GI Embryology

Question 1

What does folding create?

Answer 1

Lateral folding of the embryo creates the ventral body wall and the primitive gut becomes tubular.

Craniocaudal folding creates cranial and caudal pockets from yolk sac endoderm (beginning primitive gut development)

Question 2

Describe the beginning of the development of the GI Tract

Answer 2

• Development of the GI tract begins when during the fourth week folding of the embryo creates a primitive gut tube, lined with endoderm and divisible into 3 regions: foregut, mid-gut and hindgut. All parts of the adult GI tract arise from one of these regions. Each region has its particular pattern of neurovascular and lymphatic supply, which is retained into the adult.
• Development of the primitive gut tube begins in the 3rd week when it “pinches off” from the yolk sac cavity. It runs from the stomatodenum (future mouth) rostrally to proctodeum (future anus) caudally with an opening at the umbilicus. This opening into the yolk sac is known as the vitelline duct.
• Its internal lining is derived from endoderm (future epithelial linings).
• Its external lining is derived from splanchnic mesoderm (future musculature, visceral peritoneum)
• It is suspended in intraembryonic coelom by a double layer of splanchnic mesoderm.

Question 3

What are the embryonic divisions of the gut?

Answer 3

• Foregut and hindgut begin as blind diverticula
• Midgut has an opening at first and is continuous with the yolk sac
• The mesoderm surrounding the gut splits into layers: somatic which develops into the muscles and fasciae of the abdominal wall and splanchnic, which becomes the smooth muscles of the gut wall.
• The space created by the split is the coelomic cavity which eventually develops into the pleural cavity and peritoneal cavity. The primitive gut is therefore surrounded by the coelomic cavity.

Question 4

What are the adult derivatives, blood supply and innervation of the foregut?

Answer 4

Oesophagus

Stomach

Pancreas, liver & gall bladder

Duodenum (proximal to entrance of bile duct)

Celiac Trunk (left gastric, splenic and common hepatic)

Parasympathetic: Vagus Nerve (Cranial 10)

Sympathetic: Splanchnic branches of sympathetic chain ganglia ( T5-T10) - coeliac ganglion

Question 5

What are the adult derivatives, blood supply and innervation of the midgut?

Answer 5

Duodenum (distal to entrance of bile duct) - 3rd and 4th parts

Jejunum

Ileum

Cecum

Ascending colon

Proximal 2/3 transverse colon

Superior Mesenteric Artery (SMA)

Superior Mesenteric Vein (SMV)

Parasympathetic: Vagus Nerve

Sympathetic: Superior Mesenteric Ganglion & Plexus

Lymphatic drainage follows arterial supply

Question 6

What are the adult derivatives, blood supply and innervation of the hindgut?

Answer 6

Distal 1/3 transverse colon

Descending colon

Sigmoid colon

Rectum

Upper anal canal

Internal lining of bladder & urethra

Inferior Mesenteric Artery (IMA)

Inferior Mesenteric Vein (IMV)

Parasympathetic: Pelvic Splanchnic N. (S2/3/4)

Sympathetic: Inferior Mesenteric Ganglion & Plexus

Lymphatic drainage follows arterial supply

Question 7

But what structures develop to have a mixed blood supply?

Answer 7

structures that develop close to the junction between foregut and midgut will have mixed blood supply:

• Duodenum: proximal to entry of bile duct (gastroduodenal artery and superior pancraticoduodenal artery (Celiac Trunk)) and distal to entry of bile dict (inferior pancreaticoduodenal artery (SMA))
• Pancreas: head (superior pancreaticoduodenal artery and inferior pancreatico duodenal artery)

Question 8

Describe the development of the muscular and fascial layers of the abdominal wall, including the inguinal canal

Answer 8

As lateral folding of the embryo progresses the two sides of the developing anterolateral abdominal wall meet in the midline, forming the linea alba.

