Digestive System Development PDF

Digestive System Development MED-202: Histology/Embryology I Fall 2024 Annita Achilleos, PhD  Reading Material 1. Langman’s Medical Embryology: Chapter 15 2. Ronald Dudek: Embryology 5th or 6th edition: Chapter 10 3. Lecture  Learning object...

Digestive System Development MED-202: Histology/Embryology I Fall 2024 Annita Achilleos, PhD  Reading Material 1. Langman’s Medical Embryology: Chapter 15 2. Ronald Dudek: Embryology 5th or 6th edition: Chapter 10 3. Lecture  Learning objectives Outline the embryonic development of foregut, midgut, hindgut Outline the developmental stages of the oesophagus, stomach, small and large intestine. Outline derivatives of the cloaca Clinical correlates  The digestive system derives from the primitive gut tube Amniotic cavity Ectoderm Endoderm Mesoderm Embryonic Yolk sac body cavity Gut tube 1. The primitive gut tube is derived from the dorsal part of the yolk sac, which is incorporated into the body of the embryo during folding of the embryo (week 4). 2. The primitive gut tube gives rise to both the respiratory and digestive systems. 3. The primitive gut tube has an endodermal lining and a mesodermal wall. Epithelial lining Connective tissue (stroma) Specific cells of Muscle glands (e.g. hepatocytes) Peritoneal components The primitive gut tube is divided into three sections: foregut, hindgut, midgut Respiratory diverticulum foregut midgut hindgut The foregut, midgut and hindgut areas are defined based on their arterial supply Celiac artery Respiratory diverticulum Superior foregut mesenteric artery Abdominal midgut aorta hindgut Inferior mesenteric artery  Foregut Derivatives: Esophagus The tracheoesophageal folds fuse to form the tracheoesophageal septum that separates the esophagus and trachea. Esophagus Esophagus The esophagus lengthens with the descent of the heart and lungs 25 days 32 days The gut tube and its derivatives are suspended from the body wall by mesenteries Mesenteries form by the double fold of peritoneum and have three functions: a. keep the organs in place b. store fat c. provide pathway for vessels, nerves, and lymphatics Dorsal mesentery  Clinical correlates: Tracheoesophageal Fistulas and Esophageal Atresia Fistula: an abnormal connection (this case between the esophagus and the trachea) Atresia: abnormal closure or absence of an orifice or passage in the body Due to defects during the formation of 90% 4% 4% the tracheoesophageal septum 1 in 3000 births Isolated (40%) In association with other birth defects (VACTERL association) 1% 1%  Clinical correlates: Achalasia − Absence or loss of ganglion cells  Failure to relax the lower esophageal Treatment sphincter − Pneumatic dilation – inserting a balloon  Food accumulation in the esophagus − Botox (muscle relaxant) − Congenital or acquired − ~10 in 100,000 Esophageal Achalasia Normal esophagus stomach Lower esophageal sphincter 5  Foregut Derivatives - Stomach The embryonic stomach appears as a fusiform dilation of the foregut Many neighbouring organs are undergoing morphogenesis at the same time Stomach Endodermal origin − Simple columnar epithelium Mesodermal origin − Smooth muscle, connective tissue, blood vessels Neural crest ~4 weeks − Enteric nervous system Unequal rate of growth of the anterior Lesser curvature and posterior walls result in the greater and lesser curvatures of the stomach Greater curvature  The stomach rotates around two axes during its morphogenesis Longitudinal 90° clockwise - longitudinal axis rotation axis - it brings the left side to the anterior - it brings the right to the posterior - unequal growth of the anterior and posterior walls  curvature 90° clockwise - anteroposterior axis - the caudal end (pylorus) shifts Anteroposterior to the right and upward axis - The cephalic end shifts to the left and downward Mesenteries: - become longer - get rearranged - affect the topology of neighbouring organs  Midgut Derivatives - Intestine − Rapid elongation of the midgut and its mesentery forms the primary intestinal loop − The primary intestinal loop will form most of the intestines 1. Lower duodenum 2. Jejunum 3. Ileum 4. Cecum 5. Appendix Transverse colon 6. Ascending colon Duodenum 7. Transverse colon Jejunum Ascending colon (proximal 2/3) Cecum Ileum Appendix  The primary intestinal loop grows rapidly and rotates simultaneously − 270° (total) rotation counterclockwise around an axis formed by the superior mesenteric artery − Elongation and rotation happen simultaneously resulting in a number of coiled loops Stomach Cecum Duodenum Vitelline Descending duct colon Jejunoileal loops Primary intestinal loop before rotation after rotation  As the primary intestinal loop elongates it enters the extraembryonic cavity − Due to lack of space, as the primary intestinal loop elongates and rotates (90°), it undergoes physiological umbilical herniation − The colon does not leave the abdominal cavity − The point of loop is connected to the yolk sac by the vitelline duct Stomach Cecum Duodenum Superior Descending Vitelline Vitelline mesenteric duct colon duct artery Jejunoileal loops 6 Weeks 8 Weeks  The intestinal loops return into the abdominal cavity 4 weeks later − The intestinal loops assume their permanent position by week 12 − As the loops return, they rotate additional 180° degrees − Both the ascending and descending parts of the colon will fuse to the posterior wall and become retroperitoneal 10 Weeks 11 Weeks  Clinical correlates: Gut Rotation Defects (Malrotations) 1 in 500 live births 1. Reversed rotation of the intestinal loop 2. Insufficient rotation - Rotation happens 