Heart Development I Dr. J.K. Brueckner Anatomy and Neurobiology [email_address]
<ul><li>The cardiovascular system is the  first body system to function in the embryo .  Formation of the primitive heart ...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Heart development:  Construction of the primitive heart tube  Heart development begins...
<ul><li>Heart Development </li></ul>Embryonic folding  brings the  two endocardial tubes  into the thorax where they meet ...
<ul><li>Heart Development </li></ul>Embryonic folding  brings the  two endocardial tubes  into the thorax where they meet ...
<ul><li>Heart Development </li></ul>Embryonic folding  brings the  two endocardial tubes  into the thorax where they meet ...
<ul><li>Heart Development </li></ul>Embryonic folding  brings the  two endocardial tubes  into the thorax where they meet ...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ).  As th...
<ul><li>Heart Development </li></ul>Angioblastic cords Endocardial tubes Splanchnic mesoderm Somatic mesoderm Parietal per...
<ul><li>Heart Development </li></ul>As the heart elongates and bends it  gradually invaginates into the pericardial cavity...
<ul><li>Heart Development </li></ul>Septum secundum RA LA Septum secundum Endocardial cushion Foramen  ovale Septum  primu...
<ul><li>Heart Development </li></ul>Truncal ridges Bulbar ridges Aortic arches Ventricle A A Before birth :  foramen ovale...
<ul><li>Heart Development </li></ul>Sagittal sections Coronal section Atrioventricular septum Concurrent with embryonic fo...
<ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in sep...
<ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in sep...
<ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in sep...
<ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in sep...
<ul><li>Heart Development </li></ul>Septum primum  grows from the roof of the common atrium.  It extends toward the endoca...
<ul><li>Heart Development </li></ul>Septum primum  grows from the roof of the common atrium.  It extends toward the endoca...
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  1. 1. Heart Development I Dr. J.K. Brueckner Anatomy and Neurobiology [email_address]
  2. 2. <ul><li>The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. </li></ul>Heart Development
  3. 3. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  4. 4. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  5. 5. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  6. 6. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  7. 7. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  8. 8. <ul><li>Heart Development </li></ul>Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region, mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords. These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes.
  9. 9. <ul><li>Heart Development </li></ul>Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development Angioblastic cords
  10. 10. <ul><li>Heart Development </li></ul>Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development Endocardial tubes Angioblastic cords
  11. 11. <ul><li>Heart Development </li></ul>Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development Angioblastic cords Endocardial tubes
  12. 12. <ul><li>Heart Development </li></ul>Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development Angioblastic cords Endocardial tubes
  13. 13. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Angioblastic cords Endocardial tubes
  14. 14. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Angioblastic cords Endocardial tubes
  15. 15. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Angioblastic cords Endocardial tubes
  16. 16. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Angioblastic cords Endocardial tubes Splanchnic mesoderm
  17. 17. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Angioblastic cords Endocardial tubes Splanchnic mesoderm Somatic mesoderm
  18. 18. <ul><li>Heart Development </li></ul>The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Also forms visceral pericardium Angioblastic cords Endocardial tubes Splanchnic mesoderm Somatic mesoderm
  19. 19. <ul><li>Heart Development </li></ul>Angioblastic cords Endocardial tubes Splanchnic mesoderm Somatic mesoderm Parietal pericardium The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . Also forms visceral pericardium
  20. 20. <ul><li>Heart Development </li></ul>As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Angioblastic cords Endocardial tubes Splanchnic mesoderm Somatic mesoderm Parietal pericardium
