Development of the GI Tract PDF

Gastrointestinal System Development of the GI Tract Welcome to the lecture on the development of the gastrointestinal tract.  Learning Outcomes After this lecture you should be able to: ▪ Describe the formation of the primitive gut tube ▪ Know the locat...

Gastrointestinal System Development of the GI Tract Welcome to the lecture on the development of the gastrointestinal tract.  Learning Outcomes After this lecture you should be able to: ▪ Describe the formation of the primitive gut tube ▪ Know the locations of the vitelline duct and allantois, and know the blood vessels associated with them ▪ List the structures derived from the fore-, mid- and hind-gut and know their blood supply ▪ Describe the development of the glands of the gastrointestinal tract ▪ Describe umbilical herniation and subsequent mid-gut rotation ▪ List the common congenital abnormalities of mid-gut and hind-gut ▪ Describe the formation of the urorectal septum and destiny of the cloacal membrane The learning outcomes for the entire lecture are shown.  Gastrointestinal System Development of the GI Tract 1. The Primitive Gut and Foregut 2. The Midgut 3. The Hindgut and Cloaca There are 3 parts to this lecture.  Gastrointestinal System Development of the GI Tract Part 1: The Primitive Gut and Foregut In this section we will discuss the origins of the primitive gut and then go on to look at the foregut. In subsequent parts we will consider the midgut and hindgut.  Learning Outcomes After this lecture you should be able to: ▪ Describe the formation of the primitive gut tube ▪ Know the locations of the vitelline duct and allantois, and know the blood vessels associated with them ▪ List the structures derived from the foregut and know their blood supply ▪ Describe the development of the glands of the gastrointestinal tract ▪ Describe umbilical herniation and subsequent mid-gut rotation ▪ List the common congenital abnormalities of mid-gut and hind-gut ▪ Describe the formation of the urorectal septum and destiny of the cloacal membrane But taking these a few at a time…. The learning outcomes for this section of the lecture are; Describe the formation of the primitive gut tube Know the locations of the vitelline duct and allantois, and know the blood vessels associated with them List the structures derived from the foregut and know their blood supply Describe the development of the glands of the gastrointestinal tract The remaining outcomes will be dealt with in subsequent sections of the lecture.  The Primitive Embryo Remember when life was simple? Well, once you were just a flat elongated disc, with as much complexity as a jam-filled biscuit! You sat in a ball of cells that connected you to the uterine wall (endometrium). This stage of primitive life is known as a blastocele. With a little early embryonic development, you soon are made into a flat biscuit with an upper layer of ectoderm (the topping) and the bottom layer (the sponge) known as endoderm. The jam filling is mesoderm. This three-layered structure is referred to as the trilaminar disc. This disc sits between two cavities. Above is the amniotic cavity and below is the yolk sac. The differentiation of the cell layers into the tissues and organs of the body is known as organogenesis. Each layer forms specific body tissues and organs. The ectoderm will become the skin and nervous system. The mesoderm becomes the muscles, vascular system and connective tissues, including cartilage and bone. It also forms the kidneys. The endoderm becomes the gut, lungs, liver and hepatobiliary system.  The Primitive Embryo The development of the gut begins in week 3 of intra-uterine life, as the flat trilaminar embryonic disc folds under cranially, caudally and laterally, incorporating part of the yolk sac. The yolk sac is probably non- functional in humans, but in other species allows a storage of nutrients (yolk storage). It does however help the transfer of nutrients to the embryo before placental circulation develops. Mesoderm invades the wall of the yolk sac during the 3rd week, and this triggers the development of the fetal vasculature. There are some primordial germ cells which appear within its wall at this time. The dorsal part of the yolk sac gives rise to gut. This is difficult to visualise without some images to show the dynamic aspects of the development. So, let’s watch a short clip.  Animation of early gut formation This is difficult to visualise without some images to show the dynamic aspects of the development. So, let’s watch a short clip.  Animation of early gut formation During the 4th week of development, a period of rapid growth, the embryo begins to change shape, from a flat trilaminar disc into a cylinder. A process known as embryonic folding. Embryonic folding occurs in two planes, a horizontal plane and the median plane, and is a result of differing rates of growth of the embryonic structures. Folding of the embryo in the horizontal plane results in the development of two lateral body folds. Folding in the median plane results in the development of the cranial and caudal folds. Folding in both of these planes takes place simultaneously, resulting in the rapid development of the embryo.  