Embryonic Development of the Cardiovascular System PDF

Embryonic development of the cardiovascular system Histology-Embryology II Katerina Menelaou, Ph.D. Lecturer, Histology-Embryology [email protected] Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart...

Embryonic development of the cardiovascular system Histology-Embryology II Katerina Menelaou, Ph.D. Lecturer, Histology-Embryology [email protected] Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Establishment of the cardiac lineage The embryo can no longer satisfy its nutritional and oxygen requirements by diffusion alone The cardiovascular system is the first major system to function in the embryo The primordial heart and vascular system appear in the middle of week 3 The heart begins to beat at 22-23 days Establishment of the cardiac lineage (Sadler 2012) Splanchnic mesoderm Cardiogenic mesoderm (Tani et al., 2020) Establishment of the cardiac lineage Cardiac progenitor cells Derived from intraembryonic mesoderm (cranial end of primitive streak) Migrate and localise on either side of the primitive streak (Moore et al., 2016) Migrate to the splanchnic mesoderm Primitive Heart Field Second Heart Field (cardiac crescent) also contains Atria cardiogenic cells Left ventricle Remaining of right Most of the right ventricle ventricle Outflow tract (Schoenwolf et al., 2021) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Establishment of laterality Pathway is expressed in the lateral plate mesoderm on the left side 5HT: serotonin PITX2: master factor for left sidedness Specifies the left side Programs heart cells in the PHF and SHF Disruption leads to laterality abnormalities (e.g. dextrocardia) (Sadler, 2012) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth  Brief anatomy of the heart Cardiologist Associates of Michigan (https://www.cardofmich.com/) Brief anatomy of the heart Epicardium / visceral pericardium: covering the outside of the tube Responsible for the formation of the coronary arteries Myocardium: muscular wall Secretes ECM, rich in hyaluronic acid Endocardium: internal endothelial lining ThoughtCo (https://www.thoughtco.com) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth  Formation of the primary heart tube Week 4: Embryonic folding Splanchnopleuric mesoderm Cranial and caudal folds Lateral folds Cardiogenic plate Angiogenic cell clusters Intraembryonic coelom / cavity Heart tube Pericardial cavity, pleural cavity, peritoneal cavity (Sadler, 2012) Formation of the primary heart tube Cardiogenic mesoderm signal from endoderm - VEGF Two endocardial heart tubes At its inferior end, each tube connects to a vitelline vein (comes from yolk sac) => blood gets into the heart tube At its superior end, each tube connects to a ventral aorta => blood exits the heart tube (Moore et al., 2016) Endocardial heart tubes => Primitive heart tube Fusion: Vitelline veins => Sinus venosus (inflow tract) Ventral aortae => Aortic sac (outflow tract) Formation of the primary heart tube (Moore et al., 2016) Heart becomes a continuous expanded tube: Endothelial tube => Inner endothelial lining => endocardium Outer cardiac myoblast layer => myocardium SHF: mesothelial cells arise from the external surface of the sinus venosus and spread over the myocardium => epicardium Cardiac jelly separates the endocardial tube from the primordial myocardium Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth  Formation of the pericardial cavity Septum transversum: a thick plate of mesodermal tissue partially dividing the thoracic from the abdominal cavities Mediastinum: a membranous partition between two body cavities or two parts of an organ Formation of the pericardial cavity A primitive pericardial cavity (pericardial coelom) appears laterally to each heart tube (Moore et al., 2016)  Formation of the pericardial cavity When the heart tubes fuse to form the primary heart tube: The pleuropericardial membranes fuse with each other The two pericardial cavities also fuse to form a single pericardial cavity Two pleural cavities are also formed (Moore et al., 2016) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Embryonic origins of the adult heart (Moore et al., 2016) https://www.youtube.com/watch?v=Vx3l2Qf0eTI Sulcus: groove, a gap where the surface of a structure is folded Truncus arteriosus: an arterial trunk that originates from both ventricles of the heart that later divides into the aorta and the pulmonary trunk Embryonic origins of the adult heart Embryonic heart Adult heart Aortic sac Aorta and pulmonary artery Truncus arteriosus Proximal aorta and pulmonary