"The adult arrangement of the gastro-intestinal tract and its division into foregut, midgut and hindgut are

determined by foetal development. Discuss the anatomical and clinical implications of this". By the third week, gastrulation has taken place and the embryo is now a tri-laminar disk divided into endoderm, mesoderm and ectoderm. The endodermal cells have migrated around the inside of the blastocyst, completing a pouch called the yolk sac. During the fourth week the primitive gut forms, and the majority of the GI tract is derived from this primitive gut. The primitive gut is composed entirely of endoderm and develops when the dorsal part of the yolk sac incorporates into the embryo during the process of folding. The endoderm of the yolk sac becomes the epithelium of the digestive tract. Soon thereafter, the mesoderm forms and splits into somatic and splanchnic layers. The splanchnic mesoderm associates with the endoderm of the primitive gut. Thus, the primitive gut is a simple endodermal tube surrounded by mesoderm. The endodermal layer of the primitive gut produces the epithelial lining and glands of most of the gastrointestinal tract. The vascular portion, smooth muscle, connective tissue, and parietal peritoneal develop from somatic mesoderm. Visceral peritoneum develops from splanchnic mesoderm. As the primitive gut continue to elongate it is said to be divided into three distinct regions the foregut, midgut and the hindgut. This distinction is brought about by first defining the midgut as the region of the primitive gut that continuous with the yolk sac. The part of the primitive gut cranial to this connection is knwn as the foregat and the part that is caudal to this connection is then known as the hind gut. Later, the dividing lines between these three regions are defined by the borders of the vascular territories of the branches of the abdominal aorta. During embryoligcal devlopment a midline artery, the dorsal artery is established and comes to lie just dorsal to the gut and gives off branches to the gut. There are three main branches which are formed the celiac trunk for the foregut, and superior mesenteric artery for the mid gut and the inferior mesenteric artery for the hind gut. At four weeks, the digestive tube remains suspended in the coelom by dorsal and ventral mesenteries. The ventral mesentery disintegrates everywhere except where major blood vessels or visceral organs have grown into it. The ventral mesentery remains intact along the path of the umbilical arteries and where the umbilical vein and liver develop. Foregut:

The foregut extends from the oropharyngeal membrane to the uperr half of the secondd part of the duodenum. The foregut can be further divided into cranial and caudal regions. Cranial foregut The cranial foregut, or pharyngeal gut, extends from the oropharyngeal membrane to

(and includes) the respiratory diverticulum (lung bud). The derivatives of the pharyngeal gut include part of mouth and tongue, pharynx, thyroid, parathyroid, thymus, lower respiratory tract, and lungs. The pharyngeal gut and stomodeum both contribute to development of the mouth. The stomodeum is an ectodermal depression in the developing face that forms the primordial mouth. After the oropharyngeal membrane, which separates the stomodeum from the pharyngeal gut, ruptures in the 5th week, the stomodeum connects the amniotic cavity and the pharyngeal gut. Pharyngeal ("branchial") arches appear during the 4th and 5th weeks on the ventral side of the pharyngeal gut. Each arch has cartilage, a cranial nerve, an aortic arch artery and muscle. Pharyngeal clefts and pouches are located between the arches. (See Pharyngeal Apparatus for more on the pharyngeal arches, clefts and pouches.) At about 4 weeks, the respiratory diverticulum (or lung bud) appears. At the end of the embryonic period, the lungs are in a pseudoglandular phase in which pulmonary lobes and segments can be identified. Caudal foregut The caudal foregut, sometimes simply called the foregut, begins after the respiratory diverticulum and extends to (and includes) the hepatocystic diverticulum. The derivatives of the caudal foregut include: esophagus, stomach, proximal duodenum, liver, gall bladder, hepatic and bile ducts, and pancreas. Esophagus About the end of the fourth week, the tracheoesophageal septum divides the foregut anteriorly into the trachea and lung buds and posteriorly into the esophagus. The epithelium of the esophagus and the esophageal glands develop from foregut endoderm. The smooth muscle of the esophagus, like that of the entire gut, develops from the splanchnic mesenchyme that surrounds the endoderm. Stomach The stomach first appears about the end of the fourth week as an elongated dilation of the foregut. The epithelial lining and gastric glands develop from foregut endoderm. Splanchnic mesoderm produces stomach smooth muscle, the lesser omentum, the dorsal mesentery (dorsal mesogaster and greater omentum), and the dorsal mesoesophagus. The dorsal border of the stomach grows more rapidly than the ventral border, forming two distinct curvature the lesser one dorsally greater curvature and a ventral lesser curvature. By the end of the 8th week, the stomach has undergone a 90 degree rotation clockwise around a cranio caudal axis. There is also additional tilting of the stomach such that greater curvature is orientated slightly inferior.

