Development of Esophagus

The esophagus elongates rapidly and reaches its final relative length by the seventh week. Its epithelium and glands are derived from the endoderm. The epithelium proliferates and partly or completely obliterates the esophageal lumen; however, recanalization normally occurs by the end of the eighth week. The striated muscle of the esophagus is derived from the mesenchyme in the fourth and sixth pharyngeal arches. The smooth muscle, mainly in the inferior third of the esophagus, develops from the surrounding splanchnic mesenchyme.

Development of Stomach

During the fourth week, a slight dilation of the tubelike foregut indicates the site of the primordial stomach. It first appears as a fusiform enlargement that is oriented in the median plane (Fig. 12-2). The primordial stomach enlarges and broadens ventrodorsally. Its dorsal border grows more quickly than its ventral border. This site of rapid growth demarcates the greater curvature of the stomach (Fig. 12-2D).

Rotation of Stomach

As the stomach enlarges, it rotates 90 degrees in a clockwise direction around its longitudinal axis. The effects of rotation on the stomach are as follows (Figs. 12-2 and 12-3):

• The ventral border (lesser curvature) moves to the right, and the dorsal border (greater curvature) moves to the left (Fig. 12-2C to F).

• Before rotation, the cranial and caudal ends of the stomach are in the median plane (Fig. 12-2B).

• During rotation and growth of the stomach, its cranial region moves to the left and slightly inferiorly, and its caudal region moves to the right and superiorly (Fig. 12-2C to E).

• After rotation, the stomach assumes its final position, with its long axis almost transverse to the long axis of the body (Fig. 12-2E). This rotation and growth explains why the left vagus nerve supplies the anterior wall of the adult stomach and the right vagus nerve innervates its posterior wall.

Figure 12–3 Illustrations of the development of the stomach and its mesenteries and the formation of the omental bursa. A, At 5 weeks. B, Transverse section showing clefts in the dorsal mesogastrium. C, Later stage, after coalescence of the clefts to form the omental bursa. D, Transverse section showing the initial appearance of the omental bursa. E, The dorsal mesentery has elongated and the omental bursa has enlarged. F and G, Transverse and sagittal sections, respectively, showing elongation of the dorsal mesogastrium and expansion of the omental bursa. H, At 6 weeks, showing the greater omentum and expansion of the omental bursa. I and J, Transverse and sagittal sections, respectively, showing the inferior recess of the omental bursa and the omental foramen. The arrows in E, F, and I, indicate the site of the omental foramen. In J, the arrow indicates the recess of the omental bursa.

Congenital Hypertrophic Pyloric Stenosis

Anomalies of the stomach are uncommon, except for hypertrophic pyloric stenosis, which affects 1 in 150 male infants and 1 in 750 female infants. Infants with this anomaly have marked muscular thickening of the pylorus of the stomach, the distal sphincteric region of the stomach. The muscles in the pyloric region are hypertrophied, which results in severe stenosis (narrowing) of the pyloric canal and obstruction to the passage of food. As a result, the stomach becomes markedly distended and its contents are expelled with considerable force (projectile vomiting). Surgical relief of the pyloric obstruction is the usual treatment.

Development of Duodenum

Early in the fourth week, the duodenum develops from the caudal part of the foregut and the cranial part of the midgut (Fig. 12-4A). The developing duodenum elongates, forming a C-shaped loop that projects ventrally (Fig. 12-4B to D). As the stomach rotates, the duodenal loop rotates to the right and lies retroperitoneally (external to peritoneum). Because of its derivation from the foregut and midgut, the duodenum is supplied by branches of both the celiac and the superior mesenteric arteries (Fig. 12-1). The lumen of the duodenum is temporarily obliterated because of the proliferation of its epithelial cells, but normally becomes recanalized by the end of the embryonic period.

Figure 12–4 Illustrations of progressive stages in the development of the duodenum, liver, pancreas, and extrahepatic biliary apparatus. A, At 4 weeks. B and C, At 5 weeks. D, At 6 weeks.

