-1 - Tamara Wahbeh - - Fareed Khdair 0 P a g e
GI Embryology Note: I included everything in the records and slides; anything in the slide not included in this sheet was not mentioned by the doctor during the lecture. In this sheet we will be covering the embryology of the foregut. We will also be covering the clinical symptoms observed in children in relation to embryological defects of the GI tract. Before talking about the foregut we must define what it is. The foregut includes the following organs: the esophagus, stomach, duodenum, liver, gall bladder, and spleen. Foregut: Symptoms related to GI tract development include Vomiting Jaundice Abdominal distension Constipation The following figure is to refresh your memory regarding the general embryological development. (You don t have to memorize anything it is just for you to go over) 1 P a g e
This figure is to show you how the GI tract develops inside the embryo generally. The part in blue is called the ectoderm, the part in red is the mesoderm, and the part in yellow is the endoderm. The first thing that occurs is folding at both sides of the embryo resulting in the formation of a proximal cavity which will develop into the foregut, and a distal cavity which will develop into the hindgut. All the parts of the GI tract either originate from the endoderm, or the mesoderm and NOT the ectoderm. This includes: Endoderm: Formation of the epithelial lining of GI tract, in addition to forming the organ parenchyma like hepatocytes and pancreas glands. Mesoderm: Formation of the Stroma (connective tissue) of the GI glands, in addition to the formation of muscles and gut peritoneum. You should also know that the only organ which is derived solely from the mesoderm is the spleen, meaning that no other parts of the embryo will contribute to its development other than the mesoderm, unlike all other organs which are formed by both the endoderm and mesoderm. 2 P a g e
This picture is important. It is showing a cross section of the embryo during its development. As you can see, the GI tract placed in the abdominal cavity starts as a small cylindrical tube extending from the mouth to the anus, and then as the embryo grows, the structures of the GI tract will start to form. However, this tube is not just hanged freely in the abdominal cavity; it must be fixed in its position and this is done by the help of the mesenteries. Anteriorly, we have the ventral mesentery, while posteriorly we have the dorsal mesentery. As you know, the mesentery is a double layer of peritoneum. Behind the dorsal mesentery the development of the spinal cord will take place, while in front of it, the GI tract (which is the small tube shown ) will develop. 3 P a g e
In addition to suspending the gut wall in the abdominal cavity, the mesenteries are also responsible for providing a pathway for nerves, blood vessels, and lymphatics to pass to the organs. The dorsal mesentery passes from the esophagus to the lower hind gut, while the ventral mesentery passes from the esophagus to the upper duodenum. So the dorsal mesentery posteriorly is much longer than the ventral mesentery anteriorly. Another name for the ventral mesentery is septum transversum. The following picture further clarifies the dorsal and ventral mesentery. Again, the dorsal mesentery attaches the gut to the posterior abdominal wall, while the ventral mesentery attaches it to the anterior abdominal wall. The orange area represents the dorsal mesentery which extends along the whole posterior abdominal wall from the esophagus to the lower hindgut. Each part of the mesentery is named according to the structure it passes behind. Behind the stomach it is called the dorsal mesogastrium, behind the duodenum it is the dorsal mesoduodenum, behind the small bowel or intestine it is the mesentery proper, and behind the colon it is the dorsal mesocolon. 4 P a g e
The blood supply also differs between the foregut, midgut, and hindgut, because of their compartmentalization during embryological development Foregut: Celiac artery Midgut: Superior mesenteric artery Hindgut: Inferior mesenteric artery Esophagus 1) Atresia If a newborn is constantly vomiting after drinking milk, we should think of performing nasogastric intubation where a nasogastric tube is inserted from the nose, passing through the pharynx, esophagus, and stomach, so that we can examine the gut wall to see if we have any developmental anomalies. As you see in the picture below, we realize that the tube coils at the level of the esophagus and does not pass down reaching the stomach like it is supposed to. This coiling is explained by the presence of esophageal atresia; meaning that the esophagus is obstructed and this is why we have regurgitation every time this newborn drinks milk. 5 P a g e
To understand why esophageal atresia could take place, we should first understand the development of the esophagus. The picture below shows a 4 week old embryo: The part in yellow is the endoderm. As you can see in blue, we have something called the lung bud or the respiratory diverticulum emerging from the ventral part of the foregut anteriorly. 6 P a g e
