Gastrointestinal system

The trilaminar disc in the embryo folds to form a tube with three layers - innermost is endoderm, middle layer of mesoderm and outer layer of ectoderm. The inner endodermal tube is divided into three regions - foregut, midgut and hindgut. The midgut is connected to the yolk sac through the vitelline duct. The endoderm forms the lining of the digestive tract and forms glands and parenchyma of liver and pancreas. Splanchnic or visceral mesoderm gives rise to the visceral peritoneum, mesentery, muscle, blood vessels and connective tissue. Somatic mesoderm forms the parietal peritoneum. Dorsal mesentery of the stomach becomes the greater omentum while the ventral mesentery becomes the lesser omentum. Neurons in the myenteric and submucosal plexuses are derived from the neural crest.

Derivatives of foregut, midgut and hindgut

Nkx2-1

This gene is expressed by cells forming the anterior wall of the foregut and leads to the development of the trachea and lungs.

Sox2

This gene is present in the dorsal wall of the foregut and causes differentiation of cells into the esophagus.

Noggin from the notochord, Wnt or wingless related integration site proteins, BMP (bone morphogenetic protein which should be low) and fibroblast growth factor also help in the above process. Hnf1 beta (hepatocyte nuclear factor) and retinoic acid regulate the development of the posterior foregut.

HOX or Homeobox genes

HOX genes are highly evolutionarily conserved, important regulators of development both in prenatal and postnatal life. They are located in four clusters on chromosomes 7p, 17q, 12q and 2q. HOX genes are ubiquitous in nature. It controls the differentiation of cells depending on positional information and proper cranio-caudal confirmation, simply meaning that the head is on top and legs are positioned inferiorly etc. Mutations can cause malformations like synpolydactyly, emphysema, lung cancer, pulmonary HT, leukemias, ovarian cancers etc.

Hedgehog genes

SHH gene(Sonic Hedgehog) codes for the Sonic Hedgehog protein. It is important for the normal growth, differentiation and patterning of the developing body. It is located on chromosome 7q. Mutations cause developmental disorders of the brain and spinal cord, eyes, limbs and many other body parts like holoprosencephaly, coloboma and microphthalmia. In holoprosencephaly, the brain fails to divide into two separate hemispheres. Microphthalmia (small underdeveloped eyes) and Coloboma (missing tissue) of the iris, retina or optic nerve can occur.

CDX2

It is a homeobox gene that codes for an intestine specific transcription factor. It is also expressed in colorectal and other gastrointestinal carcinomas, AML and Barrett’s esophagus.

Tracheo-esophageal fistula (TEF)

It is a congenital malformation causing an abnormal communication or fistula between the trachea and esophagus or causing esophageal atresia. Five types are seen -A,B,C,D and E. Type C is the most common. Type A is isolated esophageal atresia. Type B is esophageal atresia and proximal TEF. Type C is esophageal atresia and distal TEF. Type D is esophageal atresia and both proximal and distal TEF. Type E is plain TEF with no esophageal atresia, also called H type. Clinically TEF presents with poor feeding, drooling, excessive salivation, choking while feeding etc. Polyhydramnios will be seen in the fetal period. Intrauterine diagnosis can be done by ultrasound. Chest X ray after passing a nasogastric tube will show a coiled tube in the atretic esophagus. TEF may be associated with VACTERL defects, which stands for vertebral, anorectal, cardiac, tracheal, esophageal, renal and limb defects. PDA, ASD, VSD and imperforate anus are common anomalies associated with VACTERL defects. Pulmonary hypoplasia and congenital diaphragmatic hernia may also be seen.

Incomplete canalization of the esophagus can result in esophageal webs. They may be associated with TEF. They present as dysphagia and food impaction, sometimes presenting years later.

HPS (hypertrophic pyloric stenosis)

It is a congenital disorder resulting from abnormal hypertrophy and hyperplasia of the smooth muscle of the gastric pylorus causing gastric outlet obstruction. It has an incidence of 3 per 1000 live births per year. It presents between the second to sixth weeks of life and is more common in whites, males (four times more common than females) and in first born children. The risk increases more than five fold if a first-degree relative is affected. HPS presents as projectile, non-bilious vomiting typically with feeding. The infant is not ill looking and has a voracious appetite. Prolonged vomiting can lead to dehydration, hypochloremic alkalosis and unconjugated jaundice. On clinical examination, peristaltic waves may be visible and an “olive like mass” can be palpated in the right costal area or epigastrium. HPS can be identified on ultrasound as a hypertrophied and abnormally elongated pylorus greater than 14mm long and more than 3mm thick. This finding is also called a “cervix sign”. On the upper GI barium “double track” sign is seen.

Pancreas

The pancreas is formed by the fusion of the ventral and dorsal pancreatic buds, both of which are of endodermal origin. The uncinate process and lower part of the head are formed by the ventral pancreatic bud. Rest of the pancreas is formed from the dorsal pancreatic bud. Following developmental malformations are seen:

1. Annular pancreas: In this disorder a ring of pancreatic tissue encircles the second part of the duodenum causing intestinal obstruction. It happens as a result of errors in the fusion of the two pancreatic buds. Annular pancreas is often associated with Down’s syndrome, intestinal atresia, malrotation, TEF and cardiac defects. It presents clinically with bilious vomiting. No lump is palpated on abdominal examination. On imaging a “double bubble” sign is seen due to distended stomach and proximal duodenum. It is good to know though that this sign is also seen in conditions such as duodenal atresia, midgut volvulus and SMA syndrome.

2. Pancreas divisum: It is the most common developmental anomaly of the pancreas. It is caused by non-fusion or incomplete fusion of the ductal system of the ventral and dorsal pancreatic buds. As a result, the major part of the gland is drained by the smaller duct of Santorini into the minor duodenal papilla. It may cause increased incidence of recurrent pancreatitis.

3. Ectopic pancreas: Ectopic pancreatic tissue may be seen in the stomach, duodenum, jejunum or Meckel’s diverticulum.

4. Cysts: Multilocular pancreatic cysts are associated with VHL disease and ADPKD.