Duodenal Atresia

Complete occlusion of the duodenum—duodenal atresia—results from failure of reformation of the lumen (Fig. 12-5B). Most atresias involve the descending and horizontal parts of the duodenum and are located distal to the opening of the bile duct. In infants with duodenal atresia, vomiting begins within a few hours of birth. The vomitus almost always contains bile. Polyhydramnios also occurs because duodenal atresia prevents normal absorption of amniotic fluid by the intestines. A diagnosis of duodenal atresia is suggested by the presence of a “double-bubble sign” on plain radiographs or ultrasound scans. This sign is caused by a distended, gas-filled stomach and the proximal duodenum. Between 20% and 30% of affected infants have Down syndrome, and an additional 20% are premature.

Figure 12–5 Ultrasound scans of a fetus at 33 weeks gestation (31 weeks after fertilization), showing duodenal atresia. A, An oblique scan shows the dilated, fluid-filled stomach (St) entering the proximal duodenum (D), which is also enlarged because of the atresia (blockage) distal to it. B, Transverse ultrasound scan, showing the characteristic “double-bubble” appearance of the stomach and duodenum when there is duodenal atresia.

(Courtesy of Dr. Lyndon M. Hill, Magee-Women’s Hospital, Pittsburgh, PA.)

Development of Liver and Biliary Apparatus

The liver, gallbladder, and biliary duct system arise as a ventral outgrowth—hepatic diverticulum—from the caudal part of the foregut early in the fourth week (Figs. 12-4A and 12-6A). Wnt/β-catenin signaling is involved in the induction of the hepatic diverticulum. The hepatic diverticulum extends into the septum transversum (Fig. 12-6B), a mass of splanchnic mesoderm between the developing heart and the midgut. The diverticulum enlarges and divides into two parts as it grows between the layers of the ventral mesogastrium (Fig. 12-4A). The larger, cranial part of the diverticulum is the primordium of the liver, and the smaller caudal portion becomes the biliary apparatus. The proliferating endodermal cells give rise to interlacing cords of hepatocytes and to the epithelial lining of the intrahepatic part of the biliary apparatus. The hepatic cords anastomose around endothelium-lined spaces, the primordia of the hepatic sinusoids. The fibrous and hematopoietic tissue and Kupffer cells of the liver are derived from the mesenchyme in the septum transversum.

Figure 12–6 Illustrations of how the caudal part of the septum transversum becomes stretched and membranous as it forms the ventral mesentery. A, Median section of a 4-week embryo. B, Transverse section of the embryo, showing expansion of the peritoneal cavity (arrows). C, Sagittal section of a 5-week embryo. D, Transverse section of the embryo after formation of the dorsal and ventral mesenteries.

The liver grows rapidly and fills a large part of the abdominal cavity (Figs. 12-4 and Fig. 12-6C and D). Hematopoiesis (formation of various types of blood cells and other formed elements) begins in the liver during the sixth week. By the ninth week, the liver accounts for approximately 10% of the total weight of the fetus. Bile formation by the hepatic cells begins during the 12th week.

The caudal portion of the hepatic diverticulum becomes the gallbladder; the stalk forms the cystic duct (Fig. 12-4B and C). Initially, the extrahepatic biliary apparatus is occluded with epithelial cells. The stalk connecting the hepatic and cystic ducts to the duodenum becomes the bile duct, which attaches to the ventral aspect of the duodenal loop. As the duodenum grows and rotates, the entrance of the bile duct is carried to the dorsal aspect of the duodenum (Fig. 12-4C and D).

Ventral Mesentery

The double-layered ventral mesentery (Figs. 12-6C and D and 12-7) gives rise to two structures:

• The lesser omentum, which passes from the liver to the lesser curvature of the stomach (hepatogastric ligament) and from the liver to the duodenum (hepatoduodenal ligament)

• The falciform ligament, which extends from the liver to the ventral abdominal wall

Figure 12–7 Median section of the caudal half of an embryo at the end of the fifth week, showing the liver and its associated ligaments. The arrow indicates the communication of the peritoneal cavity with the extraembryonic coelom. Because of the rapid growth of the liver and the midgut loop, the abdominal cavity temporarily becomes too small to contain the developing intestines; consequently, they enter the extraembryonic coelom in the proximal part of the umbilical cord (see Fig. 12-11B).

