Saliva is a watery substance formed in the mouths of animals, secreted by the salivary glands. Human saliva is motly water with electrolytes, mucus, white blood cells, epithelial cells, glycoproteins, enzymes (such as amylase and lipase), antimicrobial agents such as secretory IgA and lysozyme. Saliva keeps the oral mucosa wet, protecting the tissues and facilitating gustation. It also hydrates and lubricates the food with mucus, to facilitate swallowing. The enzymes found in saliva begin the digestion of starches and fats in the mouth. This helps breaking down food particles entrapped within dental crevices and protects the teeth from bacterial decay.

Estimates of daily production range from 0.75 to 1.5 liters but salivation nearly stops during sleep. In humans, the submandibular gland secretes 70–75% of the saliva while the parotid gland secretes about 20–25% and small amounts are secreted by the other salivary glands.

Various animals have special uses for saliva. Some swifts use a gummy saliva to build nests on the walls of caves. Many snakes hunt with venomous saliva injected by fangs. Some caterpillars secrete silk from their salivary glands.

Anatomy of mammalian salivary glands

Salivary glands are divided into lobules containing acini and ducts. Secretory cells are found in a group, or acinus (plural acini). Each acinus is located at the terminal part of the gland connected to the ductal system, with many acini within each lobule of the gland. Each acinus consists of a single layer of cuboidal epithelial cells surrounding a lumen, a central opening where the saliva is deposited after being produced by the secretory cells. The three forms of acini are classified in terms of the type of epithelial cell present and the secretory product being produced: serous, mucoserous and mucous.

Secretions from the acini are drained by intercalated ducts which join to form striated ducts. These drain into ducts situated between the lobes of the gland (called interlobar ducts or secretory ducts). All of the human salivary glands terminate in the mouth.

Parotid gland

A pair of mainly serous salivary glands located below and in front of each ear canal, draining their secretions into the vestibule of the mouth through the parotid duct. Each gland lies posterior to the mandibular ramus and anterior to the mastoid process of the temporal bone. It has four surfaces: superficial or lateral, superior, anteromedial, and posteromedial. It also has three borders: anterior, medial, and posterior. The gland can be easily palpated as it rests immediately deep to the skin.

The parotid duct, a long excretory duct, emerges from the anterior surface of each gland, superficial to the masseter muscle. The duct pierces the buccinator muscle and opens into the mouth on the inner surface of the cheek, usually opposite the maxillary second molar. The parotid papilla is a small elevation of tissue that marks the opening of the parotid duct on the inner surface of the cheek.

The superficial temporal and the maxillary artery are the branches of the external carotid artery that supply the parotid gland. Venous return is to the retromandibular veins.

Submandibular gland

The paired submandibular gland is located next to the lower jaw, superior to the digastric muscle. It is divided into superficial (most of the gland) and deep lobes, which are separated by the mylohyoid muscle. Its products are drained by the submandibular duct or duct of Wharton. This is a 5 cm long duct drains saliva into the mouth through the sublingual caruncles on each side of the lingual frenulum on the ventral surface of the tongue.

The secretion produced is a mixture of both serous fluid (rich in salivary amylase) and mucus. Approximately 65-70% of saliva in the oral cavity is produced by the submandibular glands, even though they are much smaller than the parotid glands. This gland can be palpated at a position inferior and medial to the angle of the mandible.

Within each lobule, the acini (also called alveoli) of the submandibular glands are grouped in adenomeres. The acini within an adenomere are all composed of serous or mucous cells. The gland is classified as tubuloacinar. It has long striated ducts and short intercalated ducts.

The submandibular gland receives its blood supply from the facial and lingual arteries. The gland is supplied by sublingual and submental arteries and drained by common facial and lingual veins.

Sublingual gland

The sublingual glands are a pair of major salivary glands located inferior to the tongue, anterior to the submandibular glands. They are the smallest, most diffuse, and the only unencapsulated major salivary glands. The secretion produced is mainly mucous in nature, however, it is categorized as a mucoserous (mixed) gland. Saliva is secreted through 8-20 excretory ducts known as the Rivinus ducts. The largest of all, the sublingual duct (of Bartholin) joins the submandibular duct to drain through the sublingual caruncle. Approximately 5% of saliva entering the oral cavity comes from these glands. The gland receives its blood supply from the sublingual and submental arteries.