  21. 21. <ul><li>Heart Development </li></ul>Septum secundum RA LA Septum secundum Endocardial cushion Foramen ovale Septum primum Fossa ovalis Pulmonary trunk Aorta Aorticopulmonary septum Truncus arteriosus/ bulbis cordis Truncal ridges Bulbar ridges Aortic arches Ventricle A A Before birth : foramen ovale shunts most blood entering right atrium to ther left atrium and prevents passage of blood in the opposite direction since septum primum closes against the relatively rigid septum secundum. After birth : functional closure of foramen ovale is facilitated by decreased right atrial pressure (occlusion of placental circulation) and increased left atrial pressure (due to increased pulmonary venous return). Septum primum is pressed against septum secundum and they adhere, forming fossa ovalis . Anatomical closure occurs within the 1 st postnatal year. Atrial Septal Defects (ASDs) Probe patency of foramen ovale is caused by incomplete anatomical fusion of septum primum and secundum. It is present in 25% of the population and is usually of no clinical importance. Foramen secundum defect is caused by excessive resorption of septum primum or secundum or both, leaving an opening between right and left atria. Some defects can be tolerated for a long time, with clinical symptoms manifesting as late as age 30. This is the most common clinically significant ASD. Common atrium (cor triloculare biventriculare) is caused by complete failure of septum primum and secundum to develop, resulting in formation of a single atrium. Partitioning bulbis cordis and truncus arteriosus: Formation of the pulmonary trunk and ascending aorta Without partitioning, there would be only one outflow path from the fused ventricles. Development of the aorticopulmonary septum creates two outflow paths, aorta and pulmonary trunk. Development is timed to coincide with completion of the interventricular septum so that when two separate ventricles are formed, so there will be an outflow path for each. During week 5, the aorticopulmonary septum develops from swellings in the walls of the truncus arteriosus (the truncal ridges ) and the bulbis cordis ( bulbar ridges ). These ridges are populated by neural crest cells that migrate through the pharyngeal arches to reach them. The truncal and bulbar ridges are continuous with one another, forming a complete septum, dividing the bulbis and truncus into two arterial channels, the aorta and the pulmonary trunk. Formation of the aorticopulmonary septum starts at the inferior end of the truncus and proceeds superiorly and inferiorly. The aorticopulmonary septum forms as a spiral, due to the positioning of the initial truncal and bulbar swellings and their subsequent pattern of growth. When the free edges of each ridge unite in the center of the truncus lumen, they form a spiraling wall. A split develops in the medial plane of the septum, resulting in complete separation of the ascending aorta and pulmonary trunk, with the pulmonary trunk twisting around the ascending aorta. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart.
  22. 22. <ul><li>Heart Development </li></ul>Truncal ridges Bulbar ridges Aortic arches Ventricle A A Before birth : foramen ovale shunts most blood entering right atrium to ther left atrium and prevents passage of blood in the opposite direction since septum primum closes against the relatively rigid septum secundum. After birth : functional closure of foramen ovale is facilitated by decreased right atrial pressure (occlusion of placental circulation) and increased left atrial pressure (due to increased pulmonary venous return). Septum primum is pressed against septum secundum and they adhere, forming fossa ovalis . Anatomical closure occurs within the 1 st postnatal year. Atrial Septal Defects (ASDs) Probe patency of foramen ovale is caused by incomplete anatomical fusion of septum primum and secundum. It is present in 25% of the population and is usually of no clinical importance. Foramen secundum defect is caused by excessive resorption of septum primum or secundum or both, leaving an opening between right and left atria. Some defects can be tolerated for a long time, with clinical symptoms manifesting as late as age 30. This is the most common clinically significant ASD. Common atrium (cor triloculare biventriculare) is caused by complete failure of septum primum and secundum to develop, resulting in formation of a single atrium. Partitioning bulbis cordis and truncus arteriosus: Formation of the pulmonary trunk and ascending aorta Without partitioning, there would be only one outflow path from the fused ventricles. Development of the aorticopulmonary septum creates two outflow paths, aorta and pulmonary trunk. Development is timed to coincide with completion of the interventricular septum so that when two separate ventricles are formed, so there will be an outflow path for each. During week 5, the aorticopulmonary septum develops from swellings in the walls of the truncus arteriosus (the truncal ridges ) and the bulbis cordis ( bulbar ridges ). These ridges are populated by neural crest cells that migrate through the pharyngeal arches to reach them. The truncal and bulbar ridges are continuous with one another, forming a complete septum, dividing the bulbis and truncus into two arterial channels, the aorta and the pulmonary trunk. Formation of the aorticopulmonary septum starts at the inferior end of the truncus and proceeds superiorly and inferiorly. The aorticopulmonary septum forms as a spiral, due to the positioning of the initial truncal and bulbar swellings and their subsequent pattern of growth. When the free edges of each ridge unite in the center of the truncus lumen, they form a spiraling wall. A split develops in the medial plane of the septum, resulting in complete separation of the ascending aorta and pulmonary trunk, with the pulmonary trunk twisting around the ascending aorta. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart.
