Development of the GIT 1 - PowerPoint Presentation

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Development of the GIT 1

ANA 204

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Cephalocaudal

and lateral folding of the embryo allows a part of the endoderm-lined yolk sac cavity to be 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.Primitive gut forms a blind-ending tube, the foregut and hindgut. The middle part, the midgut, remains temporally connected to the yolk sac by means of the vitelline duct, or yolk stalk.

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Development of the primitive gut and its derivatives is discussed in four sections:

Pharyngeal gut, or pharynx, extends from the buccopharyngeal membrane to the tracheobronchial diverticulumForegut 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.

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Endoderm

forms the epithelial lining of the digestive tract and gives rise to the parenchyma of glands, such as the liver and pancreas.Muscle, connective tissue, and peritoneal components of the wall of the gut are derived from splanchnic mesoderm.

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Molecular Regulation of Gut Tube Development

Dependent on

a reciprocal interaction between the endoderm (epithelium) of the gut tube and surrounding splanchnic mesoderm. Mesoderm dictates the type of structure that will form, for example descending colon from the hindgut region, through a HOX codeInduction of this HOX code is a result of sonic hedgehog (SHH) expressed throughout the gut endoderm.Mesoderm is specified by this code and instructs the endoderm to form the various components of the foregut, midgut and hindgut regions5

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Mesenteries

Double layers of peritoneum

Enclose an organ and connect it to the body wall. Suspend portions of the gut tube and its derivatives from the dorsal and ventral body wall, such organs are called intraperitonealOrgans that lie against the posterior body wall and are covered by peritoneum on their anterior surface only are considered retroperitoneal. 6

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Peritoneal ligaments

Double layers of peritoneum that pass from one organ to another or from an organ to the body wall. Mesenteries and ligaments provide pathways for vessels, nerves, and lymphatics to and from abdominal viscera.By the fifth week, 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

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Dorsal mesentery

Extends from the lower end of the esophagus to the cloacal region of the hindgut. In the stomach, it forms the dorsal mesogastrium or greater omentumIn the duodenum, it forms the dorsal mesoduodenumIn the colon, it forms the dorsal mesocolon. In the jejunum and ileam, it forms the mesentery proper.

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Ventral mesentery

Exists only in the terminal part of the esophagus, the stomach, and the upper part of the duodenumDerived from the septum transversum. Growth of the liver into septum transversum divides the ventral mesentery into: Lesser omentum, which extends 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.

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FOREGUT

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ESOPHAGUS

At 4 weeks, the respiratory diverticulum appears at the ventral wall of the foregut at the border with the pharyngeal gut.Tracheoesophageal septum partitions this diverticulum from the dorsal part of the foregut. Foregut divides into a ventral portion, the respiratory primordium, and a dorsal portion, the esophagus.At first the esophagus is short, but with descent of the heart and lungs it lengthens rapidly.Muscular coat, formed by splanchnic mesenchyme, is striated in its upper two-thirds and innervated by the vagus nerveMuscle coat is smooth in the lower third and is innervated by the splanchnic plexus.

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C L I N I C A L C O R R E L A T E S

Esophageal Abnormalities

Esophageal atresia and/or tracheoesophageal fistulaResults either from posterior deviation of the tracheoesophageal septum or from 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 canal just above the bifurcation.Atresia 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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Stenosis

May be caused by incomplete recanalization, vascular abnormalities, or accidents that compromise blood flow. Lumen of the esophagus may narrow, producing esophageal stenosis, usually in the lower third. When the esophagus fails to lengthen sufficiently and the stomach is pulled up into the esophageal hiatus through the diaphragm. The result is a congenital hiatal hernia.

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STOMACH

A

fusiform dilation of the foregut in the fourth week of development. Positional changes of the stomach are most easily explained by assuming that it rotates around a longitudinal and an anteroposterior axis.Rotates 90o clockwise around its longitudinal axis, causing its left side to face anteriorly and its right side to face posteriorly.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

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Cephalic and caudal ends of the stomach originally lie in the midline

With further growth the stomach rotates around an anteroposterior axis, such that the pyloric part moves to the right and upward and the 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.Since 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) This rotation also pulls the ventral

mesogastrium

to the right.

