OS 214 [A]: Digestion and Excretion Lec 01.1: Embryology of the Digestive Tract February 10, 2014 Blesile S. Mantaring, MD TOPIC OUTLINE I. Review of Embryonic Body Cavity Formation A. Second Week of Gestation: Bilaminar Embryonic Disc B. Development of Intraembryonic Mesoderm C. Formation of Intraembryonic Coelom D. Folding of the Embryo E. Dev’t of Mesentery 2° to Lateral Folding of Embryo F. Development of the Primitive Gut G. Recanalization of The Gut II. Development of the Foregut A. Esophagus B. Stomach C. Spleen D. Duodenum E. Liver and Biliary Tree F. Pancreas III. Development of the Midgut (5th – 10th Week) A. Development of the Intestines IV. Development of the Hindgut (5th – 7th Week) 1 o Secondary yolk sac – formed after degeneration of primary yolk sac o Allantois – out pouching of the secondary yolk sac Initially, the gut is closed on both ends (fusion of the endoderm and ectoderm) o The cephalic end has the buccopharyngeal membrane (prechordal plate – thickened circular area, indicates future head region), the future site for the mouth o The caudal end has the cloacal membrane, the future site for the anus B. DEVELOPMENT OF INTRAEMBRYONIC MESODERM This leads to the formation of 3 parts (from medial to lateral): o Paraxial mesoderm (medial) Differentiates and begins to divide into paired cuboidal bodies, somites Gives rise to axial skeleton and skeletal muscles The more somites there are, the older the embryo o Intermediate mesoderm Gives rise to the genitourinary system o Lateral plate mesoderm (focus of the lecture) Spaces formed within the lateral plate mesoderm gives rise to Legends: From the Powerpoint presentation From the lecturer From other sources (textbook, Internet, etc.) intraembryonic coelom/abdominal cavity ORIENTATION Coordinator: Dr. Angela Salvaña LO: Kei Genuino Grading System: http://uvle.up.edu.ph/mod/page/view.php?id=43587 Exemption: exemptions from finals for those with grades of 60% (final raw score) or better for the two long examinations with no failing for either. ATTENDANCE will be checked and at least 80% is required to complete the course. T/N: Hello! This trans will be largely similar to Block B’s trans (TY, Block B!) with our notes as well. Dr. Mantaring doesn’t give her PPT, and she hasn’t given us her outline as of print time, so we took from Block B’s resource folder. I. REVIEW OF EMBRYONIC BODY CAVITY FORMATION A. SECOND WEEK OF GESTATION: BILAMINAR EMBRYONIC DISC During the first week of life, the zygote undergoes divisions, forming first the morula, then the blastocyst, which is composed of the embryoblast and the trophoblast (forms placenta and membranes) Embryoblast differentiates into a bilaminar embryonic disc o epiblast o hypoblast Appearance of amniotic cavity Formation of primary yolk sac Figure 2. Schematic drawings of the human embryo during the 3rd & 4th weeks. LEFT: dorsal views of the developing embryo illustrating early formation of the brain, intraembryonic coelom, and somites. RIGHT: schematic transverse sections illustrating formation of the neural crest, neural tube, intraembryonic coelom, and somites. C. FORMATION OF INTRAEMBRYONIC COELOM Isolated spaces appear in the lateral mesoderm and cardiogenic area Figure 1. Formation and development of embryonic disc. Development of the 3 germ layers (ectoderm, mesoderm, endoderm all come from epiblast) through migration of mesenchymal cells from the primitive pit Blastocyst cavity primary yolk sac secondary yolk sac Formation of the following: o Amniotic cavity – appears within the epiblast o Primary yolk sac – from blastocyst cavity, associated with the hypoblast o Chorionic cavity – from the hypoblast Marvin, Reggie, Sha (superior to prechordal plate; mesodermal cells cannot infiltrate the prechordal plate so it proceeds superior to it) The heart develops superior to the prechordal plate Spaces coalesce to form a flat U-shaped cavity, the intraembryonic coelom Intraembryonic Coelom has three parts: o Pericardial cavity o Pericardioperitoneal canal – becomes pleural cavity o Peritoneal cavity – abdominal cavity The intraembryonic coelom divides lateral mesoderm into 2 layers: o Somatopleure (somatic or parietal layer), which is continuous with the extraembryonic mesoderm lining the