Development of the GI Tract

Question 1

State the three division of the gut and briefly where they extend from and to

Answer 1

• Foregut - extends from the pharynx down to the stomach to the cranial part of the duodenum
• Midgut - extends from the caudal part of the duodenum to the transverse colon
• Hindgut - remaining third of the transverse colon and the descending colon to the anus

Question 2

when does GI tract development occur?

Answer 2

GI tract development occurs during 3rd week to 12 weeks embryonic age (5 to 14 weeks after last menstrual period)

Question 3

Briefly summarise the stages involved in GI tract development

Answer 3

• Primary germ layer formation - ectoderm, mesoderm and endoderm
• Gut tube formation
• Regionalised changes caused by rotation, swelling and elongation
• Organs and glands produced by budding from the gut tube

Question 4

Describe how a blastocysts forms after fertilisation

Answer 4

• After fertilisation is a single fertilised cell known as a zygote which is surrounded by a protein coat called the zona pellucida
• The zygote then undergoes division via mitosis to form 2 cells then four then 8 and 16 - at this point the embryo is called a morula - has a raspberry shaped appearance and is consistent of loosely attached cells
• The embryo then undergoes compaction where the cells on the outer side of the embryo will now form epithelial cell tight junctions between those adjacent cells
• These junctions are not permeable to fluid allowing embryo to fill the central cavity of the zygote with fluid - the embryo is now considered a blastocyst
• The blastocysts consists of trophectodermal cells surrounding an inner cell mast consisting of epiblast and hypoblast cells after it develops

Question 5

When do primary germ layers form? (during which process and which part of gestation)

Answer 5

The primary germ layers are formed during the process of gastrulation

Occurs at the beginning of the third week at which point the embryo has implanted into the uterine wall

Question 6

State the role of trophectoderm cells

Answer 6

Allows the embryo to attach to the uterine wall

Question 7

State the initial structure of the primary germ layers

Answer 7

The epiblast cells form a circular structure near the uterine wall, with mesodermal cells forming underneath it and a primitive endoderm of hypoblast cells underneath this (beginning of a three layers embryo)

Hence the embryo is now a flat disc of two cell layers epiblast and hypoblast cells

Question 8

Describe the structure of the developing GI after the primary germ layers begin to form and where the primitive streak comes from

Answer 8

• The two layers of cells (epiblast and hypoblast cells) now start to separate to form other layers
• The epiblast cells begin to form amniotic cavity while the hypoblast cells form the yolk sac
• The amniotic cavity, epiblast cells, hypoblast cells and yolk sac surrounded by the trophectoderm cells form the germ disc/embryonic disc
• This germ disc/embryonic disc begins to have a cranial/caudal end - at the caudal end the primitive streak begins to form
• The primitive streak progresses from the caudal end to the cranial end of the embryo almost all the way across the disc but not quite (75% approx)

Question 9

Describe how specifically the primitive streak is formed

Answer 9

• Context -
• Epiblast - sheet of epithelial cells - cells of epiblast and hypoblast are rapidly proliferating
• The cells of the epiblast start to condense towards the midline of the embryo and as they do that they become very concentrated at that midline
• This process starts at the caudal end hence why the primitive streak starts at the caudal end and moves up to the cranial end
• The process -
• The cells in the midline now undergo another process called mesenchymal transformation - the cells stop being epithelial and detach from the hypoblast cells to form mesenchymal cells/migratory cells
• As they do this they fill the space between the epiblast and the hypoblast via process of involution
• Those cells then ingress between those two cell layers and migrate outwards while differentiating to give the three primary germ layers
• It is the concentrated area of cells in the middle which forms the primitive streak

Question 10

State the types of primary germ layers and what their roles are

Answer 10

Mesoderm -
Surrounding muscle, connective tissue and mesenteries

Endoderm -
Sometimes called the definitive endoderm - epithelium of the gut tube

Ectoderm -
- Innervation of the gut
- Formed from cells that don’t ingress and remain in the epiblast layer

Hypoblast -
Sometimes called the primitive endoderm - gives rise to extra embryonic tissue

Question 11

What does the ectoderm differentiate into?

