DIGESTIVE SYSTEM II • Microscopic anatomy of pharynx, esophagus, stomach, small and large intestine, rectum • Early embryonic development of GIT Petr Vaňhara Department of Histology and Embryology LF MU pvanhara@med.muni.cz ALIMENTARY CANAL General architecture of hollow organs General architecture of hollow organs incl. gut tube 1. Mucosa (Tunica mucosa) 2. Submucosa (Tela submucosa) 3. Tunica muscularis externa 4. Serosa/adventitia Donna Myers © 2007 Lumen Serosa/Adventitia Muscularis externa Submucosa Mucosa Four layers Lumen 1 2 3 4 GENERAL ARCHITECTURE OF HOLLOW ORGANS GENERAL ARCHITECTURE OF HOLLOW ORGANS GENERAL ARCHITECTURE OF HOLLOW ORGANS Mucosa (Tunica mucosa) - inner layer of gut tube - protective, absorption and resorption - microscopic structure depending on localization - Lamina epithelialis mucosae - Lamina propria mucosae - Lamina muscularis mucosae GENERAL ARCHITECTURE OF HOLLOW ORGANS - Lamina epithelialis mucosae - epithelium type corresponding to function of gut tube - oral cavity, pharynx, esophagus, anus – stratified squamous ep. - stomach, intestine – simple columnar - mucus - secreted by mucosal or submucosal glands (oral cavity, esophagus), secretory epithelium (stomach) or goblet cells (intestine) - Lamina propria mucosae - Layer of mucosal connective tissue – loose collagen - Fenestrated blood capillaries – transport of metabolite (intestine) - mucosal glands in some regions /esophagus) - innervations, immune system - Lamina muscularis mucosae - smooth muscles in two layers (inner circular, outer longitudinal) - small mechanical movements of mucosa facilitating secretion and absorption independently on peristaltic movements. Mucosa (Tunica mucosa) GENERAL ARCHITECTURE OF HOLLOW ORGANS Submucosa (Tela submucosa) Submucosal connective tissue - distinct layer of loose connective tissue - defines shape of mucosa (rugae, plicae) - larger blood and lymph veins nourishing mucosa, t. muscularis externa and t. serosa - innervation – nerve plexus - plexus submucosus Meissneri = groups of multipolar neurons and small ganglions, visceral sensory fibers (sympaticus) and fibers and terminal ganglions of parasympaticus (enteric nerve system) - glands - different in different regions - protective function GENERAL ARCHITECTURE OF HOLLOW ORGANS Outer muscular layers (Tunica muscularis externa) - Two concentric, thick layers of smooth muscle, separated by thin layer of connective tissue - Inner – circular, outer – longitudinal (spiral) - Myenteric (Auerbach) plexus - Peristaltic – passage through the gut tube - Local modifications of m.e. - pharyngoesophagal sphincter + external anal sphincter – skeletal muscles - stomach – third - oblique - layer - taenie coli – thickened part of longitudinal layer in colon Circular Longitudinal GENERAL ARCHITECTURE OF HOLLOW ORGANS Serosa/Adventitia (Tunica serosa/adventitia) - outermost layer of gut tube - Serosa - serous membrane of loose connective tissue (Lamina propria serosae) and single layer squamous epithelium (L. epithelialis serosae) - syn. mesothelium, visceral peritoneum - continuous with mesenterium - barrier against various pathogens , antiadhesive properties – intracoelomic movements, immune functions (Ag presentation), ECM production, etc. - Adventitia - some parts of the tube are not covered with epithelium - esophagus in thorax, parts of digestive system in peritoneal cavity in sites of fixation to the walls (duodenum, part of colon, rectum, anal canal) - connective tissue only continuous with connective tissue of the walls GENERAL ARCHITECTURE OF HOLLOW ORGANS S.E. Mutsaers / The International Journal of Biochemistry & Cell Biology 36 (2004) 9–16 Serosa/Adventitia (Tunica serosa/adventitia) 1.4m GENERAL ARCHITECTURE OF HOLLOW ORGANS Innervation of the digestive tube Enteric nervous system - self-contained nervous system - numerous ganglia, 100 x106 neurons (more than in spinal cord) - Meissner submucosal plexus and Auerbach myenteric plexus - peristaltic motility, secretory function, mucosal movements, regulation of blood flow - sensory components Parasympathetic and sympathetic supply • parasympathetic supply mostly by vagus nerve (cranial X), colon and rectum by sacral spinal nerves - vagus nerve – mostly sensory fibers (from mucosa) - secretion from glands, smooth muscle contractions - inhibits sphincters, stimulates peristaltics and secretion • sympathetic supply by splanchnic nerves - vasomotor fibers – control of blood flow - activates sphincters, inhibits peristaltics and secretion GENERAL ARCHITECTURE OF HOLLOW ORGANS - pars nasalis - pseudostratified columnar ciliated epithelium - seromucous glands - pars oralis et laryngea - nonkeratinized stratified squamous epithelium - mucous glands - collagen c.t. (lamina propria), typical tela submucosa absent - skeletal muscles PHARYNX - Mucosa - nonkeratinized stratified squamous epithelium → mechanically protects esophagal tissue - l. propria contains cardial glands (tubular mucinous) and diffuse lymphatic tissue - Submucosa - loose collagen connective tissue, defines shape of mucosa - blood and lymph veins, plexus submucosus Meissneri - submucosal glands (tubular mucinous) - diffuse lymphatic tissue ESOPHAGUS (OESOPHAGUS) - Muscularis externa - inner circular and outer longitudinal layer - plexus myentericus Auerbachi - upper third – skeletal muscle, mid third – mixed smooth and skeletal, lower third – smooth muscles only - Adventitia - neck and chest – connects esophagus with surrounding tissue - loose connective tissue - in peritoneal cavity - serosa ESOPHAGUS (OESOPHAGUS) Cardia of stomach – connection with esophagus Nonkeratinized stratified squamous epithelium → simple columnar epithelium CARDIO-ESOPHAGEAL JUNCTION - general anatomy of hollow tube - anatomical regions differ also in histologic structure - rugae gastricae (submucosa) STOMACH (VENTRICULUS, GASTER) - Gastric mucosa - simple columnar epithelium - surface epithelium produces mucus (mucinogenic granules, high content of HCO3 -, K+) = protective function - areae gastricae, foveolae gastricae STOMACH (VENTRICULUS, GASTER) - Gastric mucosa - L. propria contains large amount of glands - Gl. cardiacae - Gl. pyloricae - Gl. gastricae propriae STOMACH (VENTRICULUS, GASTER) - Gl. gastricae propriae - glands of fundus and body - simple tubular or branched - 2-4 opens to the gastric pits - four cell types of gl. gastricae propriae STOMACH (VENTRICULUS, GASTER) chief - most abundant, lower part of body and fundus of the gland - pyramidal shape, basophilic cytoplasm, RER, pepsinogenic granules parietal - neck-body junction - eosinophilic cytoplasm, high numbers of mtch., SER - complex and dynamic ultrastructure - intracellular canals in apical part with microvilli – membrane bound enzyme complexes producing H+ a Cl- (HCl originates extracellularly) neck cells - cubic, mucinous - capable of regeneration of all cell types in gastric epithelium Gl. gastricae propriae STOMACH (VENTRICULUS, GASTER) Gl. gastricae propriae Type Hormone Localization/Function D cells Somatostatin - Stomach, intestine, hepatic and pancreatic ducts EC cells Serotonin - Stomach, gallbladder, intestine - Peristaltics ECL cells Histamin - Stomach - HCl secretion G cells Gastrin - Pars pylorica, duodenum - HCl, pepsin secretion L (EG) cells Enteroglucagon - Stomach, intestine - attenuates secretion of pancreatic enzymes and peristaltics (entero)endocrine - minor, secretion - granules - different cell types with different sensitivity to various histological stainings - secretion of various biologically active compounds - DNES/APUD - GIT chemosensing - see spring semester lesson- Epithelial tissue STOMACH (VENTRICULUS, GASTER) http://luminaryvisuals.com/ GASTRIC ACID PRODUCTION AND REGULATION GENERAL ARCHITECTURE OF HOLLOW ORGANS SMALL INTESTINE - DUODENUM GASTRO-DUODENAL JUNCTION Four basic layers: mucosa, submucosa, muscularis externa, serosa mucosa and submucosa maximise the resorptive area • plicae circulares (Kerckringi) – mucosa + submucosa, ca 800, increase 2-3x, distal region of duodenum • villae (villi intestinales) – mucosa (l. propria + epithelium) 0,5-1,5 mm long, 10- 40/mm2 , 4 000 000, increase 5-10x • microvillae – apical part of enterocytes – 1- 2 μm long, 0,1 μm wide, 100 mil./mm2, increase 20x SMALL INTESTINE – ADAPTATION TO EFFICIENT RESORPTION plicae circulares (Kerckringi) – 2-3x villi (villi intestinales) – 5-10x microvilli (striated border) – 20x Simple columnar epithelium - enterocytes - goblet cells - Paneth cells - enteroendocrine cells - M-cells Intestinal mucosa Crypts of Lieberkühn 200-600x SMALL INTESTINE – ADAPTATION TO EFFICIENT RESORPTION - simple tubular structures of intestinal mucosa, depth 0,3-0,5 mm - pass through l. propria and open to lumen - different cell types - secretion of digestive enzymes - epithelial renewal - enteroendocrine cells - immune response CRYPTS OF LIEBERKÜHN (GL. INTESTINALES) Enterocytes - tall, columnar cells - nucleus located in basis of the cell - apical surface modified- microvilli (3000) + glycocalyx (0. 