Duodenum The caudal part of the foregut forms part of the duodenum. The lining of smooth muscle of the duodenum develops for the furegut endoderm and the spalnchnic mesoderm.

Liver and Biliary Tree The pancreas and liver begin as the epithelium of the foregut grows out from the digestive tract and into the dorsal and ventral mesenteries, respectively. The liver (liver epithelial cords) and biliary tree appear late in the third week or early in the fourth week as the hepatic diverticulum, an outgrowth of the ventral wall of the distal foregut. The foregut endoderm of the hepatic diverticulum produces the parenchymal of the liver (hepatocytes) and the epithelial lining of the biliary tract. The hepatocytes arrange into a series of branching and anastomosing plates in the mesenchyme of the transverse septum. These plates subsequently intermingle with vitelline and umbilical veins to form hepatic sinusoids. Besides contributing to the sinusoids, the splanchnic mesenchyme in the transverse septum also forms the stroma, the fibrous and serous coverings (liver capsule), the falciform ligament, and the blood forming, or hematopoietic tissue (Kupffer cells), of the liver. The connective tissue and smooth muscle of the biliary tract also develops from this mesenchyme. The hepatic diverticulum experiences incredible growth from the gallbladder, associated ducts, and the various lobes of the liver. The hepatic diverticulum subsequently divides into a small ventral part, the future gall bladder, and a larger cranial part, the liver primordium; the latter portion grows into the septum transversum and differentiates into the parenchyma of the liver and the lining of the biliary ducts. The bile ducts form as the connection between the hepatic diverticulum and the foregut (duodenum) narrows when strands of hepatocytes penetrate the septum transversum. The bile duct has a small ventral outgrowth that becomes the

cystic duct and expands into the gallbladder. Once developed, the hepatic and cystic ducts connect to the duodenum by the common bile duct. The entrance of the bile duct into the small intestine gradually shifts from an initial anterior position to a posterior one and passes behind the duodenum. By the sixth week, the liver performs hematopoiesis (the formation of blood cells). The liver represents 10% of the total weight of the fetus by the ninth week. As the embryo enlarges, the stomach and liver rotate to the right, producing two pockets. The mesenteries that form these pockets are the greater omentum and lesser omentum. Pancreas The pancreas develops from dorsal and ventral pancreatic buds that arise from the caudal part of the foregut. The dorsal bud appears during the fourth week opposite the hepatic diverticulum. The ventral pancreatic primordium appears during the fifth week, either as an outgrowth of the hepatic diverticulum or separately from the duodenum. The dorsal pancreatic bud grows more rapidly than the ventral and soon extends dorsally behind the duodenum into the dorsal mesentery. The duodenum grows and rotates to the right (clockwise) and carries the ventral pancreatic bud to the dorsal mesentery where it fuses with the dorsal bud during the seventh week. The dorsal bud forms the body and tail of the pancreas; the ventral bud forms the uncinate process and most of the head of the pancreas. Foregut endoderm produces the pancreatic acinar and island cells.

There is immense clinical significance of the foregut development in realtion to many congenital disorders and diseases that can occur. In the case of there could be errors in the formation of the tracheo oephageal septum in which case there would be a tracheo osepheal fistula and espheal atresia. IN the embryological development of the stomach there are various anatomic abnormalities if formation does not occur correctly. In the case of the luminal formation of the foregut region, there could be narrowing that occurs in the certain regions leading to stenosis. The most common is pyloric stenosis which occurs and at the pylorus of the stomach and is associated with projectile vomiting in infants. Another possible congenital abnormaility associated with formation of the pancreas is an annular pancreas. This occurs if the ventral bud is duplicated, the migrating lobes can completely encircle the duodenum, forming an annular pancreas. This may result in a narrowing or complete constriction of the duodenum due to constriction by the ring of pancreas. MIdgut: The midgut extends from the second part of the duodenum to two thirds of the transverse colon. The midgut is divided into two regions at the omphalo-enteric duct ("yolk stalk"): the cranial and caudal limbs. The derivatives of the cranial limb include the distal duodenum, jejunum, and proximal ileum. The derivatives of the caudal limb include the distal ileum, cecum, appendix, ascending colon, and proximal 2/3 of transverse colon.

The endoderm of the midgut produces the lining of the digestive tract from the foregut to the middle of the transverse colon. By the fifth week, the midgut elongates into a ventral U-shaped midgut loop known as the primary intestinal loop that is attached to the umbilicus by the viteline duct and the superior mesenteric artery runs down the loop. A cecal diverticulum also appears during the 5th week. By the sixth week, the continued growth of the midgut along with other organ growth forces the intestinal loop to herniate into the umbilicus Additional elongation and coiling occur outside the body of the embryo.
Around the beginning of the 8th week, the herniated intestinal loop then undergoes a 90 rotation counter-clockwise which is programmed by the left-right organization of the body. There is continued lengthening and differntiation of the jejunal-ileal region giving rise to a series of folds.

