Asist. Univ. Dr. Tulin Raluca Embryology Year 2- LP1 Asist. Univ. Dr. Tulin Raluca

The development of the digestive tract Covered topics I. The formation of serous cavities of the trunk -LECTURE II. The development of the digestive tube: foregut, midgut, hindgut. Separation of the cloaca- abnormalities. – LECTURE III. The development of the liver and portal system. The development of the pancreas. – abnormalities. LECTURE L.P. 1. Formation of the omental bursa, greater omentum and transverse mesocolon. 2. Development of the gall bladder- malformations. 3. Physiological hernia- abnormalities. 4. Development of the spleen- abnormalities. 5. Clinical implications of the most frequently occurring digestive tract malformations.

Development of the diaphragm Separation of the peritoneal cavity from the pleural cavity (they are both derived from the intra-embryonic coelom) Develops from 4 sources: Septum transversum (mesoderm)—central tendon Incompletely separates the two cavities, leaving 2 pericardioperitoneal canals on either side of the foregut Pleuropericardial folds- contain the phrenic nerves Mesentary of the esophagus- the crura of the diaphragm Myoblasts from thoracic wall (somites C3-C5)

Malformations of the diaphragm Congenital diaphragmatic hernia 1/2000 births, commonly postero-laterally More frequently unilateral, on the left (foramen of Bochdalek) If the pericardioperitoneal canals are not closed by W10 when the physiological hernia retracts, the intestinal coils (less frequently the stomach, colon, rectum) will ascend into the thoracic cavity and impede normal ventilation. Congenital hiatal hernia Rare, organs herniate through an enlarged esophageal hiatus. Usually occurs during adulthood Parasternal hernia (retrosternal) – Morgagni Rare, between then sternum and the sterno-costal surface of the diaphragm

Clinical implications The uneven growth of the lateral body walls pushes the diaphragm inferiorly from the cervical region (origin of the phrenic nerves) into the thorax Irritation of the diaphragm may produce pain in the shoulder or neck (both innervated by nerves of the cervical or brachial plexus- referred pain. Their common origin from mesenchyme explains the close contact between the diaphragm and the pericardium Similarly, the common origin of the liver and the diaphragm from the septum transversum explains the close contact between the two structures

IVC +nn. Phrenic (T8) Esophagus+ nn. Vagi (T10) Aorta+ thoracic duct (T12) Sympathetic chain – medial arcuate ligaments

Development of the digestive system

Foregut- derivatives Pharynx- larynx- respiratory system Esophagus Stomach Superior half of duodenum Liver and bile ducts Pancreas

Esophagus Esophageal atresia (and/or tracheoesophagial fistula) Polyhydramnios in uterus Surgical treatment Esophageal stenosis Narrowing of the lumen Ingustarea lumenului Incomplete recanalization Vascular abnormalities

Development of the stomach and formation of the omental bursa

Mesenteries Ventral mesogastrium (liver) Lesser omentum (liver- duodenum + stomach) – hepatoduodenal ligament contains portal triad (bile duct, portal vein, hepatic artery), forms the superior margin of the foramen of Winslow, which allows passage into the omental bursa Falciform ligament (liver-anterior body wall) contains ombilical vein which will become the round ligament of the liver (ligamentum teres) Dorsal mesogastrium (spleen) – grows over the transverse colon and the coils of the small intestine Greater omentum (4 peritoneal sheets) Transvere mesocolon (4 periotneal sheets)

Bursa omentala

Stomach malformations Pyloric stenosis Circular muscle in the region of the pylorus hypertrophies Passage of food is obstructed + frequent vomiting

Development of pancreas

Pancreas malformations Annular pancreas Occasionally associated with obstruction of the duodenum Accessory pancreatic tissue (ectopic) In the stomach In Meckel’s diverticulum

Midgut- derivaties Forms inferior half of duodenum Jejunum Ileum Cecum Apendix Ascending colon Proximal 2/3 of transverse colon

Physiological hernia During S6-S10 Primary intestinal loop (midgut) cephalic limb caudal limb Uneven elongation of cephalic and caudal limbs 270 degree counterclockwise rotation (90 degrees while herniated + 180 degrees when returned inside abdominal cavity)

