Download EMBRYOLOGY

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Digestive System
Divisions of the Gut Tube
A part of the endoderm-lined yolk sac cavity is incorporated into the embryo to form the
primitive gut. The yolk sac and the allantois remain outside the embryo. The primitive gut
is a tube, closed at both the cranial end by the buccopharyngeal membrane and at the
caudal end by the cloacal membrane. The gut tube has a foregut, midgut (continuous with
the yolk sac), and a hindgut.
With further development the primitive gut differentiates into: (1) the pharyngeal gut or
pharynx extending from the buccopharyngeal membrane to the tracheobronchial
diverticulum, (2) the foregut that exists from the pharynx to the liver, (3) the midgut that is
present from caudal to the liver up to the last 1/3rd of the transverse colon, and (3) the
hindgut that is located from the left 1/3rd of the transverse colon to the cloacal membrane.
Endoderm forms the epithelial lining of the digestive tract and gives rise to the parenchyma
of glands, such as the liver and pancreas. Parenchyma is the functional part of glands in
contrast to stroma derived from splanchnic mesoderm, which is connective tissue for
support. Gut muscle and mesentery are also from splanchnic mesoderm.
Mesenteries
Portions of the gut tube are suspended from dorsal and ventral mesenteries. Mesenteries are
double layers of peritoneum that enclose an organ and connect it to the body wall.
Intraperitoneal organs are suspended in such mesentery and retroperitoneal organs are not,
but instead, covered only on their anterior side by mesentery. Peritoneal ligaments are
thickened areas of double layered peritoneum that support organs. Nerves, vessels, adipose
tissue, and lymphatics are between the double layers of peritoneum. Mesentery is covered
with mesothelium (simple squamous epithelial cells). Initially, the whole length of the gut
tube is suspended by dorsal mesentery, but by the fifth week only the caudal part of the
foregut down to most of the hindgut is suspended in dorsal mesentery. This mesentery
extends from the lower esophagus to the cloacal membrane. About the stomach, it forms the
dorsal mesogastrium or greater omentum. At the duodenum it forms the mesoduodenum.
In the region of the colon, dorsal mesentery forms the dorsal mesocolon. Dorsal mesentery
suspends the jejunal and ileal loops in mesentery proper.
Ventral mesentery only exists at the terminal end of the esophagus, stomach, and upper
duodenum. It is derived from the septum transversum. Liver growth into the septum
transversum divides the ventral mesentery into: (1) the lesser omentum (from the liver to the
lower esophagus, stomach, and upper duodenum), and (2) the falciform ligament that
extends from the liver to the ventral body wall. In the lower free edge of the falciform
ligament is the umbilical vein, later becoming the ligamentum teres after birth.
Foregut
Esophagus
The region of the foregut just caudal to the lung bud is the esophagus. Initially, the
endodermal lining of the esophagus is stratified columnar. By the eighth week the
epithelium has partially occluded the lumen of the esophagus. In the following weeks,
vacuoles appear which coalesce, thus recanalizing the esophageal lumen. During this period
the epithelial lining is multilayered and the cells are ciliated. During the fourth month, the
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ciliated cells are replaced with stratified squamous epithelium, characterizing the mature
esophagus.
The esophageal wall has both smooth and skeletal muscle. The smooth muscle cells
differentiate from local splanchnic mesoderm. Experiments have shown that the skeletal
muscle cells arise from direct transformation of existing smooth muscle cells.
The innermost layer of the mucosa consists of epithelium derived from endoderm. The
underlying lamina propria, submucosa, and smooth muscle layers are derived from
splanchnic mesoderm.
Stomach
The early stomach is suspended from the dorsal body wall by a portion of the dorsal
mesentery called the dorsal mesogastrium. It is connected to the ventral body wall by a
ventral mesentery that also encloses the liver.
When the stomach first appears, its concave border faces ventrally, and its convex border
faces dorsally. Two concomitant positional shifts bring the stomach to its adult
configuration. The first is an approximately 90-degree rotation about its craniocaudal axis so
that its originally ventral concave border faces right and its dorsal convex border faces left.