Animation of early gut formation The cylinder consists of the 3 layers derived from the trilaminar disc. These are the endoderm the innermost layer, the ectoderm the outermost layer, and the mesoderm located in between. The endoderm is largely responsible for the formation of the gastrointestinal tract. As embryonic folding continues, the endoderm moves towards the midline and fuses, incorporating the dorsal part of the yolk sac to create the primitive gut tube. The primitive gut tube differentiates into three main parts. The foregut, midgut and hindgut. The foregut can be seen at the cranial or head end of the embryo. It is temporarily closed by the oropharyngeal membrane. Which at the end of the 4th week of development, ruptures to form the mouth. The midgut lies between the fore- and hindgut and remains connected to the yolk sac until the 5th week of development. As embryonic folding continues, the connection to the yolk sac narrows into a stalk known as the vitelline duct.  Animation of early gut formation The hind gut lies at the caudal or tail end of the embryo. It is temporarily closed by the cloacal membrane, which during the 7th week of development ruptures to form the urogenital and anal opening. As a result of embryonic folding, the major body plan is established, and the 3 germ layers continue to differentiate, giving rise to their own specific tissues and organ systems.  Mesenteries Once the folding of the trilaminar disc has taken place, the gut is trapped by the lateral and ventral abdominal walls as the anterior walls of the embryo fuse together. Only the connection through the umbilicus remains, to the remnant of the yolk sac. Either side of the gut tube is a trapped space, the coelomic cavity. This will become the peritoneal cavity in due course. The gut tube is suspended from the posterior and anterior walls by a double-folded membrane. These are the dorsal and ventral mesenteries. Around the stomach as we can see here, these mesenteries are known as the dorsal and ventral mesogastrium. The gut tube receives a blood supply from the aorta at the back of the abdomen. These arterial branches reach the gut by travelling in the dorsal mesentery. Around the umbilicus, the ventral mesentery gets in the way of the developing umbilical cord, and hence it regresses. The dorsal one remains, but the ventral one does not descend below the foregut.  Vitelline Duct and Allantois Umbilical artery By 28 days, the yolk sac continues to regress and thin out. The yolk sac doesn’t have a significant function beyond the primitive embryonic stages. In those early stages, nutrients from the sac are absorbed by vessels in its wall (vitelline veins) to aid nutrition of the embryo. However, once the placenta takes over, the vitelline circulation ceases to be important, and the yolk sac regresses. It lies within the developing umbilical cord for a short time. The umbilicus also contains another vestigial structure in humans, the allantois. This duct arises as a diverticulum of the hindgut. This has a close relationship with the yolk sac. In reptiles and birds, the allantois has a role in respiration and/or storage of urine. It is non-functional in humans, but its vessels become the umbilical artery. The allantois also regresses later in development. The proximal end of the allantois remains and will enlarge to become the urinary bladder. From the apex of the bladder, a fibrous cord can be seen in the adult, that connects the bladder to the umbilicus. If this fails to fibrose and close, it may allow urine to “weep” from the umbilicus.  Foregut Gives rise to » Pharynx and Oesophagus » Lower respiratory tract – Including larynx, trachea and lungs » Stomach and Duodenum, – proximal to opening of bile duct » Liver and pancreas – Biliary apparatus The foregut gives rise to the pharynx and oesophagus. The thoracic part of the foregut gives rise to the lower respiratory tract. The larynx, trachea and bronchial tree all arise from the foregut tube. Since this development is in tandem with that of the oesophagus, abnormalities of this development can lead to a failure of separation of the oesophagus from the airway. Below the developing diaphragm, the foregut gives rise to the stomach and part of the duodenum. The liver, gall bladder, pancreas and biliary system are all derivatives of foregut.  Lower Respiratory Tract Formation During the 3rd week of intrauterine life, the foregut develops a respiratory diverticulum. This ultimately forms the larynx, trachea and bronchial tree. To begin with, it is a simple tube, which is in continuity with the foregut. A tracheo-oesophageal septum is required to separate these two tubes from one another. The respiratory diverticulum subsequently buds into two, forming the lung buds. These will form the bronchial tree and alveoli of the lungs. The connective tissue of the lungs and respiratory tract is formed by splanchnic mesoderm that surrounds the developing endoderm of the foregut.  