**3. Physiological aspects of salivation, chewing, and swalloing**

#### **3.1. Salivation**

Minor and major salivary glands are responsible for saliva production. These exocrine glands consist of a few fundamental cell types: i) acinar cells, which are responsible for secretion of salivary components; ii) myoepithelial cells, which usually form a thin layer above the basement membrane that support acinar and ductal cells and have contractile functions that help to expel the salivary secretions from the lumen to the duct; iii) ductal cells, which are distributed in specialized segments for transportation and modulation of salivary composi‐ tion. Moreover, there are putative stem cells that reside in the ductal compartment and are related to repair and regeneration of salivary glandular tissue [19, 20].

Saliva is an exocrine secretion made by minor and major (parotid, submandibular, and sublingual) salivary glands that is expressed into the oral cavity. Saliva consists of approxi‐ mately 99% water, containing a variety of electrolytes (sodium, potassium, calcium, chloride, magnesium, bicarbonate, phosphate), carbohydrates (glucose, glycosaminoglycans), proteins (represented by enzymes, immunoglobulins and other antimicrobial factors, mucosal glyco‐ proteins, traces of albumin, and some polypeptides and oligopeptides), and traces of other biological products (urea, ammonia). Saliva exhibits pH is from 6 to 7 and varies in accordance with the salivary flow. Saliva is critical for preserving and maintaining the health of the oral tissues, allowing them to adequately perform a number of pivotal functions for taste sensation, mastication, digestion, deglutition, and speech. Also aided by the effects of saliva are tissue protection and repair, dilution of toxic substances and cleaning of microorganisms and residues. Saliva can be a useful auxiliary means of diagnosis, an indicator of risk, anda way to monitor local and systemic diseases [10, 33-37] (Table 1).

Saliva can be categorized as *whole saliva* and *specific glandular-derived saliva*. Whole saliva is representative of the typical status of the oral cavity, as it is a complex mixture of fluids from the salivary glands, the gingival crevicular fluid, mucous secretions from the oral cavity, nasal cavity, and pharynx, non-adherent oral bacterial, food remainders, desquamated epithelial


**Table 1.** Functions of saliva and main characteristics.

The muscles of the oropharynx receive innervation from the pharyngeal plexus of the vagus nerve (CN X). This network of nerve fibers provides sensory and motor innervation from the pharyngeal branches of the glossopharyngeal nerve (CN IX), the pharyngeal branch of the vagus nerve (CN X), and superior cervical ganglion sympathetic fibers (a component of the autonomic sympathetic nervous system responsible for maintaining homeostasis of the body). However, the motor innervation of the oropharynx also receives nerve fibers from the cranial part of accessory cranial nerve (CN XI). The palatine tonsils receive afferent innervation via the tonsillar plexus, which has contributions from the general somatic afferent fibers of the maxillary division of the trigeminal nerve (CN V) via the lesser palatine nerves, and general visceral afferent fibers from the tonsillar branches of the glossopharyngeal nerve (CN IX)

**3. Physiological aspects of salivation, chewing, and swalloing**

related to repair and regeneration of salivary glandular tissue [19, 20].

monitor local and systemic diseases [10, 33-37] (Table 1).

Minor and major salivary glands are responsible for saliva production. These exocrine glands consist of a few fundamental cell types: i) acinar cells, which are responsible for secretion of salivary components; ii) myoepithelial cells, which usually form a thin layer above the basement membrane that support acinar and ductal cells and have contractile functions that help to expel the salivary secretions from the lumen to the duct; iii) ductal cells, which are distributed in specialized segments for transportation and modulation of salivary composi‐ tion. Moreover, there are putative stem cells that reside in the ductal compartment and are

Saliva is an exocrine secretion made by minor and major (parotid, submandibular, and sublingual) salivary glands that is expressed into the oral cavity. Saliva consists of approxi‐ mately 99% water, containing a variety of electrolytes (sodium, potassium, calcium, chloride, magnesium, bicarbonate, phosphate), carbohydrates (glucose, glycosaminoglycans), proteins (represented by enzymes, immunoglobulins and other antimicrobial factors, mucosal glyco‐ proteins, traces of albumin, and some polypeptides and oligopeptides), and traces of other biological products (urea, ammonia). Saliva exhibits pH is from 6 to 7 and varies in accordance with the salivary flow. Saliva is critical for preserving and maintaining the health of the oral tissues, allowing them to adequately perform a number of pivotal functions for taste sensation, mastication, digestion, deglutition, and speech. Also aided by the effects of saliva are tissue protection and repair, dilution of toxic substances and cleaning of microorganisms and residues. Saliva can be a useful auxiliary means of diagnosis, an indicator of risk, anda way to

