DEVELOPMENT OF THE

HEART
DR NGUGI
 MORPHOGENESIS
• It is the earliest functional organ in the developing fetus
• Develops from splanchnic mesoderm
• Progenitor Haematoblasts and myoblast migrate cranially – form
crescent structure – by day 15
 MORPHOGENESIS

• Lateral folding apposes paired heart tube primordia and brings dorsal aortae to
midline

• Heart primordia fuse to form tubular heart- beating heart tube- D18
Fusing cardiac primordia

“conotruncus”
(outflow tract)

future
ventricles

future
atria

21 days 22 days
Langman’s fig 12-7

septum transversum
(liver & diaphragm primordium)
 LOOPING

• Looping occurs due to rapid growth of the ventricles

• Rightward (D –looping) leads to normal levocardia

• Leftward (L – looping) leads to dextrocardia

• Leads to the bilateral asymmetry of organs – heart, lungs, liver, spleen and gut-
situs solitus

• Situs inversus is a mirror image while ambiguous are other arrangements.

 Folding and rotation of heart tube

aortic roots

truncus arteriosus

bulbus cordis

ventricle

atrium

sinus venosus

22 days 23 days 24 days Langman’s fig 12-6

• Ventricle moves ventrally

and to right

• Atrium moves dorsally

and to left
Looped heart anatomy

Carlson fig 17-18

• After the looping , atrioventricular canal(AVC) is on the left while the cono-
truncus is on the right

• Incomplete AVS or conal movement leads to malalignment

• After septation, AVC shifts to the right to align atrioventricular septum with IVS-
failure lead to DILV

• The conotrucal structures after septation shift leftward- failure-DORV

• Shifting aligns the atria with ventricles and ventricles with semilunar valves

• Failure of truncal spiral leads to TGA

 CHAMBER DEVELOPMENT

• Outer curvature of looping heart is the site for active growth- chambers balloons
out.

• Inner curvature remodels to alight the inflow, AVC and outflow with the developing
chambers.

• Genes encoding gap junctions and myofibril proteins allow for development of
contractile functions and increase conduction velocity by formation of gap
junctions.

• Atria and ventricular muscle cells express specific genes that confer different
contractile , electrophysiological and pharmacological properties
 Myocardial growth

• Results from signals from epicardium, myocardium and endocardium layers

• Spongy ridges of fenestrated trabecular network grow into chambers from

outer curvature- outgrowths – increase area for myocardial oxygenation and
mass increase.

• Outer compact zone is highly proliferative – source of new cells for trabecular
layer.

• Growth of coronary vasculature into compact zone leads to thickened layer

increasing more due to compaction of inner layer

• Failure to compact leads to spongy myocardium- form of cardiomyopathy.

 Ventricles and atria

• Left ventricle is derived from the primitive heart tube

• Right ventricle is derived from migrating cells from the second heart field.

• Genes encoding for myosin heavy chains are common in both ventricles.

• Defect in either of the genes can lead to primary hypoplasia of the specific chamber.

• Growth of each chamber is dependent on haemodynamics- altered flow can lead to

secondary hypoplasia.

• Genetic factors and mutation influences can also lead to hypoplasia

• Atrial Part developed from secondary heart center. Genetic influences less known
Atrial septation
ASD TYPES
VSD
 CONOTRUNCAL
• Development results from secondary heart field (SHF), migrating neural crest cells and
surrounding pharyngeal tissue.

• Precise interaction required for normal development

• Arises from the primitive right ventricle

• Shifts to the left to override the forming IVS

• Mesenchymal cells septate the truncus - aorta and pulmonary. Neural crest cells have a
critical role in this process

• Spiral rotation results in normal alignment of the great arteries

• All of outflow myocardium derived from SHF

Persistent Truncus Arteriosus and
Great Vessel Transposition ( TGA)

Carlson fig 17-31

Pulmonary Stenosis: Tetrology of Fallot
• Pulmonary stenosis
• Overriding aorta
• Intraventricular septal defect
• Hypertrophy of right ventricle
• (Patent ductus arteriosus)… so really a “pentology”

Carlson fig 17-40

COMMON CANAL DEFECT
 Aortic arch
• Aortic sac lie distal to conotruncus

• Gives rise to 6 bilateral vessels traversing pharyngeal arches to join dorsal aortae.

• 1st ,2nd involute while 5th never forms fully

• Majority of right sided dorsal aorta undergo programmed cell death- lead to left sided arch

• 3rd give rise to proximal carotid arteries

• Lt 4th –form transverse aortic arch between LCC and lt subclavian

• Rt 4th – proximal part of right subclavian artery

• 6th – proximal pulmonary arteries and lt 6th gives rise to ductus arteriosus.
 Anomalies of the aortic arch
• Based on embryology of tissues

• 3rd arch- subtle anomalies

• 4th –interrupted arch, abberant rt subclavian artery

• 6th – patent ductus, proximal pulmonary hypoplasia or discontinuity

 Cardiac valve formation

• Proper placement and function of valves essential for septation and

unidirectional flow of blood
• Starts with formation of endocardial cushions – regional swellings in AVC
and outflow tract of looped heart.
• In AVC- post/inferior cushions fuse – form atrioventricular septum,
divide heart tube into Rt. and Lt., inlet portion of IVS, and atrial septum
superiorly.
• In outflow- truncal septum, semilunar valves , conal septum and
perimembranous septum
• Valve primordia undergoes elongation into thin valves over weeks
• Haemodynamics play a role in maturation of the valves
• Genetic , mutations and connective tissue disorders affect valve
formation.
 Conduction system
• Myocardium of initial heart beat irregularly – low density of gap junctions

• After looping , inflow and atrioventricular myocardial cells retain high

automaticity and slow conduction- later sinoatrial and AV node

• HIS bundle form from crest of IVS

• Bundle branches and purkinje fibers form from early ventricular

myocardium.

• Heart tube initially polarized craniocaudally which after looping translates

to base to apex activation
Epi-cardial and coronary vascular
• Derives from sinus venosus cells called pro-epicardial organ- specialized
group of mesothelial cells

• Also gives rise to interstitial fibroblasts of the heart

• Combined population of fibroblasts, vascular smooth muscles and

endocardial progenitor cells- migrate from looped heart- smooth
muscle cells and fibroblast envelop to form epicardium

• Coronary form from plexus formation and angiogenic remodeling to

give mature vascular tree- ie proepicardial organ coalesce to form tubes
that invade myocardium to form a network