**4. Significance of salivary secretion**

daily which is contributed by major and minor salivary glands. The resting flow of saliva is 0.2–0.4 ml/min. Salivary flow at rest refers to as unstimulated saliva, whereas salivary flow in response to a stimulus refers to stimulated saliva having a flow rate of 2–5 ml/min. The

A number of factors control the quality and quantity of saliva secreted. The control of salivary gland secretion is mediated by the autonomic nervous system (ANS). All the salivary gland cells receive ANS supply. Control of secretion is also dependent on the perception of taste and smell. The gustatory stimulus is more important than the masticatory stimulus in controlling the salivary secretion. The secretion of saliva occurs by the process of stimulus secretion coupling. This refers to the events involving release of neurotransmitter from vesicles in nerve terminals adjacent to parenchymal cells which stimulate them to discharge secretory granules, water and electrolytes as well as contraction of myoepithelial cells. Norepinephrine activates both alpha and beta adrenergic receptors, while parasympathetic transmitter like acetylcholine activate cholinergic receptors. Alpha adrenergic receptor stimulation results in protein secretion while beta adrenergic or cholinergic stimulation results in low protein secretion and secretion of water and electrolytes. Substance P stimulates alpha adrenergic and cholinergic secretion of saliva. The following flow chart (**Figure 4**) shows the events associated with stimulus secretion coupling which involves the basic process of receptor stimulation which results in increase in the concentration of a secondary messenger, which will further

Copious watery saliva is secreted in response to parasympathetic stimulation and thicker saliva in response to sympathetic stimulation. Other factors affecting saliva composition are flow rate, circadian rhythm, duration of stimulus, nature of stimulus and diet. During sleep very little saliva is secreted by major salivary glands and majority of the saliva secreted is by the minor salivary glands. Concentration of saliva depends on rate of flow and not on nature

Historically, it was suggested that parotid salivary gland secretes a hormone called parotin which was considered to have a protein-anabolic function and deficiency resulted in diseases

An increase in the flow of saliva is referred to as sialorrhea (ptyalism), while a decrease in the salivary flow is referred to as xerostomia (dry mouth). Ptyalism is observed after insertion of new orthodontic appliance, in pregnancy, epilepsy, cerebral palsy and Parkinson's disease. Xerostomia is observed in menopause, patients treated by radiation therapy, old age, prolonged use of tranquilizers, amphetamines, antihypertensive and anticonvulsant drugs. A number of systemic conditions affect the functioning of the secretion of salivary glands. Hyperthyroidism, pernicious anemia, vitamin D deficiency, multiple sclerosis and poorly controlled diabetes mellitus affect the salivary glands. Autoimmune diseases like Sjogren's syndrome, Mikulicz's disease affect the salivary gland secretion as the parenchymal elements are affected. Inflammatory, infective and neoplastic diseases also disrupt the activity of salivary gland secretion. Salivary secretion is influenced by hormones. For example antidiuretic hormone facilitates water reabsorption by striated duct, aldosterone causes increased sodium reabsorption by striated duct, testosterone and thyroxine increase salivary secretion [2, 8, 9].

normal pH of saliva is 6.4–7.4 [1, 2].

8 Salivary Glands - New Approaches in Diagnostics and Treatment

of stimulus [2–6].

trigger additional events leading to a cellular response [3–6].

such as chondrodystrophia fetalis, Kaschin-Beck disease, etc. [7].

The saliva has a number of important functions as mentioned below.

Protection: the saliva contains mucin and glycoproteins which provides it with lubricating properties and moistening the oral cavity, thus preventing friction between the oral structures during physiological functions like mastication. The constant flow of saliva provides clearance of accumulated food debris and microorganisms. Mucins also provide thermal and chemical insulation. Proteins, glycoproteins and mucins form a coating called pellicle formation. Saliva acts as a source of calcium, phosphate, fluoride, statherin and proline rich protein which maintain the integrity of enamel and repair.

