DEVELOPMENT OF CARDIOVASCULAR SYSTEM Petr Vaňhara https://www.reddit.com 10.1038/s41586-020-2797-4 10.1038/s41598-018-28715-0 Endocardium Myocardium Epicardium Septum RA LV BLOOD CIRCULATION DEVELOPMENT OF CARDIOVASCULAR SYSTEM Fully functional heart with four chambers Fitst morphological hallmarks of developing heart First activity of heart cells Tubular heart Week 2-3 BILAMINAR GERM DISCDEVELOPMENT OF CARDIOVASCULAR SYSTEM 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 Week 2-3 VASCULOGENESIS AND ANGIOGENESIS Differentiation from undifferentiated precursors (mesoderm- hemangioblasts) Growth from existing vessels DEVELOPMENT OF CARDIOVASCULAR SYSTEM Development of heart and the first embryonic vasculature DEVELOPMENT OF HEART • embryonic vasculogenesis approx. 2 days later after establishment of extra-embryonic vessels • primordial blood vessels • heart primordium in cardiogenic area → endocardial tubes • embryonic hematopoiesis from para-aortic clusters in AGM End of week 3 DEVELOPMENT OF HEART Week 3 DEVELOPMENT OF HEART Week 3 • paired endocardial 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 Development of primitive heart DEVELOPMENT OF HEART Week 4 • simple-tubular heart (cor tubulare simplex and cor tubulare sigmoideum ) • sinus venosus → atrium → ventriculus → bulbus cordis→ truncus arteriosus venous end arterial end cor tubulare simplex cor tubulare sigmoideum Paired dorsal aorta Truncus arterosus Bulbus cordis Ventriculus Paired atrium and sinus venosus Right auricle Left auricle Aorta Ventricle Sternocostal surface DEVELOPMENT OF HEART Cor tubulare simplex Cor tubulare sigmoideum Week 4 tubular heart is indeed a real structure DEVELOPMENT OF HEART DEVELOPMENT OF HEART Week 4 DEVELOPMENT OF HEART • 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 Partitioning of atrium commune DEVELOPMENT OF HEART Septum secundum Septum primum Foramen secundum Foramen ovale 91 DEVELOPMENT OF HEART DEVELOPMENT OF HEART • sinus venosus during atrial septation: - shift of sinus venosus opening to the right → right atrium - left part sinus venosus is separated → sinus coronarius Sinus coronarius R atrium L atrium • septum interventriculorum primitivum – temporary • septum interventriculare at the end of week 4 – grows cranially • foramen interventricualre – closure linked to development of aortico-pulmonary septum • pars membranacea (septi interventricularis) • pars muscularis (septi interventricularis) - medial walls of both ventricles DEVELOPMENT OF HEART Partitioning of ventriculus communis • 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 HEART • Partitioning of bulbus cordis and truncus arteriosus • 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 HEART • Development of cardiac valves DEVELOPMENT OF HEART Definitive conductive heart system provides the electrical conduction between atria and ventricles • First all muscular layers are connected • Primitive atrium – primary pacemaker • SA node in 5th weeks develops from tissues of sinus venosus • Cells of interatrial and atrioventricular septa contribute to formation of AV node and fasciculus atrioventricualris → bundle branches → ventricular myocardium Development of conductive heart system DEVELOPMENT OF HEART Week 20 DEVELOPMENT OF VASCULATURE Week 4 1 2 3 • 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 • vitelline 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 VASCULATURE Week 4 DEVELOPMENT OF ARTERIES Arteries DEVELOPMENT OF ARTERIES Dorsal aorta • originally a paired structure - fusion into a single dorsal aorta → a. descendens • aortal arches Ventral aorta • originally a tempory paired structure • fusion into the aortic sac when embryo folds DEVELOPMENT OF ARTERIES Development of large arteries – aortic arches DEVELOPMENT OF ARTERIES 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 do not develop at all or quickly degenerates 6 right: from proximal part: proximal part of a. pulmonalis dextra, distal part disappears left: from proximal part: proximal part of a. pulmonalis sinistra, from distal part: ductus arteriosus. DEVELOPMENT OF ARTERIES Aortic arches Ramus laryngeus reccurens n. vagi Right: under a.subclavia dx. Left: under arcus aortae Right Left DEVELOPMENT OF ARTERIES Branches of dorsal aorta • intersegmental arteries (parietal, dorsal) a visceral (ventral, towards primitive gut) • between somites • vascularisation of somites and their derivatives • intersegmental arteries: • neck → a. vertebralis • chest → aa. intercostales • abdomen → aa. lumbales • sacral → aa. sacrales laterales • part of 7th intersegmental artery → a. subclavia dx. • caudal end of dorsal aorta → a. sacralis media • truncus coeliacus • a. mesenterica superior • a. mesenterica inferior DEVELOPMENT OF ARTERIES Intersegmental arteries • ventral branches of dorsal aorta • aa. vitellinae (aa. omphalomesentericae) reduced to three principal vessels: 1 truncus coeliacus 2 a. mesenterica superior 3 a. mesentrica inferior DEVELOPMENT OF ARTERIES Vitelline arteries • 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 ARTERIES Veins DEVELOPMENT OF VEINS DEVELOPMENT OF VEINS Cardinal veins • main venous system of embryo • v. cardinales anteriores et posteriores, → v. cardinales communes • paired v. cardinales anteriores • 8th week: anastomosis (L→R) - → v. brachiocephalica - caudal part of left v. card. ant. disappears - right v. card. ant. + v. card. commun.: SVC • paired v. cardinales posteriores - primary vessels of mesonephros - persists as branches of v. hemiazygos and v. azygos - replaced by subcardinal and supracardinal veins • paired v. subcardinales - anastomoses also to v. cardinales posteriores - left: v. renalis, v. suprarenales, gonad veins, part of IVC • paired v. supracardinales - cranial – anastomosis – v. azygos et v. hemiazygos - caudal left v. supracardinalis disappears, right – lower part of IVC (anastomosis to v. subcardinalis) DEVELOPMENT OF VEINS Cardinal veins and development of vena cava inferior • four principal segments 1 hepatic segment (proximal part of v. omphalomesenterica = v. hepatica) 2 prerenal segment (right v. subcardinalis) 3 renal segment (anastomosis between v. subcardinalis and v. supracardinalis 4 postrenal segment (right v. supracardinalis) Vena cava superior: right v. cardinalis communis and v. cardinalis anterior DEVELOPMENT OF VEINS 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 form posthepatic part of IVC • begin in chorionic villi • due to liver growth lose connection with sinus venosus • right v. umbilicalis disappears • distal part of left v. umbilicalis forms ductus venosus (ligamentum venosum post natally) Vv. umbilicales Fetal circulation Embryonic circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM DEVELOPMENT OF CARDIOVASCULAR SYSTEM Fetal circulation Postnatal circulation DEVELOPMENT OF CARDIOVASCULAR SYSTEM Derivatives of fetal vascular structures Umbilical vein → ligamentum teres From umbilicus to porta hepatis and left v. portae Lumen of l. teres might persist Ductus venosus → ligamentum venosum (through liver from left v. portae to IVC) Umbilical arteries → ligamenta umbilicalia medialia (most of intrabdominal part) and arterie vesicales superiores Foramen ovale → fossa ovalis Adhesion of septum primum (valvula foraminis ovalis) to left part of septum secundum Bottom of fossa ovalis – septum primum Lower part of septum secundum – limbus fossae ovalis (anulus ovalis) Ductus arteriosus → ligamentum arteriosum (from left pulmonary artery to arcus aortae Thank you for attention