Again looking at the figure below, you see how the lung bud grows anteriorly from the ventral part of the foregut. When it first develops, the foregut and the lung bud are continuous spaces with an open communication between them as seen in figure A. Then as the development continues, the lung bed expands caudally (towards the posterior side of the body) and the open communication will start to close as you see in figure B by the pressure exerted inwards by the connective tissue of the mesoderm forming two ridges on both sides. These ridges are called tracheoesophageal ridges. The ridges will lastly fuse to form a complete separation between the lung bud and the foregut and now the tracheoesophageal ridge will be called the tracheoesophageal septum as seen in figure C. By this, the foregut will be divided into two portions: the distal portion (posteriorly) which is formed by the esophagus, and the ventral portion (anteriorly) which is formed by the trachea and lung buds. 7 P a g e
After this development, the esophagus would be short. It becomes longer with the descending of the lungs and heart which will pull it downwards towards the stomach. According to this, how does atresia happen? In general, atresia develops either from: I. Spontaneous posterior deviation of the tracheoesophageal septum. II. Mechanical factor pushing the dorsal wall (posterior wall) of the foregut anteriorly. Atresia can take up many forms as seen in the figure below: A: In this case the proximal end of the esophagus is a blind sac (obstructed), and the distal part is connected to the trachea by a narrow canal just above the bifurcation (fistula). This is the most common form of atresia. B: Both the proximal and distal esophagus end as blind sacs. C: Both proximal and distal ends of the esophagus are connected to the trachea through a fistula while they are both communicating with each other at the same time. D: The distal end of the esophagus is a blind sac, and the proximal part is connected to the trachea through a fistula E: Both proximal and distal ends of the esophagus are connected to the trachea through a fistula but they do NOT communicate with each other like in figure C. 8 P a g e
During embryological development, the amniotic fluid is supposed to be swallowed by the child to reach the intestinal tract, but when we have atresia, the child will not be able to do that and we develop another complication called polyhydraminos. The treatment for esophageal atresia is surgical treatment where the esophagus is removed from the trachea and the proximal and distal ends will be joined by anastomosis. 2) Esophageal Stenosis Atresia is not the only reason behind vomiting. Stenosis or strictures can also cause that. It is simply a narrowing of the esophagus usually at the lower third of the esophagus. This could happen because of: I. Incomplete recanalization II. Vascular abnormalities like ischemia, or accidents that comprise blood flow. 3) Congenital Hiatal Hernia This happens when the esophagus fails to lengthen sufficiently, so instead of lengthening the esophagus the stomach is pulled up into the esophageal hiatus through the diaphragm. Lastly, the esophagus is composed of two types of muscles derived from the surrounding splanchnic mesenchyme: I. Upper 2/3: striated muscle and is innervated by the vagus nerve II. Lower 1/3 : smooth muscle and is innervated by the splanchnic plexus 9 P a g e
Stomach: The embryologic development of the stomach differs from the esophagus. Before its development, the anterior abdominal wall is innervated by the left vagus nerve, and the posterior wall is innervated by the right vagus nerve. The stomach is simply a fusiform dilation of the foregut (wide center and narrow periphery) which appears at the fourth week of development. As seen in the picture, the dorsal mesentery is placed posteriorly while the ventral mesentery is placed anteriorly. At day 28, the stomach will rotate 90 degrees about its longitudinal axis so that the left side faces anteriorly, and the right side faces posteriorly. This rotation will cause different growth phases in the stomach where the original posterior wall of the stomach grows faster than the anterior portion, forming the greater and lesser curvatures. A clinical disorder that can cause vomiting in the stomach is pyloric stenosis. This occurs when the pylorus of the stomach becomes obstructed due to hypertrophy of the pylorus muscle. It is one of the most common disorders in infants. It develops during the period between the 3 rd and 6 th week of fetal life. It is simply corrected by surgical procedure where we form an incision to release the obstruction. 10 P a g e
As you see in the picture below, the stomach has many attachments, where it is attached to the dorsal body wall by the dorsal mesogastrium and to the ventral body wall by the ventral mesogastrium, so a consequence of the rotation and disproportionate growth to form the greater and lesser curvatures is the alteration of the position of these mesenteries. The rotation about the longitudinal axis pulls the dorsal mesogastrium to the left, creating a space behind the stomach called the omental bursa (lesser peritoneal sac). This rotation also pulls the ventral mesogastrium to the right. Again, as you see below, the dorsa mesoderm moves to the left creating the lesser peritoneal sac which is composed of the endoderm (in yellow) and the mesoderm (in red). As for the rest of the mesoderm, it will be surrounding the spleen (remember it is the only organ which is formed only by the mesoderm), and the mesoderm linking between the spleen and the stomach is now the gastrosplenic ligament, and the rest of the mesoderm after surrounding the spleen will continue to the kidney forming the splenorenal ligament. 11 P a g e
