Download File - Wk 1-2

Embryology of the Heart
Week 20
*WARNING* I have tried my best to summarise here but it is still very long unfortunately. I have
done a brief summary at the end of LO 4.
1. Demonstrate an understanding of the terminology used to describe the anatomy of the
heart and cardiac development
See italicised words within the LOs.
2. Describe the sequence of cardiac chambers, openings, valves and vessels involved in the
circulation and oxygenation of the blood in the foetus compared with the postnatal child
Foetal Circulation
 Highly oxygenated blood from the placenta enters the umbilical vein in a large stream
(sometimes under increased pressure due to uterine contractions)
 Blood under pressure bypasses the liver and enters the ductus venosus and then enters
the IVC directly where it has immediate access to the heart
 Poorly oxygenated blood can back up in the IVC due to the strength of the umbilical blood
flow
 Umbilical and systemic blood mix in the IVC
 In the right atrium, the orientation of the IVC allows a stream of blood under slightly
increased pressure to pass directly through the foramen ovale and foramen secundum
into the left atrium
 Blood from the IVC, SVC and coronary sinus, mixes in the RA and then passes into the RV
 It then leaves through the pulmonary artery towards the lungs
 The pulmonary vasculature is however not ready to accommodate the full volume of
blood that enters the pulmonary artery (only 12% of RV output passes through the lungs),
and thus some is shunted to the aorta via the ductus arteriosus
 Ductus arteriosus – protects the foetal lungs from cardiac overload, yet allows the right
side of the heart to exercise in preparation for its functioning at full capacity at birth
 The LA receives a stream of highly O2 umbilical blood through the intra-atrial shunt and a
small amt of poorly O2 blood from the pulmonary veins
 This relatively high O2 blood → LV → aorta
 Some of the first arterial branches from the aorta supply the heart and brain → need high
[O2] for normal development
 Where aortic arch begins to descend, ductus arteriosus empties poor O2 blood into it
 The mixture of high and low O2 blood → distributed to tissues and organs via thoracic and
abdo branches of aorta
 Near its caudal end → aorta gives off two large umbilical arteries → carry blood to the
placenta for renewal
Changes to circulation after birth:
 Changes occur in the morphology and organisation of the cardiovascular system after
birth, due to the onset of lung breathing
 Umbilical arteries → medial umbilical ligaments
 Left umbilical vein (right disappears) → ligamentum teres hepatis
 Ductus venosus → ligamentum venosum
 Ductus arteriosum →ligamentum arteriosum
 foramen ovale (between the two atria) closes leaving fossa ovalis in the inter-atrial
septum
Foramen Ovale Closure:
 the principle change is the closure of the foramen ovale which occurs due to changes in
pressure in the two atria
 once lung breathing begins, blood needs to pass through the pulmonary system and
therefore the pressure drops in the right atrium
 pressure rises in the left atrium with the larger volume of blood returning from the
lungs
 thus the septum primum and septum secundum are pressed together forming a
functional closure of the foramen ovale that later seals anatomically
3. Summarise the normal development of the cardiac chambers and valves from the
primitive cardiac tube
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Early embryo → derives nutrients from trophoblastic digestion of uterine mucosa
Then diffusion from the yolk sac
As embryo increases in size this becomes inadequate (most cells loose contact with surface
for diffusion to occur)
Initial components of cardiovascular system (CVS) are angiogenic cell clusters in the extraembryonic mesoderm lining the yolk sac → give rise to channels that extend into embryo
Early embryonic blood vessels that appear around neural plate in horseshoe-shape → arise
from unsegmented mesoderm that forms rostral (towards the head) to the prochordal plate
Clusters → merge → cardiogenic area of embryo
Cells → form tube-like structures → initially become the heart tubes
The paired heart tubes bulge into the midline of the intra-embryonic coelom → future
pericardial cavity
Dorsal aortae develop on either side of the midline and connect with the heart tubes
Heart tube formation
 Longitudinal and lateral folding of embryo → heart tubes fuse to form single tube which is
carried around to the region of the future thorax
 Heart tube → inner endothelial lining and outer myocardial layer
 Outer surface becomes invested in mesodermal tissue → future visceral
pericardium/epicardium
 Retained in the pericardial cavity by a dorsal mesoderm which suspends it
 Attached at proximal and distal ends by the future great arterial and venous vessels
 Dorsal myocardium breaks down → heart tube merely attached at margins of pericardium
 Heart tube itself differentiates → thicker myocardium
 Continues to elongate and develops a series of expansions
 Day 23 → too long to be accommodated in pericardium as a straight tube → bends →cardiac
loop
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Heart tube → atrial portion (initially a single chamber) and ventricular portion → connection
between the two → atrioventricular canal → region where valves will form from structures
called endocardial cushions → swellings of mesenchymal tissue covered by endocardium
The canal connects the primitive ventricle and common atrium
