Lecture 1: Development of the Alimentary and Paraalimentary Tract Flashcards
What is a stomodeum?
A depression between the brain and the pericardium in an embryo
Precursor of the MOUTH and the anterior lobe of the pituitary gland
Where does the foregut (cranial end) of the gut tube terminate?
At the buccopharyngeal membrane
Where does the hindgut (caudal end) terminate?
Cloacal membrane
What is the proctodeum?
Back ectodermal part of alimentary canal
Forms the lower part of the anal canal, below the pectinate line
Lined by stratified squamous non-keratonized and stratified squamous keratinized epithelium
Hilton’s white line
Source: http://en.wikipedia.org/wiki/Proctodeum
Where is the epithelium of the alimentary tract derived from?
The ectoderm of the stomodeum and proctodeum respectively
What is the alimentary canal?
The tubular passage that extends from mouth to anus
Functions in digestion and absorption of food and elimination of residual waste and includes the mouth, pharynx, esophagus, stomach, small intestine and large intestine
When does the vitelline duct appear? Significance?
26 days postfertilization (DPF)
Significance is that this is when the midgut region of the gut tube is no longer open to the yolk sac
What is atresia?
Congenital absence of closure of a normal body opening or tubular structure
What is recanalization?
Formation of new canals or paths, especially blood vessels through an obstruction such as a clot
Spontaneous restoration of the lumen of an occluded duct or tube
When does occlusion of the gut tube occur? When does it recanalize?
During week 6
Endodermal epithelium proliferates to occlude the gut tube
Recanalizes by week 8
When does the endodermal lining of the gut lumen differentiate into definitive mucosal epithelium?
Week 9
What happens when there is a defect in recanalization?
Stenosis
Atresia at various positions of the gut tube
What are the derivatives of the foregut?
- Pharynx
- Thoracic esophagus
- Abdominal esophagus
- Stomach
- Superior duodenum
What are the derivatives of the midgut?
- Inferior duodenum
- Jejunnum
- Ileum
- Cecum
- Appendix
- Ascending colon
- Transverse colon (right 2/3)
What are the derivatives of the hindgut?
- Transverse colon (left 1/3)
- Descending colon
- Sigmoid colon
- Rectum
Urogenital sinus and derivatives??
How do you tell what comes from foregut, midgut and hindgut?
Remember that the foregut and midgut is separated by superior and inferior duodenum, respectively
After that it is pretty easy, since the watershed area (2/3 of your way into the transverse colon) is the exact position where mid/hind gut are differentiated
What artery supplies the abdominal foregut?
CELIAC artery
i. abdominal esophagus ii. stomach iii. superior duodenum iv. and its derivatives
What artery supplies the midgut?
SUPERIOR mesenteric artery
i. inferior duodenum ii. small intestines iii. ascending colon iv. 2/3 of transverse colon
What artery supplies the hindgut?
INFERIOR mesenteric artery
i. 1/3 of transverse colon ii. descending colon iii. sigmoid colon iv. rectum
What is the thoracic foregut supplied by?
Pharynx and thoracic esophagus are supplied by aortic branches
What is a diverticulum?
An abnormal sac or pouch formed at a weak point in the wall of the alimentary tract
What is the respiratory diverticulum? When does it form?
The “lung bud”
Forms at 22 dpf
Ventral outpouching of the thoracic esophagus
When does the respiratory diverticulum bifurcate into the left and right bronchial buds?
26-28 dpf
What are the bronchial buds?
The rudiments of the two lungs
What is the process of lung formation?
- Resiratory diverticulum (22dpf)
- Bronchial buds (26-28 dpf)
- Secondary bronchial buds (5th week)
- Terminal bronchioles (Week 16)
- Respiratory bronchioles (Week 28)
- Terminal sacs aka primitive alveoli (Week 36)
What is the process of stomach formation?
- Week 4: straight tube connected to dorsal body by DORSAL MESENTERY
1a: dorsal wall of stomach grows faster than ventral wall to result in greater and lesser curvature - Week 5: caudal portion of septum transversum thins to become the ventral mesentery connecting stomach to ventral body wall
- 7-8 weeks: differential thinning of right side of dorsal mesentery results in 90 degree rotation of stomach around craniocaudal axis
What is the cardiac incisure?
The point at which lesser curvature of the stomach meets the pyloric antrum of the stomach
What is the septum transversum?
