Embryology: Gastrointestinal o Formation of Gut Tube Incorporation of yolk sac (endoderm) during body folding Gut tube extends form oropharyngeal membrane to cloacal membrane Divisions Foregut Midgut Hindgut o Histology of GI Tube (adult) Sources of GI Tube Endoderm o Epithelium o Glands Splanchnic mesoderm o Smooth muscle Circular Longitudinal o Vessels o Adventitia (Connective Tissue) o Visceral layer of peritoneum Neural Crest o Autonomic innervation Sympathetic Postganglionic fibers o Contained in pre-vertebral ganglia (ex. Celiac) Parasympathetic Preganglionic fibers o Mostly from Vagus (CN X) Ganglia o Postganglionic neurons o Organization of GI Tract Foregut Midgut Hindgut Arteries Celiac Trunk Superior Mesenteric A. Inferior Mesenteric A. Veins Splenic V. + Superior Mesenteric V. Inferior Mesenteric V. Lymphatics Parasympathetics Sympathetics Mesenteries Celiac Nodes Superior Mesenteric Nodes Inferior Mesenteric Nodes Vagus N. Vagus N. Pelvic Splanchnics nn. Celiac Ganglion Superior Mesenteric Ganglion Inferior Mesenteric Ganglion Ventral (falciform lig., lesser omentum) & Dorsal (mesentery, Dorsal (greater transverse mesocolon) omentum, gastrolienal, lienorenal) Dorsal (sigmoid mesocolon) Mesenteries o GI tube (caudal foregut thru hindgut) is initially suspended by a dorsal mesentery (double layer of peritoneum) Connects the splanchnic and parietal layers of the lateral plate mesoderm o Mesenteries conduct vessels and nerves to and from tract o Dorsal Mesentery Divisions Dorsal mesogastrium (greater omentum) Dorsal mesoduodenum Mesentery proper Dorsal mesocolon o Abdominal portion of foregut has a ventral mesentery Formed by septum transversum Growth of liver separates it into Falciform ligament Lesser omentum Foregut o Stomach Stomach appears as a dilation in the foregut just caudal to the diaphragm Dorsal side expands more than ventral side Dorsal side = greater curvature Ventral side = lesser curvature Stomach rotates 90 degrees clockwise along longitudinal axis Left side of stomach faces anteriorly o CN X follows this rotation Left vagus becomes anterior vagal trunk o Stomach also rotates along its anteroposterior axis so that the cardiac region lies on the left and the pyloric region on right Dorsal mesogastrium With longitudinal foregut rotation, dorsal mesogastrium shifts to the left and creates a space o Omental bursa (lesser peritoneal sac) Spleen o Forms from mesoderm and is populated mostly by lymphocytes Separates the dorsal mesogastrium into Gastrolienal ligament Lienorenal ligament o Mostly fuses to body wall With Anteroposterior foregut rotation the dorsal mesogastrium bulges caudally creating the greater omentum o Redundant fold develops (like an apron) o Fuses with transverse mesocolon o o o o Ventral Mesogastrium Liver grows in septum transversum forming Falciform ligament o Between the anterior body wall and liver Free edge contains the umbilical vein which in the adult turns into the ligamentum teres hepatis Lesser omentum o Between the liver and stomach o Hepatogastric ligament Liver to stomach o Hepatoduodenal ligament Liver to duodenum Free edge contains portal triad Forms roof of epiploic (omental) foramen Entrance into omental bursa (lesser peritoneal sac) Clinical Correlation Pyloric Stenosis Pyloric muscular hypertrophy o Can completely obstruct gastric outlet o Projectile vomiting without bile Duodenum Formed from caudal end of the foregut and the cephalad end of the midgut Point of junction is just distal to liver bud With foregut rotations, forms C-shaped loop Loses its mesentery to become retroperitoneal During 2nd month lumen is obliterated by proliferating epithelium and then recanalized Liver and Gallbladder Ventral diverticulum of the duodenum endoderm forms liver bud which forms: Hepatocytes Bile duct Gallbladder Liver bud penetrates septum transversum (mesoderm), forms: Hepatic sinusoids – intermingle with umbilical and vitelline veins Hematopoietic cells Connective tissue Through foregut rotation, bile duct comes to the left side of duodenum Functions of fetal liver Produce albumin Store glycogen Hematopoiesis (formation of blood cellular components) Produce bile Pancreas Ventral pancreatic bud off bile duct Forms uncinate process Dorsal pancreatic bud off duodenum Forms head, body, & tail Two buds unite during foregut rotation Ventral duct and distal dorsal duct from main pancreatic duct Dorsal duct may persist as accessory pancreatic duct o Pancreas becomes retroperitoneal with duodenum Both exocrine and endocrine pancreas (islets of langerhans) derive from endoderm Clinical Correlation GI Atresia/Stenosis Most often in esophagus & duodenum o Many others due to vascular accidents Annular pancreas Ventral pancreatic bud may split and surround duodenum May result