Oesophageal Atresia and Fistulae Sometimes the closure of the tracheo-oesophageal septum can trigger atresia of the oesophagus. This causes the developing oesophagus to divide into a proximal and distal part. Sometimes the oesophagus may communicate with the trachea, forming a tracheo-oesophageal fistula. This can occur in isolation, or in conjunction with atresia. Development of the Glands of the Foregut The liver develops in the ventral mesogastrium as a diverticulum of the foregut. From this diverticulum, the gall bladder and ventral pancreas also develop. A distinctive feature of human pancreatic development is that the organ arises as two separate and distinct rudiments which subsequently meet and fuse to form a single organ. The dorsal pancreatic bud is the first to appear around day 26. The ventral pancreatic bud arises less than a day later as an evagination at the junction between the hepatic duct and the foregut.  Development of the Pancreas During the fifth week, there is a differential growth of the wall of the foregut such that the stomach rotates to the left. The hepatic duct and associated ventral pancreas migrate around the foregut until the ventral pancreas comes into contact with the dorsal one. By the beginning of the sixth week, both parts have fused. At the same time the developing liver and stomach are expanding within the abdominal cavity. The liver moves to the right and the stomach dorsally and to the left such that the developing duodenum, pancreas and associated mesenteries are displaced to the right. The pancreas comes to lie on the left. The part derived from the ventral pancreas becomes the uncinate process and the dorsal pancreas forms the remainder. Eventually the main ducts of the dorsal and ventral divisions of the pancreas interconnect.  Gastrointestinal System Development of the GI Tract Part 2: Midgut We shall now turn our attention to the midgut.  Learning Outcomes After this lecture you should be able to: ▪ Describe the formation of the primitive gut tube ▪ Know the locations of the vitelline duct and allantois, and know the blood vessels associated with them ▪ List the structures derived from the midgut and know their blood supply ▪ Describe the development of the glands of the gastrointestinal tract ▪ Describe umbilical herniation and subsequent mid-gut rotation ▪ List the common congenital abnormalities of midgut and hindgut ▪ Describe the formation of the urorectal septum and destiny of the cloacal membrane The learning outcomes for this part of the lecture are that you should be able to List the structures derived from the midgut and know their blood supply Describe umbilical herniation and subsequent midgut rotation List the common congenital abnormalities of midgut and hind-gut The remaining outcome will be covered in the next part of this lecture.  Midgut Gives rise to » Duodenum, distal to opening of bile duct » Jejunum » Ileum » Caecum and appendix » Ascending colon » Proximal 2/3rds of transverse colon The midgut comprises a section of the fetal gut tube which will become most of the intestines, but not all. It begins distal to the hepatic diverticulum. In the adult, this is where the bile duct opens into the 2nd part of the duodenum. It incorporates the jejunum and ileum, caecum and appendix and ascending colon. The midgut ends at a point which is 2/3rds of the way along the transverse colon. In the fetus however, there is no obvious junction. The midgut connects to the yolk sac via the vitelline duct. The midgut gets its blood supply via the superior mesenteric artery.  Midgut rotation During the mid-trimester, the liver is so huge that almost the entire midgut herniates into the umbilical cord to escape its pressure. When there is an expansion of the abdominal cavity later, and hence gains a little more space, the hernia reduces and the loop of the mid-gut rotates anti-clockwise (as seen from the front). It does this around the axis of the superior mesenteric artery. The rotation is in two phases as we will see in the next slide. As the midgut is brought back into the abdominal cavity, the connection to the yolk sac is lost.  42 days 42 days Cranial Limb Superior Mesenteric Artery Caudal Limb Lateral Medial Thumb The midgut rotation can be confusing. Imagine your placing your right hand out in front of you (or can do it now if you like!), but turn your hand 90 degrees so that the thumb is pointing down. Your nailbeds should be facing inwards. OK – well your little finger is representing the proximal end of the midgut, or cranial limb. The distal end (or caudal limb) is represented by your thumb. It is 42 days of development and your midgut is ready to be thrust forward into the umbilicus and out of the abdominal cavity (that’s why your fingers are pointing forwards). As this happens (by elongation of the tube), the cranial and caudal limbs rotate by 90 degrees counter clockwise (as viewed from in front). Do that with your hand, except from your view, that would be in a clockwise direction. 