Development of heart.pdf

EMBRYOLOGY. DEVELOPMENT OF THE HEART Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES The part of the learning outcomes will be discussed in the next lecture – ‘Development of...

EMBRYOLOGY. DEVELOPMENT OF THE HEART Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES The part of the learning outcomes will be discussed in the next lecture – ‘Development of vessels. Blood supply of fetus’. EMBR.07 - Cardiovascular and Lymphatic system development EMBR.07.01 - Be able to explain the sequential formation of hemangioblasts, blood islands, endothelial lined tubes a EMBR.07.02 - Be able to explain the similarities between the heart tubes, dorsal aorta and the vitelline veins EMBR.07.03 - Be able to explain how lateral folding modifies the developing heart tube, dorsal aorta, and vitelline veins EMBR.07.04 - Be able to explain the components of the heart tube and there derivatives EMBR.07.05 - Be able to explain cardiac looping and clinical correlations EMBR.07.06 - Be able to explain the development of the atrioventricular canals EMBR.07.07 - Be able to explain the septation and further modification of the primitive atria and their clinical correlations EMBR.07.08 - Be able to explain the importance of the right-left blood shunt EMBR.07.09 - Be able to explain the septation and further modification of the primitive ventricles and their clinical correlations EMBR.07.10 - Be able to explain the formation and modification of Sinus Venosus and Truncus Arteriosus and their clinical correlations EMBR.07.11 - Be able to explain the difference between the membranous ventricular septum and the conotruncal septum EMBR.07.12 - Explain the veins of the sinus venosus- umbilical, vitelline, and cardinal EMBR.07.13 - Be able to explain the tributaries of the posterior cardinal vein and how they are modified EMBR.07.14 - Be able to explain the tributaries of the anterior cardinal vein and how they are modified EMBR.07.15 - Be able to explain how the common cardinal veins are modified EMBR.07.16 - Be able to explain how the truncus arteriosus is modified EMBR.07.17 - Be able to explain the formation and modification of fetal circulation and its shunts EMBR.07.18 - Be able to explain the development of the lymphatic system  OVERVIEW Development of separate blood vascular system starts at the beginning of the 3rd week. All components of cardiovascular system (CVS) develop from mesoderm. Development of the CVS can be studied as: 1. Development of heart 2. Development of blood vessels. Heart develops from primitive heart tube, which forms from mesenchyme in the cardiogenic area of the embryo. Heart tube forms the endocardium of the heart. Splanchnic mesoderm surrounding the primitive heart tube forms myocardium and epicardium. Primitive heart starts beating on 21-22nd day. Blood begins to circulate within the embryo by 24th day.  ESTABLISHMENT OF CARDIOGENIC AREA (FIELD, PLATE) During the 3rd week, cardiac progenitor cells develop just cranial to the primitive streak. These cells migrate through primitive streak cranially and form horseshoe shaped primitive heart field in the splanchnopleuric mesoderm by end of the 3rd week. On formation of head fold, primary heart field come to lie on dorsal side of pericardial sac. Endoderm of primitive pharynx induces vasculogenesis (formation of blood cells and vessels) in the primary heart field (via secretion of vascular endothelial growth factor – VEGF). Bottom view of the three-layered embryonic disc if the endoderm is removed. The cardiogenic zone is a horseshoe-shaped red structure in the picture ESTABLISHMENT OF CARDIOGENIC AREA (FIELD, PLATE)  ESTABLISHMENT OF CARDIOGENIC AREA (FIELD, PLATE) Small vessels join to form two (right and left) endothelial / endocardial heart tubes that give rise to the endocardium.  HEART TUBE In the 3rd week embryo folding occurs  2 endothelial heart tubes fuse and form a single heart tube. Ends of the heart tube remain bifurcated. Its cranial end is called arterial end, whereas caudal end is called venous end. FUSION OF HEART TUBES AFTER EMBRYO FOLDING FUSION OF HEART TUBES AFTER EMBRYO FOLDING  HEART TUBE Heart tube soon forms five dilatations from cranial to caudal end: 1. Truncus arteriosus 2. Bulbus cordis 3. Primitive ventricle 4. Primitive atrium 5. Sinus venosus  ARTERIAL END OF THE HEART TUBE Truncus arteriosus represents the arterial end of the heart (vide supra). Cranially, it is continuous with aortic sac having right and left horns. From each horn of aortic sac, the first pharyngeal arch artery arises and passes backward on the lateral side of the foregut to become continuous with the respective dorsal aorta.  