The umbilical vein passes in the free border of the falciform ligament on its way from the umbilical cord to the liver. The ventral mesentery, derived from the mesogastrium, also forms the visceral peritoneum of the liver.

Development of Pancreas

The pancreas develops between the layers of both mesenteries from the dorsal and ventral pancreatic buds, which arise from the caudal part of the foregut (Fig. 12-8A). Most of the pancreas is derived from the dorsal pancreatic bud, which appears first. It grows rapidly between the layers of the dorsal mesentery. Formation of the dorsal pancreatic bud depends on signals from the notochord (activin and fibroblast growth factor 2) that block the expression of sonic hedgehog (Shh) in the endoderm. Expression of pancreatic and duodenal homebox factors (PDX-1 and MafA) is critical for the development of the pancreas.

Figure 12–8 A to D, Illustrations of successive stages in the development of the pancreas from the fifth to the eighth weeks. E to G, Transverse sections through the duodenum and the developing pancreas. Growth and rotation (arrows) of the duodenum bring the ventral pancreatic bud toward the dorsal bud; the two buds subsequently fuse. Note that the bile duct initially attaches to the ventral aspect of the duodenum and is carried around to the dorsal aspect as the duodenum rotates. The pancreatic duct is formed by the union of the distal part of the dorsal pancreatic duct and the entire ventral pancreatic duct. The proximal part of the dorsal pancreatic duct usually obliterates, but it may persist as an accessory pancreatic duct.

The ventral pancreatic bud develops near the entry of the bile duct into the duodenum (Fig. 12-8A and B). As the duodenum rotates to the right and becomes C-shaped, the ventral pancreatic bud is carried dorsally with the bile duct (Fig. 12-8C to F). It soon lies posterior to the dorsal pancreatic bud and later fuses with it (Fig. 12-8G). As the pancreatic buds fuse, their ducts anastomose.

The ventral pancreatic bud forms the uncinate process and part of the head of the pancreas. As the stomach, duodenum, and ventral mesentery rotate, the pancreas comes to lie along the dorsal abdominal wall (Fig. 12-8D and G).

The pancreatic duct forms from the duct of the ventral bud and the distal part of the duct of the dorsal bud (Fig. 12-8G). In approximately 9% of people, the proximal part of the duct of the dorsal bud persists as an accessory pancreatic duct that opens into the minor duodenal papilla. The connective tissue sheath and the interlobular septa of the pancreas develop from the surrounding splanchnic mesenchyme. Insulin secretion begins at approximately 10 weeks. The glucagon- and somatostatin-containing cells develop before differentiation of the insulin-secreting cells occurs. With increasing fetal age, total pancreatic insulin and glucagon content also increases.

Annular Pancreas

Annular pancreas is an uncommon anomaly and probably results from the growth of a bifid ventral pancreatic bud around the duodenum (Fig. 12-9A to C). The parts of the bifid ventral bud then fuse with the dorsal bud, forming a pancreatic ring. The ringlike, annular part of the pancreas consists of a thin, flat band of pancreatic tissue surrounding the descending, or second, part of the duodenum. An annular pancreas may cause obstruction of the duodenum shortly after birth, but many cases are not diagnosed until adulthood. Males are affected much more frequently than females.

Figure 12–9 A and B, Illustrations of the probable embryologic basis of an annular pancreas. C, An annular pancreas encircling the duodenum. This anomaly sometimes produces obstruction of the duodenum.

Rotation of Midgut Loop

While in the umbilical cord, the midgut loop rotates 90 degrees counterclockwise around the axis of the superior mesenteric artery (see Fig. 12-11B). This rotation brings the cranial limb (small intestine) of the midgut loop to the right and the caudal limb (large intestine) to the left.

