MICROSCOPIC ANATOMY + DEVELOPMENT OF GIT liver, pancreas, salivary glands development of GIT Petr Vaňhara, PhD Department of Histology and Embryology LF MU pvanhara@med.muni.cz LIVER AND BILE DUCTS • Liver parenchyma – biggest gland in human body • C.t. capsule • Nutritive and functional blood supply • Endocrine and exocrine function • Uniform histology of all four major anatomic lobules and segments: - Hepatocytes and other cell types - C.t. stroma - Blood and lymphatic vessels - Sinusoids - Innervation - C.t. capsule - Serosa LIVER (HEPAR) CAPSULA FIBROSA HEPATIS − Serous mesothelium − Dense collagen c.t. – collagen and elastic fibers − 70-100m − Porta hepatis LIVER (HEPAR) LIVER (HEPAR) CAPSULA FIBROSA HEPATIS Porta hepatis FUNCTION • capillary stream of stomach and intestine • vena portae • interlobular veins • circumlobular venules NUTRITITION • aorta • arteria hepatica • segmental arteries • interlobular arteries • circumlobular arteriols • hepatic sinusoids • venae centrales hepatis • venae sublobulares • venae hepaticae • vena cava inferior 70% 30% IVC V. hepatica d. m. s. Porta hepatis LIVER VASCULARISATION Gartner, Hiatt: Color Textbook of Histology (2001) LIVER VASCULARISATION MICROSCOPIC SEGMENTATION OF LIVER Definitions: • Histological – liver lobulus (lobulus venae centralis) • Metabolic – liver acinus − metabolic zone 1 – 3 − oxygenation of hepatocytes • Functional unit – lobulus venae interlobularis (portal acinus) wiki MICROSCOPIC SEGMENTATION OF LIVER Liver acinus metabolic divergence dependent on arterio-venous gradients Zone I (periportal) Zone III (perivenous) oxidative processes glycogen synthesis beta-oxidation of fatty acids glycolysis catabolism of aminoacids lipogenesis gluconeogenesis ketogenesis production of urea production of glutamine synthesis of cholesterol synthesis of bile acids glycogenolysis biotransformation production of bile MICROSCOPIC SEGMENTATION OF LIVER Portal acinus bile drainage Liver lobulus venous drainage Lobulus venae centralis LIVER LOBULUS − Classical morphological unit − Polygonal cells (hexagonal), 0.7 x 2mm − Central vein − Radial cords of hepatocytes − Liver sinusoids − Portal triad, portobilliary region LIVER LOBULUS Contact of 3-4 neighboring lobuli • Interlobular artery (a. interlobularis) • Interlobular vein (v. interlobularis) • Interlobular bile duct (d. bilifer interlobularis) • Lymphatic vessels • Innervation – nervus vagus Loose interstitial c.t. LIVER LOBULUS – PORTAL TRIAD Ham: Textbook of Histology LIVER LOBULUS – CENTRAL VEIN AND PORTAL TRIAD LIVER LOBULUS – CENTRAL VEIN AND PORTAL TRIAD LIVER LOBULUS – CENTRAL VEIN • Hepatocytes arranged to cords, width 1-2 cells, often anastomoses • Sinusoids – 9-15m – Anastomosing network of flat endothelial cells – Basal membrane absent - no diffusion barrier – Fenestrations - 100nm, diaphragm absent – Intercellular space – Perisinusoidal space (of Disse) – Reticular fibers – Dispersed Kuppfer cells (monocytemacrophage system) – Perisinusoidal cells of Ito • Vena centralis – thin-walled vessel, draining blood from sinusoids LIVER PARENCHYMA – HEPATOCYTES AND LIVER SINUSOIDS • Space of Disse – Connection of space of Disse and sinusoidal lumen by fenestrated endothelium – Hepatocytes in direct contact with plasma (microvilli) – Cells of Ito LIVER PARENCHYMA – HEPATOCYTES AND LIVER SINUSOIDS LIVER SINUSOIDS https://doi.org/10.3389/fphys.2021.735573 • Fenestrations are complex structures involved in selective transport • They deteriorate with age compromising sinusoid