Chapter 14 Digestive System PDF 2024

2024 Chapter 14 Chapter 14: Digestive System Key terms and concepts: Ventral folding morphogenesis Lesser omentum Vitelline duct Omental bursa Mesente...

2024 Chapter 14 Chapter 14: Digestive System Key terms and concepts: Ventral folding morphogenesis Lesser omentum Vitelline duct Omental bursa Mesentery Rumen Cloacal membrane Non-glandular fore-stomachs Foregut Colon (transverse, ascending, descending) Midgut Rectum Hindgut Cloacal membrane Hox genes in GI patterning Urogenital sinus Liver Urorectal septum Celiac artery Anal membrane Cranial mesenteric artery Caudal mesenteric artery Meckel’s diverticulum Stomach Physiologic umbilical hernia Duodenum Umbilical hernia (defect) Dorsal mesogastrium Omphalocele Ventral mesogastrium Imperforate anus/atresia ani Greater omentum Vascular ring anomalies Learning objectives: By the end if this unit you should be able to: 1. Describe the embryonic formation of the early gut tube. 2. Name the embryonic tissues that give rise to the GI tract and its derivatives such as the liver. 3. Describe the relationship between the yolk sac and the embryonic gut tube and identify the embryonic structure that connects the developing gut to the yolk sac. 4. Explain basic mechanisms for how cranial/caudal regional identity is established in the developing GI tract. 5. Describe the development of the stomach and how gastric development diverges among different species. 6. Describe the formation of the omentum (greater and lesser) and explain the developmental basis of the formation of the omental bursa and greater omentum. 7. Describe the developmental events of liver formation, including inductive effects of nearby tissues on the gut endoderm that gives rise to the liver. 8. Give 2 reasons why the mesenteries are important to the GI tract. 9. Describe the basic vascular supply to the various segments of GI tract. 10. Explain the role of physiologic herniation in development of the abdominal organs. 11. Explain the developmental origin of Meckel’s diverticulum and related anomalies 12. Describe how the species listed in the notes differ in the degree to which different segments of the GI tract elaborate into special forms. 13. Explain the basis and describe the clinical presentation of developmental defects mentioned in the notes. 1 2024 C HAPTER 14 I. Introduction and Review A. For quite a while, we’ve been alluding to the endoderm forming the digestive system. It’s finally time to see how that works. First, though, a bit of review wouldn’t hurt. B. Endoderm and Yolk Sac 1. Remember that initially, hypoblast cells formed the primitive endoderm that lined the yolk sac at the onset of gastrulation. Subsequently, definitive endoderm formed from cells that migrated through the primitive streak during gastrulation. These cells displace the hypoblast cells to form the endoderm within the embryo. The endoderm lining the embryo is continuous with the endoderm of the yolk sac. 2. As we have seen during formation of the heart, the originally flat, disc-shaped embryo bends and folds as it grows. Due to the rapid expansion of the central nervous system, the dorsal structures overgrow the ventral ones, causing the head and tail to curve ventrally. This is referred to as craniocaudal folding. In addition, the left and right lateral edges of the embryonic disc also fold ventrally toward each other (lateral folding), eventually fusing along the midline. This whole process is sometimes referred to as ventral folding morphogenesis. 3. The cranial and caudal ends of the endodermal nascent gut tube form deep pockets that extend anteriorally and posteriorally respectively to form the foregut and hindgut elements of the GI tract. 2 2024 Chapter 14 4. At early stages, the embryo appears to be riding atop the yolk sac, with the deepest layer of the embryo (endoderm) also serving as part of the lining of the yolk sac. As craniocaudal and lateral folding proceed, the mid-gut tube is formed by folding of the lateral endoderm ventrally. The newly formed endodermal gut tube retains a connection to the endodermally lined yolk sac in the region of the mid-gut. 5. The remaining connection between the digestive tube and the yolk sac is the vitelline duct. This connection becomes increasingly narrow as time goes on, and as the yolk sac atrophies. Allantois 6. The allantois develops as an out-pouching of the hindgut at its terminus in the region that forms the cloaca. The cloaca will eventually be divided into the rectum and the urogenital sinus (which forms the bladder, urethra and a few other derivatives and is discussed with development of the urogenital tract). B. Mesodermal Layers 1. From medial to lateral, the intraembryonic mesoderm is specialized into the paraxial mesoderm, the intermediate mesoderm, and the lateral plate mesoderm. Just as the extra-embryonic mesoderm split into somatic and splanchnic layers, the intra-embryonic lateral plate also splits into splanchnic (visceral) mesoderm, and somatic (parietal) mesoderm. 