Gastrointestinal Tract Development

Transcription

Gastrointestinal Tract DevelopmentEndoderm Æ cell sheet Æ tubular gutLateral foldingVentral bending cranially Æ Head foldVentral bending caudally Æ Tail foldYolk sac is connected to the gut in the middleYolk stalk, omphalomesenteric duct, orvitelline ductYolk stalk is progressively delineated.

Embryonic GutRegions:Foregut Æ Lateral fold and head foldHindgut Æ Lateral fold and tail foldMidgut Æ Yolk Stalk RegionAnterior intestinal portal – foregut / midgut transitionPosterior intestinal portal - midgut / hindgut transitionOropharyngeal membrane ectoderm-endoderm bilayer separatingstomodeum, future mouth – ectoderm lined, from the futurepharynx – endoderm lined.Cloacal plate or Proctodeal membrane ectoderm-endodermbilayer, separates the ectoderm lined proctodeum from thegut endoderm.

Embryonic GutStraight tube suspended by the dorsal mesenteryOnly ventral connection is the transverse septumlevel of stomach and cranial duodenum.Transverse septum - mesoderm initially between developing heartand the cranial margin of the embryonic discCranial flexure displaces the transverse septum between the heartand the yolk sac –Forming the initial partition separating the thoracic andabdominal cavities Æ part of the diaphragmHindgut – evagination is the allantois

Foregut DeriviativesOropharyngeal membrane (cranial end)Pharynx (deriviatives of the pharyngeal pouches, tongue,thyroid gland)Thoracic esophagus (lung buds)Abdominal esophagusStomachCranial half of duodenum (liver, gallbladder, pancreas)Caudal end Ampulla of Vater (common bile andpancreatic ducts drain into gut)

PharynxPharyngeal:Pouches (endoderm); Grooves (ectoderm); Arches (mesoderm)

Pharyngeal PouchesPharyngeal Pouch #1 – Caudal to Arch #1Auditory tube (Eustachian tube), tympanic cavityPharyngeal Pouch #2 – Caudal to Arch #2Supratonsillar fossae associated with Palatine tonsilsPharyngeal Pouch #3 – Caudal to Arch #3Inferior parathyroid, ThymusPharyngeal Pouch #4 – Caudal to Arch #4Superior parathyroids, Postbranchial body

TongueLateral Lingual Swellings – paired lateral swellings from the 1stpharyngeal arch (ventral)2 unpaired medial swellings from the ventral midline of the pharynxTuberculum imparCopulaContribution from the 3rd and 4th pharyngeal archesOral Tongue (anterior 2/3) forms from the expansion of lateralswellings and the tuberculum impar - median sulcus of the tongueis the site of midline fusionBase of the tongue is formed from the copula with contribution fromthe 3rd and 4th pharyngeal archesThe epiglottis forms from a swelling caudal to the copula

Thyroid GlandThyroid DiverticulumMidventral thickening, between Pharyngeal Pouch 1and 2 (base of the tongue)Single outgrowth elongates in a caudal directionBifurcates to form the bi-lobed Thyroid glandThe connection – thyroglossal duct regresses about week 7The site of the thyroid diverticulum persist as the foramencecum – between the tuberculum impar and the copula

EsophagusThoracic Esophagus buds off the lung buds Æ RespiratoryTractAbdominal Esophagus – abruptly narrows – extends to theStomachDifferentiation of Epithelium:7th – 8th Week – epithelium is stratified columnar,Lumen becomes partially occludedAppearance of large vacuolesVacuoles coalesce – recanalization12th Week - Epithelium is multilayered and ciliated16th Week – Stratified squamous epithelium

StomachStomach - initially symmetrical and fusiform (spindle)Differential growth - dorsal ventral - creates the Greatercurvature of the stomach (dorsal side) and Lessercurvature (ventral side)90o rotation of the stomach around craniocaudal axisgreater curvature is to the left and caudallesser curvature is to the right and cranialDorsal mesogastrium (dorsal mesentery) – differentialgrowth is responsible for the rotation. Dorsalmesogastrium becomes the greater omentum

