The Nature of Saliva

This three-part series aims to provide a comprehensive review of the nature and functions of saliva, and the particular difficulties that can result from the lack of this almost miraculous fluid. The first article contains a general overview of the subject, parts 2 and 3 will look at the relationship between saliva and dental caries, and describe the very real problems of patients suffering from xerostomia.

nly those unfortunate individuals who suffer from xerostomia ! a dry mouth due to impaired salivary secretion ! can fully understand the impact of life without the many benefits of saliva. The mouth and throat are dry and sore, eating and speaking become difficult and painful processes, the sensation of taste is diminished and denture wearing can become an ordeal. Those with natural teeth suffer from gingival inflammation, aggravated by the discomfort of attempts at efficient toothbrushing, while the temporary relief provided by fre"uent sipping of sugar-sweetened acidified drinks, fuels an aggressive level of caries activity. #ithout help and advice, the patient$s masticatory machine painfully and progressively breaks down and even the oral mucosa loses its almost irresistible will to heal.

The aim of this paper is to present a brief review of our present knowledge of the mechanism of salivary secretion, its composition and its role in maintaining oral health. This review will lead into a discussion of the relationship between saliva and dental caries which forms the basis of the second paper in this series.

THE SECRESION OF SALIVA

&aliva is secreted a series of major and minor glands which together are capable of producing up to % litre per day,% at a flow rate which varies from '.'2 ml(min at rest to ) ml(min or more when stimulated. The secretion itself is produced by two distinct types of speciali*ed epithelial cells within a secretory apparatus which includes supportive elements, the secretory acini and ducts which transport the secretion to the oral cavity.

THE COMPOSITION OF SALIVA

+n a strange parallel, the problems faced by the physiologist in studying the composition of saliva are similar to those faced by the atomic particle physicist whose probing can produce a change in the very parameters under investigation. The collection of saliva can produce a change in its composition, and further changes occur rapidly on storage. ,nd how do we define salivaThe secretions from the three major glands are all different and in themselves

vary in their basal and stimulated states. To this variable mixture we must add the contribution from the minor glands scattered throughout the mouth together with the products of the metabolism of the oral flora, the bacterial cells themselves, des"uamated epithelial cells and finally the gingival crevicular secretions. +t is only when we add together all of these ingredients that we arrive at .whole saliva$.

#hole saliva is //0 water, and includes a mixture of inorganic ions, the major ones being 1a2, 32, 4l!, 54 3!, 4a22, 6g22, 57
89 !

, and the minor ones

including +!, &41! and :!. The resting p5 varies between ;.) and ).8 for whole saliva, while that of the pure parotid secretion, which is the easiest to obtain, varies from <.2 to ;.=. +n addition to its inorganic components, saliva contains a wide array of organic molecules, the nature and functions of which we are slowly beginning to understand. &ome are simple proteins, such as en*ymes and albumin and free amino acids. 5owever, the bulk of the organic components is made up of complex glycoproteins, the mucins. These important macromolecules consist of a protein backbone to which are attached many oligosaccharide side chains. +n order to make any sense of its constituents, we must first consider the many functions of saliva.

GENERAL MECHANICAL FUNCTIONS

+n recent years rheology has given us a greater understanding of the mechanical role of saliva in the mouth, 2 which shows us how it is the properties of the salivary mucins ! low solubility, high viscosity, elasticity and adhesiveness ! which combine to enable saliva to perform probably its most essential role, lubrication and protection of the oral mucous membrane. 9y coating and being adsorbed onto the mucosa, saliva allows oral surfaces to move against one another with minimal friction so that speech and taste are possible. , second mechanical property of saliva is its binding ability which enables food to be formed into a bolus for swallowing. 5owever, a chemical property of these very large molecules provides for another vital function> The mucins are hydrophobic, they bind to water. Thus, by coating the mucosal surface, they serve to waterproof it, preserving the hydration and vitality of the epithelial cells below.

