Development of Digestive System
Development of the Primordial Gut
Formation begins in the fourth week, closed
at cranial end by oropharyngeal membrane
and caudal end by cloacal membrane.
Dorsal part of umbilical vesicle integrated
into embryo via head, tail, and lateral folds.
Epithelium and Glands: Primarily derived
from endoderm.
Ectoderm from stomodeum (cranial) and
proctodeum (caudal).
Development of Digestive System…
• Key Factors in Development:
Fibroblast Growth Factors (FGFs): induce endoderm formation.
Activins and TGF-β superfamily contribute to endoderm development.
Mesodermal Contributions:
Derived from splanchnic mesenchyme, forming muscular and connective
tissue layers.
Mesenchymal factors and FoxF proteins regulate endodermal proliferation.
Gut Division:
Parts: Foregut, Midgut, Hindgut.
Molecular Regulation
Hox and ParaHox genes,
Sonic hedgehog (Shh)
Signals regulate regional differentiation.
Foregut
The derivatives of the foregut:
The primordial pharynx and its
derivatives
The lower respiratory system
The esophagus and stomach
The duodenum, distal to the opening of
the bile duct
The liver, biliary apparatus (hepatic
ducts, gallbladder, and bile duct), and
pancreas
The foregut derivatives are supplied by
the celiac trunk, the artery of the
foregut
Development of the Esophagus
Develops from the foregut
Tracheoesophageal Septum: Separates trachea from esophagus
Initial Length: Starts short; elongates rapidly due to heart and lung growth.
Final Length: Achieved by the seventh week of gestation.
• Epithelium Glands: Derived from endoderm.
Initial proliferation may partially or completely obliterate the lumen.
Normal recanalization occurs by the end of the eighth week
Development of the Esophagus…
• Muscular Development:
• Muscularis Externa:
Superior Third: Striated muscle from mesenchyme of caudal pharyngeal
arches.
Inferior Third: Smooth muscle from surrounding splanchnic
mesenchyme.
• Innervation:
• Vagus Nerves (Cranial Nerve X): Supply both types of muscle,
originating from caudal pharyngeal arches.
Esophageal Atresia…
Blockage of the esophagus occurs with an incidence of 1 in 3000 to 4500
live births.
Esophageal atresia is associated with tracheoesophageal fistula
It results from deviation of the tracheoesophageal septum in a posterior
direction as a result, there is incomplete separation of the esophagus
from the laryngotracheal tube.
Isolated esophageal atresia may be associated with other congenital
anomalies, e.g., anorectal atresia and anomalies of the urogenital system.
In these cases, the atresia results from failure of recanalization of the
esophagus during the eighth week of development. The cause of this
arrest of development is thought to result from defective growth of
endodermal cells.
Esophageal Atresia…
A fetus with esophageal atresia is unable to swallow amniotic fluid;
consequently, this fluid cannot pass to the intestine for absorption and
transfer through the placenta to the maternal blood for disposal.
This results in polyhydramnios.
Excessive drooling after birth, and fails oral feeding with immediate
regurgitation and coughing.
Inability to pass a catheter through the esophagus
A radiographic examination demonstrates the anomaly by imaging the
nasogastric tube arrested in the proximal esophageal pouch.
Surgical repair of esophageal atresia now results in survival rates of
more than 85%.
Esophageal Stenosis
• Narrowing of the lumen of the esophagus (stenosis) can be
anywhere along the esophagus
• But it usually occurs in its distal third, either as a web or as a
long segment of esophagus with a threadlike lumen.
• Stenosis results from incomplete recanalization of the
esophagus during the eighth week
• It may also result from a failure of esophageal blood vessels to
develop in the affected area.
• As a result, atrophy of a segment of the esophageal wall
occurs
Development of the Stomach
The distal part of the foregut is a simple tubular structure .
Around the middle of the fourth week, a slight dilation indicates the site
of the primordium of the stomach.
It first appears as a fusiform enlargement of the caudal part of the
foregut and is initially oriented in the median plane
The primordial stomach soon enlarges and broadens ventrodorsally.
During the next 2 weeks, the dorsal border of the stomach grows faster
than its ventral border; this demarcates the greater curvature of the
stomach
Development of the Stomach
Rotation of the Stomach
As the stomach enlarges and acquires its final shape, it slowly
rotates 90 degrees in a clockwise direction around its longitudinal
axis.
