Salivary Glands

1. Introduction

The human salivary glands are a group of compound exocrine glands that produce saliva, an important
fluid required for lubrication, immunity, mastication, deglutition, taste, speech, etc. The salivary glands
consist of a series of branched ducts which terminate in a spherical or tubular end pieces or acing; a
correlation can be made to a bunch of grapes, with the stems analogous to the ducts and the grapes
indicating the secretory end pieces. Serous and mucous cells are the two main types of secretory cells
present in salivary glands. gland and divided into two main groups. The major salivary glands include the
paired parotid, submandibular, and sublingual glands. Additionally, the mucosa of the upper aerodigestive
tract is lined by hundreds of small, minor salivary glands. The connective tissue forms a capsule around
the gland and extends into it, dividing groups of secretory units and ducts into lobes and lobules. Blood
vessels, lymphatic vessels and nerves that supply the gland, are present within the capsule [1].

The salivary glands are compound glands as they have more than one tubule entering the main duct, and
the architectural arrangement is tubuloacinar, where acing are secretory units. These secretory units are
merocrine as they release only the secretion of the cell from the secreting units. Myoepithelial cells are
contractile cells associated with the secretory end-pieces and intercalated ducts of the salivary gland [2].

FIGURE 1. Structural organization of salivary gland

2. Classification, structure, and anatomy of salivary glands

• On the basis of size and location, salivary glands are classified as :

A. Major salivary glands

○ Parotid

○ Submandibular

○ Sublingual

B. Minor salivary glands

○ Labial and buccal

○ Glossopalatine

○ Palatine

○ Lingual
I. Anterior lingual gland (glands of Blandin and Nuhn)

II. Posterior lingual serous gland (von Ebner’s glands)

III. Posterior lingual mucous gland

• On the basis of secretion [3], they are classified as:

○ Serous

○ Mucous

3. Development of the salivary glands

The development of the glandular tissue involves the interaction of the epithelium with the underlying
mesenchyme to form the functional part of the tissue. These epithelial-mesenchymal interactions are also
known as secondary induction in which the mesenchyme is in close proximity with the epithelium and is
required for the normal development of the epithelium. For example, epithelial-mesenchymal interactions
regulate both the initiation and growth of the glandular tissue and the eventual cytodiferentiation of cells
within the salivary glands. The mesenchyme, therefore, is required for normal development as well as
formation of the supporting part of the adult gland.

All salivary glands follow a similar development pattern. The functional glandular tissue (parenchyma)
develops as an epithelial outgrowth (glandular bud) of the buccal epithelium that invades the underlying
mesenchyme. The connective tissue stroma (capsule and septa) and blood vessels form from the
mesenchyme. The mesenchyme is composed of cells derived from neural crest and is important for the
normal differentiation of the salivary glands.

As the bud formation begins during development, the portion of the bud closest to the stomodaeum
eventually differentiates into the main excretory duct of the gland, while the most distal portion of the bud
forms the secretory end pieces or acing. The origin of the epithelial buds is believed to be ectodermal in
the parotid and minor salivary glands but endodermal in origin in the submandibular and sublingual
glands. The parotid gland originates near the corners of the primitive oral cavity by the sixth week of
prenatal life. The submandibular glands arise from the floor of the mouth at the end of the sixth or the
beginning of the seventh week in utero. The sublingual gland forms lateral to the submandibular
primordium at about eighth week. All the minor salivary glands bud from buccal epithelium but start after
their 12th prenatal week.

Stages of development

I. Bud formation, i.e., induction of oral epithelium by underlying mesenchyme: The mesenchyme
underlying the oral epithelium induces the proliferation in the epithelium which results in tissue
thickening and bud formation.

II. Formation and growth of epithelial cord: A solid cord of cells forms from the epithelial bud through
cell proliferation. Condensation and proliferation occur in the surrounding mesenchyme which is
closely associated with the epithelial cord. The basal lamina plays a role in influencing
morphogenesis and differentiation of the salivary glands through-out the development.

III. Initiation of branching in terminal parts of epithelial cord and continuation of glandular
differentiation: The epithelial cord proliferates rapidly and branches into terminal bulbs.
IV. Dichotomous branching of epithelial cord and lobule formation: The branching continues at the terminal
portion of the cord forming an extension treelike system of bulbs. As branching occurs, the connective tissue
differentiates around the branches, eventually producing extensive lobulation. The glandular capsule forms
from mesenchyme and surrounds the entire glandular parenchyma. The glandular capsule forms from
mesenchyme and surrounds the entire glandular parenchyma.

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 glands.

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

1) Different rates of cell proliferation between the outer and inner layers of the epithelial cord.

2) 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 the connective tissue septa continues at this
stage of development.

VI. Cytodiferentiation: The final stage of salivary gland development is the histodiffer-entiation of the
functional acing and intercalated ducts. Myoepithelial cells arise from the epithelial stem cells in the
terminal tubules and develop in concert with acinar cytodiferentiation.

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
expansion during development [7].

Major salivary glands

These are the largest, bilaterally paired, and situated extraorally, but their secretion reaches the oral cavity
by variable long ducts.

Parotid gland
The parotid gland is the largest of all the salivary glands and weighs about 15–30 g. It is located below
the external acoustic meatus between the ramus of the mandible and the sternocleidomastoid. It is divided
by facial nerve into a superficial and deep lobe. The superficial lobe, overlying the lateral surface of the
masseter, is defined as the part of the gland lateral to the facial nerve. The deep lobe is medial to the facial
nerve and located between the mastoid process of the temporal bone and the ramus of the mandible. An
accessory parotid gland may also be present lying anteriorly over the masseter muscle between the parotid
duct and zygomatic arch [4].
In the normal parotid salivary gland there is no true separation into superficial and deep lobes (McKenzie,
1948)

Parotid Capsule
The investing layer of the deep cervical fascia forms a capsule for the gland. The fascia splits (between the
angle of the mandible and the mastoid process) to
enclose the gland. The superficial lamina, thick and adherent to the gland, is attached above to the zygomatic
arch. The deep lamina is thin and is attached to the styloid process, the mandible and the tympanic plate. A
portion of the deep lamina, extending between the styloid process and the mandible, is thickened to form the
stylomandibular ligament which separates the parotid gland from the submandibular salivary gland.
Anatomic Landmarks
• Approximately 75% or more of the parotid gland overlies the masseter muscle; the rest is retromandibular
• Facial nerve enters the parotid fossa by passing between the stylohyoid muscle and the posterior belly of the
digastric muscle, which splits the gland into a “superficial lobe” and a “deep lobe” that are connected by an
isthmus
• Deep lobe lies adjacent to the lateral pharyngeal space—thus tumors of the deep lobe are observed as
swellings in the oropharynx
• Transverse facial artery parallels the parotid duct slightly superior to the duct
• Buccal and zygomatic branches of the facial nerve form an anastomosing loop superficial to the parotid duct

