and left sides of the embryo by the expression of critical signaling molecules (tumor growthfactor-
family of peptide growth factors and signaling peptides such as Sonic hedgehog). Inmurine models of abnormal looping, one such defect resides in the dynein gene.
420.3 Cardiac Septation
When looping is complete, the external appearance of the heart is similar to that of a matureheart; internally, the structure resembles a single tube, although it now has several bulgesresulting in the appearance of primitive chambers. The common atrium (comprising both the rightand left atria) is connected to the primitive ventricle (future left ventricle) via the atrioventricular canal. The primitive ventricle is connected to the bulbus cordis (future right ventricle) via thebulboventricular foramen. The distal portion of the bulbus cordis is connected to the truncusarteriosus via an outlet segment (the conus).The heart tube now consists of several layers of myocardium and a single layer of endocardiumseparated by cardiac jelly, an acellular extracellular matrix secreted by the myocardium.Septation of the heart begins at approximately day 26 with the ingrowth of large tissue masses,the endocardial cushions, at both the atrioventricular and conotruncal junctions (see Fig. 420-1 ).These cushions consist of protrusions of cardiac jelly, which, in addition to their role indevelopment, also serve a physiologic function as primitive heart valves. Endocardial cellsdedifferentiate and migrate into the cardiac jelly in the region of the endocardial cushions,eventually becoming mesenchymal cells that will form part of the atrioventricular valves.Complete septation of the atrioventricular canal occurs with fusion of the endocardial cushions.Most of the atrioventricular valve tissue is derived from the ventricular myocardium in a processinvolving undermining of the ventricular walls. Because this process occurs asymmetrically, thetricuspid valve annulus sits closer to the apex of the heart than the mitral valve annulus does.Physical separation of these two valves produces the atrioventricular septum, the absence of which is the primary common defect in patients with
atrioventricular canal defects
(see Chapter 426.5 ). If the process of undermining is incomplete, one of the atrioventricular valves may notseparate normally from the ventricular myocardium, a possible cause of
(seeChapter 430.7 ).Septation of the atria begins at
30 days with growth of the septum primum downward toward theendocardial cushions (see Fig. 420-1 ). The orifice that remains is the ostium primum. Theendocardial cushions then fuse and, together with the completed septum primum, divide theatrioventricular canal into right and left segments. A 2nd opening appears in the posterior portionof the septum primum, the ostium secundum, and it allows a portion of the fetal venous return tothe right atrium to pass across to the left atrium. Finally, the septum secundum grows downward, just to the right of the septum primum. Together with a flap of the septum primum, the ostiumsecundum forms the foramen ovale, through which fetal blood passes from the inferior vena cavato the left atrium (see Chapter 421 ).Septation of the ventricles begins at about embryonic day 25 with protrusions of endocardium inboth the inlet (primitive ventricle) and outlet (bulbus cordis) segments of the heart. The inletprotrusions fuse into the bulboventricular septum and extend posteriorly toward the inferior endocardial cushion, where they give rise to the inlet and trabecular portions of theinterventricular septum. Ventricular septal defects can occur in any portion of the developinginterventricular septum (see Chapter 426.6 ). The outlet or conotruncal septum develops fromridges of cardiac jelly, similar to the atrioventricular cushions. These ridges fuse to form a spiralseptum that brings the future pulmonary artery into communication with the anterior andrightward right ventricle and the future aorta into communication with the posterior and leftwardleft ventricle. Differences in cell growth of the outlet septum lead to lengthening of the segment of smooth muscle beneath the pulmonary valve (conus), a process that separates the tricuspid andpulmonary valves. In contrast, disappearance of the segment beneath the aortic valve leads tofibrous continuity of the mitral and aortic valves. Defects in these processes are responsible for
aortic arch defects
(truncus arteriosus, tetralogy of Fallot, pulmonary atresia,double-outlet right ventricle, interrupted aortic arch), a group of cardiac anomalies oftenassociated with deletions of the DiGeorge critical region of chromosome 22q11 (see Chapters
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