Organogenesis 1 - The Digestive System PDF

Overview of the digestive system The food is ingested in the mouth, where the first digestion takes place (mechanical: chewing, chemical: enzymes released by the sal...

Overview of the digestive system The food is ingested in the mouth, where the first digestion takes place (mechanical: chewing, chemical: enzymes released by the salivary glands), then it passes through the pharynx (a muscular tube divided into rhinopharynx, oropharynx and laryngopharynx) and then into the oesophagus. There is no reinopenarinx absorption/digestion in the pharynx and in the oesophagus. earingopenerinx The oesophagus crosses the diaphragm and gets into the onopaarinx abdominal cavity (only 2-3cm of it), where it connects to the stomach (located on the left). Food rests in the stomach for a few hours (mechanical digestion thanks to the thick muscle layer, chemical digestion and biochemical digestion thanks to hydrochloridic acid and proteolytic enzymes). Not much absorption. The stomach then continues into the duodenum, bein which is the first tract of the small intestine. The duodenum is bait's enaea mostly to the right and here a lot of digestion takes place (it is connected to the liver and to the pancreas, endocrine glands). The duodenum continues with the rest of the small intestine (or mesenteric intestine, it is suspended in the abdominal cavity by a mesentery that attaches it to the posterior abdominal wall). The small intestine communicates with the initial part of the large intestine (on the right) through the ileocecal valve. The small intestine is made of the duodenum, the jejunum and the ileum. The large intestine is made of the appendix, the cecum, the ascending colon, the transverse colon, the descending colon the sigmoid colon, the rectum and the anal canal. Some organs of the digestive tract lose their peritoneum envelopment (thin serous membrane made of one layer of squamous epithelia called mesothelium) totally or partially during development, thus becoming less mobile. Yellow = more mobile = enveloped anteriorly and posteriorly by peritoneum Orange = less mobile = initially intraperitoneal but then during development their mesentery adhered to the body wall and fused with it. Only their anterior surface is covered by peritoneum Red = immobile = they never had a mesentery and they developed outside the peritoneal cavity Peritoneum —> it originates from the intraembryonic coelom. It lines the wall of the peritoneal cavity (parietal peritoneum) and covers/envelops abdominal organs and some pelvic organs (visceral peritoneum). In between the two layers there is the peritoneal cavity, a very thin space filled with peritoneal fluid. Some organs are intraperitoneal, some are secondarily retroperitoneal, some are retroperitoneal. The ACTUAL peritoneal cavity is the space between then visceral and the parietal peritoneum.  The peritoneal cavity is the green space, so organs are not INSIDE the peritoneal cavity, they’re just covered by the visceral peritoneum Folding of the embryo leads to the incorporation of part of the vitelline sac in the body of the embryo and to the formation of an endoderm tube surrounded by the splanchnic mesoderm (primitive gut). The endoderm derives from the endodermal layer of the embryo and from the endoderm lining the vitelline sac. The intestinal tube is suspended inside the intraembryonic coelom by a dorsal mesentery and attached to the posterior abdominal wall by a ventral mesentery. Embryonal origin of the components of the gut wall Endoderm —> it’s going to form the mucosa of the intestinal tube (epithelium and glands) Splanchnic mesoderm —> it’s going to form the smooth muscle, the connective tissue, the blood vessels, the visceral peritoneum and the mesenteries Neural crest —> it’s going to form the enteric nervous system (ENS, a network of nerves in the digestive tract independent of the CNS) The primitive intestine is divide in three compartments Midgut —> communicates with the vitelline sac via the vitelline duct (or omphaloenteric duct) for a while Hindgut —> it dilates to form the cloaca (part of it will be the intestinal tube while another part will be part of the urinary tract). It’s divided from the proctodeum (primordial anus) by the cloacal membrane. The cloaca is in continuity with the allantois Foregut —> separated from the stomodeum (primordial mouth) by the oropharyngeal membrane The oropharingeal membrane breaks by the 4th week of development (this way the embryo will be able to swallow amniotic fluid when needed) The cloacal membrane will be divided into two portions (anal and urogenital membrane) and then it will break at the end of the 2nd month The repositioning of the septum transversum and the subsequent formation of the diaphragm leads to the division of the primitive intestine into a thoracic portion and an abdominal portion. forecic There are no mesenteries in the thoracic compartment because the serosa is reabsorbed The dorsal mesentery will be present in the adult body