External Features
The gland resembles a three sided pyramid. The apex of the pyramid is directed downwards. The gland has
four surfaces:
(1) Superior (base of the pyramid);
(2) superficial;
(3) Anteromedial; and
(4)posteromedial.
The surfaces are separated by three borders: (1) Anterior; (2) posterior; and (3) medial.
NERVE SUPPLY OF THE PAROTID GLAND

1. Parasympathetic nerves are secretomotor. They reach the gland through the auriculotemporal nerve. The
preganglionic fibers begin in the inferior salivatory nucleus; pass through the glossopharyngeal nerve, its
tympanic branch, the tympanic plexus and the lesser petrosal nerve; and relay in the otic ganglion. The
postganglionic fibers pass through the auriculotemporal nerve and reach the gland.

2. Sympathetic nerves are vasomotor, and are derived from the plexus around the external carotid artery.

3.Sensory nerves to the gland come from the auriculotemporal nerve, but the parotid fascia is innervated by
the sensory fibers of the great auricular nerve (C2
LYMPHATIC DRAINAGEOF PAROTID GLAND

The lymphatics from the parotid gland drain into the superficial and deep parotid lymph nodes, which in turn
drain into deep cervical lymph nodes. The superficial parotid nodes are located in the superficial fascia over
the gland and deep nodes, deep to parotid capsule. Few members of the group are located in the superficial
zone of the parotid gland. Conley and Arena (1963), whose account is the most frequently quoted, state that
“the gland contains from 20 to 30 lymph follicles and lymph nodes” in addition to other lymph nodes “in
association with the lateral, posterior, deep and inferior portions of the gland”.

CLINICAL ASPECTS
Pathologies associated with the salivary glands may range from infectious to non-infectious inflammatory
processes.

The key to unraveling disorders of the parotid gland is to ask the patient about a history of pain and swelling in
the region of the gland and determining the relationship of pain and swelling to meals, as acute onset of pain
on swelling with salivation is indicative of an obstructed duct. Some patients may complain about a lump in
the gland. Determine if there has been any change in the size of the mass and over what period of time this has
occurred. Also ask about constitutional symptoms (such as unintentional weight loss, night sweats, and low-
grade fevers) as this may be suggestive of a non-benign process. Other important aspects include a history of
dry mouth, a history of autoimmune disorders, and vaccination history. All of these factors are suggestive of a
diffuse issue with the glands.

Parotid Gland Stones (Sialolithiasis)

Calculi or stones in the salivary gland are more common in the submandibular gland than the parotid gland.
The presence of the stone obstructs the flow of saliva from the gland leading to acute swelling with meals. The
swelling usually resolves about an hour after the onset of symptoms. Palpation of the duct or visualization of
the duct orifice will likely reveal the offending agent. Plain radiography may also reveal the presence of the
stones, as the majority of them are radio-opaque.

Parotid Gland Inflammation (Parotitis)

Both infectious and non-infectious inflammatory processes can affect the parotid glands. Historically, the
mumps infection – caused by the mumps rubela virus (a paramyxovirus) – caused painful swelling of the
parotid glands in childhood. other pathogens that are able to incite an inflammatory response within the
salivary glands. These include:

Influenza
Coxsackie
Cytomegalovirus
Human immunodeficiency virus (HIV)
Granulomatous infections (i.e. tuberculosis)
Echovirus
The infectious processes usually result in bilateral manifestation of the disease, with painful swelling to both
glands. There are usually systemic signs of infection such as erythema (redness around the area), malaise
(generalized weakness), tenderness, and fever. These disorders are highly communicable and adequate
precaution should be taken to limit their spread.

Suppurative Sialadenitis
This process is similar to the acute parotitis, with the exception that the offending agent is bacterial in origin. It
may also occur postoperatively as well. In cases where the flow of saliva is inhibited, the static saliva acts as a
nidus (a place where the development of something is promoted) for bacterial proliferation. Situations such as
dehydration, trauma, or immunosuppression may predispose individuals to these conditions.

Patients with acute suppurative sialadenitis may have, in addition to painful swelling, cutaneous changes
(erythema) and purulent (consisting of or containing pus) discharge from the ducts of the affected gland.
Resident oral flora (Haemophilus influenza, Escherichia coli, Streptococcus pneumonia, and Staphylococcus
aureus) are common offenders isolated from cultures of the purulent discharge..

During surgical removal of the parotid gland or parotidectomy, the facial nerve is preserved by removing the
gland in two parts, superficial and deep separately. The plane of cleavage is defined by tracing the nerve from
behind forwards.

Frey’s Syndrome
Frey’s syndrome is an interesting complication that sometimes develops after penetrating wounds of the
parotid gland. When the patient eats, beads of perspiration appear on the skin covering the parotid. This
condition is caused by damage to the auriculotemporal and great auricular nerves. During the process of
healing, the parasympathetic secretomotor fibers in the auriculotemporal nerve grow out and join the distal end
of the great auricular nerve. Eventually, these fibers reach the sweat glands in the facial skin. By this means, a
stimulus intended for saliva production produces sweat secretion instead.

Submandibular gland

It is the second largest salivary gland, also known as submaxillary salivary gland, weighs about 7–16 g
and is almost the size of a walnut. It is situated in the submandibular triangle, which has a superior
boundary formed by the inferior edge of the mandible and inferior boundaries formed by the anterior and
posterior bellies of the digastric muscle. The gland is approximately J-shaped being indented by the
posterior border of the mylohyoid which divides into a larger part superficial to the muscle and a smaller
part lying deep to the muscle [4]. The submandibular gland duct, also known as Wharton’s duct, is thin-
walled, about 5 cm long, and runs forward above the mylohyoid muscle lying just below the mucosa of
the floor of the mouth in its terminal portion. The duct opens on the floor of the mouth, on the summit of
the sublingual papilla also called the caruncula sublingualis, lateral to the lingual frenulum [2].

