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DIGESTIVE GLANDS
STRUCTURE OF A SALIVARY GLAND ( 17-1 and 17-2 )
We start the discussion by reviewing the general organization and function of a salivary gland, in particular its branching ducts (see Box 17-A ). An initial discussion concerning the general features of a compound or branched gland is included in Chapter 2, Epithelial Glands | Cell Biology.
Box 17-A
Classification of exocrine glands
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Depending on the structure of the excretory duct , glands can be divided into simple (unbranched duct) and branched or compound (branched duct).
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According to the structure of the secretory units , glands can be classified as tubular or alveolar (acinar).
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Considering the secretory product , glands are serous when they secrete a watery fluid, or mucous when the secretion is thick and rich in glycoproteins.
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Taking into account the secretory mechanism , glands can be merocrine when the product is released by exocytosis (for example, the pancreas). In holocrine glands (for example, the sebaceous glands of the skin), the whole cell is the secretory product. An apocrine gland (for example, the mammary gland) releases its product together with a small amount of the apical cytoplasm of the secretory cell.
A salivary gland is surrounded by a connective tissue capsule . Partitions or septa extend from the capsule into the gland, creating lobes as large divisions. Interlobar septa continue to branch as interlobular septa , subdividing lobes into several small lobules . The amount of connective tissue decreases from the interlobar septa to the interlobular septa. It is greatly reduced within each lobule.
Septa provide appropriate conduits for the main branches of a duct to extend from the interior of a gland to its exterior and for vessels and nerves to reach the interior of a gland.
The basic histologic features of a salivary gland are the secretory units , the acini and the excretory ducts . We start with the excretory ducts inside a lobule (see 17-1 ):
- 1.
An intercalated duct , lined by low squamous-to-cuboidal epithelium , is the smallest duct connecting an acinus to a striated duct (see 17-2 ). Its diameter is smaller than an acinus. Intercalated ducts are the longest in the parotid gland.
- 2.
A striated duct is lined by cuboidal-to-columnar epithelial cells with basal infoldings containing numerous mitochondria . It is well developed in the submandibular gland. The intercalated and striated ducts are modestly developed in the sublingual gland.
- 3.
A number of striated ducts leave the lobule to connect with an interlobular duct . An interlobular duct is initially lined by cuboidal-to-columnar epithelium and becomes pseudostratified columnar . Interlobular ducts are located in interlobular septa .
- 4.
Several interlobular ducts converge to form a lobar duct present in interlobar septa . Lobar ducts are lined by stratified columnar epithelium , one of the few sites in the body with this type of epithelium.
- 5.
Several lobar ducts, lined by stratified squamous epithelium , join the main duct that drains the entire gland near the opening into the oral cavity.
The parotid, submandibular (or submaxillary) and sublingual glands are classified as branched tubuloalveolar glands .
Saliva ( 17-3 )
Saliva, amounting to a half-liter daily, contains proteins, glycoproteins (mucus), ions, water and polymeric immunoglobulin A (pIgA) attached to a secretory component (SIgA).
The submandibular gland produces about 70% of the saliva. The parotid gland contributes 25% and secretes an amylase-rich saliva. The production of saliva is under the control of the autonomic nervous system. Upon stimulation, the parasympathetic system induces the secretion of a water-rich saliva; the sympathetic system stimulates the release of a protein-rich saliva.
The mucus and water in saliva lubricate the mucosa of the tongue, cheeks and lips during speech and wallowing, dissolve food for the function of the taste buds and moisten food for easy swallowing.
The protective function of the saliva depends on the antibacterial function of three constituents:
- 1.
Lysozyme , which attacks the walls of bacteria.
- 2.
Lactoferrin , which chelates iron necessary for bacterial growth.
- 3.
SIgA , which neutralizes bacteria and viruses.
The digestive function of saliva relies on:
- 1.
Amylase (ptyalin), which initiates the digestion of carbohydrates (starch) in the oral cavity.
- 2.
Lingual lipase , which participates in the hydrolysis of dietary lipids.
Parotid gland ( 17-4 and 17-5 )
The parotid gland is the largest salivary gland. It is a branched tubuloalveolar gland surrounded by a connective tissue capsule with septa , representing a component of the stroma , the supporting tissue of the gland. Adipose cells are frequently found in the stroma.
Septa divide the gland into lobes and lobules. Septa also provide support to blood vessels, lymphatics and nerves gaining access to the acini , the main components of the parenchyma , the functional constituent of the gland.
Acini are surrounded by reticular connective tissue, a rich capillary network, plasma cells and lymphocytes. Acini consist mainly of serous secretory cells and, therefore, are classified as serous acini .
Each serous acinus is lined by pyramidal cells with a basally located nucleus. Similar to all protein-producing cells, a prominent rough endoplasmic reticulum system occupies the cell basal region. Secretory granules are visible in the apical region.