  23. 23. <ul><li>Heart Development </li></ul>Sagittal sections Coronal section Atrioventricular septum Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Formation of the aorticopulmonary septum starts at the inferior end of the truncus and proceeds superiorly and inferiorly. The aorticopulmonary septum forms as a spiral, due to the positioning of the initial truncal and bulbar swellings and their subsequent pattern of growth. When the free edges of each ridge unite in the center of the truncus lumen, they form a spiraling wall. A split develops in the medial plane of the septum, resulting in complete separation of the ascending aorta and pulmonary trunk, with the pulmonary trunk twisting around the ascending aorta. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  24. 24. <ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Atrial Septation The division of the primitive atrium occurs in two phases. A partial partition is formed before birth allowing blood flow between atria. The partition is functionally completed at birth. Blood from the right atrium then flows to the right ventricle and pulmonary trunk for delivery to the functioning lungs. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  25. 25. <ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Atrial Septation The division of the primitive atrium occurs in two phases. A partial partition is formed before birth allowing blood flow between atria. The partition is functionally completed at birth. Blood from the right atrium then flows to the right ventricle and pulmonary trunk for delivery to the functioning lungs. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  26. 26. <ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Atrial Septation The division of the primitive atrium occurs in two phases. A partial partition is formed before birth allowing blood flow between atria. The partition is functionally completed at birth. Blood from the right atrium then flows to the right ventricle and pulmonary trunk for delivery to the functioning lungs. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  27. 27. <ul><li>Heart Development </li></ul>RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Atrial Septation The division of the primitive atrium occurs in two phases. A partial partition is formed before birth allowing blood flow between atria. The partition is functionally completed at birth. Blood from the right atrium then flows to the right ventricle and pulmonary trunk for delivery to the functioning lungs. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  28. 28. <ul><li>Heart Development </li></ul>Septum primum grows from the roof of the common atrium. It extends toward the endocardial cushions, which are fusing to create the AV septum. The foramen primum is the opening between the septum primum and the endocardial cushions. Foramen primum acts as a shunt, enabling oxygenated blood to pass from right to left atrium. Foramen primum becomes progressively smaller as septum primum fuses with the endocardial cushions. The foramen primum is lost as the septum primum fuses caudally. Before foramen primum disappears, perforations in the septum primum (via cell death) coalesce to form another opening, foramen secundum . The septum secundum grows down from the roof of the atrium immediately to the right of septum primum . It gradually overlaps septum primum. RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Septum secundum RA LA Septum secundum Endocardial cushion Foramen ovale Septum primum Fossa ovalis Pulmonary trunk Aorta Aorticopulmonary septum Truncus arteriosus/ bulbis cordis Truncal ridges Bulbar ridges Aortic arches Ventricle A A Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of the primitive atrium is displaced to the left where it becomes the left auricle. Partitioning the primitive heart As the heart is bending and enlarging, its original single chamber begins to be partitioned in order to separate the systemic and pulmonary circulations. Four sets of partitions form simultaneously in the atrium and the ventricle during weeks 4-5. These partitions will separate: 1) the atria from the ventricles 2) the right and left atria 3) the right and left ventricles 4) the pulmonary trunk and ascending aorta Partitioning atria from ventricles There is a large single passageway between the primitive atrium and the primitive ventricle ( atrioventricular canal ). During week 4, swellings ( endocardial cushions ) develop on the walls of the primitive heart at the level of the atrioventricular canal. The endocardial cushions grow toward one another and fuse medially, dividing the AV canal into a right and left atrioventricar openings . The endocardial cushions do not run the entire length