2. The somatic mesoderm, fused to the overlying ectoderm (together as somatopleure), grows ventrally during lateral folding, eventually fusing along the ventral midline at the linea alba. The somatopleure thus forms the body wall. 3  2024 C HAPTER 14 3. The splanchnic mesoderm, fused to the underlying endoderm (together as splanchnopleure), will form the wall of the gut tube. The endoderm specifically forms the epithelium of the GI system, while the splanchnic mesoderm forms the connective tissue and muscle of the gut wall. 4. The cavity formed between the two mesodermal layers (intraembryonic coelom) extends at first from thoracic to pelvic regions and is continuous with the pericardial cavity. Later, membranes separate this original continuous coelom into the pleural, pericardial and peritoneal cavities. Somatic and splanchnic mesoderm cells lining the intraembryonic coelom differentiate into the mesothelial lining of each respective cavity. TRANSVERSE SECTIONS FROM THE SAME EMBRYO 5. The entire length of the gut tube is suspended from the dorsal body wall by a dorsal mesentery. Through this route, nerves, blood vessels and lymphatics enter and leave the gut. 6. Lying between the ventral body wall and the area of gut that will become stomach and proximal duodenum is a thick layer of mesoderm, the septum transversum (remember the septum transversum from heart development and look for it in liver development!). This layer partially separates the developing heart and lungs in the thoracic region from the developing abdominal organs. D. The gut is divided into three sections, which are not well defined in the embryo. Some of the boundaries listed here are the adult structures that mark the division between each section. 1. Foregut 4 2024 Chapter 14 a. This region extends from the buccopharyngeal membrane to a point just distal to the liver bud (or duodenal papillae in the adult). This includes most of the proximal (descending) part of the duodenum. b. The intra-abdominal part of the foregut and its derivatives are supplied by branches of the celiac artery. 2. Midgut a. The midgut extends from the duodenum just distal to the liver bud, to the left colic flexure and so is the longest part of the gut in the adult. b. Structures derived from the midgut are supplied by branches of the cranial mesenteric artery. 3. Hindgut a. The hindgut extends from the left colic flexure to the midpoint of the anal canal. b. Hindgut derivatives are supplied by branches of the caudal mesenteric artery. 4. Cranial-caudal patterning of the GI tract a. Patterning of the GI tube along its cranial-caudal axis to establish characteristic regional GI tract anatomy is a complex process In particular, homeobox family genes) are key regulators of GI tract patterning. Several of these genes are expressed in very specific combinatorial patterns in the developing GI and mediate regional specification of the tissue. Remember that Hox genes and other homeobox genes are transcription factors. II. Caudal Foregut A. We will save a discussion of the proximal part of the foregut (pharynx) until we discuss the development of the head. The rest of the foregut will be discussed from proximal (closest to the mouth) to distal. B. Esophagus 1. The esophagus is a narrow tube that lengthens as thoracic contents (such as the heart) descend from cervical to thoracic levels. 2. When the intraembryonic coelom is divided by the developing diaphragm, the diaphragm forms around the esophagus, creating an opening through which the esophagus can gain access to the abdomen from the thorax. 5  2024 C HAPTER 14 C. Simple Stomach (non-ruminant) 1. The stomach first appears as a dilation of the gut tube. The part of the dorsal mesentery of the gut which supports it is the dorsal mesogastrium. This part of the tube is also attached to the ventral body wall by the septum transversum, which at this stage acts as a ventral mesentery (ventral mesogastrium). 