amnion Page 1 / 6 Lec 01.1: Embryology of the Digestive Tract OS 214 o Splanchnopleure (splanchnic or visceral layer), which is continuous with the extraembryonic mesoderm covering the yolk sac Intraembryonic coelom communicates with the chorionic cavity D. FOLDING OF THE EMBRYO Occurs in the median and horizontal plane, secondary to the rapid growth of the embryo leads to the: o Formation of the head fold and tail fold in the median plane (much faster) o Formation of the lateral fold in the horizontal plane o Embryo becomes more cylindrical SEQUELAE OF BODY FOLDING 1. Remodeling of the intraembryonic coelom 2. Formation of the primitive gut from the secondary yolk sac 3. Ventral body wall is established 4. Formation of the mesentery that surrounds the primitive gut CONSEQUENCES OF LONGITUDINAL/MEDIAN FOLDING Formation of the head fold and tail fold Formation of the primitive gut o With folding, the superior portion of the secondary yolk sac becomes incorporated within the embryo, forming the primitive gut o Formation of vitelline duct or yolk stalk due to constriction of secondary yolk sac – connection of the primitive gut to secondary yolk sac o Foregut and hindgut – blind ended tubes Remodeling of the intraembryonic coelom o The intraembryonic coelom changes from a flat U-shaped cavity to a bent one with the pericardial cavity pushed to the ventral side o Sequelae of longitudinal body folding is the formation and development of the head fold and tail fold o Upper portion of secondary yolk sac gradually forms into the primitive gut o Intraembryonic coelom loses its connection with the chorionic cavity and becomes a closed cavity o Ventral movement of pericardial cavity due to the formation of the head fold Figure 4. Lateral folding. E. DEV’T OF MESENTERY SECONDARY TO LATERAL FOLDING DORSAL MESENTERY Suspends the gut from the posterior abdominal wall Extend from caudal part of foregut, midgut & major part of hindgut From esophagus to colon Parts: o Greater omentum or dorsal mesogastrium in stomach o Mesoduodenum in the duodenum o Dorsal mesocolon in the colon o Mesentery proper in the jejunal and ileal loops VENTRAL MESENTERY Suspends the gut from the anterior abdominal wall Gradually degenerates except in the foregut - distal esophagus, stomach, and upper portion of the duodenum Becomes part of the lesser omentum Foregut to duodenum Figure 5. Mesenteries. SUMMARY OF THE SEQUELAE OF FOLDING PHENOMENON Several movements affect the final position of the mesenteries o Rotation of the stomach o Movement of the duodenum o Reabsorption of the gut Thoracic Cephalic fold Lateral fold Lateral fold Abdominal wall Figure 3. Longitudinal folding. CONSEQUENCES OF LATERAL FOLDING Flat embryo becomes more cylindrical Ventral body wall is established o Two edges of the embryo meet at the ventral side, forming the ventral body wall Development of the mesentery o The mesentery surrounds the primitive gut, and suspends the gut from the posterior and anterior abdominal wall o Fusion of the splanchnic mesoderm around the gut secondary to lateral folding leads to development of the primary mesentery, which hangs the primitive gut in the abdominal wall o Two types of mesentery: Dorsal mesentery – ex. Mesocolon, mesogaster Ventral mesentery – ex. Falciform ligament, lesser omentum (gastrohepatic & hepatoduodenal ligaments) o The mesentery divides the coelom into right and left halves, until the ventral mesentery degenerates Marvin, Reggie, Sha Epigastric Close midgut and form the lateral abdominal walls Hindgut Bladder Caudal fold Hypogastric wall Figure 6. Formation of abdominal wall. BODY WALL DEFECTS Due to a failure of progression of the body folding Examples: o Cleft sternum – may result to ectopia cordis; thoracic area o Gastroschisis Herniation of abdominal contents directly into amniotic cavity Usually occurs on the right lateral to the umbilicus o Bladder and cloacal exstrophy: hypogastric area Page 2 / 6 Lec 01.1: Embryology of the Digestive Tract F. DEVELOPMENT OF THE PRIMITIVE GUT Primitive gut arises from superior part of the secondary yolk sac! G. RECANALIZATION OF THE GUT Starts with a canal proliferation of epithelium resulting to a solid structure formation of spaces (secondary cellular death due