Answer 11

Ectoderm then goes on to differentiate into ectoderm that forms part of the skin and in the midline it forms the neuroectoderm that then innervates the gut

Question 12

Summarise the formation of the three primary germ layers

Answer 12

• In the blastocyst there is a deep groove called the primitive groove surrounded by the primitive streak where cells condense into the midline there is also hensens node at the tip of the primitive streak where cell movements are initiated - secreted growth factors that patterns the tissues around it
• These cells undergo mesenchymal transformation and ingress and involute to go between the epiblast and hypoblast
• While migrating these cells then differentiate to form the mesoderm and the endoderm
• The epiblast that remains above this layer forms the ectoderm
• The ectoderm starts to become patterned by the tissue underneath (mesoderm) - notochordal cells are mesodermal cells that form a rod like structure in the midline of the embryo which underlies ectoderm and patterns ectoderm in the midline to become neural ectoderm

Question 13

Describe how the gut tube initially folds

Answer 13

• The gut tube is formed by folding sheets of cells in two directions
• The two lateral edges of the embryo will fold in towards the midline along the caudal - cranial axis - the edges of the amniotic cavity fold towards the midline
• At the same time the edges at the caudal and cranial end will fold inwards towards the middle part of the embryo

Question 14

Describe the processes which happen simultaneously while the gut tube undergoes its initial folding

Answer 14

While the gut is folding other processes are happening simultaneously

• First and main process is gastrulation where the two layer embryo becomes a three layer embryo
• The endodermal tissue in will form the gut tube epithelium itself
• Around the outside are the remains of the epiblast which is now forming the ectoderm
• There is also the area under the ectoderm which is the neural tube formed from the ectoderm which differentiated into neuroectoderm
• There is then structures of mesodermal cells on either side of the midline which will form the somites/presomitic mesoderm
• Mesoderm also forms the notochord which is patterning the tissues around it specifically the neural tube around it
• There is also the start of heart development towards the cranial end
• As the folds move in and pinch off the yolk sac , the yolk sac and the allantois make a stalk which joins to make the umbilical cord
• The folding of the embryo also brings the heart in towards a more thoracic position closer to its final positioning
• At this point the gut tube is closed at both ends- at the cranial end by the pharyngeal membrane and at the caudal end by the cloacal membrane

Question 15

Describe the main meseteries that form during gut development

Answer 15

• The mesoderm that connects the gut tube to the body wall is the mesenteries
• Between the dorsal aspect of the embryo and the gut is the dorsal mesentery
• Between the ventral aspect of the embryo and the gut in the ventral mesentery
• These mesenteries are derived from a subdivision of the mesoderm called the splanchnic mesoderm

Question 16

State in more detail what is present in the foregut, midgut and hindgut

Answer 16

• Foregut -
• Pharynx
• Oesophagus
• Stomach
• Cranial half of duodenum
• Ampulla of vater - joins the common bile duct and pancreatic duct
• Midgut -
• Caudal duodenum
• Jejunum
• Ileum
• Cecum
• Appendix
• Ascending colon
• Proximal ⅔ of transverse colon
• Hindgut -
• Distal ⅓ of transverse colon
• Descending colon
• Rectum

Question 17

Describe how based on hox genes the boundaries within the gut are formed

Answer 17

• Hox (homeotic) genes determine the positioning of body parts along the caudal cranial axis
• Highly conserved transcription factors which have conserved sequences and functions
• It is the boundaries of hox gene expression along the cranial caudal axis which specifies the position of the GI tract structures
• Combinations of hox genes expressed within the mesoderm and endoderm cause tissues to form which allows the specific formation of particular organs in particular regions of the gut tube