Lynne The ventral mesentery is only present in the upper part of the abdominal portion (will give rise to duodenum, stomach, liver, gallbladder, pancreas) and it will disappear in the adult body (except from where the liver will develop) In the thoracic cavity both mesenteries are reabsorbed —> the organs of the intestinal tube that will develop there will be surrounded by an adventitia (connective tissue) and NOT by a serosa. The serosal cavity in the abdominal region is called peritoneal cavity. The serosa is called peritoneum and it is divided into a parietal peritoneum and a visceral peritoneum Classification of organs in respect to the peritoneum: Intraperitoneal organs —> they’re covered by the peritoneum (not physically in the peritoneal cavity, just surrounded by it). Es: stomach, ileum, jejunum Secondarily retroperitoneal —> originally intraperitoneal but then some peritoneum gets reabsorbed. They’re less mobile and are Conley partly covered by the peritoneum Retroperitoneal organs —> they don’t belong to the gut tube and don’t develop in the peritoneal cavity (like kidneys). They were NEVER covered by a serosa never summoned perigee  While the intestinal tube is developing there is a concomitant development of the lower respiratory system as an out-pocketing from the foregut (respiratory diverticulum). Initially, the respiratory diverticulum and the intestinal tube are in the same compartment but then separate cavities are formed. The separation of the respiratory diverticulum from the intestinal tube may go badly and a tracheoesophageal fistula may develop (connection that shouldn’t be there) By the end of the first month the primordia of the major digestive glands is formed (liver and pancreas). The pancreas will produce hormones, insulin and glucagons important for the development of the fetus. The liver won’t have the same function as the one it has in adults (it is a site for hematopoiesis instead) Regional specification —> each portion of the swim primordial gut tube has to take a different path. This is achieved thanks to an intrinsic molecular swim pattern through the tube and the interactions between germ layers. It’s important to determine the rostro-to-caudal patterning —> it is established by factors like retinoic acid (more caudally than rostrally) and FGFs that trigger the expression of Hox genes with a very specific pattern Main developmental events of during the formation of the intestinal tract Elongation —> initially the gut tube is not long enough. For example the midgut elongates to form the ileum and the jejunum Herniation past the body wall —> some parts of the gut have to go outside of the body to be herniated Rotation and folding —> for efficient packing into the body cavity Histogenesis —> formation and maturation of cells and of tissues. It is a morphological maturation Later functional maturation —> it goes along with the morphological maturation but starts after (before the organ still doesn’t have to perform its function) Eisemann ii iigEEÉseen y Enmeshment  The vascularisation pattern in the adult is related to the embryological development —> in the abdomen, the derivatives of foregut, midgut and hindgut are vascularised by distinct branches of the aorta Celiac artery or trunk —> supplies organs originating from the foregut (stomach, superior part of the duodenum and oesophagus) Superior mesenteric artery —> supplies organs originating from the midgut (jejunum, ileum, inferior part of the duodenum and initial part of the large intestine) Inferior mesenteric artery —> supplies organs originating from the hindgut (descending colon, sigmoid colon and rectum) Innervation of the intestinal tube —> while the organs develop they receive innervation. Efferent or motor innervation —> The viscera of our as derivatives area by body are innervate by the parasympathetic or sympathetic thEmen component of the autonomic nervous system, which are usually working in antagonistic way but sometimes in derivatives a egtqymner.amby synergical ways. Abdominal foregut (esophagus, proximal duodenum, a aeriverivesgtqymner.am by liver, pancreas, gallbladder) —> supplied by the celiac artery and innervated by the greater splanchnic nerves (viscerosensory fibers reachT5-9 spinal segments). Midgut (distal duodenum to transverse colon superior) —> supplied by the mesenteric artery and innervated by the lesser and least splanchnic nerves (sensory fibers reach T10-12 spinal segments). Hindgut (descending colon to anus) —> supplied by the inferior mesenteric artery and innervated by the lumbar splanchnic nerves (sensory fibers reaches T12-L3 spinal segments). The reason why the pain from a viscera is referred to a certain region of the body depends on the fact that the information that are collected from that viscera are brought to the correspondent segment of the spinal cord, which then innervates a certain dermatomeric territory and our central nervous system makes some confusion. The digestive system until the transverse colon is innervated by the vagus