EMBRYOLOGY CARDIOVASCULAR.pdf

CARDIOVASCULAR EMBRYOLOGY ONANUGA I.O. (PhD) 7/23/2024 1  Earliest Development Cardiovascular system makes its f irst appearance while the embryo is still flat (3-4wks). Clusters of mesodermal cells specialise to form blood...

CARDIOVASCULAR EMBRYOLOGY ONANUGA I.O. (PhD) 7/23/2024 1  Earliest Development Cardiovascular system makes its f irst appearance while the embryo is still flat (3-4wks). Clusters of mesodermal cells specialise to form blood cells. Mesodermal cells around the blood cells flatten to form endothelium of blood vessels. H These clusters are called blood islands of angiogenic (“blood vessel-forming”) cell clusters. In the accompanying diagram note that these form a curve reaching well beyond the neural plate and the notochord. A m ass of m esod erm , cal l ed cardiogenic area, near the head end (H) will give rise to the heart. The sagittal section below illustrates the three germ layers, prochordal plate and the cardiogenic area. Prochordal plate 7/23/2024 2 Cardiogenic area  Head Fold With the formation of the head fold (shown in the blue circle), the cardiogenic area changes its position. Also observe that the endoderm (yellow) is beginning to form the gut tube. At this stage only the head and tail ends of the digestive tube are recognisable. In the lowest picture, the gut tube is better seen and the heart is in fact in the form of a tube (red). 7/23/2024 Heart Tube 3 1. Development of Early Blood Vessels Yolk sac → blood islands → endothelia → vessels primitive blood cells. 7/23/2024 4  Chorion, body stalk, embryonic body → blood vessels → 3 separate circulations: vitelline, chorionic, and intraembryonic. 7/23/2024 5  Development of Primitive Heart Tube 2.1 Primordium: Cardiogenic area → Intraembryonic coelom → pericardial coelom; 2 lateral cardiogenic plates →endocardial heart tubes. 7/23/2024 6 2.2 Primitive heart tube 1) Lateral fold: 2 heart tubes → single heart tube. 7/23/2024 7 2) Head fold: pericardial coelom → ventral to heart ↘ tube caudal to oropharyngeal membrane 7/23/2024 8 3) Wall of primitive heart tube Endocardial heart tube → endocardium Myoepicardial mantle → myocardium, epicardium Cardiac jelly → subendocardial tissue 7/23/2024 9  The Heart Tube In the picture on the left the relationships of the heart, the gut tube and the liver are clearer. In the magnif ied picture of the heart tube, the tail end is the venous end and the cranial end is the arterial end. The changing shape of the tube also makes it possible to recognise Heart the primitive chambers of the tube. Liver Remember that the tube is not partitioned at this stage. Hereafter, for descriptive convenience, we shall view this tube in the vertical position, with the caudal (v enous) end b el ow and the cranial (arterial) end at the top as shown below. 7/23/2024 10 3. Formation of Heart Loop 3.1 Heart tube → bulbus cordis, ventricle, atrium → truncus arteriosus, conus cordis, ventricle, atrium, sinus venosus 7/23/2024 11  The Tube Bends V B D A V SV This picture shows 3 successive stages in the growth of the tube. The tube, as it grows, cannot be accommodated within the pericardial cavity and undergoes bending. The primitive chambers of the heart are recognisable, and are labelled in the last picture. SV – sinus venosus (receives veins from the body), A – atrium, V – ventricle. The ventricle continues into the ‘bulbus cordis’ which in turn leads to the arterial end. 2 terms are used somewhat confusingly for the parts at the arterial end. 7/23/2024 12 These are conus arteriosus and truncus arteriosus. 3.2 Bulboventricular portion → bulboventricular loop → cephalic portion bends ventrally, caudally and slightly to the right 3.3 Atrium → dorsocranially and bulges laterally on each side of bulbus 3.4 Proximal part of bulbus → primitive right ventricle 7/23/2024 13  Blood Flow and Embryological Fates aortic arches aortic sac pulmonary trunk

aorta truncus arteriosus

conus arteriosus of r. ventr.