The other positional shift consists of a minor tipping of the caudal (pyloric) end of the
stomach in a cranial direction so that the long axis of the stomach is oriented somewhat
diagonally across the body.
During rotation of the stomach, the dorsal mesogastrium (greater omentum) is carried
with it, leading to the formation of a pouch-like structure called the omental bursa or lesser
sac (bursa = sac). The lesser bursa is related only to the dorsal surface of the stomach and
closely surrounding structures. Ventral mesentery (lesser omentum) between the lesser
curvature of the stomach and liver will complete the upper portion of the omental bursa
(lesser sac). The peritoneal cavity as a whole is referred as the greater sac.
Soon, after the stomach has rotated, the double layers of dorsal mesogastrium (hanging
like an apron from the greater curvature of the stomach as the greater omentum), fuse into a
single sheet covered with mesothelium. The greater omentum overhangs the transverse
colon which is enveloped in its own transverse mesocolon. Ultimately, greater omentum
adjacent to mesocolon will also fuse so that the greater omentum drapes down from both the
greater curvature of the stomach and transverse colon.
The ventral mesentery (lesser omentum) has two components. First, at its free margin is
the hepatoduodenal ligament, which contains the bile duct, portal vein, and hepatic artery.
The free margin also forms the roof of the epiploic foramen of Winslow. This foramen
allows for communication of peritoneal cavity with the omental bursa lying behind the lesser
omentum. Its second element is the hepatogastric ligament, which is a thin membrane
spanning the space between the liver and lesser curvature of the stomach.
Formation of the Duodenum
The duodenum is the juncture of the terminal foregut and cephalic part of the midgut. This
part is distal to the origin of the liver bud. As the stomach rotates, the duodenum takes on a
C – shaped loop and rotates to the right. This rotation together with the pancreas places both
structures in a retroperitoneal position. During the second month there is obliteration of the
duodenum's lumen, but later, it is recanalized. Since the foregut is supplied by the celiac
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artery, and the midgut is supplied by the superior mesenteric artery, the duodenum,
therefore, gets contributions of its circulation from both arteries.
Midgut
Formation of the Intestines
The intestines are formed from the posterior part of the foregut, the midgut, and the hindgut.
In the embryo, the yolk stalk extends from the gut tube to the yolk sac. In the adult, the site
of attachment of the yolk stalk is on the small intestine about 2 feet cranial to the junction of
the small and large intestine, the ileocecal junction. The superior mesenteric artery
supplies the gut. The superior mesenteric artery itself serves as a pivot point about which
later rotation of the gut occurs.
In the fifth week, rapid growth of the gut tube causes it to buckle out in a hairpin loop.
The major change that causes the intestine to assume their adult positions is a 2700 counterclockwise rotation of the caudal limb of the intestinal loop around the cephalic limb of the
loop from its ventral aspect. The reference point for this rotation is the superior mesenteric
artery. The main consequence of this rotation is to bring the future colon across the small
intestine so that it can readily assume its C – shaped position along the ventral abdominal
wall.
Rotation and other positional changes occur mostly due to growth of the gut relative to the
size of the abdominal cavity and length of the embryo. Consequently, the developing
intestines herniate into the body stalk (umbilical cord). Physiological umbilical herniation
of the looped intestine begins in the sixth week to the ninth week. They begin to return into
the abdominal cavity in the ninth week when it is large enough to accommodate the
intestines. The small intestines return first. As they do, they force the distal part of the
colon, which never herniated, to the left side of the peritoneal cavity. This establishes the
definitive position of the descending colon. After the small intestine returns to the abdominal
cavity, the proximal herniated part of the colon follows with its cecal end swinging to the
right and downward.
During the course of herniation, rotation, and return of the intestine to the abdominal
cavity, the intestines are suspended by mesentery of the dorsal wall. Parts of the mesentery
associated with the duodenum and colon (mesoduodenum and mesocolon) fuse with the
peritoneal lining of the dorsal body wall. The transverse and sigmoid parts of the colon are
not fused to the posterior abdominal wall.
