Digestive system
1. Microscopic anatomy of esophagus, stomach,
small and large intestine
2. Microscopic anatomy of liver, pancreas
Petr Vaňhara, PhD
Department of Histology and Embryology LF MU
PVanhara@med.muni.cz
1. Development and general structure of hollow organs/gut tube
2. Esophagus (Oesophagus)
3. Stomach (Ventriculus, Gaster)
4. Small and large intestine (Duodenum, Ileum, Jejunum, Colon)
- Tunica mucosa
- Tela submucosa
- Tunica muscularis externa
- Serosa/adventitia
- Microscopic anatomy
- Gl. oesophageae propriae
- Microscopic anatomy
- Functional modification of gastric mucosa and gastric glands
- Enteroendocrinne system
- Microscopic anatomy
- Functional modification of intestinal mucosa and Lieberkühn crypts
- Enteroendocrinne system
Development of gut tube
– cephalocaudal and lateral folding
– primitive gut (endoderm)
– oral cavity and rectum – ektoderm
– glandular parenchyma (pancreas, liver)
- endoderm of gut tube
Four regions:
• pharynx – from buccopharyngeal membrane to
tracheobronchial diverticulum
• foregut – caudal to pharyngeal tube to liver diverticulum
• midgut – caudal to liver to junction of the 2/3 of adult
transverse colon
• hindgut – left 1/3 of trasverse colon to cloacal membrane
- Esophagus
- region of foregut caudal of respiratory diveticulum
- endoderm (epithelium and glands), connective tissue - mesoderm
- Stomach
- 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.
- Intestine
- midgut – primary intestinal loop
- rotation during development
- physiological umbilical herniation
Development of gut tube
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 incl. gut tube
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
- 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)
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, muscularis
externa and serosa
- innervations – 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
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
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
S.E. Mutsaers / The International Journal of Biochemistry & Cell Biology 36 (2004) 9–16
Serosa/Adventitia (Tunica serosa/adventitia)
1.4m
Esophagus (Oesophagus)
- 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
Cardia of stomach – connection with esophagus
Nonkeratinized stratified squamous epithelium  simple columnar epithelium
Stomach (Ventriculus, Gaster)
- 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
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 extracelullarly)
neck cells
- cubic, mucinous
- capable of regeneration of all cell types in gastric epithelium
Stomach(Ventriculus, Gaster)
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 lesson spring semester 2012 - Epithelial tissue
Break
http://luminaryvisuals.com/
General architecture of hollow organs incl. gut tube
Gastroduodenal junction
General architecture of the intestine
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
Small intestine – adaptation to effective resorption
Simple columnar
epithelium
- enterocytes
- goblet cells
- Paneth cells
- enteroendocrine cells
- M-cells
Intestinal mucosa
Crypts of Lieberkühn
200-600x
Crypts of Lieberkühn (gl. intestinales)
- 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
Enterocytes
Intestinal mucosa
- 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
Microvilli
Transportion 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/
Transportion and resorption
Secretory epithelium
Mechanism of secretion
Exocrine  Endocrine  Paracrine
Merocrine  Apocrine  Holocrine
Unicellular glands
Multicellular glands
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 lesson spring semester 2015 - Epithelial tissue
Goblet cells
Intestinal mucosa
Goblet cells
Intestinal mucosa
Paneth cells
Intestinal mucosa
- 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.
M cells (microfold)
Intestinal mucosa
- epithelial cells above Peyer’s patches
and lymphatic nodules
- no microvilli
- induces immune response
- MHCII
- antigen presentation to dendritic cells
and lymphocytes
„Microfold“
Intestinal stem cells
Intestinal mucosa
- bottom of crypts of Lieberkühn
- epithelial renewal (4-5 days)
- stem cell niche
- tumour transformation
L. propria
Intestinal mucosa
- immune system – GALT
- immunologic barrier
- Peyer’s patches
Brunner’s glands
Submucose
- gl. duodenale Brunneri
- branched tuboalveolar glands, columnar
mucinous cells
- connective tissue reduced to thin septa
between glandular lobules
- open to crypts of Lieberkühn
Muscularis externa
- two layers of smooth muscle (inner circular, outer longitudinal)
- plexus myentericus Auerbachi
Serosa
- loose collagen connective tissue + simple squamous epithelium (mesothelium)
Colon
- no plicae of Kerckring, villi
- muscularis externa – longitudinal layer forms taenie coli
- surface serosa forms appendices epiploicae (adipose)
Small intestine Colon
Colon
- absorption of water, electrolytes
- deeper crypts of Lieberkühn, no Paneth cells
- abundant goblet cells
- abundant lymphatic follicles in l. propria (GALT)
Apendix
- 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
Rectum and anal canal
- Pars pelvina
- plicae transversae recti
- histological architecture identical to colon
- Canalis analis
- anulus hemorhoidalis – no L. crypts, simple columnar epithelium replaced by stratified
squamous epithelium
- rich venous plexus
- columnae rectales
- sinus rectales and valvulae rectales
- zona cutanea – typical skin
Rectum and anal canal
Microscopic anatomy of the gut tube Summary
- 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
- 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
Embryonal development
- Development of primitive gut and its derivatives, embryonic flexion, differentiation and
characteristics of individual regions and associated organs
• Sadler: Langman’s Medical Embryology, 2000
• Ovalle&Nahirney: Netter’s Essential Histology, 2008
• Klika&Vacek: Histologie, 1974
• Ross&Pawlina: Histology (a text and atlas), 2011
• Ross&Romrell: Histology (a text and atlas), 1989
• Berman: Color Atlas of Basic Histology
• Ústav histologie & embryologie LF MU, www.med.muni.cz/histol/histolc.html
• Čech S., Horký D., Sedláčková M.: Přehled embryologie člověka, Brno, LF MU, 2011
• Horký D., Čech S.: Mikroskopická anatomie, Brno, LF MU, 2011
• About.com Health's Disease and Condition, Donna Myers © 2007
• Mutsaers SE, The mesothelial cell, The International Journal of Biochemistry & Cell Biology, 2004, 36(1):9-16
• A.D.A.M. Education /University of Maryland Medical Center (UMMC)
http://www.umm.edu/; http://www.adameducation.com/index.aspx
• Science Photo Library
• Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem
Cell. 2010 Dec 3;7(6):656-70.
• Mills JC, Shivdasani RA. Gastric epithelial stem cells. Gastroenterology. 2011 Feb;140(2):412-24.
• Ohno H. M cells hold the key to gut immunity. Riken Research Frontlines. 2010. http://www.rikenresearch.riken.jp/eng/frontline/6346
• Kosinski C et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal
stem cell niche factors. PNAS 2007;104:15418-15423
• Knoblich JA. Asymmetric cell division during animal development. Nature Reviews Molecular Cell Biology 2001, 2, 11-20
• van der Flier LG, Clevers H. Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium. Annu. Rev. Physiol.
2009.71:241-260
• Southern Illionis University, http://www.siumed.edu/~dking2/erg/GI015b.htm
Study materials
References