bulbus cordis aortic vestibule of l. ventr. ventricle

atrium left horn coronary sinus sinus venosus sinus venarum right horn of right atrial wall umbilical v.

vitelline v. common cardinal v. Solid arrows: circulation Dotted arrows: embryological derivatives 7/23/2024 14  The Chambers A A A B-V Loop V Left view Front view Recognise the chambers in these 2 views. In the view from the left side, the sinus venosus is partly hidden. Note that with the bending of the tube, the atrium is now dorsal and the loop formed by the ventricle and the bulbus cordis (bulbo-ventricular loop) is ventral. I n t h7/23/2024 e ne xt s l id e w e s h a l l e xa m ine t h e int e r ior of15 t h e  Left – Right Partitioning  Interatrial septum  Interventricular septum  Spiral (aortico-pulomonary) septum  Endocardial cushions (A-V cushions)  Functional requirements  There must always be a right to left passage! 7/23/2024 16  Partitioning of Heart Chambers 4.1 Division of atrioventricular canal Subendocardial tissue → 2 endocardial cushions → fuse → right and left canals 7/23/2024 17 Formation of atrioventricular valves 7/23/2024 18  Interatrial septum  Partitioning  Right to left passage  Mechanism for closing the passage 7/23/2024 19 4.2 Partitioning of primitive atrium 1) Septum primum → endocardial cushions → foramen primum. 7/23/2024 20 2) Septum primum absorbed → foramen secundum → foramen primum closing 3) Septum secundum → cover the foramen secundum → foramen ovale 7/23/2024 21  foramen ovale 4) Blood from right to left atrium 7/23/2024 22  Atrial Partitioning III Fetus right side high pressure (high pulmonary resistance, etc.) well oxygenated blood streams through foramen ovale valve of foramen ovale closes with left atrial contraction After birth right side low pressure (low pulmonary resistance) valve remains closed (physiological closure) valve eventually fuses (anatomical closure): fossa ovalis 7/23/2024 23 From Moore & Persaud 1998  Atrial Partitioning IV probe patent