nerve (long nerve running in the head, neck, pharynx and abdomen) while the rest is innervated by the splanchnic nerves THE OESOPHAGUS The oesophagus is a muscolo-membranous tube (around 25cm in adults) that connects the pharynx with the stomach and runs in the mediastinum (connective space at the centre of our thoracic cavity). The oesophagus forms from the foregut caudal to the last part of the primordial pharynx (last pharyngeal pouch) By observing in details what happens during the development of the oesophagus we can describe the major events that characterise the histogenesis of the whole length of the digestive tube —> the lumen inside of the tube is initially occluded due to the proliferation of the cells of the wall, but very soon within the lumen some vacuoles form (process of vacuolisation). So, all throughout the length of the tube there is a process of occlusion and recanalisation. During the 7th week, if we look at the wall of the oesophagus, there is a lumen and the epithelium is stratified columnar. Then, it happens that the stratified columnar epithelium proliferates as to occlude the lumen of the oesophagus and then there is a process of vacuolisation (8th week) at the core of the tube with a consequent recanalisation (guided by molecular pattern). The new epithelium will be stratified cuboidal and ciliated. At this point we start to see the arrangement of a lamina propria, which with the epithelium will form the mucosa. Then, there is the formation of the submucosa (12th week), depending on the region there might be some glands (es: distal portion of the oesophagus). The outer most layer of the oesophagus starts to be organised into a muscle layer (34th week), with the formation of the muscularis propria, divided into circular and longitudinal muscle layers. At this point of the development, also the mucosa is much more organised, the epithelium has became a squamous stratified epithelium (with no cilia); we can also notice that within the mucosa of the oesophagus we have the formation of bands of smooth muscle tissue which are called muscularis mucosae (this is a peculiarity of the digestive system). In the oesophagus there is not a serosa, which degenerates to form an adventitia. Because we are in the oesophagus the initial part also contain skeletal muscle tissue because it is in continuity with the pharynx, which is made of skeletal muscle. When things go wrong during occlusion or recanalisation —> OESOPHAGEAL ATRESIA and STENOSIS Stenosis —> the recanalisation doesn’t take place completely so the oesophagus has a narrow passage Atresia —> recanalisation doesn’t take place at all so there is a blockage in the oesophagus Duplication —> during the process of recanalisation a septum is left in the oesophagus During fetal life this leads to an impossibility of swallowing the amniotic fluid and thus to polyhydramnions. In newborns there might be difficulties in swallowing milk and this could lead to immediate regurgitation and choking artichokes In more than 90% of cases of oesophageal atresia or stenosis there in an association with tracheo-oesophageal fistula fifffideration STOMACH The stomach is located in the abdominal cavity and it is around 29-30cm long with 10-5cm of transverse diameter. The average capacity is of 1200ml The stomach is a large sac located in the supramesocolic compartment and it originates from the last portion of the foregut along with the duodenum The stomach has 2 curvatures —> 1. Lesser curvature, concave, on the right side 2. Greater curvature, convex, on the left side Formation of the stomach Initially the region from which the stomach will originate is on the same axis as the rest of the gut tube but then a part starts to swell. The dorsal part of the sac becomes convex while the ventral part becomes concave (both still on the midline). In the dorsal mesentery (or dorsal mesogastrium) there will be the formation of the spleen and of the pancreas while in the ventral one the liver will form Rotation of the stomach There are two concomitant positional shifts —> a 90° rotation along the longitudinal axis that brings the convex it’s on the left and the concavity on the right, and then a slight tipping of the caudal end (pyloric) in the cranial direction. Now the stomach is positioned diagonally 888 Shehane Estrin leadstothetiering What happens to the dorsal and ventral mesogastrium? Dorsal mesogastrium—> it elongates and forms the omental bursa (or lesser sac, which will be behind the stomach) and the greater omentum (it is a sort of apron that covers viscera below the stomach and it originates from the lesser sac that grows below the stomach) Ventral mesogastrium —> it becomes the lesser omentum (it will form a ligamental device that connects the stomach and the duodenum with the liver) Lesser sac —> space dorsal to the stomach that derives from the elongation of the dorsal mesogastrium due to the rotation of the stomach Greater omentum —> derives from the elongation of the lesser sac downwards as to cover the other