Digestive System Development PDF

Development of the Digestive System Dila Şener Akçora, Assist. Prof. Department of Histology and Embryology October 2023  Formation of primitive gut tube...

Development of the Digestive System Dila Şener Akçora, Assist. Prof. Department of Histology and Embryology October 2023  Formation of primitive gut tube 4th week Cranial closure of orofaringeal membrane Caudal closure of cloacal membrane CEPHALOCAUDAL and LATERAL foldings of embryo = Beginning of developmental process for digestive system Formation of primitive gut tube Why is the gut tube endodormal Lateral fold Result of cephalocaudal in origin and lateral folding of the embryo, a portion of the endoderm-lined Tail fold yolk sac cavity is remain Head fold inside of the embryo to form the primitive gut. Cephalocaudal folding ▪ 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.The middle part, the midgut, temporarily connected to the yolk sac by the vitelline duct, or yolk stalk Primitive gut tube Endoderm: epithelial lining of the digestive tract, the parenchyma of glands (liver and pancreas). Mesoderm: muscle, connective tissue, and peritoneal components of the wall of the gut. Recanalization Formation of the definitive gut lumen. Proliferation of the endodermal lining completely occludes the gut tube during the sixth week. Recanalization is completed by week 9. Incomplete or abnormal recanalization may result in duplication of the lumen or stenosis of the gut tube.  Molecular Regulation of Gut Tube Development Pharyngeal gut Differentiation = Lateral folding Esophagus Endoderm: Sonic hedgehog (SHH) expression Stomach Liver Pancreas Differentiation of various regions of the gut and its derivatives…. interaction between the endoderm (epithelium) and surrounding mesoderm. SHH HOX genes Stabilization HOX genes Mesodermal factors  Mesenteries The mesentery is the splanchnic mesoderm, double layers of peritoneum that surrounds and connects the primitive gut to the body wall. Peritoneal ligaments: double layers of peritoneum that attach organ- organ or organ-body wall.  Dorsal mesentery Foregut, midgut, and hindgut are initially in broad contact with the mesenchyme of the posterior abdominal wall. By the fifth week, the connecting tissue bridge has narrowed and lower end of the esophagus to the cloacal region of the hindgut are suspended the abdominal wall by the dorsal mesentery. Dorsal mesogastrium/ Greater omentum: region of the stomach. Dorsal mesoduodenum: region of the duodenum Dorsal mesocolon: region of the colon Mesentery proper: Dorsal mesentery of the jejunal and ileal loops In the region of the stomach the dorsal mesogastrium develops into the; Splenorenal and Gastrosplenic ligaments  Ventral mesentery Derived from the septum transversum and exist only in the region of the terminal part of the esophagus, the stomach, and the upper part of the duodenum. Growth of the liver into the mesenchyme of the septum transversum divides the ventral mesentery into: Lesser omentum Falciform ligament The development and location of the mesenteries in adult are largely dictated by the rotation of the gut and the other movements of the developing stomach and G.I. tract.  Foregut Which one of below dose not originate in foregut ? Gives rise to: Esophagus Stomach The proximal part of the duodenum the opening of the bile duct The liver and pancreas  Development of Esophagus Foregut ✓ Respiratory diverticulum (lung bud) …4 weeks old embryo… ventral wall of the foregut. ✓ The tracheoesophageal septum gradually seperates this diverticulum from the dorsal part of the foregut. ✓ As a result; the 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. ✓ The muscular coat is formed by surrounding splanchnic mesenchyme.  Anomalies of the esophagus Communication Tracheo of esophageal fistula esophagus with trachea Atresia of the esophagus prevents normal passage of amniotic fluid into intestinal tract, resulting in accumulation of excess fluid in the amniotic sac (polyhydramnios). Stenosis Short esophagus  Development of Stomach The stomach develops from the caudal foregut starting at the 4th week. It begins as a dilation of the gut tube and initially oriented in median plane. Change its position by both rotating around longitudinal and anteroposterior axis. Forming...Greater curvature By 7-8th week, stomach carries out a 90°clockwise rotation around the longitudinal axis and causing: - left side to face anteriorly & right side to face posteriorly - the original posterior wall of the stomach grows faster than the anterior portion, forming greater and lesser curvatures During further growth: the stomach rotates around an anteroposterior axis, and as a result: -caudal or pyloric part moves to the right and upward. The caudal movement of the stomach results in the pyloric portion of the stomach lying at the same level as the body of the stomach -cephalic or cardiac portion moves to the left and downward The stomach thus assumes its final position, its axis running from above left to below right.  