Saliva can be categorized as *whole saliva* and *specific glandular-derived saliva*. Whole saliva is representative of the typical status of the oral cavity, as it is a complex mixture of fluids from the salivary glands, the gingival crevicular fluid, mucous secretions from the oral cavity, nasal cavity, and pharynx, non-adherent oral bacterial, food remainders, desquamated epithelial

(Figure 6).

14 Seminars in Dysphagia

**3.1. Salivation**

and blood cells, as well as traces of medications or chemical products. On the other hand, specific glandular-derived saliva is characterized as salivary production collected directly and exclusively from the output of the salivary ducts in the oral cavity. Another way to categorize the saliva flow rate is as *unstimulate*d (resting) or *stimulated*. Unstimulated salivary flow rate has a continuous and low salivary flow (basal unstimulated secretion). With regard to the stimulated salivary flow, it is responsible for most of the daily production of saliva and it is usually stimulated by several mechanical, pharmacological, gustatory, and olfactory factors. In healthy subjects, the mean whole saliva production ranges from 1 to 1.5L daily. The clinical evaluation regularly monitored of the stimulated and unstimulated *salivary flow index* (SFI) can be used to categorize the individuals as exhibiting normal, high, low, or very low salivary flow. Adults with normal stimulated salivation exhibit SFI variations between 1 and 3 mL/min, low SFI ranges from 0.7 to 1.0 mL/min, and very low SFI (hyposalivation) is characterized as less than 0.7 mL/min. On the other hand, adults with normal unstimulated salivation exhibit SFI variations between 0.25 to 0.35 mL/min, low SFI ranges from 0.1 to 0.25 mL/min, and very low SFI is less of 0.1 mL/min. The sensation of oral dryness in healthy individuals usually occurs when the whole (both unstimulated and stimulated) SFI is reduced by more than 50% of the daily production [34, 38-40].

Salivary flow and composition varies between individuals and also in the same individual once it is affected by several exogenous and endogenous factors such as age, gender, anatomic and functional aspects of salivary glands, sensory stimuli to food, posture, weight, circadian and circannual cycles, type of nutritional characteristics of the diet, frequency of chewing and bite force, physical exercises, tobacco and alcohol drinking, use of medication, fasting and nausea, and presence of systemic diseases. Decreased salivary flow and alterations in salivary composition cause a clinically significant oral imbalance manifested by increased susceptibility to oral infections (dental caries, periodontal disease, oral candidosis); burning mouth; sore tongue (glossodynia); difficulties with speech, mastication, and swallowing; altered taste sensation (dysgeusia); and halitosis [35, 36, 41-44] (Table 2).



**Table 2.** Factors associated with production and composition of saliva.

#### **3.2. Chewing**

and blood cells, as well as traces of medications or chemical products. On the other hand, specific glandular-derived saliva is characterized as salivary production collected directly and exclusively from the output of the salivary ducts in the oral cavity. Another way to categorize the saliva flow rate is as *unstimulate*d (resting) or *stimulated*. Unstimulated salivary flow rate has a continuous and low salivary flow (basal unstimulated secretion). With regard to the stimulated salivary flow, it is responsible for most of the daily production of saliva and it is usually stimulated by several mechanical, pharmacological, gustatory, and olfactory factors. In healthy subjects, the mean whole saliva production ranges from 1 to 1.5L daily. The clinical evaluation regularly monitored of the stimulated and unstimulated *salivary flow index* (SFI) can be used to categorize the individuals as exhibiting normal, high, low, or very low salivary flow. Adults with normal stimulated salivation exhibit SFI variations between 1 and 3 mL/min, low SFI ranges from 0.7 to 1.0 mL/min, and very low SFI (hyposalivation) is characterized as less than 0.7 mL/min. On the other hand, adults with normal unstimulated salivation exhibit SFI variations between 0.25 to 0.35 mL/min, low SFI ranges from 0.1 to 0.25 mL/min, and very low SFI is less of 0.1 mL/min. The sensation of oral dryness in healthy individuals usually occurs when the whole (both unstimulated and stimulated) SFI is reduced by more than 50% of the

