0 | P a g e

-1

- Tamara Wahbeh

-

- Fareed Khdair

1 | 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)

2 | 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.

3 | 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.

4 | 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.

5 | 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.

6 | 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.

7 | 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.

8 | 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.

9 | 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

10 | 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 3rd and 6th week of fetal life. It

is simply corrected by surgical procedure where we form an incision to release

the obstruction.

11 | 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.

12 | 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 5th 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.

13 | 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.

14 | 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

15 | 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

16 | 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.

17 | 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.

18 | P a g e