organs Lesser omentum —> derives from the ventral mesogastirum Greater sac —> remaining peritoneal cavity anterior and inferior to the stomach The greater omentum It continues its development downward after the rotation. It forms a pouch below the stomach, which grows to cover the intestinal loop. Part of the 2 layers then fuse with the mesocolon while the rest fuse together to form the actual greater omentum Foramen of Winslow (or epiploic foramen)—> foremen through which the lesser sac and the greater sac communicate. It is located below the lesser omentum and near the hilum of the liver. Structure of the stomach Glands of the mucosa —> gradual functional differentiation of cell types in the late fetal period —> mucus, HCL, pepsinogen and gastrin Only in the late fetal period the functional cells of the stomach will be fully mature HETEROTOPIC GASTRIC MUCOSA —> mature gastric tissue in locations where it is not normally found (es: small bowel). The gastric tissue is active and it releases chloridric acid and proteolytic enzymes so it can damage other tissues. It can occur in duplications or diverticula. It can be organised in nodules or sessile polyps. It can cause obstruction, diarrhoea (irritation of the intestinal area, the intestine contracts to release the content of the lumen as fast as possible), ulceration, bleeding (damage of the mucosa due to acidic agents), perforation (the wall of the intestinal tube can be perforated), intussusception (a part of the intestinal tube protrudes into another part of the intestinal tube due to its weakening) or abdominal pain Pyloric sphincter —> controls the communication between the stomach and the duodenum and prevents food from going into the intestine before being partially digested. The circular muscle layer of the sphincter is very thick and it allows the valve to open and close as a response to some localised endocrine factors. When activated, sphincters open so that chymus can go into the duodenum. Pyloric sphincters are controlled by the autonomic nervous system PYLORIC STENOSIS (restriction) —> caused by a thickening of the circular muscle layer (pyloric sphincter). Here the stomach is markedly distended as its trying to send food in the duodenum without being able to do it. In newborns this leads to projectile vomiting a few hours after a meal (non bilious vomit, it doesn’t contain bile so it has a color similar to that of the milk ingested). It is the most common defect of the foregut development The liver will develop in the ventral mesogastrium while the spleen and the pancreas will develop in the dorsal mesogastrium The ventral mesogastrium will partly form the liver and partly form the lesser omentum THE DUODENUM It is the first portion of the small intestine and its shortest part (20-25cm). It is the less mobile portion of the small intestine (secondarily retroperitoneal). It has a C shape and it is mostly to the right. Its upper portion develops from the foregut while its lower part develops from the midgut. In the adult the duodenum is the part of intestinal tube that receives the secretion from the extramural glands (liver and pancreas). This is because the liver and the pancreas originate from buddings of the foregut portion of the duodenum, and thus this communication is maintained in the adult. Because the duodenum becomes secondarily retroperitoneal to see it we have to remove many intraperitoneal organs From the foregut half of the duodenum two buddings originate: Liver bud (or hepatic diverticulum) —> it will develop into hepatic cords, bud of the gallbladder, biliary duct and ventral pancreatic bud Dorsal pancreatic bud While the stomach moves to the left the duodenum is pushed to the right and against the posterior abdominal wall thus leading to the re absorption of the dorsal mesogastrium. For this reason the duodenum and the pancreas (developing from it) become secondarily retroperitoneal organs The initial part of the duodenum is intraperitoneal because it is a bit more anterior as it connects with the stomach (intraperitoneal) while the distal part is secondarily retroperitoneal because it is pushed dorsally. 4 parts of the duodenum —> superior (1st) + descending (2nd) + horizontal (3rd) + ascending (4th) DUODENAL STENOSIS OR ATRESIA Also in the duodenum the process of recanalisation can take place incorrectly (same concept of the oesophagus). Stenosis —> only partial recanalisation. Atresia —> no recanalisation. Duodenal atresia is the 3rd most common atresia of the GI tract (1st: oesophageal 2nd: ileum or jejunum). In most cases this takes part in the 3rd part (horizontal) or 4th part (ascending) of the duodenum. Prenatal complications —> polyhydramnions, dilated bowels (proximal to the stenosis there is a dilation), ascites (accumulation of fluids in the tissues of the fetus). Postnatal complications —> vomit, usually bilious ( because the stenosis is after the communication of the biliary tract, so the bile from the liver is secreted and it mixes with the ingested milk). Double-bubble