Salivary Secretion

Introduction Salivary glands are accessory organs of the gastrointestinal (GI) tract. While not essential for life, their secretions are important for the hygiene and comfort of the mouth and teeth. Saliva production is an active process and occurs in large quantities relative to the weight of the salivary glands. A unique characteristic of salivary secretion is that it is almost totally under the control of the nervous system, with both branches of the autonomic nervous system (ANS) stimulating secretion, although the parasympathetic system provides a much greater stimulus than the sympathetic system.

I. Functions of Saliva Saliva serves three major categories of functions: lubrication, protection, and digestion.

• Lubrication:

    ◦ Depends primarily on its mucus content.

    ◦ Facilitates the swallowing process by mixing with food and lubricating ingested material.

    ◦ Necessary for speech.

• Protection:

    ◦ Buffers and dilutes noxious substances, such as hot solutions or foul-tasting compounds, washing them from the mouth.

    ◦ Neutralizes and dilutes corrosive gastric acid and pepsin that may enter the esophagus and mouth before vomiting, as salivary glands are strongly stimulated before emesis.

    ◦ Maintains oral hygiene by dissolving and washing out food particles from between teeth, thus reducing dental caries.

    ◦ Possesses antibacterial actions through specific constituents:

        ▪ Lysozyme, which attacks bacterial cell walls.

        ▪ Lactoferrin, which chelates iron, preventing bacterial multiplication.

        ▪ Binding glycoprotein for immunoglobulin A (IgA), which combines with IgA to form secretory IgA, active against viruses and bacteria.

    ◦ Incorporates fluoride and calcium (Ca2+) into teeth.

• Digestion:

    ◦ Dissolves and washes away food particles on taste buds, enabling the perception of taste.

    ◦ Contains two main enzymes for initial digestion:

        ▪ α-amylase (ptyalin): Cleaves internal α-1,4-glycosidic bonds in starch, producing maltose, maltotriose, and α-limit dextrins. It has a pH optimum of 7 and is rapidly denatured at pH 4, but can digest up to 75% of starch in the orad stomach before denaturation due to unmixed food. Its absence does not cause digestion defects, as pancreatic amylase is sufficient.

        ▪ Lingual lipase: Secreted by serous salivary glands of the tongue, it hydrolyzes dietary lipids. Unlike pancreatic lipase, it is active in all parts of the upper GI tract, as its activity is not affected by bile salts, medium chain fatty acids, or lecithin. It has an acidic pH optimum, allowing it to remain active through the stomach and into the intestine.

II. Composition of Saliva Saliva is a complex mixture with unique characteristics that differentiate it from other GI secretions.

• General Characteristics:

    ◦ Large volume: Approximately 1 liter per day in a normal adult, which is a remarkably large volume relative to the mass of the glands that secrete it.

    ◦ Low osmolality: Saliva is hypotonic (hyposmotic) at all rates of secretion compared to plasma.

    ◦ High K+ concentration: It contains a relatively high concentration of potassium (K+) compared to plasma.

    ◦ Low Na+ and Cl- concentrations: Conversely, it has lower concentrations of sodium (Na+) and chloride (Cl-) compared to plasma.

    ◦ High HCO3- concentration: Saliva also has a high bicarbonate (HCO3-) concentration.

    ◦ Specific gravity ranges from 1.000 to 1.010.

• Variations with Flow Rate:

    ◦ The composition of saliva varies with its flow rate. At low flow rates, saliva has the lowest osmolality and lowest Na+, Cl-, and HCO3- concentrations, but the highest K+ concentration.

    ◦ At high flow rates (e.g., up to 4 mL/minute), the composition of saliva more closely resembles that of plasma. This is because less time is available for modification as the fluid moves through the ducts. HCO3- concentration, however, remains relatively high even at high flow rates because its secretion is selectively stimulated.

• Organic Composition:

    ◦ Beyond water and electrolytes, saliva contains several important organic materials. These include the enzymes α-amylase (ptyalin) and lingual lipase.

    ◦ Other organic components are mucus, glycoproteins, lysozymes, and lactoferrin.

    ◦ Kallikrein, an enzyme produced by salivary glands, converts a plasma protein into bradykinin, a potent vasodilator that increases blood flow to the secreting glands when metabolism increases.

    ◦ Saliva also contains blood group substances A, B, AB, and O.

    ◦ The protein concentration of saliva is approximately one tenth the concentration of proteins in the plasma.

III. Mechanism of Secretion (Formation of Saliva) Saliva is produced in a two-stage process involving acinar cells and ductal cells within the functional unit called a salivon.

• Initial Saliva Production (Acinar Cells):

    ◦ The acinus, surrounded by polygonal acinar cells, secretes the initial saliva.

    ◦ This initial secretion is isotonic to plasma and has ion concentrations (Na+, K+, Cl-, HCO3-) approximately equal to those in plasma.

    ◦ Chloride (Cl-) is the primary ion actively secreted by acinar cells. This mechanism depends on the Na+/K+ pump in the basolateral membrane, which creates a Na+ gradient.

