

•
•the formation of the two atria and the two ventricles.

•the partitioning of the truncus arteriosus and formation of the aorta and pulmonary
trunk.

•the most common cardiac anomalies.

HEART FORMING REGIONS

Around 15th day of intra embryonic life, multiple cavitations start

appearing in the lateral plate mesoderm which later merge together to form a
Horseshoe-shaped Intraembryonic Coelom.

The Horseshoe shaped Coelom divides lateral plate mesoderm into two

layers which are called Splanchnopleure (connected to underlying
Endoderm) and Somatopleure (connected to overlying Ectoderm).

It’s the splanchnic layer of mesoderm which mainly forms the cardiogenic

area in the latter half of the 3rd week.

In addition to this, Neural crest cells also contribute to heart formation

especially the Aorticopulmonary septum and the Endocardial
Cushion regions.
Around 17th day of intra embryonic life, the endoderm layer of the gastrula secretes VEGF, which
causes ectodermalcells to migrate into the cranial end of the underlying mesoderm and form blood islands.

A horseshoe shaped area forms on either side of the neural plate. The blood islands formed above the Prechordal plate
(Cranial side) are called Cardiogenic or Heart-forming regions.

CRANIAL & LATERAL BODY FOLDING

Cephalic-caudal body folding ensures that the cardiogenic area and septum transversum (future diaphragm) come to
lie under and below the prechordal plate and in front of the fore gut.

Lateral body folding approximates the intra embryonic coelom in the mid line, folds of which give rise to adult
pericardial sacs which envelope the cardiogenic area in the mid-line.
Lateral folding apposes paired heart tube primordia
and brings dorsal aortae to midline
Heart primordia fuse to form tubular heart
DEVELOPMENT OF PRIMITIVE HEART TUBES

The ectodermal cells migrate into the mesoderm as cardiogenic cells which condense to form a pair of primordial
heart tubes. The pharyngeal area

mesoderm contributes further cells which form a secondary heart forming region around the primordial
heart tubes.

Further cells are contributed by the splanchnic mesoderm which form the myocardium around the
primordial heart tubes. This newly formed myocardium will start secreting hyaluronic acid and other
connective tissue components which are termed together and called as Cardiac Jelly. Cardiac jelly in
future becomes the connective tissue of the heart.

These newly formed primordial heart tubes are surrounded by pericardial cavity which provides the outer
Parietal layer of the Pericardium which is adherent to the Fibrous pericardium in the adult heart. The
Caudal or Inflow part of the Heart tube that is Sinus Venosus provides the cells which form the
visceral or inner layer of pericardium, also called EPICARDIUM.

By the 21st day the two primordial heart tubes fuse under the influence of VEGF into a single
endocardial or Heart tube. On 22nd day the embryonic heart starts beating.
DILATATIONS & DERIVATIVES OF THE HEART TUBE

The Primordial heart tube now orients itself into a cephalic INFLOW (Venous region) and a cranial
OUTFLOW (Arterial Region) ends. At this point the primitive heart tube has five dilatations which are as
following:

 Truncus Arteriosus (arterial outflow region): Forms adult aorta, pulmonary trunk and their respective semi-
lunar valves.
 Bulbus Cordis: Forms smooth parts of adult right ventricle (conus arteriosus) and left ventricle (aortic
vestibule).
 Primitive Ventricle: Forms trabeculated (rough) parts of right and left ventricles.
 Primitive Atrium: Forms trabeculated (rough) parts of right and left atria i.e., the pectinate muscles.
 Sinus Venosus: On the right side it forms Sinus Venarum (smooth part of right Atrium), superior vena cava
and the inferior vena cava. On the left side it forms coronary sinus and oblique vein of left atrium.
Formation of the Cardiac Loop

The heart tube continues to elongate and bend on day 23.

The cephalic portion of the tube bends ventrally, caudally, and to the right , and
the atrial (caudal) portion shifts dorsocranially and to the left .

This bending, which may be due to cell shape changes, creates the
cardiac loop.
It is complete by day 28.

aortic roots
truncus arteriosus
bulbus cordis

ventricle

atrium

sinus venosus
Ventricle moves ventrally
and to right

Atrium moves dorsally

and to left
The Truncus Arteriosus or the ventricular end of the heart tube grows more rapidly and tends to fold downwards,
forwards and to the right side.

Subsequently, the lower parts of the tube i.e., the primitive atria and sinus venosus tend to fold upwards, backwards
and to the left side.

