Digestive Glands

Question 1

What are the extrinsic glands of the digestive system?

Answer 1

These are located outside the wall of the alimentary canal and deliver their secretion into the lumen via ducts (exocrine secretion)

• Provide enzymes, buffers, emulsifiers, and lubricants for the digestive tract, as well as hormones, proteins, globulins, and numerous additional products

Include:
– Liver
– Gall bladder
– Pancreas
– Major salivary glands: Parotid, Submandibular and Sublingual glands (DLA)

– Minor salivary glands : located in the submucosa of different parts of the oral cavity: palatine, buccal, molar, labial and lingual glands

Question 2

Where is the liver located?

Answer 2

Location: right upper quadrant of the abdomen

Question 3

What are the functions of the liver?

Answer 3

Performs several endocrine and exocrine functions:

1. Produces and secretes most of circulating plasma proteins
   including albumins, lipoproteins (vldl), glycoproteins (haptoglobulin, transferrin), prothrombin, non-immune α- and β- globulin.
2. Modifies the structure and function of hormones including growth hormone, insulin and glucagon, thyroxin etc..
3. Storage and/or conversion of several vitamins (A,D,K) and iron.
4. Degrades drugs and toxins via oxidation and/or conjugation.
5. Homeostatic pathways includes carbohydrate, protein and
   lipid metabolism.
6. Exocrine function: bile secretion

Question 4

What is the porta hepatis?

Answer 4

region at the inferior surface of the liver where major vascular structures and ducts enter and leave the liver - hepatic artery, portal vein and hepatic ducts

Question 5

What is the parenchyma?

Answer 5

organized plates of hepatocytes separated by sinusoidal capillaries

Question 6

What is Glisson’s capsule?

Answer 6

Glisson’s capsule
• fibrous connective tissue encloses and subdivides
the liver into lobes and lobules except where the liver is attached to other structures. Continues with the connective tissue stroma of the liver

• Glisson’s capsule is covered by visceral peritoneum making the liver intraperitoneal except at the bare area (attachment to the diaphragm)

Question 7

What are sinusoidal capillaries?

Answer 7

Sinusoidal capillaries

• vascular channels between plates of hepatocytes

Question 8

What is perisinusoidal capillaries?

Answer 8

Perisinusoidal spaces

• space between the sinusoidal epithelium and the hepatocytes

Question 9

Describe the blood supply of the liver

Answer 9

Blood enters the liver at the Porta Hepatis.

• hepatic artery(25%)- fully oxygenated
• portal vein(75%)- venous blood from intestines pancreas and spleen. Rich in nutrients, endocrine secretions and blood cell breakdown products.
• sinusoids – blood from distributing branches of the hepatic artery and portal veins supply sinusoidal capillaries that bathe the hepatocytes

Question 10

Describe the veinous drainage of the liver

Answer 10

Venous drainage of the liver

• sinusoids eventually lead to a terminal hepatic venule (central vein)
• central veins from each classic lobule empty into the sublobular veins.
• sublobular veins drain into the hepatic veins which then drains into the IVC

Question 11

Describe the (classical) structural lobule

Answer 11

Liver tissue is divided into hexagonal clusters of hepatocytes radiating from a central vein ( V)→classic hepatic lobule

• At the angles of the hexagon are the portal areas/portal canals ( P) in loose stromal connective tissue. This loose connective tissue is continuous with the fibrous capsule of the liver
• Portal area contains branches of the hepatic artery, portal vein, a bile duct and a lymphatic vessel

Question 12

Describe the plates of hepatocytes and sinusoidal capillaries in the (classical) structural lobule

Answer 12

Plates of Hepatocytes:
– extends radially from the region of a
central vein(V)
– Plates are normally one cell thick in adults but 2 cells thick in small children

▪ Sinusoidal capillaries
– Endothelial channels that run in parallel
to plates of hepatocytes.
– Receive mixed blood from the vessels of the portal area and deliver it to the central vein.
– Blood flows from the periphery of the lobule toward the central vein

Question 13

Describe the surface modifications of the hepatocytes

Answer 13

Surface modifications

– Microvilli on more than one surface

Question 14

Describe the nucleus of the hepatocytes

Answer 14

Nucleus
– Usually possess one (or two), centrally placed (occasionally enlarged polypoid) round nucleus.
– Two or more nucleoli

Question 15

Describe the cytoplasm of the hepactoyte.

