Digestive System III: Accessory Organs of

N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected]

Required reading

Mescher AL, Junqueira’s Basic Text and Atlas, 12th Edition, Chapter 16: pp281-297 Ross MH and Pawlina W, Histology: A text and Atlas, 6th Edition, Chapter 18: pp628-663 Chapter 16: pp545-555

Learning objectives

1) Recognize and cite the distinctive histological features of the salivary , , and .

2) Discuss the functional role of the salivary glands, pancreas, liver and gallbladder in the processes of digestion with particular reference to their histological features.

3) Understand how changes in the structure and function of these regions can bring about the course of many common diseases.

Key terms

salivary glands serous ainus liver mucous tubule porta hepatis intercalated striated duct classic liver lobule interlobular duct portal triad parotid hepatic portal vein hepatic intralobular duct duct pancreas central vein sinusoid pancreatic acinar cells space of Disse intercalated ducts bile canaliculi centroacinar cells gallbladder sublingual gland

1 A1: Salivary glands

There are three pairs of major salivary glands The functions to:

A. (300mls/day) • Moisten and lubricate food () B. Submandibular gland (600mls/day) • Begin digestion of (amylase) C. Sublingual gland (50mls/day) • Destroy bacteria (antibacterial enzymes) D. Minor glands (50mls/day) • Reabsorb Na+ and excrete K+ (ducts) General structure of salivary glands

i. Stroma (supportive tissue) A connective tissue capsule that gives off septa. The septa divide the gland into lobes and lobules.

ii. Parenchyma (functional tissue)

1. Serous cells Pyramidal shaped secretory cells with a large circular nucleus. They have a basophilic that contains many secretory granules. The cells are organized into acini (alveoli) which have a small central into which their secretory product is released and passed into the duct system. Together with their ducts they resemble grapes (acini) attached to a stem (duct). Their secretory products are enzymes and other proteins.

2. Mucous cells Secretory cells with a basally located flat nucleus. They have a pale staining cytoplasm that contains vesicles (similar to a goblet cell). The cells are organized to form tubules rather than acini. Their secretory product is mucin which imparts the lubrication and moistening function of saliva.

3. Myoepithelial cells Contractile cells that surround the secretory units and intercalated ducts. Their cytoplasm contains actin and myosin which interact (like a ) to contract the cell and squeeze out the secretions from the surrounding acini and ducts. 3

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2 iii. Duct system Salivary glands are compound glands which means they have a branching duct system. Intralobular ducts

(located within a lobule)

Secretory units Intercalated (acini/tubules) duct

Striated

ducts

1. Intercalated ducts The secretory units (acini/ tubules) empty into numerous intercalated ducts. These ducts are lined by low cuboidal epithelial cells. They produce the antibacterial agents lysozyme and lactoferrin. Interlobular

2. Striated ducts (excretory) ducts In serous secreting glands, several intercalated ducts unite to form a striated duct. These ducts are lined by columnar epithelial cells. The cells may appear striated around their base because their basal membrane has many infoldings lined with mitochodria. The basal membrane contains many Na-K and Cl-HCO3 pumps, the infolding therefore greatly increases the surface area along which HCO - and K+ can 3 Main excretory be secreted and Na+ and Cl- can be reabsorbed. Results in hypotonic saliva. duct 3. Interlobular (excretory) ducts Several intralobular ducts unite to form an interlobular duct. These ducts are lined with simple columnar or pseudostratified epithelial cells. They are located in the connective tissue septa draining the lobules

4. Main excretory duct Eventually several interlobular ducts will unite to form a main excretory Oral duct that will empty saliva into the oral cavity. cavity

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3 Parotid gland Striated duct cells

Serous cells The parotid glands are located in each . The duct system contains striated intralobular ducts and a main excretory duct (Stensen’s duct) that empties saliva into the oral cavity near the upper molar teeth. They are branched acinar glands and as such are composed of serous cells organized into acini which secrete:

i. α-amylase For breakdown of in the . ii. Proline-rich proteins Anti-microbial proteins. They also bind Ca2+ which may help maintain the tooth enamel.