In the sixth week, the cecum becomes apparent as swelling in the caudal limb of the
midgut. The cecal enlargement becomes so prominent that the small intestine enters the
colon at a right angle. The tip of the cecum elongates without increasing its diameter, thus
becoming the wormlike appendage, the vermiform appendix. Its position is usually
retrocecal (behind the cecum).
Hindgut
The hindgut gives rise to the distal third of the transverse colon, the descending colon, the
sigmoid colon, the rectum, and upper part of the anal canal. In the early embryo the caudal
end of the hindgut terminates in the endodermally lined cloaca. The cloaca also includes the
base of the allantois, which later expands as a common urogenital sinus. A shelf of
mesodermal tissue called the urorectal septum is situated between the hindgut and the base
of the allantois. During the 6th and 7th weeks, the urorectal septum grows toward the cloacal
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membrane. At the same time, lateral mesodermal ridges extend into the cloaca. The
combined in ingrowth of the lateral ridges and growth of the urorectal septum toward the
cloacal membrane divide the cloaca into the rectum and urogenital sinus. Once the cloaca
is partitioned, the cloacal membrane becomes subdivided into an anal membrane and a
urogenital membrane, which seals the urogenital sinus from the exterior. At the end of the
eighth week the anal membrane ruptures and the hindgut is open to the exterior of the body.
The area where the urorectal septum and lateral mesodermal folds fuse with the cloacal
membrane (between the urogenital membrane anteriorly and the anus posteriorly) becomes
the perineal body.
The caudal part of the anal canal is supplied by the inferior rectal arteries: branches off
the internal pudendal arteries. The middle part of the rectum is supplied by branches off the
internal iliac arteries: the middle rectal arteries. The superior rectal artery supplies blood
to the cranial part of the rectum: a branch off the inferior mesenteric artery (the artery of the
hindgut).
Intestinal Tract Cell Histology
Three major phases are involved with in the histogenesis of intestinal epithelium: (1) an early
phase of epithelial proliferation and morphogenesis, (2) an intermediate period of cellular
differentiation in which distinctive cell types characteristic of intestinal epithelium appear,
and (3) a final phase of biochemical and functional maturation of the different types of
epithelial cells.
1. Early in the second month the epithelium of the small intestine begins a phase of rapid
proliferation that results in the epithelium temporarily occluding the lumen by 6 to 7 weeks
gestation. Within a couple weeks, recanalization of the intestinal lumen has occurred. As a
result of mesenchymal growth into the epithelium, the formation of intestinal villi
commences and the epithelium has transformed from stratified into a simple columnar type.
2. With formation of the villi, pitlike intestinal crypts also form at the base of the villi.
The crypts contain epithelial stem cells, which have a high rate of mitosis and serve as a
source of epithelial cells for the intestinal surface. When the stem cell divides, one of the
progeny retains stem cell qualities and the other continues to proliferate as it migrates up the
villus. These migrating cells differentiate into four different mature cell types: Paneth cells
(in small intestine: contain bacteriocidal lysozyme), enteroendocrine cells, goblet cells, and
enterocytes. When they reach the tip of the villus enterocytes die and are shed in the
intestinal lumen.
3. By the end of the second trimester, all cell types have differentiated, but many of the
cells do not possess adult functional patterns.
No major digestive functions occur until feeding begins at birth. The intestines of the
fetus contain a greenish material called meconium. Meconium is a mixture of lanugo hairs
and vernix caseosa sloughed from the skin, desquamated cells from the gut, bile secretion,
and other materials swallowed with the amniotic fluid.
Formation of Enteric Ganglia
The enteric ganglia are derived from neural crest. Vagal crest cells migrate from the foregut
and then spread in a wave-like fashion throughout the entire length of the gut. Later, cells
from the sacral crest enter the hindgut and intermingle with cells derived from the vagal
crests cells. At first, vagal crest cells migrate throughout the mesenchyme of the gut, but as
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smooth muscle of the intestines begins to differentiate, the vagal crest cells preferentially
distribute themselves between the smooth muscle and the serosa (outer surface of the
digestive tract), hence forming the myenteric plexuses. Glial (satellite) cells of the ganglia
differentiate from neural crest cells.
