Material

esophagus, vacuoles, lumen, cells and nuclei

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At the 16-day stage of development the esophagus is closed for approximately 1.5 mm. At the most anterior point of occlusion the pharynx is wide and somewhat crescentic, with the concavity directed ventrally. The occluded area at this level occupies only the smaller medial portion of the wide pharynx at the point where it passes into the esophagus. The larynx at this level has an oval, slit-like lumen, compressed laterally and lined with a pseudo-stratified columnar epithelium containing 2 to 4 rows of oval nuclei, many of which cen trally are in mitosis. The pharynx is lined with columnar epithelium (apparently pseudo-stratified) with 3 rows of nuclei, oval in shape peripherally and centrally. At the most cephalic point of the closure the pharynx remains widely open laterally. Only a few mitotic figures appear among these cells. In the median fused area the central cells are of irregular shape, with spheroidal nuclei, and form a mesenchyme-like syncytium. At this stage the glottis is closed for a short distance, due probably to the pressure exerted upon this por tion of the tube by the surrounding mesenchyme in the process of final cephalic division of this portion of the fore-gut into esophagus and trachea. The fusion of the lateral walls of the larnyx and the conse quent obliteration of the lumen are probably due in part also to the arytenoid swellings just appearing in this region.

Vacuoles first appear, either singly or in groups, centrally and later ally. These are the areas where the fusion-reticulum is originally less dense, because here the original lumen persisted longest. As the vacuoles form, the nuclei of the syncytium become disposed in the manner of an epithelium around these spaces, as if rearranged under pressure from within the vacuoles. The original smaller vacuoles grow in size and coalesce with adjacent vacuoles. Only very rarely is a mitotic figure seen among the central cells. Mitosis is slight at this stage, also among the peripheral cells. An extremely small, practically negligible, amount of cell-degeneration occurs among the central cells. The vacuoles tend to become confluent in a lateral direction; they are apparently empty and contain no coagulum in stained sections. Their spheroidal shape and the manner of the arrangement of the enveloping cells leave no room for doubt, however, that they were formed, at least in large part, under the influence of a fluid pressure.

In the 25-day embryo the vacuoles are larger and more numerous, and they increase in number and size caudally, where a fenestrated condition of the atretic lumen has become established.

Coincident with this fenestration, the enveloping mesenchyme (tela submucosa) of the esophagus has become looser and more vascu lar, thus permitting more readily an expansion of the tube under the pressure produced internally during the formation of the vacuoles.

This expansion is assisted also no doubt by the growth, as indicated by extensive mitotic activity, of the peripheral portion of the wall, and possibly in part also by external traction exerted by the growing mesenchyme.

At the 32-day stage the lumen of the esophagus is in the fenestrated condition throughout its greater extent, only the most cephalic por tion remaining practically solid. The lumen appears to be spanned across by delicate nucleated septa with lateral anastomoses. Where the septa join the main wall of the lumen they spread into triangular multinucleated bases. There is no sign of degeneration among the nuclei of these septa—in fact, a number of the nuclei may be in process of either mitotic or amitotic division. The trabecuhe are subse quently simply drawn into the peripheral portions of the wall and grad ually incorporated among the entodermal cells of the lining epithelium.

Discussion.

A complete discussion of the phenomenon of esophageal atresia here described must take into special consideration the following facts: (1) The inception of the atresia at the 12-day stage is coincident with the early stages of the formation of the respiratory anlages.

(2) The initial point of stenosis is spatially very closely related to the orifice of the developing laryngo-tracheal tube.

(3) The transient solidification of the esophagus progresses in a caudal direction, while the reestablishment of patency progresses in the opposite direction.

(4) The early stenosis of the esophagus, from the eleventh to the twelfth day, results largely from an alteration in the shape of the esophagus, from a tube approximately circular in cross-section to one flattened dorso-ventrally into a rectangular structure with at first a slit-like lumen and later a minute central circular aperture; the stenosis becomes an atresia at the thirteenth day through a fusion of the dorsal and ventral walls, the cells involved becoming converted into a mesen chyme-like syncytium; this process is assisted by the increase in the number of cell-layers dorsally, where mitotic activity is extensive; the factors involved in the change of shape of the esophagus are largely mechanical, incidental to inherent and extraneous tissue growth, the chief element in forcing the growth of the esophageal tube into an adaptive rectangular form being most probably the denser bilateral mesenchymal plates by whose medial approximation and fusion the original esophageo-respiratory anlage becomes converted into the esophageal and tracheal tubes.

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