Submandibular gland Striated duct cells

The submandibular glands are located inferior to the . The duct system contains striated intralobular ducts and a main excretory duct (Wharton’s duct) that empties saliva into the oral cavity via the sublingual caruncle. They are branched tubulo-acinar glands and as such are composed of a mixture of serous cells (acini) and mucous cells (tubules). The serous cell component predominates. In mixed areas, mucous tubules are capped with serous cells forming a ‘half-moon’ shaped structure . Serous cells called a Serous demilune The serous cells secrete α-amylase and proline-rich Mucous proteins, but also lysozyme (another antibacterial). cells

Mucous cells Sublingual gland

The sublingual glands are located in the floor of the oral cavity. The duct system does not contain striated intralobular ducts. The main excretory duct (Bartholin’s duct) empties saliva into the oral cavity via the sublingual caruncle. They are also branched tubulo-acinar glands composed of a mixture of serous (acini) and mucous (tubules) cells. The mucous cell component predominates. In mixed areas, the mucous tubules are capped with serous cells forming a serous demilune.

4 A2 Pancreas Centro-acinar cell The pancreas is the main enzyme producing accessory gland of the digestive system. It has an exocrine (serous acini) and an endocrine (islets of Langerhans) component.

Exocrine pancreas

Pancreatic acinar cells The exocrine pancreas is a branched acinar gland similar in structure to the parotid gland. The serous cells of the acini are packed full of secretory granules.

Centro-acinar cells The cuboidal intercalated duct cells extend into the . In these areas, the pale stained cells are Acinar cell termed centro-acinar cells. These cells secrete bicarbonate which is important for neutralization of acid in the .

Ducts Secreted enzyme enters the lumen of the acinus and travels into the intercalated ducts which unite Intercalated Non-striated to form non-striated interlobular ducts. The intralobular interlobular ducts empty into the main or accessory pancreatic ducts. is ultimately released into the duodenum at the major or minor duodenal papillae.

Enzymes

i. Trypsinogen The inactive form of the protease trypsin. Trypsinogen (left) is released into the duodenum where it is converted to trypsin Enteropeptidase (right; shown here bound to a trypsin inhibitor) by the duodenal enzyme enteropeptidase (enterokinase). Enteropeptidase cleaves a protein tail (highlighted) from trypsinogen to reveal its active site.

ii. Chymotrypsinogen The inactive form of the protease chymotrypsin. It is released into the duodenum and converted to chymotrypsin by trypsin.

iii. α-amylase (right) Digests carbohydrate/polysaccharide.

iv. Breaks down dietary fat molecules

v. Ribonuclease and Deoxyribonuclease Degrade nucleoproteins. 5 Clinical Correlation: Pancreatitis Pancreatitis is inflammation of the pancreas. Under normal conditions, pancreatic enzymes are manufactured in the serous acinar cells as pro-enzymes or zymogens (inactive forms of the enzyme). This ensures that they do not digest the cells that are making them. These zymogens are only activated when exposed to ideal conditions in the duodenum. In pancreatitis, the pancreatic enzymes (particularly trypsin) become activated in the pancreas instead of the duodenum and begin to digest the pancreatic tissue itself. It is most commonly caused by gallstones and /or excessive drug/alcohol use.

Control of pancreatic secretions (see lecture “Digestive system III”)

Enteroendocrine cells in the intestinal glands of the duodenum release the hormones secretin and cholecystokinin.

i. Secretin Produced by S-cells in the intestinal glands of the duodenum. Secretin stimulates and centro-acinar cells to produce their bicarbonate rich alkaline solution. This is effective at neutralizing acidic gastric products so that other enzymes can operate.

ii. Cholecystokinin Produced by I-cells in the intestinal glands of the duodenum. Cholecystokinin stimulates pancreatic acinar cells to release zymogen granules. It also targets smooth muscle of the gallbladder increasing bile release.

Endocrine pancreas

Identify the pale staining islets of Langerhans in the pancreas and refer to lectures on endocrine organs for more information regarding the hormones produced by these cells.

6 A3: Liver & Gallbladder

The liver is the body’s largest compound gland. It is a major metabolic and is important for degrading alcohol and drugs. It has stores glycogen, secretes glucose, plasma proteins, bilirubin (a by- product of hemoglobin breakdown) and bile salts.

Structure of the liver

i. Porta hepatis The liver is unusual in the fact that it has a dual blood supply. It receives arterial blood from the hepatic artery and also from the hepatic portal vein. In addition it manufactures bile which is passed to the gallbladder, via the , for storage.

The porta hepatis marks the point on the inferior surface of the liver where these structures enter/leave the liver.

1. Hepatic portal vein (afferent) Carries blood rich in absorbed IVC Aorta carbohydrates and proteins from the Hepatic veins intestines to the liver. The hepatic portal vein is responsible for 70-80% of blood flow through the liver.