These properties of the salivary mucins might be sufficient if the oral cavity did not have to defend itself from wide range of irritant substances inflicted on it by its owner. They include many compounds from foodstuffs and beverages ?including alcohol@, to nicotine and environmental pollutants. :ortunately, mucins decrease the permeability of the mucosa and limit the penetration not only of the exogenous irritants but also of a powerful group of

potential irritants generated within the mouth. 3 These are the proteolytic en*ymes, produced largely by the organisms of dental pla"ue and by polymorphonuclear neutrophils of the inflammatory exudate from the gingival crevice when periodontal disease is present. ?+n the stomach this same property is put to an even greater test, as it is only the barrier provided by gastric mucin that prevents the stomach wall being digested by the powerful en*yme pepsin.@

#hile the mucins provide an efficient and tenacious barrier to irritants, they allow the free passage of water. There is evidence that in dehydration, water can be absorbed across the oral mucosa, while water loss from the oral mucosa can be considerable and in the dog is a major means of excretion. 5owever, there are limits to the protection that mucins can offerA and strong acids, alkalis and caustic chemicals such as aspirin rapidly destroy the barrier and attack the underlying epithelium. +n the vast majority of individuals, wounds produced in this way or by direct mechanical trauma heal rapidly. This is in part due to the excellent blood supply to the mucosa, the antibacterial properties of saliva and the presence in saliva of factors which appears to promote wound healing, possibly by speeding coagulation and possibly also by stimulating neural and epithelial cell growth.

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The final mechanical role of saliva is the first to be recogni*ed> the physical effect of the lips, tongue and cheeks to provide an effective means of lavage and debridement for the oral cavity.

GENERAL ANTIMICROBIAL FUNCTIONS

#hile the mouth harbours a multitude of different organisms, saliva exerts a strict maternal control over their composition and number through a battery of chemical weapons. These range from simple compounds such as urea, through en*ymes, to the complex proteins of the secretory immunoglobulins. Bnder the normal conditions of the healthy mouth, these agents cooperate in maintaining the proper ecological balance of the oral flora.

,lthough urea has been recogni*ed as a potential antibacterial agent, its direct role in saliva is now regarded as minor, as it is rapidly degraded and is used by oral bacteria as a nitrogen source for the production of amino acids. The breakdown products of these protein building blocks include ammonia which raises salivary and pla"ue p5, helping to provide a natural and progressive brake to bacterial multiplication. f greater import is the presence

in saliva and pla"ue fluid of the ion hypothiocyanite ? &41 !@.8 +t is derived from a complex series of reactions which begin with the secretion of the en*yme lactoperoxidase by the parotid and submandibular glands and by pla"ue bacteria. This en*yme aids hydrogen peroxide ?produced by bacteria in

the mouth@ in oxidi*ing the relatively unreactive thiocyanate present in saliva to &41! . This ion has an inhibitory effect on bacterial en*ymes involved in

glycolysis and sugar transport. +n this way baterial metabolism is itself selfregulatory.

#hile salivary en*ymes are involved in the production of antibacterial agents, some act directly on bacterial cells. ne of the first en*ymes to be

recogni*ed in this role was lyso*yme, which is found in high concentrations in the secretion of the labial mucous glands. +ts prime method of action is probably by destabili*ing the cell wall, possibly in conjunction with certain anions and causing autolysis of the cell. Cram positive bacteria including the cariogenic Streptococcus mutans, appear to be most sensitive to its action, although the evidence for an association between salivary lyso*yme concentration and caries prevalence is e"uivocal. , second salivary en*yme with a direct antibacterial action is lactoferrin, which works by binding iron and depriving bacteria of this essential element. +t may also have a direct effect on bacterial cells.

, further way of dealing with bacteria is by causing the clumping or aggregation of the cells to the point where they cannot function or cling to the soft tissues or tooth surface. +t is thought that some of the very high molecular weight salivary mucins are involved in this mechanism, although recent work

suggests that some "uite small glycoproteins as well as en*ymes such as lyso*yme and some lipids are also active in this role.

The final major antimicrobial action of saliva is provided by the immunoglobulins ?+g@ together with the compliment system. The former are proteins characteri*ed by having four intertwined polypeptide chains, were first isolated from the gamma globulin fraction of blood serum, and have since been identified in most body fluids including saliva. Their production is stimulated by the presence of foreign agents especially proteins ?antigens@, which may be bacterial or viral components. :or each antigen a specific immunoglobulin or antibody is produced which appears to bind and deactivate the foreign protein.

