Development of the

digestive system

Yosef Tadesse

1
Outline
• Formations of the gut tube
• Mesenteries
• Pharyngeal gut
• Foregut
• Midgut
• Hindgut

2
Formations of the Gut Tube
• As a result of cephalocaudal and lateral folding
of the embryo, a portion of the endoderm-lined
yolk sac cavity is incorporated into the embryo
to form the primitive gut
• Two other portions of the endoderm-lined
cavity, the yolk sac and the allantois, remain
outside the embryo
• In the cephalic and caudal parts of the embryo,
the primitive gut forms a blind-ending tube, the
foregut and hindgut, respectively
• The middle part, the midgut, remains
temporarily connected to the yolk sac by
means of the vitelline duct, or yolk stalk
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• The primitive gut is divided into four
parts
– Pharyngeal gut
• extends from the buccopharyngeal membrane
to the tracheobronchial diverticulum
– Foregut
• lies caudal to the pharyngeal tube and
extends as far caudally as the liver outgrowth
– Midgut
• begins caudal to the liver bud and extends to
the junction of the right two-thirds and left
third of the transverse colon in the adult
– Hindgut
• extends from the left third of the transverse
colon to the cloacal membrane
6
Embryos during the fourth (A) and fifth (B) weeks of development
showing formation of the gastrointestinal tract and the various
derivatives originating from the endodermal germ layer. 7
• Endoderm forms the epithelial lining of
the digestive tract and gives rise to
the parenchyma of glands
• Muscle, connective tissue, and
peritoneal components of the wall of
the gut are derived from splanchnic
mesoderm

8
Mesenteries
• Initially the foregut, midgut, and hindgut are
in broad contact with the mesenchyme of the
posterior abdominal wall
• Dorsal mesentery
– By the fifth week, however, the connecting
tissue bridge has narrowed, and the caudal
part of the foregut, the midgut, and a major
part of the hindgut are suspended from the
abdominal wall by the dorsal mesentery
– Extends from the lower end of the
esophagus to the cloacal region of the
hindgut
9
– In the region of the lower esophagus it
forms dorsal mesentery of esophagus
– In the region of the stomach it forms the
dorsal mesogastrium or greater
omentum
– In the region of the duodenum it forms
the dorsal mesoduodenum
– Dorsal mesentery of the jejunal and ileal
loops forms the mesentery proper
– In the region of the colon it forms the
dorsal mesocolon

10
• Ventral mesentery
• Exists only in the region of the terminal
part of the esophagus, the stomach, and
the upper part of the duodenum
• Derived from the septum transversum
• Growth of the liver into the mesenchyme
of the septum transversum divides the
ventral mesentery into
– Lesser omentum, extending from the lower
portion of the esophagus, the stomach, and
the upper portion of the duodenum to the
liver
– Falciform ligament, extending from the
liver to the ventral body wall

11
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Pharyngeal gut

• Give rise to
– Oral cavity
– Pharynx
– Tongue
– Tonsils
– Salivary glands
– Thyroid gland
– Parathyroid glands
– Thymus
13
Foregut
• Give rise to
– Lower respiratory tract
– Esophagus
– Stomach
– Duodenum, proximal to the opening of the bile
duct
– Liver
– Biliary apparatus (gallbladder and bile duct
system)
– Pancreas
• Supplied by celiac artery, except the
respiratory system 14
15
Esophagus
• When the embryo is approximately 4 weeks old, the
respiratory diverticulum (lung bud) appears at the
ventral wall of the foregut at the border with the
pharyngeal gut
• The tracheoesophageal septum gradually partitions
this diverticulum from the dorsal part of the foregut
• In this manner the foregut divides into
– ventral portion - respiratory primordium
– dorsal portion - esophagus
• At first the esophagus is short, but with descent of the
heart and lungs it lengthens rapidly
• Its epithelium and glands are derived from endoderm