Answer 15

Cytoplasm
– Foamy appearance due to glycogen (with H&E)
– Lipofuscin granules
– Lipid droplets
– Smooth endoplasmic reticulum
– Rough Endoplasmic reticulum and free ribosomes +++++
– Lysosomes and peroxisomes – Multiple Golgi regions
– Abundant mitochondria

Question 16

Describe the hepatocyte surfaces in an adhacent neighboring hepatocytes

Answer 16

– Form small, tunnel-like bile canaliculi (arrows and arrowheads in images A & B) that are special intercellular spaces.
– Occluding junctions at each surface
– Microvilli extend into the bile canaliculus
from each hepatocyte.
– Exocrine function

Question 17

Describe the hepatocyte surface on the basal surface

Answer 17

– Adjacent to the sinusoids
– Has contact with the perisinusoidal space of Disse (D)
– Microvilli assist in the transfer of materials
to and from hepatocytes. It is here that
the endocrine secretion of the liver also
take place

Question 18

Describe the hepatic sinusoids

Answer 18

• Hepatic sinusoids have a discontinuous endothelium with numerous large fenestrations without diaphragm.
• Additionally, large intercellular gaps exist between endothelial cells
• Lined by Kupffer cells (stellate sinusoidal macrophages), phagocytic cells from the monocyte lineage

Question 19

What is the impact of the peri-sinusoidal space (Space of Disse)

Answer 19

The Space of Disse (D)is an electron microscopic feature of the liver which lies between the hepatocyte and the sinusoids.

Functions
Exchange of material between the bloodstream and the hepatocytes (which do not contact the bloodstream)

Question 20

What are the components of the Peri-sinusoidal space (Space of Disse)?

Answer 20

Components:
1. Stellate-shaped fat storing cells called Ito cells (which preferentially store vitamin A).
– Modified pericytes
– After liver injury they lose fat stores, differentiate
into myofibroblasts & produce collagen→fibrosis

2. Reticular fibers→maintain the architecture of the
   sinusoids)
3. Unmyelinated nerve fibers
4. Short, blunt microvilli of hepatocytes

Question 21

What is the purpose of the portal lobule, functional lobule?

Answer 21

Emphasizes the liver’s exocrine function. In many exocrine glands, the duct is in the center of a lobule.

• Triangular region whose three apices are neighboring central veins, the triangle will have a portal area (yellow circle) in its center

Question 22

Describe the biliary tree and flow of bile

Answer 22

Flow of bile and blood occurs in opposite directions. Bile is conducted away from the center of the classic lobule via intrahepatic and extrahepatic system of ducts.

1. Bile Canaliculi (arrow/arrowheads in image A and green circle in image B)
   • Formed by tight junctions between adjacent hepatocytes and contain short blunt microvilli
   • Receive the exocrine secretion of the liver (bile) and convey bile to canals of Herring
2. Canals of Herring
   • Harbor hepatocyte stem cell niche
   • Partially lined by hepatocytes and partially lined by specialized cells called cholangiocyte

Question 23

Explain the significance of the biliary tree

Answer 23

Cholangiocytes have numerous apical microvilli and a primary cilium that senses changes in bile flow resulting in alterations of cholangiocyte secretion.

– Initially cuboidal in small ducts then columnar in large intra hepatic and all extrahepatic ducts. Bile flow can be summarized as follows:

Hepatocyte→bile canaliculi (hepatocytes)→canals of Herring (cholangiocytes and hepatocytes)→intrahepatic bile ductules (in the peri-portal space (cholangiocytes))→interlobular bile (hepatic) ducts found in the portal area (cholangiocytes)→eventually hepatic ducts (cholangiocytes)

Question 24

What is the significance of a liver acinus of rappaport?