A thick mass of cranial mesenchyme that gives rise to thoracic diaphragm and ventral mesentery of foregut
What causes the rotation of the stomach? Significance?
A differential thinning of the right side of the dorsal mesentery
90 degree rotation around craniocaudal axis
Rotation causes duodenum to adhere to the dorsal body wall
Forms the lesser sac of the peritoneal cavity, dorsal to the stomach
Rotation is CLOCKWISE (if you are looking down at the rotation or if you are standing superiorly over the rotation)
Where is the greater curvature of the stomach located at first?
Dorsal
Where is the lesser curvature of the stomach located at first?
Ventral
What is the epiploic foramen?
AKA omental foramen
Foramen of Winslow
Passage between the greater sac (general cavity of abdomen) and the lesser sac
What is the lesser sac?
The cavity in the abdomen formed by the lesser and greater omentum
What are the secondarily retroperitoneal structures?
Structures that were initially suspended from the dorsal mesentery but got attached to the body wall
i. duodenum
ii. pancreas
iii. colon
What structures retroperitoneal?
- kidney
2. bladder
How does the liver form?
Day 22, hepatic plate appears on ventral side of duodenum
Cells proliferate a few days later (Day 25) to form the hepatic diverticulum
Grows into ventral mesentery
Diverticulum gives rise to liver cords
What do liver cords give rise to?
- hepatocytes
- bile canaliculi
- hepatic ducts
Comes from hepatic diverticulum that appears on ventral side of duodenum
What connects the liver to the ventral body wall?
Falciform ligament
Comes from ventral mesentery that holds liver to ventral body wall
What is the region of the ventral mesentery connecting the liver to the stomach?
Lesser omentum
What is the lesser omentum?
The region of the ventral mesentery connecting the liver to the stomach
What happens to the lesser omentum when stomach rotates?
It is repositioned from a sagittal to a coronal plane
Reduces connection between greater and lesser peritoneal sacs to epiploic foramen
How is the gallbladder and cystic duct formed?
Cystic diverticulum forms as a second endodermal thickening on ventral side of duodenum
Caudal to hepatic diverticulum
Gives rise to gallbladder + cystic duct
What is the cystic duct?
The duct that joins the gall bladder to the common bile duct
How does the pancreas form?
Day 26 DORSAL pancreatic bud forms on duodenum OPPOSITE of the hepatic diverticulum
A VENTRAL pancreatic bud grows into the ventral mesentery (inferior to liver) by day 32
Main duct of ventral bud connects to the bile duct
Week 5: bile duct and ventral pancreatic bud migrate around the duodenum to the dorsal mesentery
Week 6: pancreatic buds fuse to form the definitive pancreas
After fusion, duct from dorsal bud degenerates to leaveventral bud as only attachment (via main pancreatic duct) to the duodenum
Fuses to the body wall to become secondarily retroperitoneal
When does the ileum get distinguished from the colon?
Week 5
How does the ileum get distinguished from the colon?
By the presence of a CECAL primordium at the junction between the two
What is the cecum?
The junction between the ileum and the ascending colon
What is the primary intestinal loop?
A dorso ventral hairpin fold
Caused by the fact that the ileum lengthens more rapidly than abdominal cavity
Cranial end = ileum
Caudal end = ascending and transverse colon
What is attached to turn of the primary intestinal loop (most ventral extreme)?
The vitelline duct
Why does the primary intestinal loop herniate into the umbilicus?
Because of the continued elongation of midgut and growth of abdominal organs
How does the cranial and caudal ends of the primary intestinal loop rotate?
Counter-clockwise
A total of 270 degrees
90 degrees by week 8
Another 180 degrees by week 10
When does the primary intestinal loop rotate by 180 after it is already rotated by 90?
Because it is retracted into the abdominal cavity
What happens from week 8 to week 10?
Midgut differentiation
Lengthening and folding of jejunum and ileum
Formation of vermiform appendix
When are the small and large intestines attached in final positions?
Week 11
What happens after large intestine returns to the abdominal cavity (retraction of the primary intestinal loop)?
The dorsal mesenteries retracts and the cecum and ascending colon get attached to the dorsal body wall, making them secodnarily retroperitoneal
What is the descending colon suspended by?
Dorsal body wall after dorsal mesentery retracts
Secondarily retroperitoneal
What is the sigmoid colon suspended by?
Dorsal mesentery
Peritoneal
What does the distal end of the hindgut form?
