Microscopical of the small and large intestines. Histology the , and the

Dr. Zsuzsanna Tóth Semmelweis University Department of Anatomy, Histology and Embryology General histology of the GI tract

Serosa: mesothel and subserosa: lamina propria, or adventitia (loose connective tissue) Longitudinal layer

Myenteric or Auerbach's plexus muscularis externa

Circular layer

Submucosa

Enteric nervous plexus (Meissner’s plexus)

Muscularis mucosae mucosa Epithelium and lamina propria Enteric nervous system

longitudinal

Myenteric plexus Multipolar neurons circular

Regulation of the motility of the GI tract Regulation of secretory activity and and local blood (motoneurons) flow (secretomotor and vasodilatator neurons)

• eosophagus - m. sphincter ani internus • control: autonomic nervous system, • input: chemo- and mechanoreceptors enteroendocrine cells, digestive enzymes Small Intestine (duodenum, jejunum, ileum)

brush border (microvilli) v. portae hepatis

1mm

Circular folds of Kerckring

Villi Length: approx 5 m Increase of surface area : circular folds -3X, villi-10X, microvilli-20X→ 600X Intestinal glands (crypts of Lieberkühn)

epithelium lamina shedding dead enterocytes propria lacteal

crypta

l. muscularis mucosae

• simple tubular glands • mucosal structures • epithelial cell renewal- stem cells Circular folds

submucosa

Tunica mucosa and submucosa Brunner glands (duodenal glands)

• only in the duodenum • branching tubular mucous glands • produce alcaline mucus - neutralizes the acidic chyme entering from the stomach - protection of the mucosal cells -provides optimal pH for the digestive enzymes • produce epidermal growth factor • open into the crypts Pylorus-duodenum transition

Muscularis externa layer in the small intestine: continous, outer longitudinal, inner circular layers pyloric sphincter (ps) muscle: formed by the circular layer of the tunica muscularis Small intestinal cell types

goblet cell

goblet cell enteroendocrine cell Paneth cell Enterocye lubrication regulatory antibacterial agents absorbtion hormones digestion Paneth cell

crypts

t. submucosa l. muscularis mucosae small intestinal stem cell Smooth muscle cells Human jejunum H&E

Crypts: all the cell tpyes Villi: enterocyte, goblet cell, enteroendocrine cell

Crosnier et al. Nature Reviews Genetics 7, 349–359 (May 2006) | doi:10.1038/nri1840 Intestinal villi

simple columnar epithelium

epithelium lamina propria

lamina propria Goblet cell lacteal

bed smooth musle cells l. musc.mucosae

villous contractions: lymph and blood is pushed toward larger vessels Immune defense within the GI tract Mucosa or gut associated lymphatic tissue (MALT, GALT)

lamina propria: • cell rich connective tissue • diffusely distributed lymphoid cells and plasma cells enterocytes submucosa: capillary scattered solitary lymphoid follicles

plazma cells plasma cells: secretory IgA goblet cell production

lamina propria GALT: Peyer’s patches in the ileum

• aggregated lymphoid nodules in the mucosa and submucosa • anti-mesenterial location, approx. 100 nodules in humans GALT: vermiform appendix-”intestinal tonsil”

Goblet cells mesoappendix

tunica serosa

• no villi • crypts • circularly arranged lymphatic nodules • thick muscularis externa • serosa Duodenum Jejunum Ileum Colon

P

B

Mucosa: Intestinal villi and Lieberkühn crypts (intestinal glands) no villi, deep crypts

Submucosa: Brunner glands Peyer’s patches Tunica muscularis in the large intestine