tract Bulbus cordis: Proximal 3rd Trabeculated part of right ventricle Conus cordis Outflow tracts of both ventricles Primitive ventricle Left ventricle Primitive atrium Anterior portion of right atrium, left atrium Sinus venosus Posterior portion of right atrium, vena cavae and coronary sinus https://www.youtube.com/watch?v=Vx3l2Qf0eTI Cardiologist Associates of Michigan (https://www.cardofmich.com/) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Cardiac looping A process that causes the heart to: Fold on itself Assume its normal position in the left part of the thorax with the atria posteriorly and the ventricles anteriorly Week 4 Cardiac tube begins to bend on day 23 Bending creates the cardiac loop Cardiac looping is complete by day 28 Cardiologist Associates of Michigan https://www.youtube.com/watch?v=Vx3l2Qf0eTI Cardiac looping Tube elongates: Cells are added from the SHF to the cranial end of the tube Essential for: Normal formation of: Part of the right ventricle Outflow tract region Looping process Walls thicken (traberculation) Sections move The initially adjacent regions of the heart tube become repositioned with respect to one another and with the great vessels “Remodeling” of the tube into a multichambered organ with distinct inlet and outlet components Cardiac looping The heart tubes are held inside the pericardial cavity by blood vessels at both ends The heart tube starts folding into a C shape: The truncus arteriosus and bulbus cordis move down (Sadler, 2012) into the right (top portion of the C) The primitive ventricle bends to the right of the midline and a little to the front (middle portion of the C) Primitive atrium and sinus venosus (bottom of the C) Growing ventricle moves to the left, crosses the midline, covering (Moore et al., 2016) the primitive atrium Cardiac looping: Animation https://www.youtube.com/watch?v=a0qyagIgBPw What can go wrong? Cardiac looping and heart defects: Dextrocardia The heart points toward the right side of the chest instead of the left Congenital condition - Autosomal recessive genes Affects 1:12000 people Two types: Dextrocardia situs inversus: the tip of the heart and its four chambers are pointing towards the right side of the body Medline Plus Dextrocardia with situs inversus totalis: the other (https://medlineplus.gov/) organs (e.g. liver, stomach, and spleen) are in the opposite position, or in mirror-image reversal, to where they should be Diagnosis: Maximum heart sounds on the right of the chest instead of the left CT scan or MRI to confirm Symptoms: Most are asymptomatic The Royal Children's Hospital, Melbourne (https://www.rch.org.au/home/) Symptoms might be due to associated conditions Cardiac looping and heart defects: DORV (double outlet right ventricle) Congenital heart defect 1:6000 – 1:10000 newborns Associated with Ventricular Septal Defect (VSD) Inhibition of lengthening of the heart tube during cardiac looping Outflow tract defect: Both the aorta and pulmonary artery arise from the right ventricle The RV carries oxygen-poor blood, which is then circulated throughout the body via the aorta Symptoms: Cyanosis Medline Plus Difficulty breathing (https://medlineplus.gov/) Heart murmur (extra sound in the heartbeat, diagnosed using a stethoscope) Tachycardia Treatment: Open heart surgery within the first year of life Cardiac looping and heart defects: Tetralogy of Fallot Congenital heart defect Most common cyanotic congenital heart malformation - 1:1000 newborns Failure during the last step of cardiac looping Outflow tract defect Four abnormalities: Pulmonary stenosis (obstructed right ventricular outflow) Ventricular septal defect Dextroposition of the aorta (straddling or overriding both ventricles) Right ventricular hypertrophy Symptoms: Cyanosis Difficulty breathing Cleveland Clinic Heart murmur (https://my.clevelandclinic.org/) Seizures Treatment: Surgery to relieve the obstruction of the pulmonary trunk and repair the ventricular septal defect Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth  Embryo, placenta, umbilical vesicle Circulation through the primordial heart Sinus venosus Sinuatrial valve Primordial atrium Atrioventricular canal Primordial ventricle Ventricle contraction Bulbus cordis Truncus arteriosus (Moore et al., 2016) Aortic sac Blood enters the sinus venosus from the: Embryo, through the common cardinal veins Pharyngeal arch arteries Developing placenta, through the umbilical veins Dorsal aorta Umbilical vesicle, through the vitelline veins Embryo, placenta, umbilical vesicle Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Partitioning