of the heart. The atrioventricular valves (left bicuspid/mitral valve and right tricuspid valve) are formed later by fibrosis and thinning of the endocardial cushion tissue. The endocardial cushions also participate in formation of the membranous portion of the interventricular septum and in closure of foramen primum . In ultrasonography, this region appears as a cross, with the atrial and ventricular septa forming the post and the endocardial cushions forming the horizontal cross bar. The integrity of this cross is an important sign in cardiac ultrasounds. If the cushions fail to fuse, the result is persistent atrioventricular canal . Atrial Septation The division of the primitive atrium occurs in two phases. A partial partition is formed before birth allowing blood flow between atria. The partition is functionally completed at birth. Blood from the right atrium then flows to the right ventricle and pulmonary trunk for delivery to the functioning lungs. Before birth : foramen ovale shunts most blood entering right atrium to ther left atrium and prevents passage of blood in the opposite direction since septum primum closes against the relatively rigid septum secundum. After birth : functional closure of foramen ovale is facilitated by decreased right atrial pressure (occlusion of placental circulation) and increased left atrial pressure (due to increased pulmonary venous return). Septum primum is pressed against septum secundum and they adhere, forming fossa ovalis . Anatomical closure occurs within the 1 st postnatal year. Atrial Septal Defects (ASDs) Probe patency of foramen ovale is caused by incomplete anatomical fusion of septum primum and secundum. It is present in 25% of the population and is usually of no clinical importance. Foramen secundum defect is caused by excessive resorption of septum primum or secundum or both, leaving an opening between right and left atria. Some defects can be tolerated for a long time, with clinical symptoms manifesting as late as age 30. This is the most common clinically significant ASD. Common atrium (cor triloculare biventriculare) is caused by complete failure of septum primum and secundum to develop, resulting in formation of a single atrium. Partitioning bulbis cordis and truncus arteriosus: Formation of the pulmonary trunk and ascending aorta Without partitioning, there would be only one outflow path from the fused ventricles. Development of the aorticopulmonary septum creates two outflow paths, aorta and pulmonary trunk. Development is timed to coincide with completion of the interventricular septum so that when two separate ventricles are formed, so there will be an outflow path for each. During week 5, the aorticopulmonary septum develops from swellings in the walls of the truncus arteriosus (the truncal ridges ) and the bulbis cordis ( bulbar ridges ). These ridges are populated by neural crest cells that migrate through the pharyngeal arches to reach them. The truncal and bulbar ridges are continuous with one another, forming a complete septum, dividing the bulbis and truncus into two arterial channels, the aorta and the pulmonary trunk. Formation of the aorticopulmonary septum starts at the inferior end of the truncus and proceeds superiorly and inferiorly. The aorticopulmonary septum forms as a spiral, due to the positioning of the initial truncal and bulbar swellings and their subsequent pattern of growth. When the free edges of each ridge unite in the center of the truncus lumen, they form a spiraling wall. A split develops in the medial plane of the septum, resulting in complete separation of the ascending aorta and pulmonary trunk, with the pulmonary trunk twisting around the ascending aorta. Abnormal Division of the Truncus Arteriosus 1) Persistant Truncus Arteriosus is caused by abnormal neural crest cell migration such that there is only partial development of the AP septum. Only large vessel leaves the heart, receiving blood from both ventricles and is associated clinically with marked cyanosis. 2) Transposition of the Great Arteries is the most common cause of cyanotic heart disease in newborns (“blue babies”; early cyanosis). Often correlated with diabetic mothers. The aorticopulmonary septum grows in a straight line rather than in a spiral. The aorta arises from the rt. ventricle and pulmonary trunk from lt. ventricle. Incompatible with life unless an accompanying shunt (VSD-ventricular septal defect, patent foramen ovale, patent ductus arteriosus) exists 3) Tetrology of Fallot is caused by abnormal neural crest cell migration such that truncus arteriosus is not divided equally, resulting in a condition where the pulmonary trunk has a small diameter ( pulmonary stenosis ) while the aorta has a large