Answer 24

• A functional lobulation in the liver based on blood flow.
• Two adjoining portal areas (P) are shared by two neighboring classical lobules

• Hepatocytes are divided into three functional zones

• Zone1
– first to be “exposed” to the entering blood
– first to show changes after bile stasis

• Zone3
– last to be “exposed”
– firsttoshowischemicnecrosisandfat accumulation
• Consider possible implications during toxemia and hypoxemia!

Question 25

What is the clinical significance of congestive heart failure?

Answer 25

* Decreased output from the right side of heart results in back up of blood in the sinusoids of the liver (congestion) * Decreased blood to the left side of the heart leads to decreased output from the left side of the heart and decreased oxygenated blood to the liver - hypoperfusion and hypoxia * Zone 3 of the liver acinus is the first to be affected by this condition. The hepatocytes in this zone are the last to receive blood as it passes along the sinusoids; as a result, these cells receive a blood supply already depleted in oxygen. Additionally, • Centrilobular necrosis - hepatocytes in zone 3, which is located around the central vein, undergo ischemic necrosis. Typically, no noticeable changes are seen in zones 1 and 2, representing the periphery of a classic lobul Zone 3: note the presence of multiple round vacuoles, which indicates extensive lipid accumulation

Question 26

What is the clinical significance of hepatic steatosis?

Answer 26

• Frequently associated with fatty liver disease due to: – (1) chronic alcohol or – (2) metabolic syndrome→non- alcoholic fatty liver * Increased intrahepatic lipid droplets * Signet ring appearance of hepatocyte * Hepatomegaly • Can progress to cirrhosis

Question 27

What is the significance of liver cirrhosis?

Answer 27

• Diffuse liver damage from fatty liver disease, toxins, infections etc. ✓Collagen is deposited in all portions of the lobule ✓Alterations in the sinusoidal endothelial cells * Net result is severe blood flow disruption and decrease in hepatocyte function * Can lead to increased pressures inn the portal system * Nodular appearance is due to extensive fibrosis surrounding nodular clusters of healing hepatic tissue

Question 28

How is the Gallbladder shaped?

Answer 28

Small, pear-shaped organ. • Stores and concentrates bile manufactured by the liver. • Storage volume is approximately 40 to 60 ml. • Muscle wall contracts to force the bile in its lumen into the duodenum, where the bile acts to emulsify fats. • Contraction is facilitated by the hormone cholecystokinin.