of the primordial heart Valvuloseptal morphogenesis: Structural and functional partitioning of the heart into four chambers Septation (formation of septal structures) Partitioning of the atrioventricular canal Partitioning of the atrium Partitioning of the sinus venosus Partitioning of the ventricles Partitioning of the bulbus cordis and truncus arteriosus Valvulogenesis (formation of valves) Atrioventricular valves Semilunar valves Days 28-37 of gestation Partitioning of the primordial heart: Septal formation (Sadler, 2012) Two actively growing ridges One single mass of tissue approach each other until they actively grows and expands fuse, dividing the lumen into until it reaches the opposite two separate canals side of the lumen e.g. Endocardial cushions e.g. Septum primum, septum secundum Partitioning of the primordial heart: Septal formation (Sadler, 2012) Two expanding portions of the wall merge, forming a septum Such a septum never completely separates two cavities Leaves a narrow communicating canal between the two expanded sections e.g. Such a septum partially divides the atria and ventricles  Partitioning of the primordial heart: The atrioventricular canal (Moore et al., 2016) (D'Souza, 2016) Week 4 of development The primordial atrium and the primordial ventricle initially communicate through the atrioventricular canal Mesoderm proliferates on the anterior and posterior wall of the atrioventricular canal => four endocardial cushions form (superior, inferior, two lateral) Endocardial cushions fuse => left and right atrioventricular canals form These canals partially separate the primordial atrium and primordial ventricle Partitioning of the primordial heart: The atria (D'Souza, 2016) Weeks 4-6 of development Septum primum Grows from the root of the primordial atrium towards the endocardial cushions Divides the primordial atrium into right and left halves Oxygenated blood passes from the right to left atrium through a large opening called the foramen primum (ostium primum) Partitioning of the primordial heart: The atria (D'Souza, 2016) Perforations appear in the central part of the septum primum, and form a new opening, the foramen secundum (ostium secundum) The septum primum fuses with the endocardial cushions and the foramen primum becomes progressively smaller and then disappears Blood moves from the right to the left atrium through the foramen secundum Partitioning of the primordial heart: The atria (D'Souza, 2016) A thick crescentic muscular fold, the septum secundum, grows from the ventrocranial wall of the right atrium, just adjacent to the septum primum. The upper part of the septum primum disappears, forming a flap-like valve between the two, called the foramen ovale (oval foramen) The flap-like mechanism allows only unidirectional flow of blood from the right atrium to the left during fetal life The foramen ovale permanently closes after birth Partitioning of the primordial heart: The ventricles The interventricular septum separates the left and right ventricles Muscular portion: The medial walls of the expanding ventricles become apposed and gradually merge The muscular portion forms in the floor of the primordial ventricle It has a crescent-shaped interventricular foramen, which permits communication between the two ventricles, until week 7 Membranous portion: Closure of the interventricular foramen forms the membranous part of interventricular septum Once it closes, the pulmonary trunk communicates with the right ventricle and the aorta with the left ventricle (D'Souza, 2016)  Partitioning of the primordial heart: The sinus venosus Weeks 4-10 of development Initially the right and left horns are of the same size Left-to-right shunts in the venous system: Left horn of sinus venosus: becomes smaller and smaller, eventually forms the coronary sinus Right horn of sinus venosus: enlarges progressively, becomes incorporated into the right atrium, forming the smooth-walled part of the right atrium, the sinus venarum The remainder of the right atrial wall has a rough trabeculated appearance The boundaries of the smooth and rough parts (D'Souza, 2016) are marked internally by a vertical ridge, the crista terminalis, and externally by a shallow Coronary sinus: the major venous groove, the sulcus terminalis tributary of the greater cardiac venous Superior and inferior vena cavae bring all the system; it is responsible for draining most of the deoxygenated blood leaving the blood from the cranial and caudal regions of the myocardium body into the enlarged right horn Partitioning of the