Surfaces of the submandibular gland

The superficial part of the submandibular gland has three surfaces—inferolateral, lateral, and medial.
The inferolateral surface is covered by: (1) the superficial fascia containing the platysma and the cervical
branch of the facial nerve; (2) the deep fascia; and deep to this (3) the facial vein and a
few submandibular lymph nodes. (Most of the lymph nodes lie in the groove between the submandibular gland
and the mandible.) The facial artery grooves the posterosuperior part of this surface, then loops
anteroinferiorly between the gland and the medial pterygoid muscle, and appears at the inferior margin of the
mandible. The lateral surface is related to the medial pterygoid,
facial artery, and mandible. The medial surface extends from the mylohyoid line inferiorly to the bellies of the
digastric muscle. It is related to the mylohyoid, hyoglossus, hypoglossal, and lingual nerves and the
submandibular ganglion. The posterior part of the medial surface is in contact with the pharynx. This surface
is grooved by the facial artery. The submandibular duct arises from the medial surface of the gland and passes
anteriorly in the angle between the side of the tongue and mylohyoid.

The deep part of the gland is a thin, flat process which extends anteriorly on the lateral side of the duct
superior to the mylohyoid. are transverse sections through the head at the level of the submandibular
glands.

Nerves and vessels of the submandibular gland

(1) The sensory nerves to the gland are carried by the lingual nerve. (2) The parasympathetic secretomotor
supply is from the nerve cells in the submandibular ganglion. The preganglionic
parasympathetic fibers to the ganglion come through the chorda tympani branch of the facial nerve and the
lingual nerve. (3) The sympathetics are carried by a plexus on the facial artery.

The arterial supply to the submandibular gland is from several small branches of the facial and submental
arteries.
CLINICAL ASPECTS OF SUBMANDIBULAR GLAND

1) Excision of the submandibular gland for calculus or tumor is done by an incision below the angle of the
jaw. Since the marginal mandibular branch of the facial nerve passes poster inferior to the angle of the jaw
before crossing it, the incision must be placed more than 2.5 cm below the angle to preserve the nerve.

2) The chorda tympani supplying secretomotor fibers to submandibular and sublingual salivary glands lies
medial to the spine of sphenoid. The auriculotemporal nerve supplying secretomotor fibers to the parotid gland
is related to lateral aspect of spine of sphenoid. Injury to spine may involve both these nerves with loss of
secretion from all three salivary glands.

Sublingual gland
 It is the smallest of all the three major salivary glands that is almond shaped and weighs about 3–4 g. The
gland lies above the mylohyoid, below the mucosa of the floor of the mouth, medial to the sublingual
fossa of the mandible, and lateral to the genioglossus [4]. It comprises of one main gland duct with
various small ducts. The main duct, Bartholin’s duct, opens with or near the submandibular duct. Several
smaller ducts, duct of Rivinus, open independently along the sublingual fold [2].

Vessels and nerves of the sublingual gland

The arterial supply to the sublingual gland is from the sublingual branch of the lingual artery.
The nerve supply is from branches of the lingual nerve. The lingual nerve contains post-ganglionic
parasympathetic fibers from the cells of the submandibular ganglion. It also contains sensory and post-
ganglionic sympathetic fibers

Sublingual Salivary Gland and Cyst Formation

The sublingual salivary gland, which lies beneath the sublingual fold of the floor of the mouth, opens into the
mouth by numerous small ducts. Blockage of one of these ducts is believed to be the cause of cysts under the
tongue.
Minor salivary glands

The minor salivary glands are placed below the epithelium in almost all parts of the oral cavity. These
glands comprise numerous small groups of secretory units opening via short ducts directly into the mouth.
 They lack a distinct capsule, instead mixing with the connective tissue of the submucosa or muscle fibers
of the tongue or cheeks [2].

2.2.1. Labial and buccal glands

These glands are present on the lips and cheeks and comprise of mucous tubules with serous demilunes
[1, 2].

2.2.2. Glossopalatine glands

These are located to the region of the isthmus in the glossopalatine fold but may extend from the posterior
extension of the sublingual gland to the glands of the soft palate [1, 2].

2.2.3. Palatine glands

These are located in the glandular aggregates present in the lamina propria of the posterolateral aspect of
the hard palate and in the submucosa of the soft palate and uvula [1, 2].

2.2.4. Lingual glands

The glands of the tongue can be divided into various groups [1, 2]. The anterior lingual glands (glands of
Blandin and Nuhn) are present near the apex of the tongue. The ducts open on the ventral surface of the
tongue near the lingual frenulum. The posterior lingual mucous glands are present lateral and posterior to
vallate papillae and in association with lingual tonsil. The ducts of these glands open on the dorsal surface
of the tongue. The posterior lingual serous glands (von Ebner’s glands) are located between the muscle
fibers of the tongue below the vallate papillae, and the ducts open into the trough of circumvallate
papillae and at the rudimentary folate papillae on the sides of the tongue.

4. STRUCTURE

1. Terminal secretory units

The functional unit of a salivary gland is the terminal secretory unit called acini. Regardless of size and
location, the terminal secretory unit is made up of epithelial secretory cells, namely, serous and mucous
acing. The serous and mucous cells along with myoepithelial cells are arranged in an acinus or acing 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 canaliculated that
increase the size of the luminal surface of the cells

MUCOUS CELLS:
The secretory end pieces 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 end pieces. 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:

• The secretion of mucous cells has little or no enzymatic activity and is responsible mainly for
lubrication and protection of the oral tissues.

• The ratio of carbohydrates to protein is greater, and large amount of sialic acid and occasionally
sulfated sugars are present [2].

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].

Myoepithelial cells
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 siting on a rock. The myoepithelial cells located around
the secretory end pieces 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 low of saliva from the acing,
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.

2. DUCTS
It consists of hollow tubes that connect initially with the acinus, i.e., secretory end pieces, 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.

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 end pieces. 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.

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 micro-scope. 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.

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 pseudostratiied 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. 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.

5. Histology

5.1. Major salivary glands

• Parotid glands: The parotid gland is a purely serous gland, and all the acinar cells are similar in
structure to the serous cells. 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 acing. The connective tissue septa
contain numerous fat cells which increase in number with age and leave an empty space in histologic
sections.

