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.

Only 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

frequent sipping of sugar-sweetened acidified drinks, fuels an aggressive level

of caries activity. Without 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.

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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

Saliva is secreted a series of major and minor glands which together are

capable of producing up to 1 litre per day,1 at a flow rate which varies from

0.02 ml/min at rest to 7 ml/min or more when stimulated. The secretion itself is

produced by two distinct types of specialized 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

In 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. And how do we define saliva?

The secretions from the three major glands are all different and in themselves

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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, desquamated epithelial cells and finally the gingival crevicular

secretions. It is only when we add together all of these ingredients that we

arrive at ‘whole saliva’.

Whole saliva is 99% water, and includes a mixture of inorganic ions, the

major ones being Na+, K+, Cl–, HCO3–, Ca++, Mg++, HPO4B–, and the minor ones

including I–, SCN– and F–. The resting pH varies between 6.7 and 7.4 for whole

saliva, while that of the pure parotid secretion, which is the easiest to obtain,

varies from 5.2 to 6.8. In 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. Some are simple proteins, such as enzymes

and albumin and free amino acids. However, 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. In order to make any sense of its constituents, we

must first consider the many functions of saliva.

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GENERAL MECHANICAL FUNCTIONS

In 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. By

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. A second mechanical property of saliva is its binding ability which

enables food to be formed into a bolus for swallowing. However, 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.

Fortunately, mucins decrease the permeability of the mucosa and limit the

penetration not only of the exogenous irritants but also of a powerful group of

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potential irritants generated within the mouth.3 These are the proteolytic

enzymes, produced largely by the organisms of dental plaque and by

polymorphonuclear neutrophils of the inflammatory exudate from the gingival

crevice when periodontal disease is present. (In 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 enzyme pepsin.)

While 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.

However, there are limits to the protection that mucins can offer; and strong

acids, alkalis and caustic chemicals such as aspirin rapidly destroy the barrier

and attack the underlying epithelium. In 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 recognized: 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

While 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 enzymes, to the complex proteins of the secretory

immunoglobulins. Under the normal conditions of the healthy mouth, these

agents cooperate in maintaining the proper ecological balance of the oral flora.

Although urea has been recognized 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 plaque pH, helping to provide a natural and

progressive brake to bacterial multiplication. Of greater import is the presence

in saliva and plaque fluid of the ion hypothiocyanite (OSCN–).4 It is derived

from a complex series of reactions which begin with the secretion of the

enzyme lactoperoxidase by the parotid and submandibular glands and by

plaque bacteria. This enzyme aids hydrogen peroxide (produced by bacteria in

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the mouth) in oxidizing the relatively unreactive thiocyanate present in saliva

to OSCN– . This ion has an inhibitory effect on bacterial enzymes involved in

glycolysis and sugar transport. In this way baterial metabolism is itself self-

regulatory.

While salivary enzymes are involved in the production of antibacterial

agents, some act directly on bacterial cells. One of the first enzymes to be

recognized in this role was lysozyme, which is found in high concentrations in

the secretion of the labial mucous glands. Its prime method of action is

probably by destabilizing the cell wall, possibly in conjunction with certain

anions and causing autolysis of the cell. Gram positive bacteria including the

cariogenic Streptococcus mutans, appear to be most sensitive to its action,

although the evidence for an association between salivary lysozyme

concentration and caries prevalence is equivocal. A second salivary enzyme

with a direct antibacterial action is lactoferrin, which works by binding iron

and depriving bacteria of this essential element. It may also have a direct effect

on bacterial cells.

A 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. It is thought that some of the very high molecular

weight salivary mucins are involved in this mechanism, although recent work

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suggests that some quite small glycoproteins as well as enzymes such as

lysozyme and some lipids are also active in this role.

The final major antimicrobial action of saliva is provided by the

immunoglobulins (Ig) together with the compliment system. The former are

proteins characterized 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. For each antigen a specific immunoglobulin or

antibody is produced which appears to bind and deactivate the foreign protein.

We now recognize three groups of immunoglobulins. The highest group

(termed IgG) with molecular weights of about 150,000 are found in internal

body fluids, extravascular tissue fluid and inflammatory exudate. The heavy

IgM group is confined to blood. It is the intermediate IgA group which is

secreted into the saliva by plasma cells around the acini and ducts; although

secretory IgA (S-IgA) differs from the IgA also found in plasma by being

coupled to a glycoprotein. When gingival inflammation is present, as is often

the case, IgG is found in the crevicular exudate and probably contributes to the

concentration of about 1.5 mg/100 ml found in whole saliva compared with a

typical figure of 20 mg for S-IgA. As to the efficacy of Ig in the action of polio

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vaccine and indeed may be partly responsible for the lack of convincing

evidence for the transmission of the HIV virus by saliva.

Compliment is a series of nine proteins which are formed in sequence

beginning with an antigen – antibody reaction resulting in a product which

binds to bacterial cell walls causing lysis. While present in saliva, its role in

maintaining the ecological balance is not fully determined and its manipulation

is beyond our present ability.