functions LIVER PARENCHYMA – LIVER SINUSOIDS LIVER SINUSOIDS LIVER PARENCHYMA – HEPATOCYTES AND LIVER SINUSOIDS KUPFFER CELLS • Liver macrophages • Mononuclear phagocyte system • Phagocytosis of particles, damaged erythrocytes and pathogens LIVER PARENCHYMA – OTHER CELL TYPES LIVER PARENCHYMA – HEPATOCYTES AND LIVER SINUSOIDS CELLS OF ITO • Star-shape (stellate, perisinusoidal) cells • Lipid droplets • Deposition of vitamin A • Fine reticular c.t. • Antigen presenting cells (lipid antigens) LIVER PARENCHYMA – OTHER CELL TYPES • Polygonal cells of liver parenchyma • 20x30m • Irregular trabecules between sinusoids • Usually one central nucleus. Bi- and multinuclear cells common (20%) • Nucleoli • Lysosomes • Glycogen • Functional surfaces: – Bile pole – secretory – membranes of neighboring hepatocytes form bile canaliculli – Blood pole - absorptive - sinusoidal – microvilli oriented to space of Disse – Membranes with intercellular junctions HEPATOCYTES – ULTRASTRUCTURE HEPATOCYTES BILIARY AND BLOOD POLES OF HEPATOCYTE HEPATOCYTES – ULTRASTRUCTURE • Long mitochondria with flat or tubular cristae • Apparent RER, SER and Golgi • Glycogen, lipid droplets, lysosomes, peroxisomes HEPATOCYTES – ULTRASTRUCTURE Erythrocyte Tight junctionBile canaliculus Kupfer cells Cells of Ito Nucleus Space of Dissé From plasma: Glucose, aminoacids, bile acids Blood proteins (serum albumin, fibrinogen, prothrombin, complement, transferrin, etc.) Space of Dissé HEPATOCYTES – ULTRASTRUCTURE • Synthesis and metabolism − Proteosynthesis – RER + Golgi (plasma proteins – albumins, prothrombin, fibrinogen) − Metabolisms of lipids – SER, peroxisomes (lipidic conversion of fatty acids and glucose, lipoprotein synthesis) − Metabolism of glucose and saccharides - synthesis of glycogen, glycogenolysis and gluconeogenesis (insulin / glucagon) HEPATOCYTES – FUNCTIONS • Detoxication: SER (steroids, barbiturates, polyaromatic, lipid soluble compounds, etc., endo- and exotoxins) • ROS • Peribilliary located lysosomes (autophagy, degradation of endocyted molecules) • Metabolism and deposition of vitamins and trace elements • Bile production: • Recycling of bile acids (90%), 10% de novo synthesis, conjugation of toxic bilirubin and glukuronic acid to nontoxic complex bilirubin-glucuronid • SER HEPATOCYTES – FUNCTIONS Bile acids Bilirubin Steroids Drugs K+ Tight junction Bile canaliculus Cholestasis Biotransformation and conjugation HEPATOCYTES – FUNCTIONS ENTEROHEPATIC CIRCULATION HEPATOCYTES – FUNCTIONS − Resorption in terminal ileum − Vena portae − Sinusoids Hepatocytes − Bile canaliculli − Intra and extrahepatic ducts − Duodenum Blood pole Bile pole ENTEROHEPATIC CIRCULATION HEPATOCYTES – FUNCTIONS Billiary canaliculli - intercellular space between hepatocytes - 1-2m - no true wall, formed by membranes of hepatocytes - intercellular junctions Canals of Herring - simple squamous epithelium Interlobular bile ducts - cholangiocytes - cubic or low columnar epithelium + c.t. Lobar bile ducts - ductus hepaticus dexter et sinister - high simple columnar epithelium Ductus hepaticus, ductus cysticus, ductus choledochus - mucosa - fibromuscular layer INTRAHEPATIC EXTRAHEPATIC BILE DUCTS INTRAHEPATIC BILE DUCTS http://alexandria.healthlibrary.ca/documents/notes/bom/unit_4/unit%204%202005/L- 39%202008%20%20histology%20of%20the%20pancreas.xml INTRAHEPATIC BILE DUCTS INTRAHEPATIC BILE DUCTS INTRAHEPATIC BILE DUCTS Central vein Circulobular venule Portal arteriole Interlobular bile ducts Canals of Hering Bile canaliculli