The salivary glands in mammals are

exocrine gland Exocrine glands are glands that secrete substances on to an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of ...

s that produce saliva through a system of ducts. Humans have three paired major salivary glands (

parotid The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the ma ...

submandibular The submandibular ganglion (or submaxillary ganglion in older texts) is part of the human autonomic nervous system. It is one of four parasympathetic ganglia of the head and neck. (The others are the otic ganglion, pterygopalatine ganglion, and cil ...

, and sublingual), as well as hundreds of minor salivary glands. Salivary glands can be classified as

serous In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The flu ...

, mucous, or seromucous (mixed). In serous secretions, the main type of protein secreted is

alpha-amylase α-Amylase is an enzyme (EC 3.2.1.1; systematic name 4-α-D-glucan glucanohydrolase) that hydrolyses α bonds of large, α-linked polysaccharides, such as starch and glycogen, yielding shorter chains thereof, dextrins, and maltose: :Endohyd ...

, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that breaks down starch into maltose and

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

, whereas in mucous secretions, the main protein secreted is

mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...

, which acts as a lubricant. In humans, 1200 to 1500 ml of saliva are produced every day. The secretion of saliva (salivation) is mediated by parasympathetic stimulation; acetylcholine is the active neurotransmitter and binds to

muscarinic receptors Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

in the glands, leading to increased salivation. The fourth pair of salivary glands, the tubarial glands discovered in 2020, are named for their location, being positioned in front and over the

torus tubarius The base of the cartilaginous portion of the Eustachian tube (auditory tube) lies directly under the mucous membrane of the nasal part of the pharynx, where it forms an elevation or cushion, the torus tubarius or torus of the auditory tube, behind ...

. However, this finding from one study is yet to be confirmed.

Structure

The salivary glands are detailed below:

Parotid glands

The two

parotid gland The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the ma ...

s are major salivary glands wrapped around the mandibular ramus in humans. These are largest of the salivary glands, secreting saliva to facilitate mastication and swallowing, and

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

to begin the digestion of starches. It is the serous type of gland which secretes

(also known as ''ptyalin''). It enters the

oral cavity In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on t ...

via the parotid duct. The glands are located posterior to the mandibular ramus and anterior to the

mastoid process The mastoid part of the temporal bone is the posterior (back) part of the temporal bone, one of the bones of the skull. Its rough surface gives attachment to various muscles (via tendons) and it has openings for blood vessels. From its borders, ...

of the

temporal bone The temporal bones are situated at the sides and base of the skull, and lateral to the temporal lobes of the cerebral cortex. The temporal bones are overlaid by the sides of the head known as the temples, and house the structures of the ears. ...

. They are clinically relevant in dissections of

facial nerve The facial nerve, also known as the seventh cranial nerve, cranial nerve VII, or simply CN VII, is a cranial nerve that emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of taste ...

branches while exposing the different lobes, since any

iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 27 ...

lesion will result in either loss of action or strength of muscles involved in

facial expression A facial expression is one or more motions or positions of the muscles beneath the skin of the face. According to one set of controversial theories, these movements convey the emotional state of an individual to observers. Facial expressions are ...

. They produce 20% of the total salivary content in the oral cavity. Mumps is a

viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...

, caused by infection in the parotid gland.

Submandibular glands

The submandibular glands (previously known as submaxillary glands) are a pair of major salivary glands located beneath the lower jaws, superior to the

digastric muscle The digastric muscle (also digastricus) (named ''digastric'' as it has two 'bellies') is a small muscle located under the jaw. The term "digastric muscle" refers to this specific muscle. However, other muscles that have two separate muscle belli ...

s. The secretion produced is a mixture of both

serous fluid In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...

and

mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...

, and enters the

via the submandibular duct or Wharton duct. Around 70% of saliva in the oral cavity is produced by the submandibular glands, though they are much smaller than the parotid glands. This gland can usually be felt via palpation of the neck, as it is in the superficial cervical region and feels like a rounded ball. It is located about two fingers above the Adam's apple (laryngeal prominence) and about two inches apart under the chin.