postnatal foramen ovale

(not an ASD) 7/23/2024 From Moore & Persaud 1998 24 4.3 Development of sinus venosus 1) Right horn enlarges (due to left-to-right shunts of blood in venous system) orifice Sinus-atrial → right; Receives sup. and inf. vena cava; Right horn → right atrium (smooth walled part). 7/23/2024 25 2) Left horn degenerates → coronary sinus, oblique vein of left atrium; Pulmonary vein and its branches → left atrium (smooth walled part) 7/23/2024 26  The Ventricular Septum Three Parts – Interventricular septum – AV Cushions – Spiral Septum (aorticopulmonary) 7/23/2024 27 4.4 Partitioning of the primitive ventricle 1) Apical ventricle wall → muscular interventricular septum → interventricular foramen 7/23/2024 28 2) Endocardial cushion, right and left bulbar ridges → membranous interventricular septum → interventricular foramen closed 7/23/2024 29 4.5 Division of truncus and bulbus 1) Truncal ridges + Bulbar ridges → aorticopulmonary septum 7/23/2024 30 2) Aorticopulmonary septum → spiral course → pulmonary trunk → right ventricle aorta → left ventricle 7/23/2024 31 3) Truncus swellings → hollowed out at upper surface → semilunar valves 7/23/2024 32  Conducting system  Initial pacemaker lies in caudal part of left cardiac tube  Sinus venosus later takes up the function  As sinus gets incorporated into right atrium, nodal tissue comes to lie near opening of SVC  AVN and Bundle of His - from cells in left wall of sinus venosus, cells of atrioventricular 7/23/2024 canal. 33  INTERMISSION!!! 7/23/2024 34  FOETAL CIRCULATION 7/23/2024 35  Introduction  The fetal CVS is designed to serve prenatal needs and permit modif ications at birth that establish the neonatal circulatory pattern.  Normal respiration in the newborn infant is dependent on normal circulatory changes occurring at birth, which result in oxygenation of the blood occurring in the lungs when fetal blood flow through the placenta ceases. 7/23/2024 36  Introduction  Prenatally, the lungs do not provide gas exchange and the pulmonary vessels are vasoconstricted.  The 3 vascular structures most important in the transitional circulation are  the ductus venosus (DV),  foramen ovale, and  ductus arteriosus (DA). 7/23/2024 37  IVC : Blood from placenta – Ductus venosus  Foramen ovale  Ductus arteriosus 7/23/2024 38  Foetal Circulatio n  Highly oxygenated, nutrient-rich blood returns under high pressure from the placenta in the umbilical vein. 7/23/2024 39  Foetal Circulation  On approaching the liver, approximately half of the blood passes directly into the Ductus Venosus, a fetal vessel connecting the umbilical vein to the IVC, consequently, this blood 7/23/2024 40 bypasses the  Fetal Circulatio n  The other ½ of the blood in the umbilical vein sinusoids of the liver IVC through the hepatic veins. 7/23/2024 41  Fetal Circulation  Blood flow through the DV is regulated by a sphincter mechanism close to the umbilical vein. When the sphincter contracts, more blood is diverted to the portal vein and hepatic sinusoids and less to the DV 7/23/2024 42  Fetal Circulation  The sphincter prevents overloading of the heart when venous flow in the umbilical vein is high (e.g., during uterine contractions). 7/23/2024 43  Foetal Circulation  After a short course in the IVC, the blood enters the right atrium of the heart.  Because the IVC also contains poorly oxygenated blood from the lower limbs, abdomen, and pelvis, the blood entering the right atrium is not as well oxygenated as that in the umbilical vein, but it still has a high oxygen content. 7/23/2024 44  Foetal Circulation  Most blood from the IVC is directed by the crista dividens (inferior border of the septum secundum), through the oval foramen into the left atrium. 7/23/2024 45  Foetal Circulation  Here it mixes with the relatively small amount of poorly oxygenated blood returning from the lungs through the pulmonary veins. 7/23/2024 46  Foetal Circulation  The fetal lungs use oxygen from the blood instead of replenishing it.  From the left atrium, the blood then passes to the left ventricle and leaves through the ascending 7/23/2024 47  Foetal Circulation  The arteries to the heart, neck, head, and upper limbs receive well-oxygenated blood from the ascending aorta.  The liver also receives well-oxygenated blood from the umbilical vein.  The small amount of well-oxygenated blood from the IVC in the right atrium that does not enter the foramen ovale mixes with poorly oxygenated blood from the SVC and coronary sinus and passes into the right ventricle.  This blood, with a medium oxygen content, 7/23/2024 48 leaves through the pulmonary trunk.  Foetal Circulation  Approximately 10% of this blood flow goes to the lungs; most blood passes through the DA into the descending aorta to the fetal body and returns to the placenta through the umbilical arteries.  