to apoptosis) recanalization (secondary formation of a canal) Occurs in the entire primitive gut No recanalization causes formation of atresia or stenosis which can occur in any part of the GI tract II. DEVELOPMENT OF THE FOREGUT Pharnyx & derivatives (oral cavity, tongue, tonsils, salivary glands) Esophagus Stomach Duodenum proximal to bile duct Arises as diverticula from foregut: o Tracheobronchial tree o Liver o Biliary apparatus o Pancreas o Respiratory system OS 214 The stomach then rotates 90° clockwise along its longitudinal axis, in effect the: o Lesser curvature (from ventral side) becomes situated in the right side; right side faces posteriorly o Greater curvature (from dorsal side) becomes situated in the left side; left side faces anteriorly o This explains how the left vagal trunk supplies anterior structures and the right vagal trunk supplies posterior structures o LARP – Left goes Anterior, Right goes Posterior It then rotates in an anteroposterior (AP) axis o Cranial region or cardiac portion moves inferiorly & to the right o Caudal region or pyloric part moves superiorly & to the left o Long axis in the stomach becomes nearly transverse MOVEMENT OF THE MESENTERY Rotation of the stomach about the longitudinal axis pulls the dorsal mesentery (originally midline) to the left and forms the omental bursa or lesser peritoneal sac (opening: Foramen of Winslow) Rotation about the AP axis pulls the dorsal mesentery down, forming the greater omentum A. ESOPHAGUS A partition called the tracheoesophageal septum separates the lung bud from the foregut, bringing about: o Dorsal esophagus o Ventral trachea and lung buds Displacement/deviation of septum may cause atresia or stenosis Elongates secondary to the descent of the heart and the lungs into the pleural cavity 7 weeks AOG – esophagus has reached its final relative length. Its epithelium (from endoderm) proliferates until the lumen is obstructed By the end of 8 weeks AOG – esophagus undergoes recanalization to reform the lumen Figure 8. Rotation of stomach and formation of the curvatures. C. SPLEEN Mesodermal proliferation in the dorsal mesogastrium Because of the rotation of the stomach, the spleen which was also in the midline moves to left Persists as an intraperitoneal organ Figure 7. Successive stages in the development of the tracheoesophageal septum during the 4th and 5th weeks. A, B, C are lateral views showing the partitioning of the foregut into the esophagus and laryngotracheal tube. D, E, F, are transverse sections showing formation of the tracheoesophageal septum and showing how it separates the foregut into the laryngotracheal tube and esophagus. Figure 9. Movement of spleen and pancreas due to stomach rotation. COMMON ESOPHAGEAL ANOMALIES Esophageal atresia with or without tracheoesophageal fistula – tracheoesophageal septum is displaced Esophageal stenosis – more posterior displacement of septum Short esophagus leading to congenital hiatal hernia – esophagus did not lengthen As heart grows, esophagus is pulled down. Congenital diaphragmatic hernia is a defect wherein the esophagus did not come down. Atresia/fistula is a defect wherein the septum did not divide. B. STOMACH The stomach begins as a fusiform dilatation in the foregut, initially a midline structure. It is attached to the body wall through the dorsal (mesogastrium) and ventral mesentery The dorsal or posterior wall of the stomach grows faster than the ventral wall, resulting in the formation of the curvatures of the stomach o Dorsal/posterior wall – greater curvature o Ventral wall – lesser curvature (anterior side grows slower) Marvin, Reggie, Sha D. DUODENUM Parts 1. First ascending (T12-L1) 2. Descending (L1) 3. Transverse (L3-L4) 4. Terminal ascending (L1-L2) Derived from the: o Terminal part of the foregut o Cephalic part of the midgut With the rotation of the stomach, the duodenum becomes a Cshaped loop Rotation of stomach pushes duodenum to the left and to the back It swings from its initial midline position to the left side of the abdominal cavity and adheres to the body wall then loses its mesentery and becomes retroperitoneal First 5 cm will still have the mesentery (intraperitoneal) and is still movable The lumen of the duodenum is obliterated by