The document discusses the embryological development of the gastrointestinal tract. It describes how the foregut, midgut, and hindgut develop from the primordial gut tube and how their development and rotation leads to the normal anatomy. It further discusses common anomalies that can occur due to disruptions during development, such as esophageal atresia, intestinal atresia, Hirschsprung's disease, and anorectal malformations. Precise spatial and temporal gene regulation governs gastrointestinal development, and perturbations can result in congenital anomalies.

1. EMBRYOLGIC BASES OF GIT
MALFORMATION &
MALROTATION
By : Dr. Mestet Y. (AAU)
1

2. Outline
• Events at early week of development
• Development and anomalies of the foregut
• Development and anomalies of the midgut
• Development and anomalies of the hindgut
• References
2

3. week 1 - Cleavage
- Implantation
3

4. Week 2: Formation of Bilaminar
Disc
4

5. Week 3: Trilaminar disc
(Gastrulation)
The 1st sign: primitive
streak
It appears as a
thickening of the
epiblast at the caudal
end of the embryonic
disc.
Mesoderm exists
between the ectoderm
and endoderm except
at 3 sites.
5

6.  Week 4, Body Folding
6
 Formation of Gut tube
a. Lateral Folding.

7. b. Cephalocaudal folding
• Effect of Folding
Curved embryo.
Closure of ventral body wall
Embryo lies within the amniotic cavity as the amnion is pulled down
as the head and tail and two lateral folds move ventrally.
Formation of primordial gut tube.
7

8. Development of Primordial Gut
• Endoderm: epithelial
lining& parenchyma of
glands
• Splanchnic mesoderm:
other layers
• Neural crest cells
• Embryonic development
depend on a precisely
coordinated interaction of
genetic and environmental
factors.
8

9. Regional patterning of the primordial
gut tube - the Hox code
• Hox genes are
helpful in
regional
patterning
• Hox gene
expressions &
interction
determines the
morphologically
Site &
formation of
major
sphincters (red
circles) of GIT.
Carlson fig 15-01

10. Development of foregut
A. Development of pharynx
• At 4th week, The primordial
pharynx derived from the
foregut.
• The endoderm of the pharynx
lines the internal aspects of the
pharyngeal arches &
pharyngeal pouches
• Extends from the
buccopharyngeal membrane to
the tracheobronchial
diverticulum.
10

11. B. Development of the
Esophagus
At 4 weeks just distal
to primordial
pharynx, a
diverticulum grows,
which soon gives
ventral lung bud.
• Partitioned by
Tracheoesophageal
septum
11
A, @ the end of
3rd week
B & C, During
4th week

12. Cont’d• Short first but it
elongates
• final length by 7th wk.
• The epithelium
proliferates and
obliterates the lumen
and later recanalization
occurs by the end of the
8th week.
• sphincters?
12

13. Esophageal Anomalies
A, Esophageal atresia &/or TEF
Failure of recanalization at 8th week b/c of arrest of
development defective growth of endodermal
cells.
- Due to spontaneous posterior deviation of TE
septum or
- mechanical factor pushing dorsal wall of foregut
anteriorly
 VACTERL
B, Esophageal stenosis /web/–
- comprised blood supply / failure of esophageal
blood vessels to develop in the affected area,
incomplete recanalization,
C, Congenital Hiatal Hernia:-
- Failure of esophagus to lengthen sufficiently &
stomach being pulled up in to esophageal hiatus.
D. Bronchopulmonary foregut malformation
13

14. C. Development of
Stomach
• Appears as fusiform dilation of
foregut in 4th wk
• Appearance and Position
change, due to growth rate
difference in various regions of
its wall and change in position
of the surrounding organs.
• Final shape: at 7thweek
• Attached to dorsal & ventral
body wall by dorsal & ventral
mesogastrium.
14
.

15. Effect of gastric's disproportionate
growth & rotation
• Rotation of the stomach
about
 Its longitudinal axis pulls
the dorsal mesogastrium
to the left, creating
omental bursa (lesser sac)
 its anteroposterior axis
leads the dorsal
mesogastrium continúes
growing down to forms
greater omentum
15

16. Cont’d
• The lesser omentum and
falciform ligament form from
septum transversum
(primodium of ventral
mesogastrium).
• When liver cords grow into the
septum, it thins to form
(1) the peritoneum of the liver;
(2) the falciform ligament,
extending from the liver to the
ventral body wall; and
(3) the lesser omentum, extending
from the stomach and upper
duodenum to the liver
16