The lumen of the acinus collects the secretory products, which are transported by long intercalated ducts to the less abundant striated ducts (see 17-5 ).
The secretory product of the serous acini is modified by the secretion of the striated duct and then transported by interlobular ducts and lobar ducts to the oral cavity by a main excretory duct (Stensen's duct) . See Box 17-B for pathology conditions.
Box 17-B
Parotid gland: Mumps, rabies, autoimmunity and tumors
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In addition to its role in the production of saliva, the parotid gland is the primary target of the rabies and mumps virus transmitted in saliva containing the virus. The mumps virus causes transient swelling of the parotid gland and confers immunity. Two complications of mumps are viral orchitis and meningitis . Bilateral orchitis caused by the mumps virus can result in sterility.
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Sjögren's syndrome is a systemic autoimmune disease that affects primarily women. Two forms of the syndrome are characterized: (1) Primary Sjögren's syndrome, defined by a significant reduction or cessation in the production and secretion of saliva by the parotid glands and tears. (2) Secondary Sjögren's syndrome, characterized by dry mouth and dry eye associated with an autoimmune connective tissue disease (rheumatoid arthritis, systemic lupus erythematosus or scleroderma).
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The parotid gland is the most frequent site for slow-growing benign salivary gland mixed tumor (pleomorphic adenoma). It consists of myxochondroid zones with ductal epithelial and mesenchyme-like myoepithelial cells. Its surgical removal is complicated by the need to protect the facial nerve running through the parotid gland. Enucleation of mixed tumors results in a multifocal high recurrence rate.
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Warthin tumor (papilloma cystoadenoma lymphomatosum), the second most common benign salivary gland tumor, occurs in the parotid gland with a high-risk incidence in smokers. The tumor stroma consists of a papillary arrangement of lymphoid tissue centers surrounded by squamous, mucous and sebaceous epithelial cells. This tumor may develop from intraparotid or periparotid lymph nodes.
Submandibular (submaxillary) gland (see 17-4 )
The submandibular gland is a branched tubuloalveolar gland surrounded by a connective tissue capsule. Septa derived from the capsule divide the parenchyma of the gland into lobes and lobules. Although both serous and mucous cells are present in the secretory units, the serous cells are the predominant component . Mucous cell–containing acini are capped by serous demilunes .
The intercalated ducts are shorter and the striated ducts are longer than those in the parotid gland . Adipocytes are not frequently seen in the submandibular gland. The main excretory duct of the submandibular gland (Wharton's duct) opens near the frenulum of the tongue.
Sublingual gland (see 17-4 )
Contrasting with the parotid and submandibular glands, which are surrounded by a dense connective tissue capsule, the sublingual gland does not have a defined capsule. However, connective tissue septa divide the glandular parenchyma into small lobes.
The sublingual gland is a branched tubuloalveolar gland with both serous and mucous cells , although most of the secretory units contain mucous cells. The intercalated and striated ducts are poorly developed . Usually each lobe has its own excretory duct that opens beneath the tongue.
Exocrine pancreas ( 17-6 to 17-8 )
The pancreas is a combined endocrine and exocrine gland . The endocrine component is the islet of Langerhans and represents about 2% of the pancreas volume.
The main function of the endocrine pancreas is the regulation of glucose metabolism by hormones secreted into the bloodstream (see discussion of the islet of Langerhans in Chapter 19, Endocrine System).
The exocrine pancreas is a branched tubuloacinar gland organized into four anatomic components:
- 1.
A head , lying in the concavity of the second and third parts of the duodenum.
- 2.
A neck , in contact with the portal vein.
- 3.
A body , placed anterior to the aorta.
- 4.
A tail , ending near the hilum of the spleen.
The pancreas lies close to the posterior abdominal wall in the upper abdomen; therefore, it is protected from severe trauma.
Blood is provided by vessels derived from the celiac artery, the superior mesenteric artery and the splenic artery. The venous drainage flows into the portal venous system and the splenic vein. Efferent innervation is through the vagus and splanchnic nerves.
The pancreas has structural similarities to the salivary glands:
- 1.
It is surrounded by connective tissue but does not have a capsule proper.
- 2.
Lobules are separated by connective tissue septa carrying blood and lymphatic vessels, nerves and excretory ducts.
The functional histologic unit of the exocrine pancreas is the acinus (see 17-6 to 17-8 ). The lumen of the acinus is the initiation of the secretory-excretory duct system and contains centroacinar cells that are unique to the pancreas . Centroacinar cells are continuous with the low cuboidal epithelial lining of the intercalated duct . Centroacinar cells and the epithelial lining of the intercalated duct secrete HCO 3 – , Na + and water. The secretion of HCO 3 – is maintained by the cystic fibrosis transmembrane conductance regulator (CFTR) that also provides Cl – .