effect —> radiological sign of duodenal stenosis. The stomach and the duodenum can be seen under x-ray as dark bubbles. Between the two bubbles (stomach and duodenum) there is the pyloric sphincter so there is no dark spot. The duodenum and the stomach however are abnormal because they Two are dilated (because of a duodenal stenosis that doesn’t allow bubbles food to pass through). Duodenal atresia is usually associated with other congenital problems (like Down syndrome, in 25-40% of cases). Other associated anomalies include VACTERL (vertebral anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula, oesophageal atresia, renal anomalies and radial aplasia, and limb anomalies), malrotation, annular pancreas, biliary tract abnormalities, and mandibulofacial anomalies. THE PANCREAS The pancreas is both an endocrine and exocrine gland. It originates from the foregut portion of the duodenum and for this reason it secretes its exocrine products (pancreatic enzymes) in the duodenum even in the adult. The pancreas develops in the two layers of the dorsal mesogastrium. In particular, the pancreas originates form the fusion of the dorsal pancreatic bud and the ventral pancreatic bud during the repositioning of the duodenum The bile duct (where the ventral pancreatic bud is located) rotates over development and is relocated dorsal to the duodenum. This way the ventral and dorsal pancreatic bud can fuse together. Most of the pancreas originates from the dorsal pancreatic bud (including the main pancreatic duct, which will connect to the bile duct) while from the ventral pancreatic duct the uncinate process and part of the head of the pancreas originate. ANNULAR PANCREAS Sometimes the rotation doesn’t take place correctly and the ventral pancreatic bud rotates in front of the duodenum rather than behind. Now the duodenal tube is squeezed between the ventral and dorsal pancreatic bud that are fusing together (and is therefore constricted). This condition may be detected only in the adult or not at all (the constriction might not be too tight). Approximately 50% of patients may be asymptomatic for life and discover the abnormality incidentally. In adults annular pancreas can lead to peptic ulcers (the pancreas sends enzymes to the duodenum but the duodenum isn’t able to move them forward as it should so the enzymes accumulate in the wall of the duodenum + the acidic content of the stomach remains too much time in the duodenum and it can damage its mucosa), duodenal obstruction or pancreatitis. In newborns/fetus it can lead to polyhydramnions, feeding intolerance, non-biliary vomiting (bile can proceed because the duodenum is not completely shut + the obstruction is above the papilla of Vater, namely the region where the pancreas communicates with the biliary duct) Double bubble sign According to some intrinsic factors some parts of the pancreas will become exocrine (Notch is active) while others will become endocrine (Notch is inactive). Insulin and glucagon controlling sugar metabolism are present in the fetal circulation during the third month or earlier because the fetus is metabolically active so the metabolism of glucose is very important. For this reason the endocrine pancreas needs to be very active. The number and functioning of endocrine pancreatic islets is regulated by glucose level during embryonic and fetal life. The number of pancreatic islets and their function may be affected by: Intrauterine growth restriction (IUGR) usually due to placental insufficiency Maternal diabetes (babies with hyperinsulinism) Fetal malnutrition (might also be related to placental malfunctioning due to IUGR) For this reason the endocrine pancreas needs to be active VERY EARLY!!! Many intestinal problems in development are caused by a bad communication between the splanchnic mesoderm and the endoderm. Remember that during development the budding takes place in the endoderm but the whole GÌ tract is still covered by mesoderm. During rotation the pancreas becomes mostly secondary retroperitoneal ECTOPIC PANCREAS abnormal pancreatic tissue in places where it shouldn’t be (mostly in the stomach, in the duodenum, in the jejunum or in the ileal diverticulum of Meckel). This is also a phylogenetic remnant (in some animals the pancreas develops in the duodenum). It is usually asymptomatic but it may lead to gastrointestinal symptoms like gastrointestinal bleeding (to determine where it comes from we have to look at its color and at its digestion state), obstruction or cancer (the ectopic tissue may transform into cancer tissue). LIVER, BILIARY TREE and GALLBLADDER Gallbladder (or cholecyst) —> sac in which bile is stored Biliary tree —> communication ducts Liver —> organ Hepatic diverticulum —> hepatic cords —> bile duct, gallbladder duct (gallbladder and cystic duct + ventral pancreatic bud) The bile duct is in connection with the duodenum. Often time a sing of tumour of the head of the pancreas is Jaundice. This is because the bile duct is carried behind the first portion of the duodenum and