BGD B Lecture notes Lecture 1: GIT Development Mark Hill Trilaminar contributions • Overview: o A simple tube is converted into a complex muscular, glandular and duct network that is associated with many organs • Contributions: o Endoderm – epithelium of the tract, glands, organs such as the liver/pancreas/lungs o Mesoderm (splanchnic) – muscular wall, connective tissue o Ectoderm (neural crest – muscular wall neural plexus Gastrulation • Process of cell migration from the epiblast through the primitive streak o Primitive streak forms on the bilaminar disk o Primitive streak contains the primitive groove, the primitive pit and the primitive node o Primitive streak defines the body axis, the rostral caudal ends, and left and right sides Thus forms the trilaminar embryo – ectoderm, mesoderm, endoderm • Germ cell layers: o ectoderm – forms the nervous system and the epidermis epithelia 2 main parts • midline neural plate – columnar epithelium • lateral surface ectoderm – cuboidal, containing sensory placodes and skin/hair/glands/enamel/anterior pituitary epidermis o mesoderm – forms the muscle, skeleton, and connective tissue cells migrate second migrate laterally, caudally, rostrally until week 4 o endoderm – forms the gastrointestinal tract epithelia, the respiratory tract and the endocrine system cells migrate first and overtake the hypoblast layer line the primary yolk sac to form the secondary yolk sac • Membranes: o Rostrocaudal axis Ectoderm and endoderm form ends of the gut tube, no mesoderm At each end, form the buccopharyngeal and cloacal membranes o Buccopharyngeal membrane Breaks down to form oral cavity At the rostral end o Cloacal membrane Breaks to form the anus, urinary and genital openings At the caudal end Folding • Stage 8: Week 3, days 17-19, 1-1.5mm o Folding of the flat disk Folds ventrally, away from the amniotic side Folds some of the yolk sac inwards, some stays outside • Embryo grows but yolk sac doesn’t, thus after folding, it remains as a remnant • In animals, it is used for nutrition, but in humans it has been replaced by the placenta Endoderm • Forms gastrointestinal tract o GIT doesn’t carry out post-natal function until after birth However, it is necessary developmentally for the fetus to practice: secretions/contractions o Note: allantois – structure of the endoderm that extends into the placental cord • Forms the linings of two tracts: o Digestive tract o Respiratory tract Outgrowth of the digestive tract: respiratory diverticulum Bifurcates into two bronchi lungs o Buds give ruse to the liver, gall bladder and pancreas o Pharynx – the common chamber in the anterior region Endoderm gives rise to the tonsils, thyroid, thymus and parathyroid glands GIT • By the 4 th week: o 3 parts: foregut, midgut and hindgut o 2 specialised regions: buccopharyngeal membrane and the cloacal membrane These are appositions of the ectoderm with the endoderm directly without mesoderm Oral cavity • Forms through the breakdown of the buccopharyngeal (oropharyngeal/oral) membrane o Open to the amniotic sac Allows swallowing of amniotic fluid which is important for muscular development • Formed mainly from the pharynx lying within the pharyngeal arches Foregut • Partitions into the oesophagus and respiratory diverticulum during weeks 3 and 4 Canalisation • Process: o Week 5 – endoderm in the GIT wall proliferates o Week 6 – endoderm proliferation results in total occlusion of the gut lumen o Weeks 7-8 – tissue degeneration results in reformation of the hollow gut tube o Week 8 – GIT endoderm is a tube once more Ie: process is recanalisation – hollow solid hollow • Abnormalities o Can lead to: Duplications – two tubes Stenosis – narrowing of tubes Atresia – blockage of tubes Liver • Arises at the embryonic junction o Externally: where the ectoderm of the amnion meets the endoderm of the yolk sac o Internally: where the foregut meets the midgut o At the septum transversum – mesenchymal structure Provides support where blood vessels and liver begin to form • Liver bud o Derived from the endoderm o Differentiates to form the hepatic diverticulum which gives rise to ramifying hepatic primordium cells (hepatoblasts) Hepatoblasts form hepatocytes and biliary cells Diverticulum generates the gall bladder and then divides into right and left hepatic buds o 3 connecting stalks: cystic duct, 2 hepatic ducts Fuse to form the bile duct Reflects the liver’s exocrine functions • Hepatic buds o Left hepatic bud gives rise to: left lobe, quadrate lobe and caudate lobe of liver (anatomically left) o Right hepatic bud gives rise to the right lobe o Made up of hepatocytes Produce bile from week 13 that accumulates in the hindgut • Forms the meconium of the newborn o Ie: the first stool which is made