Development of the GI Tract

• A blastocele refers to the stage in intrauterine life in which the embryo is just a flat, elongated disc located with a ball of cells that connect the disc to the endometrium (uterus wall).

  With a little further embryonic development, the flat disc becomes a structure known as the trilaminar disc.
• The trilaminar disc has 3 layers: the ectoderm (top layer), the mesoderm (middle layer), and the endoderm (bottom layer). Each of these 3 layers will go onto forming certain tissues and organs of the body:

  • the ectoderm will become the skin and nervous system.
  • the mesoderm will become the muscles, vascular system, and connecting tissue (including bone and cartilage).
  • the endoderm will become the gut, liver, lungs, and hepatobiliary system.
• The trilaminar disc sits between 2 cavities: the amniotic cavity above, and the yolk sac below.
• The development of the primitive GI tract begins in week 3 of intrauterine life. The flat trilaminar disc folds under cranially, caudially, and laterally, incorporating part of the yolk sac in the process.
• The yolk sac is mostly non-functional in humans, apart from helping to transfer nutrients to the embryo before placental circulation develops.
• The mesoderm invades the wall of the yolk sac during the 3rd week of primitive GI tract development, and this event triggers the development of the foetal vasculature. The dorsal part of the yolk sac gives rise to the gut. There are also some primordial germ cells that appear in the wall at this time.
• The 4th week of development is a period of rapid growth, as the embryo begins to change shape from a flat trilaminar disc into a cylinder in a process known as embryonic folding.
• Embryonic folding occurs in 2 planes: a horizontal plane and a vertical/median plane. This is due to the differing growth rates of different embryonic structures. Folding of the embryo in the horizontal plane results in the development of 2 lateral folds. Folding in the median plane results in the development of the cranial and caudal folds. Folding in these 2 planes occurs simultaneously, which results in rapid embryonic development.
• The cylinder consists of 3 layers derived from the trilaminar disc: the endoderm becomes the innermost layer, the mesoderm becomes the middle layer of the cylinder, and the ectoderm becomes the outermost layer. The endoderm is largely responsible for the formation of the GI tract.

  As embryonic folding continuous, the endoderm moves towards the midline and fuses to incorporate part of the yolk sac to create the primitive gut tube.
• The primitive gut tube divides into 3 parts: the foregut, the midgut, and the hindgut.

  The foregut lies at the cranial end of the embryo, and is temporarily closed by the oropharyngeal membrane. This membrane ruptures to form the mouth at the end of the 4th week of development.
• The midgut lies between the foregut and hindgut, and remains connected to the yolk sac until the 5th week of development. As embryonic folding continues, the connection between the midgut and yolk sac narrows into a stalk called the vitelline duct.

  The hindgut lies at the caudal end of the embryo, and is temporarily closed by the cloacal membrane. The cloacal membrane ruptures to form the urogenital and anal opening during the 7th week of development.
• Once embryonic folding has been complete, the gut is trapped by the lateral and ventral abdominal walls as the anterior abdominal walls fuse together. Only the connection through the umbilicus to the remnant of the yolk sac remains. On either side of the gut tube is a trapped space known as the coelomic cavity. The coelomic cavity will eventually become the peritoneal cavity.
• The gut tube is suspended from the posterior and anterior abdominal walls by a double-folded membrane known as the dorsal and ventral mesenteries (respectively).

  The gut tube receives a blood supply from from the aorta located at the back of the abdomen. The arterial branches reach the gut by travelling through the dorsal mesentery.

  Around the umbilicus, the ventral mesentery would get in the way of the developing umbilical cord, so it regress, and doesn't descend below the foregut.
• By 28 days (week 4), the yolk sac continues to regress and thin out, as the yolk sac doesn't have a significant function in humans beyond the primitive embryonic stages. In these early stages, nutrients from the yolk sac are absorbed by vessels in the wall (vitelline veins) to provide nutrition to the embryo. However, once the placental circulation takes over, the vitelline circulation ceases to be important and the yolk sac regresses. It lies within the developing umbilical cord for a short time.
• The allantois is another non-functioning structure within humans. It's a duct that arises as a diverticulum of the hindgut. It has a close relationship with the yolk sac and while it is non-functional in humans, its vessels do become the umbilical artery. The allantois also regresses later in development.