• One opening is left, at the umbilicus
• Each side of the anterolateral abdominal wall is formed by 3 layers of muscle: the external oblique, internal oblique and transversus abdominis
• Anteriorly there is a fourth muscle, the rectus abdominis
• Deep to all the muscles’ layers is the transversalis fascia
• Externally lie the superficial fascia and skin
• The muscles of the abdominal wall are all from somatic mesoderm

The inguinal canal is an oblique passage through the layers of the abdominal wall, in males allowing the passage of the developing testis into the scrotum.

• The testis does not pierce the abdominal wall; it pushes them out ahead of its passage, forming the fascial coverings of the spermatic cord.

Question 9

Explain the developmental basis of umbilical and inguinal hernia

Answer 9

• Umbilical hernia: a congenital malformation, where the intestines protrude through the abdominal wall. It is common in babies, as the gut forms outside of the abdomen and later returns through an opening that becomes the umbilicus. If this opening is a potential site of weakness, abdominal contents can push against it and herniate outwards.
• The inguinal canal remains a potential site of weakness and hernia formation throughout life as abdominal contents can push against it and herniate through.

Question 10

Describe how the coelomic cavity develops

Answer 10

Coelomic Cavity: the mesoderm surrounding the gut splits into Somatic and Splanchnic and the space between them forms the Coelomic Cavity via lateral folding.

• The intraembryonic coelom begins as one large cavity, which is later subdivided by the future diaphragm into the abdominal and thoracic cavities.

Question 11

Describe how the peritoneum and peritoneal cavity develop

Answer 11

the peritoneal membrane lines the abdominal cavity and invests the viscera. During it’s development it grows, changes shape and specalises

• The peritoneal cavity is a potential space only, as under normal conditions it should contain nothing apart from a tiny amount of serious fluid (lubricated surface)

Question 12

What are mesenteries? And describe the fate of the embryonic dorsal and ventral mesenteries.

Answer 12

• The developing gut is attached to the roof of the abdominal cavity by a fold of condensed mesoderm known as the dorsal mesentery.
• A mesentery is a double layer of peritoneum suspending the gut tube from the abdominal wall

Allow a conduit for blood and nerve supply
Allow motility where needed

• A similar fold, the ventral mesentery attaches the foregut only to the floor.
• The mesenteries become the various peritoneal folds and reflections that suspend the gut and give passage to vessels and nerves in the adult.
• Their shape often becomes complex due to the complexity of the changes in shape and position undergone by the developing gut.

Question 13

How do the Greater and Lesser Peritoneal Sacs develop?

Answer 13

: the dorsal and ventral mesenteries in the region of the foregut divide the cavity into left and right sacs.

The left sac contributes to the Greater Peritoneal Sac and the right sac contributes to the Lesser Peritoneal Sac which comes to lie behind the stomach.

Question 14

Explain how the Greater and Lesser Omenta develop

Answer 14

• The greater and lesser omenta are specialized regions of the peritoneum.
• As the stomach expands and rotates, its dorsal mesentery is drawn into a sac, the omental bursa, which becomes the greater omentum. The Greater Omentum is the first structure seen when the abdominal cavity is opened anteriorly, connecting the greater curve of the stomach to the transverse colon.
• The ventral mesentery becomes the less omentum. The lesser Omentum connects the lesser curve of the stomach to the liver. Its free edge conducts the portal triad (key anatomical structure)

Question 15

Describe the development and rotation of the stomach

Answer 15

• The stomach is the widest part of the foregut. Initially it is symmetrical, then as it enlarges it expands unevenly, mainly towards the left. It also rotates so that its original left side becomes anterior and the original right side comes to lie posteriorly.
• the faster growth of the dorsal border creates the greater curvature.
• The primitive stomach also rotates in two directions, around the longitudinal axis and the anteroposterior axis.
• Greater and lesser curvature come to lie first on right and left side.
• Stomach rotation shifts cardia and pylorus from the midline, pushing greater curve inferiorly. The stomach lies obliquely
• The recess of the peritoneal cavity behind the lesser omentum and stomach becomes the lesser sac – stomach roation contributes to moving the lesser sac behind the stomach
• Creates the greater omentum
• Stomach rotation puts the vagus nerves anterior and posterior to the stomach instead of left and right

