Development of Cardiovascular system

Part 1

CV1.4 To understand the development of the heart and

blood vessels, and their developmental anomalies.
sdcosta@auamed.net
Required textbook:
Sadler TW; Langman’s Medical Embryology, 2019,14th
edition, LWW.
Required reading:Chapter13:page no.175-212

Solve the problems at the end of the chapters,

Answers to the problems are explained in the
last pages of the required book.
sdcosta@auamed.net
Required text book:
Sadler TW; Langman’s Medical Embryology, 2019,14th edition, LWW.
Required reading: Chapter 13
http://auamed.idm.oclc.org/login?url=http://meded.lwwhealthlibrary.com/book.aspx?bookid=1362
• Establishment and Patterning of the Primary Heart Field & clinical correlates (laterality and heart defects)
• Formation and Position of the Heart Tube
• Formation of the Cardiac Loop
• Clinical Correlates-Abnormalities of Cardiac Looping
• Development of the Sinus Venosus
• Formation of the Cardiac Septa
• Septum Formation in the Common Atrium
• Formation of the Left Atrium and Pulmonary Vein
• Septum Formation in the Atrioventricular Canal
• Atrioventricular Valves
• Clinical Correlates-Heart Defects, ASD, Endocardial cushions, Tricuspid atresia, Ebstein anomaly
• Septum Formation in the Truncus Arteriosus and Conus Cordis
• Septum Formation in the Ventricles
• Semilunar Valves
• Clinical Correlates :Heart Defects, VSDs, Tetralogy of Fallot, Persistent (common) truncus arteriosus, Transposition of the great vessels, DiGeorge
sequence, Valvular stenosis, Ectopia cordis
• Formation of the Conducting System of the Heart
• Vascular Development
• Arterial System-Aortic Arches
• Vitelline and Umbilical Arteries
• Clinical Correlates- Arterial System Defects, coarctation of the aorta, Abnormal origin of the right subclavian artery, double aortic arch,
• Venous System- Vitelline Veins, Umbilical Veins, Cardinal Veins,
• Clinical Correlates-Venous System Defects
• Summary, • Problems to Solve sdcosta@auamed.net
Learning objectives:
Given a clinical scenario/image, the student should be able to:
FO1.29.8. Describe the process of gastrulation, formation of the 3 germ layers
(week 3) and neurulation (week 4).
CV1.4.1: Recognize the germ layers (gastrulation) contributing to the
development of the cardiovascular system.
GI1.3.3. Describe the process of cranio-caudal and lateral folding of the
embryo with emphasis on associated ventral body wall defects.
CV1.4.2: Recognize the development of the heart tube, its dilatations, and
their fate.
FO1.29.9. Enumerate the derivatives of ectoderm, mesoderm, endoderm,
neural crest, and their roles in developing basic tissues and organ systems.
NB1.2.3. Enumerate the derivatives of the neural tube and neural crest cells.
CV1.4.3: Recognize the development of the atria, ventricles, and interatrial and
interventricular septum.
sdcosta@auamed.net
 3rd week:

➢ Epiblast of the bilaminar disc, through the process of gastrulation forms:

❖All the 3 germ layers
❖Endoderm
❖Mesoderm
❖Ectoderm
➢ The cells of these germ layers will give rise to all the tissues and organs in the
embryo. sdcosta@auamed.net 5
 Major derivatives of the embryonic germ layers

(urogenital
System)
Neural crest

sdcosta@auamed.net
Folding of embryo (Week3-4)
• End of 3rd week;
• Flat embryonic disc becomes
cylindrical-head fold, tail fold &
lateral folds
• Head & tail fold: caused by growth
of neural tube
• Lateral folds: caused by growth of
somites
• Margins of four folds- bound the
primitive umbilical opening

sdcosta@auamed.net 7
Learning objectives:
Given a clinical scenario/image, the student should be able to:
FO1.29.8. Describe the process of gastrulation, formation of the 3 germ layers
(week 3) and neurulation (week 4).
CV1.4.1: Recognize the germ layers (gastrulation) contributing to the
development of the cardiovascular system.
GI1.3.3. Describe the process of cranio-caudal and lateral folding of the
embryo with emphasis on associated ventral body wall defects.
CV1.4.2: Recognize the development of the heart tube, its dilatations, and
their fate.
FO1.29.9. Enumerate the derivatives of ectoderm, mesoderm, endoderm,
neural crest, and their roles in developing basic tissues and organ systems.
NB1.2.3. Enumerate the derivatives of the neural tube and neural crest cells.
CV1.4.3: Recognize the development of the atria, ventricles, and interatrial and
interventricular septum.
sdcosta@auamed.net
 Formation of heart tube
Development of the primitive heart tube:3rd week
A pair of endocardial heart tubes appears within the
cardiogenic area at the cranial end of embryo
These are derived from the splanchnic layer of mesoderm

3rd week (day 16): two heart tubes fuse -lateral folding of
embryo
Mesoderm surrounding the heart tubes –myocardium &
epicardium
Laterality is established during gastrulation (specifies cells
contributing to form right and left sides of heart)
The primitive heart begins to beat around the 19-20th day of
embryonic development (4th week)
sdcosta@auamed.net
Dorsal view of a late presomite embryo (approximately
18 days). Progenitor heart cells have migrated and
formed the horseshoe-shaped heart tube located in the
splanchnic layer of lateral plate mesoderm.
Figure showing effects of the rapid growth of the brain
on positioning of the heart. D. 22 days.
sdcosta@auamed.net
Molecular regulation of establishing the cardiogenic field

A combination of upregulation of bone morphogenetic proteins (BMPs) and downregulation of WNTs results in

expression of the transcription factor NKX2.5, the master gene for heart development

NKX2.5 is conserved from the Tinman gene that regulates heart development in Drosophila.
TBX5 –cardiac septation

Molecular Regulation of Looping:

NODAL & LEFTY2 = PITX2

extracellular matrix deposition

NKX2.5 = HAND1 & HAND2

HAND1 = left ventricle

HAND2 = right ventricle sdcosta@auamed.net

Fusion produces a single tube with aortic and venous poles.
The heart tube sprouts aortic arch vessels from the (aortic)
outflow region; the venous pole remains paired.

