9. The intestinal tube and its derivatives (with the exception of the pharyngeal gut). Malformations

Page created on August 9, 2020. Not updated since.

Learning objectives

• What is the gut tube, and when is it formed?
• What are the parts of the gut tube?
• What are the derivatives of the foregut?
• Which artery supplies the foregut?
• Describe the formation of the oesophagus
• Describe the formation of the stomach
• Describe the formation of the liver
• Describe the formation of the pancreas
• What are the derivatives of the midgut?
• Which artery supplies the midgut?
• Describe the formation of the primary intestinal loop
• Describe the physiological umbilical herniation
• Describe the rotation of the midgut
• What are the derivatives of the hindgut?
• Which artery supplies the hindgut?
• Describe the separation of the cloaca
• What is oesophageal atresia?
• What is pyloric stenosis?
• What is biliary atresia?
• What is annular pancreas?
• What is omphalocoele?
• What is Meckel diverticulum?
• What is volvulus?
• What is Hirschsprung disease?

The gut tube

The gut tube, also called the intestinal tube, is formed as a result of cephalocaudal and lateral folding of the embryo. This tube has three parts:

• The foregut, which extends from the oropharyngeal membrane to the liver bud
• The midgut, which begins where the foregut ends and extends to the point where the distal third of the transverse colon begins
• The hindgut, which begins where the midgut ends and extends to the cloacal membrane

The pharyngeal gut, which extends from the oropharyngeal membrane to the respiratory diverticulum, is part of the foregut. It will give rise to the pharynx.

The epithelium of the intestinal tract, as well as the hepatocytes and exocrine and endocrine cells of the pancreas, arise from the endoderm. Splanchnic mesoderm gives rise to the stroma of the pancreas, as well as the muscle, connective tissue, and peritoneal components of the intestinal wall.

Molecular regulation of gut tube development

The signalling molecule retinoic acid (RA) is important in differentiating the different parts of the gut tube into the adult structures. RA initiates epithelial-mesenchymal interactions between the endoderm and mesoderm of the gut, which will stimulate the release of sonic hedgehog (SHH) from the endoderm, which will stimulate HOX genes in the mesoderm.

Development and derivatives of the foregut

The foregut gives rise to the oesophagus, trachea and lung buds, the stomach, and the duodenum all the way to the ampulla of Vater. The liver, pancreas, and biliary system develop as outgrowths from the upper part of the duodenum.

The adult remnants of the foregut are supplied by the coeliac trunk.

Formation of oesophagus

At 4 weeks the respiratory diverticulum appears at the ventral wall of the foregut, at the border with the pharyngeal gut. A septum, called the tracheoesophageal septum, gradually grows to separate the respiratory diverticulum from the part of the foregut which will become the oesophagus.

Formation of the stomach

Also in the fourth week, a dilation of the foregut appears. This dilation will eventually form the stomach, but first it must undergo two rotations.

The first rotation is along the longitudinal axis. The dilation of the foregut rotates along its longitudinal axis for 90 degrees. This causes the left side of the dilation to face anteriorly and the right side to face posteriorly. This explains why the left vagus nerve lies anteriorly to the stomach while the right one lies posteriorly.

The second rotation is along the anteroposterior or sagittal axis. The left side of the dilation grows faster than the right, which forms the greater and lesser curvatures of the stomach, and gives the stomach it’s characteristic shape.

Formation of the liver and biliary system

The hepatic diverticulum, also called the liver bud, appears in the third week as an outgrowth at the distal end of the endoderm of the foregut. This diverticulum rapidly proliferates and penetrates the septum transversum, leaving a narrow connection which will form the bile duct. The gallbladder forms from an outgrowth of the bile duct.

The hepatic diverticulum eventually form liver cords, which intermingle with vitelline and umbilical veins; these veins form the hepatic sinusoids. The liver cords themselves give rise to the hepatocytes, while haematopoietic cells, Kupffer cells, and the connective tissue of the liver originates from mesoderm of the septum transversum.

Formation of the pancreas

The pancreas develops from two buds, a ventral and a dorsal bud, which fuse to form the pancreas. These buds originate from the endodermal lining of the duodenum. Both the exocrine and endocrine cells of the pancreas originate from these endodermic buds.

Development and derivatives of the midgut

The midgut gives rise to the duodenum distal to the ampulla of Vater and all the intestines up until the point where the distal third of the transverse colon begins.

The midgut remains temporarily connected to the yolk sac through the vitelline duct.

The adult remnants of the midgut are supplied by the superior mesenteric artery.

