Organisation of the Body
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| Congenital heart defects | Cardiovascular anomalies are the most common life threatening congenital defect in babies
20% of all congenital defects in live births
Overriding aorta
Enlarged right ventricle
Stenotic pulmonary trunk
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| Formation of the cardiac crescent | Splanchnic lateral plate mesoderm inducted to form the cardiac crescent
Two heart fields meet rostrally
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| Induction of cardiac mesoderm | Lateral endoderm secretes Bmp2 which induces cardiac mesoderm formation
Inhibitors of Bmp2 e.g. Chordin and noggin produced by notochord and midline endoderm to repress cardiogenic formation
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| Endocardial tubes | Angiogenic clusters coalesce to form angiogenic tubes
Condensation of mesoderm
Rostral to neural plate
Fuse in the midline by rostral folding
Mesodermal cells for cardiomyocytes
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| Formation of linear heart tube | Lateral folding brings regions to the midline
The left and right dorsal aorta form - undergo remodelling in adults
Cardiac jelly - ECM
Endocardial tubes surrounded by myocardium
Flat sheet undergoes doral folding
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| Regionalisation of the early heart tube | Dorsal aorta
Truncus arteriosus
Bulbus cordis
Primitive ventricle
Primitive atrium
Sinus venosus
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| Contractile activity | Initiates prior to LHT formation
Blood flows caudal to cranial through the heart tube
SV - atrium - ventricle - Bulbus cordis - aortic arch
Seen as soon as sarcomeres develop
Cardiac TnT present before- not in correct position so no contraction
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| Dorsal Mesocardium | Linear heart tube is attached to the body by the dorsal mesocardium
This breaks down forming the transverse sinus, freeing the heart tube allowing it to grow and change shape
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| Looping of the linear heart tube | Occurs between days 23-38
4 chambers are brought to the correct spatial arrangement
An intrinsic property of heart tubes - can dissect out heart and it will still fold
Has an effect on direction of blood flow
First sign of left right asymmetry
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| How to the ventricles and atrial move in looping | Ventricles proliferate rapidly and push down and out
Atria are pushed up and back
Atria therefore move behind the linear heart tube and lie superior to the primitive ventricle
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| Asymmetry of the heart | Pitx2 is only expressed on the left
The node induced left right differences first seen in the heart tube where dissimilar left right gene expression may be involved in looping
HAND1 in left
HAND2 in right
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| Septation of the heart | Takes place between weeks 4-7
Separation of common atrium into left and right
Separation of common atrioventricular canal
Division of outflow tract
Separation of ventricle into left and right
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| Cardiac jelly | Mesenchymal cells migrate into it
The atrioventricular canal is populated by endocardial cells
The outflow tract is populated by neural crest cells
Endocardial cushions are formed from cardiac jelly and endocardial cells
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| Formation of endocardial cushions | Migration of mesenchymal cells remodels the ECM
Form bulges which meets to form walls of the chambers
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| Atrioventricular canals | The superior and inferior cushions fuse separating the left and right atrioventricular canals
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| Atrial septation | Begins at the end of 4th week
Crescent shaped septum primum grown down from the roof of the common atrium and extends towards endocardial cushions
Foramen primum - space between septum primum and endocardial cushions
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| Septum primum | Grows down and starts to fuse with the atrioventricular septum
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| Septum secundum | Programmed cell death created perforations called foramen secundum at the top of the septum primum
Thick muscular SS starts to grow down to the right of the SP but does not fuse with S intermedium
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| Formation of Foramen Ovale | Gap left by the SS is the foramen ovale, which acts as a right to left inter atrial shunt for blood
Only SP can be displaced as it in thinner - blood only travels one direction
Atrial septal defects - excessive cell death in septum primum
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| Blood flow through embryonic heart | Two separate streams
Blood from placenta enters right atrium via IVC and tends to flo through foramen ovale into left atrium
Blood returning from embryo enters right atrium via SVC and flows into right side of the ventricle
Leave via Truncus Arteriosus
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| Septation of ventricles and outflow tract | These are interlinked processes depending on haemodynamic forces generated by blood flow through the heart and left to right shift in symmetry
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| Ventricular septation | Interventricular septum grows from the base of the heart upwards towards the endocardial cushions
Interventricular septum defects are the most common congenital heart defect
Commonly affects membranous part of septum
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| Outflow tract septation | The process of IV septation is continuous with the septation of the outflow tract
Haemodynamic forces cause by the 2 spiralling blood streams act on the cardiac jelly rich wall of the outflow tract
Pressure causes formation of spiral ridges that fuse
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| Septation of aortic and pulmonary outflow | Fusion of the ridges separates the aortic and pulmonary outflow
Around the end of 7th week, the ridges fuse with the atrioventricular septum and muscular interventricular septum, forming the membranous interventricular septum
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| Neural crest contribution to conotruncal ridges | Neural crest cells in the occipital region populate the conotruncal ridges of the outflow tract
Neural crest abnormalities are commonly linked with heart abnormalities
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| Outflow tract abnormalities | Defects in neural crest migration can lead to abnormalities of the outflow tract
No septation - persistent truncus arteriosus
No spiralling - transposition of the great vessels
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| Tetralogy of Fallot | Abnormal blood flow can lead to problems of septation of outflow tract e.g. Fallots tetralogy
Leads to pulmonary stenosis, interventricular septal defect, over riding aorta and hypertrophy of the right ventricle
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| Formation of atrio-ventricular valves | Form between 5-8 weeks
Endocardial cells migrate into cardiac jelly
Ventricular layer is hollowed out and thinned by cell death to form valve leaflet
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| The aortic arch system | Forms the future aortic and pulmonary trunks
Five pairs of aortic arches form - I, II, III, IV and VI (V is residual)
Not all present at once
Lies in pharyngeal arches
Many vessels lost or remodeled
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| Aortic arch remodelling | Aortic arches start to form the aortic and pulmonary trunks at 4th week
Arch I and II regress
Arch III - carotid arteries
Arch IV and VI form aortic arch and pulmonary trunk
Connection between them - ductus arteriosus - acts a bypass for circulation
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| Venous return to the heart | Venous drainage returns to the heart via the cardinal, umbilical and vitelline veins
Initially bilaterally symmetrical but is remodelled so that all the systemic venous blood drains into the right side of the heart via SVC and IVC
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| Venous system changes | Affected by growing liver which surrounds vitelline and umbilical veins that form a capillary network in the liver
Ductus venosus develops to shunt blood entering from the left umbilical vein past the liver to the IVC
Right umbilical vein regresses
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| Foetal circulation | Umbilical vessel open
Shunts open ; ductus venosus, foramen ovale and ductus arteriosus
Allows heart and brain to receive blood rich in oxygen and nutrients
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| Foetal circulation after birth | Pressure in left atrium increases
Umbilical artery walls contract - becomes medial vesicular ligament
Umbilical vein closes - becomes ligamentum teres
Ductus venosus-ligamentum venosum
Foramen ovale-fossa ovale
Ductus arteriosus-ligamentum arteriosum
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