• 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 striated ducts are usually longer.
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 demilunes and may be present at the blind
ends of the tubules. The intercalated and striated ducts are poorly developed, and mucous tubules open directly
into ducts lined with cuboidal or columnar cells without typical basal striations.

Figure: Histology of serous gland

Figure 3 Histology of mixed gland

5.2. Minor salivary glands

• Labial and buccal glands: The glands of the lips and cheeks are a mixed gland consisting of mucous
tubules with serous demilunes. The intercalated ducts appear variable in length, and the intralobular
ducts possess only a few cells with basal striations.

• Glossopalatine glands: The glands present in the region of isthmus in the glossopalatine fold are purely
mucous gland.

• Palatine glands: Palatine glands are a purely mucous gland, and the excretory ducts may have an
irregular contour with large distensions as they course through the lamina propria.

• Lingual glands: In anterior lingual glands, the anterior portion of the glands is chiefly mucous in
nature, whereas the posterior portions are mixed. The posterior lingual glands are purely mucous
glands, but von Ebner’s glands are purely serous gland.
 SALIVA
PHYSIOLOGY OF SALIVA

Formation and secretion of saliva

The oral cavity is kept moist by a film of fluid called saliva, which constantly coats its inner surfaces and
occupies the space between the lining oral mucosa and the teeth. It is a complex fluid, produced by the
salivary gland, whose important role is maintaining the well-being of mouth. The whole saliva that bathes the
oral cavity is primarily a mixture of secretions from the paired major (parotid, submandibular, sublingual)
glands and the numerous minor (labial, buccal, palatine, and lingual) glands.
The formation of saliva occurs in two stages:

1. Formation of macromolecular components: The structure of acinar cells consists of abundant RER,
prominent Golgi complexes, and numerous secretory vesicles. Synthesis of secretory proteins begins
with gene transcription and manufacture of mRNA to carry the sequence information from the nucleus
to ribosome in the cytoplasm. Protein synthesized in the RER is settled to the Golgi complexes in
transport vesicles. After fusion of their unit membrane with surface cell membrane, they rupture and
they are released to the external environment. Rupture and rearrangement of the lipid layer of both
permit the continuity of the granule membrane and cell membrane.

2. Formation of fluid components: After appropriate stimulation it is thought that the free Ca++ is
released from storage site within the endoplasmic reticulum. Free cytoplasmic Ca2+ concentration can
increase five- to tenfold in a second after such a stimulation which brings out significant
compensatory changes that include the opening of the two membrane ion channels for passage of K+
and Cl−. When K+ is released from the cell, a compensatory uptake of Na+ and Cl− occurs. The Cl−
exits the cell between the channels at luminal surface, and Na+ enters the lumen through the
paracellular pathway. The result of these ionic relocations is a lux of water into the lumen via the
osmotic coupling of NaCl and H2O.
 Figure 5 Formation of Saliva

SECRETION OF SALIVA
 Secretion of saliva is initiated by reflexly induced nerve impulses,
 Control of salivation depends on neurotransmitter release from the nerve endings in the salivary glands,
which will be further elaborated below under the physiological aspect. (Bullock, 2007, p.517-519)
 Saliva is secreted into the ducts by acinar cells that line the beginning of the salivary duct.
 Hormones such as androgens, estrogens, glucocorticoids and peptides also influence salivary composition.
 Salivary reflexes are caused by thought aroma, or taste of food or by the presence of food in the alimentary
canal.

 Autonomic Nervous Control

The ANS controls both the volume and type of saliva secreted.
 Salivary gland metabolism and growth are controlled by ANS.
 The autonomic nervous system can be divided into two different
types; sympathetic and parasympathetic nerves.
(Mese et al., 2007, p.711-713)
 Parasympathetic Nerves:
Taste and mastication are the principal stimuli (unconditioned reflex) but others such as sight, thought and
smell of food (conditioned reflex) also play a role. Taste and mechanical stimuli from the tongue and other
areas of the mouth excite parasympathetic nerve impulses in the afferent limbs of the salivary reflex which
travel via the glossopharyngeal (CN IX), facial (CN VII), vagal (CN X) (taste) and the trigeminal (CN V)
(chewing) cranial nerves..
These afferent impulses are carried to the salivary nuclei located approximately at the juncture of the pons and
the medulla. In turn impulses from the salivary centres can be modulated i.e. stimulated or inhibited by
impulses from the higher centres in the central nervous system; for example, the taste and smell centres in the
cortex and the lateral hypothalamus where the regulation of feeding, drinking and body temperature occurs.
Also, in stressful situations dry mouth sometimes occurs, as a result of the inhibitory effect of higher
centres on the salivary nuclei. The secretory response of the gland is then controlled via the glossopharyngeal
nerve synapsing in the otic ganglion, the postganglionic parasympathetic fibers carrying on to the parotid
gland and via the facial nerve synapsing in the submandibular ganglion and carrying on to the sublingual and
submandibular glands.

 most active during the day.

 mainly responsible for the secretion of water and electrolytes but low in proteins
 parasympathetic innervation to the salivary glands is transmitted via cranial nerves.
 whilst eating it creates more watery, or serous saliva; predominantly produced by the parotid
gland, and partly by the submandibular gland.
 it turns up the flow of saliva by releasing a chemical, acetylcholine (ACh), which stimulates the
glands to make more saliva.
 Salivary flow rates and enzymatic secretions are increased by parasympathetic nervous system
activity.
 At high flow rates, less time for reabsorption and secretion, thus saliva contains a
lower concentration of Na+ and Cl- and higher concentrations of K+.
 At low flow rates there is more time for reabsorption and secretion, thus saliva
contains a higher concentration of Na+ and Cl- and lower concentrations of K+.
 HCO3- concentration increases when salivary flow increases because HCO3-
secretion is increased when salivary glands are stimulated by parasympathetic nervous
system. (Mese et al., 2007, p. 711-713)
 if these glands get diseased, damaged, or affected by drugs, they may not make enough saliva, leading
to dry mouth or a condition known as hypofuntion.. (Fejerskov & Kidd, 2003, p. 6-13)

Sympathetic Nerves:
The relevant efferent sympathetic nerves originate in the spinal cord, synapse in the superior cervical
ganglia and then travel along blood vessels to the salivary glands.
  may occur when in certain situations, fear, stress or anger are aroused, or during hard physical
exercise.
 mainly responsible for the secretion of proteins accompanied by exocytosis in acinar cells
 produces predominantly thicker mucus saliva by inducing changes in the reabsorption of electrolytes
mainly produced by the sublingual and partly the submandibular glands
 affects the salivary gland secretions indirectly by innervating the blood vessels that supply the glands.