primordial heart: The bulbus cordis and truncus arteriosus (D'Souza, 2016) Week 5: Truncal ridges form after mesenchymal cells in the walls of the truncus arteriosus proliferate Bulbar ridges form after mesenchymal cells in the walls of the bulbus cordis proliferate Partitioning of the primordial heart: The bulbus cordis and truncus arteriosus PT: Pulmonary trunk A: Aorta (D'Souza, 2016) Week 6: The bulbar and truncal ridges (conotruncal ridges) undergo 180-degrees spiralling and fuse, forming a spiral aorticopulmonary septum This septum divides the bulbus cordis and the truncus arteriosus into two distinct channels, the ascending aorta and pulmonary trunk Partitioning of the primordial heart: Atrioventricular valves Ventricular side of both left and right atrioventricular canals: Endocardial cells proliferate => valvular apparatuses form: Mitral and Tricuspid => Atria separate from the ventricles The valves remain attached to the ventricular wall by muscular cords Over time, the muscular tissue in the cords degenerates and is replaced by dense connective tissue The valves then consist of connective tissue covered by endocardium They are connected to thick trabeculae in the wall of the ventricle, the papillary muscles, by means of chordae tendineae Two valve leaflets (mitral valve) form in the left atrioventricular canal, and three valve leaflets (tricuspid valve) form on the right side (D'Souza, 2016) Partitioning of the primordial heart: Semilunar valves (Sadler, 2012) When the truncus arteriosus partitions: Swellings of subendocardial tissue develop around the orifices of the aorta and pulmonary trunk Primordia of the semilunar valves These develop around the orifices of the aorta and pulmonary trunk (aortic valve and pulmonic valve, respectively) Partitioning of the primordial heart: Semilunar valves (D'Souza, 2016) These swellings / tubercles hollow out at their upper surface, and reshape to form the semilunar valves Neural crest cells also contribute to the formation of these valves Partitioning of the primordial heart: Animation https://www.youtube.com/watch?v=RjQc7qGgniU What can go wrong? Septation and heart defects: Persistent atrioventricular canals Atrioventricular septal defect (AVSD) Failure of the dorsal and ventral endocardial cushions to fuse Persistent left-to-right shunting of blood after birth The tricuspid and mitral valves do not develop normally Blood that should be moving forward from the ventricle into either the pulmonary artery or the aorta instead flows backward into the atria This leakage of the mitral or tricuspid valves is called regurgitation There is one "common" valve separating the heart’s upper and lower chambers instead of two separate valves Abnormal growth of the atrial and ventricular septum Complications: Pulmonary hypertension Congestive heart failure Cleveland Clinic (https://my.clevelandclinic.org/) Septation and heart defects: Atrial septal defects (ASD) Congenital heart disease Associated with sex and autosomal chromosome abnormalities Common in partial and complete trisomies, including trisomy 21 (Down syndrome) 2:1 in females than males A hole in the atrial septum Shunting of blood from the left atrium to the right atrium The bigger the ASD, the more likely it is to cause symptoms and require treatment Four main types: Ostium secundum ASD: formed in the middle of the atrial septum, most common (80% of all ASDs) Ostium primum ASD: formed in the lower part of the atrial septum, associated with other heart conditions (tricuspid or mitral valve defect, atrioventricular septal defect), associated with Down Syndrome Sinus venosus ASD: formed in the back part of the atrial septum, liked with defects in the right pulmonary vein and the vena cavae Unroofed coronary sinus ASD: missing or incomplete wall between the coronary sinus and the left atrium (1% of all ASD) Cleveland Clinic (https://my.clevelandclinic.org/) Septation and heart defects: Ventricular septal defects (VSD) Most common type of congenital heart defects (25% of cases) More frequent in males than in females A hole in the ventricular septum Mixing of blood between the two ventricles Extra blood goes to the lungs The bigger the VSD, the more likely it is to cause symptoms and require treatment Four main types: Membranous VSD: most common, hole in the upper section of the intraventricular wall Muscular VSD: 20% of cases, usually more than one hole Inlet VSD: the hole is found just below the tricuspid valve in the right ventricle and the mitral valve in the left ventricle Cleveland Clinic Outlet (conoventricular) VSD: the