Biochemistry of tooth tissues and of saliva: chemical content, peculiarities of metabolism in enamel, dentin, pulp and cement, mechanisms of mineralization, physical-chemical properties and biochemical content of saliva, role of the , , F, vitamins a

Biochemistry of tooth tissues and of saliva: chemical content, peculiarities of metabolism in enamel, dentin, pulp and cement, mechanisms of mineralization, physical-chemical properties and biochemical content of saliva, role of the , , F, vitamins and hormones. Biochemical changes at tooth- jaw system pathology.

n     Composed of mineralized calcium phosphate (specifically, the calcium phosphate phase called hydroxyapatite (HAP) í Ca10(PO4)6(OH)2) within a matrix of collagen fibrils

 n     The HAP of teeth is not compositionally pure

       its composition can actually be better represented as

       (Ca, Sr, Mg, Na, H2O, [])10(PO4, HPO4, CO3P2O7)6(OH, F, Cl, H2O, O, [])2

       where [] represent crystal lattice defects

Enamel is 95% HAP and is consequently less tough than bone. Enamel gains mechanical strength by interweaving HAP crystals. Enamel initially starts with a high protein content, but these are removed and the voids backfilled with HAP as the tooth matures HAP is a living mineral that is continually grown, dissolved & remodeled in response to signals of internal (e.g., pregnancy) and external (e.g., gravity, exercise) origin.

1.     TOOTH ENAMEL, is the hardest part of the tooth Enamel acts as a protective tissue that covers the exposed part of a tooth, the crown. 

2.     DENTIN , is the tissue that forms the mainl mass of a tooth. It supports the enamel and absorbs the pressure of eating.

3.     DENTAL PULP, a soft connective tissue containing nerves and blood vessels, that nourish the tooth.

4.     CEMENTUM, covers the dentine outside of the root (under the gum line) and it is attached to the bone of the jaw with little elastic fibers

5.     GUMS, the tough pink-colored skin that covers the bone of the jaw and supports the tooth along with the alveolar bone.

6.     PERIODONTAL LIGAMENT, the tissue between the cementum and the alveolar bone. It consists of tough little elastic fibers that keep the tooth attached to the jaw.

7.     ALVEOLAR BONE, the bone of the jaw that keeps the tooth in its place, it feeds and protects it.

Salivary glands are nonexcitable effector organs in which a large amount of fluid and electrolytes is transferred from the interior of the body to the outside. The amount of fluid translocated each day through salivary glands approaches 750 ml, which represents approximately 20% of total plasma volume.

Saliva is secreted to the mouth by three major paired salivary glands (submandibular, parotid, and sublingual glands) and by numerous minor mucous glands, at a rate of approximately 0.025 ml.min-1. The relative contributions of each of these glands to the total amount of saliva secreted average 65 per cent from the submandibular, 23 per cent from the parotid, 8 per cent from the minor mucous, and 4 per cent from the sublingual.

Both of the two major parenchymal sites of the salivary glands, the acini and the striated ducti, participate in salivary secretion. Transport of water and electrolytes, and synthesis of enzymes, proteins, mucin and other organic components, occur in the acini, which secrete a fluid isotonic with plasma. This fluid is then modified in the ductus system, by both reabsorption and secretion of electrolytes. The majority of oral secretions are contributed by the sub-mandibular and parotid glands, which equally provide 80 to 90 per cent of the saliva. The remainder is formed by sublingual and minor salivary glands. One thousand to 1500 ml of saliva is produced daily. Saliva contributes to the digestion of food and to the maintenance of oral hygiene. Without normal salivary function the frequency of dental caries , gum disease (gingivitis), and other oral problems increases significantly.

These glands may contain mucous secreting cells, serous cells or a mixture of both.

Serous cells produce a watery saliva that contains the enzymes amylase and lysozyme, IgA (immunoglobulin A), and lactoferrin (an iron binding compound).