Cloaca
An expansion that is sealed by cloaal membrane
What is the cardiac incisure?
The point at which lesser curvature of the stomach meets the pyloric antrum of the stomach
What is the septum transversum?
A thick mass of cranial mesenchyme that gives rise to thoracic diaphragm and ventral mesentery of foregut
What causes the rotation of the stomach? Significance?
A differential thinning of the right side of the dorsal mesentery
90 degree rotation around craniocaudal axis
Rotation causes duodenum to adhere to the dorsal body wall
Forms the lesser sac of the peritoneal cavity, dorsal to the stomach
Rotation is CLOCKWISE (if you are looking down at the rotation or if you are standing superiorly over the rotation)
Where is the greater curvature of the stomach located at first?
Dorsal
Where is the lesser curvature of the stomach located at first?
Ventral
What is the epiploic foramen?
AKA omental foramen
Foramen of Winslow
Passage between the greater sac (general cavity of abdomen) and the lesser sac
What is the lesser sac?
The cavity in the abdomen formed by the lesser and greater omentum
What are the secondarily retroperitoneal structures?
Structures that were initially suspended from the dorsal mesentery but got attached to the body wall
i. duodenum
ii. pancreas
iii. colon
What structures retroperitoneal?
- kidney
2. bladder
How does the liver form?
Day 22, hepatic plate appears on ventral side of duodenum
Cells proliferate a few days later (Day 25) to form the hepatic diverticulum
Grows into ventral mesentery
Diverticulum gives rise to liver cords
What do liver cords give rise to?
- hepatocytes
- bile canaliculi
- hepatic ducts
Comes from hepatic diverticulum that appears on ventral side of duodenum
What connects the liver to the ventral body wall?
Falciform ligament
Comes from ventral mesentery that holds liver to ventral body wall
What is the region of the ventral mesentery connecting the liver to the stomach?
Lesser omentum
What is the lesser omentum?
The region of the ventral mesentery connecting the liver to the stomach
What happens to the lesser omentum when stomach rotates?
It is repositioned from a sagittal to a coronal plane
Reduces connection between greater and lesser peritoneal sacs to epiploic foramen
How is the gallbladder and cystic duct formed?
Cystic diverticulum forms as a second endodermal thickening on ventral side of duodenum
Caudal to hepatic diverticulum
Gives rise to gallbladder + cystic duct
What is the cystic duct?
The duct that joins the gall bladder to the common bile duct
How does the pancreas form?
Day 26 DORSAL pancreatic bud forms on duodenum OPPOSITE of the hepatic diverticulum
A VENTRAL pancreatic bud grows into the ventral mesentery (inferior to liver) by day 32
Main duct of ventral bud connects to the bile duct
Week 5: bile duct and ventral pancreatic bud migrate around the duodenum to the dorsal mesentery
Week 6: pancreatic buds fuse to form the definitive pancreas
After fusion, duct from dorsal bud degenerates to leaveventral bud as only attachment (via main pancreatic duct) to the duodenum
Fuses to the body wall to become secondarily retroperitoneal
When does the ileum get distinguished from the colon?
Week 5
How does the ileum get distinguished from the colon?
By the presence of a CECAL primordium at the junction between the two
What is the cecum?
The junction between the ileum and the ascending colon
What is the primary intestinal loop?
A dorso ventral hairpin fold
Caused by the fact that the ileum lengthens more rapidly than abdominal cavity
Cranial end = ileum
Caudal end = ascending and transverse colon
What is attached to turn of the primary intestinal loop (most ventral extreme)?
The vitelline duct
Why does the primary intestinal loop herniate into the umbilicus?
Because of the continued elongation of midgut and growth of abdominal organs
How does the cranial and caudal ends of the primary intestinal loop rotate?
Counter-clockwise
A total of 270 degrees
90 degrees by week 8
Another 180 degrees by week 10
When does the primary intestinal loop rotate by 180 after it is already rotated by 90?
Because it is retracted into the abdominal cavity
What happens from week 8 to week 10?
Midgut differentiation
Lengthening and folding of jejunum and ileum
Formation of vermiform appendix
When are the small and large intestines attached in final positions?
Week 11
What happens after large intestine returns to the abdominal cavity (retraction of the primary intestinal loop)?
The dorsal mesenteries retracts and the cecum and ascending colon get attached to the dorsal body wall, making them secodnarily retroperitoneal
What is the descending colon suspended by?
