The major salivary glands (together accounting for about 90% of the fluid production) include the paired parotid glands, which are located opposite the maxillary first molars, and the submandibular and sublingual glands, which are found in the floor of the mouth. Minor glands (that produce less than 10% of the total volume of saliva) are found in the lower lip, tongue, palate, cheeks, and pharynx.
The terms major and minor refer to the anatomic size of the glands. Major glands do produce more saliva than minor glands, but the quality of content and thus the type of protection varies. Paradoxically, it could be argued that the minor salivary glands are the most important because of their protective components.
The parotid glands are "serous" glands, for their acinar cells contain only serous-secreting cells, whose secretions are devoid of mucin compared to that of the submandibular and sublingual glands, which contain both serous- and mucin-secreting cells. The parotid glands produce a thin, watery, and amylase-rich fluid on stimulation which accounts for up to 50% of the mouth volume of saliva under stimulated conditions, whereas it contributes much less (20%) to the unstimulated saliva secretion.
As compared with the parotid, the submandibular glands (comprising both serous and mucous acinar cell types) secrete a more viscous, mucin-rich saliva. They contribute predominantly (65%) to the unstimulated saliva secretion, and less (35%) to saliva under stimulated conditions. The viscosity of the submandibular saliva usually decreases with increasing flow rate since the serous cells have a greater response to stimulation than do the mucin-secreting cells.
The sublingual glands, which contribute with 1–2% of the unstimulated volume of whole saliva, mainly consist of mucous acinar cells and also produce a thick, viscous mucin-rich saliva.
The minor glands, although they produce less than 10% of the total volume of saliva, play an important role in lubricating the mucosa, as even in the absence of local stimuli they produce saliva. The minor glands, which are distributed throughout the oral mucosa (labial, buccal, lingual, palatinal mucosa), are mixed glands largely comprising mucous acinar cells. However, the palatinal glands are strictly mucous, whereas the lingual von Ebner’s glands are strictly serous.
Figure
The types of cells found in the salivary glands are acinar cells, various duct system cells, and myoepithelial cells.
Acinar cells, in which saliva is first secreted, determine the type of secretion produced from the different glands. Two basic types of acinar epithelial cells exist: serous cells secrete a watery fluid, essentially devoid of mucus, whereas mucous cells produce a very mucus-rich secretion. Secretion can be classified as serous, mucous, or mixed; serous secretions are produced mainly from the parotid gland, mucous secretions from the minor glands, and mixed serous and mucous secretions from the submandibular and sublingual glands (in sublingual glands secretion is mostly mucous).
Duct system cells found in the salivary ducts are classified as intercalated, striated, and excretory. Intercalated duct cells are the first duct network connecting acinar secretions to the rest of the gland. These cells are not involved in the modification of electrolytes, as are the remaining duct cells. Striated cells are second in the network, functioning as electrolyte regulation in resorbing sodium. The final duct cells, the excretory duct cells, contribute by continuing sodium resorption and secreting potassium. Excretory duct cells are the last part of the duct network before saliva reaches the oral cavity.
Myoepithelial cells, which are long cell processes wrapped around acinar cells, contract on stimulation to constrict the acinar. This function, secreting or “squeezing out” accumulating fluid, is the result of a purely neural process.
The acinar cells secrete the salivary fluid, and the ductal cells secrete some protein and modify the ionic composition of the saliva as they convey it to the mouth.
The zonula occludens, a tight junction that resides at the apical pole of the cell, separates the apical and basolateral plasma membranes. Within this zonula occludens, the lateral membranes of adjacent cells closely approximate one another. These sites of intimate contact, colloquially termed membrane "kisses", are thought to represent the physical sites at which diffusion of molecules across the zonula occludens is impeded. Junctions between acinar cells are highly permeable, those between intercalated duct cells are less permeable, and junctions between striated duct cells are essentially impermeable. The tight junctions in the resting rat parotid gland are impermeable to tracers of molecular weight > 1,900.
Salivary glands have a high blood flow. The external carotid arteries enter the submandibular and sublingual glands along with the main ducts and nerves, thereby creating a hilum, although this hilum is not as clearly defined as in larger organs such as the kidney. Within the glands, the vessels follow the subdivision of the secretory duct tree so that each lobule has a distinct and separate blood supply. The direction of the blood flow is countercurrent to the direction of the salivary flow.