hole is found just before (https://my.clevelandclinic.org/) the pulmonary valve in the right ventricle and the aortic valve in the left ventricle, connecting the two chambers Septation and heart defects: Transposition of the great arteries Congenital heart defect Failure of the aorticopulmonary septum to spiral The pulmonary artery and the aorta have switched positions The pulmonary artery connects to the left ventricle The aorta is connected to the right ventricle Oxygen-poor blood flows through the right side of the heart and back to the body without passing through the lungs Oxygen-rich blood flows through the left side of the heart and directly back into the lungs without being pumped to the rest of the body Symptoms: Cyanosis Mayo Clinic (https://www.mayoclinic.org/) Shortness of breath Weak pulse Complications: Hypoxia Heart failure Death Septation and heart defects: Persistent truncus arteriosus The spiral aorticopulmonary septum fails to completely descend The aortic and pulmonic trunks are left undivided at their outflow The two great arteries (aorta and pulmonary artery) have a single origin from the heart Blood from both ventricles passes across a VSD into the single arterial trunk The lung circulation is exposed to very high pressure and increased blood flow Heart failure often develops in the early weeks of life Treatment: Insertion of a tube containing a valve placed to connect the right ventricle to the pulmonary artery The VSD is also closed with a patch Operation needs to be performed in the first six months of life The Royal Children's Hospital, Melbourne, https://www.rch.org.au/home/ Valve development and heart defects: Tricuspid atresia Congenital heart defect Absence of the tricuspid valve Blood can't flow from the right atrium to the right ventricle Underdeveloped right ventricle Associated with ASD and VSD Insufficient oxygen to the body Symptoms: Tiredness Shortness of breath Cyanosis Diagnosis: Prenatal ultrasound scan Chest X-ray Mayo Clinic Electrocardiogram (https://www.mayoclinic.org/) Treatment: Medication to lower blood pressure and strengthen the heart muscles Surgery to improve blood flow through the heart and to the lungs (the tricuspid valve cannot be replaced) Valve development and heart defects: Ebstein anomaly Congenital heart defect The tricuspid valve is in the wrong position and the valve's leaflets are malformed Blood leakage backwards into the right atrium Inefficient heart Heart enlargement Heart failure Symptoms: Shortness of breath Fatigue Cyanosis Cardiac arrhythmias Mayo Clinic (https://www.mayoclinic.org/) Treatment: Medication to control heart rate and heart rhythm Surgery to repair the tricuspid valve Valve development and heart defects: Aortic valve stenosis The aortic valve opening is narrowed The heart must work harder to pump enough blood into the aorta and to the rest of the body Thickened and enlarged left ventricle Weakened heart muscle Heart failure Causes Congenital heart defect Calcium built up in the valve causes stiffening Rheumatic fever Symptoms: Heart murmur Shortness of breath Fatigue Mayo Clinic (https://www.mayoclinic.org/) Dizziness Treatment: Surgery to replace the valve Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Formation of the conductive system of the heart The network of nodes, specialised cells, and electrical signals that keep the heart beating There are two types of cells that control the heartbeat: Conducting cells carry the electric signals Muscle cells control your heart’s contractions The cardiac conduction system sends the signal to start a heartbeat It also sends signals that tell different parts of the heart to relax and contract This process of contracting and relaxing controls blood flow through the heart and to the rest of the body Nodes: groups of cells that can be either nerve or muscle tissue Formation of the conductive system of the heart For each heartbeat, electrical signals travel through the conduction pathway of the heart Initially, the pacemaker for the heart lies in the caudal part of the left cardiac tube Later, the sinus venosus assumes this function The sinus venosus is incorporated into the right atrium Pacemaker tissues lie near the opening of the superior vena cava, forming the sinoatrial (SA) node The excitation signal is created by the Cleveland Clinic (https://my.clevelandclinic.org/) sinoatrial (SA) node Formation of the conductive system of the heart The excitation signal travels to: The left and right atria, telling them to contract The atrioventricular (AV) node, delaying the signal until your atria