Dorsal mesogastrium becomes the greater omentum

Stomach rotation moves the duodenum to the left and cranially

Liver is Derived from the DuodenumEndodermal thickening – ventral side of DuodenumHepatic diverticulum - grows ventrally into thetransverse septumHepatic diverticulum branches into many Hepatic cordsthat form hepatocytes and the drainage ducts (bilecanaliculi, hepatic ducts).Gastrohepatic omentum – connection to the stomach –becomes the lesser omentumFalciform ligament – ventral mesentery connection tothe body wall

Gallbladder / Cystic DuctCystic diverticulum arises from a ventral endodermalthickening just posterior to the hepaticdiverticulumThe cystic diverticulum gives rise to the gallbladderand cystic duct.Hepatic duct and cystic duct merge to form thecommon bile duct

PancreasPancreas forms from two distinct outgrowths from theduodenumDorsal pancreatic bud grows into the dorsal mesenteryVentral pancreatic bud sprouts from the hepatic diverticuluminto the ventral mesentery caudal to the forminggallbladerThe main duct of the ventral pancreas bud merges at theproximal end of the common bile ductThe mouth of the common bile duct is displaced to the dorsalmesentery

PancreasThe dorsal and ventral pancreatic rudiments fuseThe dorsal duct degenerates and the dorsal and ventral partsmerge their duct systems. The ventral duct becomes themain pancreatic duct (Duct of Wirsung)Where the common bile duct and pancreatic ducts empty intothe duodenum is called the Ampulla of VaterExocrine function - acinar cells - production of digestiveenzymesEndocrine function - islets of langerhans - production ofinsulin and glucogon (β cells and α cells)

SpleenThe Spleen is an intra-abdominal organ that is not anendodermal derivitiveThe Spleen is mesodermal and develops in the dorsalmesogastriumThe Spleen is a vascular lymphatic organThe Speen moves to the left side of the abdominal cavitywith the rotation of the stomach.Initially a hematopoietic organ, later gets colonized by Tlymphocyte precursor cells

Dorsal mesogastrium becomes the greater omentum

Formation of the IntestineMidgut derivatives:Caudal half of duodenumJejunumIleumCecumAppendixAscending colonRight 2/3 of transverse colonHindgut derivatives:Left 1/3 of transverse colonDescending colonSigmoid colonRectumCloacal membrane at caudal end

Primary Intestinal LoopThe intestine is essentially a long straight tube, but it’sdevelopment is complicated by its length.Two important points of reference:Yolk Stalk – near border of small and large intestineSuperior Mesenteric Artery – branch of Dorsal AortaIleum – elongates too rapidly for the size of the abdominalcavity causing a herniation into the umbilicusDorsal-ventral hairpin - called the primary intestinal loop.

Intestine DevelopmentCranial part of loop gives rise to most of the ileumCaudal loop becomes part of ileum, the ascending colonand 2/3 of the transverse colonInitially - the loop does a 90o counterclockwise rotation(viewed from the front) - cranial loop Æ right,caudal loop Æ leftJejunum and Ileum lengthens resulting in a series of foldscalled the jejunal-ileal loops

RetractionCecum defines junction between small and largeintestines – producing the appendixRetraction of the loop into the abdomenAssociated with a 180o rotation - total rotation is270oCecum lies just inferior to the liverThe cecum moves in a cranial to caudal direction to lie inthe lower left abdomen

Ascending and Descending ColonDorsal mesentery associated with the ascending anddescending colon shortens and disappearsThese regions adhere directly to the dorsal body wallTransverse colon does not become fixed

CloacaCloaca (latin sewer) - where allantois andgastrointestinal tract mergeCloaca is partitioned into the rectum (posterior) and theprimitive urogenital sinus (anterior) - by thegrowth of the urorectal septumUrorectal septum is the composite of two septal system Tourneux fold (central) and Rathke folds (lateral)Urorectal septum fuses with cloacal membrane - formingthe urogenital membrane and the anal membrane