The DA protects the lungs from circulatory overloading and allows the right ventricle to strengthen in preparation for functioning at full capacity 7/23/2024 at birth. 49  Foetal Circulation  Because of the high pulmonary vascular resistance in fetal life, pulmonary blood flow is low.  Approximately 10% of blood from the ascending aorta enters the descending aorta; 65% of the blood in the descending aorta passes into the umbilical arteries and is returned to the placenta for reoxygenation.  The remaining 35% of the blood in the descending 7/23/2024 aorta supplies the viscera and50 Circulation before and after Birth Circulation before birth Placental circulation: umbilical A. & V. ductus venosus foramen ovale ductus arteriosus 7/23/2024 51 Transitional Neonatal Circulation  Important circulatory adjustments occur at birth when the circulation of fetal blood through the placenta ceases and the infant's lungs expand and begin to function  The oval foramen, DA, DV, and umbilical vessels are no longer needed 7/23/2024 52 Changes after birth Umbilical arteries → lat. & med. umbilical ligaments Umbilical vein → ligamentum teres hepatis Ductus venosus → ligamentum venosum Ductus arteriosus → ligamentum arteriosum Foramen ovale → oval fossa 7/23/2024 53 Transitional Neonatal Circulation  Aeration of the lungs at birth is associated with a: 1. Dramatic decrease in pulmonary vascular resistance 2. Marked increase in pulmonary blood flow 3. Progressive thinning of the walls of the pulmonary arteries; the thinning of the walls of these arteries results mainly from stretching as the lungs increase in size with the first few breaths 7/23/2024 54 Transitional Neonatal Circulation  Because of increased pulmonary blood flow and loss of flow from the umbilical vein, the pressure in the left atrium is higher than in the right atrium.  The increased left atrial pressure functionally closes the oval foramen by pressing the valve of the oval foramen against the septum secundum 7/23/2024 55 Transitional Neonatal Circulation  The output from the right ventricle now flows into the pulmonary trunk.  Because pulmonary vascular resistance is lower than the systemic vascular resistance, blood flow in the DA reverses, passing from the descending aorta to the pulmonary trunk 7/23/2024 56 Transitional Neonatal Circulation  The right ventricular wall is thicker than the left ventricular wall in fetuses and newborn infants because the right ventricle has been working harder in utero.  By the end of the first month, the left ventricular wall thickness is greater than the right because the left ventricle is now working harder.  The right ventricular wall becomes thinner because of the atrophy 7/23/2024 57 Transitional Neonatal Circulation  The DA constricts at birth but there is often a small shunt of blood via the DA from the aorta to the pulmonary trunk for 24 to 48 hours in a normal full-term infant.  At the end of 24 hours, 20% of ducts are functionally closed, 82% by 48 hours , and 100% at 96 hours.  In premature infants and in those with persistent hypoxia, the DA may remain 7/23/2024 58 open much longer.  Transitional Neonatal Circulation  In full-term infants, oxygen is the most important factor in controlling closure of the DA and appears to be mediated by bradykinin, a substance released from the lungs during their initial inflation.  Bradykinin has potent contractile effects on smooth muscle.  The action of this substance appears to be dependent on the high oxygen content of the blood in the aorta resulting from aeration of the lungs at59 7/23/2024 Transitional Neonatal Circulation  Hypoxia and other ill-defined influences cause the local production of PGE2 and prostacyclin (PGI2), which keep the DA open.  Inhibitors of PG synthesis, such as indomethacin, can cause constriction of a patent DA (PDA) in premature infants. 7/23/2024 60 Transitional Neonatal Circulation  The umbilical arteries constrict at birth, preventing loss of the infant's blood.  The closure of fetal vessels and the oval foramen is initially a functional change.  Later, anatomic closure results from proliferation of endothelial and fibrous tissues 7/23/2024 61  Derivatives of Fetal Vascular Structures  Because of the changes in the cardiovascular system at birth, certain vessels and structures are no longer required.  Over a period of months, these fetal vessels form nonfunctional ligaments.  Fetal structures, such as the oval foramen, persist as anatomic vestiges 7/23/2024 62  Congenital Heart Defects Acyanotic Cyanotic volume load pressure load ↑ pulmonary flow↓ pulmonary flow left-to-right shunts obstr. ventric. outflow atrial septal defect pulmonary valve stenosis transpos. of gr. vessels tetralogy of Fallot ventricular septal defect aortic valve stenosis single ventricle pulmonary atresia AV canal coarctation of aorta truncus arteriosus tricuspid atresia patent ductus arteriosus total anomalous pulm.