The ventral border (lesser curvature) moves to the right and the
dorsal border (greater curvature) moves to the left.
The original left side becomes the ventral surface and the original
right side becomes the dorsal surface.
Rotation of the Stomach
Before rotation, the cranial and caudal ends of the stomach are in the
median plane .
During rotation and growth of the stomach, its cranial region moves
to the left and slightly inferiorly, and its caudal region moves to the
right and superiorly.
After rotation, the stomach assumes its final position with its long axis
almost transverse to the long axis of the body.
The rotation and growth of the stomach explain why the left vagus
nerve supplies the anterior wall of the adult stomach and the right
vagus nerve innervates its posterior wall.
Rotation of the Stomach…
The stomach is suspended from the dorsal wall of the
abdominal cavity by a dorsal mesentery-the primordial dorsal
mesogastrium
This mesentery is originally in the median plane, but it is carried
to the left during rotation of the stomach and formation of the
omental bursa or lesser sac of peritoneum
The primordial ventral mesogastrium attaches to the
stomach.
The ventral mesogastrium also attaches the duodenum to the
liver and the ventral abdominal wall
Omental bursa
Isolated clefts develop in the mesenchyme forming the thick
dorsal mesogastrium
The clefts soon coalesce to form a single cavity, the omental
bursa or lesser peritoneal sac
Rotation of the stomach pulls the dorsal mesogastrium to the left,
The omental bursa expands transversely and cranially
lies between the stomach and the posterior abdominal wall.
This pouchlike bursa facilitates movements of the stomach.
Congenital Hypertrophic Pyloric Stenosis
Anomalies of the stomach are uncommon except for hypertrophic
pyloric stenosis. This anomaly affects one in every 150 males and
one in every 750 females.
In infants with this anomaly a marked muscular thickening of the
pylorus region of the stomach
This results in severe stenosis of the pyloric canal and obstruction of
the passage of food.
As a result the infant expels the stomach's contents (projectile
vomiting).
Surgical relief of the pyloric obstruction (pyloromyotomy) is the usual
treatment.
Development of the Duodenum
Early in the fourth week, the duodenum begins to develop from the caudal part of the
foregut
The junction of the two parts of the duodenum distal to the origin of the bile duct
The developing duodenum grows rapidly, forming a C-shaped loop that projects
ventrally
As the stomach rotates, the duodenal loop rotates to the right and comes to lie
retroperitoneally
Because of its derivation from the foregut and midgut, the duodenum is supplied by
branches of the celiac and superior mesenteric arteries
During the fifth and sixth weeks, the lumen of the duodenum becomes progressively
smaller and is temporarily obliterated because of the proliferation of its epithelial cells.
The duodenum becomes recanalized by the end of the embryonic period
By this time, most of the ventral mesentery of the duodenum has disappeared.
Development of the Liver and Biliary
Apparatus
The liver, gallbladder, and biliary duct system arise as a ventral
outgrowth-hepatic diverticulum-from the caudal or distal part of
the foregut early in the fourth week
Hepatic diverticulum and the ventral bud of the pancreas develop
from two cell populations in the embryonic endoderm.
FGFs interact with the bipotential cells and induce formation of the
hepatic diverticulum.
The diverticulum extends into the septum transversum, a mass of
splanchnic mesoderm between the developing heart and midgut.
The septum transversum forms the ventral mesentery in this region.
Development of Liver
The hepatic diverticulum enlarges rapidly and divides into two parts:
The larger cranial part of the hepatic diverticulum is the primordium
of the liver.
Endodermal cells give rise to hepatocytes
Epithelial lining of the intrahepatic part of the biliary apparatus.
The hepatic cords anastomose around endothelium-lined spaces, the
primordia of the hepatic sinusoids.
Mesenchyme cells in the septum transversum forms:
The fibrous and hematopoietic tissue
Kupffer cells of the liver
Development of Liver…
The liver grows rapidly and, from the 5th to 10th weeks, fills a large
part of the upper abdominal cavity
The quantity of oxygenated blood flowing from the umbilical vein into
the liver determines the development and functional segmentation of
the liver.
Initially, the right and left lobes are approximately the same size, but
the right lobe soon becomes larger. Hematopoiesis begins during the
sixth week, giving the liver a bright reddish appearance.
By the ninth week, the liver accounts for approximately 10% of the
total weight of the fetus.