Saliva has important functions :

  • Cleanses the mouth due to the bactericidal action of lysozyme and IgA (immunoglobulin A [one of the immune system's antibodies] )plus the constant backward flow towards the oesophagus
  • Creates a feeling of oral comfort by it's lubricating action
  • Dissolve food chemicals so that they can stimulate the tongue's taste buds
  • Help to form a bolus (ball of food) by the action of mucins thus facilitating swallowing
  • Contain a digestive enzyme called salivary amylase (ptyalin) which starts the process of breaking down complex starchy sugars

The submandibular salivary gland secretes a mixed product containing both serous and mucous secretions although the serous component is the larger. They are roughly ovoid in shape and are situated below the mandible (jaw bone) to the left and right. Their ducts open into the floor of the mouth on either side of the tongue's frenulum.

The parotid salivary glands secrete a serous product only. They are situated on either side of the head in front of the ears. They have long ducts which open into the mouth opposite the second molar tooth on either side.

The sublingual glands produce a mainly mucous product. They are situated just uner the back of the tongue again in a left and right pair. Their ducts open close to those of the submandibular glands.

In addition there are numerous smaller groups of salivary gland tissue scattered diffusely in the submucosa.

The most important are:

  • lingual glands in the submucosa and muscle layers of the dorsal surface of the tongue
  • minor sulblingual glands close to the larger major sublingual glands (other tongue glands are found on the inferior surface of the tip of tile tongue and on its lateral borders)
  • labial glands on the inner surface of the lips
  • palatine glands in tile submucosa of the soft and hard palates
  • tonsillar glands in the mucosa associated with the palatine and pharyngeal tonsils
  • buccal glands in the submucosa lining the cheeks.
  • The labial, sublingual, mlnor lingual and buccal glands are composed predominantly of mucous cells, but some serous cells may be present.
  • The palatine and lateral lingual glands are entirely mucous secreting

 

Both the sympathetic and the parasympathetic nervous systems innervate the salivary glands. It is evident that the sympathetic nervous system, although its role in salivation is still controversial, influences the blood flow to the salivary glands and activates myoepithelial cells within the salivary ducts. These myoepithelial cells expedite the flow of saliva by squeezing saliva out of the salivary glands.

 Saliva Composition

Saliva is characteristically a colorless dilute fluid, with a density ranging from 18 to 35. Its pH is usually around 6.64, and varies depending on the concentration of CO2 in the blood. When blood CO2 concentration is increased, a higher fraction of CO2 is transferred from the blood to the saliva, and salivary pH decreases. If CO2 is low in blood, on the other hand, salivary pH increases as a result of a low transfer of blood CO2 to salivary glands.

Although a variety of components is always present in saliva, the total concentration of inorganic and organic constituents is generally low when compared to serum. The fraction of saliva represented by water usually exceeds 0.99. Of the inorganic constituents, sodium and potassium (and perhaps calcium) are the cations of major osmotic importance in saliva; the major osmotically active anions are chloride and bicarbonate. Although the percentage of total proteins in saliva is low in comparison to serum, specific proteins, such as the enzyme amylase, are synthesized in the salivary glands and may be present in saliva in concentrations exceeding those of serum. Other organic components existing in saliva include: maltase, serum albumin, urea, uric acid, creatinine, mucine, vitamin C, several amino acids, lysozime, lactate, and some hormones such as testosterone and cortisol. Some gases (CO2, O2, and N2) are also present in saliva. Saliva contains immunoglobins such as Ig A and Ig G, at an average concentration of 9.4 and 0.32 mg%, respectively. The concentration of potassium, calcium, urea, uric acid, and aldosterone are highly correlated to those existing in plasma. This high degree of correlation has not been shown, however, between salivary and plasma concentrations of phosphate. The physiological significance of other constituents of saliva, such as trace minerals, epithelial growth factor, neural growth factor, several enzymes and some proteins (kallikreins, calmodulin) remains unknown.