Question 16

Describe the development of the foregut and midgut and hindgut

Answer 16

• Initially the foregut ends blindly at the oropharyngeal membrane and the hindgut at the cloacal membrane. When the membranes break down, the gut becomes open to the exterior at the future mouth and anus.
• At first the midgut is connected to the yolk sac; this connection eventually closes.
• The foregut forms part of the mouth, the pharynx, oesophagus, stomach and the first and second parts of the duodenum. The lungs, liver and pancreas form as foregut outgrowths
• Abnormal narrowing of the oesophagus may occur. The primordia of the trachea and lungs form at the junction with the pharynx.
• This is a potential site for developmental anomalies such as the trachea-oesophageal fistulae and oesophageal atresia
• The most distal part of the foregut becomes the first and second parts of the duodenum. Abnormal narrowing at the gastroduodenal junction may occur (pyloric stenosis).

Question 17

What’s a Peritoneal reflection?

Answer 17

Peritoneal Reflection: a change in direction e.g. from parietal peritoneum to mesentery or from mesentery to visceral peritoneum or from visceral peritoneum etc

Question 18

Understand why some abdominal organs possess mesenteries and some are retroperitoneal

Answer 18

Some parts of the GI tract, e.g. the jejunum and ileum remain suspended from the posterior abdominal wall by a mesentery and remain mobile. In other parts e.g. the ascending and descending colon and the duodenum, the mesentery adheres and fuses with the peritoneum on the posterior abdominal wall, leaving the organ covered by peritoneum and immobile (retroperitoneal).

STRUCTURES THAT ARE NOT SUSPENDED WITHIN THE ABDOMINAL CAVITY ARE RETROPERITONEAL
Retroperitoneal: were never in the peritoneal cavity and never had a mesentery e.g. aorta, vena cava, kidneys

Question 19

What is meant by secondarily retroperitoneal?

Answer 19

began development invested by peritoneum, had a mesentery but with successive growth and development the mesentery is los through fusion at the posterior abdominal wall e.g. the ascending and descending colon and the duodenum

Question 20

Describe the development of the duodenum

Answer 20

• the duodenum and its mesentery is pushed to the right and then against the posterior abdominal wall during development due to rotation of the stomach and the large size of the liver. The peritoneum of posterior abdominal wall is ‘squished together’ with the duodenum and its mesentery, growing over it. This is FUSION FASCIA. Since fusion fascia is avascular, you can remove it to make the duodenum mobile again without causing any damage.
• Develops from caudal foregut and cranial midgut
• Grows rapidly, forming a C-shaped loop (around the pancreas) when the stomach rotates
• In the 5th and 6th weeks the lumen of the duodenum is obliterated due to the lining growing so quickly. It is recanalised by the end of the embryonic period.
• NBL the duodenal cap is not retroperitoneal!

Question 21

Describe the development of the respiratory primordium

Answer 21

in the 4th week, a respiratory diverticulum forms in the ventral wall of the foregut at the junction with the pharyngeal gut. This becomes the respiratory primordium ventrally and the oesophagus dorsally, divided by the tracheoeophageal septum.

Consequences of abnormal positioning of the tracheoesophageal septum: a variety of oesophageal abnormalities occur in up to 1 in 3,000 live births

Question 22

Describe the development of the foregut-derived glands

Answer 22

Formed in the Ventral Mesentery: liver, biliary system, part of the pancreas (ucinate process and inferior head)

Formed in the Dorsal Mesentery: pancreas (superior head, neck, body and tail)

NB: everything is endoderm derived

Question 23

Describe the development of the liver

Answer 23

• the liver is the earliest GI tract associated gland. It develops from the hepatic bud within the ventral mesentery. The liver occupies a large proportion of the abdomen during development

[*] The liver develops as a hepatic bud, an outgrowth of the foregut-midgut boundary. It grows into the ventral mesentery, dividing it into two parts – the falciform ligament and the lesser omentum.