Minor salivary glands

There are 800 to 1,000 minor salivary glands located throughout the oral cavity within the submucosa of the oral mucosa in the tissue of the buccal, labial, and lingual mucosa, the soft palate, the lateral parts of the hard palate, and the floor of the mouth. They are 1 to 2 mm in diameter and unlike the major glands, they are not encapsulated by connective tissue, only surrounded by it. The gland has usually a number of acini connected in a tiny lobule. A minor salivary gland may have a common excretory duct with another gland, or may have its own excretory duct. Its secretion is mainly mucous and the innervation is provided by the facial cranial nerve (CN VII).

Von Ebner's glands

Von Ebner's glands are serous salivary glands which reside adjacent to the fossae of the circumvallate and foliate papillae just anterior to the terminal sulcus. These glands secrete many enzymes including lingual lipase and begin lipid hydrolysis in the mouth. They empty their serous secretion into the fossae of the foliate and circumvallate papillae. This secretion presumably flushes material from the moat to enable the taste buds to respond rapidly to changing stimuli.

Von Ebner's glands are innervated by cranial nerve IX, the glossopharyngeal nerve.

Innervation

Salivary glands are innervated by the parasympathetic and sympathetic divisions of the autonomic nervous system. Parasympathetic stimulation evokes a copious flow of saliva. In contrast, sympathetic stimulation produces either a small flow rich in protein or no flow at all.

• Parasympathetic innervation to the salivary glands is carried via cranial nerves. The parotid gland receives its parasympathetic input from the glossopharyngeal nerve (CN IX) via the otic ganglion, while the submandibular and sublingual glands receive their parasympathetic input from the facial nerve (CN VII) via the submandibular ganglion.

• Sympathetic innervation of the salivary glands takes place via spinal nerves in the thoracic segments T1-T3. The pre-ganglionic neurons synapse in the superior cervical ganglion. The postganglionic neurons release norepinephrine which binds β-adrenergic receptors on the acinar and ductal cells of the salivary glands and leads to increased salivation.

In the absence of food, parasympathetic stimulation keeps saliva flowing at appropriate levels for speech, swallowing, rest and sleep. Salivation increases when you smell, see, taste or think about food, even if you do not eat it. Drooling is an extreme instance of overproduction of saliva. During times of stress, such as before speaking in public, sympathetic stimulation takes over inhibiting parasympathetic stimulation thus reducing salivation. This results in the symptom of dry mouth that we associate with anxiety. If you dehydrate, salivation is reduced causing the mouth to feel dry and prompting you to drink water.

While you are eating, food chemicals stimulate taste receptors on the tongue. These send neural signals to the superior and inferior salivatory nuclei in the brain stem. These two nuclei then send back parasympathetic stimuli through the glossopharyngeal and facial nerves to stimulate salivation. Even after you swallow food, salivation is increased to cleanse the mouth and to water down and neutralize any irritating chemical remnants, such as that hot sauce in your burrito. Most saliva is swallowed along with food and is reabsorbed, so that fluid is not lost.

Development

The salivary glands arise as epithelial buds in the oral cavity between week 6 to 7 and extend into the underlying mesenchyme. The first sign is a thickening of the epithelium on the side of the tongue, outside the dental lamina in the labiogingival sulcus.

The parotid salivary glands are the first major salivary glands formed. The epithelial buds of these glands are located on the inner part of the cheek. These buds grow posteriorly toward the developing ears and branch to form solid cords with rounded terminal ends near the developing facial nerve. Later, at around 10 weeks of prenatal development, these cords are canalized and form ducts, with the largest becoming the parotid duct for the parotid gland. The rounded terminal ends of the cords form the acini of the glands. Secretion by the parotid glands via the parotid duct begins at about 18 weeks of gestation.

The submandibular salivary glands appear late in the sixth week of prenatal development. They develop from epithelial buds in the sulcus surrounding the sublingual folds on the floor of the primitive mouth. Solid cords branch from the buds and grow posteriorly, lateral to the developing tongue. The cords of the submandibular gland later branch further and then become canalized to form the ductal part. The submandibular gland acini develop from the cords’ rounded terminal ends at 12 weeks, and secretory activity via the submandibular duct begins at 16 weeks. Growth of the submandibular gland continues after birth with the formation of more acini. Lateral to both sides of the tongue, a linear groove develops and closes over to form the submandibular duct.