Both parasympathetic and sympathetic stimuli result in an increase in salivary gland secretions.
 Both serous and mucous saliva are produced however the amount of each is altered depending on which
nerves (parasympathetic or sympathetic) are in control.
 Finally, both parasympathetic and sympathetic nervous stimulation can lead to myoepithelium contraction
which causes the expulsion of secretions from the secretory acinus into the ducts and eventually to the oral
cavity. (Fejerskov & Kidd, 2003, p.6-13) (Mese et al., 2007, p.711-713) ( Bullock, 2007, p. 517-519)
 E.g. Lysyl-bradykinin stimulates the blood vessels and capillaries of the salivary gland to vasodilate and
increased capillary permeability respectively. The resulting increased blood flow to the acinar allows
production of more saliva. (Bullock, 2007, p. 517-519)
(Reference from 4,6 & 7: Saliva and Oral Health, Salivary Secretion, Taste and Hyposalivation, NMS
Physiology )

Figure 4 Flowchart on the Innervation of Saliva through the Autonomic Nervous System
Blood supply

The blood supply to the glands also influences secretion. An extensive blood supply is required for the rapid
secretion of saliva. There is a concentration of capillaries around the striated ducts where ionic exchange takes
place whilst a lesser density supplies the terminal secretory acing.
The main arterial supply to the parotid gland is by the superficial temporal and external carotid arteries.
Venous drainage is provided by numerous veins which drain into the retromandibular and external jugular
veins. Lymph drainage goes mainly via the superficial and deep parotid nodes to the deep cervical nodes. The
submandibular gland takes its arterial blood supply from branches of the facial artery and a few branches of
the lingual artery. Venous drainage is via the common facial and lingual veins and lymph drainage goes via
the submandibular lymph nodes and the deep cervical and jugular chains. The sublingual gland is served by
the sublingual branch of the lingual artery as well as the submental branch of the facial artery and drainage is
by the submental branch of the facial vein. Lymph drainage goes to the submandibular lymph nodes.

Innervation of the GLANDS by the NERVES

(Fejerskov & Kidd, 2003, p. 6-13)

 Formation of saliva is due to a unilateral, central reflex because stimulation of one side of the mouth induces
ipsilateral salivation where the flow rate is dependent on the intensity of the stimulus applied.
 A portal system consisting of 2 capillary networks in series: 1) dense network with ducts and 2) acing end
piece, provides a rich blood supply to the salivary glands. this arrangement is crucial for the production of
saliva since the fluid, originates from the capillaries and the interstitial fluid.
 Stimulation of the parasympathetic supply to the glands can easily overcome the sympathetic vasoconstrictor
tone. This leads to vasodilatation and an increased blood flow, resulting in increased secretion of saliva from
the gland.
 The autonomic nerves, that are parasympathetic fibers of the facial and glossopharyngeal nerves and
sympathetic fibers that follow the blood vessels supplying the glands, act together to produce saliva.
 Via activation of specific cell surface membrane receptors on the richly innervated secretory end piece and
ductal gland tissue, both types of the autonomic nervous system cause salivation to the mouth.
 In general, the parasympathetic pathway provides the main control of the salivary glands.
 Formation of saliva is not dependent on pressure filtration but rather due to active transport of solutes by the
gland tissue and a dramatic increase in the metabolic turnover on stimulation.
 The flowchart below explains how the nerves mentioned above will activate the respective neurotransmitters
to affect the volume and composition of saliva.
 The effect of the neurotransmitters on the formation of saliva will be further elaborated below, under
physiological process.

Quantity, Quality
The autonomic nervous system controls the quality and quantity of the secreted saliva.

The quality of saliva refers to the composition of saliva, whereas the quantity refers to the amount of saliva
secreted.

The type and quantity of saliva secreted is important in maintaining the overall health of the oral cavity.

Quantity

In unstimulated saliva, there is a basal level of saliva secretion to the mouth. However, the amount of saliva
secreted from the salivary glands is under the influence of higher centers in the brain, wherein the
parasympathetic pathway provides the main control of salivary glands. Stimulation of the parasympathetic
supply to the glands can easily overcome the sympathetic vasoconstrictor tone.

The higher centers are linked to the salivary nuclei in the brain. When the masticatory and/or gustatory
afferents are stimulated, they pass the message on to the salivary nuclei, which in turn relays the message on to
the higher centres. The higher centres will then process the stimulus and pass the response message (to
increase or decrease secretion of saliva) to the salivary nuclei. The salivary nuclei will then increase
parasympathetic or sympathetic stimulation of the parasympathetic or sympathetic nerves, which synapses
with the effector salivary glands to increase or decrease saliva flow rate accordingly.

Parasympathetic stimulation from the brain in response to stimulus from the masticatory and/ or gustatory
afferents causes increased secretion of saliva and increased blood flow (vasodilation) to the salivary glands for
the further production and secretion of additional saliva from the glands. The outcome is watery saliva with a
high flow rate and relatively low protein content (in parasympathetic stimulation), whereas sympathetic
stimulation leads to reduced blood flow to the salivary glands, a lower flow rate and much thicker saliva. As a
result of this central control, unstimulated saliva is usually inhibited during sleep, fear and mental depression.

Many other factors also influence the amount of saliva secreted, e.g. water balance of body and situational
changes such as the composition of the diet

(Ole Fejerskov & Edwina Kidd, 2003, pgs 11 (Fig 2.3 Reflex arch of Salivary Secretion),13-18.)

The quantity of the saliva affects the ability of saliva to carry out its functions in the oral cavity. For example,
increased salivary flow is stimulated immediately after the beginning of mastication of food. The mouth
responds with increased salivary flow to firstly lubricate the oral cavity to prevent abrasion and damage to the
oral mucosa, and secondly allow the food to be softened and dissolve allowing tasting of the food.

The importance of the regulation of the quantity of the saliva can also be seen in physiological diseases such
as salivary gland hypofunction, wherein the lack of saliva results in dental caries and other conditions.

Quality of Saliva
The quality of saliva varies with the quantity of saliva produced. As flow rate increases, the concentrations of
total salivary protein, sodium, total calcium, chloride and bicarbonate increases to varying extents whilst the
total concentration of phosphate decreases.

