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Dr. THAAER MOHAMMED DAHER ALSAAD SPECIALIST IN GENERAL SURGERY M.B.Ch.B. (MBBS) F.I.B.M.S. (PhD) SENIOR LECTURER ISM MSU
Cardiovascular System
Heart development
The cells reside in the splanchnic layer of the lateral plate mesoderm, they are induced by the underlying
dorsal aortae
removal of the amnion. Prospective myoblasts and hemangioblasts reside in the splanchnic mesoderm in front of the neural plate and on each side of the embryo.
Transverse section to show the position of the blood islands in the splanchnic mesoderm layer.
Cephalocaudal section through a similarstaged embryo showing the position of the pericardial cavity and cardiogenic field.
Formation and Position of the Heart Tube 2/4 As a result, the crescent part of the horseshoe-shaped area expands to form the future outflow tract and ventricular regions. Thus, the heart becomes a continuous expanded tube consisting of an inner endothelial lining and an outer myocardial layer. It receives venous drainage at its caudal pole and begins to pump blood out of the first aortic arch into the dorsal aorta at its cranial pole. The developing heart tube bulges more and more into the pericardial cavity. Initially, the tube remains attached to the dorsal side of the pericardial cavity by a fold of mesodermal tissue, the dorsal mesocardium.
The dorsal mesocardium disappears, creating the transverse pericardial sinus, which connects both sides of the pericardial cavity. The heart is now suspended in the cavity by blood vessels at its cranial and caudal poles. During these events, the myocardium thickens and secretes a thick layer of extracellular matrix, rich in hyaluronic acid, that separates it from the endothelium. In addition, mesothelial cells from the region of the sinus venosus migrate over the heart to form the epicardium.
This outer layer is responsible for formation of the coronary arteries, including their endothelial lining and smooth muscle.
The head folds (HF) are expanding and curving over the heart (H) and pericardial cavity (asterisk). The intestinal opening (arrow) of the gut into the primitive pharynx and the endoderm (E ) of the open region of the gut tube are shown.
Figures showing effects of the rapid growth of the brain on positioning of the heart.
20 days
The following shows Transverse sections through embryos at different stages of development, showing formation of a single heart tube from paired primordia.
Cephalic end of an early somite embryo. The developing endocardial heart tube and its investing layer bulge into the pericardial cavity. The dorsal mesocardium is breaking down
Frontal section through the heart of a 30-day embryo showing the primary interventricular foramen and entrance of the atrium into the primitive left ventricle. Note the bulboventricular flange. Arrows, direction of blood flow.
1/4
The heart tube continues to elongate and bend on day 23. The cephalic portion of the tube bends ventrally, caudally, and to the right.
The atrial (caudal) portion shifts dorsocranially and to the left . This bending, creates the cardiac loop. It is complete by day 28. While the cardiac loop is forming, local expansions become visible throughout the length of the tube.
The atrial portion, initially a paired structure outside the pericardial cavity, forms a common atrium and is incorporated into the pericardial cavity. The atrioventricular junction remains narrow and forms the atrioventricular canal, Atrioventricular canal connects the common atrium and the early embryonic ventricle.
Scanning electron micrograph of a mouse embryo equivalent to 19 days in the human, showing coalescence of the blood islands by vasculogenesis into a horseshoeshaped heart tube (arrows) lying in the primitive pericardial cavity under the cranial neural folds (asterisks).
Scanning electron micrograph of a mouse embryo at a stage similar to that shown in the diagram.
The head folds (HF) are expanding and curving over the heart (H) and pericardial cavity (asterisk). The intestinal opening (arrow) of the gut into the primitive pharynx and the endoderm (E ) of the open region of the gut tube are shown.
The heart tube (arrows) is horseshoe shaped in the pericardial cavity beneath the neural folds (stars)
11.4
The crescent portion of the horseshoe expands to form the ventricular and outflow tract regions, while lateral folding brings the caudal (venous) poles of the horseshoe together
Fusion of the caudal regions is complete, leaving the caudal poles embedded in the septum transversum (arrowheads). Cardiac looping has also been initiated. Asterisk, pericardial cavity; large arrow, anterior intestinal portal.
Heart induction. BMPs secreted in the posterior portion of the primitive streak and periphery of the embryo, in combination with inhibition of WNT expression by crescent in the anterior half of the embryo, induce expression of NKX2.5 in the heart forming region of the lateral plate mesoderm (splanchnic layer). NKX2.5 is then responsible for heart induction.
atrium is wide.
This shift is caused primarily by left-to-right shunts of blood, which occur in the venous system during the fourth and fifth weeks of development.