Sublingual glands

The sublingual glands are a pair of major salivary glands located inferior to the tongue, anterior to the submandibular glands. The secretion produced is mainly mucous in nature, but it is categorized as a mixed gland. Unlike the other two major glands, the ductal system of the sublingual glands does not have intercalated ducts and usually does not have striated ducts, either, so saliva exits directly from 8-20 excretory ducts known as the Rivinus ducts. About 5% of saliva entering the oral cavity comes from these glands.

Tubarial salivary glands

The tubarial glands are suggested as a fourth pair of salivary glands situated posteriorly in the

nasopharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...

and nasal cavity, predominantly with mucous glands, and its ducts opening into the dorsolateral pharyngeal wall. The glands were unknown until September 2020, when they were discovered by a group of Dutch scientists using with prostate-specific membrane antigen

PET-CT Positron emission tomography–computed tomography (better known as PET-CT or PET/CT) is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography (PET) scanner and an x-ray computed tomography (CT) scan ...

. This discovery may explain mouth dryness after radiotherapy despite the avoidance of the three major glands. However, these findings from just one study need to be confirmed. On the other hand, an interdisciplinary group of scientists disagree with this new discovery. They believe that an accumulation of minor salivary glands has been described.

Minor salivary glands

Around 800 to 1,000 minor salivary glands are located throughout the oral cavity within the submucosa of the

oral mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...

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 or between muscle fibers of the tongue. 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. Their secretion is mainly mucous in nature and have many functions such as coating the oral cavity with saliva. Problems with dentures are sometimes associated with minor salivary glands if dry mouth is present. The minor salivary glands are innervated by the seventh cranial or facial nerve.

Von Ebner's glands

Von Ebner's glands Von Ebner's glands, also called Ebner's glands or gustatory glands, are exocrine glands found in the mouth. More specifically, they are serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae ju ...

are found in a trough circling the

circumvallate papillae Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...

on the dorsal surface of the tongue near the terminal sulcus. They secrete a purely serous fluid that begins

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...

. They also facilitate the perception of

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

through secretion of digestive enzymes and proteins. The arrangement of these glands around the circumvallate papillae provides a continuous flow of fluid over the great number of taste buds lining the sides of the papillae, and is important for dissolving the food particles to be tasted.

Nerve supply

Salivary glands are innervated, either directly or indirectly, by the parasympathetic and sympathetic arms of the autonomic nervous system. Parasympathetic stimulation evokes a copious flow of saliva. * Parasympathetic innervation to the salivary glands is carried via cranial nerves. The parotid gland receives its parasympathetic input from the

glossopharyngeal nerve The glossopharyngeal nerve (), also known as the ninth cranial nerve, cranial nerve IX, or simply CN IX, is a cranial nerve that exits the brainstem from the sides of the upper medulla, just anterior (closer to the nose) to the vagus nerve. ...

(CN IX) via the

otic ganglion The otic ganglion is a small parasympathetic ganglion located immediately below the foramen ovale in the infratemporal fossa and on the medial surface of the mandibular nerve. It is functionally associated with the glossopharyngeal nerve and inn ...

, while the submandibular and sublingual glands receive their parasympathetic input from the

(CN VII) via the

submandibular ganglion The submandibular ganglion (or submaxillary ganglion in older texts) is part of the human autonomic nervous system. It is one of four parasympathetic ganglia of the head and neck. (The others are the otic ganglion, pterygopalatine ganglion, and ci ...

. These nerves release acetylcholine and substance P, which activate the IP3 and DAG pathways respectively. * Direct sympathetic innervation of the salivary glands takes place via preganglionic nerves in the thoracic segments T1-T3 which synapse in the superior cervical ganglion with postganglionic neurons that release norepinephrine, which is then received by β₁-adrenergic receptors on the acinar and ductal cells of the salivary glands, leading to an increase in cyclic adenosine monophosphate (cAMP) levels and the corresponding increase of saliva secretion. Note that in this regard both parasympathetic and sympathetic stimuli result in an increase in salivary gland secretions, the difference lies on the composition of this saliva, once sympathetic stimulus results particularly in the increase of amilase secretion, which is produced by serous glands. The sympathetic nervous system also affects salivary gland secretions indirectly by innervating the

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s that supply the glands, resulting in vasoconstriction through the activation of α₁ adrenergic receptors, lessening the saliva's water content.