Digestion: water and mucin content of saliva aids in bolus formation during the process of mastication. Saliva contains salivary amylase (ptyalin) which helps in digestion of starch and lingual lipase secreted by von Ebner's gland breaks down triglycerides.

by generalized exocrinopathy. In this condition, saliva contains increased calcium levels, ele-

Secretions of Human Salivary Gland http://dx.doi.org/10.5772/intechopen.75538 11

Sjogren's Syndrome is associated with reduction in lacrimal and salivary secretions. It is characterized by the presence of a lymphocytic infiltrate (predominantly CD4+ T-cells) in the salivary gland parenchyma. A low resting flow rate and abnormally low stimulated flow rate of whole saliva. An antibody p53 can also be detected in the saliva of patients diagnosed with oral squamous cell carcinoma (SCC). Viral diseases like measles, mumps, and rubella can be detected, polymerase chain reaction (PCR)-based identification of virus in saliva is a useful method for the early detection of HSV-1 reactivation in patients with Bell's palsy. Acute hepatitis A (HAV) and hepatitis B (HBV) can be diagnosed based on the presence of

Saliva can be used for monitoring of anti-epileptic drugs as a positive correlation between salivary and serum carbamazepine levels has been observed. In another study, salivary levels of phenobarbital and phenytoin demonstrated excellent correlations with serum levels of these medications. Other drugs that can be identified in saliva are amphetamines, barbiturates, ben-

Steroid hormones can be detected in saliva. Salivary cortisol levels were found to be useful in

Recent focus on the potential role of periodontal disease as a risk factor for cardiovascular and cerebrovascular diseases [13, 14] and the occurrence of pre-term low-birth-weight babies [15]

Salivary markers as potential diagnostic tests for periodontal disease include proteins of host origin (i.e., enzymes, immunoglobulins), phenotypic markers, host cells, hormones (cortisol),

Salivary levels of MMP-8 and IL-1β appear to serve as biomarkers of alveolar bone loss and

National Institute of Dental and Craniofacial Research, has highlighted the use of saliva for translational and clinical application by use of salivary proteome and the salivary transcrip-

Gene therapy has been developed to deliver growth hormone in deficiency states by salivary

The secretions of salivary gland form an integral part of maintaining the physiology of the oral cavity. Saliva is the most important and essential secretion of the salivary glands. Saliva itself has varied functions in the oral cavity and provides additional insight and details of the systemic status of the individual as well. With the advancement in the field of proteomics,

vated levels of sodium and a decrease in flow rate [8, 9].

Immunoglobulin M antibodies in saliva [8, 9].

hence periodontitis [8, 9, 11].

**5. Conclusion**

gland expression of growth hormone [16].

zodiazepines, cocaine, phencyclidine (PCP), and opioids [8–10].

bring new importance to this aspect of salivary analysis [8–15].

bacteria and bacterial products, ions and volatile compounds [8, 9, 11].

tome for early detection, disease progression and therapeutic monitoring [8, 9].

identifying patients with Cushing's syndrome and Addison's disease [12].

Antimicrobial activity: mucins aid in providing a physical barrier to infections by preventing attachment of microorganisms to tooth and tissue surface. Presence of secretory immunoglobulin A provides immune defense. Peroxidase, lysozyme, lactoferrin, histatin, mucins, agglutinin, defensins and cathelicidin also help in providing antimicrobial activity.

Buffering: bicarbonate, phosphate, basic proteins, urea and ammonia help maintain the pH and neutralization of acids.

Tissue repair: salivary glands release growth factors, trefoil proteins into saliva which aid is tissue repair and regeneration.

Taste: saliva acts as a solvent in which molecules from food items can dissolve and reach the taste buds, epidermal growth factor and carbonic anhydrase VI maintains taste buds.

Role of saliva in periodontal pathology: saliva exerts a major influence on plaque initiation, maturation and metabolism. The first step in plaque formation is formation of pellicle followed by plaque formation and maturation [1–6, 8, 9].