Broken line, the entrance of the sinus venosus into atrial cavity
24 days
ACV, anterior cardinal vein; PCV, posterior cardinal vein; UV, umbilical vein; VIT V, vitelline vein; CCV, common cardinal vein
24 days
35 days
35 days
5 weeks
fetal stage
5 weeks
fetal stage
The crista terminalis forms the dividing line between the original trabeculated part of the right atrium and the smooth-walled part (sinus venarum), which originates from the right sinus horn.
Scanning electron micrograph of a similarstaged mouse heart showing initial formation of the septum primum; septum spurium is not visible. Note the atrioventricular canal (arrow
High magnification of the interatrial septum (arrows) of a mouse embryo. The foramen ovale is not visible.
A and B. Septum formation by two actively growing ridges that approach each other until they fuse
endocardial cushions.
If, for example, a narrow strip of tissue in the wall of the atrium or ventricle should fail to grow while areas on each side of it expand rapidly, a narrow ridge forms between the two expanding portions. When growth of the expanding portions continues on either side of the narrow portion, the two walls approach each other and eventually merge, forming a septum. Such a septum never completely divides the original lumen but leaves a narrow communicating canal between the two expanded sections. It is usually closed secondarily by tissue contributed by neighboring proliferating tissues. Such a septum partially divides the atria and ventricles.
CLINICAL CORRELATES
Because of their key location, abnormalities in endocardial cushion formation contribute to many cardiac malformations, including atrial and ventricular septal defects and defects involving the great vessels (i.e., transposition of the great vessels and tetralogy of Fallot). Since cells populating the conotruncal cushions include neural crest cells and since crest cells also contribute extensively to development of the head and neck, abnormalities in these cells, produced by teratogenic agents or genetic causes, often produce both heart and craniofacial defects in the same individual.
1/3
At the end of the fourth week, a sickle-shaped crest grows from the roof of the common atrium into the lumen. This crest is the first portion of the septum primum. The two limbs of this septum extend toward the endocardial cushions in the atrioventricular canal. The opening between the lower rim of the septum primum and the endocardial cushions is the ostium primum. With further development, extensions of the superior and inferior endocardial cushions grow along the edge of the septum primum, closing the ostium primum. Before closure is complete, however, cell death produces perforations in the upper portion of the septum primum. Coalescence of these perforations forms the ostium secundum, ensuring free blood flow from the right to the left primitive atrium.
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When the upper part of the septum primum gradually disappears, the remaining part becomes the valve of the oval foramen. The passage between the two atrial cavities consists of an obliquely elongated cleft through which blood from the right atrium flows to the left side. After birth, when lung circulation begins and pressure in the left atrium increases, the valve of the oval foramen is pressed against the septum secundum, obliterating the oval foramen and separating the right and left atria. In about 20% of cases, fusion of the septum primum and septum secundum is incomplete, and a narrow oblique cleft remains between the two atria. This condition is called probe patency of the oval foramen; it does not allow intracardiac shunting of blood.
30 days (6 mm).
30 days (6 mm).
33 days (9 mm)
33 days (9 mm)
Newborn
The atrial septum from the right; same stage as previous picture.
Coronal sections through the heart to show development of the smooth walled portions of the right and left atrium. Both the wall of the right sinus horn (blue) and the pulmonary veins (red) are incorporated into the heart to form the smoothwalled parts of the atria.
The superior and inferior cushions, in the meantime, project further into the lumen and fuse,
resulting in a complete division of the canal into right and left atrioventricular orifices by the end of the fifth week.
Lateral cushion
Frontal section through the heart of a day 35 embryo. At this stage of development blood from the atrial cavity enters the primitive left ventricle as well as the primitive right ventricle.
Pulmonary channel
Right superior truncus swelling
IV Aortic sac
Aortic arches
Atrioventricular Valves
Formation of the atrioventricular valves and chordae tendineae. The valves are hollowed out from the ventricular side but remain attached to the ventricular wall by the chordae tendineae.
Atrioventricular Valves
After the atrioventricular endocardial cushions fuse, each atrioventricular orifice is surrounded by local proliferations of mesenchymal tissue. When the bloodstream hollows out and thins tissue on the ventricular surface of these proliferations, valves form and remain attached to the ventricular wall by muscular cords. Finally, 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. In this manner two valve leaflets, constituting the bicuspid, or mitral, valve, form in the left atrioventricular canal, and three, constituting the tricuspid valve, form on the right side.
CLINICAL CORRELATES
Heart Defects Heart and vascular abnormalities make up the largest category of human birth defects, accounting for 1% of malformations among live-born infants. The incidence among stillborns is 10 times as high. It is estimated that 8% of cardiac malformations are due to genetic factors, 2% are due to environmental agents, and most are due to a complex interplay between genetic and environmental influences (multifactorial causes). Classic examples of cardiovacular teratogens include rubella virus and thalidomide. Others include isotretinoin (vitamin A), alcohol, and many other compounds. Maternal diseases, such as insulin-dependent diabetes and hypertension, have also been linked to cardiac defects. Chromosomal abnormalities are associated with heart malformations, with 6 to 10% of newborns with cardiac defects having an unbalanced chromosomal abnormality.