5 m) = striated border (cuticle) - tight intercellular connections, interdigitations Function: - digestion – enzymatic complexes on microvilli membrane - absorption and transport – passive, facilitated i active - lipid uptake - chylomicrons 1m 0,1m CELLS OF INTESTINAL MUCOSA Microvilli CELLS OF INTESTINAL MUCOSA Principles of transport and resorption Transport of glucose from intestinal lumen to blood stream Na+/K+ ATPase - basolateral surface - concentration gradient Na+ and K+ K+ gradient generates negative membrane potential Na+/glucose symport on apical surface Facilitated diffusion by glucose uniporter (GLUT2) in basolateral membrane Acidification of stomach fluid by parietal cells Apical membrane - H+/K+ ATPase + Cl− a K+ canals Basolateral membrane – anion antiporter HCO3 − and Cl− ions Combined activity of ion channels a cells keeps the electroneutrality and neutral cytoplasmic pH while reaching high extracellular concentration of H+ and Cl− in lumen of stomach http://www.ncbi.nlm.nih.gov/books/NBK21502/ CELLS OF INTESTINAL MUCOSA Jádra F-aktin Mucin v sekrečních granulech - Cylindrical glandular epithelial cells - Apical surface – apocrine/merocrine secretion of mucin - Basal part – RER, GA, nucleus, mitochondria - Mucinogenic granules - see spring semester (crash course) lesson on Epithelial tissue Goblet cells CELLS OF INTESTINAL MUCOSA Goblet cells CELLS OF INTESTINAL MUCOSA Paneth cells - basal part of crypts of Lieberkühn - basophilic cytoplasm - GA located above nucleus - acidophilic (red) granules - immune system - secretion granules contain biologically active substances e.g. lysozym) - influence intestinal microflora Enteroendocrine cells - similar to gastric enteroendocrine cells - regulate pancreatic secretions - homeostatic axis (brain-intestine-adipose tissue) - cholecystokinin, secretin, GIP, motilin, neurocrine peptides etc. CELLS OF INTESTINAL MUCOSA M cells (microfold) - epithelial cells above Peyer’s patches and lymphatic nodules - no microvilli - induces immune response - MHCII - antigen presentation to dendritic cells and lymphocytes „Microfold“ CELLS OF INTESTINAL MUCOSA Intestinal stem cells - bottom of crypts of Lieberkühn - epithelial renewal (4-5 days) - stem cell niche - tumour transformation CELLS OF INTESTINAL MUCOSA L. propria - immune system – GALT - abundance of reticular fibers - immunologic barrier - Peyer’s patches CONNECTIVE TISSUE OF INTESTINAL MUCOSA Brunner’s glands - gl. duodenale Brunneri - branched tuboalveolar glands, columnar mucinous cells - alkaline secretion - connective tissue reduced to thin septa between glandular lobules - open to crypts of Lieberkühn CONNECTIVE TISSUE OF INTESTINAL MUCOSA Muscularis externa - two layers of smooth muscle (inner circular, outer longitudinal) - plexus myentericus Auerbachi Serosa - loose collagen connective tissue + simple squamous epithelium (mesothelium) OUTER LAYERS OF INTESTINAL WALLS - general architecture of hollow organs - plicae of Kerckring, villi absent - muscularis externa – longitudinal layer - taenie coli - surface serosa - appendices epiploicae (adipose) Small intestine Colon COLON COLON - absorption of water, electrolytes - deeper crypts of Lieberkühn, no Paneth cells - abundant goblet cells - abundant lymphatic tissue in l. propria (GALT) - absorption of water, electrolytes - deeper crypts of Lieberkühn, no Paneth cells - abundant goblet cells - abundant lymphatic tissue in l. propria (GALT) COLON - develops from and is connected to caecum 8-10 cm (0,5-1cm) - continuous longitudinal layer of m. externa - lymphatic follicles reaching submucosa - irregular crypts of Lieberkühn with Paneth cells APPENDIX RECTUM AND ANAL CANAL - Ampula recti - 10-12cm - plicae transversales recti (3) - histological architecture identical to colon - anorectal junction (linea anorectalis) - Canalis analis - 3 cm - simple columnar e. gradually replaced by stratified