2. Parts of the stomach grow faster than other parts (differential growth), creating an asymmetrical dilation. The dorsal surface grows fastest, creating the bulging greater curvature. The ventral surface grows less quickly forming the concave lesser curvature. 3. At the same time that the stomach is developing, other abdominal organs are also growing rapidly, forcing the originally straight, midline gut tube to shift its position within the small abdominal cavity. As a result, the stomach begins to rotate approximately 90 along its longitudinal axis, so that the original dorsal surface (greater curvature) now lies to the left. The stomach then rotates approximately 90 around its dorso-ventral axis. The concavity of the lesser curvature is now facing the right and is angled somewhat cranially. 4. Dorsal mesogastrium (greater omentum) a. As the stomach rotates, its dorsal mesentery grows at a tremendous rate, becoming a large mesenteric sac (greater omentum) that is thrown to the left and caudally by the shift in position of the stomach. In the adult, it will lie ventral to the other contents of the abdominal cavity. The space inside the sac is the omental bursa. 5. We will discuss the ventral mesogastrium, from which the lesser omentum is formed, when we talk about the liver. D. Ruminant Stomach 1. The stomach of ruminants (cows, sheep, goats, deer, etc.) initially begins like that of a simple stomach. It also rotates 90 longitudinally, placing the surface to which the greater omentum attaches on the left side, just like the simple stomach 2. There is only one stomach in a cow, but it has four parts. The non-glandular forestomachs (rumen, reticulum, and omasum) and the glandular portion (abomasum) all develop from the original single stomach dilation. 6  2024 Chapter 14 a. The rumen is the largest part of the stomach in an adult cow, and takes up a huge percentage of the volume of the abdomen. Along with the reticulum and the omasum, these chambers grind and sift the food, mixing it with fluid and with bacteria that break down the hard to digest substances in grass, hay and grain. b. The abomasum contains the glands of the ruminant stomach, and is roughly comparable to the pyloric portion of the simple stomach. 3. Throughout most of prenatal life, the stomach of a fetal calf doesn’t look terribly different from that of a dog. There are bulges that will become the forestomachs, but the most prominent portion is the abomasum. Even after birth, while the calf is suckling, the abomasum is about twice as large as the rumen and reticulum combined. It is only later, as the diet changes, that the forestomachs grow to reach their adult size. 4. The omasum develops as an outpocketing along the lesser curvature, and so will be best seen on the right side. The rumen is an outgrowth of the greater curvature, and so is best seen from the left, and is attached to the greater omentum. F. Liver 1. Endodermal cells from foregut in the region of the future proximal (descending) duodenum will give rise to the liver. Signals from the septum transversum (mesoderm) and from the cardiac mesoderm signal the nearby ventral endoderm to become specified to become liver. The signals from the septum transversum are BMP’s (bone morphogenetic proteins), while the signals from the cardiac mesoderm (developing heart) are FGF’s (fibroblast growth factors). 2. The ventral gut endoderm specified to become liver forms a bud that grows ventrally into the adjoining septum transversum to form the liver and biliary system. This connection with the duodenum will remain in the adult as the bile duct. 3. The endodermal cells grow as branching cords of cells that become the functional cells of the liver (hepatocytes and bile ducts). Note that the hepatocytes and biliary epithelial cells thus share an endodermal precursor. The blood vessels that cross the septum transversum on the way to the heart (umbilical and vitelline veins) are broken up by these invading cords of cells, forming the hepatic sinusoids 7  2024 C HAPTER 14 4. The fetal liver contains hepatic hematopoietic tissue, and the liver is an important hematopoietic organ in the fetus. It is interesting that in adult animals, to varying degrees depending on species, the liver can support hematopoiesis under conditions such as disease with markedly increased demand for hematopoiesis. 