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In the fifth week of development, the

spleen primordium appears as a mesodermal proliferation between the two leaves of the dorsal mesogastrium.Dorsal mesogastrium lengthens and fuses with the peritoneum of the posterior abdominal wall. Posterior leaf of the dorsal mesogastrium and the peritoneum along this line of fusion degenerate. 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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Lengthening and fusion of the dorsal

mesogastrium

to the posterior body wall determine the final position of the pancreas. Organ grows into the dorsal mesoduodenum and its tail extends into the dorsal mesogastrium. Pancreas is originally covered by peritoneum, but later fuse with the posterior body wall to become retroperitoneal, are said to be secondarily retroperitoneal.As a result of rotation of the stomach about its anteroposterior axis, the dorsal mesogastrium bulges down over the transverse colon and small intestinal loops like an apron.

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The double-leafed apron is the greater

omentum whose layers fuse to form a single sheet hanging from the greater curvature of the stomach. Posterior layer of the greater omentum fuses with the mesentery of the transverse colon.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(a) the peritoneum of the liver(b) the falciform ligament, extending from the liver to the ventral body wall(c) the lesser omentum, extending from the stomach and upper duodenum to the liver.

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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). The free margin of the lesser omentum connecting the duodenum and liver (hepatoduodenal ligament) contains the bile duct, portal vein, and hepatic artery (portal triad). This free margin also forms the roof of the epiploic foramen of Winslow, which is the opening connecting the omental bursa (lesser sac) with the rest of the peritoneal cavity (greater sac).

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Stomach Abnormalities

Pyloric

stenosisOccurs when the circular and the longitudinal musculature of the stomach in the region of the pylorus hypertrophies.Develop during fetal life. Extreme narrowing of the pyloric lumen, and the passage of food is obstructed, resulting in severe vomiting. In few cases the pylorus is atretic. Other malformations of the stomach, such as duplications and a prepyloric septum, are rare.22

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DUODENUM

Terminal

part of the foregut and the cephalic part of the midgut form the duodenum.Junction of the two parts is 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 with growth of the head of the pancreas, swings the duodenum to the left side of the abdominal cavity.Duodenum and head of the pancreas press against the dorsal body wallDorsal mesoduodenum fuses with the adjacent peritoneum. Both layers disappear, and the duodenum and head of the pancreas become fixed in a retroperitoneal position

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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.During the second month, the lumen of the duodenum is obliterated by proliferation of cells in its walls which is recanalized shortly.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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LIVER AND GALLBLADDER

Liver

primordium appears in the middle of the third week An outgrowth of the endodermal epithelium (hepatic diverticulum, or liver bud) at the distal end of the foregut.Consists of rapidly proliferating cells that penetrate the septum transversumHepatic cells continue to penetrate the septum, the connection between the hepatic diverticulum and the foregut (duodenum) narrows, forming the bile duct. A small ventral outgrowth is formed by the bile

duct, and this outgrowth gives rise to the

gallbladder

and the

cystic

duct

.

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Epithelial liver cords intermingle with the

vitelline and umbilical veins, which form hepatic sinusoids. Liver cords differentiate into the parenchyma (liver cells) and form the lining of the biliary ducts. Hematopoietic cells, Kupffer cells, and connective tissue cells are derived from mesoderm of the septum transversum.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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Peritoneal connection

between the foregut and the ventral abdominal wall are known as the ventral mesogastrium.This portion of the septum, which consists of densely packed mesoderm, 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; it is the bare area of the liver.

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Large nests of proliferating cells, which produce red and white blood cells, lie between hepatic cells and walls of the vessels.

This activity subsides during the last 2 months of intrauterine life, and only small hematopoietic islands remain at birth. Weight of the liver is then only 5%of the total body weight.At 12th week, bile is formed by hepatic cells. 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. As a result, its contents take on a dark green color. Positional changes of the duodenum, the entrance of the bile duct shifts from its initial anterior position to a posterior one, and consequently, the bile duct passes behind the duodenum.

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Molecular Regulation of Liver Induction

All of the foregut endoderm has the potential to express liver-specific genes

and to differentiate into liver tissue.Expression is blocked by factors produced by ectoderm, non-cardiac mesoderm, and the notochord. Action of these inhibitors is blocked by fibroblast growth factors (FGFs) secreted by cardiac mesoderm. Once this “instruction” is received, cells in the liver field differentiate into both hepatocytes and biliary cell lineages, a process that is partially regulated by hepatocyte nuclear transcription factors (HNF3 and 4).30

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C L I N I C A L C O R R E L A T E S

Liver and Gallbladder Abnormalities

Accessory hepatic ducts and duplication of the gallbladder are also common and usually asymptomatic. They become clinically important under pathological conditions. Extrahepatic biliary atresia. Among patients with extrahepatic biliary atresia, 15 to 20% have patent proximal ducts and a correctable defect, but the remainder usually die unless they receive a liver transplant. Another problem with duct formation lies within the liver itself; it is intrahepatic

biliary

duct

atresia

and

hypoplasia

.

