**4. Structure**

#### **4.1. Terminal secretory units**

The functional unit of a salivary gland is the terminal secretory unit called acini [1, 2]. Regardless of size and location, the terminal secretory unit is made up of epithelial secretory cells, namely, serous and mucous acini. The serous and mucous cells along with myoepithelial cells are arranged in an acinus or acini with a roughly spherical or tubular shape and a central lumen.

**Serous cells**: They are pyramidal in shape with a broad base on the basement membrane, and the apex faces the lumen. The serous cells have a spherical nucleus placed at the basal region of the cell along with numerous secretory granules in which macromolecule components of saliva are stored and are present in the apical cytoplasm. The granules are zymogen granules and are formed by glycosylated proteins which are released into a vacuole. The serous cells show acid phosphates, esterases, glucuronidase, glucosidase, and galactoside activity. The central lumen usually has fingerlike extensions located between adjacent cells called intercellular canaliculi that increase the size of the luminal surface of the cells [2].

**Mucous cells**: The secretory endpieces that are composed of mucous cells typically have a tubular configuration; when cut in cross section, these tubules appear as round profiles with mucous cells surrounding central lumen of larger size than that of serous endpieces. The nucleus is oval or flattened in shape and located above the basal plasma membrane. Sometimes, mucous cells have bonnet- or crescent-shaped appearance, which is made up of serous cells and are also known as demilunes first described by Giuseppe Oronzo Giannuzzi in 1865. The presence of demilunes is not clearly known, but these demilunes occur as a result of artifact during tissue preparation. Nowadays, recent studies like rapid freezing, freeze substitution, and three-dimensional reconstruction techniques have shown that serous cells align with mucous cells to surround a common lumen. The mucous cells show accumulation of large amounts of secretory product that pushes the nucleus and endoplasmic reticulum against the basal cell membrane.

The mucous secretion differs from secretion of serous in two important aspects:


In routine histological sections, the secretion of mucous cell appears unstained, and they are strongly stained when special stains like PAS, alcian blue, mucicarmine, etc. are used [1].

#### **4.2. Myoepithelial cells**

producing extensive lobulation. The glandular capsule forms from mesenchyme and sur-

• Different rates of cell proliferation between the outer and inner layers of the epithelial cord. • Fluid secretion by the duct cells which increases the hydrostatic pressure and produces a lumen within the cord. Further branching of the duct and structure and growth of

**VI. Cytodifferentiation:** The final stage of salivary gland development is the histodifferentiation of the functional acini and intercalated ducts. Myoepithelial cells arise from the epithelial stem cells in the terminal tubules and develop in concert with acinar

Parasympathetic nerves play an important role in epithelial tubulogenesis in the developing salivary gland which involve epithelial-mesenchymal interaction. The neurotransmitter, i.e., vasoactive intestinal peptide (VIP) and its receptor VIPR1, regulates various steps like epithelial proliferation, duct elongation, and lumen formation through cAMP or protein kinase A (PKA) pathway, thus linking epithelial tubulogenesis with parasympathetic neuronal function. Neurotrophic factor neurturin (NRTN), secreted by the buds, binds its receptor GFR alpha 2 and promotes functional nerve outgrowths to ensure parallel development of nerves and epithelium. Cystic fibrosis transmembrane conductance regulator (CFTR) causes lumen

The functional unit of a salivary gland is the terminal secretory unit called acini [1, 2]. Regardless of size and location, the terminal secretory unit is made up of epithelial secretory cells, namely, serous and mucous acini. The serous and mucous cells along with myoepithelial cells are arranged in an acinus or acini with a roughly spherical or tubular shape and a central lumen. **Serous cells**: They are pyramidal in shape with a broad base on the basement membrane, and the apex faces the lumen. The serous cells have a spherical nucleus placed at the basal region of the cell along with numerous secretory granules in which macromolecule components of saliva are stored and are present in the apical cytoplasm. The granules are zymogen granules and are formed by glycosylated proteins which are released into a vacuole. The serous cells show acid phosphates, esterases, glucuronidase, glucosidase, and galactoside activity. The central lumen usually has fingerlike extensions located between adjacent cells called intercel-

lular canaliculi that increase the size of the luminal surface of the cells [2].

**V. Canalization of presumptive ducts:** Canalization of the epithelial cord, with the formation of a hollow tube or duct, usually occurs by the sixth month in all the major salivary

The two main theories to explain the mechanism of canalization are:

the connective tissue septa continues at this stage of development.

rounds the entire glandular parenchyma.

glands.

68 Histology

cytodifferentiation.

expansion during development [7].

**4.1. Terminal secretory units**

**4. Structure**

These are the contractile cells associated with secretory endpiece and intercalated duct of the salivary glands. These cells are present between the basal lamina and the secretory or duct cells and are joined to the cells by desmosomes. They appear similar to smooth muscle but are derived from the epithelium. They are also known as basket cells or octopus sitting on a rock. The myoepithelial cells located around the secretory endpieces have stellate-shaped, numerous branching processes with a flattened nucleus and scanty perinuclear cytoplasm, but the cells associated with intercalated ducts have more fusiform shape and are elongated with fewer processes. These cells accelerate the initial flow of saliva from the acini, reduce luminal volume, support the underlying parenchyma, reduce the back permeation of fluid, and also help to maintain the patency. They maintain the cell polarity and structural organization of cells. They secrete various tumor suppressor proteins such as protease inhibitors and antiangiogenesis factors which provide a barrier against invasive epithelial neoplasm.