Small intestine Age Length (cm) 20W 125 30 200 TERM 275 1 year 380 10 years 500 20 years 575 Elonagation of small intestine is proportional until 3rd trimester Length doubles in last trimester Elongation continues post-natally but slows after 1 year Duodenum 25 cm Jejunum 1,4 m Ileum 3,5 m Apendix 2-20 cm Ascending colon

Migration of neural crest cells into the developing GI tract W5- neural crest cells migrate to midgut. W7- they colonize entire length of primitive gut (anterior-posterior) Auerbach myenteric plexus- between the circular and longitudinal muscle layers – motor and secretory innervation to both (sympathetic + parasympathetic) Meissner submucous plexus – forms 2-3 days after the myenteric plexus. Innervates the muscularis mucosa Interstitial cells of Cajal- possess intrinsic pacemaker property, located between smooth muscle cells. Derived from mesoderm.

Malformations Omphalocoel Gastroschisis Enlarged umbilicus Herniated intestinal coils are contained within a sac (amniotic membrane) 2,5/10,000 births Physiological hernia does not return into abdominal cavity Mortality rate 25% Gastroschisis Abdominal wall defect, lateral to umbilicus Herniated organs are not contained within sac 1/10,000 births (associated with consumption of cocaine) High survival rate

Meckel’s diverticulum Present in 2-4% of all adults Approximately 40-60 cm from ileocecal (Bauhin) valve, on the antimesenteric border of ileum Usually asymptomatic May contain gastric mucosa or pancreatic tissue May form direct communication between umbilicus and intestinal tract- vitelline fistula

Development of the liver 2 origins Outgrowth of endoderm gives rise to liver bud (inferior limit of the of the foregut) Hepatocytes Hepatic sinusoids (formed by fragmentation of vitelline and umbilical veins) Mesoderm of septum transversum Hematopoietic cells Kupffer cells Connective tissue (Glisson capsule)

Clinical implications W10- liver makes up 10% of body weight and carries out hematopoietic function (synthesis of formed elements in blood ) M7- hematopoietic function stops At birth- liver makes up 5% of body weight W12 – biliary secretion begins (cystic duct, bile duct, gall bladder are already formed) into GI tract

Hematopoiesis Initially- yolk sac and para-aortic sac in splanchnopleura (aorto-gonado-mesonephros) AGM W5 –liver (main site until W8) W8- SPLEEN- is never a main site (as in mice) –M8 W12- bone marrow W15- thymus PERIPHERAL BLOOD – IMPORTANT SOURCE OF STEM CELLS (PRENATALLY)

Hematopoiesis

Malformations of liver and bile ducts Variations in hepatic lobulations- not clinically significant Accessory hepatic ducts Duplication of the gall bladder Extrahepatic biliary atresia 1/15,000 live births, most frequently in Asia Treatment- liver transplant Jaundice, dark colored urine, colorless stool Intrahepatic atresia/stenosis 1/100,000 live births Fetal infections May be lethal

Liver lobes

Extrahepatic biliary atresia

Hindgut Forms Distal 1/3 of transverse colon Descending colon Sigmoid colon Rectum (anal canal- superior part, up to pectinate line) Clinical implications The different origins of the 2 parts of the transverse colon (proximal 2/3 and distal 1/3) explains there different blood supplies The different origins of the rectum explains the different blood supplies, innervation and lymphatic drainage of this structure

Cloaca- division W6 Clinical implications Superior Inferior– last 2 cm of anal canal Origin Endoderm Ectoderm Blood supply Inferior mesenteric artery Internal iliac arteries (middle and inferior rectal arteries) Venous drainage Superior rectal veins (venous plexus) Inferior and middle rectal veins--- IVC Lymphatic drainage Internal iliac lymph nodes Inguinal lymph nodes Innervation Visceral sensory Somatic sensory

Clinical implications The different lymphatic drainage of the anal canal explains the different types of metastasis above or below the pectinate line The different innervation explains the absence of perceived pain from lesions above the pectinate line

Hirschsprung’s Disease Congenital megacolon Absence of parasympathetic ganglia from the intestinal wall (normally derived from neural crest cells) Rectum and sigmoid colon are frequently affected (sacral nerve supply) The entire colon is rarely affected (Vagus nerve is effective guide for migrating neural crest cells- this condition rarely occurs proximal to splenic flexure)

Ano-rectal abnormalities Due to abnormal division of the cloaca Imperforate Anal membrane fails to break down Rectouteral or rectovaginal fistulas 1/5000 births