• The muscular coat and connective tissue are formed

by surrounding splanchnic mesenchyme
• The lumen is temporarily obliterated by proliferation
of epithelium, recanalize later 16
Successive stages in development of the respiratory diverticulum and
esophagus through partitioning of the foregut. A. At the end of the third
week (lateral view). B,C. During the fourth week (ventral view). 17
Esophageal Abnormalities
• Esophageal atresia and/or
tracheoesophageal fistula
– Results either from spontaneous posterior
deviation of the tracheoesophageal septum or
from some mechanical factor pushing the dorsal
wall of the foregut anteriorly
– In its most common form the proximal part of
the esophagus ends as a blind sac, and the
distal part is connected to the trachea by a
narrow canal just above the bifurcation
– Atresia of the esophagus prevents normal
passage of amniotic fluid into the intestinal
tract, resulting in accumulation of excess fluid in
the amniotic sac (polyhydramnios)
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• Esophageal stenosis
– narrowing of the lumen
– usually in the lower third
– caused by incomplete recanalization,
vascular abnormalities, or accidents that
compromise blood flow
• Congenital hiatal hernia
– the esophagus fails to lengthen
sufficiently and the stomach is pulled up
into the esophageal hiatus through the
diaphragm

20
Stomach
• The stomach appears as a fusiform
dilation of the foregut in the fourth
week of development
• During the following weeks, its
appearance and position change
greatly as a result of the different
rates of growth in various regions of
its wall and the changes in position of
surrounding organs
• It rotates around a longitudinal and
an anteroposterior axis
21
• Rotation along longitudinal axis
– stomach rotates 900 clockwise around its
longitudinal axis
– results in its left side to face anteriorly
and its right side to face posteriorly
– hence the left vagus nerve, initially
innervating the left side of the stomach,
now innervates the anterior wall; similarly,
the right vagus nerve innervates the
posterior wall
– during this rotation the original posterior
wall of the stomach grows faster than the
anterior portion, forming the greater and
lesser curvatures 22
• Rotation along anteroposterior axis
– during further growth the stomach
rotates around an anteroposterior axis
– the cephalic and caudal ends of the
stomach originally lie in the midline
– as a result of this rotation, the caudal or
pyloric part moves to the right and
upward and the cephalic or cardiac
portion moves to the left and slightly
downward
– the stomach thus assumes its final
position, its axis running from above left
to below right
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• Changes in the position of mesenteries
– the stomach is attached to the dorsal body
wall by the dorsal mesogastrium and to
the ventral body wall by the ventral
mesogastrium
– its rotation and disproportionate growth
alter the position of these mesenteries
• 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)
– pulls the ventral mesogastrium to the right
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Elongation of the dorsal mesogastrium and
expansion of the omental bursa
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• Development and position of spleen
– As this process continues in the fifth week of
development, the spleen primordium appears as
a mesodermal proliferation between the two
leaves of the dorsal mesogastrium
– With continued rotation of the stomach, the dorsal
mesogastrium lengthens, and the portion between
the spleen and dorsal midline swings to the left
and fuses with the peritoneum of the posterior
abdominal wall
– The posterior leaf of the dorsal mesogastrium and
the peritoneum along this line of fusion degenerate
– The spleen, which remains intraperitoneal, is then
connected to the body wall in the region of the left
kidney by the lienorenal ligament and to the
stomach by the gastrolienal ligament
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• Rotation about the anteroposterior axis
– As a result of rotation of the stomach
about its anteroposterior axis, the dorsal
mesogastrium bulges down
– It continues to grow down and forms a
double-layered sac extending over the
transverse colon and small intestinal loops
like an apron (greater omentum)
– Later its layers fuse to form a single sheet
hanging from the greater curvature of the
stomach
– The posterior layer of the greater
omentum also fuses with the mesentery of
the transverse colon
35
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• Lesser omentum and falciform
ligament
– Form from the ventral mesogastrium,
which is derived from mesoderm of the
septum transversum
– When liver cords grow into the septum, it
thins to form
• peritoneum of the liver
• falciform ligament, extending from the liver to
the ventral body wall
• lesser omentum, extending from the stomach
and upper duodenum to the liver
– The free margin of the falciform ligament
contains the umbilical vein, which is
obliterated after birth to form the round
ligament of the liver (ligamentum teres
hepatis) 39
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Stomach Abnormalities
• Pyloric stenosis
– Occurs when the circular and, to a lesser
degree, the longitudinal musculature of
the stomach in the region of the pylorus
hypertrophies
– There is an extreme narrowing of the
pyloric lumen, and the passage of food is
obstructed, resulting in severe vomiting
– In a few cases the pylorus is atretic