total anomalous pul return w/o obstruction return w/ obstruc 7/23/2024 63 6. Congenital Malformations Atrial septal defect Excessive resorption of the septum primum; Inadequate development of the septum secundum. 7/23/2024 64  (Ostium) Secundum ASDs Most common ASD (females>males) Usually due to problems with septum primum Atrial Septal Defects (ASD) (perforated or too short), but sometimes

septum secundum or both septa AV septal defect (AV canal) Endocardial cushion problems so that septum

Secundum ASDs primum never fuses with cushion tissue Patent foramen (ostium) primum Valve defects Sometimes no fusion of endocardial

cushions: AV septal defect 20% of Downs patients Sinus venosus ASDs: very rare Primum ASDs & Sinus venosus ASD AV canal 7/23/2024 65 From Moore & Persaud 1998 Ventricular septal defect Defect of the membranous septum, isolated or associated with other abnormalities. 7/23/2024 66 Tetralogy of Fallot Unequal division of conus cordis; ventricular 4 defects: pulmonary stenosis, overriding aorta, septal defect, hypertrophy of right ventricle; Causing cyanosis. 7/23/2024 67  Decreased pulmonary load defects: Tetralogy of Fallot 5-7% of all CHDs Four co-occurring heart defects Pulmonary stenosis Ventricular septal defect Cyanotic Overriding aorta (dextroposition) Right ventricular hypertrophy Asymmetrical fusion of bulbar & truncal ridges ↓ pulmonary flow tetralogy of Fallot pulmonary atresia tricuspid atresia total anomalous pulm.

return w/ obstruction 7/23/2024 68 From Moore & Persaud 1998 Persistent truncus arteriosus Truncoconal ridges fail to fuse and descend; Truncus overrides both ventricles; Accompanied by ventricular septal defect; Cyanosis, blood to lungs increased. 7/23/2024 69 Transposition of great vessels Truncoconal septum failing to follow its spiral course and descending straight downward; Aorta originates from right ventricle, pulmonary artery from left; Usually combined with patent ductus arteriosus. 7/23/2024 70  Increased pulmonary load defects: TGA Cyanotic Transposition of the Great Arteries (d-TGA) ↑ pulmonary flow transpos. of gr. vessels single ventricle truncus arteriosus total anomalous pulm.

return w/o obstruction From Moore & Persaud 1998 Most common cyanotic neonatal

heart defect Failure of aorticopulmonary septum to

take a spiraling course 7/23/2024 Fatal without PDA, ASD, & VSD 71 Patent ductus arteriosus Ductus arteriosus fails to be closed after birth; Isolated or combined with other defects. 7/23/2024 72 Tricuspid atresia Absence or fusion of tricuspid valves; Patent oval foramen & ventricular septal defect; Underdeveloped right ventricle 7/23/2024 73 Pulmonary valvular atresia (or stenosis) Pulmonary valves are fused for variable distance; Hypoplastic right heart; Patent oval foramen and patent ductus arteriosus. 7/23/2024 74 Aortic valvular atresia and stenosis Aortic valves are fused for variable distance; Aorta, left ventricle, left atrium underdeveloped; Accompanied by patent ductus arteriosus. 7/23/2024 75  Increased pressure load defects: Valve stenosis Pulmonary or aortic stenosis Unequal partitioning of the truncus arteriosus Acyanotic Deviation of the aorticopulmonary septum One side expanded, other side stenosed pressure load obstr. ventric. outflow pulmonary valve stenosis aortic valve stenosis coarctation of aorta 7/23/2024 76 From Moore & Persaud 1998  Increased pressure load defects: Aortic coarctation Acyanotic Constriction of the aorta distal to

pressure load the left subclavian artery Typically near ductus arteriosus

(lig. arteriosum) obstr. ventric. outflow Preductal (= infantile) Postductal (= “adult”) Juxtaductal pulmonary valve stenosis aortic valve stenosis coarctation of aorta 7/23/2024 77 From Moore & Persaud 1998 From Cahill, 1997  Increased pressure load defects: Aortic coarctation Collateral Circulation Subclavian → IMA →

intercostals → aorta Subclavian → IMA →

sup. epigastr. → inf.

epigastr. → iliac →

aorta Subclavian → cervical

& scap. branches →

intercostals → aorta Subclavian → vertebral

→ ant. spinal costals & lumbars →

aorta From7/23/2024 Cahill, 1997 78