HEPATOCYTESCHOLANGIOCYTES INTRAHEPATIC BILE DUCTS Žlučový kanálek Mucosa - lateral folds - simple columnar epithelium (cholangiocytes) - mucinous glands in c.t., goblet cells Fibromuscular layer - dense network of collagen and elastic fibers - leiomyocytes d. hepaticus communis + d. cysticus → d. choledochus papilla duodeni major m. sphincter ampullae hepatoduodenalis (sphincter of Oddi) Bile modification EXTRAHEPATIC BILE DUCTS - Wall 1-2mm - Mucous coat - Muscle layer - Serosa/adventitia Mucosa - mucosal folds - 20-50m simple columnar epithelium with microvilli - intercellular junctions - lamina propria mucosae - loose collagen c.t. with mucinous tuboalveolar glands - lamina muscularis mucosae absent Muscular layer (Muscularis propria) - 3D network of smooth muscle cells, - elastic fibers Large layer of serous c.t. (l. propria serosae) GALL BLADDER (VESICA FELLEA) BILE CONCENTRATION - Bile secretion by liver– ca 0,8-1l daily - Gall bladder volume 15-60 ml - Water resorption GALL BLADDER (VESICA FELLEA) GALL BLADDER (VESICA FELLEA) GALL BLADDER (VESICA FELLEA) mucosa Muscularis propria serosa GALL BLADDER (VESICA FELLEA) GALL BLADDER (VESICA FELLEA) PANCREAS • Compound, serous, tuboalveolar gland • Exocrine and endocrine character – pancreatic acinus – Islets of Langerhans • Major duct (Wirsungi) opens to Vater papilla as a common bile and pancreatic duct • Dense collagen c.t. capsule • Septs – blood cells, innervation, and interlobular ducts PANCREAS PANCREAS • Pyramidal epithelial cells • Pancreatic digestive enzymes • Intercalated ducts • Serous acinar cells – Polarized secretory cells – Basophilic – Apex – Golgi and zymogenic granules – Microvilli – Intercellular junctions • Centroacinar cells – Centrally located nucleus, squamous character – Continuous with intercalated ducts PANCREAS – PANCREATIC ACINUS PANCREAS – PANCREATIC ACINUS PANCREAS – PANCREATIC ACINUS PANCREAS – PANCREATIC ACINUS • Centroacinar cells • Intercalated ducts – simple squamous epithelium + basal membrane • Intralobular and interlobular ducts – simple cubic – low columnar epithelium • Major pancreatic ducts – D. pancreaticus major – Wirsungi and D. pancreaticus accessorius - Santorini – bilayered columnar epithelium and dense collagen c.t. – intramural mucinous tubular glands, goblet cells, EC cells PANCREAS – PANCREATIC DUCTS • ca 1000-2000 ml daily • alkalic pH (8.8), HCO3 - (intercalated duct epithelium) • mucin (epithelium of large ducts) • Hydrolases – Trypsinogen – Chymotrypsinogen – Proelastases – Carboxypeptidases – Pancreatic lipase – Amylases – … Hormonal regulation (secretin, cholecystokinin) + parasympaticus PANCREAS – EXOCRINE FUNCTION Glucagon ▪ Glycogen consumption in tissues and muscles ▪ Increase of blood glucose Insulin ▪ Increase of membrane permeability for glucose ▪ Glucose oxidation in tissues ▪ Decrease of blood glucose ▪ Synthesis of glucan in muscles and liver Somatostatin ▪ Inhibition of GIT hormones Pancreatic polypeptide ▪ Autoregulation of pancreatic secretion PANCREAS – ENDOCRINE FUNCTION • Clusters of pale cells • ca 1,5  106 • Thin c.t. capsule • Cords of epithelial cells • No ducts • Sinusoids • General characteristics of APUD cells • A, B, D, PP cells A cells: 20%, glucagon B cells: 60-70%, insulin D cells: minor, somatostatin PP cells: minor, pancreatic polypeptide PANCREAS – ISLETS OF LANGERHANS PANCREAS – ISLETS OF LANGERHANS BRIEF HISTORY OF DIABETES TREATMENT Frederick M. Allen „starvation diet“ 1921 DM (I) • Cachexy • Vision loss • Limb loss • Diabetic