This dextral looping tends to place the chambers of heart in their adult anatomic positions where the right ventricle
forms most of the right
Levo-Dynein is a protein which is involved in the formation of Cilia. However, Levo-Dynein also functions to
create symmetry within the human body. An abnormality of Levo-dynein can lead to symmetry problems such
as, Situs Inversus a condition in which the viscera are present on the opposite side of their normal anatomical
location. It can also lead to Dextrocardia,
MESOCORDIUM & TRANSVERSE SINUS

Post the cranial-caudal body folding, the embryonic heart tubes come to lie in front of the fore gut. This is before the
fusion of the primordial heart tubes into a single Heart tube. At this point the primordial heart tubes are connected to
the fore gut via the Mesocordium. The Mesocordium itself is a derivative of peritoneum. Subsequently, a gap appears
within the Mesocordium which is called transverse sinus and this eventually results in degeneration of Mesocardium,
following which the Pericardial cavity is thus separated from the Fore gut.
Heart chamber
Distal part or
truncus arteriosus Roots of aorta and pulmonary trunk
Bulbus cordis
Conus cordis Infundibulum of right ventricle and vestibule of left ventricle (smooth parts
Proximal part Right ventricle (trabeculated part)
Trabeculated (rough) parts of both ventricles.
Primitive ventricle

Primitive atrium Trabeculated (rough) parts of both atria.

Sinus venosus Smooth part of right atrium (sinus
venarum). Right horn
left horn Coronary sinus.
VENOUS SYSTEM
During the 4th week, three main pairs of veins drain into the left and right horns → sinus venosus → primitive atrium. As
follows;
A. Vitelline veins: receive blood from the yolk sac and gut (poorly oxygenated).
B. Umbilical veins: return blood from the placenta (well oxygenated).
C. Short common cardinal or somatic (somatic=body) veins: Union of the anterior (drains cranial part of the embryo) and posterior
(drains caudal part of the embryo) cardinal veins; carry blood from the embryo’s body (poorly oxygenated).
The sinus venosus open into the primitive atrium by sinoatrial (SA) orifice flanked –surrounded- by right and left venous
valves.

cardinal veins
sinus venosus

vitelline veins
umbilical veins
4th week
receives blood from
right and left sinus horns

5th week

Obliteration
R umbilical vein
left vitellin vein
The right horn forms the smooth posterior wall of the right atrium.
The left horn and body atrophy and form the coronary sinus.
The left common cardinal vein forms the oblique vein of the left atrium.
Primordial
pulmonary vein

Left Atrium
Primordial left atrium

Entrance of four
pulmonary veins

Smooth-walled part of left atriumRight

There are four small pulmonary veins (2 from each lung bud) form the left and right pulmonary veins, union of the latter
forming a single common pulmonary vein. Later, it opens and gets absorbed into the left atrium. Then, two pulmonary
veins are absorbed and lastly, four separate branches are open in the left atrium.

There is a vertical or dividing muscular line separates the posterior smooth wall of the right atrium from the anterior
rough wall called crista terminalis, its lower part is formed by upper part of the right venous valve, but the upper part is
formed from septum spurium. The crista terminalis is marked externally by the sulcus terminalis.

The rough Trabeculated anterior part of the right atrium is derived from the primordial common atrium.
Endocardial Cushion Development and Myocardialization

When the tube heart initially forms, the myocardial and endocardial cell layers are separated by an acellular sub-stance
traditionally called “cardiac jelly” . Cardiac jelly can be regarded as a basement membrane,

Cardiac jelly condenses into opposing swellings at the outflow and AV regions of the early, looped heart. The
resulting endocardial cushions function in combination with the specialized contractile properties of the AV junction
and outflow tract myocardium to prevent reversal of blood flow [93].

The AV endocardial cushions also function as the substrate for the formation of the mesenchymal tissues of the crux
of the heart, including the AV valves and central fibrous body

. Endocardial cushions of the embryonic outflow tract participate in the formation of the aorticopulmonary
septum, semilunar valves, and conus septum

Mesenchymal cell population that populates the originally acellular cardiac jelly also migrates into the AV cushions,
but not the outflow tract cushions
Myocardialization is the process in which the mesenchyme of the endocardial cushions is replaced by myocardium

All of the septal structures inside the heart – the interventricular septum, the atrial septum, and the conal septum –
are created in part by fusion of nonmyocardial mesenchymal cushions

Myocardialization is responsible for the formation of the myocardial conus septum and the and anterior outlet
portions of the interventricular septum.