Dorsal body wall after dorsal mesentery retracts
Secondarily retroperitoneal
What is the sigmoid colon suspended by?
Dorsal mesentery
Peritoneal
What does the distal end of the hindgut form?
Cloaca
An expansion that is sealed by cloaal membrane
What is the allantois?
A small diverticulum
Extends from cloaca into the connecting stalk (future umbilicus)
What happens to the cloaca?
Divides into posterior rectum and anterior primitive urogenital sinus
Urorectal septum is formed
Week 4-6
What forms the urorectal septum?
3 folds of tissue
Superior fold = Tourneux fold
Inferior folds = Rathke folds
What is the perineum?
The zone of fusion between urogenital membrane and anal membrane
What is the proctodeum?
AKA anal pit
Formed by mesenchyme surrounding anal membrane that proliferates into a raised ectodermal structure
Invaginates into anorectal canal in week 8
What is the pectinate line?
The line between the inferior 1/3 of anorectal canal and superior 2/3
What is the embryologic derivation of anorectal canal?
Inferior 1/3 = ectodermal
Superior 2/3 = endodermal
Because of proctodeum (which is ectodermal)
What are the three esophageal anomalies that happen as a result of embryological malformation?
- Esophageal atresia
- Esophageal stenosis
- Short esophagus
What are the two ways esophageal atresia can occur?
- tracheoesophageal fistula
2. failure of recanalization (associated with anorectal atresia)
What is a fistula?
An abnormal CONNECTION between an organ, vessel or intestine and another structure
What are most cases of esophageal atresia associated with?
Tracheoesophageal fistula (abnormal connection)
85%
When the septum separating the trachea and esophagus is displaced caudally
What are the sequelae to tracheoesophageal fistula that causes esophageal atresia?
A fetus cannot swallow and dispose of amniotic fluid
Accumulation of amniotic fluid
Polyhdramnios
In a newborn, the first swallow is normal but the fluid is suddenly expelled and respiratory distress occurs
What is polyhydraminos?
When there is an accumulation of amniotic fluid
This can happen with a baby with esophageal atresia due to tracheoesophageal fistula
-Cannot swallow and dispose of amniotic fluid
What are the key characteristics of esophageal stenosis?
Narrowing of the esophagus
Due to incomplete recanalization
Occurs anywhere along esophagus
What are the key characteristics of a short esophagus?
A failure of esophagus to elongate because stomach is displaced into the thoracic cavity
Called congenital hiatal hernia
What is a congenital hiatal hernia?
When the esophagus fails to elongate and stomach goes through diaphragm
What are the three embryological anomalies of the stomach?
- Congenital hypertrophic Pyloric Stenosis
- Duodenal Stenosis
- Duodenal Atresia
What are the key characteristics of Congenital Hypertrophyic Pyloric stenosis?
Stomach anomaly
Involves a thickening of the pylorus, resulting in severe stenosis, obstruction to food passage
Newborns with this condition display a distended stomach and PROJECTILE VOMITING
What is the pylorus?
The region of the stomach that connects to the duodenum
Divided into two parts
i. pyloric antrum (connects to body of stomach)
ii. pyloric canal (connects to duodenum)
What are the key characteristics of duodenal stenosis?
Stomach anomaly
Narrowing of dudodenal lumen due to incomplete RECANALIZATION
Characterized by expulsion of stomach contents that contain BILE
What are the key characteristics of duodenal atresia?
Stomach anomaly
COMPLETE blockage of duodenum occurs in 30% of Down’s infants and 20% of premature births
Failure of recanalization
Vomiting begins within few hours and expels bile
What are the anomalies of the liver and cystic ducts?
- Duct anomalies (variations in the shape of hepatic, cystic and bile ducts)
- Extrahepatic Biliary atresia
What are the key characteristics of extrahepatic biliary atresia?
1/10,000 births Obstruction of bile duct Failure to canalize OR Liver infection in the fetus Clinical sympoms = JAUNDICE
What are the anomalies of the pancreas?
- Accessory Pancreatic tissue
2. Anular Pancreas
What are the key characteristics of Accessory Pancreatic Tissue?
Inappropriate interaction of pancreatic mesenchyme with nonpancreatic endodermal epithelium
Results in formation of pancreatic tissue in stomach, duodenum and ileal (Meckel’s) diverticulum
What are the key characteristics of Anular pancreas?