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PANCREAS

Formed

by two buds originating from the endodermal lining of the duodenum. Dorsal pancreatic bud is in the dorsal mesentery, the ventral pancreatic bud is close to the bile duct. 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. Ventral bud comes to lie immediately below and behind the dorsal bud. Later the parenchyma and the duct systems of the dorsal and ventral pancreatic buds fuse.Ventral bud forms the uncinate

process and inferior part of the head

of

the

pancreas. The remaining part of the gland is derived from the dorsal

bud.

Main

pancreatic duct (of

Wirsung

) is formed by the distal part of

the

dorsal

pancreatic duct and the entire ventral pancreatic

duct

.

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The proximal part of the dorsal pancreatic duct either is obliterated or persists as a small channel, the

accessory pancreatic duct (of Santorini). The main pancreatic duct, together with the bile duct, enters the duodenum at the site of the major papilla; the entrance of the accessory duct (when present) is at the site of the minor papilla. In about 10% of cases the duct system fails to fuse, and the original double system persists.In the third month of fetal life, pancreatic islets (of Langerhans) develop from the parenchymatous pancreatic tissue and scatter throughout the pancreas.Insulin secretion begins at approximately the fifth month. Glucagon- and somatostatin-secreting cells also develop from parenchymal cells. Splanchnic mesoderm surrounding the pancreatic buds forms the pancreatic connective tissue.

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MOLECULAR REGULATION OF PANCREAS DEVELOPMENT

Fibroblast growth factor (FGF)

and activin (a TGF-β family member) produced by the notochord repress SHH expression in gut endoderm destined to form pancreas.Master gene for pancreatic development - pancreatic and duodenal homeobox 1 (PDX) gene is upregulated. Paired homeobox genes PAX4 and 6: cells expressing both genes become β (insulin), δ (somatostatin), and γ (pancreatic polypeptide) cells; those expressing only PAX6 become α (glucagon) cells.35

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Pancreatic

Abnormalities

Occasionally, the right portion of the ventral bud migrates along its normal route, but the left migrates in the opposite direction.Annular pancreas is formed around the duodenum which constricts the duodenum and causes complete obstruction.Accessory pancreatic tissue may be in the distal end of the esophagus to the tip of the primary intestinal loop or mucosa of the stomach and in Meckel’s diverticulum36

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Midgut

In the 5-week-old embryo,Suspended from the dorsal abdominal wall by a mesenteryCommunicates with the yolk sac by vitelline duct or yolk stalk.Begins distal to the entrance of the bile duct into the duodenumTerminates at the junction of the proximal two-thirds of the transverse colon with the distal third. Supplied by the superior mesenteric artery

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Elongation

of the gut and its mesentery resulting in formation of the primary intestinal loop. Cephalic limb of the loop develops into the distal part of the duodenum, the jejunum, and part of the ileum. Caudal limb becomes the lower portion of the ileum, the cecum, the appendix, the ascending colon, and the proximal two-thirds of the transverse colon.

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PHYSIOLOGICAL HERNIATION

Rapid elongation of the cephalic limb. Abdominal cavity temporarily becomes too small to contain all the intestinal loopsLoops enter the extraembryonic cavity in the umbilical cord during the sixth week of development

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ROTATION OF THE MIDGUT

Primary intestinal loop rotates around an axis formed by the superior mesenteric artery. Rotation is counterclockwise and amounts to 270◦ Rotation occurs during herniation (about 90◦) and during return of the intestinal loops into the abdominal cavity (remaining 180◦). Elongation of the loop continues, and the jejunum and ileum form a number of coiled loops. Large intestine also lengthens

but

does not participate in the coiling phenomenon.

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RETRACTION OF HERNIATED LOOPS

In the 10th week, herniated intestinal loops return to the abdominal cavity. Regression of the mesonephric kidney, reduced growth of the liver, and expansion of the abdominal cavity play important roles may cause this.Proximal portion of the jejunum is the first part to re-enter the abdominal cavityLie on the left side. Other loops settle more and more to the right.

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Cecal

budA small conical dilation of the caudal limb of the primary intestinal loopLast part to re-enter the abdominal cavity.Lies in the right upper quadrant directly below the right lobe of the liver before descending into the right iliac fossa Distal end of the cecal bud forms a narrow diverticulum, the appendix.AppendixDevelops during descent of the colonFinal position is posterior to the cecum or colon.

