The vascular system appears in the middle of the third week,

The entire cardiovascular system,heart,blood vessels,and blood cell,originates from the mesodermal germ layer.
Cardiac progenitor cells lie in the epiblast,( immediately lateral to the 1 primitive streak.)
.

cardiogenic field
By the union of blood islands units and form a tube surrounded by myoblasts. later develops into the pericardial cavity As a result of cephalic folding the heart and pericardial cavity move first to the cervical region and finally to the thorax.

Although initially paired, tubes formed, by the 22nd day of development, the two tubes fuses and form a single, slightly bent heart tube consisting of an 1. inner endocardial tube 2. and a surrounding myocardial mantle.
3

the tube remains attached by the dorsal mesocardium With further development it 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 the heart tube consists of three layers: (a) the endocardium, (b) the myocardium, (c) the epicardium or visceral pericardium This outer layer is responsible for formation of the coronary arteries
4

The caudal end will form atrial structures by high concentrations of retinoic acid (RA). During these events, the myocardium thickens and separates from the endothelium Epicardium: is derived from mesothelial cells 1-cells on the septum transversum form most of the epicardium.

2-The remainder cells originating in the outflow tract region.

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 Bulbus Cordis
refers to the outflow tract in early embryo 3 parts 1) distal - forms truncus arteriosus (aorta and pulmonary artery) 2) middle - conus arteriosus ventricular outflow tract 3) proximal - right ventricle trabeculate part 6

cardiac loop
The heart tube continues to elongate and bend

on day 23.
The cephalic portion of the tube bends ventrocaudally, and to the right and the atrial (caudal) portion shifts dorsocranially and to the left This bending, which may be due to cell shape changes, creates the cardiac loop.

It is complete by day 28.

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During the 4th to 7th weeks,

the heart undergoes looping followed by septation into a typical four chambered structure

Clinical Correlates
Abnormalities of Cardiac Looping
Dextrocardia, in which the heart lies on the right side because the heart loops to the left instead of the right. Dextrocardia may coincide with situs inversus, a complete reversal of asymmetry in all organs. Situs inversus, 1. which occurs in 1/7,000 individuals, usually is associated with normal physiology& a slight risk of heart defects. In other cases, sidedness is random, such that some organs are reversed and others are not; this is heterotaxy. These cases are 9 classified as laterality sequences.

laterality sequences
laterality sequences.
1. Patients with these conditions appear to be predominantly left-sided bilaterally or right-sided bilaterally. The spleen reflects the differences: those with left-sided bilaterality have polysplenia; those with right-sided bilaterality have asplenia or hypoplastic spleen. They have increased incidences of other malformations, especially heart defects. Genes regulating sidedness are expressed during gastrulation.
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2. 3. 4. 5.

DEVELOPMENT OF THE SINUS VENOSUS

In the middle of the 4th week, the sinus venosus receives venous blood from the right and left sinus horns

Each horn receives blood from three important veins: (a) the vitelline or omphalomesenter ic vein, (b) the umbilical vein, (c) the common 11 cardinal vein.

At first, communication between the sinus and the atrium is wide.

Soon, the entrance of the sinus shifts to the right
12 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

Septum formation in the heart in part arises from

1. development of endocardial cushion tissue in the atrioventricular canal (atrioventricular cushions) 2. and in the conotruncal region (conotruncal swellings ). 13

Septum Formation in the Atrium.

The septum primum, a sickle-shaped crest descending from the roof of the atrium, begins to divide the atrium into two but leaves a lumen, the ostium primum, for communication between the two sides Later, when the ostium primum is obliterated by fusion of the septum primum with the endocardial cushions, the ostium secundum is formed by cell death with an interatrial opening left, the oval foramen, which persists.

14

Only at birth, when pressure in the left atrium increases, do the two septa press against each other and close the communication between the two. Abnormalities in the atrial septum may vary from total absence to a small opening known as probe patency of the oval foramen

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Septum Formation in the Atrioventricular Canal.

Four endocardial cushions surround the atrioventricular canal. Fusion of the
opposing superior and inferior cushions divides the orifice into right and left atrioventricular canals. Cushion tissue then becomes fibrous and forms the mitral (bicuspid) valve on the left and the tricuspid valve on the right).

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Septum Formation in the Ventricles.

The interventricular septum consists of a thick muscular part and a thin membranous portion formed by (a) an inferior endocardial atrioventricular cushion, (b) the right conus swelling, and (c) the left conus swelling In many cases, these three components fail to fuse, resulting in an open interventricular foramen.

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Formation of the atrioventricular valves and chordae tendineae. The valves are hollowed out from the ventricular side but remain attached to the 19 ventricular wall by the chordae tendineae.

Clinical Correlates
Heart Defects
Heart and vascular abnormalities account for 1% of malformations among live-born infants. And itis 10 times higher among stillborns Causes: 1) 8% of cardiac malformations (genetic factors), 2) 2% (environmental agents), 3) mostly (genetic and environmental influences)= (multifactorial).
Classic examples of cardiovascular teratogens include 1) rubella virus 2) thalidomide. 3) retinoic acid 4) alcohol. 5) Maternal diabetes& or hypertension. 6) Chromosomal abnormalities 7) genetic syndromes, including craniofacial abnormalities, 20

E.g.: 1) DiGeorge syndrome. 2) Goldenhar syndrome. 3) Down syndrome.

Genes regulating cardiac development are being identified and mapped, and mutations that result in heart defects are being discovered.
Mutations in the TBX5 gene result
in 1) 2) 3) 4) 5)

Holt-Oram syndrome,characterized by
preaxial (radial) limb abnormalities atrial septal defects. Defects in the interventricular septum may also occur. .Holt-Oram syndrome is inherited as an autosomal dominant trait with a frequency of 1/100,000 live births.

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hypertrophic cardiomyopathy
1) Mutations in a number of genes regulating production of sarcomere proteins 2) result in sudden death in athletes&general population. 3) autosomal dominant

Atrial septal defect (ASD)

A. B. C. D. i. ii. iii. is a congenital heart abnormality with an incidence of 6.4/10,000 births 2:1 prevalence in female to male infants caused by excessive resorption of the septum primum. failure of development of the septum secundum. complete failure of the septum primum and septum secundum to form.

Figure 12.19 A. Normal atrial septum formation. B,C. Ostium secundum defect caused by excessive resorption of the septum primum. D,E. Similar defect caused by failure of development of the septum secundum. 23 F. Common atrium, or cor triloculare biventriculare, resulting from complete failure of the septum primum and septum secundum to form.

 Tricuspid atresia, involves obliteration of

the right atrioventricular orifice characterized by the absence or fusion of the tricuspid valves. Tricuspid atresia is always associated with (a) patency of the oval foramen, (b) ventricular septal defect, (c) underdevelopment of the right ventricle, and (d) hypertrophy of the left ventricle
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Septum Formation in the Bulbus. The truncus region is divided by the spiral aorticopulmonary septum into the two main arteries The conus swellings +the inferior endocardial cushion, close the interventricular foramen. Many vascular abnormalities, such as 1) transposition of the great vessels 2) pulmonary valvular atresia, result from abnormal division of the conotruncal region;

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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. B. Valves in the atrioventricular orifices under normal conditions. C. Split valves in a persistent atrioventricular canal. D,E. Ostium primum defect caused by incomplete fusion of the atrioventricular 26 endocardial cushions

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