Modified outer longitudinal layer: plicae semilunares • Teniae coli (muscle bands): gastrum o from the cecum to the sigmoid colon 1. free, 2. mesocolic, 3. omental teniae

o converge at the roof of the appendix 3. 2. o sigmioid colon: 2 bands only

o appendices epiloicae are attached to them haustrum 1. teniae o plicae semilunares-musosa and submucosa

o sacculations-haustra

o haustra disappears if theniae are dissected off

Circular layer: • continous • forms sphincters and valves Tunica mucosa of the colon • epithelium: enterocytes, goblet cells, enteroendocrine cells columnar epithelium (enterocytes) • enterocytes -water and electrolite reabsorbtion -no digestive function • the number of goblet cells increases caudally - thick mucin layer • deep crypts Rectum – intestinal part

lymphatic nodule

lymphatic nodules goblet cells

mucus between crypts

• The longitudinal muscle layer is continous, there are no teniae. • Epiploic appendages are missing. • More goblet cells, deeper crypts, than in the colon. • Several solitary lymphatic nodules (GALT). • No semilunar folds, but transverse folds are present. Rectum – anal canal

transverse folds Lieberkühn crypts rectum pars intestinalis

anal canal

stratified keratinized squamous epithelium

pectinate line cutaneous zone pigments, hair, intermediate zone sebaceous gl, cirumanal gl. sebaceous gl, hemorrhoids

• columnar zone:

o columns of Morgagni- stratified squamous non-keratinized epithelium

o sinus anales – simple columnar epithelium • intermediate zone (haemorrhagica): stratified squamous non-keratinized epithelium • cutaneous zone: stratified squamous keratinized epithelium, pigmented Next slide: QR code for attendance tracking! Histology of the liver, and the biliary system The liver tissue is organized into units called lobules

vena cava portal triad Hepatic lobule

interlobular • Hexagonal shaped functional unit consisting of interlobular sublobular mainly . interlobular artery • Lobules are separated by connective tissue – interlobular septa. • Branches of the portal vein, the hepatic artery and

the hepatic duct follow the corners of the hexagon and are called portal triad. • Blood flows from the perifery of the lobule toward

the center (red arrows). • In the center of the hexagon there is a central vein. • The central (=centrilobular) vein gathers blood and transports it to the sublobular vein, and then into the interlobular septa hepatic vein. Intensive blood supply facilitates the work of hepatocytes

sinusoids • Sinusoids are dilatated . portal (Glisson’s) triad: • Blood from the perilobular vessels falls into the sinusoids and from them to the central vein. • Arterial and venous blood get interlobular artery mixed in the sinusoids. interlobular vein 3 • Sinusoids separate the hepatic interlobular duct plates. • They form anastomoses, thus at least one surface of a is perilobular vein surrounded by blood.

hepatic plates • Hepatic cells in the lobule form on cell layer-thick plates. • Within the plates hepatocytes perilobular artery are arranged in radial cords. • The cords are actually branching, interconnected sheets. central vein

peribiliar plexus Portal triad The site at which blood enters the lobule and bile leaves it.

capsule • connective tissue

interlobular artery • round or oval shape • muscular media • may contain red blood cells

lymph vessel • irregular shape • very delicate wall • no red blood cells

Nerves may be present. interlobular vein interlobular • irregular shape • round or oval shape • thin wall, only endothelial lining • simple cuboidal (small ones) • surrounding or columnar (larger ones) epithelium • may contain red blood cells Human liver tissue

1 2

6 c v c v 3 hepatic lobule

5 4

Interlobular septa are less definitive in humans. Central vein with hepatic cords and sinusoids around

CV

Hepatocytes: • main cell type in the parenchyma • have large, round euchromatic nuclei, and one or more nucleoli • binucleate cells are common (paired nuclei) Concepts of liver lobules

Portal lobule: Hepatic acinus:

Emphasizes the bile secretion. Emphasizes the blood supply. Liver acinus

acinus perilobular vessels

1/6 1/6

perilobular vessels perilobular CV CV liver acinus

According to the deacreasing oxygen gradient toward the central vein, the acinus is divided into 3 zones. Hepatocytes in the zones have different functions. Zone 1: first to receive both nutrients and toxins last to die in case of ishemia and the first to regenerate first to take up glucose to store as glycogen first to show morphological changes following bile duct occlusion Zone 3: first to show ischemic necrosis first to show accumulation in obese persons last to respond to toxic substances and bile stasis Zone 2: intermediate zone The and the

