BMS 200 Cardiovascular Embryology PDF

Cardiovascular Embryology BMS 200 Amna Noor Learning Outcomes Relate the histologic and anatomic features of each cardiac structure to its function: Endocardium, myocardium, Purkinje fibres; Atrioventricular valves, semi-lunar valves, chordae tendinae, fibrous skeleton (including the left a...

Cardiovascular Embryology BMS 200 Amna Noor Learning Outcomes Relate the histologic and anatomic features of each cardiac structure to its function: Endocardium, myocardium, Purkinje fibres; Atrioventricular valves, semi-lunar valves, chordae tendinae, fibrous skeleton (including the left and right trigones as well as the fibrous rings); Visceral, parietal, and fibrous pericardium Describe the vascular distribution of the following coronary arteries and veins/sinuses: Right coronary artery, SA-nodal artery, right marginal artery, posterior interventricular artery; Left coronary artery, circumflex artery, left marginal artery; Coronary sinus, great cardiac vein, middle cardiac vein Briefly describe the nervous innervation of the heart Describe the physiologic function of the following subcellular structures: Gap junctions, desmosomes, fascia adherens Relate the surface anatomy of the precordium to the following cardiac structures: Cardiac apex, base of the heart, mitral valve, tricuspid valve, aortic valve, pulmonic valve, right ventricle, right atrium Learning Outcomes Describe the process of vasculogenesis and angiogenesis in the embryo Relate the processes of lateral folding, cephalic folding, and cardiac bending to the development of cardiac structures in the early embryo Describe the development of the truncus arteriosus, bulbus cordis, sinus venosus, umbilical vessels, vitelline vessels, dorsal aorta, and cardinal veins as the embryo becomes the fetus Describe the contribution of the endocardial cushions and neural crest cells to septal, valvular, and outflow structures in the embryonic heart Describe the development of the atrial and ventricular septae and the foramen ovale Describe the anatomy of the fetal shunts and the changes they undergo immediately after parturition Describe the basic epidemiology, embryological pathogenesis, clinical features, and prognosis of the following congenital cardiac disorders: Atrial septal defects, ventricular septal defects, coarctation of the aorta, patent ductus arteriosus Clinical Case A mother presents to your clinic with her new son – he is 4 months of age. She is curious about feeding options and whether supplements impact a child’s health early in development. The baby seems quite well and is developing appropriately for his age. As you listen to his heart you hear a clear systolic murmur over the precordium. Pre-Assessment If you place a stethoscope at the 2nd right intercostal space at the sternal border, what cardiac structure are you likely listening to? A. The aortic valve 3 B. The pulmonic valve These are all left of the sternum C. The tricuspid valve D. The mitral valve Pre-Assessment What structure brings oxygenated blood to the embryonic heart? A. The cardinal vein B. The umbilical artery C. The dorsal aorta D. The umbilical vein Pre-Assessment What is the papillary muscle attached to? A. The chordae tendinae of a semilunar valve B. The chordae tendinae of an atrioventricular valve C. Both the left and right aspects of the interventricular septum D. Both the left and right aspects of the interatrial septum  Mediastinum It is the middle of the thorax: & ▪ Between the mediastinal pleura ▪ Posterior to the sternum ▪ Anterior to the vertebrae ▪ Superior to the diaphragm ▪ Separates the two lateral pleural cavities Base of the heart - separates the superior and inferior mediastinums Subdivisions: ▪ Superior ▪ Inferior ↳ Anterior Middle Posterior Mediastinum Heart The heart and pericardial sac are approximately 2/3rd to the left and 1/3rd to the right of the median plane (middle mediastinum).  Heart Lower border of 2nd left costal cartilage 2.5 cm Upper border of 3rd from left sternal line right costal cartilage 1 - Th cm from sternal line 7th right sternocostal The apex ~ 9 cm left of articulation midsternal line Heart – Anterior View Connection b/n aorta and pulmonary arteries It is a remnant of a shunt that was in embryos since embryos do not use their lungs, therefore do not use the pulmonary artery Heart – Posterior View -O -  Heart - Open Anterior view or posterior? Apex pointing towards the left w Shunt that takes blood from right atrium into left atrium in embryo Auscultatory Locations - Heart Mitral valve (apex): 5th intercostal space at the midclavicular line. Tricuspid valve: lower left sternal border in the 4th/5th intercostal space. Aortic valve: 2nd right intercostal space near the right sternal border. Pulmonic valve: 2nd left intercostal space near the left sternal border. Pericardium Fibrous membrane that encloses the heart and the roots of the great vessels. * 35 ▪ Anchors and protects the heart ▪ Prevents overfilling ▪ Allows it to work in a friction-free environment Two layers: ▪ Outer fibrous pericardium (tough, inelastic CT) ▪ Inner serous pericardium. Parietal layer (inner surface of the pericardium) Visceral layer (lines outer surface of the heart = epicardium) The fibrous pericardium is continuous with the central tendon of the diaphragm (pericardiophrenic ligament). ↳ Chamber Walls The wall of each heart chamber consists of three layers, from superficial to deep: 1. Endocardium: a thin internal layer (endothelium and subendothelial connective tissue) or lining membrane of the heart that also covers its valves 2. Myocardium: a thick, helical middle layer composed of cardiac muscle 3. Epicardium: a thin external layer (mesothelium) formed by the visceral layer of serous pericardium Pericardium & Epicardium Epicardium is the outermost layer of the heart wall, also called the visceral layer of the serous pericardium ▪ The serous pericardium is composed mainly of mesothelium. Subepicardial layer of loose CT contains the coronary vessels, nerves and ganglia, also an area of fat storage of the heart. Myocardium Components Contains contractile cells and impulse generating/ conducting cells: Cardiomyocytes are the individual muscle cells that make up the myocardium. Striated, uninuclear, often with one or two branches Full of myofibrils and mitochondria Purkinje fibers are specialized cardiac muscle fibers that play a crucial role in the conduction of electrical signals within the heart. Glycogen-filled, large diameter fibres, gap junctions, few myofibrils or mitochondria Pale-staining Myocardium Components 2 on the left Papillary muscles: located in the ventricles of the heart. 3 on the right ▪ Connected - to the AV valves by chordae tendineae. Pectinate muscles: muscular structures found in the walls of the atria, particularly in the right atrium. ▪ Contribute to the contraction of the atria. Trabeculae carneae: irregular, mesh-like ridges or muscular columns found on the inner walls of the ventricles. ▪ Structural support for ventricles & maintain integrity of myocardium. ↳ Bumpy walls prevent suction from occurring during systole that would occur if the walls were smooth 2 Used in right ventricle in regards to conduction Histology - Myocardium Intercalated discs (arrows) have desmosomes and gap junctions. ⑧ O Histological Features Intercalated discs: ▪ Desmosomes: hold cells together; prevent cells from separating during contraction ▪ Gap junctions: directly connect the cytoplasm of 2 cells – allow ions to pass from cell to cell; - - electrically couple adjacent cells Allows heart to be a functional syncytium, a single coordinated unit ▪ Fascia adherens: anchors actin filaments, helps to transmit contractile forces Endocardium " Most interior layer of the heart The endocardium forms the lining of the atria and ventricles and is composed of: · ▪ Simple squamous epithelium (endothelium) ▪ Underlying layer of fibroelastic connective tissue with scattered fibroblasts ▪ Deeper layer of subendothelial fibroelastic CT. Contains: small blood vessels & nerves, Purkinje fibers Endocardial cells are specialized cells that make up the endocardium. ▪ Form the inner lining of the AV and semilunar valves, ensuring they open and close efficiently during the cardiac cycle. Histology – Purkinje Fibres Purkinje fibres 1 Simple squamous Histology - Valve Cardiac Muscle Fibers Cardiac muscle cells: striated, short, branched, fat, interconnected – Uninuclear cells Nucleus is situated at the center of the cell body – Cells connected at intercalated discs Many gap junctions populate the intercalated discs – Contain numerous large mitochondria (25–35% of cell volume) that afford resistance to fatigue – Rest of volume composed of sarcomeres Z discs, A bands, and I bands all present – T tubules and cisternae present Sarcoplasmic Reticulum is simpler than in skeletal muscle T-tubules are larger  Fibrous Skeleton The cardiac muscle fibers are anchored to the fibrous skeleton of the heart. G This is a complex framework of dense collagen/fibroblastic tissue forming four fibrous O * rings that surround the orifices of the valves, a right and left fibrous trigone (formed by * connections between rings), and the membranous parts of G the interatrial and interventricular septa. Fibrous Skeleton Functions: ▪ Keeps the orifices of the AV and semilunar valves patent and prevents them from being overly distended (trigones). ▪ Provides attachments for the leaflets and cusps of the valves. ▪ Provides attachment (origin and insertion) for the myocardium. ▪ Forms an electrical “insulator” by separating the impulses of the atria and ventricles and by surrounding and providing passage for the initial part of the AV bundle of the conducting system of the heart. Left vs. Right Sides Features Right Side Left Side Myocardial Walls More trabeculated, Less trabeculated, less