#### **4.3. Ducts**

It consists of hollow tubes that connect initially with the acinus, i.e., secretory endpieces, and extends to the oral cavity. It is not a pipeline or conduit for the passageway for the saliva, but it actively participates in the production and modification of saliva.

On the basis of location, ducts are of two types:

• **Intralobular ducts**: Those ducts which are within the lobule. The intercalated and striated ducts are intralobular ducts.

• **Interlobular ducts**: Those ducts which lie within the connective tissue within the lobules of the gland. The excretory ducts are interlobular ducts.

occasional leukocytes, fat cells, and plasma cells. Collagen and reticular fibers are also embedded in a ground substance which is composed of proteoglycans and glycoproteins. It consists of a surrounding capsule that delineates the gland from the adjacent structures. Blood vessels and nerves are also present that supply the parenchymal components, i.e., glandular components and excretory ducts. The plasma cells present in the connective tissue produce

Salivary Glands

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http://dx.doi.org/10.5772/intechopen.81213

• **Parotid glands:** The parotid gland is a purely serous gland, and all the acinar cells are similar in structure to the serous cells (**Figures 2** and **3**). Under the electron microscope, serous granules may have a dense central core, and the intercalated ducts are long branching along with pale-staining striated ducts, are numerous, and stand out evidently against the more densely stained acini. The connective tissue septa contain numerous fat cells which

• **Submandibular glands:** The submandibular gland is a mixed gland with both serous and mucous secretory units, but the serous units predominate. The mucous terminal portions are capped by demilunes of serous cells. Under the electron microscope, the intercalated ducts appear shorter in submandibular gland than those of the parotid, whereas the stri-

• **Sublingual glands:** The sublingual gland is also a mixed gland, but the mucous secretory units predominate. The mucous cells are present in tubular pattern along with serous

increase in number with age and leave an empty space in histologic sections.

immunoglobulins that are secreted into saliva by transcytosis.

**5. Histology**

**5.1. Major salivary glands**

ated ducts are usually longer.

**Figure 2.** Histology of serous gland [3].

#### *4.3.1. Intercalated duct*

These are lined by single layer of cuboidal epithelium and are surrounded by myoepithelial cell bodies, and their processes typically are found along the basal surface of the duct. Under the light microscope, the intercalated ducts are difficult to identify as they are compressed between the secretory units. Under the electron microscope, the intercalated ducts have centrally placed nuclei and a small amount of cytoplasm containing some rough endoplasmic reticulum and a small Golgi complex. A few secretory granules may be found in the apical cytoplasm, especially in the cells located near the endpieces. The apical cell surface has a few short microvilli projecting into the lumen, and lateral surfaces are joined by junctional complexes. The macromolecule components, i.e., lysozyme and lactoferrin, are stored in the secretory granules of the intercalated duct and contribute to the saliva.

#### *4.3.2. Striated ducts*

The striated ducts receive the primary saliva from the intercalated ducts which constitute the largest portion of the duct system and are lined by columnar cells with a centrally placed large, spherical nucleus and pale, acidophilic cytoplasm. Under the electron microscope, the basal cytoplasm of the striated duct cells is partitioned by deep infoldings of the plasma membrane producing numerous sheetlike folds that extend beyond the lateral boundaries of the cell and interdigitate with similar folds of adjacent cells. Between the membrane infoldings, a large amount of radially oriented mitochondria are located in the portion of the cytoplasm. The combination of infoldings and mitochondria accounts for the striations seen in the light microscope. These ducts are involved in active transport and are considered as site of electrolyte reabsorption especially of sodium and chloride and secretion of potassium and bicarbonate. They also synthesize and secrete glycoproteins such as kallikrein and epidermal growth factor.

#### *4.3.3. Excretory ducts*

These ducts are located in the connective tissue septa between the lobules of the gland and are larger in diameter than striated duct. These ducts are lined by pseudostratified epithelium with columnar cells extending from the basal lamina to the ductal lumen and small basal cells that sit on the basal lamina. As the smaller ducts join to form large excretory ducts, the number of basal cell increases, and scattered mucous (goblet) cells may be present. The main excretory duct may become stratified near the oral opening. Tuft or brush cells with long stiff microvilli and apical vesicles are seen and are considered as receptor cells as they show nerve endings adjacent to the basal portion of the cell. Dendritic cells are also seen and play an important role in immune surveillance.

#### **4.4. Connective tissue elements**

The cells that are found in the connective tissue of the salivary glands are similar to those in other connective tissues of the body and include fibroblasts, macrophages, mast cells, occasional leukocytes, fat cells, and plasma cells. Collagen and reticular fibers are also embedded in a ground substance which is composed of proteoglycans and glycoproteins. It consists of a surrounding capsule that delineates the gland from the adjacent structures. Blood vessels and nerves are also present that supply the parenchymal components, i.e., glandular components and excretory ducts. The plasma cells present in the connective tissue produce immunoglobulins that are secreted into saliva by transcytosis.