Return of Midgut to Abdomen

During the 10th week, with enlargement of the abdominal cavity, the intestines return to the abdomen (reduction of the physiologic midgut hernia) (Fig. 12-11C and D). The small intestine returns first, passing posterior to the superior mesenteric artery, and occupies the central part of the abdomen. As the large intestine returns, it undergoes a further 180-degree counterclockwise rotation (Fig. 12-11C₁ and D₁). Later, it comes to occupy the right side of the abdomen. The ascending colon becomes recognizable as the posterior abdominal wall progressively elongates (Figs. 12-11E and 12-13A).

Figure 12–13 Fixation of the intestines. A, Ventral view of the intestines before their fixation. B, Transverse section at the level shown in A. The arrows indicate areas of subsequent fusion. C, Sagittal section at the plane shown in A, illustrating the greater omentum overhanging the transverse colon. The arrows indicate areas of subsequent fusion. D, Ventral view of the intestines after their fixation. E, Transverse section at the level shown in D after disappearance of the mesentery of the ascending and descending colon. F, Sagittal section at the plane shown in D, illustrating fusion of the greater omentum with the mesentery of the transverse colon and fusion of the layers of the greater omentum.

Cecum and Appendix

The primordium of the cecum and the appendix appears in the sixth week as a swelling on the antimesenteric border of the caudal limb of the midgut loop (Figs. 12-11C to E and 12-14A). Initially, the appendix is a small diverticulum of the cecum. It subsequently increases rapidly in length so that at birth it is a relatively long tube arising from the distal end of the cecum (Fig. 12-14D). After birth, the unequal growth of the walls of the cecum results in the appendix entering its medial side (see Fig. 12-14E). The appendix is subject to considerable variation in position. As the ascending colon elongates, the appendix may pass posterior to the cecum (retrocecal appendix) or the colon (retrocolic appendix).

Figure 12–14 Successive stages in the development of the cecum and appendix. A, At 6 weeks. B, At 8 weeks. C, At 12 weeks. D, At birth. Note that the appendix is relatively long and is continuous with the apex of the cecum. E, Adult. Note that the appendix is now relatively short and is located posterior to the cecum.

Congenital Omphalocele

Congenital omphalocele results in persistence of the herniation of the abdominal contents into the proximal part of the umbilical cord (Figs. 12-15 and 12-16). This is caused by failure of the body walls to fuse at the umbilical ring because of defective growth of mesenchyme. Herniation of the intestines occurs in approximately 1 in 5000 births; herniation of the liver and intestines occurs less frequently (1 in 10,000 births). The size of the hernia depends on its contents. The abdominal cavity is proportionately small when an omphalocele is present because the impetus for it to grow is absent.

Figure 12–15 An infant with an omphalocele. The defect resulted in herniation of intra-abdominal structures (liver and intestine) into the proximal end of the umbilical cord. The omphalocele is covered by a membrane composed of peritoneum and amnion.

(Courtesy of Dr. N.E. Wiseman, Department of Surgery, Children’s Hospital, Winnipeg, Manitoba, Canada.)

Figure 12–16 Ultrasonogram of the abdomen of a fetus (28 weeks’ gestation), showing a large omphalocele, with much of the liver protruding from the abdominal wall. The mass also contains a small, membrane-covered sac (arrows). The umbilical cord was integrally involved in the anomaly.

(Courtesy of Dr. C.R. Harman, Department of Obstetrics, Gynecology and Reproductive Sciences, Women’s Hospital and University of Maryland, Baltimore, MD.)

Cloaca

The expanded terminal part of the hindgut, the cloaca, is an endoderm-lined chamber that is in contact with the surface ectoderm at the cloacal membrane (Fig. 12-21A and B). This membrane is composed of the endoderm of the cloaca and the ectoderm of the proctodeum (Fig. 12-21C and D). The cloaca receives the allantois ventrally (Fig. 12-21A).

Figure 12–21 Illustrations of successive stages in the partitioning of the cloaca into the rectum and the urogenital sinus by the urorectal septum. A, C, and E, Views from the left side at 4, 6, and 7 weeks, respectively. B, D, and F, Enlargements of the cloacal region. B₁, D₁, and F₁, Transverse sections of the cloaca at the levels shown in B, D, and F, respectively. Note that the postanal gut, or tailgut (shown in B), degenerates and disappears as the rectum forms from the dorsal part of the cloaca (shown in C). The arrows indicate the growth of the urorectal septum.