• The hepatic bud forms the hepatocytes and the duct system of the liver, while the ventral mesentery forms its vascular and connective tissue components.
• The common bile duct joins the main pancreatic duct to enter the duodenum together at the duodenal papilla which marks the boundary from foregut to midgut.
• Failure of the duct system to canalize can cause biliary stenosis or atresia. Outflow of bile is obstructed and the infant becomes jaundiced soon after birth.

Question 24

Describe the development of the pancreas

Answer 24

[*] The pancreas is a foregut derivative. It forms from two portions: the dorsal and ventral pancreatic buds at the junction of the fore- and midgut, roughly halfway along the duodenum. Differential growth and rotation of the duodenum bring the two buds together on its left. They fuse;

• The dorsal bud forming most of the gland while the ventral bud forms most of its duct system, as well as the ucinate process and part of the head.

Abnormalities in the rotation process can lead to an annular (ring-shaped) pancreas. This is rare but important because it can obstruct the duodenum.

Question 25

Describe the umbilical vein

Answer 25

The umbilical vein from the placenta runs along the free border of the falciform ligament, then through the developing liver (ductus venosus). After birth these channels close down forming the ligamentum teres and ligamentum venosum

Question 26

Describe the physiological herniation of the midgut loop

Answer 26

[\*] The midgut is connected to the yolk sac at its midpoint by the vitelline duct (narrowing of the primitive gut tube) [\*] It grows faster than the abdominal cavity – elongates enormously and quickly runs out of space due to the large size of the developing liver, so that it makes a loop that has the SMA as its axis. It has cranial and caudal limbs. It lies in the sagittal plane. [\*] In the 6th week it comes to protrude through the abdominal wall into the proximal part of the umbilical cord, alongside the umbilical vessels as the abdominal cavity is too small to accommodate it and the liver. . This is known as “physiological herniation” because it is a normal process – elongation of the primary loop is very rapid during the 6th week. The growth of the liver is also very rapid and the abdominal cavity is too small to accommodate both.

Question 27

What does it look like at ~58 days of fertilization?

Answer 27

Question 28

Describe the first rotation of the midgut loop

Answer 28

* While inside the umbilical cord, the midgut loop rotates around the axis formed by the artery to lie in the horizontal plane. * First Rotation (90 degrees): during herniation into the umbilical cord, the midgut rotates around the axis formed by the SMA in a counter clockwise direction (cranial limb moves to the front, caudal to the back). * Even during rotation elongation of the small intestinal loop continues and the jejunum and ileum form a number of coiled loops. The large intestine likewise lengthens, but does not particulate in the coiling phenomenon.

Question 29

Describe the second and third rotations of the midgut loop

Answer 29

In week 10 (approximately) the midgut loop returns to the abdominal cavity, undergoing further rotation as it does so. The midgut turns 90 degrees counter clockwise twice. The midgut loop therefore undergoes a 270 degrees total counter clockwise rotation.

Question 30

Which limb goes in first during rotation? And what are the derivatives of each limb?

Answer 30

[\*] The cranial limb (future jejunum and ileum) are the first to go back, moving to the left hand side with the cecal bud returning last. When the cecal bud has returned to the abdomen, it descends, moving the caecum to the right lower quadrant. [\*] These rotations account for the positions of the small and large intestines and the twisted appearances of the mesentery of the small intestine. [\*] Cranial limb derivatives: distal duodenum, jejunum, proximal ileum [\*] Caudal limb derivatives: distal ileum, cecum, appendix, ascending colon, proximal 2/3 transverse colon

Question 31

What are the different types of rotational abnormalities?