    ◦ Na+/K+/2Cl- cotransporters accumulate Cl- inside the cell, which then diffuses into the lumen via electrogenic ion channels.

    ◦ An Na+/H+ exchanger also contributes by promoting intracellular HCO3- accumulation, which is then exchanged for Cl-.

    ◦ Na+ moves paracellularly through tight junctions into the lumen to maintain electroneutrality, and water follows passively down its osmotic gradient, both paracellularly and transcellularly (via aquaporin 5 channels).

    ◦ Myoepithelial cells, which surround the acinar cells and intercalated ducts, contract to expel formed saliva into the main duct in response to neural stimulation. This contraction also prevents retrograde movement of juice and distention of the acinus.

• Saliva Modification (Ductal Cells):

    ◦ As the initial saliva moves through the striated ducts, its composition is modified by the columnar epithelial cells lining them.

    ◦ Na+ and Cl- are actively reabsorbed from the saliva into the tissue. This process relies on Na+ channels in the apical membrane and the Na+,K+-ATPase in the basolateral membrane.

    ◦ K+ and HCO3- are actively secreted into the saliva. K+ is secreted through apical channels, while HCO3- is concentrated intracellularly via an Na+/HCO3- transporter and then leaves the cell via the cAMP-activated cystic fibrosis transmembrane regulator (CFTR) Cl- channel or a Cl-/HCO3- exchanger at the apical membrane.

    ◦ The duct epithelium is relatively impermeable to water. Because more solutes (Na+ and Cl-) are reabsorbed than secreted (K+ and HCO3-), an osmotic gradient is created, causing the final saliva to become hypotonic.

    ◦ Aldosterone can act at the luminal membrane of ductal cells to increase the absorption of Na+ and the secretion of K+ by increasing the numbers of their channels.

IV. Regulation of Salivary Secretion The regulation of salivary secretion is distinct from other GI secretions primarily due to its exclusive neural control and the complementary actions of both autonomic branches.

• Autonomic Nervous System (ANS) Control:

    ◦ Salivation is almost entirely controlled by the ANS.

    ◦ Unlike gastric and pancreatic secretions, salivary flow is not regulated by GI hormones.

    ◦ Both the parasympathetic and sympathetic branches stimulate secretion, which is unusual in the GI tract.

• Parasympathetic Stimulation:

    ◦ Exerts a much greater influence on salivary secretion volume than sympathetic stimulation.

    ◦ Mediated by preganglionic fibers in cranial nerves VII (facial) and IX (glossopharyngeal).

    ◦ The primary neurotransmitter is Acetylcholine (ACh), which acts on muscarinic cholinergic receptors on acinar and duct cells.

    ◦ ACh binding leads to the formation of inositol triphosphate (IP3) and the subsequent release of Ca2+ from intracellular stores, as well as Ca2+ entry from outside the cell.

    ◦ This pathway increases the volume of acinar cell secretion.

    ◦ Parasympathetic fibers also innervate surrounding blood vessels, causing vasodilation and increasing blood flow, which supports high rates of secretion.

    ◦ Stimulates myoepithelial cell contraction, enhancing saliva expulsion.

    ◦ Increased cellular activity due to parasympathetic stimulation leads to gland growth.

    ◦ Anticholinergic drugs (e.g., atropine) inhibit saliva production, leading to dry mouth (xerostomia).

    ◦ Stimuli include chewing, consuming spicy or sour-tasting foods, smelling food, conditioned reflexes, and nausea.

• Sympathetic Stimulation:

    ◦ Mediated by norepinephrine, which binds to β-adrenergic receptors on acinar and duct cells.

    ◦ This results in the formation of cyclic adenosine monophosphate (cAMP).

    ◦ Agonists elevating cAMP lead to a greater increase in enzyme and mucus content.

    ◦ Produces a biphasic change in blood flow to the salivary glands: an initial decrease due to α-adrenergic receptor activation and vasoconstriction, followed by an increase due to vasodilator metabolites.

    ◦ Section of sympathetic fibers has little effect compared to parasympathetic.

• Complementary Effects of Dual Innervation:

    ◦ The dual autonomic regulation is unusual in that both systems stimulate secretory, metabolic, trophic, muscular, and circulatory functions in similar directions.

    ◦ For example, parasympathetic nerves stimulate the secretion of watery saliva, while sympathetic nerves constrict blood vessels, reducing blood flow and resulting in the production of a thicker, more viscous saliva.

• Other Mediators:

    ◦ Vasoactive intestinal peptide (VIP) and substance P, also released from neurons in salivary glands, can contribute to secretion by increasing intracellular Ca2+.

    ◦ Kallikrein is released when salivary gland metabolism increases, converting plasma protein into bradykinin, which contributes to increased blood flow to the secreting glands.

• CNS Integration:

    ◦ The central nervous system integrates external events to either stimulate or inhibit salivary gland activities. For instance, sleep, fear, dehydration, and fatigue lead to glandular inhibition.