Salivary flow and composition varies between individuals and also in the same individual once it is affected by several exogenous and endogenous factors such as age, gender, anatomic and functional aspects of salivary glands, sensory stimuli to food, posture, weight, circadian and circannual cycles, type of nutritional characteristics of the diet, frequency of chewing and bite force, physical exercises, tobacco and alcohol drinking, use of medication, fasting and nausea, and presence of systemic diseases. Decreased salivary flow and alterations in salivary composition cause a clinically significant oral imbalance manifested by increased susceptibility to oral infections (dental caries, periodontal disease, oral candidosis); burning mouth; sore tongue (glossodynia); difficulties with speech, mastication, and swallowing; altered taste

> ⋅ Although with increasing age the salivary gland tissue undergoes atrophy and gradually is replaced by a fibro-adipose tissue, increasing age *per se* seems to not interfere significantly in

⋅ Unstimulated salivary flow seems to be more affected by advanced age (it is lower in elderly)

⋅ Although the findings are conflicting, it appears that women exhibit low unstimulated and stimulated salivary flow compared to males as a result of a smaller size of the salivary glands

⋅ Salivary flow and its composition depend on the individual contribution of each major salivary gland (parotid, submandibular and sublingual) and minor salivary glands. In unstimulated salivary flow, the parotid, submandibular, sublingual, and minor glands contribute 20%, 65%-70%, 7%-8%, and <10%, respectively. When the salivary flow is stimulated, the parotid gland contributes with over 50% of the total salivary secretion;

daily production [34, 38-40].

16 Seminars in Dysphagia

Age

Gender

Anatomic and functional aspects of salivary glands

sensation (dysgeusia); and halitosis [35, 36, 41-44] (Table 2).

**Factors Main characteristics**

production and salivary composition;

compared to stimulated salivary flow.

and the influence of female sex hormones.

Chewing is a complex integrative physiological mechanism involved in the early stages of digestion and absorption of nutrients. During chewing, the food particles are reduced in size and consistency due to manipulation of food by oral soft tissues and crushing of food by the occlusal surfaces of teeth. The saliva facilitates the chewing mechanism by moistening and coalescing the food particles. The chewed food is kept trapped laterally by the tongue and buccal mucosa and becomes soft and slippery to ensure an adequate swallowing and further processing in the gastrointestinal tract. Chewing involves the participation of diverse ana‐ tomical structures such as teeth, bone (mandible and maxilla), accessory and masticatory muscles, and sensory-motor activities. Biomechanically, the chewing in humans occurs in a stereotypical way: after ingestion of food it is transported from the front of the mouth to the occlusal surfaces of the post-canine teeth. Following this, the food is subjected to a series of masticatory cycles needed to process the food, making it softer and disintegrated until the food becomes more difficult to chew. At this stage, when food is ready to be swallowed, it is propelled posteriorly into the oropharynx where the food accumulates until it is finally swallowed [11, 13].

