DEVELOPMENT OF CARDIOVASCULAR SYSTEM Petr Vaňhara, PhD Dept. of Histology and Embryology Faculty of Medicine, Masaryk University http://i45.tinypic.com/2vhsrqb.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM Fully functional, four-chamber heart Fitst morphological hallmarks of developing heart First activity of heart cells Cor tubulare simplex & sigmoideium Week 2-3 BILAMINAR GERM DISC DEVELOPMENT OF CARDIOVASCULAR SYSTEM File:Stage5 bf11b.jpg Consider the embryonic developmental context DEVELOPMENT OF CARDIOVASCULAR SYSTEM •rapid growth of embryo •insuffcient supply by diffusion •first vascularisation develops outside embryo – yolk sac, chorion and connecting stalk •bipotential (hem)angioblasts in blood islands •vasculogenesis and angiogenesis •blood cells formation • https://embryology.med.unsw.edu.au/embryology/images/c/ce/Stage5_bf11L.jpg Week 2-3 DEVELOPMENT OF CARDIOVASCULAR SYSTEM •embryonic vasculogenesis approx. 2 days later after establishment of extra-embryonic vessels •primordial blood vessels •heart primordium in cardiogenic area •embryonic hematopoiesis from para-aortic clusters in AGM • End of week 3 Trilaminar germ disc is too big to be nourished by a simple diffusion Heart and vessels are essential for embryo to develop DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 3 Heart develops from embryonic mesoderm. Currently, we can trace the heart cell precursors back to primitive streak. Specific cells are already determined to cardiac fate here. Image result for yolk sac vasculature DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 1 2 3 Three embryonic blood circuits have their evolutionary importance. Human is, however, a placental mammal, yolk sac and allantois are therefore obsolete, but their vessels acquire new functions. •embryonic circulation: heart tube ® truncus arteriosus ® aortal arches ® paired dorsal aorta ® caudally fuse into single aorta dorsalis ® capillary beds ® paired cardinal veins (drain pre- and postcardinal veins) ® ductus Cuvieri ® sinus venosus • •vitelinne circulation: dorsal aorta ® aa. omphalomesentericae ® fuse into single a. omphalomesenterica ® vv. omphalomesentericae + vv. umbilicales ® paired truncus vitelloumbilicalis ® sinus venosus • •umbilical circulation: dorsal aorta ® aa. umbilicales ® chorion ® vv. umbilicales + vv. omphalomesentericae ® paired truncus vitelloumbilicalis ® sinus venosus DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 Essential for understanding of arrangement of postnatal blood circulation. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 6 Week 7 Week 8 Postnatal Week 4 Development of veins illustrates well the change of symmetric embryonic circulation to definitive vascular arrangement. Compare the anatomy of early developmental stages with the post natal situation It is not necessary to memorize this slide. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 3 •paired endothelial heart tubes (cor tubulare duplex) derived from embryonic splanchnopleura in cardiogenic area •flexion of the embryo ® medial fusion of paired tubes into simple-tubular heart (cor tubulare simplex) •visceral mesoderm constitutes myoepicardial layer: myocardium and epicardium •cardiac jelly ® subendocardial connective tissue •heart starts beating day 21-22 •blood starts flow ~week 4th • Blood cells Endocardium Myocardium Primitive heart development DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 3-4 Heart develops from a simple tube that folds and forms finaly a heart with 4 chambers. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 •simple-tubular heart (cor tubulare simplex and cor tubulare sigmoideum ) •sinus venosus ® atrium ® ventriculus ® bulbus cordis® truncus arteriosus • Image result for simple tubular heart Important ;-) Paired dorsal aorta Truncus arterosus Bulbus cordis Ventriculus Paired atrium and sinus venosus Right auricle Left auricle Aorta Ventricle Sternocostal surface DEVELOPMENT OF CARDIOVASCULAR SYSTEM Cor tubulare simplex Cor tubulare sigmoideum Week 4 Cor tubulare simplex/sigmoideum is not theoretical structure, it really exists. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Not so complicated, separate the morphogenesis to individual steps 2 endothelial tubes Fusion Cor tubulare simplex Folding of cor tubulare simplex Cor tubulare sigmoideum DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 4 DEVELOPMENT OF CARDIOVASCULAR SYSTEM •septum primum grows from dorso-cranial wall towards endocardial cushions •incoplete closure ® foramen (ostium) primum •by apoptosis ® foramen secundum •septum secundum ® surrounds foramen ovale •valvula foraminis ovalis from septum primum • • •foramen ovale: crucial embryonic shunt •foramen ovale patens • •after atrial septation: -opening of sinus venosus shifts to the right -rest of sinus venosus ® sinus coronarius - Image result for septum primum Image result for fetal heart circulation Partitioning of atrium commune Primitive heart tube divides to chambers Very important! DEVELOPMENT OF CARDIOVASCULAR SYSTEM • •sinus venosus during atrial septation: -shift of sinus venosus opening to the right ® right atrium -left part sinus venosus is separated ® sinus coronarius Gray477.svg Image result for sinus coronarius Sinus coronarius R atrium L atrium DEVELOPMENT OF CARDIOVASCULAR SYSTEM Very important slide - septation of atrium and development of foramen ovale. Criticial circulatory shunt. •septum interventriculorum primitivum – temporary •septum interventriculare at the end of week 4 – grows cranially •foramen interventricualre – closure linked to development of aortico-pulmonary septum • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Partitioning of ventriculus communis Wrong septation of atria and ventricles can cause serious congenital disorders of CVS Consider the time periods of development. •5th week – ridges in bulbus and truncus from neural-crest mesenchyme •180° spiraling – spiral aortico-pulmonary septum •pulmonary trunk twists around aorta • •bulbus cordis is embedded into the definitive ventricles: •right ventricle: conus arterious (infundibulum) ® pulmonary trunk •left ventricle: aortic vestibule • • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Image result for partitioning of bulbus cordis and truncus arteriosus •Partitioning of bulbus cordis and truncus arteriosus Critical developing event. See the tetralogy of Fallot. •semilunar valves develop by the partitioning of truncus arteriosus from three swellings of endocardial tissue •neural crest origin •AV valves (tricuspid and mitral) develop similarly at AV canals • DEVELOPMENT OF CARDIOVASCULAR SYSTEM •Development of cardiac valves https://embryology.med.unsw.edu.au/embryology/images/a/a1/Stage_22_image_178.jpg File:AV Canal Division (Superior View).jpg File:AV Valves.jpg File:Semilunar Valves.jpg Disorders of development of valves are one the most common. DEVELOPMENT OF CARDIOVASCULAR SYSTEM https://embryology.med.unsw.edu.au/embryology/images/1/1f/Basic_Heart_Development_Timeline.jpg This slide is good to know. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Week 20 Heart USG of week 20 of pregnancy. Why there is a space between the left and right atrium? Image result for branchial arteries fish File:Embryonic Circulations.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM Embryonic development of CVS in humans resembles arrangement of CVS in lower vertebrates. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Development of large arteries – aortic arches Humans do not need gills. The vessels acquire new functions. Výsledek obrázku pro aortic arches Výsledek obrázku pro aortic arches 1 mostly disappears, a. maxillaris 2 mostly disappears, a. stapedia and a. hyoidea 3 proximal parts aa. carotides communes, distal parts of aa. carotides internae 4 right: proximal part of a. subclavia dextra (distal part from dorsal aorta and 7th intersegmental artery); left: arcus aortae (aorta develops from aortic sac and left dorsal aorta) 5 does not develop or quickly degenerates 6 right: from proximal part: a. pulmonalis dextra, distal part disappears left: from proximal part: a. pulmonalis sinistra, from distal part: ductus arteriosus. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Aortic arches Aortic arches and dorsal aortae are paired structures. •aa. vitellinae (aa. omphalomesentericae) reduced to three principal vessels: 1truncus coeliacus 2a. mesenterica superior 3a. mesentrica inferior • • DEVELOPMENT OF CARDIOVASCULAR SYSTEM Vitelline arteries Image result for mesenteric arteries Image result for primitive gut vascularisation Nutritive function of yolk sac is not significant. •First, aa. umbilicales are ventral branches of dorsal aorta •Later, aa. umbilicales are continuations to aa. iliacae communes and aa. communes internae. •Abnormally, a single a. umbilicalis develop (can result in growth retardation of fetus) •After birth: proximal parts of aa. umbilicales form aa. iliacae internae and aa. vesicales superiores. Distal parts obliterate. • • Umbilical arteries DEVELOPMENT OF CARDIOVASCULAR SYSTEM Image result for umbilical circulation Clinically important https://www.trando-med.com/Content/upload/2018253296/201810231014364855.jpg DEVELOPMENT OF CARDIOVASCULAR SYSTEM •four primary segments 1hepatic segment (proximal part of the right vitelline vein = hepatic vein) 2prerenal segment (right subcardinal vein) 3renal segment (subcardinal – supracardinal anastomosis) 4postrenal segment (right supracardinal vein) •Anomalies of venae cavae • •Double SVC: persistence of left anterior cardinal vein; Abnormal CVC opens to right atrium through sinus coronarius •Left SVC: right anterior cardinal vein and v. cardinalis communis degenerate •Absence of hepatic segment of IVC: blood drained through v. azygos and hemiazygos into right atrium. Vv. hepaticae opens to right atrium individually. •Double IVC: absence of anastomoses between primitive caudal veins. Inferior vena cava Venous system is complicated with a number of anastomoses (see anatomy and cavo-caval anastomoses) It is not necessary to memorize this slide. DEVELOPMENT OF CARDIOVASCULAR SYSTEM Vv. omphalomesentericae •bring blood from yolk sac •septum transversum •sinus venosus (together with umbilical veins as trunci vitelloumbilicales) •growth of liver – separation of omphalomesenteric veins to proximal (yolk sac-liver) and distal parts (liver-heart) •distal parts form anastomoses and develop into v. portae •proximal parts dorm posthepatic part of IVC •begin in chorionic villi •due to liver growth lose connection with sinus venosus •proximal parts of both veins disappear •distal part of right v. umbilicalis disappears •distal part of left v. umbilicalis forms ductus venosus Vv. umbilicales Important for understanding of development of definitive structures. Important for development of ductus venosus DEVELOPMENT OF CARDIOVASCULAR SYSTEM Teratology •Acardia •Ectopia cordis •Dextrocardia •Atrial septal defects •Ventricular septal defects •Stenosis of truncus pulmonalis •Atresia pulmonaris •Tetra (penta)llogy of Fallot •Coartaction of aorta •Ductus arteriosus apertus • https://www.wikiskripta.eu/images/2/2d/Defekt_koarktace.png https://www.wikiskripta.eu/images/5/5c/Defekt_fallot.png https://www.wikiskripta.eu/images/1/11/Defekt_pda.png https://www.wikiskripta.eu/images/2/2e/Defekt_septum_sinove.png https://www.wikiskripta.eu/images/f/f7/Defekt_septum_komorove.png Every step in CVS morphogenesis can go wrong. Výsledek obrázku pro primitive blood circulation Výsledek obrázku pro fetal blood circulation Fetal circulation Embryonic circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM Very important slide I Image result for blood circulation Image result for blood circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM Very important slide II Thank you for attention