up of liver produce and debris from swallowing amniotic fluid • Liver is richly vascularised o An important site of hemopoiesis in the embryo Initially, yolk sac acts as primary site before stem cells migrate to the liver and then finally to the bone marrow o Majority of hemopoiesis is in fetal RBC formation • Other structural origins o Vitelline veins form Sinusoids – small blood vessels with a discontinuous endothelium o Mesenchyme forms Connective tissue Kupffer cells – specialised liver macrophages Stomach • Foregut tube begins to dilate forming an enlarged lumen – week 4 • Dorsal border grows more rapidly than ventral o Establishes curvature of the stomach (1 st rotation) • 2nd rotation – in the longitudinal axis 90 degrees o Liver (ventral mesentery) and spleen (dorsal mesentery) are attached to mesentery and thus rotate with stomach • Dorsal mesentery grows and hangs down as an apron-like fold: the greater omentum • Embryonic mesogastrium Pancreas • Arises from 2 sources: o Hepatic diverticulum (ventral) o Duodenum (dorsal) • Differentiates into specific cells for endocrine (hepatic) and exocrine (duodenal) functions • Fusion arises from rotation • Abnormalities o Dorsal pancreatic bud loses the duodenal duct, 10% of the population retain it and have a dual duct system Spleen • Arises within the dorsal mesogastrium as proliferating mesenchyme – week 5 • Hemopoietic function o Stem cells arise from the yolk sac wall o Generates red and white cells in the 2 nd trimester Midgut • Midgut herniation o The developing kidney and liver take up the abdominal space and so the developing midgut is forced outside the abdomen into the umbilicus o This herniation remains until week 11 of development • Rotation occurs as part of the elongation of the GIT o This allows correct placement of the gut with its mesentery (dorsomesogastrium) in the abdominal cavity o Midgut is connected by the dorsal mesentry to the body surface – attached to the posterior body wall Thus the vascular and nerve supply is maintained • Particularly important is the mesenteric artery thus rotation occurs around its axis to prevent occlusion Hindgut • Cloaca development o Begins as a common urogenital sinus o A septum bifurcates the sinus into urinary and rectal components Blood supply • Covers the entire surface of the yolk sac o Connects to the embryo through the yolk stalk • Arteries o Arise from the dorsal aorta o Contribute to adult GIT arteries • Veins o Empty into sinus venosus o Contribute to the adult portal system • Arteries define areas of the gut: o Celiac artery – foregut o Superior mesenteric artery – midgut o Inferior mesenteric artery – hindgut Mesentery • Common dorsal mesentery generates the mesenteries of the GIT o Thus, gut is attached to the dorsal body wall, not the ventral o Embryonically, dorsal mesentery is made up of two folds, these fuse to form the greater omentum Hangs down infront of the midgut like an apron carrying vascular and nerve supply • Ventral mesentery o Remains at the level of the liver o Contributes to the lesser omentum and the falciform ligament Abnormalities • Impact on the GIT lumen • Atresia – interruption of the lumen o Oesophageal, duodenal, extrahepatic-biliary, anorectal • Stenosis – narrowing of the lumen o Duodenal, pyloric • Failure of the midgut to return to the body cavity Lecture 2: Nutritional requirements for normal growth and development Jennifer Cohen Definitions • Infant – young offspring of humans • Neonate – newborn, less than a month old • Toddler – 12-36 months, beginning to walk • Child – human between the ages of birth and puberty Growth • Expected growth o Infants Average birth weight 3.5kg • Initial weight loss of up to 10% body weight in first 5-7 days, regained by day 10-14 Average weight increases over the next 12 months • Months 0-3: 200g/week; months 3-6: 150g/week; months 6-9: 100g/week; months 9-12: 50-75g/week • Overall weight triples in the first 12 months Length increases by 25cm o Toddler 2nd year of life, gain of 2.5kg weight and 12cm length • Growth slows down and nutritional requirements decrease Average growth rate from this point onwards continues steadily at 2kg/year and 10cm/year and declines with age to 6cm/year until puberty o Puberty – growth spurt Occurs at 10-11 years in girls, 12-13 years in boys Measuring growth • Standards o Height Children <24 months measure length Children 24-36 months measure either length or height depending on behaviour of child Children >36 months measure height Length can be inaccurate because babies don’t like being measured and don’t sit still o Weight Bare weight, 0-12 Light clothing, no shoes for older children o Head circumference Measured until 2 years Tape placed over the supraorbital ridges and over