#e now recogni*e three groups of immunoglobulins. The highest group ?termed +gC@ with molecular weights of about %<',''' are found in internal body fluids, extravascular tissue fluid and inflammatory exudate. The heavy +g6 group is confined to blood. +t is the intermediate +g, group which is secreted into the saliva by plasma cells around the acini and ductsA although secretory +g, ?&-+g,@ differs from the +g, also found in plasma by being coupled to a glycoprotein. #hen gingival inflammation is present, as is often the case, +gC is found in the crevicular exudate and probably contributes to the concentration of about %.< mg(%'' ml found in whole saliva compared with a typical figure of 2' mg for &-+g,. ,s to the efficacy of +g in the action of polio

vaccine and indeed may be partly responsible for the lack of convincing evidence for the transmission of the 5+D virus by saliva.

4ompliment is a series of nine proteins which are formed in se"uence beginning with an antigen ! antibody reaction resulting in a product which binds to bacterial cell walls causing lysis. #hile present in saliva, its role in maintaining the ecological balance is not fully determined and its manipulation is beyond our present ability.

#hile the find of oral immunology held the promise of an anti-caries vaccine and even a vaccine against periodontal disease, the efforts of Eehner and co-workers in 9ritain and 9owen in the Bnited &tates, have so far failed to produce an effective and acceptable agent, although our understanding of this highly complex subject has been greatly extended. The possible antimicrobial actions of saliva are summari*ed.

pH CONTROL

The final major function of saliva is the maintenance of oral and oesophageal p5, which is achieved by a series of buffer systems. +n stimulated saliva it is largely due to the bicarbonate ion, which provides =<0 of the total buffering capacity of about %'6-e"uiv(litre< and provides an effective buffer against fluctuating p5. The bicarbonate ion concentration of resting saliva is

low, and therefore its buffering capacity is provided by histidine-rich peptides, phosphates and amino acids, together acids. ; &ince this function is of great importance in its relation to pla"ue p5 and caries, it is discussed in more detail in the next paper in this series.

9efore leaving this brief review of the functions of saliva, mention should be made of the increasingly important use to which saliva samples are put in the diagnosis of systemic disease and the detection of metabolic products and exogenous chemicals and drugs.)

THE CONTROL OF SALIVAR SECRETION

The secretory apparatus is under the control of the autonomic nervous system and recent research has confirmed that the sympathetic and parasympathetic nerves work together in a complex manner to stimulate secretion and not, as once thought, in a simple and opposing fashion. = These systems respond to taste and tactile stimuli from the oral cavity as well as visual and olfactory stimuli and stimuli from higher cerebral centres. +ndeed, just reading the words .lemon drops$ is sufficient to produce an immediate increase in flow rate in many mouths.

, more powerful stimulus is mastication. 1umerous studies have shown that the chewing of something as unpalatable as paraffin wax can produce a

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ten-fold increase in salivary flow. Fecent work has shown that stimulation of mechanoreceptors in the periodontal membrane is an important part of this mechanism. There is evidence that the texture of the food being chewed is an important factor in determining salivary stimulation. 1evertheless it has been convincingly demonstrated that taste stimuli are potentially the most potent, / with acids being the most effective.;

+t would appear that the compositions of saliva produced by sympathetic and parasympathetic stimulation differ. This is probably related to the actual secretory mechanism is which the initial secretion is produced by the acini and is fairly isotonic and chloride ions. +t is then modified during passage through the duct system by the removal of some sodium and chloride and the secretion of bicarbonate. The control of this complex mechanism is affected by certain steroids as well as nervous activity.

This combination of factors results in a wide variation of salivary flow rate. :or basal whole saliva in adults, flow rates vary from '.'2 to 2.)< ml(min, while the rates for paraffin wax stimulation vary from '.2 to <.=< ml(min. %' ne of the most effective salivary stimulants is citric acid placed n the tongue, and in a recent study a <0 solution produced a maximum flow rate of ).') ml(min.; #ithin this wide range there are a number of related factors. ,s one might except, the basal secretion rate increases with age up to about %< years,

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beyond which few differences are found. %' ?,lthough there is evidence that the glands of the elderly lose their capacity for increased secretion on stimulation, %% and show a decline in basal flow rates from the minor labial and submandibular glands.@ 9ody weight is not significantly related to basal secretion, but the stimulated flow rate does appear to be related to individual gland weight, while the evidence for a sex difference is e"uivocal.