Microanatomy

The gland is internally divided into lobules.

Blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

s and nerves enter the glands at the hilum and gradually branch out into the lobules.

Acini

Secretory cells are found in a group, or acinus. 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.

Ducts

In the duct system, the lumina are formed by

intercalated duct In anatomy and physiology, a duct is a circumscribed channel leading from an exocrine gland or Organ (anatomy), organ. Types of ducts Examples include: Duct system As ducts travel from the acinus which generates the fluid to the target, the du ...

s, which in turn join to form striated ducts. These drain into ducts situated between the lobes of the gland (called interlobar ducts or secretory ducts). These are found on most major and minor glands (exception may be the sublingual gland). All of the human salivary glands terminate in the mouth, where the saliva proceeds to aid in digestion. The released saliva is quickly inactivated in the stomach by the acid that is present, but saliva also contains enzymes that are actually activated by stomach acid.

Gene and protein expression

About 20,000 protein-coding genes are expressed in human cells and 60% of these genes are expressed in normal, adult salivary glands. Less than 100 genes are more specifically expressed in the salivary gland. The salivary gland specific genes are mainly genes that encode for secreted proteins and compared to other organs in the human body; the salivary gland has the highest fraction of secreted genes. The heterogeneous family of proline-rich, human salivary glycoproteins, such as PRB1 and PRH1, are salivary gland-specific proteins with highest level of expression. Examples of other specifically expressed proteins include the digestive amylase enzyme

AMY1A Alpha-amylase 1 is an enzyme that in humans is encoded by the ''AMY1A'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth' ...

, the mucin

MUC7 Mucin-7 is a protein that in humans is encoded by the ''MUC7'' gene. In animals, the MUC7 gene is found in most placental mammals, but not marsupials. Human variations Humans carry either a five or six tandem repeat version of the gene. In other ...

and statherin, all of major importance for specific characteristics of saliva.

Aging

Aging of salivary glands shows some structural changes, such as: * Decrease in volume of acinar tissue * Increase in fibrous tissue * Increase in adipose tissue * Ductal hyperplasia and dilation In addition, changes occur in salivary contents: * Decrease in concentration of secretory IgE * Decrease in the amount of mucin However, no overall change in the amount of saliva secreted is seen.

Function

Salivary glands secrete saliva, which has many benefits for the oral cavity and health in general. The knowledge of normal salivary flow rate (SFR) is extremely important when treating dental patients. These benefits include: * Protection: Saliva consists of proteins (for example; mucins) that lubricate and protect both the soft and hard tissues of the oral cavity. Mucins are the principal organic constituents of mucus, the slimy viscoelastic material that coats all mucosal surfaces. * Buffering: In general, the higher the saliva flow rate, the faster the clearance and the higher the buffer capacity, hence better protection from dental caries. Therefore, people with a slower rate of saliva secretion, combined with a low buffer capacity, have lessened salivary protection against microbes. * Pellicle formation: Saliva forms a pellicle on the surface of the tooth to prevent wearing. The film contains mucins and proline-rich glycoprotein from the saliva. The proteins (statherin and proline-rich proteins) within the salivary pellicle inhibit demineralisation and promote remineralisation by attracting calcium ions. * Maintenance of tooth integrity: Demineralization occurs when enamel disintegrates due to the presence of acid. When this occurs, the buffering capacity effect of saliva (increases saliva flow rate) inhibits demineralisation. Saliva can then begin to promote the remineralisation of the tooth by strengthening the enamel with calcium and phosphate minerals. * Antimicrobial action: Saliva can prevent microbial growth based on the elements it contains. For example, lactoferrin in saliva binds naturally with iron. Since iron is a major component of bacterial cell walls, removal of iron breaks down the cell wall, which in turn breaks down the bacterium. Antimicrobial peptides such as histatins inhibit the growth of'' Candida albicans'' and ''Streptococcus mutans''. Salivary immunoglobulin A serves to aggregate oral bacteria such as'' S. mutans'' and prevent the formation of dental plaque. * Tissue repair: Saliva can encourage soft-tissue repair by decreasing clotting time and increasing wound contraction. * Digestion: Saliva contains amylase, which hydrolyses starch into glucose, maltose, and dextrin. As a result, saliva allows some digestion to occur before the food reaches the stomach. * Taste: Saliva acts as a solvent in which solid particles can dissolve and enter the taste buds through oral mucosa located on the tongue. These taste buds are found within foliate and circumvallate papillae, where minor salivary glands secrete saliva.