Between primitive ventricle and arterial outflow → bulbus cordis → becomes the right
ventricle
LV arises from original primitive ventricle
The bends in the heart tube then occur at set places: the bulboventricular groove and the
atrioventricular groove
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Bulbus cordis → becomes conus cordis that leads from both future ventricles and is the
outflow tract which leads on to the truncus arteriosus → continues to form the proximal
parts of the aorta and pulmonary trunk
Proximal third of bulbus cordis and future RV become trabeculated, while the conus remains
smooth-walled
Septation of the heart tube
 Atria → 4th week
 Common atrium → ridge develops in roof → septum primum (primary septum)
 Grows towards the endocardial cushions of the atrioventricular canal
 Opening that persists between the septum and cushion → ostium primum (primary
foramen)
 further growth → ostium primum closes → but before this → small holes appear in the
septum → merge to form ostium secundum (secondary foramen)
 by this means blood is allowed to flow between the two atria (NB for foetal circulation)
 while septum primum develops → another septum develops to the right of it → septum
secundum (secondary septum) → grows over septum primum but never completely divides
the atria and leaves the opening of the → foramen ovale
 the septum primum filling the foramen become the valve of the foramen ovale → essential
mechanism allowing O2 rich blood from placenta in right side of heart to pass to systemic
circulation without passing through pulmonary circulation
 pressure on R side is enough to force open the flap and allow blood into LA → increase in
pressure on L side of heart after birth and commencement of lung breathing → flap closes →
fossa ovalis
Septum formation in the ventricle
 myocardium grows → increase in size and internal volume of ventricles
 remodelling of ventricular wall → trabeculation
 tissue develops from floor of ventricle midway between R and L sides → grows towards
endocardial cushions = muscular component of interventricular septum
 never reaches the cushions and leaves a small gap → filled by two components;
o further growth of endocardial cushions
o down growths from the septum that divides the truncus arteriosus
 these two = membranous part of septum → accommodates the atrioventricular bundle →
this the only connecting tissue between the atria and the ventricles is this conducting tissue
→ ensures sequential contraction of atria followed by ventricles → as otherwise electrically
isolated
Septum formation in the outflow tracts of the heart
 initially truncus arteriosus → single lumen
 septum develops dividing the future ascending aorta and pulmonary trunk
 5th week → pair of ridges appear opposite each other within conus cordis and truncus
arteriosus = R and L truncoconal swellings
 The 2 ridges approach one another and form the aorticopulmonary septum and separates
the two major outflow tracts of the two ventricles
 Septum develops as a spiral structure → accounts for the spiralling of the aorta and
pulmonary trunk
Development of the venous drainage into the heart
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Blood drains to common atrium via series of veins – initially symmetrical and forms the sinus
venosus
Middle 4th week, sinus venosus receives blood from the right and left sinus horns. Each horn
receives blood from:
 Vitelline veins → drain yolk sac
 umbilical veins → drain placenta
 Common cardinal veins → into which drain the anterior and posterior cardinal veins: by
these two veins all the blood from the body of the embryo drains to the atria
Original symmetry of horns is soon lost as venous blood shunts from L to R
R sinus horn becomes proximal IVC and SVC
L side largely disappears apart from the part that becomes the coronary sinus
As R sinus horn and VCs enlarge → gradually drawn to posterior wall of atrium = sinus
venarum → represents the smooth-walled portion of the atrium
Primitive atrium → displaced anteriorly as muscular pouch = right auricle
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Smooth and rough parts are separated by a ridge/crest = crista terminalis (corresponding to
sulcus terminalis = groove on exterior of heart)
Parallel array of pectinate muscles project from this crest into auricular part of chamber
In the foetal heart → lower part of crista terminalis = valve of IVC → arranged to direct blood
through the foramen ovale into the LA – disappears after birth
Pulmonary veins develop in situ between heart and lungs and enter LA
Gradually the single opening of the pulmonary vein changes as further parts of the two sets
of veins are drawn into the wall of the LA → forms smooth-walled component
Valve formation in the atrioventricular canal and truncus arteriosus
 2 swellings of mesenchyme in wall of atrioventricular canal = endocardial cushions
 appear after 4th week at superior and inferior borders of atrioventricular canal
 soon after → 2 further swellings on R and L
 subsequent growth → superior and inferior fuse forming R and L atrioventricular canals →
from the margins of which the two atrioventricular valves arise
 remodelling → 2 flap valves: bicuspid/mitral on left and tricuspid on right
 as consequence of the remodelling → parts of the walls of the ventricles become so thin →
that muscular cords connecting the valves with the wall are replaced by connective tissue →
the chordae tendinae
 in the truncus arteriosus → similar sequence of swellings occurs to form the semilunar