42
Duodenum
• Formed from terminal part of the foregut
and cephalic part of the midgut
• The junction of the two parts is directly
distal to the origin of the liver bud
• As the stomach rotates, the duodenum
takes on the form of a C-shaped loop and
rotates to the right
• This rotation, together with rapid growth of
the head of the pancreas, swings the
duodenum from its initial midline position
to the right side of the abdominal cavity
43
• The duodenum and head of the pancreas
press against the dorsal body wall, and
the right surface of the dorsal
mesoduodenum fuses with the adjacent
peritoneum
• Both layers subsequently disappear, and
the duodenum and head of the pancreas
become fixed in a retroperitoneal
position
• The dorsal mesoduodenum disappears
entirely except in the region of the pylorus
of the stomach, where a small portion of
the duodenum (duodenal cap) retains its
mesentery and remains intraperitoneal
44
• During the second month, the lumen
of the duodenum is obliterated by
proliferation of cells in its walls
• However, the lumen is recanalized
shortly thereafter
• Since the foregut is supplied by the
celiac artery and the midgut is
supplied by the superior mesenteric
artery, the duodenum is supplied by
branches of both arteries

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• Duodenal Stenosis/Atresia
– Arise due to partial or incomplete
recanalization of the duodenum

– May also occur due to anular pancreas

pressure

50
Liver and gallbladder
• Liver
– The liver primordium appears in the
middle of the third week as an outgrowth
of the endodermal epithelium at the
distal end of the foregut - hepatic
diverticulum, or liver bud
• consists of rapidly proliferating cells that
penetrate the septum transversum
(mesodermal plate between the pericardial
cavity and the stalk of the yolk sac)

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• Bile duct
– While hepatic cells continue to penetrate
the septum, the connection between the
hepatic diverticulum and the foregut
(duodenum) narrows, forming the bile
duct
• Gallbladder and cystic duct
– A small ventral outgrowth is formed by
the bile duct and gives rise to
gallbladder and cystic duct

53
• Hepatic sinusoids
– During further development, epithelial liver
cords intermingle with the vitelline and
umbilical veins, which form hepatic
sinusoids
• Parenchyma (liver cells)
– Liver cords differentiate into the
parenchyma (liver cells) and form the
lining of the biliary ducts
• Hematopoietic cells, Kupffer cells,
and connective tissue cells
– derived from mesoderm of the septum
transversum 54
• Lesser omentum and falciform
ligament
– When liver cells have invaded the entire
septum transversum, mesoderm of the
septum transversum lying between the
liver and the foregut and the liver and
ventral abdominal wall becomes
membranous, forming the lesser
omentum and falciform ligament,
respectively

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• Visceral peritoneum
– Mesoderm on the surface of the liver
differentiates into visceral peritoneum
except on its cranial surface
– In this region, the liver remains in contact
with the rest of the original septum
transversum
– This portion of the septum will form the
central tendon of the diaphragm
– The surface of the liver that is in contact
with the future diaphragm is never
covered by peritoneum - bare area of
the liver
57
• Growth of liver
– In the 10th week of development the
weight of the liver is approximately 10% of
the total body weight
• attributed to
– large numbers of sinusoids
– hematopoietic function
» Large nests of proliferating cells, which produce
red and white blood cells, lie between hepatic
cells and walls of the vessels
» This activity gradually subsides during the last 2
months of intrauterine life, and only small
hematopoietic islands remain at birth
– The weight of the liver is then only 5% of
the total body weight
58
• Biliary system
– Bile formation by hepatic cells begins at
approximately the 12th week
– Meanwhile, since the gallbladder and
cystic duct have developed and the cystic
duct has joined the hepatic duct to form
the bile duct, bile can enter the
gastrointestinal tract
– Because of positional changes of the
duodenum, the entrance of the bile duct
gradually shifts from its initial anterior
position to a posterior one, and
consequently, the bile duct passes behind
the duodenum 59
Liver and Gallbladder
Abnormalities
• Variations in liver lobulation
– common but not clinically significant
• Accessory hepatic ducts and duplication of
the gallbladder
– common and usually asymptomatic
• Extrahepatic biliary atresia
– ducts, which pass through a solid phase in
their development, fail to recanalize
• Intrahepatic biliary duct atresia and
hypoplasia
– problem with duct formation within the liver
itself
– may be caused by fetal infections 60
Pancreas
• Pancreas is formed by two buds originating
from the endodermal lining of the duodenum
– dorsal pancreatic bud
• in the dorsal mesentery
– ventral pancreatic bud
• close to the bile duct
• When the duodenum rotates to the right and
becomes C-shaped, the ventral pancreatic bud
moves dorsally in a manner similar to the
shifting of the entrance of the bile duct
• Finally the ventral bud comes to lie
immediately below and behind the dorsal bud

