Development of the Digestive System
The development of the digestive system begins as a simple blind-ended gut tube. The accessory digestive organs form as outpouchings from the primitive gut tube, whereas formation of the intestines require them to first protrude out into the umbilical cord (physiological herniation) before retracting back into the abdominal cavity. Understanding the origins of the foregut, midgut, and hindgut, as well as their accompanied derivatives will provide more insight behind the intricate vascularization and the mesenteries of the abdominal cavity.
The primitive gut is formed when a portion of the yolk sac becomes incorporated into the embryo, which occurs due to the cephalocaudal and lateral folding of the embryo. The portions that remain outside the embryo are the yolk sac and the allantois. The primitive gut forms a blind-ended tube on both the cephalic and caudal ends of the embryo, forming the foregut and the hindgut, respectively. The middle part forms the midgut, but remains temporarily connected to the yolk sac via the vitelline duct (yolk stalk).
The development of the primitive gut and its derivatives are generally divided into four sections:
- the proximal foregut
- the distal foregut
- the midgut
- the hindgut
First, the proximal foregut consists of the pharyngeal gut (pharynx), which extends from the oropharyngeal membrane to the respiratory diverticulum. This region is crucial to the development of the pharyngeal apparatus and ultimately the head and neck. Second, the distal foregut extends from the pharyngeal tube to the liver bud. Third, the midgut extends from the liver bud to the junction between the right two-thirds and the left third of the transverse colon. Fourth, the hindgut extends from the left third of the transverse colon to the cloacal membrane.
In the abdominal cavity, the gut tube and its derivatives are suspended from the dorsal and ventral body wall by mesenteries; these are double layers of peritoneum that enclose organs and connect them to the body wall. Such organs are known as intraperitoneal organs (i.e. stomach), whereas organs that lie directly on the posterior body wall and are covered by peritoneum on their anterior surface are known as retroperitoneal organs (i.e. kidneys). Mesenteries between two organs or one organ and the body wall are known as peritoneal ligaments. Together, mesenteries and peritoneal ligaments serve as a conduit for vessels, nerves, and lymphatics to and from the abdominal organs.
The gut tube, being initially in contact with the posterior abdominal wall, becomes suspended from it by the dorsal mesentery. At the stomach, the dorsal mesentery forms the dorsal mesogastrium (or the greater omentum); at the duodenum, it forms the mesoduodenum; at the jejunum and ileum, it forms the mesentery proper; and at the colon, it forms the dorsal mesocolon.
On the other hand, the ventral mesentery suspends only the lower esophagus, the stomach, and the upper duodenum to the ventral body wall. The ventral mesentery is derived from the septum transversum (a mass of splanchnic mesoderm separating the pericardial and peritoneal cavities) and eventually becomes divided by the growing liver into the lesser omentum and the falciform ligament; the former extends from the lower esophagus, the stomach, and the upper duodenum to the liver, whereas the latter extends from the liver to the ventral body wall.
The free margin of the falciform ligament serves as a conduit for the umbilical vein, which becomes obliterated after birth to form the round ligament of the liver. The free margin of the lesser omentum that connects the duodenum and the liver (hepatoduodenal ligament) forms the portal triad, thus serving as a gateway for the bile duct, the portal vein, and the hepatic artery. This free margin also forms the roof of the epiploic foramen of Winslow, a gateway which connects the omental bursa with the rest of the peritoneal cavity.
The foregut gives rise to the:
- the lower respiratory system
- the esophagus
- the stomach
- the proximal half of the duodenum
- the liver
- the biliary apparatus
- the pancreas
The derivatives of the foregut, except for the pharynx and the lower respiratory system, are mostly supplied by the celiac artery (trunk).
During the third week of gestation, a respiratory diverticulum (lung bud) forms as an outgrowth from the ventral wall of the proximal foregut. While the lung bud continues to expand, it becomes separated from the foregut, which forms the esophagus. Initially, the esophagus is short, but becomes rapidly elongated as a result of the growth and relocation of the heart and lungs.
During the fourth week of gestation, the rudimentary stomach appears as a fusiform-shaped dilation of the distal foregut. Subsequently, its appearance and position drastically changes; the latter can be better understood by visualizing a longitudinal axis and an antero-posterior axis around which the stomach rotates.
The stomach rotates 90 degrees clockwise around its longitudinal axis, resulting in its left side facing anteriorly and its right side posteriorly. This explains why the left vagus nerve innervates the anterior wall, as it once innervated the left side of the stomach, whereas the right vagus nerve innervates the posterior wall, as it once innervated the right side. Concurrent with this rotation, cellular proliferation occurs much faster in the posterior wall of the stomach than in the anterior wall, resulting in the formation of the greater and lesser curvatures, respectively.
The stomach also rotates around its antero-posterior axis, resulting in the caudal end (pyloric part) to move upward and to the right and the cranial end (cardiac part) slightly downward and to the left. Thus, the stomach assumes its final position, with its pylorus located superiorly to the left and its cardia inferiorly to the right.