Salivary proteins may play a role in plaque mineralization. It is indicated that esterase, pyrophosphatase, acid phosphatase and lysozyme may be involved. Persons with heavy calculus, have higher levels of salivary glycoproteins than non-calculus formers [1–6, 8, 9].

Polymorphonuclear neutrophils (PMNs) reach the oral cavity by migrating through the lining of gingival sulcus. Skougaard and Bay, 1994 believe that orogranulocytic migratory rate correlates with severity of gingival inflammation and is therefore reliable index for assessing gingivitis [8–11].

The saliva acts as an important diagnostic oral fluid owing to its ease and non-invasive mode of collection. A number of components secreted in saliva can be assessed and used to assess diseased states.

A few of the components used as specific biomarkers for detection of periodontal disease include immunoglobulins (Ig) such as IgA, IgM, IgG which interfere in adherence and bacterial metabolism and are present in increased concentration in saliva of chronic and aggressive periodontal patients. Nonspecific markers for aggressive periodontitis include mucins which interfere with the colonization of Aggregatibacter actinomycetemcomitans (A. a), lactoferrin which inhibits microbial growth/increased correlation with A. a. Markers for chronic periodontitis include lysozyme which regulates biofilm accumulation and peroxidase which interferes with biofilm accumulation. Nonspecific markers for both chronic and aggressive periodontitis include histatin which neutralizes lipopolysaccharide and enzymes known to affect periodontium and C-reactive proteins which are present in increased concentrations in saliva and serum of patients with periodontitis [8].

Other areas where saliva can be used for diagnosis of diseases and conditions include cystic fibrosis, which is a genetically transmitted disease of children and young adults characterized by generalized exocrinopathy. In this condition, saliva contains increased calcium levels, elevated levels of sodium and a decrease in flow rate [8, 9].

Sjogren's Syndrome is associated with reduction in lacrimal and salivary secretions. It is characterized by the presence of a lymphocytic infiltrate (predominantly CD4+ T-cells) in the salivary gland parenchyma. A low resting flow rate and abnormally low stimulated flow rate of whole saliva. An antibody p53 can also be detected in the saliva of patients diagnosed with oral squamous cell carcinoma (SCC). Viral diseases like measles, mumps, and rubella can be detected, polymerase chain reaction (PCR)-based identification of virus in saliva is a useful method for the early detection of HSV-1 reactivation in patients with Bell's palsy. Acute hepatitis A (HAV) and hepatitis B (HBV) can be diagnosed based on the presence of Immunoglobulin M antibodies in saliva [8, 9].

Saliva can be used for monitoring of anti-epileptic drugs as a positive correlation between salivary and serum carbamazepine levels has been observed. In another study, salivary levels of phenobarbital and phenytoin demonstrated excellent correlations with serum levels of these medications. Other drugs that can be identified in saliva are amphetamines, barbiturates, benzodiazepines, cocaine, phencyclidine (PCP), and opioids [8–10].

Steroid hormones can be detected in saliva. Salivary cortisol levels were found to be useful in identifying patients with Cushing's syndrome and Addison's disease [12].

Recent focus on the potential role of periodontal disease as a risk factor for cardiovascular and cerebrovascular diseases [13, 14] and the occurrence of pre-term low-birth-weight babies [15] bring new importance to this aspect of salivary analysis [8–15].

Salivary markers as potential diagnostic tests for periodontal disease include proteins of host origin (i.e., enzymes, immunoglobulins), phenotypic markers, host cells, hormones (cortisol), bacteria and bacterial products, ions and volatile compounds [8, 9, 11].

Salivary levels of MMP-8 and IL-1β appear to serve as biomarkers of alveolar bone loss and hence periodontitis [8, 9, 11].

National Institute of Dental and Craniofacial Research, has highlighted the use of saliva for translational and clinical application by use of salivary proteome and the salivary transcriptome for early detection, disease progression and therapeutic monitoring [8, 9].

Gene therapy has been developed to deliver growth hormone in deficiency states by salivary gland expression of growth hormone [16].
