Key points

Introduction

Saliva is one of the most versatile, multifunctional substances produced by the body and has a critical role in the preservation of oropharyngeal health. When dysfunction occurs, the effects on the oral environment can lead to severe consequences in the overall patient’s health and in their quality of life. This article reviews the role of saliva, the hyposalivation and xerostomia, various disease processes, and their management.

Introduction

Saliva is one of the most versatile, multifunctional substances produced by the body and has a critical role in the preservation of oropharyngeal health. When dysfunction occurs, the effects on the oral environment can lead to severe consequences in the overall patient’s health and in their quality of life. This article reviews the role of saliva, the hyposalivation and xerostomia, various disease processes, and their management.

Hyposalivation and xerostomia

Although the terms hyposalivation and xerostomia have been and are used interchangeably, they are actually 2 different entities. Hyposalivation is an objective finding of a decreased salivary production. The term xerostomia is the subjective feeling of having dry mouth. Normal, unstimulated salivary secretory rates vary between 800 and 1500 mL per day or 0.3 to 0.4 mL per minute. A flow rate less than 0.1 mL per minute has been determined to be significantly abnormal. A decrease in saliva production by 50% generally will result in the feeling of dry mouth, but xerostomia may occur in patients with a normal salivary flow. For the most part, this article mostly covers the management of hyposalivation, but it will touch on the treatment modalities for xerostomia patients with normal salivary flow rates.

Normal salivary function

Saliva can be empirically divided into 2 components, mucinous and serous. These 2 components combine to form whole saliva. Whole saliva is secreted by the paired major salivary glands and the thousands of minor salivary glands. There are 3 types of major salivary glands: the parotid, the submandibular, and the lingual (sometimes called the sublingual) glands. The parotid glands mostly secrete serous saliva. The submandibular glands secrete both mucinous and serous saliva. The lingual glands and the minor salivary glands secrete only mucinous saliva.

Saliva also contains hundreds of other substances, such as desquamated cells, glycoproteins, bacteria, debris, complex mixtures of proteins, lipids, ions, and other substances. Although the purpose of many of these components is understood, there are others whose function still remains unknown.

The salivary glands are innervated along the parasympathetic cholinergic pathway. When the gustatory centers are stimulated, acetylcholine is released from the nerve endings and binds to the muscarinic receptors on the salivary gland cells, particularly the muscarinic 3 receptor (M3R), triggering the release of intracellular calcium from the endoplasmic reticulum. These calcium ions activate the transmembrane sodium potassium pump, which increases the intraductal concentration of sodium ions. An ionic gradient then pulls the chloride ions from the ductules, which in turn creates an osmotic gradient that results in the secretion of fluid from the cells.

Salivary mucins

Salivary mucins serve the important function of sequestering water in the oral mucosa, acting as a lubricating agent, and as a protective layer for the hard and soft tissues of the mouth. Molecularly, they comprise oligosaccharide side chains attached to a central protein strut. The major viscoelastic mucins are the gel-forming MUC5B mucin and the nonpolymeric MUC7 mucin. These specific mucins lubricate the mucosa, protecting it from frictional and chemical damage. They also coat ingested food, allowing it to be smoothly swallowed. Mucins also surround the teeth, further protecting the teeth from demineralization and mechanical damage. It has been hypothesized that a loss or a change in concentrations of these molecules is the main etiologic factor in the development xerostomia.

Salivary minerals

Saliva is rich in minerals, specifically sodium, potassium, calcium, hydrogen, bicarbonate, phosphate, zinc, magnesium, and others. These minerals, along with the salivary proteins, create an osmotic gradient between the intracellular fluid in the salivary cells and the extracellular fluid in the glandular ductules. This osmotic gradient is the driving force that brings the intracellular fluid through the transmembranous channels into the glandular ductules.

The oral pH normally stays in the range of 6.0 to 7.0 and is maintained by the different ions found within the saliva. These ions, particularly bicarbonate and phosphate, stabilize the pH and thereby limit the demineralization of the teeth from bacterial acid and acidic food and drinks. As well as buffering the oral pH, the calcium, phosphate, and fluoride ions that are present in the saliva also remineralize the teeth. The pH range is also necessary for the activation of salivary amylase, the enzyme that begins the hydrolysis of starch into sugars. Finally, by keeping the pH stable, the equilibrium of the oral microbiota is maintained, preventing the overgrowth of Candida and other organisms. The zinc ions that are found in the saliva are crucial for the activation of the taste buds, and for this reason, patients with hyposalivation manifest a decrease or loss in their taste sensation.

Immune system function

There are immune system components found in the saliva. The salivary glands, particularly the parotid glands, contain B cells and plasma cells that excrete salivary Immunoglobulin A (IgA), which binds to the mucins covering the mucosa. In turn, the IgA binds to bacteria, fungi, and viruses, blocking microbial attachment to the mucosa. Other substances that are part of the oral immune system are histatins, lactoperoxidase, lactoferrin, and secretory leukocyte protease inhibitor. These substances also serve to limit the concentration of the oral microbes, helping to further prevent bacterial and fungal overgrowth.

Disease entities

The exact number of patients who have hyposalivation and/or subjective xerostomia is unclear. Meta-analysis of different studies shows a prevalence that ranges from 5% to 47%. This large range is due to a variation in methodology and definitions in the different studies. Regardless of the disparity of the prevalence range, when evaluating the data based on age, it is clear that 20% of the patients 65 years or older have some type of salivary gland abnormality. Ship and colleagues reported that medication-induced hyposalivation is the most common cause of dry mouth in this age category because most older adults take at least one xerogenic medication. The other major diseases that cause hyposalivation are advanced Sjögren syndrome (SS) and head and neck radiation. In these entities, the prevalence of salivary dysfunction is nearly 100%.

Medication-induced salivary gland dysfunction

More than 400 medications can cause salivary gland dysfunction, and 80% of the most commonly prescribed medications have been reported to cause hyposalivation.

It has been found that the incidence and severity of the hyposalivation are directly proportional to the number of medications that the patient is taking. Of the patients over the age of 65, 88% took 1 prescription medication; 76% took 2 prescription medications, and 37% took 5 or more prescription medications.

Medications that have an anticholinergic effect cause the most hyposalivation. The mechanism of this action is at the M3R. Anticholinergic medications decrease the amount of acetylcholine released by the parasympathetic nerves, disabling cell function. The most common xerogenic drug categories are sedative agents, antihistamines, anti-Parkinson, antihypertensive, and antidepressants medications ( Table 1 ).

Radiation-induced hyposalivation

Radiation therapy is commonly used in the treatment of head and neck malignancies. It causes apoptosis (cell death) of the tumor cells. Unfortunately, when the salivary glands are within the field of radiation, it also damages the salivary acinar and stem cells population, causing a permanent degeneration of the salivary glands. Following radiation, the glands atrophy and become nonfunctional and fibrotic. This damage typically occurs when the exposure dose is 60 Gy or more, although the exact mechanism that leads to gland damage is not clearly understood.