During the 10th week, the instestine beginning withdraiwing back into the ceolemic acivity. As this occurs it rotates counter-clockwise a further 180 degrees The cecal diverticulum continues to develop and moves inferiorly, producing the cecum and appendix. The remainder of the midgut produces the ascending colon and. right (proximal) half to two-thirds of the transverse colon (hepatic flexure). The ascending & descending colon adhere to the dorsal body wall and become secondarily retroperitoneal and the transverse & sigmoid colon remain suspended. The smooth muscle of the midgut and the dorsal mesentery of the large and small intestines develop from the splanchnic mesoderm.
Clinical Applications: There can be congenital abnormalities formed if development of the midgut does not take place properly. When there is physiological hernia and the umbilical rings does not close loops of the midgut may remain outside the abdominal cavity resulting in a

condition known as omphalocele. This condition can also occur id during the 10th week of development there is no retraction of the intestinal contents. Furthermore, a condtion known as MIckels diverticulum can also occur. Under normal emrbyoligcal development, the viteline duct regresses between the 5 8th week, however in the case of Mickels Diverticulum there is a persitant vitelline duct. It remains as adiverticulum projecting from the wall of the ileum within 100 cm of the cecum but may arise anywhere in the small intestine on the antimesenteric side of the bowel.

There can also be sever abnormalities associated with the rotation of the mid gut contents during embryological development. In the case of non roation of the gut, the primary gut loop fail to rotate the 180 degree counterclockwise rotation as it enters the abdominal cavity, although the earlier 90 degree rotation may happen normally. This results in the jejunum and ileum end up on the right side of the body and the colon ends up on the left side. There can also be reverse rotation of the gut where the initial 90 degree rotation occurs normally, but the 180 degree rotation occurs clockwise instead of counterclockwise (so net is 90 degree clockwise). IN this case the duodenum is anterior to the transverse colon and it does not become secondarily retroperitoneal, but the transverse colon does instead. There can also be mal roation of the intestinal contents which is when the cranial end of the primary intestinal loop undergoes the initial 90 degree rotation only and the caudal limb undergoes only the later 180 degree rotation. This will cause the distal end of the duodenum to be fixed on the right side of the abdominal cavity and the cecum is fixed near midline just inferior to the pyloris. The abnormal position of the cecum may cause the duodenum to be enclosed by a band of peritoneum (Ladds bands). Hind Gut: The hind gut contains the distal transverse colon, descending colon, sigmoid

colon, rectum and cloaca. The cloaca is the common urogenital sinus which will later become partitioned into an anterior urinary and posterior GIT rectal component.

The hindgut extends into the caudal part of the embryo where it forms a large chamber, the cloaca. The allantois, a tubular extension of the cloaca that receives urinary wastes from the fetus, projects from the body and into the body stalk. Fusion of the yolk stalk and body stalk produce the umbilical stalk, or umbilical cord. The hindgut extends from the midgut to the cloacal membrane that separates the hindgut from the proctodeum. The proctodeum (anal pit) is an invagination of surface (epidermal) ectoderm that develops in the hindgut and develops into the anus. The cloacal membrane ruptures making the hindgut continuous with the outside of the embryo through the anus. A band of mesenchymal cells called the urorectal septum grows caudally during the fourth through seventh week until it forms a complete partition that separates the cloaca into the dorsal (posterior) anal canal and ventral (anterior) urogenital sinus that retains connection to the allantois. With completion of the urorectal septum, the cloacal membrane is separated into an anterior urogenital membrane and a posterior anal membrane. The anal membrane ruptures toward the end of the seventh week to form the anal opening that is lined with ectodermal cells. About this time, the urogenital membrane ruptures to provide further development of the genital and urinary systems. The endoderm of the hindgut produces the lining and glands of the gastrointestinal tract from the distal end of the midgut to the upper part of the anal canal. During the 6th week, the enodermal epithelium of the gut tube proliferates until it completely occludes the lumen. The
vacuoles develop and coalesce until the tube is recanalized. During the 9th week

mucosal epithelium differentiates from the endodermal lining. The mesodermal coating gives rise to the submucosa and smooth muscle layers.

Abnormalities : There are various abnormal rotation of the hind gut leading to a condition known as volvulus. This occurs when the midgut lies free with only duodenum

and proximal colon attached to the posterior abdominal wall. It can also occur as suspended regions of the gut twist around themselves constricting the intestine and compromising the blood supply.