are empty of blood The bundle of His (centre bundle of nerve fibres), carrying the signal to the Purkinje fibres The Purkinje fibres to your ventricles, causing them to contract The atrioventricular node (AV) and bundle Cleveland Clinic of His derive from two sources: (https://my.clevelandclinic.org/) Cells in the left wall of the sinus venosus Once the sinus venosus is incorporated into the right atrium, these cells lie in their final position at the base of the interatrial septum Cells from the atrioventricular canal Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Vascular development Blood vessel development occurs by two mechanisms: Vasculogenesis: the process of blood vessel formation, occurring by coalescence of angioblasts (de novo production of endothelial cells) Major vessels including dorsal aorta and cardinal veins Angiogenesis: the formation of new blood vessels from pre-existing ones (vessels sprout from pre-existing vessels) The remainder of the vascular system Controlled mainly by: Vascular endothelial growth factor (VEGF) Arterial system Venous system Embryonic system Adult system Aortic arches Vitelline veins Vitelline system Portal system Vitelline arteries Umbilical veins Cardinal system Caval system Umbilical arteries Cardinal veins Umbilical system Disappears Coronary arteries Vascular development: Arterial system – Aortic arches Each pharyngeal arch receives its own artery, called the aortic arches The aortic arches arise from the aortic sac and are embedded in the mesenchyme of the pharyngeal arches There are five aortic arches: I, II, III, IV, VI Aortic arch V either never forms, or forms incompletely and then regresses The outflow channel is divided into: Ventral aorta Pulmonary truck The aortic sac forms left and right horns: Left: Proximal segment of the (Sadler, 2012) aortic arch Right: Brachiocephalic artery Vascular development: Arterial system – Aortic arches (Sadler, 2012) Vascular development: Arterial system – Aortic arches Arch Arterial derivative Blood supply Maxillary artery Blood supply to many facial structures I Hyoid artery Blood supply to the larynx and thyroid gland II Stapedial arteries – regress by week 10 Common carotid artery Carotid arteries supply blood to the brain, III First part of the internal carotid artery neck, and face Sprouts to become the external carotid artery Part of the arch of the aorta The main and largest artery of the human IV left body Left subclavian artery Blood supply to the left arm IV right Proximal segment of the right subclavian artery Blood supply to the right arm Left pulmonary artery Moves deoxygenated blood from the heart to VI left the lungs Ductus arteriosus during fetal life Connects the aorta and the pulmonary artery Proximal segment of the right pulmonary artery Moves deoxygenated blood from the heart to VI right the lungs Vascular development: Arterial system – Vitelline arteries (Sadler, 2012) The vitelline arteries supply blood to the yolk sac They then fuse and form arteries in the dorsal mesentery of the gut Celiac mesenteric arteries (blood supply to the foregut - liver, spleen, pancreas, and some of the stomach and duodenum) Superior mesenteric arteries (blood supply to the midgut - small intestine, ascending colon, and a large portion of the transverse colon) Vascular development: Arterial system – Umbilical arteries The umbilical arteries carry deoxygenated blood from fetal circulation to the placenta During the 4th week, each artery acquires a second connection with the dorsal branch of the aorta, the common iliac artery (blood supply to the lower extremities - legs, reproductive organs and pelvic (Sadler, 2012) region) The umbilical arteries give rise to the inferior mesenteric arteries (blood supply to the hindgut - distal third of the transverse colon, the descending colon, the sigmoid colon, the rectum, and the upper portion of the anal canal) After birth: Proximal portions of the umbilical arteries persist as the internal iliac artery (primary artery supplying the pelvic viscera) and superior vesical arteries (blood supply to the upper portion of the bladder) Distal parts are obliterated to form the medial umbilical ligaments Vascular development: Arterial system – Coronary arteries They are derived from three sources: Sinus venosus Venous endothelial precursor cells dedifferentiate, migrate, and invade the myocardium These cells differentiate into coronary endothelial cells of arteries and capillaries Epicardium Epicardial cells undergo epithelial-to-mesenchymal transition The epicardium-derived mesenchymal cells