 In animals, saliva is produced in and secreted from the salivary glands. It is a fluid containing

Electrolytes: (2-21 mmol/L sodium, 10-36 mmol/L potassium, 1.2-2.8 mmol/L calcium, 0.08-0.5 mmol/L magnesium, 5-40 mmol/L cloride, 2-13 mmol/L bicarbonate, 1.4-39 mmol/L phosphate)

Mucus. Mucus in saliva mainly consists of mucopolysaccharides and glycoproteins;

Antibacterial compounds (thiocyanate, hydrogen peroxide, and secretory immunoglobulin A)

Various enzymes. The major enzymes found in human saliva are alpha-amylase, lysozyme, and lingual lipase. Amylase starts the digestion of starch before the food is even swallowed. It has pH optima of 6.7-7.4. Human saliva contains also salivary acid phosphatases A+B, N-acetylmuramyl-L-alanine amidase, NAD(P)H dehydrogenase-quinone, salivary lactoperoxidase, superoxide dismutase, glutathione transferase, glucose-6-phosphate isomerase, and tissue protein. The presence of these things causes saliva to sometimes have a foul odor.

Healthy people produce about 1.5 L of saliva per day.

Amylase:- found in two forms

1- α-amylase (in saliva and pancreatic juice) which is endoglycosidase that attack starch randomly. Inactivated by the acidity of the stomach.

2- β-amylase (from plant origin) which is exoglycosidase cleaves maltose from the non-reducing end to produce β-maltose.

 Regulation of saliva secretion

Secretion of saliva is usually elicited in response to stimulation of the autonomic innervation to the glands. Although no direct evidence for modification of salivary flow by hormones has been demonstrated in humans, catecholamines might also be involved in the control of saliva electrolytes and protein concentrations. Both salivary output and composition depend on the activity of the autonomic nervous system, and any modification of this activity can be observed indirectly by alterations in the salivary excretion. Although normal salivary secretion is dependent on the cooperation of sympathetic and parasympathetic nerves, the nervous control of saliva secretion is not identical in all salivary glands: secretion of saliva from sublingual and minor mucous glands is mainly elicited in response to cholinergic stimulation, whereas secretion from the other glands is evoked mainly by adrenergic innervation. In any case, it is generally acknowledged that parasympathetic nerve impulses create the main stimulus for salivary control in general. Parasympathetic stimulation results in a copious flow of saliva low in organic and inorganic compounds concentrations. Sympathetic stimulation, on the other hand, produces a saliva low in volume. In addition, saliva evoked by action of adrenergic mediators is generally higher in organic content and its concentration of certain inorganic salts is also higher than saliva evoked by cholinergic stimulation. The higher organic content of saliva evoked by adrenergic stimulation trough the activity of adenyl-cyclase, includes elevated levels of total protein, especially the digestive enzyme alpha-amilase. High concentrations of alpha-amilase in saliva are indeed considered to be the best indicator of adrenergic evoked secretion of saliva. The levels of inorganic compounds, i.e., Ca++, K+ and HCO3-, are usually higher with sympathetic stimulation.

Besides the type of autonomic receptor being activated, the two other parameters that can affect salivary composition are the intensity and the duration of stimulation to the glands. The differences in composition between saliva collected after a change in the intensity or the duration of stimulation appear to be due to alterations in membrane permeability of secretory cells leading to changes in the rate at which electrolytes are lost from these cells.

The secretory cells are not the only glandular elements that respond to stimulation of the sympathetic innervation. Myoepithelial cells and blood vessels of the glands also respond to such innervation, and these responses can in turn modify the quantity and composition of the elaborated saliva. It has been shown, for example, that sympathetic stimulation to salivary glands can produce a markedly increased degree of vasoconstriction. Finally, other factors such as circannual rhythms and reflexly induced secretomotor responses might also influence salivary secretion.