5. The liver grows quickly in size, eventually occupying most of the septum transversum between the stomach and the ventral body wall. The peritoneal cavity enlarges around the liver, eliminating most of the septum transversum. Consequently, the septum transversum remains as the visceral peritoneum on the surface of the liver, and as the now thin and membranous falciform ligament and lesser omentum. a. Falciform ligament - mesentery between the ventral abdominal wall and the liver. Atrophies to a great extent in most domestic species. b. Umbilical vein (round ligament of the liver in the adult) - found in the free caudal edge of the falciform ligament, running from the deep surface of the umbilicus to the liver. G. Lesser Omentum - mesentery between the liver and the stomach/duodenum 1. Within its caudal free edge are the bile duct, portal vein and hepatic arteries. a. Main peritoneal cavity vs. omental bursa The only mesentery connecting the gut tube to the ventral body wall is the ventral mesogastrium/duodenum (septum transversum). Caudal to this point, there is no ventral mesentery. Prior to rotation of the stomach, in order to move from the left cranial part of the peritoneal cavity to the right cranial part of the peritoneal cavity, you simply had to first move caudally, under the free edge of the lesser omentum (with its bile duct, portal vein, etc.), then cranially up to the right side. b. After the rotation of the stomach, the part of the peritoneal cavity that was originally on the cranial right is now caught dorsal to the stomach, and extends into the pocket created by the enlarging greater omentum. This space is the omental bursa, and can still be entered by passing “under” the free edge of the lesser omentum, although that opening, the epiploic foramen, is now much smaller. The epiploic foramen is bordered not only by the bile duct and portal vein ventrally in the lesser omentum, but dorsally by the caudal vena cava in the body wall. 8  2024 Chapter 14 G. Other organs 1. Gall bladder: The gall bladder forms from an offshoot of endodermal cells of the hepatic bud, and so in the adult the gall bladder will be connected to the bile duct by the cystic duct. 2. Pancreas: The pancreas develops from two outgrowths of endodermal cells, a ventral bud at the base of the hepatic bud, and a dorsal one a bit more caudally on the duodenum. As the pancreas develops, it grows into the dorsal mesentery of the duodenum and adjacent greater omentum. The functional cells of the pancreas (the exocrine acinar cells, the endocrine islet cells, as well as the duct cells) are all derived from multipotent endoderm. 3. Spleen: The spleen is formed from a condensation of mesodermal cells in the dorsal mesogastrium (greater omentum), between the two layers of mesothelium. Note that while the digestive organs that we have discussed (GI, liver, gall bladder and pancreas) are derived from endoderm, the spleen is formed from a condensation of mesodermal cells in the dorsal mesogastrium (greater omentum), between the two layers of mesothelium. Midgut Development A. Overview of the midgut 1. The gut, liver and mesonephros (precursor of the kidney- forms from intermediate mesoderm) grow so rapidly that the expansion of the abdominal cavity can’t keep up, so the part of the gut tube with the longest mesentery (midgut) herniates into the umbilicus. Eventually, the growth of the abdominal cavity catches up and the gut returns to the coelom. However, during this period of herniation and return, the gut undergoes approximately a 180-270 rotation around the axis of the cranial mesenteric artery. B. Herniation of the midgut 1. The midgut grows quickly, forming a U-shaped loop of gut. Initially, the vitelline duct connects the apex of the loop to the yolk sac. The point where the vitelline duct is attached to the gut will become part of the ileum in the adult. The axis of the loop is the cranial mesenteric artery (derived from the vitelline arteries). 