Aortic arch
vessels

Pericardial
Bulbus sac
Ventricle
cordis
Atrium

sdcosta@auamed.net
Heart Tube Folding

❖ The primitive heart tube receives blood

from the developing placenta at its inferior
aspect
❖ called the sinus venosus.

❖ This blood then flows cranially through the

primitive atrium, ventricle, bulbus cordis
❖ and then out the truncus arteriosus into
the aortic arch system.

sdcosta@auamed.net
Primitive heart tube dilatations and their fate
Smooth part of left atrium
incorporation of parts
Truncus Ascending aorta
arteriosus of pulmonary veins
Pulmonary trunk
Smooth part of right ventricle (conus arteriosus)
Smooth part of left ventricle (aortic vestibule)

Trabeculated portions of the right and left ventricle

Trabeculated portions of the right and left atrium

(pectinate muscle)
Left horn-Coronary sinus
Right horn-Smooth part of right atrium (sinus
sdcosta@auamed.net
venarum)
 In normal heart development, the
primitive heart tube undergoes a
rightward dextral loop (D-looping) to
establish the normal left-sided positioning
of the heart.

sdcosta@auamed.net
 Heart tube folds upon itself in an “S” bend, the bulbus cordis & truncus
arteriosus down to right and the sinus venosus swinging up to the left

Ends on
28th day

This folding brings the atria & ventricles into their normal
position. The heart is sdcosta@auamed.net
still a single tubular passageway for
blood.
 Clinical correlates
Abnormalities of cardiac looping:
Dextrocardia :
Heart lies on the right side instead of left
It occurs when the heart loops to the left instead
of right
Defect may be induced during gastrulation /when
laterality is established
Associated with situs inversus (complete reversal
of asymmetry of all organs)
Defect in left-right dynein (involved in L/R
asymmetry) seen in Kartagener syndrome (primary
ciliary dyskinesia)

In this condition where do you feel the APEX BEAT?

sdcosta@auamed.net
Learning objectives:
Given a clinical scenario/image, the student should be able to:
FO1.29.8. Describe the process of gastrulation, formation of the 3 germ layers
(week 3) and neurulation (week 4).
CV1.4.1: Recognize the germ layers (gastrulation) contributing to the
development of the cardiovascular system.
GI1.3.3. Describe the process of cranio-caudal and lateral folding of the
embryo with emphasis on associated ventral body wall defects.
CV1.4.2: Recognize the development of the heart tube, its dilatations, and
their fate.
FO1.29.9. Enumerate the derivatives of ectoderm, mesoderm, endoderm,
neural crest, and their roles in developing basic tissues and organ systems.
NB1.2.3. Enumerate the derivatives of the neural tube and neural crest cells.
CV1.4.3: Recognize the development of the atria, ventricles, and interatrial and
interventricular septum.
sdcosta@auamed.net
 Major derivatives of the embryonic germ layers

(urogenital
System)
Neural crest

sdcosta@auamed.net
sdcosta@auamed.net 20
Atrial septal development
Around the 30th day of development
the atrium and ventricle become partitioned with the appearance of endocardial cushions (neural crest
derivative) in atrioventricular (AV) canal.
The interatrial septum develops from a septum primum and septum secundum,
A septal opening, called the foramen ovale remains until birth, shunting blood from the right
to left atrium
When pressure in the left atrium increases, two septa press each other and close the foramen
ovale.

sdcosta@auamed.net
Clinical correlates
Atrial Septal Defects (ASDs): left-to-right shunt, noncyanotic
Down syndrome, heart murmur

B,C. Ostium secundum defect: caused by

D E:Ostium secundum defect: caused by failure of
excessive resorption of the septum primum. development of the septum secundum.

D,E. Ostium primum defect: caused by incomplete fusion

of the atrioventricular endocardial cushions.
sdcosta@auamed.net
Clinical correlates
Atrial Septal Defects (ASDs): left-to-right shunt , non-cyanotic

F. Common atrium, or cor triloculare biventriculare, resulting

from complete failure of formation of the septum primum and
septum secundum

Premature closure of the oval foramen:

-Occasionally, the oval foramen closes during prenatal life
- Leads to massive hypertrophy of the right atrium & ventricle & underdevelopment of the
left side of the heart.
- Death usually occurs shortly after birth sdcosta@auamed.net
Interventricular septal (IV) development
IV septum begins at 4th week & completes at the end of 7th week.
Thick muscular component: formed by
septum from the base of the ventricle
Membranous part (small part):formed by
Right conus swelling
Left conus swelling
Inferior endocadial AV cushions(neural crest derivative)

sdcosta@auamed.net
Clinical correlates
Ventricular Septal Defects (VSDs):
Associated with failure of migration of neural crest cells into the endocardial cushions
Non-cyanotic

Membranous VSD; of the interventricular septum.

Blood shunts from the left – to-right ventricle
through the interventricular foramen (arrows) Non-
cyanotic. Patients complain excessive fatigue upon
exertion.
Overtime, the Increased pulmonary blood flow causes
pulmonary hypertension due to the narrowing of pulmonary
arteries.
This increases pulmonary resistance, which leads to an
increase in right ventricular pressure resulting in reverse blood
flow (right sdcosta@auamed.net
to left) (late cyanosis)