The sublingual salivary glands are the last major salivary glands to develop. They appear in the eighth week of prenatal development. They originate from epithelial buds in the sulcus surrounding the sublingual folds on the floor of the mouth, lateral to the developing submandibular gland. These buds branch and form into cords that canalize to form the sublingual ducts associated with the gland. The rounded terminal ends of the cords form acini.

Composition of saliva

Saliva is essentially (98 to 99.5 percent) water. The remaining 4.5 percent is a complex mixture of ions, glycoproteins, enzymes, growth factors, and waste products. The most important ingredient in saliva is likely the enzyme salivary amylase for initiating the breakdown of carbohydrates. Food does not spend enough time in the mouth to allow all the carbohydrates to break down, but pancreatic amylase can continue the job in the intestines. Bicarbonate and phosphate ions function as chemical buffers, maintaining saliva at pH 6.35 to 6.85. Salivary mucus helps lubricate food, facilitating movement in the mouth, bolus formation, and swallowing. Saliva contains immunoglobulin A, which prevents microbes from penetrating the epithelium, and lysozyme, which makes saliva antimicrobial. Saliva also contains epidermal growth factor (EGF), which maintains and renovates the epithelium of the digestive tube.

Each of the major salivary glands secretes a unique formulation of saliva according to its cellular makeup. For example, the parotid glands secrete a watery solution that contains salivary amylase. The submandibular glands have cells similar to those of the parotid glands, as well as mucus-secreting cells. Their saliva also contains amylase but in a liquid thickened with mucus. The sublingual glands contain mostly mucous cells, and they secrete the thickest saliva with the least amount of salivary amylase.

Saliva sampled in the mouth contains water, electrolytes, mucus, antibacterial compounds and various enzymes.

• Water: 99.5%

• Electrolytes: 

  • 2–21 mmol/L sodium (lower than blood plasma)

  • 10–36 mmol/L potassium (higher than plasma)

  • 1.2–2.8 mmol/L calcium (similar to plasma)

  • 0.08–0.5 mmol/L magnesium

  • 5–40 mmol/L chloride (lower than plasma)

  • 25 mmol/L bicarbonate (higher than plasma)

  • 1.4–39 mmol/L phosphate (higher than plasma)

  • Iodine (concentration is usually higher than plasma but varies with diet)

• Mucus (mucopolysaccharides and glycoproteins) 

• Antibacterial compounds (thiocyanate, hydrogen peroxide, and secretory immunoglobulin A)

• Epidermal growth factor (EGF): regenerates spithelium.

• Various enzymes

  • α-amylase, or ptyalin, secreted by the acinar cells of the parotid and submandibular glands. Starts the digestion of starch in the mouth at neutral pH.

  • Lingual lipase, which is secreted by the acinar cells of the sublingual gland. It has a pH optimum around 4.0 so it is not activated until entering the acidic environment of the stomach.

  • Kallikrein, an enzyme that catalyzes the production of bradykinin, a vasodilator. It is secreted by the acinar cells of all three major salivary glands.

  • Antimicrobial enzymes

    • Lysozyme

    • Salivary lactoperoxidase

    • Lactoferrin

    • Immunoglobulin A

  • Proline-rich proteins (function in enamel formation, Ca2+-binding, microbe killing and lubrication)

  • Minor enzymes include salivary acid phosphatases A+B, N-acetylmuramoyl-L-alanine amidase, NAD(P)H dehydrogenase (quinone), superoxide dismutase, glutathione transferase, class 3 aldehyde dehydrogenase, and glucose-6-phosphate isomerase.

• Cells: some white blood cells and many bacterial cells.

• Opiorphin, a pain-killing substance found in human saliva.

• Haptocorrin, a protein which binds to Vitamin B12 to protect it against degradation in the stomach.

Clinical issues

Sialolithiasis is the development of a salivary calculus or stone which may block the duct causing pain and swelling of the gland. Symptoms occur in 0.5% of the population, most commonly in the submandibular duct of men. The stones can grow to several millimeters in diameter and their removal may involve hydration, massage, shock waves or surgery.

Dysfunctions of the salivary gland usually present as hypofunction (reduced production of saliva) which causes xerostomia (dry mouth). Salivary gland dysfunction is a predictable side-effect of radiotherapy in the head and neck region. Chemotherapy may also impair salivary flow. Both treatments tend to injury the epithelial cells of the salivary glands due to their high metabolism.

