Digestive system

Digestive system

1. Introduction

   • Endodermal derivative, 4th week gestation, Flat intraembryonic endoderm fold into gut tube, boundaries, Segmentation along anterior posterior axis, intestinal pouch, reflected in blood supply, yolk sac, vitelline duct, merkel diverticulum, asymmetric expression of nodal and FGF4, gradient expression of Hox 9-13, Sox2 and foxa2, elongates and diverticulum of major glands

2. Foregut

   • 5 derivatives, pharyngeal region, respiratory system oesophagus stomach and part of duodenum. Foregut rapid expansion contributes to cardiac primordium rotation in craniocaudal direction
     • Oesophagus
       • Caudal to lung buds, initially short, differential growth rates, pharynx ascends, final relatively length@ week 7. Endodermal epithelium lining proliferates and occludes lumen, recanalized at week 8/9, excessive recanalization= duplication of gut tube
       • oesophagus epithelium is endoderm in origin but connective tissue is splanchnic mesoderm
       • Histological differentiation at week 12, mature stratified squamous epithelium by 34weeks
     • Stomach
       • Initial formation directed by Hoxa5, Gradient expression of FGF10 from gastric mesoderm directing regional differentiation of epithelium glandular characteristics, Bounded to body wall by dorsal ventral mesogastrium+ Spleen, pancreas and liver, Greater curvature, rotate around longitudinal and antero-posterior axis so right face is now posterior, greater curvature is now right, stomach diagonal assuming spatial position of adult, Right vagus also posterior, Rotation also alters position of mesenteries, dorsal mesentery grows outwards to left and billows out to form greater omentum, hangs over as double flat, omental bursa., pyloric stenosis
     • Duodenum (up to entrance of bile duct)
       • Duodenum partly foregut partly midgut, rapid expansion at week 5, C shape loop, loop apex, gives rise to liver, pancreas, gall bladder, pancreas= 2 outgrowth buds, dorsal pancreatic bud from foregut, ventral pancreatic bud from hepatic bud, rotation of duodenum due to differential growth rates, ventral pancreatic bud carried dorsally to fuse, 2 ducts fuse and join common bile duct@ duodenal papilla, Ventral- uncinate process and head of pancreas, dorsal- everything else, Defects: annular pancreas
       • Gall bladder cystic diverticulum from hepatic bud,
       • hepatic bud outgrowth, invade septum transversum, fibrous reticular parts,

3. Midgut

   • Derivatives: Lower duodenum (distal to bile duct onwards), Jejunum, Ileum, Large intestine, Proximal 2/3 of transverse colon
   • Rapid growth and extension, exceeds length of embryo, hairpin loop with yolk sac stalk attached at apex, , further elongation by FGF-9 from epithelium stimulates fibroblast proliferation, lack of space so physiological umbilical hernia, umbilical coelom body stalk week6, Rotates along SMA, week 10 does back in and rotates, order of return determines definitive position, jejunum first left, rest of midgut right, caecum last,
   • Midgut loop suspended by mesentery while coiling and herniating, Shape of mesentery regulates return to gut, asymmetric expression of PitX2 in left side of dorsal mesentery regulates shape therefore regulates looping/rotation (Davies et al 2008), Appropriate spatial orientation, mesenteries fuse with peritoneal lining, Defects: Omphalocele in patau13, External to body cavity in transparent amnion and peritoneal membrane sac, abnormal looping

4. Hindgut

   • Derivatives: distal transverse colon all the way to superior 2/3 of anal canal, including epithelium of urinary bladder and urethra
   • Cloaca, allantois, extends into connecting stalk, evaginating into the mesoderm, foetal bladder- yolk sac, continuous with future urogenital sinus, removes urinary waste, but placenta does it, eventually degenerates, urachus, median umbilical ligament, bladder-umbilicus
   • Cloacal membrane, urorectal septum, UGS and rectum, perineum, cloacal membrane break down into anal canal+ opening of UGS, upper 2/3 of anal canal is derived from hind gut and endoderm origin, proctodeum forms lower 1/3 of anal canal so ectoderm origin, diff embryological origin reflected in blood supply, Defects :anal atresia, faecal incontinence, Shh pathway directs cloaca development as Gli2/3 mutation= imperforate anus