90° clockwise - Total rotation of 90° only (instead of 270°) - Mispositioning of the colon to the left (!) (1) (2)  Clinical correlates: Gut Rotation Defects (Malrotations) 3. Volvulus - Twisting of the intestine and due to malrotation  Blood supply is compromised leading to necrosis  Bowel obstruction Large Stomach intestine Volvulus Small intestine childrenshospital.org  Clinical correlates: Body Wall Defects 1. Omphalocele Organs are covered in a thin, − Herniation of abdominal viscera transparent sac through the umbilical ring − Due to failure of the intestinal loop to return back from its physiological herniation − 1 - 3.8 per 10,000 births − Genetic (chromosomal abnormalities) and environmental (alcohol, tobacco, SSRIs) causes cdc.gov − Isolated omphalocele (90% survival rate) − Associated with other birth defects (70% survival rate)  Clinical correlates: Body Wall Defects 2. Gastroschisis − Protrusion of abdominal viscera through the body wall − Due to abnormal closure of the body wall − 1 in 2000 births, but is has been dramatically increasing − More common in teenage mothers − Alcohol and tobacco use − Genitourinary infections cdc.gov − Not associated with chromosomal abnormalities or other major birth defects Foregut Derivatives – Liver and Gallbladder Foregut Derivatives – Liver and Gallbladder The hepatic diverticulum (or liver bud) appears on the foregut as a proliferating outgrowth of the endodermal epithelium of the foregut  FGF2 inhibits the liver inhibitors at the hepatic region promoting development of the liver bud The rapidly proliferating cells of the liver bud penetrate the septum transversum (mesenchyme, mesoderm) Liver bud Septum transversum ~3.5 weeks ~4.5 weeks  Foregut Derivatives – Liver and Gallbladder As the hepatic cells penetrate the septum Bile duct transversum, the connection between the liver bud and foregut narrows, forming the bile duct Liver An outgrowth is formed on the ventral side of the bile duct giving rise to the gallbladder and the cystic duct 5 weeks  Fetal functions of the liver and gallbladder  Hematopoietic function - In week 10 of development, the weight of the liver is ~10% of the total body weight - During fetal development, the liver is a major center for haematopoiesis - Liver haematopoiesis gradually subsides during the last two months of fetal life - The weight of the liver eventually drops to 5% of the total weight  Bile production - Hepatic cells start forming bile at week 12 of development  Foregut Derivatives - Pancreas Pancreas an organ of the digestive and endocrine systems - Digestive: an exocrine gland that secretes pancreatic juice into the duodenum to neutralize acid (bicarbonate) and break down carbohydrates, proteins and fats (digestive enzymes) - Endocrine: an endocrine gland that secretes insulin (and other hormones) to regulate blood sugar levels  Foregut Derivatives - Pancreas Stomach 4 weeks 5 weeks C 5 weeks 6 weeks D Formed by two buds, During gut rotation, Ventral and dorsal dorsal and ventral, from the ventral bud pancreatic buds the endoderm of the moves dorsally fuse primitive gut tube  Clinical correlates: Pancreas Divisum − Failure of the pancreatic ducts to fully fuse − 6-10% occurrence − 95% is asymptomatic − Rarely it can cause pancreatitis  Clinical correlates: Biliary atresia A blockage in the ducts that carry bile from the liver to the gallbladder - Congenital defect - 1 in 15,000 - Failure of the bile ducts to develop normally  Bile from the liver to the gallbladder is blocked  The bile accumulates inside the liver  Can lead to liver damage and cirrhosis  Can lead to liver failure - Isolated or with other birth defects (heart, spleen, intestine, kidneys) Treatment - Connect the liver to the small intestine  Hindgut Derivatives 1. Distal 1/3 of the transverse colon 2. Descending colon 3. Sigmoid 4. Rectum 5. Upper part of the anal canal − The endoderm of the hindgut gives rise to the lining of the bladder and urethra Transverse colon Descending colon Cloaca Hindgut Sigmoid colon Rectum Rectum Anus  The hindgut ends in the posterior portion of the cloaca − The cloaca: − is an endoderm-lined pouch − is a common chamber for the hindgut and the urinary systems − it will form the urogenital sinus (anteriorly) and the anus (posteriorly) Cloacal membrane − covers the cloaca − formed by surface ectoderm and endoderm The urorectal septum grows caudally separating the hindgut (posteriorly) and the primitive urogenital sinus (anteriorly). Urorectal septum 5 Weeks 7 Weeks 8 Weeks The cloaca separates into the anorectal canal and the urogenital sinus Rupture of the cloacal membrane creates: − the anal opening − an opening for the urogenital sinus Urinary bladder Perineal Urorectal body septum Surface ectoderm proliferates and invaginates to form the anal pit Anal membrane (former Anorectal canal cloacal membrane) breaks down 8 Weeks  Clinical correlates: Hindgut abnormalities Urorectal and rectovaginal fistulas Due to defects during the formation of the cloaca and/or the urorectal septum - the cloaca may be too small - the urorectal septum may not extend far enough Urorectal fistula Rectovaginal fistula  Clinical correlates: Hindgut abnormalities Rectoperineal fistula Imperforate anus − Defects in the epithelial-mesenchymal − Failure of the anal membrane to signalling break down  Summary Formation of the primitive gut and sub-divisions. Development of oesophagus and clinical correlates. Development of stomach, small and large intestine. Clinical abnormalities related to small and large intestine. Derivatives of the cloaca and clinical correlates. Thank you