diameter ( overriding aorta ). Because the AP septum is not positioned correctly, it fails to align with the interventricular septum, resulting in a VSD = ventricular septal defect . This condition is associated with marked cyanosis and is characterized by 4 classic malformations: 1) pulmonary stenosis 2) right ventricular hypertrophy 3) overriding aorta 4) VSD Formation of the interventricular septum Division of the primitive ventricle into right and left ventricles begins during week 4 when formation of the interventricular septum is initiated. In the adult, this septum is composed of a muscular and a membranous region. The muscular part develops first and is formed by growth of a muscular ridge upward from the ventricular floor near its apex. There is open communication between the two ventricles until the end of the seventh week through the interventricular foramen , the space between the cushions and the muscular septum. This foramen is closed by development of the membranous portion of the septum. Three tissues contribute to the membranous septum, including the right and left bulbar ridges (which grow to divide the bulbis cordis and truncus arteriosus) as well as cells proliferating from the endocardial cushions . After the interventricular foramen is closed, the pulmonary trunk communicates with the right ventricle and the aorta opens into the left ventricle. Ventricular Septal Defects (VSDs) VSDs are the most common type of cardiac defect, accounting for 25% of congenital heart disease. Most people with this defect experience a massive left to right shunt of blood, resulting in pulmonary hypertension . As pulmonary resistance increases, the shunt changes to a right to left shunt, which causes cyanosis ( Eisenmenger’s syndrome ). If left uncorrected, VSD usually leads to death from congestive heart failure. 1) Membranous VSD : This type is the most common VSD. A patent interventricular foramen is due to the failure of the membranous part of the IV septum to develop. This results from faulty fusion of the bulbar ridges and the endocardial cushions. 2) Muscular VSD : Openings in this less common form of VSD may occur anywhere in the muscular part of the interventricular septum. Multiple defects in the wall are termed “Swiss Cheese VSD.” Excessive cavitation of the ventricular wall results in perforations in the muscular septum. 3) Common ventricle : The interventricular septum fails to form completely and results in a three chambered heart (cor triloculare biatriatum). Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches Ascending aorta and pulmonary trunk Truncus arteriosus Trabeculated left ventricle Primitive ventricle Trabeculated right ventricle Bulbis cordis Outflow tract for both ventricles: conus arteriosus (infundibulum) for right ventricle and aortic vestibule just below aortic valve for left ventricle Conus cordis (upper bulbis cordis) Smooth part of left atrium Primitive pulmonary veins Coronary sinus Left horn of sinus venosus Smooth part of the right atrium (sinus venarum) Right horn of sinus venosus Auricles of right and left atria Primitive atria Adult Derivative/s Embryonic structure
  29. 29. <ul><li>Heart Development </li></ul>Septum primum grows from the roof of the common atrium. It extends toward the endocardial cushions, which are fusing to create the AV septum. The foramen primum is the opening between the septum primum and the endocardial cushions. Foramen primum acts as a shunt, enabling oxygenated blood to pass from right to left atrium. Foramen primum becomes progressively smaller as septum primum fuses with the endocardial cushions. The foramen primum is lost as the septum primum fuses caudally. Before foramen primum disappears, perforations in the septum primum (via cell death) coalesce to form another opening, foramen secundum . The septum secundum grows down from the roof of the atrium immediately to the right of septum primum . It gradually overlaps septum primum. RA LA Septum primum Coronal sections Lateral view (from rt atrium) Perforations in septum primum Septum primum Endocardial cushion Foramen secundum Septum secundum RA LA Endocardial cushion Foramen ovale Septum primum Fossa ovalis Pulmonary trunk Aorticopulmonary septum Truncus arteriosus/ bulbis cordis Truncal ridges Bulbar ridges Aortic arches Ventricle A A Dorsal aorta Ant. Cardinal v. Post. Cardinal v. Umbilical v. Umbilical a. Vitelline v. Vitelline a. Aortic arches Cranial capillaries Sinus venosus Atrium Ventricle Bulbis cordis Truncus arteriosus Aortic arches A V BC Endocardial cushion A Ventricle BC Atrioventricular septum Primitive AV canal Rt. AV orifice Lt. AV orifice RA LA RV LV Sagittal sections Coronal section Cross sections through atrioventricular