Lec 5 - CVS Dev I PDF

Development of the Cardiovascular System-I Asist. Prof. Dr. Seda Karabulut  Vasculogenesis and angiogenesis are the fundamental processes by which new blood vessels are formed. Vasculogenesis is defined as the differentiation of endothelial precursor cells, or angioblasts, into endothelia...

Development of the Cardiovascular System-I Asist. Prof. Dr. Seda Karabulut  Vasculogenesis and angiogenesis are the fundamental processes by which new blood vessels are formed. Vasculogenesis is defined as the differentiation of endothelial precursor cells, or angioblasts, into endothelial cells and the de novo formation of a primitive vascular network. Angiogenesis refers to the growth of new capillaries (new blood vessels that lack a fully developed tunica media) from preexisting blood vessels  The cardiac crescent forms in cardiogenic area within the splanchnic mesoderm. The intraembryonic coelom becomes the embryonic body cavity, which is divided into three well-defined body cavities during the fourth week): a pericardial cavity, two pericardioperitoneal canals connecting the pericardial and peritoneal cavities, and a large peritoneal cavity.  Pericardiac mesoderm forms the heart-forming regions. The cranial-most portion of the cardiac crescent swings ventrally and caudally to lie ventral to the newly forming foregut endoderm.  Through vasculogenesis a pair of endocardial tubes develop within each limb of the cardiac crescent. Vascular endothelial growth factor (Vegf) derived from the endoderm is thought to direct a subset of cells within the cardiac crescent into an endothelial/endocardi al cell lineage.  As the embryo folds, the right and left sides of the cardiac crescent are brought together. The two limbs of the crescent fuse in the midline, caudal to the head fold and ventral to the foregut.  These endocardial tubes coalesce into a single tube as the limbs of cardiac crescent join to make the primitive heart tube.  The cardiovascular system is the first major system to function in the embryo. On the right: Drawing of the embryonic cardiovascular system (26 days) showing vessels on the left side only. The umbilical vein carries well-oxygenated blood and nutrients from the chorionic sac to the embryo. The umbilical arteries carry poorly oxygenated blood and waste products from the embryo to the chorionic sac.  The primary heart tube is composed of an endocardial tube, cardiac jelly and a myocardial tube. The innermost endothelial tube becomes the endocardium. The outermost myocardial tube –a mass of splanchnic mesoderm containing cardiomyocytic progenitors- form the myocardium. Myocardium secretes a thick layer of extracellular matrix, the cardiac jelly. Later, splanchnic mesoderm that migrates from the coelomic wall near the liver into the cardiac region forms the epicardium.  The tubular heart elongates and develops alternate dilations and constrictions forming: truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and sinus venosus.  The primitive heart tube begins to elongate and simultaneously bend into a C-shaped structure, with the bend extending toward the right side. The end result of cardiac looping is to bring the four presumptive chambers of the future heart into their correct spatial relationship to each other.  Aortic sac Blood enters the sinus venosus from the: Embryo through the common cardinal veins (poorly oxygenated; the paired posterior cardinal veins draining the trunk and the paired anterior cardinal veins draining the head region) Developing placenta through the umbilical veins (well-oxygenated) Umbilical vesicle through the vitelline veins (poorly oxygenated) Blood leaves the truncus arteriosus into the aortic sac, from which it is distributed to the pharyngeal arch arteries. Blood leaves the truncus arteriosus into the aortic sac, from which it is distributed to the pharyngeal arch arteries.  Toward the end of the fourth week, atrioventricular endocardial cushions form on the dorsal and ventral walls of the atrioventricular canal. These cushions approach each other and fuse, dividing the atrioventricular canal into right and left atrioventricular canals.  These canals partially separate the primordial atrium from the ventricle, and the cushions function as atrioventricular valves. The endocardial cushion tissue contains endocardial-derived cells and neural crest cells.  The primordial atrium is divided into right and left atria by the formation and subsequent modification and fusion of two septa: the septum primum and septum secundum.  The septum primum grows toward the fusing endocardial cushions from the roof of the primordial atrium, partially dividing the atrium into right and left halves. As this crescent-shaped septum develops, a large opening—the foramen primum—forms between its free edge and the endocardial cushions. The foramen primum closes when the septum primum fuses with the atrioventricular cushions  Before the foramen primum disappears, perforations produced by apoptosis appear in the central part of the septum primum. These perforations coalesce to form the foramen secundum.  The septum secundum grows from the muscular ventrocranial wall of the atrium, immediately adjacent to the right of the septum primum. The foramen ovale is the opening between the upper and lower limbs of the septum secundum.  During embryonic life, blood is shunted from the right atrium to the left atrium via the foramen ovale.  