CARDIAC EMBRYOLOGY EARLY DEVELOPMENT OF HEART Dr.Santhosh Narayanan
FORMATION OF TRILAMINAR EMBRYO
CARDIOGENESIS MOLECULAR DEVELOPMENT OF HEART DEVELOPMENTAL ABNORMALITIES The Beginning
DAY 0 - FERTILISATION DAY 1 -4 - CELL DIVISION- MORULA DAY 5-6 - BLASTOCYST DAY 7-10 - IMPLANTATION
Bilaminar embryo (Days 11-14) EPIBLAST HYPOBLAST
The Amnion and Yolk sac Primitive streak week 3
Gastrulation - Week 3 Neurulation Neurulation
Derivatives of Germ layers The Cardiogenesis
CARDIOGENESIS Formation of bilateral heart fields Formation of the heart tube Folding of the heart tube Looping of the heart tube
Chamber specification and compaction Cardiac precursor cells
First heart field Second heart field
Neural crest cells Pro epicardium The "Cardiac Crescent"
The second heart field 3rd Heart field
The Cardiac Neural crest Sequence of Events Day I8 - Cardiac precursor cells seen in the
form of blood islands Day 20 - First intraembryonic blood vessels Day 21- Folding, heart tube formation,looping Day 22 heart starts to beat
Day 28 embryonic circulation established Folding of Embryo CRANIOCAUDAL AXIS More rapid growth of the neural tube forming
the brain at its cephalic end. Growth in this direction will cause the embryo to become convex shaped. LATERAL FOLDING Two lateral edges of the germ disk fold forming
a tube-like structure Folding of embryo Arterial end of the heart tube
proximal part called the conus a distal part called truncus arteriosus. The truncus continues distally with the aortic sac. Venous end
The sinus venosus vitelline vein from the yolksac umbilical vein from the placenta common cardinal vein from the bodywall
Looping Looping Mechanism of looping
Differential growth of the heart tube in comparison with foregut Differential growth within the heart tube itself Posterior, leftward, slower growth and anterior, rightward, faster growth resulting in
RIGHTWARD LOOPING Bending of the heart tube at the inflow as well as within the ventricular segment eventually positions the inflow and future left
ventricular segments posteriorly and to the left, with the future right ventricle and outflow segments anteriorly and to the right b
Convergence Movement of the outflow tract and the atrioventricular canal into a more midline position
Alignment Wedging Seperation (septation) of the primitive
ventricles and outflow tract into systemic (aorta) and pulmonary (pulmonary artery) trunks is created by a process called wedging The counterclockwise rotation of the outflow tract with movement of the future aortic valve
position behind the pulmonary trunk Convergence and Wedging Myocardial Compaction
Emergence of trabeculations Trabecular remodelling Emergence of trabeculations Emerge after looping of the primitive heart
tube At the end of the fourth week of gestation Trabeculation patterns are ventricle-specific trabeculations in the LV are generally thicker and the corresponding intertrabecular spaces
larger Trabecular remodeling After completion of ventricular septation at 8 weeks of gestation in
Increase in ventricular volumes results in compression of the trabeculations with an increase in the thickness of the compacted myocardium Compaction process coincides with the
invasion of epicardial coronary arteries Evolution of human heart Progressive displacement of the inflow structures from a caudal position to a dorsal
(fishes) and cephalad (reptiles) position. Septation of the atrium in a right and a left cavity (amphibians). Development of the right ventricle (RV) from the proximal part of the conus arteriosus.
Septation starting at the interventricular groove separating the left from RV (crocodiles). Development of a high-pressure left ventricle
(LV) and a low-pressure RV. Disappearance of the sinus venosus and the conus arteriosus (birds and mammals). Molecular development of heart
Genes in induction of crescent Anterior (cranial) endoderm induces a heart-forming region by inducing the
transcription factor NKX2.5. The signals require secretion of BMPs 2 and 4 secreted by the endoderm
and lateral plate mesoderm. Concomitantly, the activity of WNT proteins (3a and 8) secreted by the
neural tube, must be blocked because they normally inhibit heart development.
The combination of BMP activity and WNT inhibition by crescent and cerberus causes expression of NKX2.5. Genes in differentiation
Right left asymmetry Signalling networks NOTCH BMP
WNT FGF SEMAPHORIN Developmental abnormalities
From Fertilization to Primitive Heart Tube -Abnormal development at this stage of embryogenesis results in embryonic death because of the critical nature of the early
circulation to the further growth Abnormal left right signalling HETEROTAXY SYNDROMES -Right Isomerism
-Left Isomerism -Situs inversus with dextrocardia Heterotaxy spectrum
Right Isomerism Cardiac : The sinus nodes are paired because bilateral superior vena cavae are attached to bilateral morphologic right atria. The P-wave axis is normal because the right sinus node is
usually the dominant atrial pacemaker The atrioventricular conduction system is equipped with 2 nodes often connected by a sling of tissue Supraventricular tachycardia is attributed to reentry between paired atrioventricular nodes.