coma • Renal failure • Cardiac failure • Death BRIEF HISTORY OF DIABETES TREATMENT 11th of January 1922, 14 year old Leonard Thompson became the first person in the world with autoimmune diabetes (type 1 diabetes) to receive insulin, isolated (“discovered”) by Frederick Banting and Charles Best 27th of July 1921 (the exact date is debated). Leonard was believed to have had the disease ~3 years when his father approved the experimental trial, and had only a few days left when he was drifting in and out of diabetic coma due to his high glucose and ketoacidosis (1). Within the first 24 hours improvement was seen, but they failed. Twelve days later, the 23d of January, the team (now including biochemist James Collip) resumed the administration of the extract and finally they were was successful. Remarkable progresses was seen and Leonard left the clinic in the Spring 1922, and lived 13 more years but passed away at age 27, eventually of pneumonia http://www.diabethics.com/science/99-years-since-first-patient-received-insulin/ F.G. Banting, C. Best a Pes 408 1922 1923 BRIEF HISTORY OF DIABETES TREATMENT BRIEF HISTORY OF DIABETES TREATMENT Timeline indicating key genetic discoveries in the context of our understanding of the hormone insulin and its use therapeutically. BRIEF HISTORY OF DIABETES TREATMENT • small (gll. labiales, buccales, retromolares, palatinae, gll. lingualis anterior, gll. Ebneri, gll. Weberi) • large (gl. parotis, gl. submandibularis, gl. sublingualis) SALIVARY GLANDS Tuboalveolar salivary galnds Secretory units • Serous acini • Serous demilunes • Mucous tubules Ducts • Intercalated – striated – interlobular - main Mucous tubules Serous demilunes Serous acini Striated duct Main duct LARGE SALIVARY GLANDS GL. PAROTIS GL. PAROTIS SALIVARY GLANDS – GL. PAROTIS SALIVARY GLANDS – GL. PAROTIS GL. PAROTIS – STRIATED DUCTS SALIVARY GLANDS – GL. SUBMANDIBULARIS GL. SUBMANDIBULARIS – DEMILUNES OF GIANUZZI SALIVARY GLANDS – GL. SUBLINGUALIS DEVELOPMENT OF GIT DEVELOPMENT OF FACE DEVELOPMENT OF FACE stomodeum nasal placode stomodeum 2nd pharyngeal arch processus maxillares processus mandibularis 2nd pharyngeal arch DEVELOPMENT OF FACE DEVELOPMENT OF FACE 4th week DEVELOPMENT OF FACE • nasal pits surrrounded by paired prominences – medial and lateral nasal prominence • area triangularis (nose) • intermaxilary segment (medial part of upper lip, part of upper jaw, primary palate) DEVELOPMENT OF FACE • maxillary prominences fuse with 1. intermaxillary segment 2. lateral nasal prominences • sulcus nasolacrimalis DEVELOPMENT OF FACE DEVELOPMENT OF FACE - PALATE • primary palate (intermaxillary segment) • secondary palate (lateral palate shelves) DEVELOPMENT OF FACE - PALATE DEVELOPMENT OF TONGUE Pharyngeal arches: I. tuberculum linguale laterale (dx. wt sin.) (paired) and tuberculum impar → apex and corpus III and IV. copula and eminentia hypobranchialis → radix DEVELOPMENT OF VESTIBULUM ORIS Vestibular lamina • Dental lamina • Labiogingival lamina 1. Mandible 2. Dental lamina 3. Dental papilla 4. Enamel organ 5. Labiogingival lamina 6. Meckel's cartilage 7. Oral epithelium 8. Tongue http://www.chronolab.com/atlas/embryo/histo_head.htm 1. Eye 2. Mandibular bone 3. Maxillary bone 4. Nasal cavity 5. Nasal septum 6. Oral cavity 7. Palatine process 8. Tongue • Nasal canals – primitive choans • Nasal septum – from area triangularis – fusing with secondary palate DEVELOPMENT OF VESTIBULUM NASI DEVELOPMENT OF TOOTH Interactions of ectoderm and mesenchyme • primary dental