head of the pancreas. For this reason the bile duct can be occluded by cancer cells and so the bile starts to settle in the biliary tree and in the tissues. BILIARY ATRESIA Atresia of the biliary tree It can lead to: Progressive neonatal jaundice, onset soon after birth White clay-coloured stools (feces, they’re white because there’s not enough bilirubin) Dark-coloured urine (there’s more bilirubin in the blood than it should be, so when blood passes through the kidney they have to filter more) Average survival 12-19 months, 100% mortality without surgery Leading indication for paediatric liver transplantation At least 70% of children with biliary atresia will undergo liver transplantation, 50% of them by 2 years of age. The liver is mostly intraperitoneal because it develops in the ventral mesogastrium. The liver occupies almost all the ventral mesogastrium as it grows a lot and it eventually comes into contact with the septum transversum (future diaphragm). Where this contact happens the serosa is reabsorbed so the area remains bare. That area is going to be called the bare area of the liver This growing leads to the disappearance of the ventral mesogastrium (mostly occupied by the liver) what remains of the ventral mesogastrium gives rise to ligaments. The lesser omentum is what remains of the ventral mesogastrium between the lesser curvature of the stomach, the initial part of the duodenum and the liver. The lesser omentum will give rise to the hepatogastric ligament (from liver to stomach) and hepatoduodenal ligament (from liver to duodenum). The portion of ventral mesogastrium that remains anterior to the liver will form the falciform ligament (between the liver and the anterior abdominal wall). The coronary ligament will surrounds the bare area of the liver  THE SPLEEN The spleen develops in the mesenchyme of the dorsal mesogastrium (it DOES NOT develop from the intestinal tube but from the mesenchyme between the two layers of the dorsal mesogastrium). From the 4th to the 5th month the spleen will be a site for haematopoiesis. From the 14th to the 18th week it will develop its lobular shape and T-cells precursors will start entering. Starting from week 23rd some B-cells precursors will start entering the spleen as well During its development the liver envelops vessels that enter the inflow portion of the heart. At this point the heart is located rostrally to the diaphragm and to the liver. Some vessels become the sinusoids of the liver. During this process the right umbilical vein degenerates and only the left umbilical vein remains. The left vitelline vein degenerates while the right vitelline vein becomes the portal vein. The liver causes a massive rearrangement of the blood system over development Portal vein —> brings blood from spleen, gallbladder, stomach and intestinal tube to the liver Derivatives of the foregut are supplied by the celiac trunk artery (except from the duodenum which is both supplied by the celiac trunk and from the superior mesenteric artery) Midgut derivatives: Lower portion of the duodenum jejunum ileum coecum physiological Appendix herniation ascending colon 2/3 of the transverse colon Hindgut derivatives: Last third of transverse colon Descending colon Sigmoid colon Rectum Jardinehits  Upper portion of the anal canal Urinary bladder and primitive urethra DEVELOPMENT OF THE MIDGUT The intestinal tube needs to be elongated, especially in the region where there is more absorption. There are 2 problems: 1. The abdominal cavity is not big enough yet 2. The kidneys are developing thus taking away space In the region of embryo where the future umbilicus will form the intraembryonic coelom is still in communication with the extraembryonic coelom and the midgut is still in communication with the vitelline sac through the vitelline duct. For this reason the midgut develops OUTSIDE of the abdominal cavity and renters and is rearranged so that everything is in the right place The midgut portion of the duodenum forms a loop that herniates outside of the abdominal cavity (in the umbilical cord) From the 6th to the 10th week the physiological herniation is present, after the 10th week everything has to go back in the abdominal cavity. In the midgut loop we can see a rostral limb and a caudal limb, which will then rotate on the axis of the superior mesenteric artery first of 90° and then of 180° counterclockwise. The vitelline duct will be present only up until the herniation is present, when the herniation goes back into the abdominal cavity and the abdominal cavity closes the vitelline duct degenerates. Position of the midgut derivatives in respect to the peritoneum Some of them are reabsorbed and therefore some organs become secondarily retroperitoneal: Ascending colon (same will be for the descending) Some remain intraperitoneal: Jejunum and Ileum (Mesentery, mesenterial intestine), Coecum, (mesocecum), Transverse colon (mesocolon or transverse mesocolon) resin The more ventral an organ is the more intraperitoneal it is The mesocolon is a