Anal Canal

The superior two thirds of the adult anal canal are derived from the hindgut; the inferior one third develops from the proctodeum (Fig. 12-22). The junction of the epithelium derived from the ectoderm of the proctodeum and that derived from the endoderm of the hindgut is roughly indicated by an irregular pectinate line located at the inferior limit of the anal valves (Fig. 12-22). This line also indicates the approximate former site of the anal membrane. At the anus, the epithelium is keratinized and continuous with the skin around it. The other layers of the wall of the anal canal are derived from splanchnic mesenchyme.

Figure 12–22 The rectum and anal canal, showing their developmental origins. Note that the superior two thirds of the anal canal are derived from the hindgut, whereas the inferior one third of the anal canal is derived from the proctodeum. Because of their different embryologic origins, the superior and inferior parts of the anal canal are supplied by different arteries and nerves and have different venous and lymphatic drainages.

Because of its hindgut origin, the superior two thirds of the anal canal are supplied mainly by the superior rectal artery, the continuation of the inferior mesenteric artery. Its nerves are from the autonomic nervous system. The inferior one third of the anal canal, because of its origin from the proctodeum, is supplied mainly by the inferior rectal arteries, branches of the internal pudendal artery. The inferior part of the anal canal is supplied by the inferior rectal nerve and is sensitive to pain, temperature, touch, and pressure.

The differences in blood supply, nerve supply, and venous and lymphatic drainage of the two parts of the anal canal are important clinically because the characteristics of carcinomas involving the two parts differ. Tumors in the superior part are painless and arise from the columnar epithelium, whereas those in the inferior part are painful and arise from the squamous epithelium.

Congenital Megacolon

In infants with congenital megacolon, or Hirschsprung disease (Fig. 12-23), a part of the colon is dilated because of the absence of autonomic ganglion cells in the myenteric plexus distal to the dilated segment of colon. The enlarged colon—megacolon—has the normal number of ganglion cells. The dilation results from failure of peristalsis in the aganglionic segment, which prevents movement of the intestinal contents. Males are affected more than females (4 to 1). Congenital megacolon results from failure of neural crest cells to migrate into the wall of the colon during the fifth to seventh weeks of development. Of the genes involved in the pathogenesis of Hirschsprung disease, the RET proto-oncogene accounts for most cases.

Figure 12–23 Radiograph of the colon, after a barium enema, in a 1-month-old infant with megacolon (Hirschsprung disease). The distal aganglionic segment is narrow, with a dilated proximal colon full of fecal material. Note the transition zone (arrow).

(Courtesy of Dr. Martin H. Reed, Department of Radiology, University of Manitoba and Children’s Hospital, Winnipeg, Manitoba, Canada.)

Imperforate Anus and Anorectal Anomalies

Imperforate anus occurs in approximately 1 in 5000 newborn infants, and it is more common in boys (Figs. 12-24 and 12-25C). Most anorectal anomalies result from abnormal development of the urorectal septum, resulting in incomplete separation of the cloaca into urogenital and anorectal parts (Fig. 12-25A). Lesions are classified as low or high, depending on whether the rectum ends superior or inferior to the puborectalis muscle.

Figure 12–24 Female neonate with membranous anal atresia (imperforate anus). In most cases of anal atresia, a thin layer of tissue separates the anal canal from the exterior.

(Courtesy of A.E. Chudley, M.D., Section of Genetics and Metabolism, Department of Pediatrics and Child Health, Children’s Hospital, Winnipeg, Manitoba, Canada.)

Figure 12–25 Illustrations of various types of anorectal anomalies. A, Persistent cloaca. Note the common outlet of the intestinal, urinary, and reproductive tracts. B, Anal stenosis. C, Membranous anal atresia. D and E, Anal agenesis with a perineal fistula. F, Anorectal agenesis with a rectovaginal fistula. G, Anorectal agenesis with a rectourethral fistula. H and I, Rectal atresia.