61
• Later the parenchyma and the duct systems
of the dorsal and ventral pancreatic buds
fuse
• Ventral bud forms
– uncinate process
– inferior part of the head of the pancreas
• Dorsal bud forms
– the remaining part of the gland
• Main pancreatic duct
– formed by the distal part of the dorsal pancreatic
duct and the entire ventral pancreatic duct
• Accessory pancreatic duct
– formed by the proximal part of the dorsal
pancreatic duct
• In about 10% of cases the duct system fails
to fuse, and the original double system
persists 62
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Pancreatic Abnormalities
• Annular pancreas
– The ventral pancreatic bud consists of two
components that normally fuse and rotate
around the duodenum so that they come to lie
below the dorsal pancreatic bud
– Occasionally, however, the right portion of the
ventral bud migrates along its normal route, but
the left migrates in the opposite direction
– In this manner, the duodenum is surrounded by
pancreatic tissue, and an annular pancreas is
formed
– The malformation sometimes constricts the
duodenum and causes complete obstruction 65
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• Accessory pancreatic tissue
– May be found anywhere from the distal
end of the esophagus to the tip of the
primary intestinal loop
– Most frequently it lies in the mucosa of the
stomach and in Meckel’s diverticulum

67
Midgut
• The midgut gives rise to duodenum
immediately distal to the entrance of
the bile duct, jejunum, ileum, cecum,
appendix, ascending colon and the
proximal two-thirds of the transverse
colon
• Over its entire length the midgut is
supplied by the superior mesenteric
artery