Effects Of Exercise On Saliva Secretion And Its Composition

Several studies have shown decreases in salivary levels of immunoglobin A (s-Ig A) in response to high-intensity exercise. Lower resting levels of s-IgA have indeed been reported in cross-country skiers and in elite swimmers, when compared to matched controls of sedentary individuals. The levels of s-IgA decrease following intense exercise, and return to normal levels after 60 minutes from cessation of activity. Since Ig A represents the first line of defense against potentially pathogenic viruses, the exercise-induced decrease in s-IgA could contribute to the higher incidence of upper respiratory infections associated to strenuous athletic training. However, endurance exercise performed at lower intensities (i.e., training protocols within the guidelines recommended by the American College of Sports Medicine), does not seem to alter normal s-IgA levels.

Salivary flow rate appears to be modified during physical activity, according to most studies. Nevertheless, interpretation of the results obtained in these studies is sometimes difficult due to some methodological limitations, concerning mainly exercise protocols and saliva collection procedures. During exercise, salivary levels of total protein can be increased, since saliva secretion is then mainly evoked by action of adrenergic mediators. Exercise is indeed known to increase sympathetic activity and the high protein concentration following exercise may be due to increased ß-sympathetic activity in salivary glands. This elevated levels of protein could also be caused by the increase in blood catecholamines associated to exercise. During prolonged exercise at low to moderate intensities (lower than 60% of O2max), salivary secretion does not seem to be significantly modified. At higher intensities, however, salivary secretion decreases. Factors associated to high-intensity exercise such as an increased ß-adrenergic activity, dehydration, or evaporation of saliva through hyperventilation (although less probable) have been proposed to explain this lower secretion of saliva at high workloads.

Salivary levels of cortisol are considered to be a good indicator of the adrenocortical response to exercise by some authors, since salivary cortisol closely reflects plasma free cortisol levels, presenting advantage over total cortisol measurements. During exercise, salivary and serum concentrations of cortisol are indeed very similar. In addition, both salivary and blood levels of cortisol increase with exercise intensity until a certain exercise level, at which such increase loses it linearity. This inflection point in the increase of salivary and blood levels of cortisol coincides in most of the cases with the onset of blood lactate accumulation. It has been suggested that this lactate accumulation might activate chemoreceptors within the working muscles, which in turn could stimulate the hypothalamic-pituitary axis. However, a true cause-to-effect-relationship between these variables remains to be proven. Both increases of cortisol and lactate levels could occur as a result of a marked sympathetic activity or an increase in blood catecholamines which take place at exercise intensities above anaerobic threshold.

The effects of exercise on the salivary and serum levels of Na+ and K+ have also been studied. Prolonged exercise does not appear to have a significant effect on the serum Na+ and K+. On the other hand, the salivary Na+ concentration markedly increases whereas no noteworthy changes seem to occur in salivary K+, in response to prolonged exercise. In addition, this increase in the salivary Na+/K+ ratio is positively correlated to the exercise-induced increase in salivary protein concentration.

In our laboratory, we have studied the relationship between anaerobic threshold and variations in salivary electrolytes (Na+, K+, Cl-) in response to incremental exercise. Our results evidenced that salivary Na+ and Cl- showed a dual response to exercise: their levels decreased or remained stable during early phases of exercise, until a certain exercise level, at which they began to show a systematic increase. In contrast, K+ levels did not significantly vary during physical activity. The inflection point in the salivary Na+ and Cl- was highly correlated (r= 0.82; p<0.01) with lactate threshold, suggesting the possibility of determining anaerobic threshold with a noninvasive method involving saliva analysis.

These changes in the concentration of salivary electrolytes which occur at a certain exercise intensity might be elicited in response to sympathetic stimulation. This sympathetic stimulation might induce changes in salivary flow and in both reabsorption and secretion of electrolytes in secretory cells. The decreased in saliva secretion associated to exercise could also be the result of a reduction of blood flow to salivary glands caused by elevated adrenal-sympathetic activity. The results of our investigations demonstrate the existence of a catecholamine threshold highly correlated with blood lactate increases (r= 0.84, p<0.01) during incremental exercise. This catecholamine response which occurred at or close to lactate threshold was in turn well correlated (r=0.75, p<0.05) to the point ("saliva threshold") at which salivary electrolytes (especially Na+) showed an inflection point. Although further research in this field is necessary, our experiments suggest that saliva composition analysis might be a good estimate of the adrenal-sympathetic response during exercise. We therefore propose this new noninvasive method for anaerobic threshold determination. We believe that its potential applications in both clinical and exercise physiology areas are numerous.

