Septation of the respiratory and digestive tracts in human embryos: crucial role of the tracheoesophageal sulcus.

Abstract

Esophageal atresia and tracheoesophageal fistula, common malformations of the respiratory and digestive tracts, are of unsettled pathogenesis. Part of the difficulty in understanding these abnormalities arises from the uncertainties about the normal developmental processes in the region. This study examined the development and fate of the tracheoesophageal septum. Normal human embryos from the Carnegie Embryological Collection and fetuses from the Hopkins Pathology Collection were examined, and reconstructions of selected specimens were made from photomicrographs of serial histologic sections. The results show that the lung bud appears in Carnegie stage 12, rapidly enlarges, and bends caudally, thereby producing a sulcus between the foregut and the respiratory system on its caudal aspect. The cranial aspect of this tracheoesophageal sulcus remains fixed at the levels of the first cervical vertebra throughout subsequent embryonic and fetal development. At the same time the trachea and esophagus elongate to bring those part of the respiratory and digestive systems into their definitive anatomic positions. Examination of the tracheoesophageal sulcus shows that its growth-limiting properties may be explained by its catenoidal configuration. Catenoidal, or saddle-shape, sulci have been shown to have similar regional growth-limiting properties in the embryonic heart. These regions contrast with outwardly convex regions in both the developing heart and lung where growth of the tissues occurs. The observations made here suggest that the origin of the tracheoesophageal malformations must be sought in a configurational abnormality in the area of the developing lung bud in Carnegie stage 12.