Bile formation by hepatic cells begins during the 12th week
Development of Gallbladder
The small caudal part of the hepatic diverticulum becomes the
gallbladder, and the stalk of the diverticulum forms the cystic
duct
The stalk connecting the hepatic and cystic ducts to the
duodenum becomes the bile duct.
Initially, this duct attaches to the ventral aspect of the duodenal
loop; however, as the duodenum grows and rotates, the entrance
of the bile duct is carried to the dorsal aspect of the duodenum
The bile entering the duodenum through the bile duct after the
13th week gives the meconium (intestinal contents) a dark green
color.
Development of the Pancreas
The pancreas develops from dorsal and ventral pancreatic buds of
endodermal cells, which arise from the caudal or dorsal part of the foregut
Most of the pancreas is derived from the dorsal pancreatic bud.
The larger dorsal pancreatic bud appears first and develops a slight
distance cranial to the ventral bud.
It grows rapidly between the layers of the dorsal mesentery.
The ventral pancreatic bud develops near the entry of the bile duct into the
duodenum and grows between the layers of the ventral mesentery. As the
duodenum rotates to the right and becomes C shaped, the ventral
pancreatic bud is carried dorsally with the bile duct
It soon lies posterior to the dorsal pancreatic bud and later fuses with it.
Development of the Pancreas…
The ventral pancreatic bud forms the uncinate process and part of the
head of the pancreas.
As the stomach, duodenum, and ventral mesentery rotate, the pancreas
comes to lie along the dorsal abdominal wall.
As the pancreatic buds fuse, their ducts anastomose.
The pancreatic duct forms from the duct of the ventral bud and the distal
part of the duct of the dorsal bud
The proximal part of the duct of the dorsal bud often persists as an
accessory pancreatic duct that opens into the minor duodenal papilla,
located approximately 2 cm cranial to the main duct. The two ducts often
communicate with each other. In approximately 9% of people, the
pancreatic ducts fail to fuse, resulting in two ducts.
Development of the Pancreas…
The parenchyma of the pancreas is derived from the endoderm of the pancreatic buds
Early in the fetal period, pancreatic acini begin to develop from cell clusters around
the ends of these tubules
The pancreatic islets develop from groups of cells that separate from the tubules and
come to lie between the acini.
Insulin secretion begins during the early fetal period (10 weeks).
The glucagon- and somatostatin-containing cells develop before differentiation of the
insulin-secreting cells.
Glucagon has been detected in fetal plasma at 15 weeks.
The connective tissue sheath and interlobular septa of the pancreas develop from the
surrounding splanchnic mesenchyme.
When there is maternal diabetes mellitus, the insulin-secreting beta cells in the fetal
pancreas are chronically exposed to high levels of glucose. As a result, these cells
undergo hypertrophy to increase the rate of insulin secretion.
MIDGUT
The derivatives of the midgut are
Small intestine, including the duodenum distal to the opening of the bile duct
Cecum , appendix, ascending colon, and the right one half to two thirds of the transverse colon
These derivatives are supplied by the superior mesenteric artery, the midgut artery
As the midgut elongates, it forms a ventral, U-shaped midgut loop of the intestine-that projects
into the the extraembryonic coelom in the proximal part of the umbilical cord.
At this stage, the intraembryonic coelom communicates with extraembryonic coelom at the
umbilicus
This midgut loop of the intestine is a physiologic umbilical herniation, which occurs at the
beginning of the sixth week
The loop communicates with the umbilical vesicle through the narrow omphaloenteric duct
(yolk stalk) until the 10th week.
Mid gut…
The physiologic umbilical herniation occurs because there is not
enough room in the abdominal cavity for the rapidly growing midgut.
The shortage of space is caused by massive liver and the kidneys
The midgut loop of intestine has a cranial limb and a caudal limb and
is suspended from the dorsal abdominal wall by an elongated
mesentery
The cranial limb grows rapidly and forms small intestinal loops,
The caudal limb little change except for development of the cecal
swelling (diverticulum), the primordium of the cecum, and appendix
Rotation of the Midgut
The midgut loop rotates 90
degrees counterclockwise
around the axis of the superior
mesenteric artery
This brings the cranial limb of
the midgut loop to the right
The caudal limb to the left.
During rotation, the cranial limb
elongates and forms intestinal
loops (e.g., primordia of jejunum
and ileum).
Rotation of the Midgut…
During the 10th week, the intestines return to the abdomen
Due to the enlargement of the abdominal cavity, and decrease in the size of the liver and kidneys are
important factors.