muscle mass, more muscle mass, thinner thicker AV Valves Tricuspid (3 Mitral/ Bicuspid (2 leaflets, 3 sets of leaflets, 2 sets of papillary muscles: papillary muscles: anterior, posterior, anterior and septal) posterior) Conduction System SA node and AV - nodes are in the right atrium Features of the Heart Interatrial Septum: Separates the right and left atria ▪ Note: Fossa Ovalis Interventricular Septum: Separates the right and left ventricles ▪ Inferior: Large, muscular ▪ Superior: Small, membranous ▪ Corresponds to the anterior and posterior IV sulcus. Features of the Heart Auricles: ▪ Increase the capacity of the atrium and the volume of blood can be contained. Conduction System – SA Node Pacemaker of the heart. Located near the opening of the SVC in the RA. Sends ~70 impulses/ min. The contraction signal spreads myogenically in both atria. Innervated by the sympathetic division of the autonomic nervous system and is inhibited by the parasympathetic division.  Conduction System The AV node is located on the floor of the RA near the opening of the coronary sinus, at the junction with IV septum. D Only electrical connection between atria and ventricles (slows it down). Distributes the signal to the ventricles through the AV bundle (of His). Sympathetic stimulation speeds up conduction, and parasympathetic stimulation slows it down. The AV bundle passes from the AV node through the fibrous skeleton of the heart and along the membranous part of the IVS. Conduction System At the IVS, the AV bundle divides into right and left bundles and form subendocardial branches (Purkinje fibres), which extend into the walls of the respective ventricles. The subendocardial branches of the right bundle stimulate the muscle of the IVS, the anterior papillary muscle through the septomarginal trabecula (moderator band), and the wall of the right ventricle. The left bundle divides near its origin into approximately six smaller tracts, which give rise to subendocardial branches that stimulate the IVS, the anterior and posterior papillary muscles, and the wall of the left ventricle. The AV node is supplied by the AV nodal Left side does not have moderator band so directly activate papillary muscles artery, the largest and usually the first IV Right side has moderator band which moderates the septal branch of the posterior IV artery. muscular activity in the right ventricle Innervation of the Heart The heart is supplied by autonomic nerve fibres from the cardiac plexus, which is divided into superficial and deep portions. ▪ Located on the anterior surface of the bifurcation of the trachea and at the posterior aspect of the aorta and pulmonary trunk. The cardiac plexus is formed of both sympathetic and parasympathetic as well as visceral afferent fibres conveying reflexive and nociceptive fibres from the heart. Innervation of the Heart The parasympathetic supply is from the presynaptic fibres of the vagus nerves. is Postsynaptic parasympathetic cell bodies (intrinsic ganglia) are near the SA and AV nodes and along the coronary arteries. Visceral afferent components of the cardiac plexus travel with the sympathetic (pain sensation) and parasympathetic (baroreceptors and chemoreceptors). Innervation of the Heart *Note the phrenic nerve within the pericardium. Vasculature of the Heart Coronary arteries/ cardiac veins supply and drain the myocardium. End circulation: only source of blood supply Note: The endocardium and some of the subendocardial tissue receive oxygen and nutrients through diffusion or microvasculature. Vessels are typically embedded in fat and run beneath the epicardium. ▪ Parts of these blood vessels are embedded within the myocardium to ensure the myocardium receives oxygen and nutrients. The blood vessels of the heart are autonomic control. Coronary Arteries Right and left: first branches of the aorta, supply the myocardium and epicardium. Arise from aortic sinuses, superior to the aortic valve, and pass around opposite sides of the pulmonary trunk. The coronary arteries supply both the atria and the ventricles. Right Coronary Artery The right coronary artery (RCA) runs in the coronary/ atrioventricular sulcus. Gives an ascending SA nodal brand at its origin. Continues in the sulcus and gives the right marginal branch which supplies the right border. Turns left, gives posterior O * interventricular branch, also. called the right posterior descending (RPD). At the posterior junction of the interatrial and interventricular septum, gives rise to the AV nodal branch. Right Coronary Artery Left Coronary Artery The left coronary artery (LCA) arises from the left aortic sinus of the ascending aorta, passes between the left auricle and the left side of the pulmonary trunk, and runs in the AV sulcus. Splits into 2 branches: ▪ Anterior IV branch (supplies walls of the ventricles) Provides a diagonal 8 branch ▪ Circumflex branch (supplies walls of LV & LA) Provides a marginal branch Left Coronary Artery * Dominance The dominance of the coronary arterial system is defined by which artery gives rise to the posterior interventricular - (IV) branch. - Cardiac Veins Cardiac veins empty into the coronary sinus or into the right atrium. The coronary sinus, the main vein of the heart, runs from left to right in the posterior part of the coronary sulcus. 