Fetal heart circulation In the fetus, there is an opening between the right and left atrium (the foramen ovale), and most of the blood flows through this hole directly into the left atrium from the right atrium, thus bypassing pulmonary circulation. The continuation of this blood flow is into the left ventricle, and from there it is pumped through the aorta into the body. Some of the blood entering the right atrium does not pass directly to the left atrium through the foramen ovale but enters the right ventricle and is pumped into the pulmonary artery. In the fetus, there is a special connection between the pulmonary artery and the aorta, called the ductus arteriosus, which directs most of this blood away from the lungs (which are not being used for respiration at this point as the fetus is suspended in amniotic fluid)  The transitional circulation refers to the period of time when fetal circulation transforms into the neonatal phenotype. Soon after birth, this phase starts when the umbilical cord is clamped, and the lungs aerate following the first few breaths The transition from the fetal to the neonatal circulation includes Elimination of the placental circulation, Lung expansion, Increase in lung blood flow so that the entire cardiac output can be accommodated, Closure of the foramen ovale, ductus arteriosus, and ductus venosus.  Immediately after birth, functional closure of the foramen ovale is facilitated both by a decrease in right atrial pressure from occlusion of placental circulation and by an increase in left atrial pressure due to increased pulmonary venous return. At approximately 3 months, the septum primum and septum secundum fuse forming the oval fossa (fossa ovalis). This completes the formation of the atrial septum. Blood enters the sinus venosus from the: Embryo through the common cardinal veins (poorly oxygenated; the paired posterior cardinal veins draining the trunk and the paired anterior cardinal veins draining the head region) Developing placenta through the umbilical veins (well-oxygenated) Umbilical vesicle through the vitelline veins (poorly oxygenated) Blood leaves the truncus arteriosus into the aortic sac, from which it is distributed to the pharyngeal arch arteries.  The inflow to the heart is remodeled between weeks 4 and 8 so that all systemic blood flows into the future right atrium. The left sinus venosus horn is reduced and pulled to the left. It loses its connection with the left anterior cardinal vein and becomes the coronary sinus. The left anterior cardinal vein becomes connected to the right anterior cardinal vein.  The right sinus venosus horn is incorporated into the wall of the right atrium. It becomes the smooth part of the internal wall of the right atrium—the sinus venarum.  A remnant of the right vitelline vein becomes the terminal segment of the inferior vena cava.  During the 4th week, the pulmonary vein originates within the caudal dorsal mesocardium. The pulmonary vein promptly branches into right and left pulmonary branches, which bifurcate again to produce a total of four pulmonary veins. These veins then grow toward the lungs. As the atrium expands, the primordial pulmonary vein and its main branches are gradually incorporated into the wall of the left atrium.  Division of the primordial ventricle into two ventricles is first indicated by a median ridge—the muscular interventricular septum—in the floor of the ventricle near its apex. Myocytes from both the right and left primordial ventricles contribute to the formation of the muscular interventricular septum. The interventricular foramen is located between the free edge of the muscular interventricular septum and the fused atrioventricular cushions.  Closure of the interventricular foramen and formation of the membranous interventricular septum result from the fusion of tissues from three sources: the right bulbar ridge, the left bulbar ridge, and the endocardial cushion.  During the 5th week, active proliferation of cells in the walls of the bulbus cordis results in the formation of bulbar ridges.  The bulbar ridges and truncal ridges are derived mainly from the neural crest cells. The truncal and bulbar ridges grow and twist around each other in a spiral fashion. The spiral orientation of the bulbar and truncal ridges, possibly caused in part by the streaming of blood from the ventricles. Aorticopulmonary septum development  When the ridges fuse a spiral aorticopulmonary septum is formed. The aorticopulmonary septum is continues with the membranous interventricular septum.  The aorticopulmonary septum divides the bulbus cordis and the truncus arteriosus into two arterial channels, the aorta and the pulmonary trunk. Because of the spiraling of the aorticopulmonary septum, the pulmonary trunk twists around the ascending aorta.  The semilunar valves develop from three swellings of subendocardial tissue around the orifices of the aorta and pulmonary trunk. These swellings are hollowed out and reshaped to form three thin-walled cusps. Semilunar valve leaflets originate from endocardial-derived cushion tissue.  The atrioventricular valves (tricuspid and mitral valves) develop similarly from localized proliferations of tissue around the atrioventricular canals.  Cavitation of the ventricular walls forms a sponge-like mass of muscular bundles—trabeculae carneae. Other tissue bundles become the papillary muscles and tendinous cords (chordae tendineae). The tendinous cords run from the papillary muscles to the AV valves