Answer 31

[\*] Abnormalities of rotation are common causing abnormal positioning of midgut derivatives e.g. appendix on the left. * Incomplete rotation: midgut makes only one 90 degrees rotation =\> left sided colon (we need full rotation to allow the cranial limb to get to the left side of the abdominal cavity) * Reversed rotation: midgut makes only 90 degrees rotation CLOCKWISE =\> transverse colon passes posterior to the duodenum (so the transverse colon can wrap around and occlude the duodenum – the duodenum is very mobile rather than retroperitoneal and can potentially get trapped by the loops) * Incomplete or reversed rotation leads to hypermobile guts [\*] Major complication of midgut defects: Volvulus: a bowel obstruction where a loop of bowel has abnormally twisted in on itself – much more likely with hypermobile guts. Could lead to strangulation and ischaemia. [\*] If an abnormally large opening between the abdominal cavity and the umbilical cord persists, an umbilical hernia may be present at birth. [\*] Meckel’s diverticulum is a persistent yolk sac remnant in the midgut

Question 32

What complications could there be due to abnormal rotation?

Answer 32

Question 33

How can you distinguish the large intestine from the small intestine?

Answer 33

Although the large intestine has a dual origin from the mid- and hindgut, all parts except the rectum share 3 distinguishing anatomical features that distinguish it from the small intestine: * Taenia coli (3 separate longitudinal ribbons of smooth muscle on the outside of the ascending, transverse, descending and sigmoid colons) * Haustrations (small pouches which gives the colon its segmented appearance – can be seen on barium radiographs) * Appendices epiploice (small pouches of the peritoneum filled with fat and situated along the colon, not in the rectum)

Question 34

Describe the division of the cloaca

Answer 34

[\*] At first the hindgut ends blindly at the cloaca (blind ending diverticulum), which separates it from the proctodaeum (anal pit) at 6 weeks. The hindgut is separated from the outside by the cloacal membrane. The cloaca then undergoes an anteroposterior division. [\*] Cloacal Partitioning: a wedge of mesoderm grows down into the cloaca, dividing it into the urogenital sinus anteriorly and the anorectal canal posteriorly. The urorectal septum separates the urinary tract anteriorly and GI tract posteriorly.

Question 35

Describe the development of the anal canal

Answer 35

[\*] When the membrane ruptures, the hindgut (ectodermal origin) is connected to the exterior; the anal canal therefore has a dual origin. This is reflected in the histology of its mucosa and in its blood and nerve supply. Imperforate anus is caused by failure of cloacal membrane to rupture. * The perineal body contributes to the pelvic floor * Only the superior part of the anal canal is derived from the hindgut (ectodermal origin). The inferior part is derived from endoderm. The line at which the two parts of the anal canal meet is called the Pectinate line.

Question 36

Describe the neurovascular supply and epithelium above and below the pectinate line

Answer 36

* Above the Pectinate Line: blood supply is inferior mesenteric artery, innervation S2/S3/S4 pelvic parasympathetic, columnar epithelia and lymph drainage is via internal iliac nodes * Below the Pectinate Line: blood supply is pudendal artery, innervation S2/S3/S4 pudendal nerve, epithelium is stratified squamous (non keratinized) and lymph drainage is superifical inguinal nodes. * The only sensation that is possible above the Pectinate line is stretch. Below the pectinate line, the tissue is sensitive to temperature, touch and pain due to its somatic innervation by the pudendal nerve (S2/S3/S4)

Question 37

Explain about visceral pain

Answer 37

[\*] Visceral pain is poorly localized. The diffuse pattern reflects the development of the structure: * Foregut and its derivatives: epigastrium * Midgut: perumbilical * Hindgut: suprapubic But the parietal peritoneum receives somatic innervation