68
• Primary intestinal loop
– Development of the midgut is
characterized by rapid elongation of the
gut and its mesentery, resulting in
formation of the primary intestinal loop
– At its apex, the loop remains in open
connection with the yolk sac by way of the
narrow vitelline duct
– Has 2 limbs above and below vitelline duct
• Cephalic limb
– develops into distal part of the duodenum, jejunum,
and part of ileum
• Caudal limb
– develops into lower portion of ileum, cecum,
appendix, ascending colon, and proximal two-thirds of
the transverse colon
69
Physiological herniation
• Development of the primary intestinal
loop is characterized by rapid elongation,
particularly of the cephalic limb
• As a result of the rapid growth and
expansion of the liver, the abdominal
cavity temporarily becomes too small to
contain all the intestinal loops, and they
enter the extraembryonic cavity in the
umbilical cord during the sixth week of
development
• This phenomenon is called
physiological umbilical herniation
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Rotation of the midgut
• Coincident with growth in length, the primary
intestinal loop rotates around an axis formed by the
superior mesenteric artery
• When viewed from the front, this rotation is
counterclockwise, and it amounts to
approximately 2700 when it is complete
• Even during rotation, elongation of the small
intestinal loop continues, and the jejunum and
ileum form a number of coiled loops
• The large intestine likewise lengthens considerably
but does not participate in the coiling phenomenon
• Rotation occurs during herniation (about 900) as
well as during return of the intestinal loops into the
abdominal cavity (remaining 1800)
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Retraction of herniated loops
• During the 10th week, herniated intestinal
loops begin to return to the abdominal cavity
• Factors responsible for this return is not
precisely known
– the following play important roles
• regression of the mesonephric kidney
• reduced growth of the liver
• expansion of the abdominal cavity
• The proximal portion of the jejunum, the first
part to reenter the abdominal cavity, comes
to lie on the left side
• The later returning loops gradually settle
more and more to the right
74
• The cecal bud, which appears at about the
sixth week as a small conical dilation of the
caudal limb of the primary intestinal loop, is the
last part of the gut to reenter the abdominal
cavity
– Temporarily it lies in the right upper quadrant
directly below the right lobe of the liver
– From here it descends into the right iliac fossa,
placing the ascending colon and hepatic flexure
on the right side of the abdominal cavity
• During this process the distal end of the cecal
bud forms a narrow diverticulum, the appendix
– Since the appendix develops during descent of the
colon, its final position frequently is posterior to the
cecum (retrocecal)
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Successive stages in development of the cecum and
appendix. A. 7 weeks. B. 8 weeks. C. Newborn.
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Mesenteries of the intestinal loops
• Mesenteries of ascending and
descending colons
– when the ascending and descending
portions of the colon obtain their
definitive positions, their mesenteries
press against the peritoneum of the
posterior abdominal wall
– After fusion of these layers, the
ascending and descending colons are
permanently anchored in a
retroperitoneal position
82
• Appendix, lower end of the cecum, and
sigmoid colon
– retain their free mesenteries
• Transverse mesocolon
– fuses with the posterior wall of the greater
omentum but maintains its mobility
• Mesentery of jejunoileal loops
– at first continuous with that of the ascending
colon
– when the mesentery of the ascending mesocolon
fuses with the posterior abdominal wall, the
mesentery of the jejunoileal loops obtains a new
line of attachment that extends from the area
where the duodenum becomes intraperitoneal to
the ileocecal junction 83
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Abnormalities of the Mesenteries
• Mobile ascending colon
– Persistence of a portion of the mesocolon
– In the most extreme form, the mesentery of the
ascending colon fails to fuse with the posterior
body wall
– Such a long mesentery allows abnormal
movements of the gut or volvulus of the cecum
and colon
• Retrocolic hernia
– Incomplete fusion of the mesentery with the
posterior body wall may give rise to retrocolic
pockets behind the ascending mesocolon
– Results in entrapment of portions of the small
intestine behind the mesocolon 86
Body Wall Defects
• Omphalocele
– Herniation of abdominal viscera through
an enlarged umbilical ring
– The viscera are covered by amnion
– The origin of the defect is a failure of the
bowel to return to the body cavity from
its physiological herniation