+t is amongst the group of factors related to time or condition that the greatest variations are found.%2 The state of body hydration is a sensitive factor in determining flow rate, while reduced rates have been reported in standing rather than in winter, although the latter may be due to the relative state of hydration. There is a well-documented circadian variation of wide amplitude, with an acrophase ?peak value@ in the afternoonA < however, flow rate falls to almost *ero during sleep. &ome olfactory stimuli promote salivary flow, while previous stimulation reduces the response to further stimulation. :inally, but of great practical significance, there are a great number of drugs which have an effect, usually inhibitory, on flow rate.%3

There is an intimate relationship between the composition of saliva and flow rate which results in the concentration of protein and most ionic species increasing with flow rate from the parotid and sub mandibular glands.

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5owever, the secretion of potassium and fluoride varies little, and secretion of phosphate and magnesium falls.

, number of systemic disorders and local conditions are associated with a reduced conditions are associated with a reduced flow rate. These include &jGgren$s syndrome, post-radiation xerostomia and salivary duct calculi.

These are discussed in the final paper in this series. ,ll these variations in salivary flow are linked to changes in composition. The most relevant to dental caries are the increase in p5, buffering capacity and mineral ion concentrations with flow rate, which will be discussed in the second paper.

:orm this brief review, saliva emerges as a complex but vital fluid, produced in response to need and adapted to meet the many re"uirements of a healthy mouth.

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Refere!"e#

%. Henkins C1. The 7hysiology and 9iochemistry of the 6outh 8th edn. xford> 9lackwell, %/)=.

2. &hwart* 15. The rheology of saliva. J Dent Res %/=)A ;;>;;'-;;8.

3. ,dams I. The mucous barrier and absorption through the oral mucosa. J Dent Res 1975A <8>9%/-92;.

8. 7ruitt 36. The salivary peroxidase system ! thermodynamics, kinetics and antibacterial properties. J Oral Pathol %/=)A %;>8%)-82'.

<. Iawes 4. +norganic constituents of saliva in relation to caries. +n> Cuggenheim 9, ed. Cardiology Today. Jurich> 3arger, %/=8A pp. )'-)8.

;. #atanube I, Iawes 4. The effects of different foods and concentrations of citric acid on the flow rate of whole saliva in man. rch Oral !iol %/==A 33> %-<.

). :erguson I9. 4urrent diagnostic uses of saliva. J Dent Res %/=)A ;;> 82'828.

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=. Carrett HF. The proper role of nerves in salivary stimulation, a review. J Dent Res %/=)A ;;> 3=)-3/).

/. #atanube I, Iawes 4. , comparison of the effect of testing and chewing foods on the flow rate of whole saliva. rch Oral !iol %/==A 33>);%-);8.

%'. Tylenda 4,, &hip H,, :ox F4, 9ocum 9H. Kvaluation of submandibular salivary flow rate different age groups. J Dent Res %/==A ;)> %22<-%22=.

%%. 5enit*e B, 9irkhed 5, 9jorn 5. &ecretion rate and buffer effect of resting and stimulated whole saliva as a function of age and sex. S"ed Dent J %/=3A )> 22)-23=.

%2. Iawes 4. 7hysiological factors affecting salivary flow rate, oral sugar clearance and the sensation of dry mouth in man. J Dent Res %/=)A ;;> ;8/;<3.

%3. 6ason I3, 4hisholm I6. Sali#ary $lands in %ealth and Disease. Toronto> #9 &aunders, %/)<.

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Further Rea$i!%

6andel +I. The functions of saliva. J Dent Res %/=)A ;;> ;23-;2).

&peirs FE. &aliva and dental health. Dent &pdate %/=8A %%> <8%-<<2 and ;'<;%%.

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