In humans, the AV membranous septum is the only nonmyocardial septal structure derived from endocardial
cushion tissue
Toward the end of the 4th week, mesenchymal cells of the dorsal and ventral walls of the primitive atrium form the
endocardial cushions on their respective sides. The two endocardial cushions (future AV valves) increase in size, approach
each other and fuse together to form septum that divides the atrioventricular (AV) canal into right and left AV canals.

Clinical considerations of the AV canal;

A. Persistent AV canal: Non fusion of the AV cushions combined with interatrial and IV septal defects.

B. B. Ostium primum defect: Partial fusion of the AV cushions with the septum primum. The ostium primum is never
closed.

C. Tricuspid atresia: Agenesis or failure of tricuspid valves to form. This anomaly blocks blood stream from the atrium to
the ventricle on the right side. It’s usually associated clinically with: 1. patent foramen ovale, 2. hypertrophy of left
ventricle, 3. underdeveloped right ventricle. 4.and ,ts (VSDs)efecd eptumsentricular vinter

D. Ebstein’s anomaly: Displacement of the tricuspid valves towards the right ventricle leads to hypertrophy or enlargement
of the right atrium.
Partitioning of:
1- Atrioventricular canal.
2- Common atrium.
3- Common ventricle.
4- Bulbus cordis.
It begins by the
middle of 4th week.
It is completed by
the end of 5th week.
Atrial Septum

The primitive atrium partitioned into right and left atria by the
interatrial septum.
It develops in several steps;
A. Descending of the incomplete septum primum from the roof of the
primitive atrium towards the AV endocardial cushions. The
remainder part between the septum primum and AV cushions is
called ostium (=opening) primum.
B.
B. With the further growing of the septum primum, it fuses with AV
cushions to close the ostium primum leaving a cranial foramen (caused
by apoptosis) called ostium secundum.

C
•So the septum primum bounds
a foramen called ostium primum.

•It serves as a shunt, enabling

the oxygenated blood to pass
from right to left atrium.
. On the right hand of the septum primum, a C-shaped
septum secundum appears and overlaps the ostium
secundum.

A gap left by the septum secundum called foramen ovale

and it’s valve formed by septum primum
40

43
. On the right hand of the septum primum, a C-
shaped septum secundum appears and overlaps the
ostium secundum. A gap left by the septum
secundum called foramen ovale and it’s valve formed
by septum primum.

D. At birth, when the lung circulation begins the

pressure in the left atrium increases and exceeds
that of the right atrium the foramen ovale functionally
(passage of blood from the right atrium to the left
atrium) closes due to anatomical fusion of the two
septa and becomes fossa ovale.

Later in life, the septum primum represents → fossa

ovale;
septum secundum represents → (annulus)limbus
ovalis (fossa ovale’s margin).
Atrial Septal Defects (ASDs) are most common in females than males;
A. Patent foramen ovale: In 25% of hearts, septum secundum fails to develop and the foramen ovale remains open
between the two atria.
B. Premature closure of the foramen ovale in the intrauterine life results in hypertrophy of the right aspect of the
heart and underdevelopment of the left aspect. Shortly, this fetus will die after birth.
C. Ostium secundum defects: a large opening between two atria caused by excessive resorption of septum secundum
or septum primum or both.
D. Common atrium or (cor triloculare biventriculare) is the most serious condition. It defined as complete absence of
the interatrial septum. Thus, the heart consists of one -common- atrium and two ventricles.
The Atrioventricular Junction Segment
and Atrioventricular Valve Development
The electrophysiologic and physiologic properties of the junctional myocardium between the primitive atria and
ventricles are critical to the preseptated heart,
However, myocardial continuity between the AV junctional myocardium, the atrial myocardium, and the ventricular
myocardium must be interrupted for the development of the fibrous crux of the heart and correct functioning of
conduction system ,

its accomplished by formation of a layer of fibrous insulation called the annulus fibrosis that will completely interrupt
myocardial continuity between the AV myocardium and the ventricular myocardium, with the exception of the
penetrating bundle of His specialized myocardium.

In the mature heart the remnants of AV junction myocardium become incorporated into the myocardium of the definitive
atrium

Fibrous interruption of AV myocardial continuity results from the fusion of mesenchymal cell populations of the AV
endocardial cushions with a mesenchymal cell population found in the atrioventricular sulcus on the external surface
of the looped heart.
there are four endocardial cushions in the AV junction.