50 days You have mimicked stage 1 of the rotation of the midgut. After that bit of hard work, it’s time to pull your fingers back in from the umbilical cord and as you do, turn another 180 degrees in the same direction. 76 days Caudal Limb Cranial Limb You have now replicated stage 2 of the midgut rotation. Well done! Lets watch another short animation to see all of that in action.  Midgut rotation 2 Note the cranial limb is in green, the caudal limb is in blue. The cranial limb will form the small bowel, the caudal limb the large bowel, at least the parts making up the midgut. The foregut is in yellow and hindgut in pink. These are retained in the abdominal cavity during all of this. The cranial limb undergoes a high degree of folding prior to its rotation, whilst the caudal limb does not. Note the swelling appearing on the proximal end of the caudal limb – this is the developing caecum, the start of the large bowel.  3rd Stage of Midgut Rotation In the final part of the movement, the caecum has to descend on the right side of the abdominal cavity, from top right to bottom right in order to take up its adult position in the right iliac fossa. This is referred to as the 3rd stage of midgut development.  Abnormal Rotation of Midgut (not included in the lecture presentation) If the third phase fails to occur, then the colon may remain on the left- hand side of the abdominal cavity. The small bowel lies on the right- hand side of the abdomen, and the caecum is to the left of the duodenum. This arrangement makes the small intestine prone to rotation with subsequent interruption of its blood supply. Reversed and Non-Rotation of Midgut (not included in the lecture presentation) The rotation of the midgut is a complex sequence of the development of the gut and is prone to complications (malrotations). It has been estimated that as many as 1 in 500 live births result in a congenital anomaly of this development. Most of these anomalies do not result in life threatening conditions, indeed most are asymptomatic and hence the majority of these go undetected. In a non-rotation of the midgut, there is a failure of the second phase of rotation. The first phase usually still occurs, that is the first 90 degrees of counter-clockwise rotations takes place, but the subsequent 180 degrees does not. This results in the small bowel on the right-hand side of the abdomen and the large bowel on the left. It is possible that the 2nd phase of the rotation of the midgut is in a reverse direction. Again, the 1st phase usually occurs in the normal counter-clockwise rotation by 90 degrees. The second rotation by 180 degrees is clockwise, hence there is a net rotation of 90 degrees clockwise. This puts the duodenum in front of the transverse colon, and it can no longer be retroperitoneal. Although, this is often asymptomatic, it may on occasion constrict the transverse colon, or the blood vessels to the duodenum.  Omphalocoele Failure of the gut to return to the abdominal cavity causes omphalocoele, which must be distinguished from an umbilical hernia. A hernia occurs after the gut has returned to the abdominal cavity, whilst an omphalocoele is a failure of the midgut to reach the abdominal cavity to begin with. An omphalocoele is a fairly common occurrence, appearing in 1 in every 6000 births. It usually requires surgical intervention after birth to replace the gut in its “normal” position, and to close off the umbilicus.  Gastroschisis (not included in the lecture presentation) A gastroschisis is a protrusion of the gut through a small opening in the anterior abdominal wall. This opening is usually just right of the umbilicus. Unlike omphalocoele, a gastroschisis is not associated with a sac, and the intestines are exposed. There are many theories for the occurrence of gastroschisis, but it still remains an unexplained phenomenon. It is linked with maternal smoking, drug abuse, or other causes of low birth weight. There is a possible genetic link, as it is found to run in families as an autosomal recessive. There is a known link to the use of aspirin by the mother. Hence, the actual cause is multifactorial and poorly understood.  Meckel’s Diverticulum In the early embryo, the midgut is continuous with the yolk sac. Later, the neck of the yolk sac constricts to form a vitello-intestinal duct. The duct normally disappears but it may persist in whole or in part. Most commonly the proximal part persists, giving rise to a Meckel’s diverticulum. This occurs in approximately 2% of the population. When I was a student, great play was made of the relationship this structure had with the number 2. It was said to be 2 inches long, 2 feet from the iliocaecal junction, and present in 2% of the population. Yes, it was a long time ago as a matter of fact (since you ask)! I have discovered that the information given by my old Professors was only 2% true! Now that we no longer use feet and inches, much less attention is given to such statistics. However, it is important that you appreciate that inflammation of this diverticulum will mimic pain from an inflamed appendix. Before you remove that appendix, it might be an idea to check whether the patient is one of those 2%!  