junction Endocardial cushions Atrioventricular septum The cardiovascular system is the first body system to function in the embryo . Formation of the primitive heart and vascular system begins during week 3 and the heart starts beating by the beginning of week 4. This precocious cardiac development is necessary because diffusion becomes insufficient to satisfy the rapidly growing embryo by week 4. Functionally, the embryonic heart must act as a single pump that maintains blood flow through the body into the placenta where fetal wastes are exchanged for oxygen and nutrients. It must be prepared, however, for the radical changes that occurs at birth when the placental circulation is abruptly cut off and breathing is initiated. Heart development: Construction of the primitive heart tube Heart development begins during week 3. At the rostral end of the embryonic body in an area called the cardiogenic region , mesodermal cells aggregate to form longitudinal cellular strands termed angioblastic cords . These cords are located ventral to the pericardial coelom. The angioblastic cords canalize (hollow out) to form two parallel endocardial heart tubes . Embryonic folding brings the two endocardial tubes into the thorax where they meet along midline and fuse to form a single tube. Fusion of the endocardial tubes begins at the cranial end of the heart and proceeds caudally. Impact of Lateral Folding on Early Heart Development The fused endocardial tubes form the inner lining of the heart ( endocardium ). As the heart tubes fuse, the mesoderm surrounding the pericardial coelom forms two layers: a thick, inner gelatinous matrix (cardiac jelly) and an outer muscular layer ( myocardium) . As the heart elongates and bends it gradually invaginates into the pericardial cavity . It is initially suspended from the dorsal wall by dorsal mesocardium , but this degenerates, forming a communication (transverse pericardial sinus) between left and right sides of the pericardial cavity. As a result, the heart is anchored only at its cranial and caudal ends. Differentiation of the Primitive Heart Tube Concurrent with embryonic folding, the tubular heart elongates and develops dilations and series of constrictions that subdivide the primitive heart. Blood enters the caudal end of the tube, the sinus venosus (which receives blood from 1. the body via the common cardinal veins 2. the placenta via the umbilical veins 3. the yolk sac via the vitelline veins). From the sinus venosus, blood flows cranially into the primitive atrium . From the atrium, blood enters the primitive ventricle . From the ventricle, blood is pumped to the bulbis cordis which drains into truncus arteriosus . The truncus is continuous cranially with the expanded aortic sac from which the aortic arches arise. Blood flows from the aortic arches into the dorsal aortae in order to reach the embryonic body, the placenta and the yolk sac. Folding of the primitive heart tube brings the four putative chambers of the adult heart into the correct spatial relationship with one another. As the heart tube begins to lengthen, it bulges and bends to the right within the pericardial cavity. The bulbis cordis and ventricle grow faster than other regions, initiating folding of the tubular heart. Bulbis cordis moves inferiorly, ventrally, and to the right. Primitive ventricle moves to the left, while the primitive atrium moves posteriorly and superiorly. Bending of the heart tube also partitions the sinus venosus into right and left horns and it gradually shifts to the right to empty into the right atrium. In isolated dextrocardia , the heart is abnormally positioned on the right side of the thorax and is associated with other severe cardiac anomalies. Dextrocardia with situs inversus accompanies inversion of other viscera such as the liver and is not associated with other cardiac anomalies. Atrial Wall Remodeling Right atrial wall: The right side of the sinus venosus is incorporated into the right posterior wall of the primitive atrium, displacing the original right half ventrally and to the right. The portion of the atrium that consists of the incorporated sinus venosus is called the sinus venarum , while the original right side of the primitive atrium becomes the right auricle. Left atrial wall: During week 4, the primitive atrium sprouts a pulmonary vein that divides to produce a total of 4 pulmonary veins that grow toward the lungs where they anastomose with veins developing in the mesoderm around the bronchial buds. Much of the left atrial wall is formed by the incorporation of the primitive pulmonary vein and its branches, giving it a smooth appearance. The trabeculated left side of

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