The composition of saliva also depends on the type of gland from which it is secreted, the nature of stimulus
applied (e.g. taste/chewing) and the time period in which the stimulus is applied. For example, saliva samples
collected in early time period after stimulation has markedly lower salivary protein, sodium concentration as
compared to saliva sample collected following 15 minutes of sustained stimulation due to the higher flow rate
of saliva induced with stimulation.

The quality of saliva also affects the ability of saliva to carry out its functions in the oral cavity. Taking the
example of the lack of the major buffer system in the oral cavity, the bicarbonate pH buffer, due to a mutation
in the gene coding for carbonic anhydrase VI (hence a lack of functional carbonic anhydrase VI). The inability
of the oral cavity to buffer itself adequately against the production of lactic acid by the oral microbes after a
glucose-rich meal would result in the integrity of the tooth enamel being gradually compromised over time as
the acid "eats" the enamel, with the eventual result being dental caries.
The regulation of the quantity and quality of saliva in response to situational changes can therefore be seen to
be important in allowing saliva to fulfill its functions in the oral cavity. The functions of saliva are explored in
greater detail in the rest of the page below.

Flow rate
Salivary flow rate exhibits circadian variation and peaks in the late afternoon; the acrophase. Normal salivary
flow rates are in the region of 0.3-0.4 ml/min when unstimulated and 1.5-2.0 ml/min when stimulated,
although both rates have wide normal ranges (see Chapter 3). Approximately 0.5 – 0.6 liters of saliva is
secreted per day. The contribution of the different glands to whole saliva varies according to the level of
stimulation. For unstimulated saliva, about 25% comes from the parotid glands,
60% from the submandibular glands, 7-8% from the sublingual gland and 7-8% from the minor mucous
glands. During sleep, flow rate is negligible. For highly stimulated saliva the contribution from the parotids
increases to an estimated 50%, the submandibular contribute 35%, the sublingual 7-8% and 7-8% comes from
the minor mucous glands.
Many drugs used for the treatment of common conditions such as hypertension, depression and allergies (to
mention but a few), also influence salivary flow rate and composition.
The determination of a patient’s salivary flow rate is a simple procedure. Both unstimulated and stimulated
flow rates can be measured and changes in flow can be monitored over time to establish a norm for that
patient.
Other clinical investigations of salivary function such as sialography and scintiscanning require referral for
specialist evaluation.

COMPOSITION OF SALIVA
The composition of saliva varies according to many factors including the gland type from which it is secreted.
The average compositions of both unstimulated and chewing stimulated whole saliva are shown in Table 1.2.
 Introduction to Composition of Saliva

Saliva is a dilute fluid, over 99% being made up of water. The concentrations of dissolved solids(organic and
inorganic) are characterized by wide variation, both between individuals and within a single individual.

The relative proportion contributed to the whole saliva by each of the gland pairs depends on the degree of
stimulation. Thus, under resting conditions, the submandibular glands contribute 69%, the parotid glands 26%,
and the sublingual glands 5% (mean values) of the total secretion derived from these three major gland pairs.
Under conditions of increased exogenous stimulation, the submandibular glands again account for the largest
and the sublingual glands for the smallest fraction of the total secretion from the major glands, but the relative
proportion of the total secretion contributed by the parotid glands increases. Thus, the submandibular glands
contribute 63.7%, the parotid glands 34%, and the sublingual glands only 2.8%. It has also been established
that the mucosal and labial glands in the oral cavity make some contribution to the total volume of saliva
under stimulated conditions.
 (Youngt and Schneyer, 1981, P.1 )

Organic composition of saliva proteins

Proteins comprise the bulk of the organic content of saliva but identification of each of them has been more
difficult. In studies on human parotid saliva, the presence of at least 20 separate protein fractions has been
reported, while in submandibular saliva 21 fractions have been found.
(Youngt and Schneyer, 1981, P27)

Alpha-Amylase

 Major digestive enzyme of saliva.

 80% is synthesized in the parotid glands, 20% in the sub-mandibular glands.
 most abundant, accounting for as much as 40-50% of the total salivary gland-produced protein
 60-120mg/100ml in parotid saliva, (30% of parotic saliva)
 25mg/100ml in submandibular saliva
 Hydrolyzes alpha-1,4 bonds of starches such as amylase and amylopection
 Maltose is the major end-product (20% is glucose)
 Several isoenzymes present, both glycosylated and non-glycosylated,
 Molecular weights ranging from 54 to 57 kDa, depending on the degree of glycosylation

Antimicrobial proteins
Most of the proteins in saliva exhibit antimicrobial functions and they are thus grouped under one category.
Summarized below are the quality, quantity, origin and brief description of functions of each individual
protein component of saliva.
( Amerongen and Bolscher and Veerman, Page 2, Table 1)
 OTHER ORGANIC COMPOUNDS

Free amino acids

 low concentrations (below 0.1mg/100ml).

Urea
 about 12-20mg/100ml.
 Hydrolysed by many bacteria with the release of ammonia, leading to a rise in pH.

Carbohydrates

 Normally only traces of free carbohydrates exist in saliva.

 Glucose present at concentrations 0.5-1mg/100ml, but may be raised in diabetics.

Lipids

 Secreted by major salivary glands.

 Concentration 80-100mg/l.
 Comprised of neutral lipids (about 75%), glycolipids (20-30%) and phospholipids (2-5%)
 Neutral lipids are mainly free fatty acids, cholesterol, monoglycerides, diglycerides and triglycerides.
 Minor salivary glands contain more lipids (about 400mg/l), glycolipids forming the major group.
 Majority of lipids in all saliva secretions are associated with proteins
 Inorganic Composition of Saliva

Hydrogen Ions (Ole Fejerskov & Edwina Kidd, 2008.)