These positions are

called

retrocecal

or

retrocolic

,

respectively.

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MESENTERIES OF THE INTESTINAL LOOPS

Mesentery of the primary intestinal loop is also called the mesentery properDorsal mesentery twists around the origin of the superior mesenteric artery. Mesenteries of the ascending and descending portions of the colon press against the peritoneum of the posterior abdominal wall. Ascending and descending colons are permanently anchored in a retroperitoneal position. Appendix, lower end of the cecum, and sigmoid colon retain their free mesenteries .

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Transverse

mesocolon fuses with the posterior wall of the greater omentum but maintains its mobility. Extends from the hepatic flexure of the ascending colon to the splenic flexure of the descending colon.Mesentery of the jejunoileal extends from the area where the duodenum becomes intraperitoneal to the ileocecal junction.

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Abnormalities of the Mesenteries

Normally the ascending colon, except for its most caudal part, fuses to the posterior abdominal wall and is covered by peritoneum on its anterior surface and sides. Persistence of a portion of the mesocolon gives rise to a mobile cecum. A long mesentery allows abnormal movements of the gut or even volvulus of the cecum and colon.

Incomplete

fusion of the mesentery with the posterior

body wall

may give rise to

retrocolic

pockets behind the ascending

mesocolon

.

Retrocolic

hernia

is entrapment of portions of the small intestine behind

the

mesocolon

.

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Body Wall Defects

Omphalocele Failure of the bowel to return to the body cavity from its physiological herniation during the 6th to 10th weeks.Herniation of abdominal viscera through an enlarged umbilical ring. Viscera include liver, small and large intestines, stomach, spleen, or gallbladder and are covered by amnion.

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Gastroschisis

Herniation of abdominal contents through the body wall directly into the amniotic cavity.Occurs lateral to the umbilicus usually on the right, through a region weakened by regression of the right umbilical vein. 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.

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Vitelline

Duct AbnormalitiesIn 2 to 4% of people, a small portion of the vitelline duct persists, forming an outpocketing of the ileum, Meckel’s diverticulum or ileal diverticulum. Vitelline duct may transform into fibrous cords forming a large cyst, an enterocystoma, or vitelline cyst. Fibrous cords may twist around the fibrous strands and become obstructed, causing strangulation

or

volvulus

.

Vitelline

duct

may remain patent over

its entire length, forming a direct communication between

the

umbilicus nd

the

intestinal

tract

-

known

as

umbilical fistula or

vitelline

fistula

.

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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 270◦ counterclockwise. When rotation amounts to 90◦ only, 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 to the right, resulting in left-sided colon.Reversed rotation of the intestinal loop occurs when the primary loop rotates 90◦ clockwise.Duplications of intestinal loops and cysts may occur anywhere along the length of the gut tube.

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Gut

Atresias and StenosesAtresias and stenoses occur mostly in the duodenum, fewest occur in the colon, and equal numbers occur in the jejunum and ileum.Vascular accidents causing atresias 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 narrowing

or complete loss of that

region.

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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. Endoderm of the hindgut forms the internal lining of the bladder and urethra.Terminal portion enters into the posterior region of the cloaca, the primitive anorectal canal; the allantois enters into the anterior portion, the primitive urogenital

sinus.

Cloaca

is an

endoderm-lined

cavity covered at its ventral boundary by surface ectoderm.

Boundary

between the endoderm and the ectoderm forms the

cloacal

membrane.

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Urorectal

septum separates the region between the allantois and hindgut. - 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 lies 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

.

Tip of

the

urorectal

septum forms the

perineal

body.

Proliferation

of ectoderm closes the

caudalmost

region of the anal

canal

which later

recanalizes

.

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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. 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. Junction between the endodermal and ectodermal regions of the anal canal is delineated by the pectinate line, just below the anal columns.Epithelium changes

from

columnar to stratified

squamous

epithelium.

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Hindgut Abnormalities

Rectoanal atresias, and fistulas are caused by abnormalities in formation of the cloaca. If the posterior portion of the cloaca is too small and the posterior cloacal membrane is short, the opening of the hindgut shifts anteriorly. If the defect in the cloaca is small, the shift is small, - Low opening of the hindgut into the vagina or urethra- Location of the hindgut opening shifts more anteriorly to a higher location Rectoanal atresias and fistulas are due to ectopic positioning of the anal opening and not to defects in the

urorectal

septum.

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Imperforate anus

No anal opening. Occurs because of a lack of recanalization of the lower portion of the anal canal.Congenital megacolon 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.