10 Chapter 1 GENERAL INTRODUCTION Human saliva is produced by three pairs of major salivary glands and multiple minor salivary glands. The major salivary glands are the parotid, the submandibular, and the sublingual glands. The parotid glands mostly secrete serous saliva. The submandibular glands secrete both mucinous and serous saliva. The sublingual glands and the minor salivary glands secrete only mucinous saliva [1]. The minor glands comprise approximately 600– 1000 glands, distributed throughout the mouth except for the anterior part of the palate [2, 3]. Only recently, and surprisingly to many in the salivary and anatomical fields, a report was published in 2020 describing the location of a potential ‘new’ salivary gland, the ‘tubarial gland’ [4]. The glands were proposed to be situated close to the torus tubarius, a structure in the human nasopharynx composed of cartilage, which supports the auditory tube. Though, it is questioned whether the tubarial glands are bona fide salivary glands and the quest to their identity is currently under investigation [5-7]. The major salivary glands are responsible for 90% of the total volume of saliva, while the minor glands are responsible for <10% of the total secretion. Although the contribution of these minor glands is limited quantitatively, the ingredients in saliva secreted by these glands are essential for the local protection and moistening of the mucosal surface [2]. The salivary flow is regulated by the autonomic nervous system, with the parasympathetic response primarily responsible for stimulating secretion of watery saliva and the sympathetic system involved in salivary protein production [8, 9]. Healthy, unstimulated salivary secretion rates vary between 800 and 1500 mL per day or 0.25-0.35mL/min, but can increase upon stimulation, e.g. by chewing and taste, up to 1.0-3.0 mL/min [1, 10, 11]. The salivary flow rate and salivary composition are dependent upon the type and duration of the stimulus, and the glands that secrete the saliva [8]. Besides, the circadian rhythm affects the salivary secretion rate as well [10, 12]. This circadian rhythm has a high amplitude with a peak in saliva secretion in the late afternoon, while the flow rate is virtually negligible during sleep [10]. Saliva is considered as fundamental for the maintenance of the oral cavity homeostasis [2], due to its multiple functions including moistening and lubrication, microbial homeostasis, wound healing, tooth mineralization, and pH buffering (Figure 1) [10, 11, 13]. Additionally, saliva is involved in digestion and taste perception [10]. Although saliva consists of 99% water, its functions are effectuated by a great variety of compounds including ions, peptides and proteins such as glycoproteins and immunoglobulins (Figure 1) [14].
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