Right Isomerism- Associations
common atrium, common atrioventricular valve, Morphologic single ventricle,
Functional single ventricle (hypoplasticright or left), pulmonary stenosis or atresia, absent coronary sinus total anomalous pulmonary venous connection bilateral ductus arteriosus.
Ventricular and great arterial connections are usually discordant. Left Isomerism More prevalent in women
The pulmonary veins can be connected in a symmetric fashion, 2 to the right-sided atrium and 2 to the left-sided atrium The most distinctive and the most diagnostically useful clinical feature is inferior vena caval interruption with
azygous continuation, in which the suprarenal segment of the inferior cava is absent, and the infrarenal segment continues as the azygos or hemiazygous vein Fetal complete heart block is presumptive evidence of in utero left isomerism
Left Isomerism Sinus node is absent or hypoplastic. The atrial pacemaker is therefore ectopic, and the P-wave axis is abnormal.
The ectopic atrial pacemaker can shift from 1 site to another or may fire slowly (ectopic atrial bradycardia Malpositions due to looping defects
Situs solitus with Dextrocardia Isolated dextrocardia with AV concordance and NRGA The base-to-apex axis points to the right, right hemidiaphragm is lower
The embryonic straight heart tube initially bends rightward (dloop) but fails to move into the left chest. Congenital heart defects: ventricular septal defect left SVC to the coronary sinus coarctation of the aorta
secundum atrial septal defect anomalous pulmonary venous connections complete AV septal defect ECG
atrial activation is normal, and the P-wave frontal plane axis is 70 to 80 the frontal plane QRS axis exhibits a rightward shift or right-axis deviation a gradual and progressive reduction in the QRS Rwave voltage is observed
Corrected Transposition of the Great Arteries Isolated Dextrocardia with AV and VA Discordance and Left Anterior Aorta
most common form of dextrocardia Situs Inversus Situs inversus with Dextrocardia
Incidence 1 in 8,000 The thoracic and abdominal viscera are mirror images of normal morphologic right bronchus is concordant with the morphologic right atrium and a
trilobed lung usually occurs with a structurally normal heart ECG
Situs inversus with Dextrocardia: reversed ventricular activation and reversed repolarization. lead 1: QRS negative & the T wave inverted, lead aVR resembles aVL and vice versa, right precordial leads resemble leads from
corresponding left precordial sites. Septal Q waves appear in right precordial leads because septal depolarization is from right to left. Situs inversus with Dextrocardia
Inverted Normally Related Great Arteries (Left Posterior Aorta) Situs inversus totalis with persistence of normal AV and VA connections CHD :
VSD TOF pulmonary atresia complete AV septal defect OS ASD.
Situs Inversus with Dextrocardia, Atrioventricular Concordance, and Ventriculoatrial Discordance with Left Anterior Aorta
Inverted form of complete TGA The hemodynamics and physiology identical to TGA ECG : inverted P-wave axis because of the atrial
inversion more evidence of associated right and left ventricular hypertrophy because of transposition physiology
Situs Inversus with Dextrocardia Atrioventricular and Ventriculoatrial Discordance, with Right Anterior Aorta Inverted form of corrected TGA Rare
Situs Inversus with Dextrocardia, AV Discordance, and VA Concordance with Inverted NRGA Represents the inverted form of isolated
ventricular inversion extremely rare cardiac abnormalities common atrium common AV valve
severe right ventricular hypoplasia. MCQ'S 1.Coronary vessels develop from
A. FHF B.SHF C.Neural Crest D.Proepicardium
Answer D 2.All of the following are false except A.Right isomerism is associated with ectopic
pacemaker B.Lungs are trilobed in left isomerism C.Complete heart block is presumptive evidence of right isomerism D.Interrupted IVC is seen in left isomerism
Answer D 3.Intraembryonic blood vessels are seen on
A. Day 18
B.Day 19 C.Day 20 D.Day 22 Answer C
4.All of the following are correctly matched except
A- NKX 2.5- Cardiac crescent induction B. eHand- RV myocyte
C. TBX5- Septation D. GATA factors -Heart tube formation Answer B
5.Which of the following is false A.Mesocardia is always associated with congenital heart defects B.CCTGA-AV concordance with VA discordance C.Situs inversus with dextrocardia usually
occurs with a structurally normal heart D.Right hemidiaphragm is lower in situs solitus with dextrocardia Answer B
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