 Hyper-salivation may be associated with many disorders such as herpetic stomatitis, irritation by dentures and pregnancy, but drooling does not occur in these cases unless the ability to hold secretions within the mouth or the ability to swallow secretions is impaired. Patients with hyper-salivation may expectorate repeatedly, but this is not drooling. It is the difference between salivary production and the ability to swallow saliva that results in drooling rather than the absolute production of saliva.  

Difficulty in swallowing saliva is encountered at three levels of function: the oral, pharyngeal and oesophageal components of deglutition. Some of the common disorders associated with drooling, classified according to the presumable level of malfunction, are as follows: oral (cerebral palsy, Parkinson's disease, motor-neurone disease, seventh-nerve palsy, facial disfigurement and radical cancer surgery); pharyngeal (motor-neurone disease, myasthenia gravis and polymyositis); and oesophageal (carcinoma or stricture).

Salivary Dysfunction

Too much or too little saliva can affect oral health and quality of life. Lack of saliva leads to dental decay, oral yeast infections, taste problems, bad breath, difficulty speaking and swallowing, and recurrent salivary glands infections. Too much saliva can cause social problems and may be a sign of an underlying medical problem. We evaluate salivary problems by medical history review, head, neck and oral examination, diagnostic imaging, and salivary function measurements. Management strategies for improving salivary function and preserving oral health are developed for each individual.  

Tooth Erosion

Dental or tooth erosion is defined as a dissolving of tooth surfaces caused by acidic substances. (This is different than tooth surface loss caused by caries-producing bacteria.) Generally, in a given individual, all or most tooth surfaces are affected. Sources of acid may be from outside of one's own body (dietary or environmental) or from inside the body (e.g. acids from the stomach). Erosion may also be related to salivary function. Evaluation of this condition includes a medical history review, head, neck, and oral examination, and salivary function measurements. Treatment depends on the cause of the erosion.

Taste Disorders

The following taste disorders are evaluated and treated:

  • Loss of taste
  • Persistent unusual or unexpected tastes
  • Perversions of taste (for example, when something sweet tastes salty)

Evaluation includes medical history review, head, neck and oral examination, diagnostic imaging, salivary function assessment, and testing of ability to taste and smell.

Good mouth care is important to maintain quality of life. Speaking, the pleasure of eating, and the normal handling of saliva are taken for granted by most of us. It may be difficult to imagine the impact mouth disorders have on patients. As the mouth is largely hidden, the patient, family, and caregivers may not recognize problems when they occur. As an exercise, the reader is encouraged to consciously hold his or her mouth open for several minutes. Saliva will begin to pool about the lower teeth. At the same time the tongue will dry. Drooling eventually will occur. Suddenly, what we have taken for granted, swallowing spit, becomes precious.

Palliative Care Note
In end-of-life care examination and reexamination of the mouth is one of the most important tasks.

Xerostomia (Dry Mouth)

Common causes of xerostomia are

  • medications (anticholinergic agents, opioids to a lesser degree, clonidine)
  • dehydration
  • mouth breathing
  • surgery or radiotherapy to the mouth
  • infections of the mouth

Dry mouth is very prevalent and troublesome. As this list suggests, treatable causes are common. Taking patients off of unnecessary anticholinergic medications, for example, can be of great help. Other causes, such as dehydration, radiation-related xerostomia, and mouth breathing may be harder to address directly.