the proliferation of cells, and then is recanalized (no recanalization leads to atresia/stenosis) Page 3 / 6 Lec 01.1: Embryology of the Digestive Tract OS 214 Also, as a result of the rotation of the duodenum, the pancreas becomes retroperitoneal as well. Development of the Pancreatic Duct o Main duct/Duct of Wirsung: entire ventral pancreatic duct + distal part of the dorsal bud duct o Accessory duct of Santorini: proximal part of dorsal bud duct ANOMALY: ANNULAR PANCREAS Sometimes the ventral bud may have two separate buds. One bud moves back while the other moves front, embracing the duodenum and forming an annular pancreas Figure 10. Development of the duodenum. E. LIVER AND BILIARY TREE The liver bud develops at the distal end of the foregut o Hepatic cell cords grow towards the septum transversum o Cell cords surround vitelline veins which form hepatic sinusoids The septum transversum is a mesodermal tissue that grows from the ventral wall, which separates the heart from the liver As the hepatic cells penetrate the septum, the connection between the liver bud/hepatic diverticulum and the duodenum narrows to become the common bile duct. The common bile duct has a small ventral outgrowth, which later on becomes the gallbladder. (Cystic duct – constriction between bile duct and gallbladder) The liver divides the ventral mesentery o The lesser omentum between esophagus, stomach, and upper part of duodenum to liver, composed of the hepatogastric and hepatoduodenal portions o The falciform ligament between the liver and ventral body wall, containing the umbilical vein (ligamentum teres hepatis or round ligament of the liver) III. DEVELOPMENT OF THE MIDGUT (5th – 10th week) Common bile duct divides proximal and distal part of duodenum. o Parts of the duodenum proximal to common bile duct come from the foregut and is supplied by the celiac trunk o Distal to the duodenum are from midgut and is supplied by SMA Derivatives of the midgut include: o Small intestines including most of the duodenum o Cecum o Appendix o Ascending colon o 2/3 of the transverse colon Supplied by the superior mesenteric artery (SMA) A. DEVELOPMENT OF THE INTESTINES DEVELOPMENT OF THE INTESTINAL LOOP The midgut elongates forming the primary intestinal loop, with two limbs: o Cranial limb – from which the following structures are derived: distal duodenum, jejunum, proximal ileum o Caudal limb – from which the following structures are derived: distal part of ileum and proximal part of the large intestines (Cecum, appendix, ascending colon, proximal 2/3 of the transverse colon). Note that a cecal bud develops from the caudal limb that becomes the cecum. The vitelline duct connects apex of the intestinal loop to yolk sac. Note that the duct lies within the umbilical cord. F. PANCREAS Figure 12. Intestinal loop and its rotations. PHYSIOLOGICAL UMBILICAL HERNIATION The intestinal loop will start to grow longer but due to the very small abdominal cavity, the developing mesonephric kidney, and liver, there is no space for intestinal loop to grow; hence, there is physiologic umbilical hernia. The abdominal organs grow much faster than abdominal cavity! At about 6-8 weeks AOG, physiological umbilical herniation occurs. o The primary intestinal loop is forced to herniate into the extraembryonic cavity through the umbilicus into the umbilical cord (physiological hernia) because there is not enough space to grow intraembryonically o As herniation occurs, the loop undergoes 90o counterclockwise longitudinal rotation about the SMA Figure 11. Development of the pancreas. The pancreas is the last organ that develops in the foregut The pancreas originates as two pancreatic buds: o The dorsal pancreatic bud is in the dorsal mesentery o The ventral pancreatic bud is near the bile duct When the duodenum rotates and becomes C-shaped, the ventral pancreatic bud moves dorsally, caudally and posterior to the dorsal bud. The buds then fuse. o Ventral pancreatic bud becomes the uncinate process and head of the pancreas! o Dorsal bud body and tail of the pancreas! Marvin, Reggie, Sha Figure 13. Physiological umbilical herniation. Page 4 / 6 Lec 01.1: Embryology of the Digestive Tract Rotation of the midgut – the midgut loop undergoes a 90° counterclockwise