The muscles of mastication exhibit an adductor action (i.e., a motion that pulls a structure or part towards the midline of the midsaggital plane of the body) of mandible, while the lateral pterygoid muscle abducts (i.e., a motion that pulls a structure or part away from the midline of the midsaggital plane of the body). All four move the mandible laterally. Another accessory muscle, the sternohyomastoid is responsible for opening the mandible in addition to the lateral pterygoid. Anteriorly, the muscles of the lips (orbicularis oris) ensure the closing of the mouth in order to avoid escaping of the food. Posteriorly, at the moment of swallowing, the simul‐ taneous contraction of perioral and jaw muscles, together with opening of the pharyngeal ring, causes a squeeze of the food toward the fauces. The coordinated activity of the trigeminal (CN V) and facial (CN VII) nerves during chewing may be controlled by the direct projections from the parvocellular reticular nucleus to the trigeminal and facial nuclei. Muscle activity during chewing requires complex neuromuscular control with a central pattern generator and peripheral feedback regulatory mechanisms. A distinctive population of brainstem neurons located on the corticobulbar projections play a role at the onset of rhythmicity of the chewing movements and swallowing mechanisms while peripheral afferent nerves modulate the activity of the brainstem central pattern generators. The rhythmicity of chewing movements may also be affected by basal ganglia dysfunctions. Only a small part of the muscle activity observed during chewing is needed for the basic rhythmic movements of the jaw. The peripheral feedback mechanisms that control masticatory muscle activity are supported by periodontal mechanoreceptors (rapidly conducting trigeminal sensory afferent neurons that innervate specialized receptors in the periodontal ligament of the teeth, located closest to collagen fibers) and muscle spindles (afferent sensory proprioceptors located within the belly of a muscle that primarily detect changes in the length of this muscle). Notably, muscle activity seems to start just when the intake food promotes resistance during chewing. The information provided by these mechanoreceptors is important for the specification of the forces used when food is manipulated and positioned between the teeth and prepared for chewing. Moreover, information about mechanical properties of food as well as the spatial contact patterns with the dentition is also provided by these mechanoreceptors. In this way, during cortical stimu‐ lation, the central pattern generator produces stereotyped open-close cycles that are mainly dependent on peripheral information about the position and velocity of the mandible, the forces acting on the mandible and on the teeth, and the length and contraction velocity of the muscles involved [45-47].

There are several factors that determine the performance of the masticatory system and, so, of chewing. Among them: the quantity and the total occlusal area of teeth, bite force, neuromus‐ cular control of jaw movement, performance of food manipulation by the tongue, cheeks, and teeth, breakage behavior, taste and texture of food, number of chewing cycles until swallowing of food, and salivary flow [11, 48-50] (Table 3). Experimentally, the masticatory function of individuals might be evaluated and measured by using subjective and objective strategies. The subjective masticatory function (chewing ability) might be evaluated by interviewing subjects as to their own assessment of that function. In turn, the objective masticatory function (chewing performance) has often been measured by determining an individual's capacity to fragment a test food. The chewing performance can be determined by quantifying the degree of fragmen‐ tation of an artificial test food (Optosil, a silicon rubber commonly used as a dental impression material, 8 cubes of edge size of 5-8 mm) after a fixed number of chewing cycles (range from 10 to 160 cycles). The degree of fragmentation considers the size of food fragments forced through a stack of sieves. The distribution of particle sizes of the comminuted food can be adequately described by a Rosin-Rammler distribution function which is characterized by two variables only. In each sieve, the amount of test food is weighed and the median particle size of the particles is calculated from the weight distribution of particle sizes [51, 52].

tomical structures such as teeth, bone (mandible and maxilla), accessory and masticatory muscles, and sensory-motor activities. Biomechanically, the chewing in humans occurs in a stereotypical way: after ingestion of food it is transported from the front of the mouth to the occlusal surfaces of the post-canine teeth. Following this, the food is subjected to a series of masticatory cycles needed to process the food, making it softer and disintegrated until the food becomes more difficult to chew. At this stage, when food is ready to be swallowed, it is propelled posteriorly into the oropharynx where the food accumulates until it is finally

The muscles of mastication exhibit an adductor action (i.e., a motion that pulls a structure or part towards the midline of the midsaggital plane of the body) of mandible, while the lateral pterygoid muscle abducts (i.e., a motion that pulls a structure or part away from the midline of the midsaggital plane of the body). All four move the mandible laterally. Another accessory muscle, the sternohyomastoid is responsible for opening the mandible in addition to the lateral pterygoid. Anteriorly, the muscles of the lips (orbicularis oris) ensure the closing of the mouth in order to avoid escaping of the food. Posteriorly, at the moment of swallowing, the simul‐ taneous contraction of perioral and jaw muscles, together with opening of the pharyngeal ring, causes a squeeze of the food toward the fauces. The coordinated activity of the trigeminal (CN V) and facial (CN VII) nerves during chewing may be controlled by the direct projections from the parvocellular reticular nucleus to the trigeminal and facial nuclei. Muscle activity during chewing requires complex neuromuscular control with a central pattern generator and peripheral feedback regulatory mechanisms. A distinctive population of brainstem neurons located on the corticobulbar projections play a role at the onset of rhythmicity of the chewing movements and swallowing mechanisms while peripheral afferent nerves modulate the activity of the brainstem central pattern generators. The rhythmicity of chewing movements may also be affected by basal ganglia dysfunctions. Only a small part of the muscle activity observed during chewing is needed for the basic rhythmic movements of the jaw. The peripheral feedback mechanisms that control masticatory muscle activity are supported by periodontal mechanoreceptors (rapidly conducting trigeminal sensory afferent neurons that innervate specialized receptors in the periodontal ligament of the teeth, located closest to collagen fibers) and muscle spindles (afferent sensory proprioceptors located within the belly of a muscle that primarily detect changes in the length of this muscle). Notably, muscle activity seems to start just when the intake food promotes resistance during chewing. The information provided by these mechanoreceptors is important for the specification of the forces used when food is manipulated and positioned between the teeth and prepared for chewing. Moreover, information about mechanical properties of food as well as the spatial contact patterns with the dentition is also provided by these mechanoreceptors. In this way, during cortical stimu‐ lation, the central pattern generator produces stereotyped open-close cycles that are mainly dependent on peripheral information about the position and velocity of the mandible, the forces acting on the mandible and on the teeth, and the length and contraction velocity of the

