Embryology of the Heart - Weebly



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

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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

• 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 extra-embryonic 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

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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

• [pic]

• 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

• 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

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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

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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

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Development of the venous drainage into the heart

• 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

• 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

• 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 |Main Derivative |Artery |

|First |tubotympanic recess, middle ear cavity, auditory tube and |maxillary artery |

| |tubal tonsil | |

|Second |palatine tonsil (also pharyngeal and lingual tonsil) |stapedial artery (small artery supplying stapedial |

| | |muscle, smallest skeletal muscle, which stabilizes |

| | |stapes of the ear) |

|Third |Dorsal: inferior parathyroid glands (parathyroids III) |common carotid/internal carotid |

| |Ventral: thymus gland (fuses with contralateral side) | |

|Fourth |Dorsal: superior parathyroid glands (parathyroids IV) |right – right subclavian artery |

| |Ventral: fuses with ultimobranchial body |left – aortic arch |

|Fifth |Ultimobranchial body: fuses with lateral lobes of thyroid |right – right pulmonary artery |

| |gland; gives rise to the parafollicular cells (C cells) |left – pulmonary artery and ductus arteriosus |

| |which produce calcitonin | |

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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:

▪ large portions of the original aortic arches disappear

▪ there are asymmetries for some arch pairs

• 1st 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

• 5th 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

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Summary

• CVS is one of the first body systems to develop in order to carry O2 and nutrients around the embryo

• 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 |Incomplete closure of the ventricular septum. 30% exist as a single anomaly, the rest are |32 |

|defect |associated with other structural defects, such as tetralogy. | |

|Atrial septal defect |Abnormal opening in the atrial septum that allows communication of blood between the left and |8 |

| |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.) | |

|Patent ductus |Persistence after birth of the normal communication between the pulmonary arterial system and the |8 |

|arteriosus |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 right-to-left) with its associated consequences. | |

|Tetralogy of Fallot |Includes four associated features: |8 |

| |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. | |

| |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 |8 |

| |sometimes poststenotic dilation of the pulmonary artery. | |

|Aortic stenosis or |Narrowing and obstruction of the aortic valve present from birth. There are three major types of |8 |

|atresia |stenosis: valvular, subvalvular, and supravalvular. Pressure hypertrophy of the left ventricle | |

| |usually develops. | |

|Coarctation of aorta |Narrowing or constriction of the aorta which typically results in hypertension in the upper |6 |

| |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. | |

|Transposition of great|Transposition implies ventriculoarterial discordance, such that the aorta arises from the right |5 |

|vessels |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. | |

|Atrioventricular |Results from abnormal development of the embryologic AV canal, in which the superior and inferior |4 |

|septal defect |endocardial cushions fail to fuse adequately, resulting in incomplete closure of the AV septum and| |

| |inadequate formation of the tricuspid and mitral valves. | |

|Truncus arteriosus |Arises from a developmental failure of separation of the embryologic truncus arteriosus into the |1 |

| |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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