The rotational changes of the stomach also alter the position of the mesenteries. Recall that the stomach is attached to the dorsal and ventral walls via the dorsal mesogastrium and the ventral mesentery, respectively. The rotation of the stomach around the longitudinal axis pulls the dorsal mesogastrium to the left and the ventral mesentery to the right: this creates a space behind the stomach known as the omental bursa (lesser peritoneal sac).
During the fourth week of gestation, the duodenum begins to develop from two sources: the caudal part of the foregut and the cranial part of the midgut, where the junction lies just distal to the origin of the bile duct. The developing duodenum forms a C-shaped loop that initially projects ventrally. However, once the stomach rotates, the duodenum rotates to the right and becomes pressed against the posterior abdominal wall, thus becoming retroperitoneal. Due to its dual origin, the duodenum is supplied by branches of the celiac trunk and the superior mesenteric artery.
Liver and Biliary Apparatus
The development of the liver begins during the fourth week of gestation, with the appearance of the hepatic diverticulum (liver bud) as an outgrowth from the ventral wall of distal foregut. The stalk connecting the diverticulum and the foregut narrows and forms the bile duct, whereas the gallbladder and the cystic duct form as a ventral outgrowth from the bile duct. Initially, the bile duct opens anteriorly into the duodenum, but ends up posteriorly due to the rotational changes of the duodenum.
As mentioned earlier, the hepatic diverticulum extends into ventral mesentery. This positions the future liver between the foregut and ventral abdominal wall, and divides the ventral mesentery into the lesser omentum and the falciform ligament. During the following weeks, the liver occupies a large portion of the upper abdominal cavity. Further development and segmentation of the liver is determined by the oxygenated blood flowing from the umbilical vein into the liver. Similar to the stomach, cellular proliferation occurs much faster on one side, resulting in a larger right lobe and a smaller left lobe.
Furthermore, the mesoderm surrounding the surface of liver differentiates into the visceral peritoneum except on its cranial surface. The latter lies in direct contact with the septum transversum, from which the central tendon of the diaphragm forms. Hence, this surface remains in contact with the future diaphragm and is never covered in visceral peritoneum; this surface is known as the bare area of the liver. Although much of the liver is derived from the foregut, hematopoietic cells, connective tissue cells, and Kupffer cells all derive from the mesenchyme of the septum transversum. Thus, the development of a functional liver depends on both the foregut and the septum transversum.
The pancreas is formed by two separate pancreatic buds that later join. Specifically, the dorsal pancreatic bud forms as an outgrowth from the dorsal wall of the duodenum, whereas the ventral pancreatic bud forms as an outgrowth from the ventral wall of the duodenum along with the bile duct. When the duodenum rotates and takes its C-shape form, it pulls the ventral pancreatic bud dorsally and inferior to the ventral pancreatic bud. Subsequently, the pancreatic buds along with their rudimentary duct systems fuse to give rise to the pancreas.
The ventral pancreatic bud forms the uncinate process and the inferior part of the head of the pancreas. The dorsal pancreatic bud forms the superior part of the head, the neck, and the body of the pancreas. The distal part of the dorsal pancreatic duct and the entire ventral pancreatic duct form the main pancreatic duct (of Wirsung).
The proximal part of the dorsal pancreatic duct either becomes obliterated or persists as the accessory pancreatic duct (of Santorini). Thus, the pancreas and its duct systems assume their final shape; the main pancreatic duct joins the bile duct and enter the duodenum at the major papilla, whereas the accessory duct (if present) enters the duodenum at the minor papilla.
The midgut gives rise to the:
- distal half of the duodenum
- the jejunum
- the ileum
- the cecum
- the appendix
- the ascending colon
- the proximal two-thirds of the transverse colon
The derivatives of the midgut are supplied by the superior mesenteric artery.
During the fifth week of gestation, the midgut undergoes a rapid elongation that occurs much faster than that of the abdominal cavity, resulting in the formation of the primary intestinal loop. At its apex, the loop remains in open communication with the yolk sac via the vitelline duct, while the superior mesenteric artery runs along the axis of the loop. The cranial limb of the loop will develop into the inferior half of the duodenum, the jejunum, and proximal half of the ileum. The caudal limb of the loop will develop into the distal half of the ileum, the cecum, the ascending colon, and the proximal two-thirds of the transverse colon.
By the sixth week, the continuing elongation of the midgut, combined with the pressure exerted by the dramatic growth of the abdominal organs, force the primary intestinal loop to protrude into the umbilicus (physiological herniation). Concurrently, the loop rotates 90 degrees counterclockwise around the axis of the superior mesenteric artery, resulting in the cranial limb to move caudally and to the embryo’s right, and the caudal limb to move cranially and to the embryo’s left. While this rotation takes place until the eighth week of gestation, the lengthening jejunum and ileum develop into a series of folds known as the jejunal-ileal loops, whereas the expanding cecum gives rise to a wormlike diverticulum, the vermiform appendix.
During the tenth week, the herniated midgut retracts into the abdomen. The mechanism responsible for this retraction is not fully understood, but may involve the increase in size of the abdominal cavity. As the intestinal loops reenter the abdomen, it rotates an additional 180 degrees counterclockwise around the axis of the superior mesenteric artery, thus having travelled for a total of 270 degrees. As a result, the cecum, being initially positioned under the liver, becomes displaced inferior, pulling down the proximal hindgut to form the ascending colon.