horizontal mesentery that allows us to divide the abdominal cavity into a supramesocolic compartment and a inframesocolic compartment. Some intraperitoneal organs are above the mesocolon (supramesocolic organs) while others are below (inframesocolic organs). Part of the duodenum is in the supramesocolic compartment while the rest is in the inframesocolic compartment While the greater omentum is forming the mesocolon adheres to part of it. As derivatives of the midgut loop there are the caecum and the appendix, which are completely intraperitoneal. During development the appendix positions in different places in different individuals. Usually the appendix is retrocaecal ABNORMAL ROTATION AND FIXATION OF THE MIDGUT LOOP: Malrotation is the most common congenital problem of the small intestine. It can manifest both during infancy and adulthood through acute abdominal pain usually alongside bilious vomit, volvuli, chronic abdominal pain or gastroesophageal reflux (fluids going in the opposite direction) Bilious vomiting in a newborn is a medical emergency as it can be caused by a malrotation or by a volvulus of the small intestine. If untreated, these can cause intestinal ischemia/stroke and necrosis of a long intestinal segment Volvolus —> when an intestinal loop rotates on itself. It has to be treated very quickly otherwise the circulation of that segment might be damaged and the piece might undergo necrosis (and thus it would have to be removed). Malrotation —> spectrum of anatomic abnormalities resulting from incomplete or abnormal rotation and fixation of the intestine during early fetal development. Variants of malrotation might include incomplete rotation, non rotation or reversed rotation Malrotation is usually asymptomatic unless it leads to a volvulus or if it causes other complications (like duodenal cecum intheoneappendix compartment subeepatic compression) VOLVULUS A loop of intestine that twists around itself and the mesentery that supports it, resulting in a bowel obstruction. Symptoms may include abdominal pain, abdominal bloating (the content of the intestine isn’t able to pass through), vomiting, constipation and bloody stool (blood in the feces due to gastrointestinal bleeding). The onset of symptoms may be rapid or gradual. The mesentery may become so tightly twisted that blood flow in that portion is cut off resulting in ischemic bowel. In this situation there may be abdominal pain when touched and fever Internal hernias —> a loop of intestine herniates in the supramesocolic compartment instead of the inframesocolic one. As a result of malrotation anomalous bands of peritoneum may form. The most common type of bands are the bands of Ladd, which extend from an abnormally positioned caecum to the right abdominal wall causing obstruction of the duodenum. Clinical signs may include poor feeding and bilious vomiting in neonates. The most severe complication is volvulus. 3 feelIm MECKEL’S DIVERTICULUM It is the most common congenital anomaly of the GI tract (2% of individuals). It is caused by an incomplete obliteration of the vitelline duct that causes a congenital sacculation of the wall of the ileum at the antimesenteric side. It is usually localised within the final 100cm before the ileocecal valve Basically a little sac of intestinal tissue originates from the ileum because the vitelline duct doesn’t degenerate completely. This can cause volvuli or problems in the passage of food through the ileum. There might either be a fistula or a fibrous cord which could contain blood vessels or could develop a vitelline cyst. The diverticulum might present with an heterotopic mucosa, like fibrouscord gastric, pancreatic or even endometrium. This could lead to an ulceration, bleeding or the perforation of the diverticulum (due to the chloridric acid secreted by the gastric tissue or by the replacement of endometrium). Heterotopic mucosa is clinically associated to symptoms resembling cyst appendicitis (for its location) and bright red or dark red stools. It can cause volvuli and strangulation The color of blood coming out of the intestinal tract has to be taken into account as it can tell us where the problem is. If it is darker it usually comes from the lower tract of the intestinal tube as it has been exposed to digestive enzymes and other factors while if it bright red it probably comes from the upper portion of the intestinal tube. PATHOLOGICAL HERNIATION of MIDGUT DERIVATIVES through the ANTERIOR ABDOMINAL WALL Omphalocele —> failure of the midgut loop to re enter the abdominal cavity during the 10th week. It is caused by a problem in the formation of the body wall (impaired growth of mesoderm and ectoderm). Typically there is an herniation of intestine and liver into the umbilical cord. These herniations are covered by the peritoneum and by the amniotic membrane. Omphalocele is usually associated to other congenital anomalies and to some cardiovascular and urogenital system defects. Omphalocele can be detected thanks to high concentration of alpha- fetoprotein (AFP) Umbilical hernia —> it is more common in premature infants. The intestine returns normally into the body cavity but then part of the musculature of the abdominal wall (rectus muscles) fails to close around the umbilical ring. Variable amounts of peritoneum and bowel can protrude and in this instance they are covered by skin rather than by the amniotic membrane. It can happen if the baby cries or stretches too much because more pressure is applied on the abdominal cavity. It may develop later in life. Most of the times (95%) the hole closes completely by the 5th year. Gastroschisis —> defect of the formation of the abdominal wall on the side. This causes a massive evisceration of intestinal loops and possibly other organs. It happens mostly to the right and the viscera protrude in the amniotic cavity and are not covered by peritoneum (more severe, the peritoneum doesn’t develop correctly and the viscera are more damaged). Organs are exposed to the amniotic fluid and so they thickens and get covered with adhesions. The cause is unclear DEVELOPMENT OF THE HINDGUT The hindgut derivatives don’t herniate (they remain the abdominal wall) and they’re supplied by the inferior mesenteric artery. The cloaca (terminal part of the hindgut after dilating, in continuity with the allantois) is associated to the cloacal membrane and the proctodeum. The cloaca will be divided into an anterior portion (urogenital sinus) and a posterior portion (anorectal canal) The urorectal septum is a mesodermal septum that extends towards the cloacal membrane and the proctodeum. Once the urorectal septum reaches the cloacal membrane the urogenital sinus and anorectal canal are formed. The urinary bladder and urethra are ventral to the anorectal canal. In females and in males the urethra is different (uterovaginal canal). In females between the urinary bladder and the urethra there will be the uterus and the vagina. The cloacal membrane gets divided into an urogenital membrane (ventral) and an anal membrane (dorsal) which will eventually break. ANAL CANAL The upper portion of the anal canal originates from the upper part of the cloaca (hindgut) while the lower portion originates from the proctodeum. In the upper part the epithelium is simple columnar while in the lower part the epithelium is squamous stratified (because the ectoderm gives rise to the epidermis, which is squamous stratified). The white line is where the squamous epithelium becomes very close to that of the skin Because of the different types of innervation (the skin is highly innervated and so has many pain receptors, in contrary to viscera), if a patient develops a carcinoma in the upper part of the anal canal it is usually painless while if it is in the lower portion it is very painful (because of the size of the cancer which grows to obstruct the anal canal). IMPERFORATE ANUS and ANORECTAL ANOMALIES They’re usually caused by abnormalities in the formation of the urorectal septum Anal stenosis —> restriction of the anal canal Persistent anal membrane —> closed anal membrane Anoperineal fistula —> the opening is too anterior in respect to the anal pit Rectocovaginal fistula —> connection between the rectum and the uterovaginal canal, feces come out of the vagina Rectourethral fistula —> connection between rectum and urethra Rectal atresia —> closure of the rectum Meconium —> water, amniotic fluid, maybe bile and whatever floats in the amniotic fluid (like lanugo, tiny hair a baby has when he’s born). Earliest stool of mammalian infants. It is viscous and sticky like tar, it is very dark olive green and it is almost odourless. It should be completely passed by the end of the first few days afterbirth, with the stools progressing towards a yellowish color (digested milk). In case of imperforate anus or other anorectal anomalies there might be a defective or absent passage of meconium DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM In the intestinal tube there is a net of neurons called enteric nervous system (basically the brain of the gut). The enteric nervous system originates from the neural crest of the vagal region and sacral region. The cells undergo a ETM transition and reach the tissue where they should be and where they start to differentiate forming the submucosa plexus and myenteric plexus. Most of the hindgut derivatives originate from the cells of the sacral neural crest. If the process of migration doesn’t take place correctly then problems arise HIRSCHPRUNG’S DISEASE or AGANGLIONIC MEGACOLON (or congenital megacolon) Caused by a defect in the migration of neural crest cells in the distal portion of the large intestine. There is a dilation of the intestine proximal to the defect because the ganglions aren’t present and so whatever is in the intestine isn’t moved around. Peristalsis doesn’t take place as it should and so feces stagnate in the proximal regions. This can lead to a delay in the passage of meconium, constipation, vomit or abdominal pain. It is usually detected during the first year of life. O