valves in the aorta and pulmonary trunk
4. Summarise the development of the aortic and pharyngeal arches, and the embryological
derivation of the carotid, subclavian and pulmonary arteries
Pharyngeal arches
 give rise to:
o the cartilages, muscles and bones involved in chewing and swallowing
o contribute to the muscles used in facial expressions and speech
 begin to develop early in the 4th week from mesenchyme derived from the neural crest
 5 pairs of pharyngeal arches, numbered 1,2,3,4 and 6, form in craniocaudal sequence, and
by the end of the 5th week, all appear as rounded swellings on the surface
 the 5th pharyngeal arch is rudimentary and soon disappears
 each pharyngeal arch consists of a core of mesenchyme, has an outer covering of ectoderm
and is lined internally by endoderm
 the ectoderm appears as the pharyngeal clefts (grooves) between the arches and the
endoderm as the pharyngeal pouches
 the first pair of pharyngeal arches gives rise to the upper and lower jaw as well as playing a
major role in the development of the face and palate
 the mesenchyme in each arch differentiates into a bar of cartilage, the associated muscle
and an aortic arch artery
 each arch also contains a cranial nerve that enters it from the brain stem of the developing
brain
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the cranial nerves carry the motor fibres to supply the muscles derived from the pharyngeal
arches and also carry the sensory fibres to the developing skin covering them and the
mucosal tissue lining them
during further development, many pharyngeal arch muscles migrate from their site of origin
to reach their final destination, but they retain their original innervation – thus the origin of
each muscle can be determined from its nerve supply
Main derivatives of the Pharyngeal Pouches
Pharyngeal
Pouch
First
Second
Third
Fourth
Fifth
Main Derivative
Artery
tubotympanic recess, middle ear cavity,
auditory tube and tubal tonsil
palatine tonsil (also pharyngeal and lingual
tonsil)
maxillary artery
Dorsal: inferior parathyroid glands
(parathyroids III)
Ventral: thymus gland (fuses with contralateral
side)
Dorsal: superior parathyroid glands
(parathyroids IV)
Ventral: fuses with ultimobranchial body
Ultimobranchial body: fuses with lateral lobes
of thyroid gland; gives rise to the parafollicular
cells (C cells) which produce calcitonin
stapedial artery (small artery supplying
stapedial muscle, smallest skeletal muscle,
which stabilizes stapes of the ear)
common carotid/internal carotid
right – right subclavian artery
left – aortic arch
right – right pulmonary artery
left – pulmonary artery and ductus
arteriosus
Development of the arterial system
 arterial system of the embryo includes the aortic arches and the paired dorsal aortae
 the L and R dorsal aortae unite to form the descending aorta which passes the length of the
embryo supplying visceral and somatic structures as it does so
 the umbilical arteries from the placenta drain the embryo of deoxygenated blood
Aortic Arches
 the outflow channel of the heart is the dilated distal portion of the truncus arteriosus, the
aortic sac
 this sac contributes vessels to the pharyngeal arches which develop in the future neck region
around week 4 onwards
 within each pharyngeal arch, the artery develops and meets with the branch from the aortic
sac, forming five to six pairs of aortic arches
 initially there is symmetry in development, but changes soon result in an asymmetrical
pattern
 The aortic sac divides into a R and L dorsal aorta
 which continue to the body of the embryo where they fuse, just inferior to the heart,
forming a single vessel
 in subsequent development:
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 large portions of the original aortic arches disappear
 there are asymmetries for some arch pairs
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1 pair – largely disappears except for a small portion that persists as the maxillary artery
2nd pair – largely disappears
3rd pair – form the common carotid arteries, external carotid and proximal parts of the
internal carotid arteries (the distal part of the internal carotids form from the dorsal aortae)
4th pair – different on the two sides
 R side forms proximal portion of the right subclavian artery
 L side forms part of the arch of the aorta
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5 pair – if exists at all, consists only of a few capillary loops
6th pair – also asymmetric. The proximal part of the 6th arch pair form the pulmonary
arteries with the pulmonary trunk forming from the truncus arteriosus
 L side – the distal part of 6th arch persists as ductus arteriosus, which is an important
bypass channel for the oxygenated blood from the placenta to avoid passing into the
lungs
 R side – forms distal portion of R subclavian artery
The L subclavian artery forms from the 7th intersegmental artery which is a branch of the
dorsal aorta
Summary
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CVS is one of the first body systems to develop in order to carry O2 and nutrients around the
embryo
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Heart tube develops from unsegmented mesoderm at the rostral (head) end of the embryo,
and during longitudinal and lateral folding, it is carried around to its future thoracic position,
within the future pericardial cavity
The tube undergoes septation separating the atria, ventricles and great vessels. Atrial
septation involves the development of two septa: the septum prima and septa secundum.