Question 18

Describe anatomically what separates the sections of the gut

Answer 18

The three regions of the gut are defined by the arterial blood supply
- All regions of the gut are supplied by the aorta
- 5 arterial branches to the thoracic oesophagus
- Celiac artery supplies blood to the foregut
- Superior mesenteric artery supplies blood to the midgut
- Inferior mesenteric artery supplies blood to the hindgut

Question 19

How does arterial blood supply to the GI tract change

Answer 19

When it first forms the gut is surrounded by plexus of blood vessels joining the vitelline vessels to the aorta

Plexus resolves to form the arteries that supply the GI tract from the aorta

Question 20

Describe how the gut is innervated

Answer 20

• Sympathetic ganglia develop next to the major branches of the aorta
• Post ganglionic sympathetic axons innervate the same tissues that the arteries supply with blood
• Celiac ganglion to the foregut, superior mesenteric ganglion to the midgut and inferior mesenteric ganglion to the hindgut

Question 21

Describe how the stomach develops via expansion and rotation

Answer 21

• The stomach begins as a bulge within the gut tube - the gut tube begins to swell asymmetrically so that it swells more towards the dorsal aspect than the ventral aspect
• Hence on the dorsal side the stomach is convex while the ventral side the stomach is concave
• Two branches of the vagal nerve lie on either side of the gut tube
• During the swelling the stomach also undergoes a rotation, rotating 90 degrees in a clockwise direction
• After rotation the left branch of the vagal trunk lies ventral (towards the front of the person) and the right branch lies dorsal (towards the back of the person)
• There is then a further rotation along the cranial caudal axis so that the area of greater curvature lies more caudally and the lesser curvature area lies more cranially
• At the outlet of the stomach there is a constriction called the pylorus which is a muscular sphincter controlling flow of food from stomach to the intestine

Question 22

Describe the mesenteries attached to the stomach

Answer 22

• Between the dorsal aspect of the body wall and the gut tube (stomach) is the dorsal mesogastrium
• Between the stomach and the ventral body wall is the ventral mesogastrium
• The ventral mesogastrium is subdivided into 2 distinct components- between the stomach and liver is the less omentum and between the liver and ventral body wall is the falciform ligament

Question 23

Describe how rotation of the stomach affects positioning of other structures

Answer 23

• As the stomach rotates the dorsal mesogastrium is drawn with it
• As the mesogastrium expands as its drawn down it will extend down and enclose a space called the omental bursa as its two sides fuse together
• As it extends down it will also fuse with posterior parts of the body wall to fix other structures into place and make them retroperitoneal meaning they are outside of the peritoneal space
• The ascending and descending colon are made secondarily retroperitoneal - initially in peritoneal space before being covered by mesogastrium and now attached to the body wall no longer in the peritoneum - the same happens with the pancreas and parts of the duodenum

Question 24

State what pyloric stenosis is, what causes it and its incidence rate

Answer 24

Gastric outlet obstruction caused by smooth muscles hypertrophy
3 in 1000 incidence
Projectile vomiting shortly after feeding
Pyloric channel elongation
Length > 16mm, wall > 4mm and diameter > 14mm - need these dimensions to diagnose pyloric stenosis

Question 25

Describe how the liver buds out from the foregut

Answer 25

• Many organs bud from the foregut - from the epithelial endoderm itself
• Liver is induced to bud off from the gut endoderm at a specific location because of signals from the heart - the heart moves when the embryo folds to be in its final adult positioning
• Hepatic diverticulum (region of the epithelial gut tube that starts to grow out) grows into the mesenchyme of the septum transverse
• This will start to extend chords - finger like projections of that simple epithelial tube - bile drainage ducts and blood vessels proliferate and are arranged as sinusoids
• The liver grows rapidly and will eventually exceed the size of the septum transverse expanding into the ventral mesentery
• As the stomach rotates as it develops it causes the liver to also rotate- the stomach rotates to the left side of the body while the liver rotates to the right side