There are several factors that determine the performance of the masticatory system and, so, of chewing. Among them: the quantity and the total occlusal area of teeth, bite force, neuromus‐

swallowed [11, 13].

18 Seminars in Dysphagia

muscles involved [45-47].



**Table 3.** Factors related to chewing and mains characteristics.

#### **3.3. Swallowing**

The process of swallowing includes the voluntary effort to ingest food and an involuntary effort of bolus preparation and transport. During early stages of swallowing, the bolus, which represents food particles bound together under viscous forces determined by components of saliva, is transported from the oral cavity and pharynx to the esophagus [14, 15, 53-55].

Briefly, swallowing mechanisms might be summarized as follows: in the oral cavity, where the initial preparation of swallowing occurs, the food is chewed, moistened, and coalesced. During chewing, the food particles are continuously moved towards the occlusal surface of the teeth through the actions of the tongue and masticatory muscles. A premature spillage of the bolus into the pharynx is avoided by the approach of the soft palate to the tongue that creates a glossopalatal seal, while various movements of the mandible are important for the adequate grinding of the bolus. When the bolus is ready for swallowing, the tongue forms a slit containing the bolus with the lateral edges curved upwards. The soft palate closes the nasopharynx, the larynx is elevated and closed, the pharyngeal constrictor muscles (superior, middle, and inferior) contract and the cricopharynx muscles relaxes. The tongue then contracts from anterior to posterior pushing the bolus back into the pharynx, the whole process taking about one second. The true cords, the false cords, the epiglottis and the aryepiglottic folds constrict to form a barrier of several layers to protect the airway and prevent aspiration. Elevation of the larynx occurs by the contraction of the suprahyoid musculature and relaxation of the cricopharyngeus musculatures. With this relaxation, negative pressure is created in the upper oesophagus, which helps in the movement of the bolus towards to stomach. The oropharyngeal stage has a short duration (less than a second), although it may vary depending on size of the bolus. Moments before the bolus enters the oropharynx, the soft palate elevates to close the nasopharynx, avoiding the regurgitation of the bolus through the nose, while the hyoid bone elevates and draws the larynx upwards and epiglottic folds down to protect its entrance. The tongue base moves in contact with the posterior pharyngeal wall, accompanied by an anterior movement of the hyoid. The cricopharyngeus muscle begins its relaxation resulting in the opening of the upper esophageal sphincter. The rhythm and pattern of the swallowing mechanism is involuntary controlled by a central pattern generator located in the medulla. Moreover, during the oropharyngeal stage of swallowing, it the participation of the voluntary cranial nerves trigeminal (CN V), abducens (CN VI), and hypoglossal (CN XII) is fundamental for muscle voluntary control. The involuntary control (sensitive) of the orophar‐ yngeal stage of swallowing involves the pivotal participation of the glossopharyngeal (CN IX) and vagus (CN X) cranial nerves. The esophageal phase starts after bolus passage through the upper esophageal sphincter and is characterized by a single primary peristaltic wave move‐ ment travelling at 3-4 cm/sec. After opening of the lower esophageal sphincter, the bolus is directed towards the stomach. Several secondary peristaltic waves occur spontaneously in an hour helping to clear residue and any gastric reflux. The oesophageal transit time varies with age [15, 53, 54, 56, 57].