33 The coronary sinus receives the great cardiac vein (of anterior IV sulcus), middle cardiac vein (of posterior IV sulcus), and small cardiac veins (from the inferior margin). The left posterior ventricular vein and left marginal vein also open into the coronary sinus. Cardiac Veins The first part of the great cardiac vein, the anterior interventricular vein, begins near the apex and runs with the anterior IV artery. At the coronary sulcus, it turns left, and its second part runs with the circumflex branch of the LCA to reach the coronary sinus. ▪ Note: Blood is flowing in the same direction within a paired artery and vein! The great cardiac vein drains the areas of the heart supplied by the LCA. Small and middle cardiac veins drain the right side of the heart. The middle cardiac vein (posterior IV vein) accompanies the posterior interventricular arterial branch. BMS 150 Review Vasculogenesis → development of brand-new blood vessels from mesodermal cells (angioblasts) Angiogenesis → “sprouting” of existing blood vessels formed by vasculogenesis ▪ Connects blood vessels to each other  Vasculogenesis and Angiogenesis Primitive circulation develops by week 3 Mesenchymal cells → angioblasts → blood islands – begins in extraembryonic mesoderm before intraembryonic mesoderm (umbilical vesicle and allantois) Small cavities appear within the blood islands Angioblasts flatten to form endothelial cells that “coat” the inside of the cavities in the blood island – ~ early endothelium Vasculogenesis and Angiogenesis The endothelium-lined cavities fuse to form networks of channels = vasculogenesis Vessels “sprout” into adjacent areas by endothelial budding and fuse with other vessels = angiogenesis Mesenchyme surrounding the channels develops into the muscular and connective tissue of a blood vessel Development of the Embryonic Vessels (BMS 150-Review) Three paired veins drain into the tubular heart of a 4-week embryo ✓ Vitelline vein return poorly oxygenated blood from the umbilical vesicle. o Follow the omphaloenteric duct (former yolk stalk) into the embryo o They then enter the sinus venosus (venous end of the embryonic heart) ✓ Umbilical vein carry well-oxygenated blood from the chorion to the fetus ✓ Common cardinal veins return poorly oxygenated blood from the body of the embryo ✓ Dorsal aorta – blood to the embryo ✓ Umbilical artery – Returns blood to the placenta Poorly oxygenated blood 50 BMS150 - Review Lateral folding brings the heart tube into the anterior part of the embryo, positioning it within the chest cavity. Cranial folding brings the heart tube ventrally and caudally ▪ The intra-embryonic coelom near the heart tube develops into the pericardial cavity, pleural cavity, and peritoneal cavity ▪ The paired heart tubes are connected with the extra- embryonic vessels once the heart starts to beat on day ⑧D 21 ▪ The red blood cells develop first in the extra-embryonic vessels Allantois, umbilical vesicle vessels ▪ By the 5 - th week RBCs arise from the dorsal aorta D  Development of the Heart At around 18-19 days of gestation, the heart and great vessels begins to form in a special region of the embryo called the cardiogenic area. Paired, longitudinal endothelial-lined channels—the endocardial heart tubes—develop during the 3rd week and fuse to form a primordial heart tube *Initially, the heart is “superior” (rostral) to the oropharyngeal membrane – at the end of the fourth week it is inferior (caudal) Establishment of the Heart Primary Heart Field: ▪ Earliest region involved in heart development, located in the anterior lateral plate mesoderm. ▪ Gives rise to the initial heart tube, which forms during the third week of development. This tube eventually differentiates into a portion of the atria and the left ventricle. Secondary Heart Field: ▪ Located adjacent to the PHF; visceral mesoderm ventral to the pharynx. ▪ Contributes to the elongation of the heart tube. It forms the right ventricle, the outflow tract of both ventricles (conus cordis and truncus arteriosus), and parts of the atria. Neural Crest Cells: ▪ Originate from the neural tube. ▪ Contributes to the cardiac outflow tract and the aorticopulmonary septum. Laterality Both the PHF and the SHF exhibit left–right patterning. SHF: Cells on the right side contribute to the left of the outflow tract region and those on the left contribute to the right; it explains the spiralling nature of the pulmonary artery * - - and aorta. - Cardiac Loop As the outflow tract lengthens, the cardiac tube begins to bend on day 23. The cephalic portion of