While the find of oral immunology held the promise of an anti-caries

vaccine and even a vaccine against periodontal disease, the efforts of Lehner

and co-workers in Britain and Bowen in the United States, 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 summarized.

pH CONTROL

The final major function of saliva is the maintenance of oral and

oesophageal pH, which is achieved by a series of buffer systems. In stimulated

saliva it is largely due to the bicarbonate ion, which provides 85% of the total

buffering capacity of about 10M-equiv/litre5 and provides an effective buffer

against fluctuating pH. The bicarbonate ion concentration of resting saliva is

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low, and therefore its buffering capacity is provided by histidine-rich peptides,

phosphates and amino acids, together acids.6 Since this function is of great

importance in its relation to plaque pH and caries, it is discussed in more detail

in the next paper in this series.

Before 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.7

THE CONTROL OF SALIVARY 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.8 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. Indeed,

just reading the words ‘lemon drops’ is sufficient to produce an immediate

increase in flow rate in many mouths.

A more powerful stimulus is mastication. Numerous 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. Recent 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. Nevertheless it has been

convincingly demonstrated that taste stimuli are potentially the most potent,9

with acids being the most effective.6

It 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. It 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. For basal whole saliva in adults, flow rates vary from 0.02 to 2.75 ml/min,

while the rates for paraffin wax stimulation vary from 0.2 to 5.85 ml/min.10

One of the most effective salivary stimulants is citric acid placed n the tongue,

and in a recent study a 5% solution produced a maximum flow rate of 7.07

ml/min.6 Within this wide range there are a number of related factors. As one

might except, the basal secretion rate increases with age up to about 15 years,

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beyond which few differences are found.10 (Although there is evidence that the

glands of the elderly lose their capacity for increased secretion on stimulation,11

and show a decline in basal flow rates from the minor labial and submandibular

glands.) Body 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 equivocal.

It is amongst the group of factors related to time or condition that the

greatest variations are found.12 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 afternoon;5 however, flow rate falls to

almost zero during sleep. Some olfactory stimuli promote salivary flow, while

previous stimulation reduces the response to further stimulation. Finally, but of

great practical significance, there are a great number of drugs which have an

effect, usually inhibitory, on flow rate.13

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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However, the secretion of potassium and fluoride varies little, and secretion of

phosphate and magnesium falls.

A number of systemic disorders and local conditions are associated with

a reduced conditions are associated with a reduced flow rate. These include

Sjögren’s syndrome, post-radiation xerostomia and salivary duct calculi.

These are discussed in the final paper in this series. All these variations

in salivary flow are linked to changes in composition. The most relevant to

dental caries are the increase in pH, buffering capacity and mineral ion

concentrations with flow rate, which will be discussed in the second paper.

Form this brief review, saliva emerges as a complex but vital fluid,

produced in response to need and adapted to meet the many requirements of a

healthy mouth.

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References

1. Jenkins GN. The Physiology and Biochemistry of the Mouth 4th edn.

Oxford: Blackwell, 1978.

2. Shwartz NH. The rheology of saliva. J Dent Res 1987; 66:660-664.

3. Adams D. The mucous barrier and absorption through the oral mucosa. J

Dent Res 1975; 54:B19-B26.

4. Pruitt KM. The salivary peroxidase system – thermodynamics, kinetics and

antibacterial properties. J Oral Pathol 1987; 16:417-420.

5. Dawes C. Inorganic constituents of saliva in relation to caries. In:

Guggenheim B, ed. Cardiology Today. Zurich: Karger, 1984; pp. 70-74.

6. Watanube D, Dawes C. The effects of different foods and concentrations of

citric acid on the flow rate of whole saliva in man. Arch Oral Biol 1988; 33:

1-5.

7. Ferguson DB. Current diagnostic uses of saliva. J Dent Res 1987; 66: 420-

424.

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8. Garrett JR. The proper role of nerves in salivary stimulation, a review. J

Dent Res 1987; 66: 387-397.

9. Watanube D, Dawes C. A comparison of the effect of testing and chewing

foods on the flow rate of whole saliva. Arch Oral Biol 1988; 33:761-764.

10. Tylenda CA, Ship JA, Fox RC, Bocum BJ. Evaluation of submandibular

salivary flow rate different age groups. J Dent Res 1988; 67: 1225-1228.

11. Henitze U, Birkhed H, Bjorn H. Secretion rate and buffer effect of resting

and stimulated whole saliva as a function of age and sex. Swed Dent J

1983; 7: 227-238.

12. Dawes C. Physiological factors affecting salivary flow rate, oral sugar

clearance and the sensation of dry mouth in man. J Dent Res 1987; 66: 649-

653.

13. Mason DK, Chisholm DM. Salivary Glands in Health and Disease.

Toronto: WB Saunders, 1975.

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Further Reading

Mandel ID. The functions of saliva. J Dent Res 1987; 66: 623-627.

Speirs RL. Saliva and dental health. Dent Update 1984; 11: 541-552 and 605-

611.

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