Glands of the Digestive System
Liver
In the third week, an endodermal hepatic diverticulum arises from the floor of the distal
foregut and grows into the mesenchyme of the septum transversum. As the hepatic
diverticulum takes shape, precursors of vascular endothelial cells grow into the same area.
The original hepatic diverticulum branches into many hepatic cords, which are closely
associated with the splanchnic mesoderm of the septum transversum. The mesoderm
supports the continued growth and proliferation of the hepatic endoderm. This occurs in part
through the actions of hepatic growth factor that binds to its receptors on hepatocyte
surfaces. During development, epithelial liver cords intermingle with the vitelline and
umbilical veins, which will form the hepatic sinusoids. Liver cords (endoderm) differentiate
into parenchyma (liver cells) and form the lining of the biliary ducts. Hematopoietic cells,
Kupffer cells, and connective tissue cells are derived from the mesoderm of the septum
transversum.
In addition to cords of hepatic endoderm, a system of bile ducts forms in the developing
liver. Near the area where the hepatic biliary ducts become confluent, a dilatation emerges to
become the gallbladder. Associated with the gallbladder are the hepatic ducts (draining the
liver) and the common bile duct that is formed by the union of the common hepatic duct
and cystic duct.
As it continues to expand in the septum transversum, the rapidly growing liver is covered
by a translucent layer of mesenteric tissue that now serves as the connective tissue capsule of
the liver. Between the ventral body wall is a thin, sickle-shaped piece of ventral mesentery,
the falciform ligament. The ventral mesentery between the liver and the stomach is the
lesser omentum.
Hepatic Function
One of the major functions of the liver is to produce the plasma protein, serum albumin.
Another is the synthesis and storage of glycogen. In the fetus, synthesis of urea from
nitrogenous wastes occurs. After yolk sac hematopoiesis, the embryonic liver is one of the
chief sites of intraembryonic blood formation, both red and white cells. At about 12 weeks,
the hepatocytes begin to produce bile through the breakdown of hemoglobin. Bile released
into the intestines is what gives meconium its characteristic green color.
Pancreas
The pancreas begins as separate dorsal and ventral primordia within the duodenal endoderm.
Early development of each of the two primordia is under different molecular controls.
Ventral endoderm of the hepatic diverticulum is patterned to differentiate into ventral
pancreatic tissue.
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The dorsal pancreas is induced from dorsal gut endoderm by signaling molecules
emanating from the notochord. Local signals and intracellular responses result in the
differentiation of two lineages of cells, the pancreatic exocrine cells and the pancreatic
endocrine cells.
During early growth, the dorsal pancreas becomes larger than the ventral pancreas. At
about the same time the duodenum rotates to the right and forms a C – shaped loop, carrying
the ventral pancreas and common bile duct behind it into the dorsal mesentery. The ventral
pancreas makes contact and fuses with the dorsal pancreas.
After fusion of the two parts of the pancreas, the main duct of the ventral pancreas makes
an anastomotic connection with the duct of the dorsal pancreas. The portion of the dorsal
pancreatic duct (duct of Santorini) between the anastomotic connection and the duodenum
normally regresses, leaving the main duct of the ventral pancreas (duct of Wirsung) as the
definitive outlet from the pancreas to the duodenum. The main pancreatic duct (the part
from the ventral pancreas), together with the common bile duct, enters the duodenum at the
site of the major duodenal papilla (of Vator). The papilla is formed by the underlying
muscular sphincter of Oddi.
The pancreas is a dual organ with both exocrine and endocrine functions. The exocrine
portion consists of large numbers of enzyme producing acini, which are connected to the
duct system. Epithelial cells lining the pancreatic ducts produce bicarbonate in addition to
being a conveyance for digestive enzymes. Scattered throughout the pancreas, the endocrine
portion (islets of Langerhans') is profusely vascularized and delivers its hormones through
the bloodstream. Insulin secretion begins about the fifth month.