Hydrogen ions in saliva have several sources of origin:

 secretion via glands as inorganic or organic acids
 produced by oral microbiota
 taken into oral cavity in acidic drinks
 The concentration of H+ in saliva has the greatest influence on the chemical reactions in the oral cavity:
o equilibria between calcium phosphate in dental hard tissue and surrounding liquid phase
o solubility, as well as activity, of important salivary enzymes
The variable sources of hydrogen ions as well as its ability to complex with many substances makes the acid-
base balance a complex and mutable process

Calcium Ions
The concentration of calcium in saliva is influenced by salivary flow rate:
 calcium is excreted by the glands together with proteins into the lumina of the acing by active transport
 concentration strongly affected by circadian rhythm
 either circulating as Ca++ ion or as bound calcium (to phosphate, bicarbonate, small organic ions and
macromolecules) depending on salivary pH value
 special roles of macromolecules such as statherin and histidine in oral calcium homeostasis
 normal ratio of Ca++ to bound calcium is 1:1, with Ca++ concentration increasing with decreasing pH; most
salivary calcium is in ionised form when pH is less than 4

Inorganic Phosphate
Inorganic phosphate in saliva found as phosphoric acid H3PO4 and its conjugates: H2PO4-, HPO4,2- and
PO4,3-
Its concentration is affected by salivary flow rate as well as salivary pH, and also (to a smaller extent
compared to calcium) circadian rhythm:
 concentrations of each type dependent on salivary pH; decreased pH leads to decreased concentration of the
tertiary ion
 with increased flow rate decreases total inorganic phosphate concentration
Depending on pH, inorganic phosphate can be complexed to inorganic ions or proteins. Less than 10% forms
dimer form pyrophosphoric acid - an inhibitor of calcium phosphate precipitation; and influences calculus
formation.
Functions of inorganic phosphate include
 contributes to solubility product of calcium phosphate, which is crucial in maintaining tooth structure
 important as a buffer
 an essential nutrient for oral microflora for metabolic pathways
Fluoride
The concentration of fluoride in saliva depends on fluoride in the environment, such as fluoridated drinking
water and dental products used for caries prophylaxis. Basal concentration of fluoride is less than 1 micromole
per liter, but can be much higher in places where levels of fluoride in drinking water are high. Fluoride also
enters saliva via facilitated transport over membranes of salivary gland tissue. Clearance rate of inorganic
phosphate is dependent on salivary flow rate (Ole Fejerskov & Edwina Kidd, 2008, Pg 38).

Variations in salivary composition

(Effects of Diet on Salivary Secretion and Composition, by Colin Dawes)
Factors that influence salivary composition
1. Non-Dietary
SOURCE OF SALIVA.
-The main electrolytes in human saliva are sodium, potassium, calcium, chloride, bicarbonate, and inorganic
phosphate; -There are quantitative differences in the relative proportions of these electrolytes in the major
salivary gland secretions. For instance, parotid saliva is relatively low in calcium and high in phosphate as
compared with submandibular and sublingual secretions. -Types of proteins and their concentrations are
different in the different secretions, eg, most of the salivary amylase is derived from the parotid glands.

FLOW RATE.

Flow rate has a decided influence on salivary composition. In general, as the flow rate is increased slightly
above the unstimulated rate, sodium and bicarbonate concentrations and pH increase, whereas potassium,
calcium, phosphate, chloride, urea, and protein concentrations decrease. At higher flow rates, sodium, calcium,
chloride, bicarbonate, and protein concentrations and pH increase, whereas the phosphate concentration
decreases and the potassium concentration shows little further change. The effect of flow rate on the
composition of saliva has been studied in greatest detail with parotid saliva, but limited studies suggest that
these findings also apply to the other major salivary gland secretions. Thus, flow rate is a critical variable in
any study of the effects of diet on saliva.

DURATION OF STIMULATION

-When the flow rate of stimulated parotid saliva is maintained constant for several minutes, the composition of
the saliva changes considerably with duration of stimulation. -Although almost all components of saliva show
a change in concentration during the first one or two minutes of stimulation, the concentrations of total
protein, calcium, bicarbonate, and chloride and the pH, are particularly affected and may not achieve steady
state levels even after 15 minutes of stimulation at constant flow rate. -Total protein, calcium, and bicarbonate
concentrations and pH increase with duration of stimulation, whereas the chloride concentration decreases in
proportion to the rise in bicarbonate concentration. -Hence, in any study of the effect of diet on the
composition of stimulated saliva, the duration of stimulation must be standardized.

NATURE OF THE STIMULUS

-Recent studies have shown that the nature of the stimulus decidedly influenced the protein concentration in
parotid saliva in some subjects. -14 Similar results have been reported by Caldwell and Pigman15 for
submandibular saliva. -Other studies have shown that the salivary glands respond differently to electric,
pharmacologic, and gustatory stimuli.

PLASMA COMPOSITION
-For many components of saliva collected under standardized conditions, a positive correlation exists between
the concentrations in plasma and saliva for calcium, urea, and potassium, whereas the phosphate concentration
in human saliva is relatively independent of the concentration in plasma. -At a constant flow rate, the
bicarbonate concentration in human saliva has been found to be directly related to plasma pCO2.

TIME OF DAY

-The time of day at which saliva samples are collected can have a decided influence on both salivary flow rate
and composition. -Thus in any study of the effect of diet on the composition of saliva it is always necessary to
collect samples at one particular time of day.

2. Dietary
local reflex effects and the systemic effects on salivary flow rate and composition.
-- local reflex effect: -> Foods that require vigorous mastication or that are highly flavored will cause a
decided increase in salivary flow rate. The increase in flow rate alone will affect salivary composition.
--systemic effects of diet: -> consumption of a particular diet causes either an immediate specific effect on
salivary composition that is not attributable to a change in flow rate, or a long term change in salivary flow
rate, or composition that may take some time to develop.

FLUORIDE

-The concentration of fluoride in saliva is only about 0.01 ppm. -Although it has been shown that oral
ingestion of 1 to 10 mg of fluoride can cause an increase in salivary fluoride levels over about the following
two hours, there appears to be little data on the relation of salivary fluoride concentration to the level of dietary
fluoride intake at more normal levels of intake.

UREA.-
-plaque microorganisms readily produce ammonia from urea to cause a rise in plaque pH. -the pH of plaque
from fasting subjects is always higher than that of the adjacent unstimulated saliva, which suggests that in the
absence of an external source of carbohydrate, the physiologic levels of urea in saliva are sufficient to allow
the plaque microorganisms to maintain a positive pH differential between plaque and saliva. -the level of urea
in saliva is directly related to the level in blood, and that the level of urea in blood is directly related to the
level of protein intake. Thus diets high in protein might be expected to maintain relatively high salivary urea
levels. Most of the experiments on the effect of diet on saliva have been confounded because of inadequacies
in experimental design such as too few subjects, lack of control subjects, and inadequate standardization of the
saliva collection technique.