rotation around the axis RETURN TO THE ABDOMINAL CAVITY At 10-11 weeks AOG, the intestine loop retracts back into the abdominal cavity since it is now big enough to accommodate the abdominal organs, with cranial limb returning first. This leads to: o Regression of the mesonephric kidney o Reduced growth of liver o Increased size of the abdominal cavity As the colon returns, the loop undergoes further rotation of 180° counterclockwise around the SMA from the initial rotation (total rotation: 270o) OS 214 FURTHER DEVELOPMENT AND FIXATION At 11 weeks AOG, the ascending colon elongates and the cecal bud appears in the caudal limb (the cecum descends and settles in the right lower quadrant) Vitelline duct regresses and disappears! Finally, ascending and descending colon become retroperitoneal. Their mesenteries fixate/fuse to the posterior abdominal wall. Figure 17. Fixation of the intestines. DEVELOPMENTAL ANOMALIES OF THE INTESTINES Figure 14. First stage of rotation (90°). The cranial limb retracts first going towards the left side of the abdominal cavity The caudal limb is pulled next and settles to the right of the cranial limb o The first part that enters is the jejunum, followed by the ileum, then lastly, the cecal bulb! Atresia and stenosis o During development, the gut undergoes a solid phase o If recanalization is incomplete then there are abnormalities Omphalocoele o Congenital anomaly when the intestines fail to return to the abdominal cavity in the 10th-11th week o Herniated loops produce swelling; covered only by amnion o Differentiated from gastroschisis where ventral wall failed to close o Associated with other malformations: cardiac anomalies, neural tube defects and chromosomal abnormalities o Poorer prognosis than gastroschisis Ileal or Meckel’s Diverticulum o Portion of the vitelline duct fails to degenerate o Different presentations include: Appendix-like structure in the ileum Fibrous cord attached to the umbilicus Patent vitelline duct with potential for fecal matter to leave ileum through the diverticulum and through the umbilicus (vs. patent urachus which manifests as urinal discharge in umbilicus) Figure 15. Second stage of rotation (additional 180°) midgut at 10 weeks AOG. Figure 18. Omphalocoele. Figure 19. Meckel’s Diverticulum. Figure 16. Second stage of rotation (additional 180°) midgut at 11 weeks AOG with all intestines having returned to the abdominal cavity. Marvin, Reggie, Sha Malrotation o Associated with great risk for volvulus followed by severe pain and necrosis of the twisted segment o Kinds Non-rotation – occurs when the intestines do not rotate 180 degrees as it returns into the abdominal cavity; the large intestine Page 5 / 6 Lec 01.1: Embryology of the Digestive Tract OS 214 is located at the left of the body and small intestine is on the right side Reversed rotation – occurs when the primary loop rotates 90 degrees clockwise; transverse colon passes behind the duodenum IV. DEVELOPMENT OF THE HINDGUT (5th – 7th Week) Derivatives of the hindgut include: o Distal third of the transverse colon o Descending colon o Sigmoid o Rectum o Upper part of the anal canal The cloaca is the dilated terminal chamber of the hindgut. The urorectal septum, which is a mesodermal plate, divides it into dorsal and ventral parts: o Rectum and anal canal dorsally o Tip of urorectal septum becomes the central point perineum o Urogenital sinus ventrally, which develops into the: Urinary bladder Urethra - Prostatic and membranous urethra - Whole female urethra Figure 20. Development of the hindgut. DEVELOPMENTAL ANOMALIES Failure of urorectal septum to divide the cloaca Hirschprung’s Disease o Defective migration of the neural crest cells into the hindgut o Also called aganglionic megacolon o Presents with failure to pass meconium o Neural crest cells Starts with the formation of neural tube Neural crest cells detach from the neural tube and migrate towards the entire body Imperforate Anus o Results from the failure of dilated cloacal membrane to rupture END OF TRANSCRIPTION Reggie: Opening OS 214 with a bang! Have yourself a two-part-megaembryo trans with orientation box. Marvin: Happy Valentine! :D Sino ang gigising ng Friday morning mo? :> Marvin, Reggie, Sha Page 6 / 6