Salivary fluid secrection
Scheme of electroclyte exchanges during saliva secrection
Ematic circulation of salivary glands is very important for saliva formation. Actually only in cells where there is blood passage there can be saliva formation. Important studies suggest that preassure generted by salivary secrction is dependent on blood preassure.
Parasympathetic stimulation of salivary glands causes a higher blood flow.
The current secretion model predicts that, when stimulated, salivary acinar cells lose KCl. The loss of K+ and Cl-, across basolateral and apical membranes, respectively, creates a large transepithelial potential difference. This lumen-negative potential difference drives Na+ flux between acinar cells into the lumen, and H2O follows the resulting NaCl osmotic gradient.
Sustained secretion is dependent on the activation of K+ and Cl- reuptake mechanisms located in the basolateral membranes. The net effect of simultaneously activating Cl- efflux and Cl- reuptake mechanisms is transepithelial Cl- movement, the driving force for fluid secretion. It is interesting to note that little desensitization occurs, i.e., in the continuous presence of a muscarinic agonist, salivary glands can secrete for hours.
A salivary acinar cell contains four ion transporters, the Na+/K+ adenosine triphosphatase (ATPase), a Na+-K+-2Cl- cotransporter and a Ca2+-activated K+ channel, all located in the basolateral membrane, and a Ca2+-activated Cl- channel located in the apical membrane. Fluid secretion is thought to arise from the concerted actions of these four transporters.
Understanding salivary Fuid and protein secretion
Salivary fluid secretion appears to be a two-stage process.
Figure:Salivary fluid secrection
- Upon stimulation, saliva is initially formed as a near isotonic plasma-like primary secretion in the acinar lumen (the first stage). The acinar cells forming the secretory endpiece of the salivary gland actively pump sodium ions from the blood into the lumen of the endpiece. The resulting osmotic pressure difference between the blood and the fluid in the endpiece causes water to flow from the blood, through the tight junctions between the acinar cells, and into the lumen of the endpiece. Thus, the primary secretion (as it leaves the endpiece) is thought to be almost isotonic with plasma.
- When this fluid passes along through the duct system it is modified by selective and energy-dependent reabsorption of sodium and chloride (without water, as the salivary ducts are impermeable to water) and secretion of potassium and bicarbonate – the latter especially occurring under stimulated conditions. The resulting saliva becomes increasingly hypotonic as it moves down the ductal system: the final saliva secreted to the oral cavity contains concentrations of sodium and chloride much below that of primary saliva.
Saliva modulation in sistemic deseases
- Immune general reaction, like the ones we have in transplant rejection, can act on salivary glands, reducing secrection speed and increasing Na+ e Cl- concentration.
- Cystic Fibrosis is an illness that has as targets lung and pancreas and is caracterised by a defective Cl- transporter. It causes a reduction in the salivary production and increases the quantity of Ca++ in saliva.
Cystic fibrosis and saliva
Innervation of Salivary Glands
Secretion of saliva is under control of the autonomic nervous system, which controls both the volume and type of saliva secreted. A dog fed dry dog food produces saliva that is predominantly serous, while dogs on a meat diet secrete saliva with much more mucus. Parasympathetic stimulation from the brain results in greatly enhanced secretion, as well as increased blood flow to the salivary glands.
Stimulated saliva is reported to contribute as much as 80% to 90% of the average daily salivary production. The secretion of saliva is controlled by a salivary center composed of nuclei in the medulla, but there are specific triggers for this secretion.
Salivary glands are innervated by both sympathetic and parasympathetic nerve fibers. Various neurotransmitters and hormones stimulate different receptors, different salivary glands, and different responses. When sympathetic innervations dominate, the secretions contain more protein from acinar cells, whereas predominant parasympathetic innervations produce a more watery secretion. Stimulation of one receptor often enhances and complements another receptor. Therefore, the separation of contributing stimuli and resulting secretory products is not absolute.
Three types of triggers, or stimuli, for this production are mechanical (the act of chewing), gustatory (with acid the most stimulating trigger and sweet or bitter the least stimulating), and olfactory (a surprisingly poor stimulus). Other factors affecting secretion include psychic factors such as pain, certain types of medication, and various local or systemic diseases affecting the glands themselves.