squamous e. (pecten analis) - lymphatic tissue - columnae anales - sinus anales – gll. anales - valvulae rectales zona hemorrhoidalis - at anal sinuses and columns - rich venous plexus - zona cutanea – typical skin RECTUM AND ANAL CANAL Organ Region Mucosa Submucosa Muscularis externa Serosa/ AdventitiaLEM LPM LMM Esophagus 1/3 stratified squamous e. full gll. oesophageales skeletal A 2/3 glandulae oesophageae cardiacae both 3/3 smooth S Stomach cardia simple columnar e. gll. cardiacae full three layers oblique, circular, longitudinal S fundus/ corpus gll. gast. prop. gll. pyloricaepylorus Small intestine duodenum simple columnar e. brush border goblet cells L. crypts villi úplná gll. duodenales Brunneri A+S plicae circulares jejunum SPeyer’s plaque ileum Colon and rectum apendix simple columnar e. brush border goblet cells lymph. follicles partial lymph. nodes full S caecum villi absent full taniae coli A+S colon A+S rectum columnae rectales A Canalis analis anorectal/ anocutaneous stratified squamous e. non- keratinized venous plexus partial- absent mucosal folds venous plexus inner anal sfincter A zona cutanea stratified squamous e. keratinized hair follicles, sweat glands Embryonic development EARLY EVENTS IN GIT DEVELOPMENT Four regions according to structural and molecular patterns pharynx – from buccopharyngeal membrane to tracheobronchial diverticle foregut - caudally to liver diverticle midgut - duodenum to proximal 1/3-half of colon transversum hindgut - Distal half-2/3 of colon transversum to cloacal membrane – cephalocaudal flexion – primitive gut (endoderm) – oral cavity and rectum – ectoderm – glandular parenchyma (pancreas, liver) - entoderm of primitive gut - epithelial-mesenchymal interactions - Shh a Hox morphogenetic code PRIMITIVE GUT Derivatives of primitive gut PRIMITIVE GUT VASCULARISATION Four regions according to structural and molecular patterns pharynx – buccopharyngeal membrane – tracheobronchial diverticle foregut - caudally to liver diverticle - t. coeliacus midgut - a. mesenterica sup. hindgut - left third transversal colon to cloacal membrane - a. mesenterica inf. - Esophagus - caudal part of foregut from laryngotracheal diverticle - endoderm (epithelium and glands), c.t. - mesoderm - Stomach -4th week – fusiform dilatation of foregut - symmetric - asymmetric - major and minor curvature - rotation - longitudinal and sagittal axis - definitive localization and morphology about week 8 i.u. - Gut - midgut – duodenal and umbilical loop - rotation - physilogical umbilical hernia EARLY EVENTS IN GIT DEVELOPMENT 1. Differentitation of entoderm, tube formation, A-P patterning - growth and differentiation factors during development - Simple nondifferentiated epithelium 2. Morphogenesis of villi - expansion and condensation of mesenchyme into lumen - proliferationd and paralell differentiation of temporary epithelium to simle columnar epithelium 3. Lieberkühn crypts - intestinal stem cells 4. Mesoderm-endoderm interactions EARLY EVENTS IN GIT DEVELOPMENT https://www.youtube.com/watch?v=cBSyOgjTGVU Microscopic anatomy and development of the gut tube see also the requirements for exam Summary GIT 2 - General architecture of hollow organs and gut tube: mucosa (l. epithelialis m ., l. propria, l. muscularis m.), submucosa, t. muscularis externa, serosa (l. propria s., l. epith. s.), adventitia - Pharynx – structure and microscopic anatomy - Esophagus - structure, epithelium, mucosal and submucosal glands, differences in t. muscularis ext. - Stomach – anatomical and histological structure, mucosa - areae gastricae, foveolae gastricae, gastric glands (pyloricae vs. propriae), localization, ultrastructure and function of gl. gastricae propriae and its cells (chief, parietal, neck, enteroendocrine - Small and large intestine, appendix - anatomical and histological structure, mucosa, glands (crypts of Lieberkühn, Brunner’s glands), cell types of intestinal mucosa, lymphatic system, modifications of intestinal wall - Rectum and anal canal - anatomical and histological structure, mucosa, epithelium, description of associated structures - Early events of GIT development - primitive gut development - specification of morphological structures https://discovery.lifemapsc.com Thank you for attention Questions? Comments? pvanhara@med.muni.cz