The intercalated ducts merge into intralobular ducts. The intralobular ducts join to form the interlobular ducts, which drain into the main pancreatic duct. The main pancreatic duct (of Wirsung) runs straight through the tail and the body, collecting secretions from ductal tributaries. It turns downward when it reaches the head of the pancreas and drains directly into the duodenum at the ampulla of Vater , after joining the common bile duct . A circular smooth muscle sphincter (of Oddi) is seen where the common pancreatic and bile duct cross the wall of the duodenum.
The exocrine pancreas lacks striated ducts and myoepithelial cells . Intercalated ducts converge to form interlobular ducts lined by a columnar epithelium with a few goblet cells and occasional enteroendocrine cells.
PANCREATIC TUMORS
The pancreatic duct–bile duct anatomic relationship is of clinical significance in pancreatic tumors localized in the pancreas head region , because compression of the bile duct causes obstructive jaundice .
Pancreatic ductal adenocarcinoma (PDAC) is the most common primary malignant tumor of the pancreas. PDAC arises in the head of the pancreas. Tumoral masses obstruct and dilate the distal common bile and pancreatic ducts.
Most PDAC tumors harbor oncogenic mutations in the gene K-ras, which cannot be targeted by drugs.
A more aggressive PDAC squamous subtype involves mutations of the KDM6A gene found on the X chromosome. In males, the KDM6A gene mutation coexists with a mutation of a related gene on the Y chromosome, UTY. Both mutations are associated with the PDAC squamous subtype.
KDM6A is a histone demethylase that modifies gene regulatory DNA sequences highly expressed in PDAC. Essentially, KDM6A exerts a tumor suppressive role, a possibility that provides a promissing therapeutic strategy for the PDAC squamous subtype.
The close association of the pancreas with large blood vessels, the extensive and diffuse abdominal drainage to lymph nodes and the frequent spread of carcinoma cells to the liver via the portal vein are factors contributing to the ineffectiveness of surgical removal of pancreatic tumors.
Cystic tumors of the pancreas are not neoplastic. This category includes serous cystoadenomas (with cysts containing a clear fluid) and mucinous cystoadenomas (with cysts filled with a mucoid product). Untreated mucinous cystoadenomas evolve into an infiltrating tumor (mucinous cystoadenocarcinoma).
Less common are the endocrine tumors of the pancreas that can be detected as isolated pancreatic masses or a component of the multiple endocrine neoplasia syndrome, type 1 (MEN1) .
MEN1 is an autosomal dominant hereditary endocrine cancer syndrome characterized primarily by tumors of the parathyroid glands, gastroenteroendocrine cells and adenohypophysis. This tumor type does not show activation of the K -ras gene or p53 gene inactivation.
Endocrine tumors of the pancreas can be well differentiated (with structural evidences of endocrine function) or moderately differentiated. Gastrinomas, insulinomas and glucagonomas are examples of endocrine tumors showing cytoplasmic secretory granules. These tumors belong to the category of syndromic functioning tumors (associated with a syndrome). For example, gastrinomas produce the Zollinger-Ellison syndrome , that, as you remember from our discussion in Chapter 15, Upper Digestive Segment, is characterized by multiple peptic ulcers caused by continuous stimulation of HCl production by parietal cells in the stomach.
Functions of the pancreatic acinus ( 17-9 ; see 17-7 )
The pancreatic acinus is lined by pyramidal cells joined to each other by apical junctional complexes, which prevent the reflux of secreted products from the ducts into the intercellular spaces.
The basal domain of an acinar pancreatic cell is associated with a basal lamina and contains the nucleus and a well-developed rough endoplasmic reticulum. The apical domain displays numerous zymogen granules and the Golgi apparatus (see 17-7 ).
The concentration of about 20 different pancreatic enzymes in the zymogen granules varies with the dietary intake. For example, an increase in the synthesis of proteases is associated with a protein-rich diet . A carbohydrate-rich diet results in the selective synthesis of amylases and a decrease in the synthesis of proteases. Amylase gene expression is regulated by insulin, an event that stresses the significance of the insuloacinar portal system .
The administration of a cholinergic drug or of the gastrointestinal hormones cholecystokinin and secretin increases the flow of pancreatic fluid (about 1.5 to 3.0 L/day) (see 17-9 ).
The polypeptide hormone cholecystokinin , produced in enteroendocrine cells of the duodenal mucosa, binds to specific receptors of acinar cells and stimulates the release of zymogen .
Secretin is released when acid chyme enters the duodenum. Secretin is produced in the duodenum, binds to receptors on the surface of centroacinar cells and intercalated ductal cells and triggers the release of water and HCO 3 – and Na + through a Na + –HCO 3 – cotransporter into the pancreatic ducts.
HCO 3 – ions and the alkaline secretion of Brunner's glands, present in the submucosa of the duodenum, neutralize the acidic gastric chyme in the duodenal lumen and activate the pancreatic digestive enzymes.
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