the tube bends ventrally, caudally, and to the right; and the atrial (caudal) portion shifts dorsocranially and to the left. * This bending creates the cardiac loop by day 28. Cardiac Loop The atrial portion forms a common atrium and is incorporated into the pericardial cavity. The bulbus cordis forms the trabeculated part of the right ventricle. The midportion, the conus cordis, will form the outflow tracts of both ventricles. The distal part of the bulbus, the truncus arteriosus, will form the roots and proximal portion of the aorta and pulmonary artery. ▪ Bulboventricular loop When looping is completed, the smooth-walled heart tube begins to form primitive trabeculae in two sharply defined areas. The primitive ventricle, which is now trabeculated, is called the primitive left ventricle. Likewise, the trabeculated proximal third of the bulbus cordis is called the primitive right ventricle. Summary Embryonic Structure Adult Structure Sinus Venosus Smooth part of atria, coronary sinus, nodal tissue Atrium Rough part of the atrium Ventricle Left ventricle Bulbus Cordis Trabeculated part of the right ventricle, outflow tracts of the ventricles (conus cordis) Truncus Arteriosus Outflow Tract (Pulmonary Trunk & Aorta)  Early Development of the Heart ❖ Blood flows from the sinus venosus into the primordial atrium, from there to primordial ventricle ❖ Ventricle contracts, pushing blood into the bulbus cordis and truncus arteriosus 3) o Passes cranially to the pharyngeal arches arteries o Passes caudally to the dorsal aorta Distributed to the placenta, umbilical vesicle, and the rest of the embryo 58 Endocardial Cushions Towards the end of the 4th week, endocardial cushions form on the dorsal and ventral walls of the atrioventricular (AV) canal ▪ As these masses of tissue are invaded by mesenchymal cells during the 5th week, the AV endocardial cushions approach each other and fuse, dividing the AV canal into right and left AV canals em m e ▪ These canals partially separate the primordial atrium from the primordial ventricle, and the endocardial cushions function as AV valves. ▪ The endocardial cushions are involved in the development of the atrial and ventricular septa, as well as the atrioventricular valves  Development of partitioning between the left and right sides - atria During embryonic life, the blood from all chambers mixes, such that the heart acts like just one massive chamber However, the basic structure for separate right- and left-sided circulations must be developed and ready to operate once the child is born  Development of partitioning - atria Key events: Septum primum grows from the roof of the atria towards the endocardial cushions – The space underneath is - called the foramen primum - * - It meets the endocardial cushions (primordial septum) and abruptly becomes holey and forms another foramen (foramen secundum) – this will remain until birth 3 Development of partitioning - atria The septum secundum now starts to develop, on the right side of the septum primum between the two flaps remains the foramen - secundum - Note how the development of the septum primum, the septum secundum, and the foramen secundum allow one-way shunting of blood from right to left If pressure in the left atrium increases, the valve (formed by what?) will close Atrial Septum Remnant of septum primum is now called the “valve of the oval foramen” Blood flows from the right atrium to the left atrium through the foramen ovale by pushing through the septum primum.  Ventricular partitioning The ridge of the interventricular septum grows towards the endocardial cushions Until the seventh week, there is a crescent-shaped Interventricular (IV) foramen between the free edge of the IV septum and the fused endocardial cushions usually closes by the end of the 7th week The superior part is called the membranous IV septum Ventricular outflow At 6 weeks, the aorticopulmonary septum, formed partially by neural crest cells, descends into the developing heart from the endocardial cushions. This septum separates the outflow tracts into the aorta (left outflow tract) and the pulmonary artery (right outflow tract). The spiralization of the aorticopulmonary septum helps align the aorta and pulmonary artery with their respective ventricles, allowing for proper oxygenated and deoxygenated blood flow after birth.  