Formation of omental bursa after rotation Stomach is attached to the dorsal body wall by the dorsal mesogastrium and ventral body wall by the ventral mesogastrium. Its rotation and disproportionate growth alter the position of these mesenteries. Rotation around the longitudinal axis pulls the dorsal mesogastrium to the left, creating a space behind the stomach called the omental bursa (lesser peritoneal sac).  With continued rotation of the stomach, the dorsal mesogastrium lengthens and fused with the posterior body wall. These changes also determine the final position of the PANCREAS  As a result of anteroposterior axis rotation, the dorsal mesogastrium bulges down and forms a double-layered sac.... greater omentum. Later, its layers fuse to form a single sheet hanging from the greater curvature of the stomach.  The Lesser Omentum and Falciform Ligament Develop from ventral mesogastrium. 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; and (c) the 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). Clinical correlation: Congenital pyloric stenosis Congenital defect in which the opening of the pylorus is too narrow due to hypertrophy in circular and longitudinal muscles. Food is thus unable to pass into the duodenum and stomach is enlarged. Most children with pyloric stenosis usually manifest forceful, "projectile" vomiting within the first 1-2 weeks of life.  Formation of duodenum By the 4th week....terminal part of foregut and cephalic part of midgut As the stomach rotates...duodenum has C- shaped loop & rotates to the right...fixed in a retroperitoneal position. Since duodenum has two origin; it is supplied by branches of celiac artery and superior mesenteric artery  Recanalization During 2nd month, lumen of the duodenum is oblitered by cell proliferation. However lumen is recanalized shortly after. Recanalization defects Polyhydramniosis Stenosis: Stomach contents (which typically include bile) are expelled by vomiting. Atresia: Few hours after birth, newborns with atresia vomit, and the vomit always contains bile. 1/3 of affected infants have Down syndrome & 20% are premature. Liver and Gallbladder Liver primordium appears in the middle of 3rd wk as an outgrowth of endodermal epithelium: hepatic diverticulum, or liver bud….rapidly proliferating cells that penetrate the septum transversum (mesodermal plate between the pericardial cavity and the stalk of the yolk sac)  During further development epithelial liver cords; Fuse with the vitelline and umbilical veins and form hepatic sinusoids 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.  While hepatic cells continue to penetrate the septum, connection between the hepatic diverticulum and the foregut (duodenum) narrows.... bile duct. Small caudal part of hepatic diverticulum forms the gallbladder. Stalk of hepatic diverticulum forms the small ventral outgrowth … the cystic duct.  In the 10th wk of... weight of the liver... 10% of the total body weight due to large numbers of sinusoids & hematopoietic function. This activity gradually decreases during the last 2 months of intrauterine life...at birth liver weight...5%. Bile formation by hepatic cells...begins approx. on 12th week. Positional changes of the duodenum... bile duct passes behind the duodenum.  Gallbladder abnormalities The most significant anomaly is biliary atresia. Causes: Failure in recanalization, failure in formation of the hepatic hilum, as well as immunological reactions or infections that develop in the late fetal period. Immediately after birth, jaundice and clay-colored feces are observed. The infant may die when the biliary atresia is not corrected surgically and if the liver transplant is not conducted. Duplication  Pancreas The pancreas develops as an outgrowth of the duodenum. It develops as two pancreatic buds: the dorsal pancreatic bud and the ventral pancreatic bud. When duodenum rotates right to become C-shaped, ventral pancreatic bud moves & fuses with dorsal bud to form body and tail of the pancreas. Ventral pancreas giving rise to the head and uncinate process of the pancreas.  How is the main The main pancreatic duct (Wirsung)...distal part of dorsal pancreatic duct made. pancreatic bud & entire ventral pancreatic bud. Accessory pancreatic duct (Santorini)...proximal part of dorsal pancreatic bud  Histogenesis of Pancreas ✓ Parenchyma of pancreas… pancreatic bud endoderm ✓ Serous acinus (exocrine pancreas) develops in early fetal period ✓ Islets of Langerhans...3rd month.... scattered among pancreas ✓ Insulin secretion begins...10th week ✓ Pancreatic connective tissue...surrounding visseral mesoderm  Annular Pancreas The ventral pancreas may consist of two lobes. If the lobes migrate around the duodenum in opposite directions to fuse with the dorsal pancreatic bud, an annular pancreas is formed. Annular pancreas is an abnormal ring of pancreatic tissue that encircles the duodenum. This portion of pancreas can constrict the duodenum and block or impair the flow of food to the rest of the intestines. Symptoms from annular pancreas are nausea & vomiting, feeling of fullness after eating & feeding problems in newborns. Surgical bypass of the obstructing segment of duodenum is the usual treatment for this disorder  Midgut Cephalic limb gives rise to: Distal part of the duodenum Jejunum Upper part of ileum Caudal limb gives rise to: Lower part of ileum Cecum Appendix Ascending colon proximal two-thirds of transverse colon  In the 5-week embryo, the midgut is suspended from the dorsal abdominal wall by a short mesentery and communicates with the yolk sac by the vitelline duct or yolk stalk Development of the midgut is characterized by rapid elongation of the gut & its mesentery, resulting in formation of the primary intestinal loop The midgut is supplied by.... superior mesenteric artery.  