The small intestine returns first, passing posterior to the SMA and occupies the central part of the
abdomen.
As the large intestine returns, it undergoes a further 180-degree counterclockwise rotation
Later it comes to occupy the right side of the abdomen.
Rotation of the Midgut…
Rotation of the stomach and duodenum causes the duodenum
and pancreas to fall to the right. The colon presses the duodenum
and pancreas against the posterior abdominal wall
As a result, most of the duodenal mesentery is absorbed
As the intestines enlarge, lengthen, and assume their final
positions, their mesenteries are pressed against the posterior
abdominal wall.
The mesentery of the ascending colon fuses with the parietal
peritoneum on this wall and disappears; consequently, the
ascending colon also becomes
Other derivatives of the midgut loop (e.g., the jejunum and ileum)
retain their mesenteries.
Cecum and Appendix
The primordium of the cecum and appendix-the cecal swelling (diverticulum)-appears in
the sixth week as an elevation on the the caudal limb of the midgut loop
The apex of the cecal swelling does not grow as rapidly as the rest of it; thus, the
appendix is initially a small diverticulum of the cecum
The appendix increases rapidly in length so that at birth it is a relatively long tube arising
from the distal end of the cecum
After birth, the wall of the cecum grows unequally, with the result that the appendix
comes to enter its medial side.
The appendix is subject to considerable variation in position.
As the ascending colon elongates, the appendix may pass posterior to the cecum
(retrocecal appendix) or colon (retrocolic appendix).
It may also descend over the brim of the pelvis (pelvic appendix). In approximately 64%
of people, the appendix is located retrocecally
HINDGUT
The derivatives of the hindgut are
The left one third to one half of the transverse colon
The descending colon
Sigmoid colon
Rectum
Superior part of the anal canal
The epithelium of the urinary bladder and most of the urethra
All hindgut derivatives are supplied by the inferior mesenteric artery
The descending colon becomes retroperitoneal as its mesentery fuses
with the peritoneum on the left posterior abdominal wall and then
disappears
The mesentery of the sigmoid colon is retained, but it is shorter than in
the embryo.
Cloaca
• The expanded terminal part of the hindgut, the cloaca
• An endoderm-lined in contact with the surface ectoderm at the
cloacal membrane
• This membrane is composed of endoderm of the cloaca and
ectoderm of the proctodeum or anal pit
• The cloaca receives the allantois ventrally which is a fingerlike
diverticulum.
Partitioning of the Cloaca
The cloaca is divided into dorsal and ventral parts by urorectal septum between the allantois and
hindgut.
As the septum grows toward the cloacal membrane, it develops forklike extensions that produce
infoldings of the lateral walls of the cloaca.
These folds grow toward each other and fuse, forming a partition that divides the cloaca into two
parts
The rectum and cranial part of the anal canal dorsally
The urogenital sinus ventrally
• By the seventh week, the urorectal septum has fused with the cloacal membrane
• Dividing it into a dorsal anal membrane and a larger ventral urogenital membrane
• The area of fusion of the urorectal septum with the cloacal membrane is represented in the adult by the
perineal body, the tendinous center of the perineum.
• This fibromuscular node is the landmark of the perineum where several muscles converge and attach.
• The urorectal septum also divides the cloacal sphincter into anterior and posterior parts.
• The posterior part becomes the external anal sphincter, and the anterior part develops into the
superficial transverse perineal, bulbospongiosus, and ischiocavernosus muscles.
• This developmental fact explains why one nerve, the pudendal nerve, supplies all these muscles.
• Mesenchymal proliferations produce elevations of the surface ectoderm around the anal membrane. As a
result, this membrane is soon located at the bottom of an ectodermal depression-the proctodeum or
anal pit
• The anal membrane usually ruptures at the end of the eighth week, bringing the distal part of the
digestive tract (anal canal) into communication with the amniotic cavity.
Anal Canal
The superior two thirds of the adult anal canal
are derived from the hindgut
The inferior one third develops from the
proctodeum
The junction of the epithelium derived from the
ectoderm of the proctodeum and the endoderm
of the hindgut is indicated by pectinate line
This line indicates the composition of the anal
epithelium changes from columnar to stratified
squamous cells.
At the anus, the epithelium is keratinized and
continuous with the skin around the anus.
The other layers of the wall of the anal canal
are derived from splanchnic mesenchyme.