Formation of the primary intestinal loop

The midgut rapidly elongates due to proliferation, resulting in the formation of the primary intestinal loop. The vitelline duct is connected to the apex of this loop. The cephalic (superior) limb of the loop gives rise to the distal part of the duodenum, the jejunum, and part of the ileum. The caudal (inferior) limb gives rise to the distal part of the ileum, the coecum, the appendix, the ascending colon, and the proximal two thirds of the transverse colon.

Physiological umbilical herniation

Because of the rapid elongation of the midgut the abdominal cavity eventually becomes too small to contain all the intestinal loops. This causes part of the midgut to herniate out into the umbilical cord. This is called the physiological umbilical herniation, and it occurs around week 6.

Rotation of the midgut

While the midgut is herniated through the umbilical cord, the herniated midgut rotates 90 degrees along an anteroposterior axis formed by the superior mesenteric artery. The rotation is counterclockwise, as if rotating the steering wheel to turn the car left.

As the abdominal cavity expands with growth the herniated midgut eventually retracts into the abdominal cavity. This occurs during week 10. During the retraction, the herniated midgut rotates another 180 degrees, for a grand total of 270 degrees of counterclockwise rotation.

Coecum and appendix

The coecum forms from a coecal bud, which forms at the caudal limb of the primary intestinal loop. The coecal bud is the last part of the midgut to be retracted into the abdominal cavity.

The distal end of the coecal bud forms a narrow diverticulum, which becomes the appendix.

Development and derivatives of the hindgut

The hindgut gives rise to the rest of the intestines, up until the second third of the anal canal. The rest of the anal canal originates from ectoderm.

The adult remnants of the hindgut are supplied by the inferior mesenteric artery.

Separation of the cloaca

The distal end of the hindgut connects to the posterior portion of the cloaca. The allantois connects to the anterior portion of the cloaca, which forms the urogenital sinus. The allantois is separated from the hindgut by the urorectal septum.

The septum eventually grows to separate the cloaca into two openings, the anus and the urogenital sinus. The distal one third of the anal canal is derived from ectoderm, while the proximal two thirds are derived from endoderm of the hindgut. The junction between the endodermal and ectodermal regions form the pectinate line.

Malformations

Oesophageal atresia and tracheoesophageal fistula

Oesophageal atresia is a condition where the upper oesophagus is not connected to the lower oesophagus, instead ending in a blind sac. In many cases oesophageal atresia is accompanied by a tracheoesophageal fistula, a communication between the trachea and the lower oesophagus. This is caused by posterior deviation of the tracheoesophageal septum.

Affected infants should not be fed orally until the defect has been surgically corrected.

Pyloric stenosis

Pyloric stenosis refers to an excessively thick (hypertrophic) pyloric sphincter, which causes the lumen of the pylorus to be extremely narrow. This causes very characteristic projectile vomiting. The cause is unknown. The treatment is surgical.

Biliary atresia

Biliary atresia refers to a defect where a part of the extrahepatic bile ducts, most commonly the common bile duct, are obliterated and therefore doesn’t conduct bile. Because the liver can’t excrete bile it takes excessive damage. Many infants die unless they receive a liver transplant. Biliary atresia is the most common cause of liver transplant in infants.

Annular pancreas

If the fusion of the dorsal and ventral pancreatic buds doesn’t occur properly, an annular (ring-formed) pancreas may be formed. This pancreas surrounds the duodenum, sometimes constricting the duodenum and causing obstruction.

Omphalocoele

An omphalocoele is a herniation of abdominal organs through the umbilical ring. These organs may include liver, intestines, stomach, spleen, etc. The hernia is covered by amnion. This malformation occurs due to failure of the midgut to retract into the abdominal cavity in week 10. It often occurs with other malformations.

Meckel diverticulum

Meckel diverticulum is the most common congenital anomaly of the GI tract, affecting 2% of the population. The vitelline duct is usually obliterated within week 6, but if it persists it forms the Meckel diverticulum. It is located 50 cm proximal to the ileocoecal junction.

Meckel diverticulum is usually asymptomatic, but can ulcerate and bleed, causing painless blood in the stool.

Malrotation

Multiple malformations can occur if the intestines don’t rotate properly. If the intestines twist intestinal obstruction (ileus) and/or compromise of blood supply may occur, both of which can be lethal. This twisting is called volvulus.

Rarely the intestines rotate only 90 degrees. This causes a left-sided colon, with the coecum on the left side.

Rarely the intestines rotate 90 degrees clockwise rather than counterclockwise. This causes the transverse colon to pass behind the duodenum and the superior mesenteric artery.