in duodenal stenosis Midgut o Yolk sac remains connected to midgut loop by vitelline duct o Midgut elongates rapidly, forming the primary intestinal loop Cephalic limb will form the duodenum, jejunum and proximal 2/5 of ileum Caudal limb will form distal 3/5 of the ileum, cecum, ascending colon, and proximal 2/3 of the transverse colon Vitelline duct remains connected at apex of the loop o Loop herniates into umbilical cord during the 6th week o o o o Midgut Rotation 270 degree counterclockwise Around superior mesenteric artery First 90 degrees when loop herniated into umbilical cord Cephalic limb on right Caudal limb on left Remaining 180 degrees when the loop returns to the abdomen Cephalic limb enters first and goes to the left Caudal limb enters last and goes to the right Cecum descends into right iliac fossa Appendix develops during this descent Mesenteries Mesentery proper is twisted in midgut rotation Ascending and descending colon are pushed against posterior abdominal wall and lose their mesenteries Transverse mesocolon fuses with greater omentum Clinical Correlation Omphalocele Failure of the midgut loop to return from umbilical cord herniation o Associated with other defects (heart, neural tube) o Gut Rotation Defects Partial or reversed midgut rotations May cause obstruction volvulus Meckle’s Diverticulum Persistent vitelline duct Hindgut o Develops into the distal 1/3 of transverse colon, descending colon, sigmoid colon, rectum and upper part of the anal canal o Terminal hindgut enters the cloaca o Urorectal septum separates cloaca into anorectal canal and the urogenital sinus o Cloacal membrane (proctodeum) breaks down o Upper 2/3 of anal canal from hindgut, lower 1/3 from ectoderm – line of union is the pectinate line o Embryology: Urogenital system o Kidneys Develop from intermediate mesoderm Amniotic fluid comes from embryonic kidneys o o 3 phases of development (cranial to caudal) Pronephros o Never functional Mesonephros o Briefly functional Metanephros o Definitive kidney Mesonephric Kidney Upper thoracic through upper lumbar region Structure Excretory tubule (~35 pair) o Associates with dorsal aorta Renal corpuscle o Presumptive urine (plasma) o Glomerulus Tuft of capillaries o Bowman’s capsule Mesonephric duct o Collecting duct, leads to cloaca Functional between 6-10 weeks With developing gonad, forms the urogenital ridge Paramesonephric duct develops Parallels mesonephric duct o Important in genital duct development Metanephric Kidney Becomes adult kidney Develops in a similar manner to the mesonephric kidney Collecting system Ureteric bud o Outgrowth of the mesonephric duct near cloaca o Penetrates metanephric tissue o Forms Renal pelvis Major/minor calyces Collecting tubules o Ureteric bud will become the ureter o Each collecting tubule covered by metanephric cap, forms renal vesicles Nephron Renal vesicle o Bowman’s capsule o Proximal convoluted tubule o Loop of Henle o Distal convoluted tubule Glomerulus ~1 million nephrons form until birth, none after o Kidneys ascend to their final position and receive arteries from the aorta at successively higher levels Functional at ~12th week Urine contributes to amniotic fluid Clinical correlation Renal agenesis o “Lack of origin” o Unilateral Birth with only one kidney o Bilateral Birth without kidneys Fatal within minutes to hours w/o treatment Pelvic kidney o Failure of kidney to ascend to normal position o Increased incidence of ureteric obstruction Horseshoe kidney o Kidneys fuse at inferior pole o Failure to ascend Bladder and Urethra Come from endoderm around cloaca Cloaca divided into urogenital sinus and anorectal canal by the urorectal septum Urogenital sinus can be divided into Urinary bladder o Continuous with the allantois (urachus, median umbilical ligament) Pelvic part o Prostatic & membranous urethra Phallic part o Penile urethra Caudal part of mesonephric ducts (intermediate mesoderm) absorbed into the urogenital sinus resulting in separate openings for the ureter and genital duct o o Ducts switch positions Trigone of bladder forms from absorbed mesonephric duct tissue, later overgrown by endodermally – derived bladder epithelium Gonads (intermediate mesoderm) Genital ridges form by proliferation of mesodermal epithelium near the mesonephric kidneys Germ cells (1000-2000)arise from endoderm in yolk sac, migrate to the genital ridges forming primitive sex cords Germ cells surrounded by support cells from genital ridge epithelium (intermediate mesoderm) “Intermediate mesoderm creates a home for the germ cells to live” Testis XY genotype leads to production of testis-determining factor (SRY [Sex – region of Y chromosome] gene product) from support cells Primary sex cords proliferate, form testis cords Composed of germ calls (pre-spermatogonia) + support cells (preSertoli cells) These remain solid until puberty where they then transform into seminiferous tubules, the site of sperm production o Connects to mesonephric tubule and these connections become efferent ductules Testis cords in the hilum form tubules celled rete testis Dense connective tissue covering (tunica albuginea) forms around testis Leydig cells form from mesenchyme of the genital ridge, start to produce androgens in 8th week which will affect the development of the ducts and genitalia. The fetal Leydig cells involute in weeks 17-18. Reappear at puberty. o o Ovary XX sex chromosome – absence of testis-determining factor Primary sex cords degenerate in the medulla of the ovary Surface epithelium (support cells) of the ovary proliferates forming follicular cells Follicular cells surround germ cells (oogonia) to form primordial follicles Follicles remain close to the surface of the ovary Oogonia proliferate by mitosis (up to the 4th month) then enter prophase of the 1st meiotic division where they stay until recruited for ovulation after puberty (now called primary oocytes) ~6-7 million at peak, ~1-2 million at birth, ~400,000 at puberty, ~400 ovulate Thecal cells (produce estrogens) form from mesenchyme of genital ridge Male genital ductus Rete testis establishes contact with remaining mesonephric tubules which form the efferent ductules Mesonephric duct will form Epididymis Ductus (vas) deferens Seminal vesicles Ejaculatory ducts Under the influence of Mullerian Inhibiting Substance (MIS) from support cells, the paramesonephric ducts degenerate, except for o o o Appendix testis Prostatic utricle Prostate gland develops from urogenital sinus (endoderm) Female genital ducts Cranial opening of the paramesonephric ducts comes to lie close to the ovary – form the uterine tube Caudally, the two paramesonephric move medially forming the broad ligament then fuse to form the uterine canal Mesonephric ducts degenerate except for Epoophoron Paroophoron Gartner’s cysts Vagina Sinovaginal bulb grows out of urogenital sinus and fuses with the fused paramesonephric ducts (uterine canal) Later canalizes to form most of the vagina Upper part of the vagina and the vaginal fornices form from the paramesonephric ducts The lumen of the vagina closed by a thin membrane, the hymen External genitalia Indifferent stage Mesenchyme around cloacal membrane forms cloacal folds o Urethral folds o o Anal folds Urethral folds unite cranially to form genital tubercle Second pair of elevations form genital swellings Male – stimulate by androgens Genital tubercle elongates to form phallus o Urethral folds fuse to form the penile urethra Genital swellings fuse to form the scrotum Female – stimulate by estrogens Genital tubercle form clitoris Urethral folds form labia minora Genital swellings form labia majora Clinical correlation Hypospadias (males) o Failure of urethral folds to fuse fully Summary of Homologous Structures Male Female Testis Ovary Spermatogonia Oogonia Support Cells Sertoli cells Follicular Cells Mesenchymal Cells Leydig Cells Thecal Cells Semiferous Tubules __ __ Primordial Follicles Gonads Germ Cells Medulla Cortex Genital Ducts Mesonephric Ducts (& tubules) Efferent Ductules, Epididymis, Ductus Degenerate (ex., Deferens, Ejaculatory Duct, Epoophoron, Paraoophoron) Seminal Vesicles Degenerate (ex., Appendix Testis, Prostatic Utricle) Uterine Tube, Uterus, Upper Vagina Prostate, Membranous & Prostatic Urethra Urethra, Lower Vagina Penile Urethra Labia Minora Genital Tubercle Penis Clitoris Genital Swellings Scrotum Labia Majora Paramesonephric Ducts External Genitalia Urogenital Sinus Urethral Folds o Descent of Testes Gubernaculum testis develops from mesenchyme and extends from testes to scrotal swellings Through differential body growth testes are “pulled” into the scrotal sacs and carry layers from the abdominal wall with them Peritoneum evaginates along the gubernaculum forming the processus vaginalis Proximal part degenerates Distal part forms the tunica vaginalis surrounding the testes in the scrotum Clinical Correlation Congenital Hernia o Patent processus vaginalis allows intestinal loops to herniate o Cysts from processus vaginalis are called hydroceles o o Cryptorchidism o Undescended testis Clinical Correlation Defects in Sex Differentiation Klinefelter Syndrome – 47 chromosomes, XXY o Male phenotype o Infertility, gynecomastia, impaired sexual maturation Pseudohermaphroditism – 46 chromosomes, XX or XY o Male or female o Genotype masked by external phenotype due to disturbance of normal sex steroid production Testicular feminization – 46 chromosomes, XY o Defect in androgen receptors o Female external phenotype o Uterus and upper vagina absent (due to MIS secretion) o