Common atrium, or cor triloculare biventriculare, resulting from complete failure of the septum primum and septum secundum to form
CLINICAL CORRELATES
Furthermore, 33% of children with chromosomal abnormalities have a congenital heart defect, with an incidence of nearly 100% in children with trisomy 18. Finally, cardiac malformations are associated with a number of genetic syndromes, including craniofacial abnormalities, such as DiGeorge, Goldenhar, and Down syndromes.
CLINICAL CORRELATES
Genes regulating cardiac development are being identified and mapped and mutations that result in heart defects are being discovered.
Heart-hand syndromes (Holt-Oram syndrome). Atrial septal defect (ASD). cortriloculare biventriculare. premature closure of the oval foramen. persistent atrioventricular canal. ostium primum defect. Tricuspid atresia
CLINICAL CORRELATES
Tricuspid atresia is always associated with
(a) patency of the oval foramen, (b) ventricular septal defect, (c) underdevelopment of the right ventricle, (d) hypertrophy of the left ventricle.
A. Normal heart.
B. Tricuspid atresia. Note the small right ventricle and the large left ventricle.
A. Persistent common atrioventricular canal. This abnormality is always accompanied by a septum defect in the atrial as well as in the ventricular portion of the cardiac partitions.
D and E. Ostium primum defect caused by incomplete fusion of the atrioventricular endocardial cushions.
During the fifth week, pairs of opposing ridges appear in the truncus. These ridges, the truncus swellings, or cushions, lie on the right superior wall (rightsuperior truncus swelling) and on the left inferior wall (left inferior truncus swelling) (Fig. 11.17). The right superior truncus swelling grows distally and to the left, and the left inferior truncus swelling grows distally and to the right. Hence, while growing toward the aortic sac, the swellings twist around each other, foreshadowing the spiral course of the future septum (Figs. 11.22 and 11.23). After complete fusion, the ridges form the aorticopulmonary septum, dividing the truncus into an aortic and a pulmonary channel.
Frontal section through the heart of a 30-day embryo showing the primary interventricular foramen and entrance of the atrium into the primitive left ventricle. Note the bulboventricular flange. Arrows, direction of blood flow.
Frontal section through the heart of a 7week embryo. Note the conus septum and position of the pulmonary valves
Frontal section through the heart of an embryo at the end of the seventh week. The conus septum is complete, and blood from the left ventricle enters the aorta. Note the septum in the atrial region
Semilunar Valves
When partitioning of the truncus is almost complete, primordia of the semilunar valves become visible as small tubercles found on the main truncus swellings. One of each pair is assigned to the pulmonary and aortic channels, respectively A third tubercle appears in both channels opposite the fused truncus swellings. Gradually the tubercles hollow out at their upper surface, forming the semilunar valves. Recent evidence shows that neural crest cells contribute to formation of these valves.
6th week
7th week
9th week
CLINICALCORRELATES
Ventricular septal defect (VSD). Tetralogy of Fallot.
(a) a narrow right ventricular outflow region, a pulmonary infundibular stenosis. (b) a large defect of the interventricular septum; (c) an overriding aorta that arises directly above the septal defect; (d) hypertrophy of the right ventricular wall because of higher pressure on the right side..
Ectopia cordis. Persistent truncus arteriosus. Transposition of the great vessels. Valvular stenosis;
aortic valvular stenosis /atresia.
Normal heart.
Isolated defect in the membranous portion of the interventricular septum. Blood from the left ventricle flows to the right through the interventricular foramen (arrows).
Tetralogy of Fallot.
Tetralogy of Fallot. A. Surface view. B. The four components of the defect: pulmonary stenosis, overriding aorta, interventricular septal defect, and hypertrophy of the right ventricle.
Blood from the left ventricle flows to the right through the interventricular foramen (arrows).
A. Normal heart.
The only access route to the lungs is by way of a patent ductus arteriosus.
Arrow in the arch of the aorta indicates direction of blood flow. The coronary arteries are supplied by this retroflux. Note the small left ventricle and the large right ventricle. Patent ductus arteriosus
(a) cells in the left wall of the sinus venosus, (b) cells from the atrioventricular canal.
Once the sinus venosus is incorporated into the right atrium, these cells lie in their final position at the base of the interatrial septum.
Vascular Development
NEXT LECTURE
19 days
19-20 days
20 days
21 days
22days
23-29 days
23-29 days
30 days
5th week
5th week
7th week-neonatal
7th week-neonatal
7th week-neonatal
7th week-neonatal
Main intraembryonic and extraembryonic arteries (red) and veins (blue) in a 4-mm embryo (end of the fourth week). Only the vessels on the left side of the embryo are shown