The relationships between dehydration, thirst, and dry mouth are complex and frequently misunderstood. While systemic dehydration undoubtedly contributes to decreased saliva production, rehydration with fluids, for example, does not necessarily correct the problem and may be associated with undesired side effects, such as worsening respiratory secretions. Side effects of medications, especially anticholinergic agents and opioids, and mouth breathing may significantly contribute to this symptom

 Difficulty Handling Saliva, Drooling, and Sialorrhea

In rare cases patients may produce excess saliva. More commonly, they have difficulty handling normally produced saliva because of alterations in mouth anatomy or because of impaired neurologic control of the swallowing reflex. The latter, often manifested by drooling, is the more common. Drooling carries a great social stigma and can be very disturbing to patients and families. Patients with Parkinson's disease, amyotrophic lateral sclerosis, cerebral vascular accidents, dementia, and developmental disorders are prone to this. Patients in the very advanced stages of dying may also experience difficulties as they loose their swallowing and cough reflexes.

Usually, the underlying cause is untreatable. However, anticholinergic agents can be of some help in decreasing salivary flow. Care should be taken in using systemically absorbable agents, as they can produce troubling side effects. In addition, for some patients the dry mouth that results from medication may be as troubling as the earlier drooling. Studies in developmentally delayed children and more recent studies of adults who drool suggest that glycopyrrolate may be effective in decreasing salivary production with little, if any, systemic toxicity. Glycopyrrolate is an anticholinergic agent that is poorly absorbed from the GI tract and that minimally crosses the blood-brain barrier if given systemically (as it often is in anesthesia). I have had some success with this agent. Tablets of 1 mg can be dissolved in a small amount of water and held in the mouth (or swabbed onto mucosa if unable to be held) and then spit out. This is usually given BID or TID. If swallowed, glycopyrrolate will have a strong local anticholinergic effect on the GI tract and decrease motility and secretion into the gut. This will worsen constipation or treat diarrhea but decrease the systemic effect, as only 5% of the drug is absorbed. As the goal of therapy is to reduce the production of saliva, not to dry the mouth completely, the mouth should be moistened with artificial saliva if secondary xerostomia results.

Candidiasis

Candidal infections of the mouth occur frequently, especially in patients who are on steroids and in diabetics. Thrush is relatively easy to recognize. White cottage cheese-like plaques are found, often associated with tenderness, dysphagia, and altered taste (dysgeusia). More difficult to recognize are the atrophic forms, both acute and chronic. Acute atrophic candidiasis usually presents as a reddened tongue with depapillation, which is also associated with dysgeusia. It is my impression that this form may be more common in patients with xerostomia, as inadequate moisture exists to create classic thrush. Vitamin deficiencies, poor nutrition, and xerostomia itself may all create a similar picture, making definitive diagnosis difficult on exam alone. Chronic atrophic candidiasis is similar to acute (reddened mucosa, especially in the area where upper dentures are in contact with the palate) and is most common in elderly patients with dentures. It is often associated with angular cheilitis, which is painful.

A variety of antifungals can be employed in therapy. Nystatin suspension is often well tolerated, as it is a liquid. Because efficacy relates to drug contact time with the mucosa, some caregivers make small "popsicles" with toothpicks for patients to suck on. Some strains of candida are resistant and may respond better to other agents. Mycelex troches are typically given five times a day, although less frequent administration can be given to the dying. Patients with significant xerostomia may have trouble dissolving troches. Systemic agents, such as fluconazole are rarely required and are expensive. Fluconazole may be indicated for resistant strains and when candida is suspected beyond the GI tract, such as when a patient has new-onset hoarseness with a sore throat in association with oral candida (often indicative of laryngeal involvement).

Viral and Bacterial Infections

Immuno-suppressed patients are at a higher risk for both viral (predominantly herpes simplex) and bacterial infections. Herpes infections should be suspected when such patients have new-onset pain or odynophagia (common with esophageal herpes); it is best treated with acyclovir. Patients with xerostomia appear to be at higher risk of bacterial parotitis and present with the sudden onset of a firm, warm, painful swelling under the angle of the jaw. They may be susceptible because of decreased salivary flow from the parotid gland. Broad-spectrum treatment with an antibiotic such as Augmentin is usually effective.