17. Anomalies of the stomach
I. Hypertrophic pyloric
stenosis
• B/c of musculature hypertrophies of
pylorus
 Genetic:
excessive gastrointestinal growth factors
that facilitate pyloric hypertrophy. Eg.
excessive substance P, decreased
neurotrophins, deficient nitric oxide
synthase, and gastrin hypersecretion
More on identical twin
 Environmental factors
feeding (breast vs formula), seasonal
variability, exposure to erythromycin, and
transpyloric feeding in premature infants.
17

18. II. Gastric Volvulus
• Primary or Secondary.
• axis of gastric rotation.
 Mesenteroaxial: rotation
about the gastric short
axis.
 Organoaxial: rotation
around the long axis of
the stomach.
18

19. D. Development of duodenum
• At 4th week Initially
midline
• C-shaped loop and rotates
to the right due to
 rotation of stomach
 rapid growth of the head
of the pancreas
• Reanalyze during the 11th
week
• Why secondarily
retroperitoneal?
• Blood supply
19

20. Duodenal Anomalies
Duodenal stenosis
• from incomplete recanalization
usually involves the 3rd and/or
4th parts of the duodenum.
Duodenal Atresia
• Complete failure of recanalization
• other congenital anomalies are
often associated
• Most are seen in 2nd and 3rd part
distal to bile duct opening
• bile containing vomitus
• polyhhdramnios
• IX: double bubble sign on
radiography
20

21. Cont’d
21

22. Development of the Liver and ventral pancreas
It is specified by Cardiac mesoderm and septum
transversum
• ALL foregut endoderm has the potential to develop into either liver or pancreas but local signals
repress these fates (mesodermal Wnts ↓ Liver; mesodermal Wnts + endodermal Shh ↓ Pancreas)
• FGFs and BMPs from cardiac mesoderm and septum transversum inhibit Wnt signaling, but the
endoderm still expresses Shh and thus develops into liver.
• Meanwhile, endoderm just caudal to liver bud is out of reach from the FGFs and BMPs but still sees
Wnts, so the tissue does NOT become liver. Unlike the rest of the endoderm, it does NOT express
Shh and so develops into pancreas.
ventral pancreas

23. Development of dorsal pancreas
Is specified by signaling from the notochord
Signaling from the notochord represses Shh in caudal foregut
endoderm, which permits dorsal pancreatic differentiation.
Larsen’s fig 14-05

24. Development of Biliary tree
• At middle of the third week
• As an outgrowth the distal end of
the foregut
• The liver bud penetrate the
septum transversum
• Narrowing between the hepatic
diverticulum and duodenum form
bile duct
• Ventral outgrowth from bile duct
gives gallbladder and the cystic
duct
• Extra hepatic biliary tree initial
occlude & later canalized
• Rotation of the duodenum brings
the ventral and dorsal pancreas
together
• Why bare area of liver?
24

25. Hepatic & biliary Anomalies
• Accessory hepatic ducts
 From mis-regulation in
hepatic induction
• Extrahepatic biliary
atresia
 From failure to recanalize
 Jaundice soon after birth
• Intrahepatic biliary duct
atresia and hypoplasia
 Fetal infections
25

26. Pancreatic anomalies
Annular pancreas
occurs when the ventral
pancreatic bud fuses with
the dorsal bud both
dorsally and ventrally,
thereby forming a ring of
pancreatic tissue around
the duodenum

27. Pancreas divisum
(4% incidence)
Accessory pancreatic
duct

28. Development of the Mid gut
• Midgut maturation
involves four distinct
stages:
• (1) physiologic
umbilical herniation
• (2) rotation;
• (3) retraction; and
• (4) fixation.
28

29. Rotation of the Midgut
29
• While it is in the
umbilical cord, the mid
gut loop rotates 90°
CCW around the axis of
SMA.
• This brings the cranial
limb(small intestine) to
the right and caudal
part(large intestine) to
the left.

30. Return of the Midgut to the
Abdomen
30
• Occurs during the 10th
week
• The small intestine returns
first, passing posterior to
the SMA and occupies the
central part of the
abdomen.
• As the large intestine
returns, it undergoes a
further 180-degree CCW
rotation and later it comes
to occupy the right side of
the abdomen

31. Summary of Mid Gut
Rotation
 Along AP axis
 270 degree
 Counterclockwise
 Effect
 - Jejunum to left side
 - ileum & cecum on rt. Side
 - distal side is colon
31

32. Anomalies of Midgut Rotation
32

33. Development of cecum & appendix
• Cecal swelling (diverticulum)-at 6th wk
• Its apex does not grow as rapidly as the rest of it
• Appendix appear as diverticulum of distal cecal bud
during descent of colon at 10th week
• Why retrocecal & posteromedial to cecum mostly?
33