Salivary secretion is regulated by a reflex arch comprising afferent receptors and nerves carrying impulses induced by actions on gustation and mastication, a central connection (salivation center), and an efferent part consisting of parasympathetic and sympathetic autonomic nerve bundles that separately innervate the glands. The secretory reflex arch is also under influence of higher centers in the brain. Saliva may be secreted in the absence of exogenous stimuli referred to as the resting or unstimulated salivary flow.
Initiation of salivation by an unconditioned reflex. The afferent part is activated by stimulation of various sensory receptors including chemoreceptors in the taste buds and mechanoreceptors in the periodontal ligament. The afferent nerves carrying impulses to the salivary nuclei (salivation center) in the medulla oblongata are the facial, glossopharyngeal and vagal nerves (taste) and the trigeminal nerve (chewing). Olfaction and stretch of the stomach are other afferent inputs that can initiate formation of saliva.
Initiation of salivation by a conditioned reflex. The sight and thought of food may lead to some formation of saliva. The salivary nuclei also receive impulses from other centers of the brain resulting in facilatory or inhibitory effects on salivation depending on, for example, the emotional state.
Efferents. The salivary nuclei direct signals to the efferent part of the reflex consisting of parasympathetic (facial and glossopharyngeal nerves) and sympathetic autonomic nerves that separately innervate the glands. The sympathetic nerves, running from the sympathetic trunk, follow the blood vessels supplying the glands. Release of neurotransmitters from postganglionic neurons of both branches of the autonomic nervous system elicits secretion of saliva to the oral cavity. The facial nerve provides parasympathetic control of the submandibular, sublingual, and minor glands (except von Ebner’s gland), whereas the glossopharyngeal nerves control the parotid glands.
Increased salivary secretion in response to chewing is the result of a masticatory-salivary reflex, which has been found to be primarily unilateral and dependent on the applied stimulus intensity. In the oral cavity chewing activates mechanoreceptors in the periodontal membrane. Chewing compresses the teeth into the periodontal membrane, which activates the mechanoreceptors, followed by transmission of impulses through the trigeminal nerve to the salivation center. Salivary secretion increases with the hardness and the size of the object being chewed as well as the chewing force by the chewing muscles.
Increased salivary secretion in response to taste stimulation is, like chewing, induced reflexly. Taste sensation is traditionally divided into the four classical basic taste modalities: sweet, salty, sour, and bitter. Each modality is based on distinct transductional systems in the single receptor cell leading to depolarization of the receptor potential and generation of action potentials. This facilitates the release of neurotransmitters, stimulating gustatory afferent nerve fibers that then carry the taste signal onto the higher-order systems. Each taste receptor cell responds, however, in varying degrees to substances that fall into more than one taste category. Among additional taste modalities that have been identified is umami, which is elicited by monosodium glutamate and certain ribonucleotides. Moreover, perception of taste is affected by general sensory impulses arising from pain (‘hot spices’), food temperature and texture through the trigeminal nerve. The highest saliva stimulation is obtained with sour taste, followed by salt (NaCl), sweet, and bitter. There is no additive effect on salivary flow by giving a mixture of different taste stimuli. In fact, it elicits a lower flow rate than the sum of the separate stimuli. Furthermore, salivary flow increases with increasing concentration and amount of a separate taste stimulus. Continuous taste stimulation usually leads to varying degrees of adaptation, which is highest for sweet taste, but lowest for sour taste. Taste impulses are carried to the brain by parasympathetic nerves, many of which travel with branches of the trigeminal nerve. The sensory nerves, which carry signals in response to stimulation of taste receptors are, with regards to the tongue, the facial nerve (in particular sweet, salty and acid stimuli), whereas the glossopharyngeal nerve innervates the circumvallate papillae, the back of the tongue and also the palate. Fibers of the vagal nerve innervate taste buds in the tonsillar region, the epiglottis, the pharyngeal wall and esophagus. The taste pathway activated by inputs from the facial, glossospharyngeal and vagal nerves have ipsilateral reflex connections to the salivatory center in the brain stem. The first neurons synapse in the tractus solitarius and its nucleus, where the secondary neurons cross the midline and travel to the thalamus. Also in this region, the third neurons communicate with the postcentral gyrus-facial area and there are also projections to the olfactory cortex.
Salivary Glands Disorders
Salivary gland disorders refer to conditions that cause swelling or pain in the saliva-producing tissues around the mouth.