lamina – teeth primordia • Inititation stage • tooth bud (primordium) • cap stage • bell stage (enamel organ, ectoderm), dental pulp (mesenchyme) DEVELOPMENT OF TOOTH • bell stage – enamel, differentiation of odontoblasts from cells of dental pulp • enamel prisms and dentin matrix • dental sac DEVELOPMENT OF TOOTH • enamel organ (inner and outer ambelobalsts, stratum intermedium stellate reticulum - pulp) – prisms • odontoblast differentiation - dentin matrix, (processes of odontoblasts = Tomes fibers) DEVELOPMENT OF TOOTH root development – tooth eruption cervical loop → Hertwig epithelial root sheath DEVELOPMENT OF TOOTH DEVELOPMENT OF TOOTH ABNORMALITIES OF FACE DEVELOPMENT - CLEFTS • upper lip (cheiloschisis) – lateral (uni, bi), medial • lower lip – medial, always combined (jaw, tongue) – gnathoschisis et cheiloschisis inf. • oblique cleft (fissura orbitofacialis) • transferse cleft (fissura transversa) Soft tissue clefts ABNORMALITIES OF FACE DEVELOPMENT - CLEFTS • upper jaw - between 2nd incisor and canine - unilateral or bilateral - always combined with palate cleft (cheilognathoschisis) • palate (palatoschisis) - primary (before foramen incisivum) - secondary (behind foramen incisivum) • combined: cheilognathopalatoschisis Hard tissue clefts http://www.youtube.com/watch?v=agmSH8_mLz0 ABNORMALITIES OF FACE DEVELOPMENT - CLEFTS PHARYNGEAL APPARATUS PHARYNGEAL APPARATUS PHARYNGEAL APPARATUS PHARYNGEAL APPARATUS Derivatives • Face including soft tissues • Mimic and mastication muscles • Tongue • Outer and middle ear • Hyoid bone • Laryngeal cartilages • Thymus • Parathyroid glands • Fossa tonsillaris (→ t. palatina) • Large arteries (for details see the lesson on cardiovascular systém development) PHARYNGEAL APPARATUS PHARYNGEAL APPARATUS Derivativeof ectodermalridge Pharyngealarch Aorticarch Cranialnerve Exampleof branchiomeric muscles Skeletal derivatives Derivativeof endodermal pouch 1. external acoustic meatus 1 mandibular a. maxillaris V. trigeminus mastica- tory incus, maleus lig. sphenomandib. Meckel cartilage middle ear cavity, tuba auditiva 2-4. disappear 2 hyoid a. stapedia a. hyoidea VII. facialis mimic stapes proc. styloideus, hyoid cartilage. fossa tonsillaris 3 a. carotis interna IX. glosso- pharyngeus m. stylopha- ryngeus hyoid cartilage thymus, parathyroid bodies (inf.) 4 a. subclavia dx. a. arcus aortae X. vagus svaly faryngu a laryngu laryngeal cartilages parathyroid bodies (sup.) EARLY EVENTS – FROM 2TH TO 3RD WEEK EARLY EVENTS – FROM 3RD TO 4THWEEK EARLY EVENTS – FROM 4TH TO 5THWEEK – cephalocaudal and lateral folding in 4th week – primitive gut from buccopharyngeal membrane to cloacal membrane Three regions of primitive gut • foregut • midgut • hindgut EARLY EVENTS – PRIMITIVE GUT • region of foregut caudal of respiratory diverticulum • esophagotracheal septum • rapid elongation: 7th week - final relative length • rapid proliferation of endoderm (epithelium and glands) that obliterates lumen – recanalization about 8th week • connective tissue and muscle tissue – mesenchyme of caudal pharyngeal arches and splanchnic mesenchyme • innervation by branches of n. vagus (caudal pharyngeal arches) 8th week DEVELOPMENT OF ESOPHAGUS DEVELOPMENT OF ESOPHAGUS ABNORMALITIES DEVELOPMENT OF ESOPHAGUS GROSS: GASTROINTESTINAL: Esophagus: Tracheoesophageal Fistula: Gross posterior view of chest contents showing blind sac of esophagus above and continuation of esophagus from carina inferiorly good example Autor Peter Anderson DEVELOPMENT OF ESOPHAGUS - FISTULA • fusiform dilatation of the foregut • different growth rates in various regions → greater and lesser curvature • rotation 90°C clockwise around longitudinal and anteroposterior axis • definitive location and shape - 2nd month i.u. 8th week DEVELOPMENT OF STOMACH • 90° ventral lesser curvature → right dorsal greater curvature → left left side → ventrally right side → dorsally cranial part → left caudally caudal part → right cranially → definitive anatomical position of left and right nervus vagus STOMACH - ROTATION • midgut – primary intestinal loop • rotation during development • physiological umbilical herniation 8th week DEVELOPMENT OF INTESTINE WEEK: late 8th EMBRYO SIZE 35 mm DEVELOPMENT OF INTESTINE INTESTINAL ROTATION INTESTINAL ROTATION - MESENTERIES • (6-) 8th week • Normal reposition in 10th week Abnormalities: • Hernia may develop postantaly, evisceration or spontaneous reposition possible (X gastroschisis) • Inomplete closure of umbilicus, may include omentum majus and small intestine, skin and connective tissue INTESTINAL ROTATION – UMBILICAL HERNIA INTESTINAL ROTATION – UMBILICAL HERNIA ABNORMALITIES ILEUM DEVELOPMENT AND ABNORMALITIES VOLVULUS • malrotation of midgut and left colon (obstruction of a. mesenterica sup. and duodenum) • reversed rotation (obstruction of colon) • abnormal ahesion of caecum to liver (subhepatic caecum) - abnormal position of appendix • caecum mobile ILEUM DEVELOPMENT AND ABNORMALITIES • often phenomenon (2-4%) • clinically relevant • vitelline cysts, volvulus of diverticle DIVERTICULUM MECKELI • cloaka - cloacal membrane - endoderm of cloaca and ectoderm of proctodeum • septum urorectalis divides cloaca to dorsal anorectal canal and ventral sinus urogenitalis • septum urorectale dividies cloacal membrane to membrana analis and membrana urogenitalis • perineum • 8th week in utero – anal membrane perforated urinary bladder urethra feminina upper part of urethra masculina vestibulum vaginae part of prostate, other glands rectum upper part of canalis analis CLOACA AND ITS DERIVATIVES • canalis analis 2/3 from hind gut 1/3 from proctodeum linea pectinata – original position of the anal membrane anocutaneous line – epithelium change from from non-keratinized stratified squamous epithelium to keratinized HIND GUT– RECTUM AND ANUS ANUS DEVELOPMENT AND ABNORMALITIES ANUS DEVELOPMENT AND ABNORMALITIES PERINEAL MUSCLES • M. sphincter cloacae is divided by urorectal septum to: → m. sphincter ani externus → m. transversus perinei superficialis m. bulbocavernosus m. ischiocavernosus nn. perineales nn. rectales inferiores n. pudendus Primitivegut Foregut vascularization: truncus coeliacus derivatives: pharynx (also pharyngeal arches contribute), esophagus, stomach, proximal duodenum, liver, bile ducts and gall bladder, pankreas, trachea, bronchi and lungs developmental events: stomach and duodenal rotation, obliteration and recanalization of esophageal and duodenal lumen Midgut vascularization: a. mesenterica superior derivatives: distal duodenum, jejunum, ileum, colon ascendens, 1/3-2/3 of colon transversum developmental events: intestinal rotation, physiological umbilical hernitation and reposition. Diverticulum Meckeli Hindgut vascularization: a. mesenterica inferior derivatives: 1/3-2/3 of colon transversum, rectum, part of analis canalis, part of urinary bladder, part of urethra, in males part of prostate and bulbourethral glands, in females vaginal vestibulum, Skenes gll, Bartholin’s gll. developmental events: septation of cloaca by