contribute to endothelial and smooth muscle cells of the coronary arteries Neural crest cells The coronary arteries invade the aorta (ingrowth of arterial endothelial cells from the arteries into the aorta) (Schoenwolf et al., 2021) Vascular development: Venous system Vitelline veins: Return poorly oxygenated blood from the umbilical vesicle Umbilical veins: Carry well-oxygenated blood from the chorionic sac Common cardinal veins: Return poorly oxygenated blood from the body of the embryo to the heart https://www.youtube.com/watch?v=AQo18Dh2tx4 Vascular development: Venous system – Vitelline veins (Sadler, 2012) The vitelline veins form a plexus around the duodenum The liver cords grow forming the hepatic sinusoids A location for mixing of the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein Left-to-right blood shunt: The right vitelline vein (right hepatocardiac channel) receives more blood and enlarges Forms the hepatocardiac portion of the inferior vena cava Gives rise to the superior mesenteric vein The left vitelline vein disappears The portal vein forms around the duodenum Vascular development: Venous system – Umbilical veins The umbilical veins pass on each side of the liver and some connect to the hepatic sinusoids The right umbilical vein and the proximal part of the left umbilical vein disappears The left umbilical vein carries blood from the placenta to the liver The left umbilical vein and the right hepatocardiac channel communicate through the ductus venosus The ductus venosus bypasses the sinusoidal plexus of the liver (Sadler, 2012) Vascular development: Venous system – Cardinal veins The cardinal veins form the main venous drainage system of the embryo: Anterior cardinal veins (to drain the cephalic part of the embryo) Posterior cardinal veins (to drain the rest of the embryo) The anterior and posterior cardinal veins join before entering the sinus horn and form the common cardinal veins (Sadler, 2012) Additional veins formed: Subcardinal veins (to drain the kidneys) Sacrocardinal veins (to drain the lower extremities) Supracardinal veins (to drain the body wall) https://www.youtube.com/watch?v=AQo18Dh2tx4 Vascular development: Venous system – Cardinal veins Formation of the vena cava system: Anastomoses appear between left and right Blood from the left is channeled to the right side Anastomosis: A natural or artificial communication between 2 blood vessels or tubular cavities that may or may not normally be joined (Sadler, 2012) Vascular development: Venous system – Cardinal veins Anastomosis between the anterior cardinal veins Left brachiocephalic vein Blood from the left side of the head and the left upper extremity is channeled to the right The terminal portion of the left posterior cardinal vein is retained as a small vessel, the superior intercostal vein (to drain the area between the ribs) The superior vena cava is formed by the Right common cardinal vein Proximal portion of the right anterior cardinal vein The anterior cardinal veins form the (Sadler, 2012) internal jugular veins (to drain the head) A plexus of venous vessels in the face form the external jugular veins (to drain the face and one side of the head) Vascular development: Venous system – Cardinal veins (Sadler, 2012) Anastomosis between the subcardinal veins Left renal vein The left subcardinal vein disappears and its distal portion remains as the left gonadal vein The right subcardinal vein becomes the main drainage channel and develops into the renal segment of the inferior vena cava Vascular development: Venous system – Cardinal veins Anastomosis between the sacrocardinal veins Left common iliac vein The right sacrocardinal vein becomes the sacrocardinal segment of the inferior vena cava The renal segment of the inferior vena cava connects to the hepatic segment => development of the inferior vena cava is complete and consists of three parts: Hepatic Renal Sacrocardinal (Sadler, 2012) The posterior intercostal veins (drain the area behind the ribs) drain into the azygos vein (right side), and hemiazygos and accessory hemiazygos veins (left side). The latter two veins ultimately drain into the azygos vein What can go wrong? Arterial system defects: Coarctation of the aorta Congenital heart defect A narrow area (stricture) is present in the aorta Restricted blood flow to the lower part of the circulation Blood pressure in the arms and head is high, whilst that in the legs is low Heart failure Treatment: Surgery (removal of the narrow part, sew ends together) Balloon catheter The Royal Children's Hospital, Melbourne, https://www.rch.org.au/home/ Arterial system defects: Vascular ring 1% - 3% of all congenital heart defects The aorta or its branches partially or completely wrap around the trachea, esophagus or both Breathing problems Feeding / digestive issues Three most common types: Double aortic arch: some of the arches that should have disappeared are still present at birth in addition to the normal arch Cleveland Clinic Right aortic arch: the aortic arch develops on the right (https://my.clevelandclinic.org/) side of the airway instead of the left side Aberrant right subclavian artery: the right subclavian artery arises directly from the aortic arch instead of originating from the brachiocephalic artery Treatment: Surgery Medline Plus (https://medlineplus.gov/) Venous system defects Double inferior vena cava The left sacrocardinal vein fails to lose its connection with the left subcardinal vein Absence of inferior vena cava The right subcardinal vein fails to make its connection with the liver and shunts its blood directly into the right supracardinal vein Double inferior vena cava Absent inferior vena cava Left superior vena cava Persistence of the left anterior cardinal vein Obliteration of the common cardinal vein and proximal part of the right anterior cardinal veins Double superior vena cava Persistence of the left anterior cardinal vein Failure of the left Left superior vena cava Double superior vena cava brachiocephalic vein to form (Sadler, 2012) Lecture outline Establishment of the cardiac lineage Establishment of laterality Brief anatomy of the heart Formation of the primary heart tube Formation of the pericardial cavity Embryonic origins of the adult heart Cardiac looping Circulation through the primordial heart Partitioning of the primordial heart Cardiac septation Valve development Formation of the conductive system of the heart Vascular development Circulation before and after birth Circulation before and after birth: Fetal circulation Blood flows from the placenta (80% oxygen) to the fetal organs through the umbilical vein Ductus venosus (mixing with blood returning from the portal system) Inferior vena cava (mixing with blood coming from the lower extremities, pelvis, and kidneys) Right atrium (mixing with blood returning from the head and limbs) Left atrium (mixing with blood coming from the lungs) Left ventricle Ascending aorta Desaturated blood flows from the superior vena cava, through the right ventricle, into the (Sadler, 2012) pulmonary trunk This blood passes directly through the ductus arteriosus into the descending aorta Circulation before and after birth: Changes at birth Cessation of placental blood flow => Pressure decreases in the right atrium Beginning of respiration Ductus arteriosus closes Mediated by bradykinin Amount of blood flowing through the lung vessels increases Pressure increases in the left atrium The ductus arteriosus forms the ligamentum arteriosum The oval foramen closes Mediated by increased pressure in the left atrium and decreased pressure on the right side The umbilical arteries close The distal parts form the medial umbilical ligaments The proximal parts form the superior vesical arteries The umbilical vein and the ductus venosus close The umbilical vein forms the ligamentum teres hepatis The ductus venosus forms the ligamentum (Sadler, 2012) venosum What can go wrong? Arterial system defects: Patent (open) ductus arteriosus Common birth defect 3:1 females:males The ductus arteriosus fails to close and form the ligamentum arteriosum at birth Aortic blood is shunted into the pulmonary artery Causation: Hypoxia Immaturity (preterm birth) Associated with maternal rubella infection during pregnancy Mayo Clinic Treatment: (https://www.mayoclinic.org/) Surgical closure Medication (NSAID in premature newborns) Bibliography Schoenwolf, G. C., Bleyl, S. B., Brauer, P. R., & Francis-West, P. H. (2021). Larsen’s human embryology (6th edition). Sadler, T. W. (2012). Langman’s medical embryology (12th ed.). Moore, K. L., Persaud, T. V. N., & Torchia, M. G. (2016). Before we are born: Essentials of embryology and birth defects (9th edition). Tani, S., Chung, Ui., Ohba, S. et al. Understanding paraxial mesoderm development and sclerotome specification for skeletal repair. Exp Mol Med 52, 1166–1177 (2020). https://doi.org/10.1038/s12276-020-0482-1 D'Souza, R. (2016). Development of the heart and the fetal circulation. In A. Fiander & B. Thilaganathan (Eds.), MRCOG Part One: Your Essential Revision Guide (pp. 185-200). Cambridge: Cambridge University Press. doi:10.1017/CBO9781107587519.014 Thank you!