Question 38

Describe the fate of the dorsal and ventral mesenteries

Answer 38

[\*] Fate: At first the mid- and hindgut are suspended by long dorsal mesenteries. In the case of jejunum, ileum, appendix, transverse colon and sigmoid colon these are retained and the gut remains mobile. [\*] These mesenteries of the duodenum, the caecum, the ascending colon, the descending colon and the rectum adhere to the peritoneum of the posterior abdominal wall so that these parts of the gut become fixed. [\*] Dorsal Mesentery becomes: * Greater omentum * Gastrolienal ligament (stomach to spleen) * Lienorenal ligament (spleen to kidney) * Mesocolon * Mesentery proper (jejunal and ileal loops) [\*] Ventral Mesentery becomes: * Lesser omentum (foregut to liver) * Falciform ligament (liver to ventral body wall)

Question 39

Explain about Meckel's Diverticulum

Answer 39

[\*] Meckel’s Diverticulum: also known as the Ilieal Diverticulum and is the most common GI abnormality. It is a ‘cul-de-sac’ in the ileum. It follows a Rule of 2’s; * 2% of the population affected * 2 feet from the ileocecal valve * 2 inches long * Usually detected in under 2’s – can be asymptomatic * 2:1 Male: Female (true in all congenital defects) * The diverticulum can contain ectopic gastric or pancreatic tissue. The ectopic tissue will secrete enzymes and acids into tissue not protected from them, causing ulceration. The reason for this is not clear. The tissue can also become inflamed and result in similar presentation to appendicitis.

Question 40

Describe Vitelline abnormalities

Answer 40

* Vitelline Duct: can persist resulting in a number of different abnormalities * Vitelline Cyst: the vitelline duct forms fibrous strands at either end * Vitelline Fistula: there is direct communication between the umbilicus and the intestinal tract. This results in faecal matter coming out of the umbilicus.

Question 41

Explain about Recanalisation

Answer 41

[\*] Recanalisation: the primitive gut is a simple tube. In some structures, cell growth becomes so rapid that the lumen is partially or completely obliterated e.g. the oesophagus, bile duct and small intestine. * Recanalisation occurs to restore the lumen (normally occurs in weeks 6-8). If it is wholly or partially unsuccessful, atresia (complete loss of lumen) or stenosis (narrowing of lumen – so material can pass through but transit is slow) of the structure can occur. * Most atresia/stenosis occurs in the duodenum. The most likely cause is incomplete canalisation but ‘vascular accidents’, where there is a loss of blood supply and that part of the gut dies, may also contribute. * Incidence: Duodenum \> Jejunum = Ileum \> Colon * In the upper duodenum, atresias are most often due to recanalization failure. In the lower duodenum, atresias are most often due to vascular accident (caused by malrotation, volvulus, body wall defects)

Question 42

Explain about Pyloric Stenosis

Answer 42

[\*] Pyloric Stenosis is a common abnormality of the stomach in infants. It is a narrowing of the exit from the stomach, resulting in characteristic projectile vomiting. * It is caused by hypertrophy of the circular muscle in the region of the pyloric sphincter (NOT DUE TO A RECANALISATION FAILURE) * Sometimes it resolves on its own, sometimes intervention is required

Question 43

Discuss defects of the abdominal wall

Answer 43

* Gastroschisis: failure of closure of the abdominal wall during folding of the embryo, leaving the gut tube and its derivatives outside the body cavity. There is no covering over the gut tube/derivatives as they herniate through the abdominal wall directly into the amniotic cavity. Recovery is normally good as defect is normally isolated. * Omphalocoele aka exomphalos: persistence of physiological herniation. A part of the gut tube fails to return to the abdominal cavity, following its normal herniation into the spinal cord. Since the umbilical cord is covered by a reflection of the amnion, this epithelial layer covers the defect. Compare but do not confuse with UMBILICAL HERNIA which has a covering of skin and subcutaneous tissue. High chance of other developmental abnormalities occurring at the same time.

Question 44

Describe Hindgut abnormalities

Answer 44

* Imperforate Anus: failure of the anal membrane to rupture * Anal/anorectal agenesis: failure of development * Hindgut fistulae: abnormal connection within the hindgut

Question 45

Describe the timeline of GI embryology

Answer 45