septum urorectale, development of perineum, rectum, anus and sinus urogenitalis and its derivatives DEVELOPMENT OF LIVER, PANCREAS AND LARGE SALIVARY GLANDS since 4th week • oropharyngeal membrane (stomodeoum-foregut) • cloacal membrane (hind gut-proctodeum) Foregut • primitive pharynx (→ and its derivatives) • lower respiratory passages (→ laryngotracheal div.) • liver and bile passages (→ hepatic div.) • pancreas (→ pancreatic div.) • oesophagus and stomach • proximal duodenum Midgut • distal duodenum, ileum, jejunum • caecum, appendix, colon ascendens, colon transversum (1/2-2/3) Hindgut • colon transversum (1/3-1/2), colon descendens, colon sigmoideum • rectum, anal canal • part of urinary system (derivatives of sinus urogenitalis) PRIMITIVE GUT DEVELOPMENT OF DIGESTIVE TUBE • Diverticulum of embryonic duodenum - liver diverticulum • Pars hepatica (parenchyma + ductus hepaticus) and pars cystica (ductus cysticus + gall bladder) form d. choledochus • Rapidly proliferating cells penetrate septum transversum (mesodermal plate between pericardial cavity and yolk sac) and growth into ventral mesentery • liver cords – parenchyma • Interactions between cells of liver cords and vv. omphalomesentericae induce development liver sinusoids • C.t. , Kupffer and hematopoietic cells – from mesoderm of septum transversum • Surface mesoderm differentiate into visceral peritoneum •10th week - 10% of body volume - hematopoiesis • 12th week - bile production EMBRYONIC DEVELOPMENT OF LIVER EMBRYONIC DEVELOPMENT OF LIVER • 4-5th week of development: two endodermal diverticles – dorsal and ventral duodenal diverticle (= pancreas dorsale et ventrale) • after rotation of duodenal loop both diverticula fuse • development of ducts: – ventral duct fuses with dorsal duct and divides it to proximal and distal part – proximal part of dorsal duct obliterates – ventral duct and distal part of dorsal duct form ductus pancreaticus major – if the proximal part of dorsal part persists, it will formsductus pancreatis accesorius • ductal system develops first, secretory acini follow • cells that are not part of ductal structures differentiate into Islets of Langerhans • since 4th month in utero - secretory activity EMBRYONIC DEVELOPMENT OF PANCREAS HISTOGENESIS OF PANCREAS ANATOMIC LOCALIZATION OF PANCREAS • Pancreas is secondary retroperitoneal Gl. parotis • develops first (6th week) • ectodermal buds from corners of stomodeum • proliferation and branching of solid cords • luminization and development of acini (10th week) • vazivo - mesenchym DEVELOPMENT OF LARGE SALIVARY GLANDS Gl. submandibularis • end of 6th week • endodermal buds from floor of stomodeum • proliferation and branching of solid cords together with tongue development • luminization and development of acini (12th week) • connective tissue– mesenchym • growths even post natally Gl. sublingualis • 8th week • multiple endodermal buds in paralingual groove • proliferation and branching of solid cords • luminization and development of glandular parenchyma • connective tissue – mesenchym • 10-12 independent ducts DEVELOPMENT OF LARGE SALIVARY GLANDS Gl. submandibularis Gl. parotis DEVELOPMENT OF LARGE SALIVARY GLANDS DEVELOPMENT OF LARGE SALIVARY GLANDS DEVELOPMENT OF LARGE SALIVARY GLANDS DEVELOPMENT OF LARGE SALIVARY GLANDS DEVELOPMENT OF LARGE SALIVARY GLANDS Further reading: Neurographics 2015 July/August; 5(4):167–177; www.neurographics.org SUMMARY pvanhara@med.muni.cz Thank you for attention http://www.med.muni.cz/histology/education/