Question 26

Describe how the pancreas buds off from the gut tube

Answer 26

• Two pancreatic buds- dorsal from the duodenal endoderm (induced by notochord) and ventral from hepatic diverticulum (induced by hepatic mesoderm)
• As duodenum rotates ventral and dorsal buds meet and fuse
• If the ventral bud is bilobed rotates and one lobe rotates around the duodenum it forms an annular pancreas which can obstruct the duodenum

Question 27

Describe how the midgut (the intestines) form

Answer 27

• Attached throughout their length by the dorsal mesentery but not a ventral mesentery
• The mesentery and gut grow at different rates leading to stereotypical folding of the gut
• A ventral branch of the aorta supplies the midgut- the superior mesenteric artery
• With a very rapid increase in length the intestines rotate around the superior mesenteric artery
• The abdomen is too small to accommodate the length of the intestines so the gut will herniate into the umbilical stalk at 6 or 7 weeks
• The gut tube first has a 90 degree rotation and characteristic loops of thee intestine start to form
• After herniation the gut then undergoes a further 180 degree rotation prior to that herniation being resolved

Question 28

State and briefly describe 3 conditions that arise from abnormal intestine development

Answer 28

• Umbilical hernia -
  Occurs when the intestines return to position normally but the rectus abdominis fails to fuse around the umbilicus so leads to a portion of the gut being covered by just skin
• Omphalocele -
  Failure of intestinal loops to return to the abdomen - hernia covered by amnion (amniotic membrane)
• Gastroschisis -
  Failure of the ventral body wall to fuse - no covering of the intestines

Question 29

Describe the most common abnormality in intestine development (yolk duct persistence)

Answer 29

• Most common abnormality
• Yolk duct is attached to the ileum near the ileo- cecal junction- apex of the midgut loop
• Persistence of the yolk duct is called Meckel’s diverticulum nd is usually asymptomatic but can contain ectopic gastric cells that lead to ulceration
• Can be connected to umbilicus by a ligament which leads to condition called volvulus where the midgut isn’t able to rotate correctly which can obstruct the ileum

Question 30

Describe Hirschsprungs disease

Answer 30

• Section of the gut which lacks enteric/parasympathetic innervation
• The aganglionic segment shows contraction
• Can lead to an enlarged colon (dilation of sections of the colon with a lack of tone and peristalsis) behind the area of contraction
• Primarily affects the hindgut - leads to constipation - hindgut because its caused by a lack of sacral neural crest cells

Question 31

Describe what neural crest cells are

Answer 31

• Neural crest cells originate from the dorsal region of the neural tube
• Contribute to a wide variety of tissues within the embryo - highly migratory so move and differentiate into lots of types of cells
• Parasympathetic innervation of the gut
• Transient population of cells- along the whole length of the embryo

Question 32

Explain how neural crest cells come to be found along the entire embryo

Answer 32

• Under influence of the notochord the neural ectoderm forms
• The neural tube begins to fold up and eventually it’s two edges fuse to form one continuous tube
• Before this fusion can happen the cells at the junction between neural ectoderm cells and non neural ectoderm cells must migrate away via epithelial mesenchymal transformation and migrate to distant sites within the embryo

Question 33

Describe the neural crest cells of the gut specifically

Answer 33

• Two main streams of neural crest cells that populate the gut
• Vagal neural crest cells and sacral neural crest cells
• The vagal neural crest cells enter in the foregut and must migrate along the entire length of the neural tube
• Cells that populate the hindgut will primarily enter through the sacral stream

Question 34

Describe how the hindgut (the anus) develops

Answer 34

• The cloaca is a transient common end of the digestive and urogenital systems including the base of the allantois (urogenital sinus)
• It is covered by the cloacal membrane which covered a small ectodermal depression called the proctoderm
• The cloacal membrane is split by the urorectal septum - splits it into a urogenital membrane and an anal membrane
• If these membranes then don’t open properly it can lead to an imperforate anus