Anorectal CanalAnorectal canal - between rectum and anusSuperior 2/3 is endodermal from hindgutInferior 1/3 is derived from the proctodeum ectodermalThe Ectodermal-Endodermal boundary in adult is markedby an irregular folding of mucosa in the anorectalcanal called the Pectinate line

Canalization and HistogenesisThe developing digestive tract lumen becomes occluded andsecondary lumina form and coalesce during recanalizationStomach – Gastric mucosa – folds called rugae, pits called gastric pits,HCl secretion begins postnatalIntestine - Intestinal Villi form by mesodermal growthduring recanalizationIntestinal Crypts form at the base of the intestinalvilliEach crypts contains a clone of Epithelial Stem Cells thatproduce intestinal cells throughout adult lifeIntestinal epithelial cells have a 4 day life span

Anomalies - ForegutEsophagus:Esophageal stenosis (narrowing) – abnormalrecanalization – impaired swallowingEsophageal atresia (abnormal opening) – abnormalbranching of the respiratory tract – impairedswallowingStomach:Pyloric stenosis – hypertrophy of smooth muscle, projectilevomitingHeterotopic gastric mucosa – Misplaced gastric mucosacells

Anomalies - ForegutLiver:Biliary atresia – abnormal hepaticduct formation – varying severitypostnatal jaundicePancreas:Annular pancreas – Pancreatic tissueencircling the duodenumsometimes causing obstructionHeterotopic pancreatic tissueMisplaced pancreatic cells

Anomalies - MidgutDuodenal stenosis and atresia – abnormalrecanalizationPersistent vitelline duct –Meckel’s diverticulum - (2-4% of population) –blind pouchFibrous cord – connection to umbilicusVolvulus – intestinal rotation Æ bowelstrangulationUmbilicoil fistula – direct opening

Anomalies – MidgutOmphaloceleFailure of the umbilicus to close - newborn with organsprotruding from the abdominal walllOrgans protruding into a thin sac of amniotic tissue fromnormal herniation - incomplete retractionOrgans in a sac of peritoneum and amniotic tissue indicates normal herniation and retraction, but asecondary herniation resulting from the failure ofthe ventral abdominal wall to close

Anomalies - MidgutAbnormal Rotation and FixationSpectrum of abnormalitiesNon-rotationReverse rotationMixed rotationSubhepatic cecum

Non-RotationCalled left-sided colon1st rotation is Normal2nd rotation is AbsentCranial loop ends up on the right sideCaudal loop on the left sideSome organs may or may not get fixed to the body wall

Reverse RotationNormal 1st rotation2nd rotation is clockwise instead of counter clockwiseNet rotation is 90o clockwiseThis is equivalent to a 270o counter clockwise rotationexcept the duodenum is ventral to the transversecolon and does not get fixed to dorsal wall,transverse colon does get fixed

Mixed RotationCranial and caudal loops behave independentlyCranial loop rotates only the 1st 90oCaudal loop only rotates the 2nd 180oResults in misplaced organs - abnormal fixationTypical outcome from abnormal rotations obstructions of the gastrointestinal tract,compression of intestinal vasculature - resulting inintestinal ischemia; compression of lymphaticvessels - resulting in gastrointestinal bleeding

Anomalies – MidgutSubhepatic Cecum

Intestinal Duplication, Diverticula,and AtresiaUnknown Causes

Anomalies - HindgutHirschsprung’s Disease – Dilation of the colon –defective neural crest migration Æ absence ofparasympathetic ganglia in the colon wallImperforate anus – absence of anal opening

Hindgut FistulaOften connectingthe hindgut to theurogenital systemPersistent Anal MembraneAnal AtresiaAnoperineal fistulaRectovaginal fistulaRectourethral fistulaRectovesical fistula

Embryonic Gut Straight tube suspended by the dorsal mesentery Only ventral connection is the transverse septum level of stomach and cranial duodenum. Transverse septum - mesoderm initially between developing heart and the cranial margin of the embryonic disc Cranial flexure displaces t