Congenital aganglionic megacolon

If neural crest cells fail to migrate into the wall of the colon the parasympathetic ganglia (Meissner and Auerbach plexuses) in the wall fail to form. The affected parts of the colon won’t have normal peristalsis, causing a functional obstruction. The colon segments proximal to the aganglionic segments will dilate, forming a megacolon. This condition is called congenital aganglionic megacolon, or Hirschsprung disease.

In most cases only the rectosigmoid region is aganglionic.

Summary

• What is the gut tube, and when is it formed?
  • It is a tube consisting off endoderm and splanchnic mesoderm
  • It is formed after cephalocaudal and lateral folding
• What are the parts of the gut tube?
  • The foregut, which extends from the oropharyngeal membrane to the liver bud
  • The midgut, which begins where the foregut ends and extends to the point where the distal third of the transverse colon begins
  • The hindgut, which begins where the midgut ends and extends to the cloacal membrane
• What are the derivatives of the foregut?
  • Oesophagus, trachea and lung buds, the stomach, and the duodenum all the way to the ampulla of Vater
  • The liver, pancreas, and biliary system
• Which artery supplies the foregut?
  • Coeliac trunk
• Describe the formation of the oesophagus
  • The tracheoesophageal septum separates the respiratory diverticulum from the part of the foregut which will become the oesophagus
• Describe the formation of the stomach
  • A portion of the foregut dilates, rotates 90 degrees along its longitudinal axis, and rotates along the anteroposterior axis, forming the stomach
• Describe the formation of the liver
  • The hepatic diverticulum grows from the endoderm of the distal end of the foregut and into the septum transversum
  • It forms the liver cords, which will give rise to hepatocytes
  • The liver cords will intermingle with vitelline and umbilical veins, which form the hepatic sinusoids
  • haematopoietic cells, Kupffer cells, and the connective tissue of the liver originates from mesoderm of the septum transversum
• Describe the formation of the pancreas
  • The pancreas is formed from the fusion of a ventral and a dorsal pancreatic bud, which originate from duodenal endoderm
• What are the derivatives of the midgut?
  • Duodenum distal to the ampulla of Vater and all the intestines up until the point where the distal third of the transverse colon begins
• Which artery supplies the midgut?
  • Superior mesenteric artery
• Describe the formation of the primary intestinal loop
  • The midgut rapidly elongates, forming a primary intestinal loop
  • The vitelline duct is connected to the apex of the loop
• Describe the physiological umbilical herniation
  • The midgut rapidly elongates, eventually becoming too small for the abdominal cavity
  • The excess midgut herniates through the umbilical cord
• Describe the rotation of the midgut
  • While herniated, and during the retraction back into the abdominal cavity, the midgut rotates 270 degrees in the counterclockwise direction
• What are the derivatives of the hindgut?
  • The distal third of the colon to the proximal third of the anal canal
• Which artery supplies the hindgut?
  • Inferior mesenteric artery
• Describe the separation of the cloaca
  • Initially, the hindgut connects to the posterior portion of the cloaca while the allantois connects to the anterior portion
  • Later, the urorectal septum will grow and separate the cloaca into the anal canal and the urogenital sinus
• What is oesophageal atresia, and why does it occur?
  • A malformation where the upper oesophagus is not connected to the lower oesophagus
  • It occurs due to posterior deviation of the tracheoesophageal septum
• What is pyloric stenosis?
  • A condition where the pyloric sphincter is excessively thick, causing obstruction at the level of the pylorus
• What is biliary atresia?
  • A malformation where part of the extrahepatic bile duct is obliterated
  • A liver transplant is needed in most cases
• What is annular pancreas, and why does it occur?
  • An annular pancreas is a ring-formed pancreas which compresses the duodenum
  • It occurs if the ventral and dorsal pancreatic buds fuse around the duodenum
• What is omphalocoele, and why does it occur?
  • An omphalocoele is a herniation of abdominal organs through the umbilical ring
  • It occurs if the midgut fails to retract into the abdominal cavity
• What is Meckel diverticulum?
  • If the vitelline duct fails to obliterate, it remains as the Meckel diverticulum
• What is volvulus?
  • Volvulus refers to twisting of the intestine which causes intestinal obstruction and compromise of blood supply
• What is Hirschsprung disease, and why does it occur?
  • Hirschsprung disease refers to the formation of megacolon proximal to an aganglionic segment of the colon
  • It occurs due to failure of neural crest cells to form parasympathetic ganglia in the colonic wall