The superior and inferior cushions are the most prominent endocardial cushion masses from their first appearance,
the lateral endocardial cushions, which are visible only after Carnegie Stage 17 (approx. 42days) .
The left lateral cushion contributes to the posterior (mural) leaflet of the mitral valve.

The right lateral cushion, which becomes continuous anteriorly with the septal endocardial cushion of the outflow
tract, contributes to the formation of the anterior and inferior leaflets of the tricuspid valve

At the end of the fifth week there is complete fusion of the superior and inferior cushions with complete division of
the canal into left and right orifices.
The AV endocardial cushions are actively reconfiguring at this time, with fusion of the superior and right lateral AV
endocardial cushions to each other.
The conal cushions are also completing their fusion during this time.
The fused outflow septum then expands apically to reach the inner curvature of the heart, anterior
to the fusing superior and right lateral endocardial cushion

the fused outflow cushions will become adherent to the myocardium of the ventriculoinfundibular
fold, establishing the anterior position of the conus septum with respect to the atrioventricular valvular
structures, and also forming the crista supraventricularis
interventricular (IV) septum
A. Thick muscular part arises as a median outgrowth from the floor (or near the apex) of the primitive ventricle. It
ascends toward the AV cushions but doesn’t reach it, leaving an opening called IV foramen.

B. Thin membranous part develops by a proliferation of mesenchymel cells that originate from the left bulbar ridge,
right bulbar ridge and AV endocardial cushions. Fusion of the AV cushions with the bulbar ridges, and further
proliferation of the membranous IV septum resulting in a closure of the IV foramen (at week 7).
including; isease (CHD), deart hongenital care the most common group of VSDs

A. Membranous VSDs (more serious).

B. Muscular portion VSDs (most common).
C. Common ventricle or (cor triloculare biatriatum) is an absence of the whole IV septum. So, the heart composed of
one common ventricle and two atria.
At the time of delamination, the atrial surfaces of the valve leaflets are composed of endocardial cushion tissue while
the ventricular surfaces are primarily myocardial.

The myocardial layer provides continuity with the evolving subvalvar tension apparatus.

As development proceeds, papillary muscles are derived by two mechanisms: from initially independent, preexisting
trabeculae coalescing together to form papillary muscles; and from delamination of myocardium into myocardial
structures that join with trabeculae or form of themselves the papillary muscles.

The mitral valve papillary muscles are derived from a single large trabecula that then separates into the two
independent papillary supports

Thus the surgically challenging group of patients with parachute mitral valve derivatives are likely due to deficiencies
in this process.
Aorticopulmonary Septum

The aorticopulmonary septum is initially formed as a

condensation of mesenchyme in the roof of the aortic sac,
between the fourth and sixth aortic arches

extracardiac origin of this mesenchyme is population of

neural crest cells . Two prongs of mesenchymal
condensations penetrate into the endocardial cushion ridges
at the truncal end of the outflow tract.

Septation moves towards the heart and is accomplished by

fusion of the prongs of neural crest derived mesenchyme. As
the septum forms, the arterial trunks thus become separated
by neural crest-derived smooth muscle cells

As aorticopulmonary septation proceeds towards the heart

and the trunks of the aorta and pulmonary artery become
distinct, the distal extent of the myocardial sleeve remains at
or below the septation complex.
Aorticopulmonary Septum
Aorticopulmonary Septum
Neural crest cells form the bulbar and truncal ridges. The ridges grow, twist around each other and finally fuse to
form a spiral aorticopulmonary (AP) septum that divide the truncus arteriosus into ascending aorta and
pulmonary trunk.

Anomalies of the AP septum;

A. Fallot’s tetralogy: A small diameter of the pulmonary trunk and large diameter of the aorta caused by unequal
division of the conus. It’s a group of four major cardiac defects, consists of; [PROV]
. )verridingoextroposition (d aortA 2. ulmonary stenosis. P 1. ight ventricle hypertrophy. R 4. SDs. V3.
B. Persistent truncus arteriosus: Failure of AP septum to develop; thus, truncus arteriosus wouldn’t be divided
into pulmonary trunk and aorta results in one large trunk leaving the heart. It’s always accompanied by
membranous VSD.
 STRAIGHT SEPTUM:
NO SEPTUM: PERSISTENT TRANSPOSITIONOF
TRUNCUS ARTERIOSUS GREAT VESSELS