87
• Gastroschisis
– Herniation of abdominal contents through
the body wall directly into the amniotic
cavity
– It occurs lateral to the umbilicus usually on
the right, through a region weakened by
regression of the right umbilical vein,
which normally disappears
– Viscera are not covered by peritoneum or
amnion, and the bowel may be damaged
by exposure to amniotic fluid
– Volvulus (rotation of the bowel) resulting
in a compromised blood supply may,
however, kill large regions of the intestine
and lead to fetal death 88
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 Vitelline Duct Abnormalities
• Meckel’s (ileal) diverticulum
– In 2 to 4% of people, a small portion of the
vitelline duct persists, forming an
outpocketing of the ileum
– In the adult, this diverticulum,
approximately 40 to 60 cm from the
ileocecal valve on the antimesenteric border
of the ileum, does not usually cause any
symptoms
– However, when it contains heterotopic
pancreatic tissue or gastric mucosa, it may
cause ulceration, bleeding, or even
perforation 90
• Enterocystoma, or vitelline cyst
– both ends of the vitelline duct transform
into fibrous cords, and the middle portion
forms a large cyst
– intestinal loops may twist around the
fibrous strands and become obstructed,
causing strangulation or volvulus
• Umbilical fistula, or vitelline fistula
– the vitelline duct remains patent over its
entire length, forming a direct
communication between the umbilicus
and the intestinal tract
– fecal discharge may then be found at the
umbilicus
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Gut Rotation Defects
Abnormal rotation of the intestinal loop
– May result in twisting of the intestine (volvulus)
and a compromise of the blood supply
– Normally the primary intestinal loop rotates
2700 counterclockwise
•Rotation that amounts to 900 only
– When this occurs, the colon and cecum are the
first portions of the gut to return from the
umbilical cord, and they settle on the left side of
the abdominal cavity
– The later returning loops then move more and
more to the right, resulting in left-sided colon
93
• Reversed rotation of the intestinal loop
– Occurs when the primary loop rotates 90 0
clockwise
– In this abnormality the transverse colon
passes behind the duodenum and lies behind
the superior mesenteric artery
Duplications of intestinal loops and cysts
– may occur anywhere along the length of the
gut tube
– most frequently found in the region of the
ileum, where they may vary from a long
segment to a small diverticulum
– may result from abnormal proliferations of
gut parenchyma 94
 Reversed rotation of the
Left-sided colon
intestinal loop
95
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• Gut Atresias and Stenoses
– Atresias and stenoses may occur
anywhere along the intestine
– Most occur in the duodenum, fewest occur
in the colon, and equal numbers occur in
the jejunum and ileum
– Atresias in the upper duodenum are
probably due to a lack of recanalization
– From the distal portion of the duodenum
caudally, however, stenoses and atresias
are most likely caused by vascular
accidents
• These accidents may be caused by malrotation,
volvulus, gastroschisis, omphalocele, and other factors
• As a result, blood supply to a region of the bowel is
compromised and a segment dies, resulting in 97
narrowing or complete loss of that region
98
Hindgut

• The hindgut gives rise to the distal

third of the transverse colon, the
descending colon, the sigmoid, the
rectum, and the upper part of the
anal canal
• The endoderm of the hindgut also
forms the internal lining of the
bladder and urethra

99
• The terminal portion of the hindgut
enters into the posterior region of the
cloaca, the primitive anorectal canal;
the allantois enters into the anterior
portion, the primitive urogenital
sinus
• The cloaca itself is an endoderm-lined
cavity covered at its ventral boundary
by surface ectoderm
– This boundary between the endoderm and
the ectoderm forms the cloacal
membrane
100
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• A layer of mesoderm, the urorectal septum,
separates the region between the allantois and
hindgut
– This septum is derived from the merging of
mesoderm covering the yolk sac and surrounding
the allantois
• As the embryo grows and caudal folding
continues, the tip of the urorectal septum
comes to lie close to the cloacal membrane,
although the two structures never make
contact
• At the end of the seventh week, the cloacal
membrane ruptures, creating the anal
opening for the hindgut and a ventral opening
for the urogenital sinus
• Between the two, the tip of the urorectal
septum forms the perineal body 102
• At this time, proliferation of ectoderm closes
the caudal most region of the anal canal
• During the ninth week, this region recanalizes
• Thus, the caudal part of the anal canal
originates in the ectoderm, and it is supplied
by the inferior rectal arteries, branches of the
internal pudendal arteries
• The cranial part of the anal canal originates in
the endoderm and is supplied by the superior
rectal artery, a continuation of the inferior
mesenteric artery, the artery of the hindgut
• The junction between the endodermal and
ectodermal regions of the anal canal is
delineated by the pectinate line, just below
the anal columns
103
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Hindgut Abnormalities
• Rectoanal atresias, and fistulas
– Caused by abnormalities in formation of the cloaca
– result from incomplete separation of the hind ­gut
from the urogenital sinus by the urorectal septum
OR
– If the posterior portion of the cloaca is too small
and consequently the posterior cloacal membrane
is short, the opening of the hindgut shifts anteriorly
• Imperforate anus
– there is no anal opening
– occurs because of a lack of recanalization of
the lower portion of the anal canal
105
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• Congenital megacolon
– Due to an absence of parasympathetic
ganglia in the bowel wall (aganglionic
megacolon or Hirschsprung disease)
– These ganglia are derived from neural
crest cells that migrate from the neural
folds to the wall of the bowel
– In most cases the rectum is involved

108