34. Jejunoileal Stenosis And Atresia
• B/c of vascuar insult
Evidence: atresias are seen
more in association with other
intrauterine vascular insults
such as fetal
 intussusception
 midgut volvulus
 thromboembolic occlusions,
 transmesenteric internal
hernias, and
 incarceration or snaring of
bowel in an omphalocele or
gastroschisis
34

35. .
 Type I: Mucosal atresia with
intact bowel and mesentery
 Type II: Blind ends separated
by a fibrous cord
 Type III(a): Blind ends
separated by a V-shape
mesenteric defect
 Type III(b): Apple-peel atresia
 Type IV: Multiple atresias
(string of sausages)

36. Vitelline Duct Anomalies
36

37. Congenital Abdominal Wall Defects
Omphalocele Gastroschisis
37

38. Gastroschisis
• Result from a defect at the
site of involution of the
second (right) umbilical
vein.
• Ventral body folds theory,
which suggests failure of
migration of the lateral folds
(more frequent on the right
side), is most widely
accepted
• Non-rotation and midgut
volvulus or vascular
thrombosis.
Omphalocele
• Due to a failure of the
viscera to return to the
abdominal cavity
• Not from a failure in body
wall closure or migration.
• 50% have associated
anomalies
38

39. Umbilical Hernia
39
• From imperfectly
closed umbilicus during
retraction of mid gut to
abdomen during the
10th week

40. Alimentary Tract Duplications
• Jejunum/ileum is the most common location but anywhere in
the GIT the.
• Two types: cystic (more common) and tubular.
• Causes: multiple theories & No single theory explains best.
 A persistent embryonic diverticulum from the GIT
 a defect in the recanalization of the lumen of GIT
 partial twinning theory as it is common in conjoined twins
 The ‘split notochord’ theory ( b/c of Enteric duplications and
spinal anomaly association )
 Fetal hypoxia
 Heterotopic gastric mucosa in 25–30% of duplications.
40

41. Cont’d
• Synchronous abdominal
duplications
Thoracoabdominal
Duplications
Extension of an esophageal
duplication into the abdomen
Small Bowel Duplications
Arise from the mesenteric side
and share a common blood
supply.
Why gastric mucosa in
duplications?
41

42. Development of the Hind gut
5 weeks 6 weeks 8 weeks
. . 42

43. Cont’d
• The urorectal septum also divides the cloacal
sphincter into anterior and posterior parts
• Mesenchymal proliferations produce
elevations of the surface ectoderm to give
anal pit
• Rupture of anal membrane at the end of the
8th week
• Enteric neurons in the hindgut arise from
neural crest.
43

44. Cont’d
• Epithelium source
• Blood supply
• innervation
44

45. Anomaly of hind gut
1. Hirschprung’s disease
(aganglíoníc megacolon)
• why aganglionosis?
1. neural crest cells never reach the
distal intestine due to early neuronal
cell death
/differentiation into ganglion cells/
b/c of
 Mutations of RET proto-oncogene
 Mutations in the endotelin and
SOX-10 genes:
2. The neural crest cells reach their
destination, but fail to survive due to
an inhospitable microenvironment.
• Why Distal portions of the bowel
mostly?
45

46. 2. Anorectal malformation
46
• Most result from abnormal development of the
urorectal septum
• low or high Lesions: based on the r/n of
rectum to the puborectalis muscle. These
classification is not useful in current
therapeutic or prognostic.
• 2/3rd anorectal malformation are high lesions.
• > 90% of low lesions have external fistula.
• Passage of meconium or flatus in the urine is
diagnostic of a rectourinary fistula.

47. Cont’d
47

48. Anal Stenosis
• Normally positioned narrow lumen anus caused by dorsal
deviation of the urorectal septum
Membranous Atresia of Anus
• From failure of the anal membrane to perforate at end of 8th
wk
Rectal Atresia
• From abnormal recanalization/ defective blood supply/ of
rectum.
• Screen for a presacral mass.
48

49. Imperforate Anus without Fistula
• Is an unusual defect (5%).
• About 50% of patients with no fistula have
Down syndrome,
• >90% of patients with Down syndrome and
imperforate anus
• patients with this defect & Down syndrome
have well-developed sacrum and have a good
prognosis in terms of bowel function.
49

50. Rectovestibular, Rectourethral &
Rectoperineal
Fistulas
50

51. Persistent Cloaca
A common channel of greater
than 3 cm
A common channel of less than 3
cm
51

52. Assessment of
Sacrum Development
How to know high or low
anorectal malformation?
52

53. Summary
• Every development is precisely regulated at
gene level.
• A perturbation in dev’tal control result
anomaly.
• Associated non GI anomalies can present with
GI anomalies & so must be ruled out.
• Prognosis of most GI anomalies depends on
other associated non GI anomalies.
• High index of suspicion, dx & timely mgt is
essential.
53

54. References
54