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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.
1
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
2
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.
3
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
4
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.
5
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
6
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
7
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
8
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
9
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
10
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,
11
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.
12
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.
13
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.
14
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.
15
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.
16