FUNCTIONS OF SALIVA
The functions of saliva are linked to its composition of water, ions, gases, buffers, and salivary proteins.
Saliva protects the teeth through mechanisms that relate to its chemical composition, as well as
mechanical effects of saliva flow, thereby determining oral health. Many of these functions are shown in
the figure below.

Functions of Saliva. Referenced from Bardow, Lagerlof, Nauntofte & Tenovuo, 2008, p. 190.

The functions of saliva are:

• Protection: The protective functions of saliva is expressed as:

a. Lubricant
 b. Mechanical washing

• Buffering: This occurs in two ways:

a. Many bacteria need a specific pH for growth; saliva prevents potential pathogens from colonizing
in the mouth by denying them optimal environmental conditions.
b. Plaque microorganisms can produce acids from sugars, which if not rapidly buffered and cleared
by saliva can demineralize enamel.

• Taste: It dissolves substances to be carried to taste buds and also contains a protein, called gustin,
which is necessary for growth and maturation of taste buds.

• Antimicrobial action: This occurs in various ways as:

a. Lactoferrin binds free iron and in doing so deprives bacteria of its essential element.

b. Lysozyme hydrolyzes the cell wall

C. Histatin proteins with antibacterial property.

D. Immunoglobulin, i.e., secretory IgA, clumps or agglutinates microorganisms.

• Maintenance of tooth integrity: Saliva is saturated with calcium and phosphate ions, and interaction
with saliva results in postoperative maturation through diffusion of such ions. This maturation
increases surface hardness, decreases permeability, and increases the resistance of enamel to caries.

• Tissue repair: The rate of wound contraction is significantly increased in saliva due to the presence of
peptides and proteins present in saliva.

• Digestive Function

 The presence of salivary amylase helps begin the process of digestion of starch breakdown in
the oral cavity.
 Glycoproteins in the saliva helps to facilitate mastication, bind masticated food into a bolus
aiding swallowing, and protects the soft mucosal surface from damage by coarse foods.
 Saliva acts a solvent to dissolve food substances thus allowing taste.

Inhibition of Dental Caries Saliva serves a

 immunological function e.g. secretory IgA

 enzymatic function via presence of peroxidase, lysozyme
 mechanical function of cleaning the tooth surface
 maintenance of supersaturation with respect to hydroxyapatite
 protective remineralization of carious lesion via ionic action e.g. fluoride, calcium

 Buffer System in the Saliva

 The salivary bicarbonate/carbonate buffer system responsible for rapid neutralization of acids produced by the
metabolism of microbes in the oral cavity.

 Formation of Dental Pellicle

 Saliva protects the tooth surface against wear by creating a film of salivary mucins and proline-rich
glycoprotein, forming the dental pellicle.

 The early pellicle proteins, proline-rich proteins (PRP) and statherin, promote remineralization of the enamel
by attracting calcium ions.

 demineralization is retarded by the pellicle proteins in concert with calcium and phosphate ions in saliva and
in the plaque fluid.

 Antibacterial, Anti-microbial, Anti-fungal Function of Salivary Proteins

o Secretory IgA prevents the adherence of oral microorganisms to the enamel pellicle via agglutination.
o Peroxidase inhibits acid production and growth of many oral microbes and fungi.
o Salivary Lysozyme assists in the lysis of bacteria in conjunction with other antibacterial systems.

 Prevention of Halitosis and Cleansing of the Oral Cavity

o Increased water in the saliva and salivary flow reduces halitosis by diluting and eliminating organic
constituents of saliva producing methyl mercaptan and H2S.
o Agglutinated bacteria, food debris and oral epithelial cells are loosened by saliva and subsequently swallowed.

 Other Functions
 Protective: provides lubrication of soft oral tissues preventing abrasion during mastication, speech etc.
 Speech facilitation

Table 1.2: The composition and chewing-stimulated whole saliva

7. CLINICAL CONSIDERATIONS
A. RADIATION CARIES: Radiation caries is a rampant form of dental decay that may occur in
individuals who receive a course of radiotherapy that include exposure of salivary glands [1, 2, 11].

• Etiology

Carious lesions are produced due to the exposure of salivary glands and reduced low of saliva,
decreased pH, decreased buffering capacity, and increased viscosity.

• Signs

Superficial lesions attack the buccal, occlusal, incisal, and lingual surfaces. It includes cementum
and dentin in cervical lesions. Lesions progress around the teeth circumferentially and resulting in
loss of the crown.

B. Sjogren’s syndrome: It consists of keratoconjunctivitis, xerostomia, and rheumatoid arthritis. The

cause of the disease can be genetic, autoimmunological, etc.

• Features include dry mouth and dry eyes due to hypofunction of lacrimal and salivary glands. Most
patients are treated symptomatically; ocular lubricants and salivary substitutes are given.

C. Xerostomia (dry mouth): It is defined as a subjective complaint of dry mouth that may result from a
decrease in the production of saliva. It is not a disease but a symptom caused by many factors.

• Etiology

○ Sjogren’s syndrome

○ Therapeutic radiation of head and neck

○ Surgical removal of salivary glands

○ Diabetes mellitus
By Christopher from Salem, OR, USA (248/365: The burnt tongue) [CC BY-SA 2.0
(http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons
 Fig 2 – Image showing the mouth of a patient suffering from xerostomia.

○ Acute viral infections involving salivary glands result in temporary xerostomia

○ Anxiety, mental stress, and depression may temporarily decrease salivary low

• Symptoms

○ Oral dryness (most common)

○ Halitosis

○ Burning sensation

○ Loss of sense of taste or bizarre taste

○ Difficulty in swallowing

○ Tongue tends to stick to the palate

○ Decreased retention of denture

• Signs

○ Saliva pool disappears

○ Mucosa becomes dry

○ Tongue shows glossitis and fissured with papilla atrophy

○ Angular cheilitis

○ Rampant caries at the cervical or cusp tip

○ Periodontitis

○ Candidiasis

8. CONCLUSION

Salivary glands are compound, exocrine, and tubuloacinar in nature secreting saliva which keeps the oral
cavity moist. The secretory units are acing, and saliva reached the oral cavity through ducts. Saliva is of
great importance to diagnostic and prognostic pathology.
 References

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[4] Chaurasia’s BD. Human Anatomy Regional and Applied Dissection and Clinical: Head, Neck and
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[5] Cutler LS, Gremski W. Epithelial-mesenchymal interaction in the development of the salivary gland.
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