When ventral pancreatic bud forms as two attached buds
When two ventral buds rotate in opposite direction to fuse with dorsal bud, a thin band of pancreatic tissue surround duodenum
Band can cause duodenal stenosis or atresia after birth
Due to inflammation and malignant disease later in life as well
What are the anomalies of the midgut?
- congenital omphalocele (intestinal or hepatic herniation into umbilical cord)
- failure of midgut to return to abdominal cavity by week 10
- Umbilical hernia
- umbilicus doesn’t close making it easier to herniate after week 10
- Gastroschisis
- Nonrotation
- Mixed rotation
- Reversed rotation
- reverse of second midgut rotation
- can cause obstruction of transverse colon
- Subhepatic cecum and appendix
- adherence of cecum to liver
- Mobile cecum
- causes variations in position of the appendix
- due to incomplete fixation of ascending colon
- Midgut volvulus
- Stenosis and atresia
- Ileal (Meckel’s) Diverticulum
What is the most common anomaly of the digestive tract?
Ileal (Meckel’s) diverticulum
When a remnant of yolk stalk remains as an outpouching of the ileum
Asymptomatic
What is an omphalocele?
A birth defect in which infant’s intestine or other abdominal organs stick out of the belly button
A type of hernia
So you can see intestines through belly button
What is gastroschisis?
A defect in ventral abdominal wall that results in extrusion of midgut structures WITHOUT involvement of the umbilical cord
Due to lateral folding of embryo during week four
What are the key characteristics of nonrotation?
Called left-sided colon
Quite commom and asymptomatic if volvulus doesn’t occur
Happens when second midgut rotation (180 degrees) fails to occur
Large intestine on left
Small intestine on right
What are the key characteristics of mixed rotation?
When midgut fails to complete final 90 degrees of rotation
Cecum becomes inferior to stomach
Can cause duodenal obstruction
What are the key characteristics of stenosis and atresia of midgut?
Failure of recanalization
Necrosis and conversion to a fibrous cord due to lack of recanalization
Can also form two parallel lumens known as intestinal duplication
What causes intestinal duplication?
Failure of recanalization
Formation of two parallel lumens
What are the anomalies of the hindgut?
- Congenital megacolon (Hirchsprung’s disease)
- Imperforate anus and anorectal anomalies
- Anorectal agenesis
- Anal stenosis
- Membranous atresia
- anus is in normal position but sealed by membrane
- Rectal atresia
- anal canal and rectum are present but don’t connect
- due to recanalization or defective blood supply
What are the key characteristics of congenital megacolon?
Hirschsprung’s disease
Results as a failure of neural crest cells to migrate normally
No neural crest cells = no enteric ganglion cells
No peristalsis in colon = dilation
HINDGUT
What are the key characteristics of anorectal agenesis
Rectum ends before reaching anal pit Fistula usually connects rectum to bladder, urethra or vagina Caused by defect in urogenital septum Characterized by i. meconium in urine (males) ii. meconium in vagina
What is meconium?
Dark green substance forming the first FECES of a newborn infant
What is the Golosow and Grobstein experiment of 1962?
Pancreas development DEPENDS on the surround mesenchyme
If mesenchyme was there, pancreatic buds grew
Lack of mesenchyme = no pancreatic buds
This means that mesenchyme released regulatory signals
Mesenchym around midgut = midgut formation
Mesenchyme around foregut = foregut formation
What is the mesenchyme inducing mechanism for hindgut and midgut?
Both have SHH expressed in gut endoderm
SHH leads to expression of Hox genes in mesenchyme
Hox genes then leads to differentiation
What is situs inversus?
When there is a reversal in left-right symmetry (or asymmetry in the case since organs are asymmetrical to begin with)
What is the significance of Nodal?
TGFbeta gene
Necessary for left-right patterning and morphogenesis of visceral organs
What is significant about Kartagener’s Syndrome?
Situs inversus (reversal of asymmetry) Failure of dynein function Ciliary defect
What is the siginificance of Pdx1?
Essential for pancreas development
Stands for pancreatic and duodenal homeobox
Expressed in dorsal and ventral bud regions of duodenum
SEEN ONLY in the MOUSE
Growth initiated but doesn’t progress
Pdx1
Essential for pancreas growth
Located in duodenal regions where pancreatic ventral/dorsal buds develop
MOUSE
What is IPF1?
Analog to pdx1
HUMANS
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