VENOUS END OF THE HEART TUBE Unfused part of sinus venosus (venous end of heart tube) forms two horns (right and left). Each horn receives three veins (from lateral to medial): 1. Common cardinal vein from the body wall 2. Umbilical vein from the placenta 3. Vitelline vein from the yolk sac FATE OF VARIOUS DILATATIONS OF THE HEART TUBE FATE OF VARIOUS DILATATIONS OF THE HEART TUBE  POSITION OF THE HEART TUBE IN RELATION TO PERICARDIAL CAVITY Before the formation of the head fold, heart tube lies in the floor of the pericardial cavity caudal to septum transversum. After the formation of the head fold, pericardial cavity and heart tube undergoes 180° rotation; Pericardial cavity and heart tube comes to lie ventral to the foregut and cranial to the septum transversum, with heart tube lying on the roof of the pericardial cavity.  POSITION OF THE HEART TUBE IN RELATION TO PERICARDIAL CAVITY Intraembryonic cavity over the heart fuse together later develops into the pericardial cavity and become located around the tube.  DORSAL MESOCARDIUM Heart tube is suspended from dorsal wall of pericardial cavity by a fold of pericardium called dorsal mesocardium. Soon, dorsal mesocardium breaks down, leaving the heart tube attached merely at the margins of the pericardium.  FORMATION OF CARDIAC WALL Endothelial heart tube is derived from the splanchnopleuric mesoderm related to the pericardial cavity. Endothelial / endocardial heart tube forms the endocardium of the heart. Splanchnopleuric mesoderm on dorsal aspect of the pericardial cavity proliferates and becomes thick to form myoepicardial mantle, which invests the front and sides of endothelial heart tube. At this stage, the heart tube is separated from myoepicardial mantle (primordial myocardium) by a cellular gelatinous CT called cardiac jelly.  FORMATION OF CARDIAC WALL Cardiac jelly is an acellular matrix secreted by developing myocardium  subsequently, it is replaced by the myocardium. Endothelial heart tube forms the endocardium of the heart. Myoepicardial mantle forms the myocardium and also to the visceral layer of pericardium (epicardium). Parietal layer of pericardium is derived from somatopleuric mesoderm. FORMATION OF CARDIAC WALL ACQUISITION OF EXTERNAL ADULT FORM OF THE HEART Formation of bulboventricular loop: bulbus cordis and primitive ventricle grow ventrally and form bulboventricular loop (U-shaped). ACQUISITION OF EXTERNAL ADULT FORM OF THE HEART Formation of transverse sinus: mesocardium connecting bulboventricular loop disappear to form a gap, that later called transverse sinus. ACQUISITION OF EXTERNAL ADULT FORM OF THE HEART Formation of S-loop: as primitive atrium and sinus venosus get freed from septum transversum, they come lie in the pericardial cavity dorso-cranial to the primitive ventricle  S-shaped cardiac loop is formed. ACQUISITION OF EXTERNAL ADULT FORM OF THE HEART ACQUISITION OF EXTERNAL ADULT FORM OF THE HEART Bulbus cordis and primitive ventricle are separated by bulboventricular sulcus that later disappears and bulbus cordis and ventricle fuse to form a single chamber. Formation of auricles: primitive atrium lies dorsal to (behind) the truncus arteriosus. On expansion, primitive atrium project forward on either side of truncus arteriosus as auricles.  CLINICAL CORRELATION A defect in cardiac looping is caused by a defect in the dynein arm of microtubules and results in Kartagener syndrome with situs inversus and dextrocardia. Situs inversus – rare, genetic condition in which some or all major visceral organs are positioned opposite from their normal position. Dextrocardia – abnormal orientation of the heart in which the apex is located to the right aspect of the mediastinum rather than the left.  CLINICAL CORRELATION Ectopia cordis - rare condition in which the heart lies exposed on the surface of the thorax. It occurs due to nonunion of two sternal plates of developing sternum. Death occurs in most of the cases during first few days of the birth.  DEVELOPMENT OF VARIOUS CHAMBERS OF THE HEART Primitive heart tube has a single lumen. This lumen is partitioned into four definitive chambers by the formation of the four septa: 1. Atrioventricular septum 2. Interatrial septum 3. Interventricular septum 4. Aorticopulmonary septum.  FORMATION OF ATRIOVENTRICULAR SEPTUM On about 28 days (end of 4th week), two swellings of mesenchymal tissue appear from walls of the canal - endocardial cushions. Neural crest cells migrate into the cushions and facilitate their development. Endocardial cushions grow and fuse together to form AV septum (septum intermedium). Septum intermedium divides the AV into right and left AV canal. FORMATION OF ATRIOVENTRICULAR SEPTUM  FORMATION OF INTERATRIAL SEPTUM Interatrial septum divides the primitive atrium into the right and left atria. It is formed by two septa – septum primum and septum secundum.  FORMATION OF INTERATRIAL SEPTUM At the end of 4th week, the septum primum starts developing from the roof of the primitive atrial chamber. It is crescent shaped and is present in an oblique plane. It grows downward towards septum intermedium (AV septum). The gap between the lower edge of septum primum and septum intermedium is called foramen primum.  FORMATION OF INTERATRIAL SEPTUM As septum primum fuses with AV septum (septum intermedium), the upper part of septum primum breaks down. The foramen thus formed is called foramen secundum (ostium secundum). A second crescent-shaped septum secundum now arises from the roof of primitive atrial chamber immediately to the right of septum primum.  