2. As time goes on, the yolk sac atrophies, and so does the vitelline duct connecting it to the midgut. Soon after the midgut loop herniates into the umbilical cord, the vitelline duct detaches from the yolk sac, allowing increased movement of the midgut loop. a. Ileal intestinal diverticulum (Meckel's diverticulum) 9  2024 C HAPTER 14 i. If the vitelline duct does not completely atrophy, there are several variations of defects that can occur. Meckel’s diverticulum is a pouch of the ileum that is the result of the persistence of the proximal part of the vitelline duct. It is usually an “incidental finding at death.” ii. If the vitelline duct remains attached to the deep surface of the umbilicus, by means of either a closed cord or a patent opening, it can inhibit normal movement of the gut in the adult. b. We often speak of the “proximal and distal limbs” of the midgut loop, each to either side of the apex. i. The cecum is a good landmark to watch to keep track of the progress of midgut rotation. The cecum lies in the distal limb. 3. While herniated into the umbilical cord, the midgut loop rotates counterclockwise, with the cecum moving to the left side of the cavity, then cranially. 4. The proximal limb grows much more rapidly than the rest of the loop, forming the coils of jejunum. C. Return of the midgut 1. The proximal limb of the loop, which will become the ascending duodenum and the coils of jejunum, is the first part of the loop to return back into the abdominal cavity. a. Omphalocele - If the midgut does not return from the umbilical cord, the animal may be born with intestinal contents lying externally, covered by the amnion (outer covering of the umbilical cord). This is not the same as an umbilical hernia (see end of chapter). 2. During the return of the loop, the midgut continues to rotate counterclockwise, until the cecum is located on the right side of the abdominal cavity. In total, the gut will 10  2024 Chapter 14 rotate approximately 270 counterclockwise during herniation and return to the abdominal cavity. 3. The twisted mesentery that attaches the jejuno-ileum to the dorsal body wall and contains the cranial mesenteric artery is such a major landmark that it is often called "The Mesentery." Its line of attachment to the dorsal wall is the root of the mesentery. 4. As a result of rotation of the umbilical gut loop, the transverse colon comes to lie cranial, and the caudal duodenal flexure lies caudal, to the root of the mesentery (and therefore to the proximal part of the cranial mesenteric artery). D. The midgut begins distal to the duodenal papillae and ends near the left colic flexure. Among domestic species there is particular variation in the development of the ascending colon and cecum. Refer to the drawings on the next page. II. Hindgut Development A. The hindgut begins at the left colic flexure and ends at the anal canal, so it primarily includes the descending colon and rectum. B. Rectum and anal canal 1. The cloaca is the original terminal end of the gut. It is a common space continuous with the hindgut, and with the distal ends of the urogenital tracts. We will talk more about it with the urogenital system. 2. The opening from the cloaca to the world outside the embryo (at this point, the amniotic cavity) is initially closed by the cloacal membrane, a site of fusion of endoderm and ectoderm. 11  2024 C HAPTER 14 3. The cloaca is later divided by the urorectal septum into the rectum dorsally and the urogenital sinus ventrally. This septum grows caudally to meet the cloacal membrane, dividing the membrane into two parts also. The anal membrane is the caudal of these two parts and normally degenerates. III. Malformations of the Digestive System A. Atresia and/or Stenosis - missing, blocked or narrowed segments of the gut anywhere along the tube. B. Aganglionosis - What would you expect to see if the autonomic nerve fibers were absent from the gut? How might this happen? 1. Congenital megacolon C. Rotation defects - surprisingly rare 1. Situs inversus -abdominal and/or thoracic organs (usually both) develop in a “mirror image” of their normal arrangement D. Omphalocele - If the midgut does not return from the umbilical cord, the animal may be born with intestinal contents lying externally, covered by the amnion. This is not the same as an umbilical hernia. E. Umbilical Hernia - a congenital or acquired defect in the abdominal wall around the umbilicus, allowing abdominal organs to herniate under the skin. What characteristic(s) would distinguish between physiologic (normal) hernia versus an abnormal umbilical hernia? F. Imperforate Anus (Atresia Ani, Persistent Anal Membrane) a. Incomplete development of the anus and/or persistence of the cloacal membrane, which can lead to megacolon. G. Vascular ring anomalies – vascular ring anomalies (e.g. persistent right aortic arch and double aortic arch) can cause constriction of the esophagus leading to megaesophagus and regurgitation following feeding 12