Clinical significance

sialolithiasis Sialolithiasis (also termed salivary calculi, or salivary stones) is a crystallopathy where a calcified mass or ''sialolith'' forms within a salivary gland, usually in the duct of the submandibular gland (also termed "Wharton's duct"). Less common ...

(a salivary calculus or stone) may cause blockage of the ducts, most commonly the submandibular ducts, causing pain and swelling of the gland. Salivary gland dysfunction refers to either

xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

(the symptom of dry mouth) or salivary gland hypofunction (reduced production of saliva); it is associated with significant impairment of quality of life. Following radiotherapy of the head and neck region, salivary gland dysfunction is a predictable side-effect. Saliva production may be pharmacologically stimulated by sialagogues such as pilocarpine and cevimeline. It can also be suppressed by so-called antisialagogues such as

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

s, antihypertensives, and

polypharmacy Polypharmacy (polypragmasia) is the simultaneous use of multiple medicines by a patient for their conditions. Most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum ...

. A Cochrane review found there was no strong evidence that topical therapies are effective in relieving the symptoms of dry mouth.

Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

treatments including

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

and

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

may impair salivary flow. Radiotherapy can cause permanent hyposalivation due to injury to the oral mucosa containing the salivary glands, resulting in xerostomia, whereas

may cause only temporary salivary impairment. Furthermore surgical removal because of benign or malignant lesions may also impair function.

Graft versus host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which remain wit ...

after

allogeneic Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, o ...

bone marrow transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

may manifest as dry mouth and many small mucoceles. Salivary gland tumours may occur, including

mucoepidermoid carcinoma Mucoepidermoid carcinoma (MEC) is the most common type of minor salivary gland malignancy in adults. Mucoepidermoid carcinoma can also be found in other organs, such as bronchi, lacrimal sac, and thyroid gland. Mucicarmine staining is one stain us ...

, a malignant growth.

Clinical tests/investigations

A sialogram is a

radiocontrast Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography ( contrast CT), projectional radiography, and fluoroscopy. Radiocontrast agents are typically i ...

study of a salivary duct that may be used to investigate its function and for diagnosing Sjögren syndrome.

Other animals

The salivary glands of some species are modified to produce proteins; salivary amylase is found in many bird and mammal species (including humans, as noted above). Furthermore, the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

glands of

venomous snake Venomous snakes are species of the suborder Serpentes that are capable of producing venom, which they use for killing prey, for defense, and to assist with digestion of their prey. The venom is typically delivered by injection using hollow or g ...

Gila monster The Gila monster (''Heloderma suspectum'', ) is a species of venomous lizard native to the Southwestern United States and the northwestern Mexican state of Sonora. It is a heavy, typically slow-moving reptile, up to long, and it is the only ve ...

s, and some

shrew Shrews (family Soricidae) are small mole-like mammals classified in the order Eulipotyphla. True shrews are not to be confused with treeshrews, otter shrews, elephant shrews, West Indies shrews, or marsupial shrews, which belong to differ ...

s, are actually modified salivary glands. In other organisms such as

insects Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of j ...

, salivary glands are often used to produce biologically important proteins such as

silk Silk is a natural protein fiber, some forms of which can be woven into textiles. The protein fiber of silk is composed mainly of fibroin and is produced by certain insect larvae to form cocoons. The best-known silk is obtained from the ...

or glues, whilst fly salivary glands contain

polytene chromosome Polytene chromosomes are large chromosomes which have thousands of DNA strands. They provide a high level of function in certain tissues such as salivary glands of insects. Polytene chromosomes were first reported by E.G.Balbiani in 1881. P ...

s that have been useful in genetic research.

References

External links

Salivary gland at the Human Protein Atlas

Illustration at merck.com

Illustration at .washington.edu
*
Medical Encyclopedia Medline Plus: Salivary gland
{{Authority control Glands of mouth Exocrine system Saliva Arthropod glands