The venous system – from week 6 to post-partum Vitelline veins: Enter the sinus venosus, and eventually the right vitelline vein forms most of the hepatic portal system and IVC, while the left disappears  The venous system – from week 6 to post-partum The anterior cardinal veins (mostly right) develop into the SVC The posterior mostly form visceral veins and part of the IVC The venous system – umbilical vein The right umbilical vein and the cranial part of the left umbilical vein between the liver and the sinus venosus degenerate Now a single umbilical vein - carries all the blood - - from the placenta to the embryo - A large venous shunt-the ductus venosus (DV)- develops within the liver connects the umbilical vein with the inferior vena cava (IVC) DV bypasses the liver so most of the blood goes straight to the heart Fetal Circulation Shunts: – The ductus arteriosus From pulmonary trunk to aorta – The foramen ovale from right atrium to left atrium – The ductus venosus Bypasses liver, fetal blood flows right into the inferior vena cava 69 Circulation After Birth Closure of the umbilical arteries: used to carry deoxygenated blood from embryo to placenta Remnant: Medial Umbilical Ligament Closure of umbilical veins: used to carry oxygenated blood from placenta to embryo Remnant: Ligamentum Teres Closure of ductus venosus: shunt that allows oxygenated blood in the umbilical vein to bypass the liver Remnant: Ligamentum Venosum Closure of foramen ovale: increased pressure in the left atrium, combined with a decrease in pressure on the right side Remnant: Fossa Ovalis Ductus arteriosus: used to connect the fetal pulmonary artery to the aorta Remnant: Ligamentum Arteriosum 70 Congenital heart disease – a quick overview over 1 million people in North America are living with congenital heart diseases – comprises about 1% of live births – can be serious illnesses that necessitate early surgical correction, or can resolve on their own over time Atrial septal defect (ASD) – Most are septum secundum ASDs (90%) – the rest are septum primum ASDs or sinus venosus defects – Usually shunts blood from the left atrium to the right atrium can increase pulmonary blood flow by 2-4X if severe – Patent foramen ovale – the septum primum does not “seal over” and the flap can open usually only with increases in intrathoracic pressures – Small ASDs may remain asymptomatic. Larger defects can lead to symptoms such as fatigue, exertional dyspnea, palpitations, and recurrent respiratory infections. Over time, they can cause right- sided heart enlargement and pulmonary hypertension. Ventricular septal defect (VSD) most are holes in the membranous septum, many are about the size of the aortic orifice some of them look like a collection of small holes – “swiss cheese” look  Ventricular septal defect (VSD) Incomplete closure of the ventricular septum will cause left-to- right shunting and is the most common anomaly at birth Clinical features Larger VSDs can lead to symptoms such as rapid breathing, poor feeding, failure to thrive, and recurrent respiratory infections. Over time, they can lead to pulmonary hypertension and right-sided heart enlargement. – Minor defects will have limited clinical significance  Patent Ductus Arteriosus (PDA) The ductus arteriosus remains patent (open) 2-3 Weeks normal A defect that causes large pressure timeline of closure differences between the aorta and pulmonary trunk can increase blood flow through the ductus arteriosus, preventing its closure. A large shunt may divert blood from the aorta to the pulmonary artery. Left ventricular hypertrophy and heart failure ensue owing to increased demand for cardiac output. In patients with large PDAs, the increased volume and pressure of blood in the pulmonary circulation eventually lead to pulmonary hypertension and cardiac complications.  Coarctation of Aorta The aortic lumen below the origin of the left subclavian artery is significantly narrowed. Constriction may be above or below the entrance of the ductus arteriosus. In the preductal type, the ductus arteriosus persists, whereas in the postductal type, which is more common, this channel is usually obliterated. Classic clinical signs associated with this condition include hypertension in the right arm concomitant with lowered blood pressure in the legs. Factors Leading to Embryological Defects 1. Interference with the left-right determination of the body axis Example: dextrocardia (heart located on the right side) or situs inversus (complete reversal of left and right organ positions). 2. Improper migration of precursor cells to their target area in the embryo For instance, improper neural crest cell migration can affect the formation of structures like the aorticopulmonary septum. 3. Improper regression of embryological structures Example: Patent Ductus Arteriosus. Class Discussion A mother presents to your clinic with her new son – he is 4 months of age. She is curious about feeding options and whether supplements impact a child’s health early in development. The baby seems quite well and is developing appropriately for his age. As you listen to his heart you hear a clear systolic murmur over the precordium. ▪ Embryological Disorder? Further Investigations? References Clinically Oriented Anatomy – Chapter 4, Mediastinal Anatomy Section Gartner and Hiatt’s Atlas and Text of Histology, 8 ed. – Chapter 9, Heart section Langman’s Medical Embryology, Chapter 13 – Cardiovascular System Rubin’s Pathology, Chapter 17: The Heart, Congenital Heart Disease section