By the eleventh week, the intestines have completely retracted into the abdomen. The dorsal mesenteries of the ascending and descending colon shorten and fold, anchoring these organs to the dorsal body wall, where they become secondarily retroperitoneal. The jejunum, ileum, cecum, and the transverse and sigmoid colon remain suspended by a short mesentery from the dorsal body wall, thus becoming intraperitoneal.
The hindgut gives rise to the distal third of the:
The derivatives of the hindgut are supplied by the inferior mesenteric artery.
During the early weeks of development, the terminal portion of the hindgut enters the posterior portion of the cloaca, whereas the allantois enters the anterior portion; the cloaca and the allantois form the future anorectal canal and the urogenital sinus, respectively. The cavity of the cloaca is lined by endoderm, whereas its ventral boundary is lined by surface ectoderm; the latter is known as the cloacal membrane.
By the seventh week of gestation, the urorectal septum (a layer of mesoderm) grows between the allantois and the hindgut. It divides the cloaca into the urogenital sinus and the anorectal canal, while its tip forms the future perineal body. The urogenital sinus forms the future bladder, parts of the urethra, and the phallus, whereas the anorectal canal develops into the rectum and most of the anal canal. Specifically, while the upper two-thirds of the anorectal canal is derived from the endoderm of the hindgut, the lower one-third is derived from the surface ectoderm of the cloaca.
Degeneration of the cloacal membrane connects the upper and lower parts of the anorectal canal, while the location of this juncture is demarcated by the pectinate line, an irregular folding of the mucosa. This is also where the epithelial lining transitions from columnar to stratified squamous. The vasculature of the anorectal canal is consistent with its dual origin: the upper two-thirds (superior to the pectinate line) is supplied by the superior rectal arteries, branches of the inferior mesenteric artery, whereas its lower one-third (inferior to the pectinate line) is supplied by the inferior rectal arteries, branches of the internal pudendal arteries.
Occasionally, a bilobed ventral pancreatic bud (a normal variation) can form, but migrate in opposite directions around the duodenum to fuse with the dorsal pancreatic duct, rather than taking its usual dorsal route. This condition is known as annular pancreas and it can cause the duodenum to be compressed, leading to gastrointestinal obstruction.
Abnormal Rotation and Fixation of Midgut
As previously mentioned, formation of the midgut requires a relatively intricate series of rotations and fixations, as well as a physiological herniation and retraction. Errors in one or more of these steps can lead to various anomalies. Rotational anomalies are often signaled during infancy or childhood by the sudden onset of acute abdominal pain, vomiting, or gastrointestinal bleeding. Although such conditions can remain clinically silent until adulthood, definitive diagnosis requires X-rays.
In non-rotation of the midgut, the primary intestinal loop fails to undergo the second 180-degree counterclockwise rotation normally when retracting back into the abdominal cavity. This causes the jejunum and the ileum to end up on the right side of the body, and the colon on the left side.
In reversed rotation of the midgut, the primary intestinal loop undergoes the initial 90-degree counterclockwise normally, but the second 180-degree rotation occurs clockwise instead of counterclockwise. The net rotation of the midgut is thus 90 degree clockwise, rather than 270 degree counterclockwise. This causes the duodenum to end up ventral to the transverse colon instead of dorsal to it. In addition, the duodenum becomes intraperitoneal, while the transverse colon becomes retroperitoneal.
In mixed rotations of the midgut, only the cephalic limb of the primary intestinal loop undergoes the initial 90-degree rotation, whereas only the caudal limb undergoes the second 180-degree rotation. This causes the distal end of the duodenum to be fixed on the right side of the abdominal cavity, and the cecum to be fixed inferior to the stomach.
Meckel’s diverticulum consists of an intestinal outgrowth projecting from the mesenteric wall of the ileum near the cecum. This is caused by failure of the vitelline duct to completely regress. Most cases of Meckel’s diverticulum are asymptomatic. However, up to 3% of individuals with this condition can develop symptoms of intestinal obstruction, gastrointestinal bleeding, or peritonitis. Symptoms can also mimic an appendicitis, involving periumbilical pain localized on the right lower quadrant.
Facts about Meckel’s diverticulum can be remembered using the “rule of two’s”: it occurs in about 2% of the population; it is 2 times more common in males; about 2% of afflicted individuals have medical symptoms; it is usually located 2 feet from the cecum; and it is typically 2 inches long.
As previously mentioned, the midgut undergoes a physiological herniation into the umbilicus before retracting back to the abdominal cavity. If a retraction does not occur, the infant may be born with an umbilical hernia or an omphalocele. In contrast to the former, an omphalocele involves a larger herniation that can consist of an entire bowel or a liver.
Gastrochisis involves the protrusion of abdominal viscera through the anterior body wall, lateral to the umbilicus (usually on the right). Unlike an omphalocele, in gastroschisis the umbilical ring closes, therefore the herniation occurs lateral to the umbilicus rather than through it.