These septa are not complete, enclosing the foramen ovale. This closes at birth as a
consequence of the differential pressures on the two sides
Ventricles: muscular outgrowth from the floor plus a membranous component from the
endocardial cushions forms the interventricular septum.
The division of the truncus arteriosus is accomplished by the appearance of the spiral
aortico-pulmonary trunk from the ascending aorta. The arterial system develops as two
dorsal aortae which fuse after the arch, just caudal to the heart
The truncus arteriosus gives rise initially to five/six pairs of aortic arches, which feed into the
two dorsal aortae. The symmetry of this pattern is lost as the adult pattern of the arches
develops.
The veins of the embryo drain into the sinus venosus, which also loses its initially symmetric
pattern. Draining into the sinus are the umbilical and vitelline veins, draining the placenta
and yolk sac respectively. The body of the embryo is drained via the anterior and posterior
cardinal veins, via the common cardinal vein into the sinus venosus.
After birth – changes in the morphology and organisation of the CVS as a result of lung
breathing. The umbilical arteries become the medial umbilical ligaments, the left umbilical
vein (the right disappears) becomes the ligamentum teres hepatis, the ductus venosus
becomes the ligamentum venosum and the ductus arteriosus becomes the ligamentum
arteriosum. The foramen ovale between the two atria closes leaving the foramen ovalis in
the interatrial septum.
5. summarise the defects of development of the heart and major blood vessels resulting in
the common forms of congenital heart disease (CHD’s)
Malformation
Description
Relative Frequency
(%)
Ventricular
septal defect
Incomplete closure of the ventricular septum. 30% exist as a single anomaly, the rest
are associated with other structural defects, such as tetralogy.
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Atrial septal
defect
Abnormal opening in the atrial septum that allows communication of blood between
the left and right atria. (Note: not to be confused with a patent foramen ovale, present
in up to one third of normal individuals, which generally does not permit flow unless
right atrial pressures are elevated.)
8
Patent ductus
arteriosus
Persistence after birth of the normal communication between the pulmonary arterial
system and the aorta of the foetus. Most often, it does not produce functional
difficulties at birth or during childhood. Obstructive pulmonary vascular disease
eventually occurs, with ultimate reversal of flow (left-to-right shunt converted to rightto-left) with its associated consequences.
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Tetralogy of
Fallot
Includes four associated features:
1) Membranous interventricular septum defect
2) Pulmonary stenosis
3) A large aorta (overriding aorta, the opening of which extends into the right ventricle)
4) Right ventricular hypertrophy.
The basic defect is an asymmetrical fusion of the truncoconal ridges and a
malalignment of the aortic and pulmonary valves.
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Due to the pulmonary stenosis and the wider-than-normal aortic opening, some poorly
O2 RV blood leaves via the enlarged aorta causing cyanosis.
This is the most common cyanotic heart lesion on young children.
patients are cyanotic from birth and exhibit severe clubbing
Pulmonary
stenosis
An obstruction at the pulmonary valve. Right ventricular hypertrophy often results, and
there is sometimes poststenotic dilation of the pulmonary artery.
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Aortic stenosis
or atresia
Narrowing and obstruction of the aortic valve present from birth. There are three major
types of stenosis: valvular, subvalvular, and supravalvular. Pressure hypertrophy of the
left ventricle usually develops.
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Coarctation of
aorta
Narrowing or constriction of the aorta which typically results in hypertension in the
upper extremities and hypotension in the lower extremities, associated with
manifestations of arterial insufficiency (i.e. claudication and coldness). There is
cardiomegaly owing to left ventricular hypertrophy.
6
Transposition of
great vessels
Transposition implies ventriculoarterial discordance, such that the aorta arises from the
right ventricle, and the pulmonary artery emanates from the left ventricle. The AV
connections are normal (concordant), with right atrium joining right ventricle and left
atrium emptying into left ventricle. The essential embryologic defect is the abnormal
formation of the truncal and aortopulmonary septa.
5
Atrioventricular
septal defect
Results from abnormal development of the embryologic AV canal, in which the superior
and inferior endocardial cushions fail to fuse adequately, resulting in incomplete
closure of the AV septum and inadequate formation of the tricuspid and mitral valves.
4
Truncus
arteriosus
Arises from a developmental failure of separation of the embryologic truncus arteriosus
into the aorta and pulmonary artery. The result is a single great artery that receives
blood from both ventricles, accompanied by an underlying ventricular septal defect,
and that gives rise to the systemic, pulmonary, and coronary circulations.
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