Question 29

Deecribe the mucosa of the gall bladder

Answer 29

``` 1. Mucosa Epithelium: • Simple columnar with microvilli(++++) • Junctional complexes at apical surface which form a barrier between the lumen and intercellular compartment • Lateral plications • Mitochondria at basal surface ``` Lamina Propria • Abundant fenestrated capillaries • Mucous glands proximal to the cystic duct→ abundant in cholecystitis No muscularis mucosae In the empty gallbladder the mucosa folds on itself→ false lumen (*)

Question 30

Describe the muscle layer of the gall bladder

Answer 30

Muscle Layer | • Thin layer of obliquely oriented smooth muscle

Question 31

Describe the connective tissue of the gall bladder

Answer 31

Connective Tissue • Dense, irregular collagenous, housing nerves and blood vessels. • Mesothelium of the peritoneum .(i.e. Serosa covers most of the gallbladder, except where the organ is attached to the liver) adventia Other features

Question 32

What is the importance of sinuses of Rokitansky-Aschoff (RA) to the gall bladder?

Answer 32

Sinuses of Rokitansky-Aschoff (RA) are deep invaginations of the mucosa into the muscular and/or connective tissue layers. * Caused by hyperplasia and herniation of epithelium. * Colonization of bacteria may cause chronic inflammation→increase risk for gallstones

Question 33

Describe the pancreas

Answer 33

* Retroperitoneal gland * Exocrine and endocrine functions. * Subdivided into the following regions: head, uncinate process, neck, body, and tail. Tail contains the highest concentration of endocrine tissue (islets of Langerhans)

Question 34

Describe the pancreas capsule

Answer 34

Composed of delicate connective tissue that subdivides the gland into lobules by forming numerous septa. • Septa convey blood and lymph vessels, nerves and ducts in and out of the gland.

Question 35

What are the classifications of the exocrine pancreas?

Answer 35

Classification • A pure serous, compound tubuloalveolar gland. Acini • Serous with centroacinar cells, the beginning of the duct system in the pancreas. Acinar Cells • Pyramidal with round basal nucleus • Basal region is strongly basophilic • Apical region is densely packed with secretory granules (zymogen) granules Intercellular Canaliculi • Lead from between acinar cells to the lumen of the acinus – look for the centroacinar cell

Question 36

Describe the pancreatic ductal system

Answer 36

Pancreatic ducts extend from within the acini as Centroacinar Cells ( C) – low cuboidal and – initial part of the intercalated duct. • No myoepithelial cells associated with the ductal system • Secretion is under hormonal control • Intercalated ducts lead into a small number of intralobular collecting ducts, which in turn empty into the large interlobular ducts. • No striated ducts in the pancreas since there is no need for extensive modification of the excretory product • Interlobular Ducts – Located between lobules in extensive connective tissue and empty into the main (or accessory) pancreatic duct. • Pancreatic Duct – The main pancreatic duct (of Wirsung), delivers the pancreatic secretions into the duodenum at the ampulla of Vate

Question 37

Explain the regulation of pancreatic secretion

Answer 37

Two hormones, released by enteroendocrine cells of the digestive tract, control the release of pancreatic secretions. • Cholecystokinin (pancreozymin) – Induces the acinar cells to release proenzymes – These proenzymes are trypsinogen, chymotrypsinogen, peptidase, pancreatic amylase and lipase, and ribo- and deoxyribonucleases. • Secretin – Induces the intercalated ducts to secrete large quantities of an enzyme-poor, alkaline fluid that probably functions in neutralizing the acidic chyme that enters the duodenum. • Sympathetics regulate pancreatic blood flow • Parasympathetics stimulate activity of acinar as well as centroacinar cells. • Pancreatic secretion – Trypsinogen converted to trypsin by enterokinase in lumen of small intestine – Trypsin a proteolytic enzyme catalyzes activation of the other inactive enzymes

Question 38

What are the main cell types of the endocrine pancreas?

Answer 38

Spherical clumps of endocrine tissue mainly in the tail region composed of several cell types distinguishable only by special stains • Cells are arranged in short cords supported by a network of reticular fibers and fenestrated capillaries Alpha Cells (A) • At the periphery and constitute 15-20% of islet • Manufacture glucagon which elevates blood glucose levels Beta Cells • Constitute the majority (70%) of islet and occupy mostly the center of each islet. • Beta cells produce insulin→lowers blood glucose levels Delta Cells Less common than the other two (5-10%) Produce somatostatin which modulates both insulin and glucagon secretion Others: Include C,E,G, and PP cells

Question 39

Expplain the significance of acute pancreatitis

Answer 39

- Acute pancreatitis is a sudden inflammation of the pancreas. - Gallstones and alcohol abuse account for almost 80% of hospital admissions for acute pancreatitis. - Blockage of the pancreatic duct by a gallstone stuck in the sphincter of Oddi stops the flow of pancreatic fluid. Usually, the blockage is temporary and causes limited damage, which is soon repaired. - If the blockage persists activated enzymes accumulate in the pancreas, overwhelm the inhibitors, and begin to digest the cells of the pancreas, causing severe inflammation.

Question 40

What is the cause of cystic fibrosis?

Answer 40

- Autosomal recessive disorder caused by mutation in CFTR gene (cystic fibrosis transmembrane conductance regulator), located on chromosome 7. - Cl ̅ channel protein is involved in the alteration of mucus and digestive secretions, sweat and tears. - Abnormal epithelial transport of Cl ̅ increases the viscosity of the secretion of the exocrine glands.

Question 41

What are the gastrointestinal manifestations of cystic fibrosis ?

Answer 41

Gastrointestinal manifestations • Pancreas is especially affected: malabsorption syndrome secondary to obstruction of pancreatic ducts * Pancreatitis and subsequent fibrosis of the pancreas * Billiary tree obstruction by gallstones * The net result of the GI involvement is malnutrition * One of the pillars of management is to give pancreatic enzyme One of the pillars of the management is to give pancreatic enzyme supplement