The dorsal mesogastrium bulges down from the omental bursa and it continues to grow down and forms a double-layered sac over the transverse colon and small intestinal loops which we call the greater omentum. Spleen As we said before, the spleen is a continuation of the mesoderm that forms the lesser peritoneal sac (omental bursa) which appears after the 5 th week of embryological development. The spleen is an intraperitoneal structure. After we finished talking about clinical cases related to vomiting, we will now talk about cases related to the liver and gall bladder. In the picture below, the baby appears to be yellow in color indicating jaundice, and his stool looks pale and clay colored. This is a sign of congenital biliary atresia where the biliary ducts are obstructed so instead of pouring the bile into the small intestine, it flows in the blood. To understand this, we must first examine the development of the liver and gall bladder. 12 P a g e
Liver and Gall Bladder: As you can see in the picture below, from the ventral mesentery, the liver bud or diverticulum will emerge. There will be an anterior outgrowth of the foregut. The liver bud is formed by the endoderm (in yellow) and as it outgrows anteriorly it will penetrate the septum transversum such that it becomes covered also by a layer of mesoderm. After that, the differentiation will begin where connection between the hepatic diverticulum and the foregut (duodenum) narrows, forming the bile duct and a small ventral outgrowth is formed by the bile duct to give the gallbladder and the cystic duct. 13 P a g e
Histologically, the liver is a hexagonal structure composed of hepatocytes. The center of this hexagon contains the central vein, and at the outer margins of the hexagon we have the portal triad which is composed of the: bile duct, hepatic artery, and portal vein. The hepatocytes and gall bladder originate from the epithelial liver cords, while the hematopoietic cells, kupffer cells, and connective tissue cells are derived from mesoderm of the septum transversum. So as you see, part of the liver is composed of the endoderm that we started with, and the other part is formed from the mesoderm after the invagination of the liver bud into it. This is clarified in the picture below: What happens to the rest of the septum transversum forming the liver? Part of what is left of it will form the falciform ligament which connects the liver to the anterior abdominal wall, and the other part will form the lesser omentum connecting the liver to the lesser curvature of the stomach. The free margin of the lesser omentum forms the roof of the epiploic foramen of Winslow: opening connecting the omental bursa (lesser sac) with the rest of the peritoneal cavity (greater sac).the free margin of the falciform ligament contains the umbilical vein. Among birth, the umbilical vein will be obliterated forming the round ligament of the liver (ligamentum teres). Now that we have understood the development of the liver, let s go back to biliary atresia. The etiology of congenital biliary atresia is actually unknown, but what happens is that during the narrowing of the foregut to form the bile duct, it will narrow down much more than needed leading to an obstruction. This will lead to the accumulation of bile in the blood instead of being secreted into the small 14 P a g e
intestine. We usually treat this by surgical procedures involving an incision in the gall bladder where we connect the small intestine to the liver so that the bile directly flows to the small intestine. If this doesn t work, we will have to do a liver transplant. Duodenum: It originates from the terminal part of the foregut and the cephalic part of the midgut. As the stomach rotates, the duodenum takes on the form of a C-shaped loop and rotates to the right. The most important thing to know about the duodenum is that during the second month, the lumen of the duodenum is obliterated by proliferation of cells in its walls. It is recanalized shortly after. This is shown below: Clinical point: Failure to recanalize will lead to duodenal atresia. The child will immediately vomit after any ingestion of milk. Since the common bile duct and the pancreatic duct will unite and secrete the bile into the second part of the duodenum, with duodenal atresia, the vomiting is usually accompanied with bile 15 P a g e
and we call it bilious vomiting. On the other hand, the clinical signs of congenital biliary atresia do not appear immediately after birth, but rather after approximately one month. Also, the presence of bile in the vomit in this case helps us in ruling out the other causes of vomiting that we have discussed previously. This is treated by surgery. Pancreas: The embryological development of the pancreas occurs in 3 stages as seen in the picture below: 1. Formation: It is formed by two buds of the endodermal lining; the dorsal pancreatic bud in dorsal mesentery & the ventral pancreatic bud which is close to the bile duct. 2. Rotation: When the duodenum rotates to the right and becomes C- shaped, the ventral pancreatic bud rotates dorsally along with the bile duct. 3. Fusion: The ventral bud fuses with the dorsal bud. 16 P a g e
Clinically: Sometimes, the right portion of the ventral bud migrates along its normal route, but the left migrates in the opposite direction. The duodenum is surrounded by pancreatic tissue, which constricts the duodenum and causes complete obstruction as shown below. This is associated with bilious vomiting, and is treated through surgery. 17 P a g e
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