2. Hepatic artery (afferent) Carries oxygenated blood from the celiac branch of the aorta to the liver.

3. Common heptic duct (efferent) 2 Carries bile, manufactured in the liver, to the gallbladder.

4. Lymphatics (efferent) Carry away from the liver to the thoracic duct. 3 4 Note that the hepatic veins leave the “Porta hepatis” liver to enter the inferior vena cava (IVC) 1 at the postero-superior aspect of the liver not at the porta hepatis.

ii. Stroma (supportive tissue) The liver is surrounded by a connective tissue capsule (Glisson’s capsule) which extends into the liver to form lobes. It surrounds the vessels/ducts as they enter/leave and run within the liver. The connective tissue eventually gives way to thin reticular fibers which support the liver cells and sinusoids.

iii. Parenchyma (functional tissue) The cells of the liver are epithelial cells called hepatocytes. They contain glycogen granules and are rich in rough . They are organized into functional units called lobules.

7 Structure of a classic liver lobule Portal triad The classic liver lobule is polyganol/hexagonal in shape with a prominent central vein, surrounded by portal triads. The lobes are defined by varying amounts of connective tissue (depending on Central species). Pigs have defined connective tissue septa vein between lobules, humans do not (as such they are harder to visualize).

i. Portal triads The portal triads are located at each ‘corner’ of the classic lobule and contain:

1. Venule (from hepatic portal vein) 2. Arteriole (from hepatic artery) 3. Bile duct (cuboidal )

ii. Sinusoids Sinusoids are large capillaries that carry Basal blood through the lobule from the lamina periphery to the central vein. They are lined by a layer of fenestrated endothelial cells that rest on top of a discontinuous basal lamina. They contain a mixture of arterial blood Fenestrated (from the hepatic artery) and venous blood endothelial (from the hepatic portal vein). cell

iii. Kupffer cells Kupffer cells are macrophages that are Hepatocytes located between sinusoid endothelial cells and within sinusoids. They are macrophages that remove bacteria or debris form and breakdown aged erythrocytes to recycle the heme. Central vein Sinusoid iv. Space of Disse The space of Disse lies between the hepatocytes and sinusoids. microvilli project into the space. Blood in the sinusoids passes through the Space of Disse fenestrations and into the space of Disse where it bathes the hepatocyte microvilli allowing the exchange of nutrients and metabolites.

8 v. Blood flow through the lobule The hepatic portal vein and hepatic artery enter the liver at the porta hepatis and branch repeatedly. Bile canaliculi A venule from the portal vein and an arteriole from Sinusoid the hepatic artery reach the portal triad. Central vein

Distributing branches run around the periphery of the lobule.

Blood enters the sinusoids from either the portal triad or from its peripheral distributing branches.

Nutrient rich blood from the venules and oxygen rich blood from the arterioles mix in the sinusoids and drain centripetally toward the central vein.

Blood from the central veins drain into a sublobar vein which empties into the hepatic veins.

The hepatic veins leave the liver and unite with the inferior vena cava.

vi. Bile canaliculi The bile canaliculi are tubular spaces that are surrounded by the plasma membranes of two adjacent hepatocytes.

Hepatocytes secrete bile into bile canaliculi which flows centrifugally toward peripherally located bile ducts in the portal spaces. These bile ducts have a distinct cuboidal epithelium. Portal triad Eventually the bile ducts empty into the hepatic ducts and leave the liver for the gallbladder. L and R hepatic ducts

Biliary tract

Follow the flow of bile through the biliary tract from the bile ducts of the portal triads to the duodenum. These duct components are lined with simple columnar epithelium and are thus distinct from surrounding and veins.

The is a smooth muscle thickening in the wall of the duodenum around the that controls the flow of bile into the duodenum. Bile duct

Note that the pancreatic duct joins the bile duct to Major duodenal release pancreatic juice simultaneously. papilla Pancreatic duct

9 Gallbladder

The gallbladder is located on the undersurface of the right liver lobe.

Function of the gallbladder

Gallbladder function includes:

i. Storage and concentration of bile by reabsorbing water. ii. Adds mucous to bile iii. If gallbladder is removed bile is stored in the . iv. Cholecystokinin causes contraction of smooth muscle in gallbladder wall.

Structure of the gallbladder

The gallbladder has a simple columnar epithelium with microvilli and a typical underlying which are folded. It has a smooth muscle muscularis that contracts to expel bile.

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