Easy exchange of large molecules between hepatocytes and blood plasma is facilitated: • the sinusoidal wall is lined with fenestrated endothel, • beside the intercellular fenestrae there are also intercellular pores in the endothelial cells, • the basal lamina is discontinous or missing, • the hepatocytes and the sinusoidal wall is separated by the perisinusoidal space – space of Disse, • plasma may enter, but red blood cells and platelets are exluded form the perisinusoidal space, • microvilli (increasing surface) of the hepatocytes extend into the space of Disse-this is the site of exchange. Reticular fiber network supports hepatocytes in the space of Disse reticular fibers in the space Silver impregnation of type III (reticular) fibers. of Disse

• Reticular fibers are in connection with the interlobular connective tissue and with the connective tissue around the central veins. • The ratio of the interstitium and the parenchyma is small, therefore the liver is vulnerable to injuries. microvilli Bile canaliculi

n

metabolites TJ

TJ

• Kupffer cells : in the sinusoids • Ito cells (hepatic stellate cells): in the perisinusoidal space Kupffer cells are resident macrophages

Kupffer cells phagocyte ink particles added intravenously.

Kupffer cells: • triangular or star shaped, smaller, migrating cells in the sinusoids • are part of the immune system – diffuse mononuclear phagocyte system (MPS) • uptake and degrade foreign and potentially harmful substances • proliferate and enlarge in response to hepatocyte damage, bacterial toxins, etc. • uptake senescent red blood cells and break down hemoglobin Hepatic stellate cells (Ito cells) store vitamin A

= Ito cell = perisinusoidal cell • strore and metabolize vitamin A • produce connective tissue of interlobular septa • contribute to liver

lipid dropplet

Cirrhosis: + + • is the end stage of chronic liver diseases activated Kupffer cells • is caused by alcoholism, cancer, hepatitis C, etc. apoptotic hepatocytes • the liver tissue is replaced by fibrous connective tissue Canals of Hering

Progenitor cells

Canals of Hering

Progenitor cells are present in the canals of Hering and around the ducts. The path of the bile within the liver

interlobular canals of Hering bile canaliculi-not real ducts bile duct (bile ductule) form a network portal vein

→ left and right hepatic duct →hylum of the liver The way of the bile outside the liver

spiral valves

Extrahepatic ducts: • simple columnar epithelium • mucous glands in the submucosa • the muscular layers thickens toward the duodenum • the regulates bile flow into the duodenum Histology of the I.

Serosa & subserosa

• The gallbladder stores, concentrates and releases bile. • CCK (): • stimulates gallbladder contraction & emptying • relaxes the sphincter of Oddi • CCK is produced by enteroendocrine cells in the small intestine • CCK is released by stimulation of dietary fat in the duodenum Note, the gall bladder does not have a layer of muscularis mucosae and submucosa! Histology of the pancreas

Exocrine pancreas: compund serous acinar gland

acini & ducts exocrine

Islet of Langerhans endocrine

Exocrine secretum: digestive enzymes - leave the pancreas through the ductal system, and get into the duodenum. Endocrine secretum: hormones - leave the pancreas through the fenestrated capillaries and get into the circulation. The structure of the lobules and the ductal system

intralobular ducts interlobular ducts cuboidal epithelium columnar epithelium

Islet of Langerhans: fenestrated intercalated duct capillaries squamous epithelium endocrine cells centroacinar cells squamous epithelium

acinar cell Duodenum main columnar epithelium

acinar cell

• Centroacinar cells belong to the initial part of the intercalated duct. • Unlike the salivaly glands, there are no myoepithelial cells and striated ducts in the pancreas Intralobular ducts are surrounded by acini, interlobular ducts are within the septa H&E, monkey

centroacinar cell

centroacinar cell

intercalated duct

enzyme production by the acinar cells: • protein synthesis in the RER - basal part of the cell is basophilic • strorage in zymogen (inactive) form - apical part (secretory vesicles) is eosinophilic • discharge of zymogen into the intercalated ducts by exocytosis Endocrine cells of the islands are arranged into cords

Light staining with HE

A cells – glucagon – increases the amount of glucose in blood B cells – insulin – decreases the amount of glucose in blood D cells -somatostatin – inhibits the other two F cells – pancreatic polypeptide – stimulates stomach chief cells, inhibits bile and bicarbonate secretion The islets of Langerhans are highly vascularised by fenestrated capillaries