Development of the Neonatal Gastrointestinal Tract

The Beginning

During gestation, the alimentary canal can be simply considered as the folding of endoderm and splanchnic mesoderm into a tube at the end of week 3 and the beginning of week 4. As the head fold forms, the cranial part of the yolk sac becomes enclosed within the embryo and becomes the foregut. Shortly thereafter, the caudal portion of the yolk sac becomes enclosed and forms the hindgut. The midgut resides between the foregut and the hindgut, near the yolk sac, which remains outside the embryo. The midgut remains in communication with the yolk sac until the yolk stalk closes during the 10th week of gestation. Initially the digestive tube ends blindly—cranially at the oropharyngeal membrane and caudally at the cloacal membrane. These membranes, made up of endoderm and ectoderm, break down, with the oropharyngeal going first at the start of week 4 followed by the cloacal at the start of week 6.

Esophagus

The esophagus serves as a complex conduit between mouth and stomach and, at the gastroesophageal junction, functions to avoid reflux of stomach contents back up the esophagus. Although this task sounds simple, the esophagus performs its roles so well that no esophageal replacement has been found that does anywhere near as good a job. All efforts are made to keep a native esophagus, even a severely compromised one, rather than go with any replacement.

The fully developed esophagus extends from the pharynx and cricopharyngeal sphincter in the neck to the lower esophageal sphincter and gastroesophageal junction in the abdomen. The blood supply to the esophagus is segmental, which is a key concept to understand for surgical planning. The upper esophagus is supplied by branches descending from the inferior thyroid artery. The middle and lower thirds of the esophagus are supplied by branches arising directly from the bronchial vessels or the descending thoracic aorta. The abdominal and lower esophagus also receive blood supply from the left gastric and inferior phrenic arteries. The full-term newborn esophagus is 10 cm in length and up to 40 cm in adulthood. There are four areas of natural anatomic constriction of the esophagus: (1) at the level of the cricopharyngeal sphincter, (2) as the aortic arch crosses anteriorly, (3) as the left main stem bronchus crosses anteriorly, and (4) at the level of the lower esophageal sphincter. Foreign bodies in the esophagus tend to lodge at one of these areas of constriction, and burns from caustic ingestion tend to be more severe in these regions.

The esophagus is differentiated from the primitive foregut during the 4th week of gestation. A tracheoesophageal septum is evident at this time, initiating the division of the trachea anteriorly from the foregut posteriorly. The septum remains at about the same level in the fetus while the body grows cranially. This leads to elongation of the esophagus, primarily from “ascent” of the pharynx rather than “descent” of the stomach. It reaches its full length, relative to the size of the developing fetus, during the 7th week of gestation. Aberrations during this phase of development result in esophageal atresia and tracheoesophageal fistulas.

The muscular wall of the esophagus is similar to that of the rest of the GI tract, with an outer longitudinal layer and a circular inner layer. The more highly developed longitudinal layer forms during the 9th week of gestation, whereas the circular layer forms during the 6th week. There is no serosa on the esophagus except in the short abdominal portion. This is clinically important when considering the resection or repair of the esophagus.

The epithelial lining of the esophagus is derived from the primitive endoderm. At the 10th week of gestation, this is ciliated, but a stratified, nonkeratinizing, squamous epithelium begins replacing the ciliated epithelium at about the fourth month of gestation. Some ciliated epithelium along the length of the esophagus may persist until birth. The striated muscle of the upper third arises from mesoderm of the branchial arches, whereas the smooth muscle of the distal two-thirds is derived from splanchnic mesenchyme. Therefore diseases of smooth muscle tend to affect the lower esophagus only.

Small glands of mucus- and bicarbonate-secreting cells with ducts opening onto the surface of the epithelium are scattered throughout the length of the esophagus, particularly in the lower third.

By 8 weeks’ gestation, immature neurons are identifiable within the wall of the esophagus. These nerves are derived from both parasympathetic and sympathetic fibers. The cervical sympathetic trunks send fibers along the inferior thyroid artery to the upper third of the esophagus, whereas the middle and lower thirds are supplied by branches from the greater splanchnic nerves. The thoracic esophagus is supplied by branches of the esophageal vagal plexus, arising directly from the vagus trunks in the chest.

The act of swallowing is initiated by impulses from the swallowing center, an area in the reticular formation of the rostral medulla where the nuclei of cranial nerves IX and X are located. The initial event in esophageal peristalsis is stimulation of the longitudinal muscle layer, which is followed by the segmental activation of the circular muscle and relaxation of the lower esophageal sphincter. The peristaltic wave begins in the pharynx and continues through to the gastroesophageal junction without interruption. Whereas primary waves are initiated from the swallowing center, secondary peristalsis is mediated by local intramural pathways to return refluxed material in the lower esophagus to the stomach.

The upper esophageal sphincter corresponds to the cricopharyngeal muscle. There is no morphologic distinction in the muscular wall of the lower esophagus that would identify this sphincter, although clearly one functionally exists. The primary role of this sphincter is to prevent the reflux of gastric contents back into the lower esophagus. The lower esophageal sphincter relaxes as the primary peristaltic wave traverses the esophageal body, and it remains open until the peristaltic wave enters the sphincter and closes it. Disordered lower esophageal sphincter function is thought to be one of the mechanisms for pathologic gastroesophageal reflux.