Malformations of the Esophagus and Stomach
Esophagus
The most common anomalies of the esophagus are associated with abnormalities of the
developing respiratory tract. Other rather rare anomalies are stenosis (constriction or
narrowing) and atresia (absence or closure) of the esophagus. Stenosis is usually due to
abnormal recanalization. Atresia is associated with respiratory tract malformation. In either
case, both lead to excessive accumulation of amniotic fluid termed, polyhydramnios.
Stomach
Pyloric stenosis consists of hypertrophy of the circular layer of muscle that surrounds the
pyloric end of the stomach. The hypertrophy leads to stenosis and impedes the passage of
food. Several hours after eating, the infant vomits violently (projectile vomiting). Although
pyloric stenosis is commonly treated by a simple surgical procedure, the hypertrophy
sometimes diminishes untreated by several weeks after birth. The cause of pyloric stenosis
may be genetic and is more common in males than females. Its averaged incidence is
reported in about 1 / 600 infants.
Malformations of the Intestinal Tract
Duodenal Stenosis and Atresia
Duodenal stenosis and atresia are rare. Typically they result from absent or incomplete
recanalization.
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Vitelline Duct Remnants
The most common family of anomalies of the intestinal tract is some form of persistence of
the vitelline (yolk) duct. The most common member of this family is Meckel's
diverticulum, which is present in 2 – 4% of the population. A typical Meckel's diverticulum
is a blind pouch a few centimeters long located at the antimesenteric border of the ileum
about 50 cm cranial of the ileocecal junction. Simple Meckel's diverticula are often
asymptomatic, but they occasionally become inflamed or contain ectopic tissue, which cause
ulceration.
In some cases a ligament connects a Meckel's diverticulum to the umbilicus, or a simple
vitelline ligament may have an associated persisting vitelline artery. Occasionally, the
intestine may rotate around the ligament causing a condition known as volvulus. This can
lead to strangulation of the bowel.
A persistent vitelline duct can take the form of a vitelline fistula, which constitutes a
direct connection between intestinal lumen and the outside the body via the umbilicus.
Rarely, a vitelline duct cyst is present.
Omphalocele
The omphalocele represents the failure of returning of the intestinal loops into the body
cavity during the tenth week. The primary defect is most likely a reduced abdominal cavity
space. After birth, the intestinal loops can easily be seen within an almost transparent sac
consisting of amnion on the outside and parietal peritoneal membrane on the inside. The
incidence of omphalocele is about 1 / 3500 births, but half of these are stillborn.
Congenital Umbilical Hernia
In congenital umbilical hernia, which is common in premature infants, the intestines return
normally to the body cavity. However, the musculature (rectus abdominis) of the body wall
fails to close the umbilical ring, allowing varying amounts of omentum or bowel to protrude
through the umbilicus. In contrast to omphalocele, the protruding tissue in an umbilical
hernia is covered by skin rather than amniotic membrane. It is most visible when the baby
cries. This is not a gastroschisis, where abdominal contents are exposed with no
membranes.
Abnormal Rotation of the Gut
Sometimes the intestines undergo abnormal or lack rotation as they return to the abdominal
cavity. In most cases these are asymptomatic, but occasionally they can lead to volvulus or
another form of strangulation of the gut.
Aganglionic Megacolon (Hirschsprung's Disease)
The basis of aganglionic megacolon is the absence of parasympathetic ganglia in the affected
walls of the colon. The unaffected areas are greatly dilated. Hirschsprung's disease appears
to be multifactorial, with both dominant and recessive mutations causing this condition.
Mutations underlying aganglionic megacolon could involve defects in the migration of
proliferation of neural crest precursor cells. Death of precursor cells before they reach their
final destination in the hindgut could reduce the number of enteric ganglia.
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The distal colon is most the affected region for aganglionosis but in a small number of
cases, aganglionic segments extend up into the ascending colon. The frequency is widely
estimated to be 1 /1000 to 1 / 30,000 births.
Recent experiments have shown that vagal crest cells migrate more efficiently to the
hindgut than do sacral crest cells.