  The proximal end of the allantois remains and will enlarge to become the urinary bladder. From the apex of the bladder, a fibrous cord connects the bladder to the umbilicus, and this is visible in the adult. If the cord fails to fibrose, it may allow urine to leak from the umbilicus.
• The foregut gives rise to:

  • the pharynx and oesophagus.
  • the lower respiratory tract (including the larynx, trachea, and lungs).
  • the stomach and the part of the duodenum proximal to the opening of the bile duct.
  • the liver and pancreas (biliary apparatus).

  The foregut is supplied by the coeliac trunk.
• The thoracic part of the foregut gives rise to the lower respiratory tract: the larynx, trachea, and bronchial tree all arise from the foregut. Since development of the lower respiratory tract is in conjunction with the oesophagus, abnormalities of this development can lead to the oesophagus and airways failing to separate.
• During the 3rd week of intrauterine life, the foregut develops a respiratory diverticulum which ultimately form the larynx, trachea, and bronchial tree. It starts as a tube continuous with the foregut. The tracheo-oesophageal septum separates the 2 tubes, and the respiratory diverticulum subsequently buds into two, forming the alveoli of the lungs.

  The connective tissue of the lungs and respiratory tract is formed by splanchnic mesoderm that surrounds the developing endoderm of the foregut.
• Sometimes, the closure of the tracheo-oesophageal septum can trigger atresia of the oesophagus. This is where the developing the oesophagus ends up dividing into a proximal and distal part.

  Sometimes a tracheo-oesophageal fistular forms, and the trachea and oesophagus are joined together at a particular point.

  An atresia and fistula can occur in isolation, or together.
• The liver develops in the ventral mesogastrium as a diverticulum of the foregut. From this diverticulum, the gall bladder and ventral pancreas also develop.
• In human pancreatic development, the pancreas arises as 2 separate, distinct rudiments which eventually meet and fuse together to form the pancreas. These rudiments are known as the dorsal pancreatic bud and the ventral pancreatic bud.
• The dorsal pancreatic bud appears first at around day 26. The ventral pancreatic bud arises soon afterwards as an evagination at the junction between the hepatic duct and foregut.
• During the 5th week of development, there is a differential growth of the wall of the foregut such that the stomach rotates to the left. The hepatic duct and ventral pancreatic bud migrate around the foregut until the ventral bud comes into contact with the dorsal pancreatic bud. Both fuse at the beginning of the 6th week.
• The developing liver and stomach are expanding within the abdominal cavity. The liver moves to the right, and the stomach moves dorsally and to the left. This causes the developing duodenum, pancreas, and associated mesenteries to be displaced to the right. The pancreas comes to lie on the left.

  The part derived derived from the ventral pancreatic bud becomes the uncinate process, and the dorsal pancreatic bud forms the remainder. Eventually, the main ducts of the dorsal and ventral pancreatic divisions interconnect.
• The midgut gives rise to:

  • the duodenum distal to the opening of the bile duct.
  • the jejunum and ileum
  • the caecum and appendix
  • the ascending colon
  • the proximal two-thirds of the transverse colon.

  The midgut is supplied by the superior mesenteric artery.

  In the foetus, there is no obvious junction to indicate the end of the midgut. In the foetus, the midgut connects to the yolk sac via the vitelline duct.
• During mid trimester, the liver is so big that is causes almost the entire midgut to herniate into the umbilical card. When there is an expansion of the abdominal cavity, the hernia reduces, and the loop of the midgut rotates anticlockwise. This anticlockwise rotation is done around the axis of the superior mesenteric artery, and occurs in 2 phases:

  1. 90 degree anticlockwise rotation at 42 days.
  2. 180 degree anticlockwise rotation at 76 days.
• The cranial limb of the midgut loop will form the small intestines, and the caudal limb of the midgut loop will form the large intestine. The cranial limb undergoes a high degree of folding prior to its rotation, whereas the caudal limb doesn't. Instead, the proximal end of the caudal limb swells; this is the developing caecum and the beginning of the large intestines.
• The caecum has to descend on the right hand side of the abdominal cavity, from top right to bottom right, to take up its adult position in the right iliac fossa. This movement of the caecum to its adult position is the 3rd stage of midgut development.
• If the 3rd stage of midgut development (caecum moving down to its adult position) doesn't occur, then the colon may remain on the left in the abdominal cavity, the small intestines on the right, and the caecum to the left of the duodenum. This arrangement makes the small intestines prone to rotation, which can interrupt its blood supply.
• In a non-rotation of the midgut, the 2nd phase of rotation (the 180 degree anticlockwise rotation) doesn't occur; only the first 90 degree anticlockwise rotation does. This results in the small intestines on the right of the abdomen and the large intestines on the left.
• In a reversed rotation, the 2nd phase of rotation may happen in the clockwise direction instead of in an anticlockwise direction. This puts the duodenum in front of the transverse colon, and so, the duodenum is no longer retroperitoneal. Although a reversed midgut rotation is generally asymptomatic, it may occasionally constrict the transverse colon, or the blood vessels to the duodenum.
• Failure of the gut to return to the abdominal cavity causes an omphalocele. An omphalocele is different from a hernia, as a hernia occurs after the gut has returned to the abdominal cavity. An omphalocele on the other hand, is a failure of the midgut to reach the abdominal cavity in the first place. An omphalocele usually requires surgical intervention after birth to replace the gut to its normal position and close off the umbilicus.
• A gastroschisis is a protrusion of the gut through an opening in the anterior abdominal wall. This opening is usually located to the right of the umbilicus. Unlike an omphalocele, a gastroschisis isn't associated with a sac, so the intestines are exposed. The cause of a gastroschisis isn't known, but it has links to material smoking, drug abuse, genetic (autosomal recessive), and the use of aspirin.
• In the early embryo, the midgut is continuous with the yolk sac. Later, the neck of the yolk sac constricts to form a vitello-intestinal duct. The duct normally disappears but it may persist in whole or in part. Most commonly the proximal part persists, giving rise to a Meckel’s diverticulum.

  Inflammation of the Meckel's diverticulum will mimic pain from an inflamed appendix.
• The hindgut gives rise to:

  • the distal third of the transverse colon
  • the descending and sigmoid colon
  • the rectum
  • the superior part of the anal canal
  • the epithelium of the urinary bladder and most of the urethra.

  The hindgut also gives rise to the allantois. The proximal part of this duct enlarges to form the foetal bladder, and also gives rise to most of the developing urethra.
• The allantois has little function in humans, but the blood vessels that go from its walls ultimately become the umbilical arteries and umbilical veins that go to the placenta in the umbilical cord. It's intraembryonic portion runs from the umbilicus to the urinary bladder. As the bladder enlarges, it involutes to form the urachus. After birth, the urachus becomes a fibrous cord known as the median umbilical ligament.
• Th cloaca is the distal part of the hindgut. The hindgut here partitions into 2 compartments by growth of a wedge of mesenchyme known as the urorectal septum. This septum pushes down through the cloaca towards the cloacal membrane, separating the urogenital tract from the future rectum and anal canal.
• Most of the urogenital membrane breaks down, but is partially in evidence in the vagina of virgin females as the hymen. The anal membrane usually ruptures at the end of the 8th week of intrauterine life.
• Complete, or partial persistence of the anal membrane leads to an imperforate anus. These are usually spontaneously ruptured during the first passage of stool, and this may cause some bleeding. Occasionally, an imperforate anus may need to be surgically incised.
• There may also be an incomplete separation of the cloaca into the urogenital and anorectal parts, leading to a rectovaginal or rectourethral fistula.

  In a rectovaginal fistula, the vagina could become infected with faecal bacteria. In a rectourethral fistular, faeces may enter the urethra and infect it.