Gastrointestinal System Development of the GI Tract Part 3: Hindgut and Cloaca This is the final part of the lecture on the development of the gastrointestinal tract. In this part we will consider the hindgut and the cloaca. The word cloaca translates from the Latin word for ‘sewer’, so I hope you can see where this is going!  Learning Outcomes After this lecture you should be able to: ▪ Describe the formation of the primitive gut tube ▪ Know the locations of the vitelline duct and allantois, and know the blood vessels associated with them ▪ List the structures derived from the hindgut and know their blood supply ▪ Describe the development of the glands of the gastrointestinal tract ▪ Describe umbilical herniation and subsequent mid-gut rotation ▪ List the common congenital abnormalities of mid-gut and hind-gut ▪ Describe the formation of the urorectal septum and destiny of the cloacal membrane The final outcomes from this lecture are that you should be able to List the structures derived from the hindgut and know their blood supply Describe the formation of the urorectal septum and destiny of the cloacal membrane  Hindgut Gives rise to » Distal 1/3rd of transverse colon » Descending colon » Sigmoid colon » Rectum » Superior part of anal canal » Epithelium of the urinary bladder and most of the urethra The hindgut is the part of the alimentary tract that will subsequently give rise to the distal 1/3rd of the transverse colon, descending and sigmoid colon and rectum. It also gives rise to the superior half of the anal canal. The distal half of the anal canal is formed by an embryological tissue called the proctodeum. Prior to birth, the hindgut and proctodeum are separated by a membrane. This membrane has to be perforated, before faeces can be passed. The hindgut also gives rise to the allantois. The proximal part of this duct enlarges to form the fetal bladder. It will also gives rise to most of the developing urethra.  Position of the Allantois Before we go much further, I would like to remind you of the allantois, as this is related to the hindgut. Although this structure has little function in humans, there are blood vessels that form in its walls that ultimately become the umbilical arteries and umbilical veins and these head off in the connecting stalk towards the placenta. Its intraembryonic portion runs from the umbilicus to the urinary bladder with which it is continuous. As the bladder enlarges, it involutes to form the urachus. After birth, the urachus becomes a fibrous cord, the median umbilical ligament.  The Cloaca The distal part of the hindgut is known as the cloaca. What a wonderful name – as I mentioned in the introduction to the lecture, it translates from the Latin as “sewer”. The pipes of the sewer are however closed, and before opening the slush-gates, the sewer has to be divided for fluids and solids (if you get the drift). The hindgut becomes partitioned into two compartments by growth of a wedge of mesenchyme. This is the urorectal septum. It pushes down through the cloaca towards the cloacal membrane. This separates the urogenital tract from the future rectum and anal canal.  Partitioning of Cloacal Membrane Once the urorectal septum reaches the cloacal membrane, the separation is complete. The site of fusion of the cloacal membrane with the urorectal septum becomes the perineal body. This usually happens in the 7th week of intrauterine life. At this point, the endoderm meets the ectoderm of the proctodeum (perineum), and the cloacal membrane is divided into a urogenital and an anal membrane. Most of the urogenital membrane breaks down but is partly in evidence in the vagina of virgin females as the hymen. The anal membrane usually ruptures at end of eighth week of intrauterine life. Malformations of the cloaca are rare, occurring in about 1 in 5000 births. A persistence of the anal membrane, either in whole or in part, leads to an imperforate anus. These usually are spontaneously ruptured during the first passage a stools and may cause blood to be noticed by a mother changing a nappy (diaper). Occasionally, an imperforate anus may have to be surgically incised. There may sometimes be an incomplete separation of the cloaca into urogenital and anorectal parts, leading to a rectovaginal or rectourethral fistula. In the case of the former, the vagina may become infected with faecal bacteria, and in the latter faeces may enter the urethra, where infection may also occur.  Gastrointestinal System Development of the GI Tract That completes this short section on the hindgut and cloaca, and indeed it brings to an end our lecture of the development of the gastrointestinal tract. In the next lecture we shall turn our attention to the Peritoneum, which also has a complicated development.