FORMATION OF INTERATRIAL SEPTUM Septum secundum grows downward toward septum intermedium. It overlaps the foramen secundum. RA and LA now communicate through the foramen ovale - oblique passage between the upper margin of septum primum and the lower margin of septum secundum. Summary: interatrial septum is formed by: a) septum primum that forms the lower part of inter-atrial septum b) septum secundum that forms the upper part of interatrial septum. FORMATION OF INTERATRIAL SEPTUM FORMATION OF INTERATRIAL SEPTUM ATRIUM ATRIUM Endocardial cushion VENTRICLE VENTRICLE FORMATION OF INTERATRIAL SEPTUM Ostium Septum secundum Primum Ostium primum FORMATION OF INTERATRIAL SEPTUM Ostium Septum secundum Primum FORMATION OF INTERATRIAL SEPTUM Ostium Septum secundum Secundum FORMATION OF INTERATRIAL SEPTUM Foramen ovale Foramen ovale  PHYSIOLOGICAL CLOSURE OF FORAMEN OVALE Foramen ovale usually closes 6 months to a year after the baby's birth. After birth LA receives blood from lungs and pressure within it becomes greater than that in the RA. As the pressure of blood in the LA increases, it pushes the septum primum to the right. It comes in opposition with septum secundum and foramen ovale is closed (physiological closure)  blood is prevented from flowing from the LA to the RA. N.B. In adults, the fossa ovalis represents the septum primum, and annulus fossa ovalis represents the lower free edge of the septum secundum.  FORMATION OF INTERVENTRICULAR SEPTUM Development of the interventricular (IV) septum begins in week 4 and is usually completed by the end of week 7. Unlike atrial septation, IV septum will develop and close completely by week 8 without any shunting between the ventricles. IV septum consists of three parts: a) muscular part, b) bulbar part, c) membranous part. These 3 parts develop from 3 different sources.  FORMATION OF AORTICOPULMONARY SEPTUM Development of the aorticopulmonary septum (AP septum) Neural crest and endocardial cells migrate to form truncal ridges and bulbar ridges from the truncus arteriosus and bulbus cordis, respectively. Truncal and bulbar ridges spiral and fuse to form the AP septum. Division of the ventricular outflow tract AP fuses and rotates 180°, dividing the outflow tract into the aorta (from the left ventricle) and pulmonary trunk (from the right ventricle).  VALVE FORMATION CLINICAL CORRELATION: Valvular anomalies may be stenotic, regurgitant, atretic (eg, tricuspid atresia), or displaced (eg, Ebstein anomaly).  CONGENITAL HEART DEFECTS (CHDS) CHDs are caused by the disruption of the normal sequence of cardiac morphogenesis. CHDs may lead to the formation of pathological connections (shunts) between the right and left heart chambers, allowing blood to flow along the pressure gradient from high pressure to low pressure. Shunts are classified according to the direction of the blood flow as: left-to-right right-to-left  CHDS – SHUNT TYPES Left-to-right shunt Oxygenated blood from the lungs is shunted back into the pulmonary circulation via an atrial septal defect (ASD), ventricular septal defect (VSD), or patent ductus arteriosus (PDA) → pulmonary hypertension Right ventricular pressure overload → right sided heart hypertrophy (cardiomegaly on X-ray) and heart failure but no cyanosis Right-to-left shunt: blood flows from the right to the left heart via a shunt → deoxygenated blood entering the systemic circulation → cyanosis ACYANOTIC CONGENITAL HEART DEFECTS Ventricular septal defect (VSD) Atrial septal defect (ASD) Patent foramen ovale Patent ductus arteriousus (PDA) Coarctation of the aorta Endocardial cushion defect Pulmonary valve stenosis  ACYANOTIC HEART DEFECTS Congenital cardiac malformations that affect the atrial or ventricular walls, heart valves, or large blood vessels. Common causes include: genetic defects (e.g., trisomies), maternal infections (e.g., rubella), maternal use of drugs or alcohol during pregnancy. Acyanotic heart defects are pathophysiologically characterized by a left-to-right shunt, which causes pulmonary hypertension and right heart hypertrophy. Symptoms depend on the extent of the malformation Infants may be asymptomatic or present with exercise intolerance, failure to thrive, and symptoms of heart failure. Acyanotic heart defects requiring treatment are repaired via catheter procedures or surgery. ACYANOTIC CONGENITAL HEART DEFECTS  CYANOTIC HEART DEFECTS Right-to-left shunt Tetralogy of Fallot Transposition of the great vessels (TGV) Tricuspid valve atresia Ebstein anomaly Total anomalous pulmonary venous return (TAPVR) Persistent truncus arteriosus Hypoplastic left heart syndrome (HLHS) General clinical features: “Blue babies”: pale gray or blue skin color caused by cyanosis Feeding problems and failure to thrive Exertional dyspnea, tachypnea, and fatigue Hypoxemia Symptoms of heart failure Nail clubbing may occur later in life. MCQ FOR SELF-CONTROL https://forms.gle/ievqWqD6RUXkoFvR9 REFERENCES