Introduction

The public and health professionals’ image of saliva has changed drastically in recent years because of abundant information about the role of saliva in health and disease that is made available for public consumption via the Internet and the media. In the view of most people, saliva was created for licking envelops and stamps. People rarely paid attention to saliva unless they were nervous, developed dry mouth, and had to deliver a public speech. Indeed, dry mouth caused by anxiety was used as a diagnostic aid by ancient societies in a lie detector test known as the rice test (Mandel, 1993). An accused was given a mouthful of dry rice to chew and swallow. If the accused was anxious because of guilt, the emotional inhibition of salivation resulting from increasing activity of the sympathetic nervous system would have interfered with adequate bolus formation and swallowing; it was interpreted as proof of wrongdoing and resulted in beheading of the accused. What used to be described as 99% water today is viewed as a fountain of information that reflects an individual’s state of health and disease. The quality and quantity of saliva, like urine and blood, are affected by a variety of medical conditions and medications, as well as the psychological status of the patient. The public and professionals are used to blood and urine tests but not a saliva test as a routine practice for risk assessment and disease prevention. Although a saliva test is less invasive than a blood test, and needs less privacy than a urine test, it has not been part of the everyday practice of medicine and dentistry in the past. However, saliva diagnostic tests are becoming more readily available to and utilized by healthcare providers in recent years.

This chapter is written in an attempt to enhance awareness among oral healthcare providers of the role of saliva in health and disease and the significant role that they could play in the early detection and recognition of salivary gland hypofunction, as well as the prevention of its associated complications.

Formation

Saliva is produced by three pairs of major glands and numerous minor salivary glands within the oral cavity. The parotid, submandibular, and sublingual salivary glands contribute to 90% of total saliva secretions. Minor salivary glands contribute to the remaining 10%. The saliva secreted by the major and minor glands collectively is referred to as whole saliva. In the resting (unstimulated) state, approximately two-thirds of the volume of whole saliva is produced by submandibular glands. Upon stimulation, the parotid glands account for at least 50% of whole saliva volume in the mouth. Sublingual glands contribute to a small percentage of unstimulated and stimulated whole saliva. Minor salivary glands contribute significantly to the lubrication of the oral mucosa because they contain a large amount of proteins. Unlike some minor salivary glands that are purely mucous in nature, parotid glands are purely serous and produce water-like secretions. Submandibular and sublingual glands are mixed. In general, the acinar (secretory) cells are responsible for production of primary saliva. The ductal cells are responsible for further modifications of saliva until it is secreted in the mouth. Saliva is 99% water and 1% proteins and salts. The normal daily production of saliva ranges from 0.5 to 1.5 L. The average whole unstimulated saliva flow rate is approximately 0.3–0.4 mL/min. This rate may decrease to 0.1 mL/min during sleeping hours and increases to approximately 4.0–5.0 mL/min during eating, chewing, and other stimulating conditions. Saliva is always hypotonic to plasma. The higher the saliva flow rate, the greater the tonicity of saliva will be. Salivary gland secretion is mainly controlled by the autonomic nervous system. Parasympathetic stimulation produces copious (watery) saliva, whereas sympathetic stimulation produces more viscous saliva (Bardow, Pedersen, & Nauntofte, 2004).

Function

Saliva plays a significant role in the protection of the intraoral structures against insults introduced by different microbial pathogens and chemical and mechanical irritants. The functions of saliva are listed in Table 4.1.

Saliva contains three buffer systems (bicarbonate, phosphate, and protein) and helps to maintain an acceptable pH in the range of 6.0–7.5 within the oral cavity. When a substance is placed in the oral cavity, the saliva flow will increase based on its taste, consistency, and concentration. When the volume of saliva is about 1.1 mL, the urge for swallowing will occur. The salivary stimulation, dilution of tastant, and swallowing will go on until the concentration of the tastants reaches a point where it no longer stimulates the flow rate. The oral clearance of different substances will be prolonged in the absence of saliva, leading to potential harm to intraoral hard and soft tissues. Saliva is supersaturated with respect to calcium hydroxyapatite under normal physiologic conditions, which prevents demineralization of the dentition. The salivary protein pellicle further protects teeth against irritants.

Human saliva contains α-amylase and lipase, which may play a role in starch digestion and triglyceride breakdown in neonates with pancreatic dysfunction. Salivary mucins play a significant role in lubricating the intraoral structures and serve as a barrier against microbial invasion. Lysozyme and lactoferrin are examples of other proteins with antimicrobial properties. Lactoferrin is believed to have antibacterial, antifungal, and antiviral properties. Salivary peroxidase has antibacterial properties, whereas histatins have been associated with antibacterial and antifungal properties. Salivary epidermal growth factor enhances the oral mucosal healing process and protects the oro-esophageal mucosa. In addition to these proteins with specific functions, saliva contains other organic components, such as glucose, urea, cortisol, sex hormones, and blood group substances, which have also been utilized in saliva as screening/diagnostic tools (Malamud & Rodriguez-Chavez, 2011).