Physiological umblical herniation As the midgut elongates, it forms a ventral, U-shaped intestinal loop that projects into extraembryonic cavity in the umbilical cord during the beginning of 6th wk….physiological umbilical herniation. Herniation normally occurs because abdominal cavity is too small to house the rapidly growing midgut & expanded liver-kidneys. Herniated intestinal loops begin to return to the abdominal cavity in the 10th week The proximal portion of the jejunum, the first part to reenter the abdominal cavity. The cecal bud, is the last part of the gut to reenter the abdominal cavity  Rotation is counterclockwise, and approx 270° when it is complete During rotation, elongation of the small intestinal loop continues, the jejunum and ileum formed number of coiled loops. The large intestine also lengthens but does not participate in the coiling phenomenon.  Abnormalities of Midgut: Body wall defects Mostly rotational abnormalities occur Omphalocele: persistance of herniation of abdominal contents into proximal part of umblical cord. Hernial sac include small-large intestines, stomach, spleen or gallbladder and are covered by a membrane composed of peritoneum & amnion. Surgical repair is required.  Body wall defects: Gastroschisis Results from a defect lateral to median plane of anterior abdominal wall. This defect permits extrusion of abdominal viscera without involving umblical cord. The viscera protrude into amniotic cavity and exposed to amniotic fluid. Viscera are not covered by peritoneum or amnion, and bowel may be damaged by exposure to amniotic fluid. Unlike omphalocele, gastroschisis is not associated with chromosome abnormalities or other severe defects. Volvulus (rotation of bowel) resulting in compromised blood supply may kill large regions of intestine and lead to fetal death.  Umblical hernia Forms during 10th wk, when intestines return to abdominal cavity, then herniate again through an defective closed umblicus. Difference versus omphalocele: protruding mass (usually greater omentum & part of small intestine) is covered by subcutaneous tissue & skin. Diameter of hernia usually ranges from 1-5 cm. The hernia protrudes during crying, straining or coughing.  Anomalies of midgut Birth defets of intestines are common. Most of them are anomalies of gut rotation: Malrotation of the gut (result from incomplete rotation and fixation of intestines). Nonrotation of gut: occurs when intestines does not rotate as it reenters abdomen. Infants with intestinal malrotation are prone to volvulus & present with bilious emesis (vomiting bile). Contrast X-ray can determine the presence of rotational abnormalities.  Ileal (Meckel’s) diverticulum Outpouching of part of ileum is common. It occurs 2% to 4% of population & prevalent in males. Clinical significance: It may become inflamed and cause symptoms that mimic appendicitis. The wall of diverticulum contains all layers of ileum &may contain small patches of gastric and pancreatic tissues. This ectopic gastric mucosa secretes acid, producing ulceration and bleeding. Ileal diverticulum is the remnant of proximal part of vitelline duct.  Hindgut Gives rise to: Distal third of the transverse colon Descending colon Sigmoid colon Rectum Upper part of anal canal  The hindgut joins with the allantois and together form the cloaca. Cloaca divides into the ventral urogenital sinus (urinary bladder&urethra) and a dorsal rectum and anal canal btw 4 to 6th weeks. The terminal portion of the hindgut enters the anorectal canal; the allantois enters the primitive urogenital sinus.  The urinary and intestinal tracts are separated as the cloaca becomes partitioned by the urorectal septum. As the embryo growths and caudal folding continues, the tip of urorectal septum comes to lie close to cloacal membrane. At the end of the 7th week, the cloacal membrane ruptures, creating the anal opening for the hindgut and a ventral opening for the urogenital sinus.  Lower third of the anorectal canal is formed by an ectodermal invagination; anal pit (proctodeum). With the degeneration of cloacal membrane (now called the anal membrane); the upper and lower parts of the anal canal fuse. The border between the the inferior end of the rectum & superior end of the anal pit is demarcated by mucosal folds called the pectinate line in the adult. This line represents fusion of endoderm & ectoderm.  Anorectal Anomalies Most of them result from abnormal development of urorectal septum, resulting in incomplete separation of cloaca into urogenital and anorectal parts. Common defect. Rectum ends blindly. Common defect. Rectum ends blindly.