Imperforate Anus
Imperforate anus includes a spectrum of anal defects that can range from a simple membrane
covering the anal opening (persistent anal membrane) to atresia of the anal canal, rectum, or
both structures. Any examination of the newborn must include a determination of the
presence of an anal opening.
Hindgut Fistulas
In many cases of anal atresia there is an associated fistula linking the hindgut with another
structure that arises from the urogenital sinus region. Common types of fistulas connect the
hindgut with the vagina, urethra, or the bladder. Other fistulas may lead to the surface of the
perineal region.
Questions
1.
The functional part of digestive system glands develops from which of the following?
a. endoderm
b. neural crest cells
c. splanchnic mesoderm
d. ectoderm
2. The falciform ligament is derived from the ____________.
a. dorsal mesentery
b. urogenital septum
c. septum transversum
d. ligamentum teres
3.
Dorsal mesentery will form, among other things, which of the following?
a. The omental bursa.
b. Greater omentum.
c. Falciform ligament
d. The epiploic foramen of Winslow
4.
After the esophagus is recanalized, what type of adult-like epithelium lines the
esophagus?
a. ciliated pseudostratified
b. simple squamous
c. transitional
d. stratified squamous
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5.
When the stomach rotates on its craniocaudal axis, its original dorsal part will finish
up facing to the ________.
a. left
b. front
c. right
d. rear
6.
Portions of the dorsal mesogastrium will finally end up as the ___________, which
hangs under the greater curvature of the stomach.
a. lesser omentum
b. hepatoduodenal ligament
c. hepatogastric ligament
d. greater omentum
7.
The duodenum gets its blood supply from which of the pairs of arterial choices.
a. celiac / inferior mesenteric
b. celiac /superior mesenteric
c. superior mesenteric / inferior mesenteric
d. vitelline / celiac
8.
In hindgut development, the _________ will ultimately partition the cloaca into the
_______________.
a. septum transversum / urogenital sinus and rectum
b. urorectal septum / urogenital sinus and rectum
c. septum transversum / midgut and foregut
d. urorectal septum / midgut and foregut
9.
The artery of the hindgut is the _____________ artery.
a. celiac
b. superior mesenteric
c. inferior mesenteric
d. internal iliac
10. Which of the following cell types is not a part of the epithelial lining of the mucosa in
the small intestine?
a. parietal cells
b. goblet cells
c. Paneth cells
d. enterocytes
11. The intramural ganglia of the digestive tract are derived from which of the following?
a. lateral mesoderm
b. splanchnic mesoderm
c. neural crest
d. hemangioblasts
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12. In the distal foregut, parenchyma of the liver and biliary system is derived from
___________ growing into the _____________.
a. mesoderm / septum transversum
b. endoderm / septum transversum
c. mesoderm / urorectal septum
d. endoderm / urorectal septum
13. The intestines of the fetus contain a greenish material called __________, which
contains bile secretion and other materials swallowed with the amniotic fluid.
a. meconium
b. alpha fetoprotein
c. surfactant
d. feces
14. The minor pancreatic duct is derived from the _________ pancreas and it is also called
the duct of ___________.
a. ventral / Wirsung
b. ventral / Santorini
c. dorsal / Wirsung
d. dorsal / Santorini
15. The ________________ drain into the duodenum through the major duodenal papilla of
Vator.
a. minor pancreatic duct / common bile duct
b. minor pancreatic duct / cystic duct
c. major pancreatic duct / common bile duct
d. major pancreatic duct / cystic duct
16. In either case, stenosis or atresia of the esophagus may lead to the condition ________.
a. oligohydramnios
b. hyaline membrane disease
c. polyhydramnios
d. meconiosis
17. Meckel's diverticulum is some form of persistence of the __________ duct and it is
associated with the __________.
a. celiac / duodenum
b. superior mesenteric / jejunum
c. inferior mesenteric / colon
d. vitelline / ileum
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18. Which of the following is due to failure of the rectus abdominis to close allowing
various amounts of omentum or bowel to protrude close to the umbilicus? Here there is
skin over the defect.
a. omphalocele
b. congenital umbilical hernia
c. aganglionic colon
d. imperforate anus