Dysfunction

Multiple medical conditions and medications can affect the quality and quantity of saliva (Bergdahl, Bergdahl, & Johansson, 1997; Sreebny & Schwartz, 1997; Antilla, Knuuttila, & Sakki, 1998; Bergdahl & Bergdahl, 2000). This chapter will focus on the potentially common factors associated with chronic salivary gland hypofunction in adults (Table 4.2). Less frequent, uncommon, and/or acute conditions such as dehydration, salivary gland neoplasm, sialosis, sialadenosis, sialorrhea, sialolithiasis, and sialadenitis will not be covered here.

Salivary cortisol level is increased as a response of the adrenal cortex to stressors such as chronic dental anxiety, stressful computer task requirements, viewing anxiety-provoking videos, and masticatory muscle activity caused by clenching teeth. Relaxation modalities, such as viewing soothing videos, listening to music, and acupuncture treatment, could lower the saliva cortisol and amylase levels (Piollet et al., 1984; Benjamins, Asscheman, & Schuurs, 1992; Miluk-Kolasa et al., 1994; Bosch et al., 1996; Stones et al., 1999; Blom & Lundeberg, 2000; Hill & Walker, 2001; Neudeck, Jacoby, & Florin, 2001; Brennan et al., 2002; Bakke et al., 2004; Hasegawa, Uozumi, & Ono, 2004; Takai et al., 2004; Hugo et al., 2008). As noted earlier, subjective dry mouth may have a psychological origin. Psychological processes are often accompanied by disturbed oral sensations and, in fact, most individuals have experienced dry mouth during a period of acute stress. Together with depression, mental stress has been reported to be associated with a dry mouth condition, either as a result of the illness itself or as an adverse effect of drugs used in the management of the psychological state (Davies & Gurland, 1961; Bolwig & Rafaelsen, 1972; Bergdahl et al., 1997). Stress may play a role, and the more anxiety there is, the lower the whole unstimulated saliva content of IgA. However, it has proved difficult to separate the effects of anxiety on salivary flow and immunoglobulin levels independently. These findings are in keeping with studies of saliva during daily relaxation. The secretory IgA rate increased significantly after relaxation (Green, Green, & Santoro, 1988).

Studies of cortisol in depressed patients have given interesting results, provided technical aspects of steroid assays are controlled. In depression, there seem to be differences in salivary cortisol between patients with endogenous and nonendogenous depression. Generally, there is a correlation between plasma adrenocorticotropic hormone (ACTH) levels and salivary cortisol, but this relationship is not present in patients with endogenous depression, suggesting either a drug effect or a disturbance of regulation of cortisol secretion (Galard et al., 1991). Self-induced vomiting and binge eating are features of bulimia nervosa. Saliva function has been studied in this group, and it is known that approximately 25% have sialadenosis (Roberts et al., 1989; Riad, Barton, & Wilson, 1991). Some studies have shown that parotid function is reduced in bulimics; that is, resting and stimulated flow rates are reduced in those with sialadenosis, and total protein and amylase levels are increased. Other studies of parotid and submandibular gland function have shown no difference in function in relation to controls, and amylase levels were equivalent.

Xerostomia is a common oral complaint associated with more than 500 medications (Sreebny & Schwartz, 1988). Polypharmacy is the most common cause of xerostomia (subjective complaint of dry mouth) and salivary gland hypofunction (objective evidence of reduced saliva flow rate) in the elderly. In May 2011, the U.S. Food and Drug Administration (FDA) added dry mouth to its consumer health information. The older population, those 65 years or older, represented 12.4% of the population in 2000 but are expected to grow to 19% by 2030. Approximately 80% of these individuals have at least one chronic medical condition, and 50% have at least two. Hypertension and heart diseases, diabetes, arthritis, and cancer are the most common medical conditions seen in older individuals. The most frequent types of medications with xerogenic potential are those with anticholinergic or sympathomimetic actions. Salivary gland hypofunction is often an overlooked condition, and many patients who take xerogenic medications may not know that they are at risk for oral complications, such as dental caries and fungal infections. Therefore, the absence of a subjective complaint of oral dryness does not indicate adequate saliva production. Accordingly, the diagnosis of drug-induced hyposalivation requires measurements of saliva output or flow rate. In addition to the xerogenic medications taken by mouth, other chemotherapeutic modalities like chemotherapy and radiation therapy lead to qualitative and quantitative salivary changes. There is an association between the severity of salivary gland hypofunction and the degree of exposure to radiation. The management of oropharyngeal cancer often involves administration of 60-GY to 70-GY radiation that can lead to a 95% reduction in the amount of salivary secretions in the involved areas (Davies, Broadley, & Beighton, 2001). The severit/>