Lack of saliva increases the risk of dental caries. Saliva has antimicrobial agents as well as ions that promote the remineralization of tooth enamel. Conditions that cause salivary gland hypofunction as well as conditions that lead the patient to sleep with the mouth open tend to be correlated with increased occurrence of cavities.

Mumps is a viral infection of the nasal passages and pharynx by the paramyxovirus and it most commonly attacks the parotid glands. Enlargement and inflammation of the parotid glands is typical, causing a characteristic swelling between the ears and the jaw. Symptoms include fever and throat pain, which can be severe when swallowing acidic substances such as orange juice. Mumps vaccines have greatly reduced the incidence of mumps, however. According to the U.S. Centers for Disease Control and Prevention (CDC), only 11 cases were reported in the US in 2011.

Diversity

The salivary glands of many species produce amylase, but in some species they are modified to produce other proteins. The venom glands of venomous snakes, Gila monsters, and some shrews are modified salivary glands. In insects, salivary glands can be used to produce silk or glues. In the salivary glands of flies, the high demand for gene transcription is met by polytene chromosomes that have thousands of DNA strands (copies) in them.

Glue to construct bird nests

Birds in the swift family, Apodidae, generally build nests on very exposed surfaces of rocks to avoid predators. They produce a viscous saliva during the nesting season to glue together materials to construct a nest. As an extreme, two species of swifts in the genus Aerodramus build nests on the walls of caves using only their saliva.

Spitting

Camels and llamas may spit at a threat as a defensive behavior. They can use it against wolves or people. In addition to a considerable volume of saliva, some stomach contents may also be added to the spit.

Wound licking

It is an instinctive response of many vertebrates to lick an injury. Dogs, cats, small rodents, horses, and primates are commonly observed licking their wounds. Saliva contains tissue factor which promotes blood clotting, and lysozymes that attack bacteria. Wound liking may increase the risk of bringing an infection into the mouth and digestive tract and it is not recommended to humans with access to clean water and medication for treating wounds. The behavior is understandable in animals living in the wild where the the benefits of sanitizing a wound with saliva may overcome the risks of infecting the mouth.

Summary

Saliva has many important roles such as lubricating the mouth, hydrating, lubricating and digesting the food before swallowing, washing away and digesting food particles from the teeth and supporting some remineralization of the enamel. Saliva is produced by major and minor salivary glands. The major glands are the parotid, submandibular and sublingual salivary glands. Minor salivary glands are very small but very numerous and distributed over the entire oral mucosa. Salivary glands vary in the composition of their product, ranging from highly serous to highly mucous. Saliva has some special uses in animals, forming the venom of vipers, being used as glue for nest building by swifts or as a defense by camels.

Key terms

Parotid salivary gland, sublingual salivary gland, submandibular salivary gland, minor salivary gland, von Ebner’s salivary gland, lobule, acinus, salivary duct, intercalated duct, striated duct, parotid duct, parotid papilla, submandibular duct, duct of Wharton, sublingual caruncle, lingual frenulum, adenomere, superficial temporal artery, maxillary artery, facial artery, lingual artery, sublingual artery, submental artery, duct of Rivinus, sublingual duct, duct of Bartholin, facial nerve, glossopharyngeal nerve, lingual lipase, salivary amylase, otic ganglion, submandibular ganglion, superior cervical ganglion, labiogingival sulcus, sublingual folds, sialolithiasis, xerostomia, polytene chromosome, Aerodramus, spit, saliva.

Figure credits

Figure 1 by OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148426

Figure 2 by Wbensmith - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=2845814

Figure 3 by Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1024, Public Domain, https://commons.wikimedia.org/w/index.php?curid=566969

Figure 4 by Vera992 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=22613296

Figure 5 by Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8305221

Figure 6 byblic Domain, https://commons.wikimedia.org/w/index.php?curid=1074079

Figure 7 by http://en.wikipedia.org/wiki/User:Jpogi (Author's own picture. Digital camera shot of human Von Ebner's Gland through a microscope) - http://en.wikipedia.org/wiki/File:Serous_secretory_acini-von_Ebner%27s.JPG, CC0, https://commons.wikimedia.org/w/index.php?curid=17801225

Figure 8 by James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24076829