Oral Physiology Four

Saliva In Health and Disease

Professor Frederick Smales

The School of Dentistry
International Medical University
 Scope of the Lecture
Saliva is a very extensive topic, but one which is important
in many ways to the dentist in everyday clinical practice.

This lecture attempts to provide a comprehensive overview

with particular reference to flow rates, and inorganic and
organic constituents in various circumstances

The dental student should read further on this important topic

during Semesters One and Two
 Based on

Chapter Six of
Oral Bioscience

Ferguson, D. B.
1999 Churchill
Livingstone
 Some Functions of Saliva
1. Protection of oral tissues by keeping them moist
2. Lubrication of soft tissues by mucinoid secretions
3. Maintenance of hard tissues by high Ca and P levels
4. Resistance to acid attack by buffering substances

5. Creation and lubrication of food boluses

6. Initiation of starch digestion by mixing of amylase

7. Control of micoflora by antimicrobial substances

 Dry Mouth or Xerostomia
Comments are made throughout this lecture on some
effects of reduced salivary secretions on oral wellbeing.

However early mention is made here of the potential for

severe effects associated with such changes

In practice the changes are not gradual but mainly

occur dramatically when secretions fall to quite low levels

That is to say there seems to be a threshold effect

That explains why textbooks often say there are no

correlations between salivary flow rates or composition
and severities of dental caries and periodontal diseases
 Fluid Flow Rates from the Various Glands
Unstimulated Stimulated

Total Oral Fluid 0.25 0.35 ml/min 1.0 -3.0 ml/min

Parotid Glands 0.0 0.11 ml/min 1.4 3.0 ml/min

Submandibular Glands 0.0 0.28 ml/min ***

Sublingual Glands --- ***

Labial Glands --- ***

Submandibular glands may form bulk of unstimulated secretions

with parotid glands the major contributors to stimulated secretion
 Collection of Fluid
from Various Glands

Using a Lashley Cannula

held over the parotid duct by suction to the outer ring, parotid
saliva can be collected at rest and during stimulation by chewing

A custom-made device allows collection of submandibular saliva

at rest only, as it dislodges during chewing stimulation
 Cellular Constituents of Oral Fluid
Bacteria 60-70 x 106/l
Begin colonising the mouth of the neonate soon after birth

Leucocytes 25-650 x l03/l

Mostly polymorphonuclear leucocytes, a few lymphocytes

(These enter the mouth via the gingival crevice

so are absent in edentulous persons and neonates)

Buccal Squames 6-600 x 103/l

Amorphous debris in saliva may be disintegrated squames
 General Ionic Composition of Oral Fluid
All of the ions present in tissue fluid are seen
in salivary secretions

However when first secreted their concentrations

are somewhat different from that origin and alter further
as the flow rates of the secretions change

A good way to learn about ionic composition of

saliva is to learn about ionic secretion

A good way to learn about how the secretions of

the ions take place and are altered is by
studying some diagrams, graphs and tables
Ionic Secretion into Acinar Fluid

The result is quite close to an isotonic fluid

Ionic Secretion into Acinar Fluid
D

B F

C E

The result is quite close to an isotonic fluid

 Na+ secreted
K+ secreted
Cl- secreted

K+ secreted
Summary of Ion
Concentrations Na+ absorbed
Changes in K+ secreted
Cl- absorbed
Salivary Secretion
HPO4 secreted
HCO3 secreted
SCN- secreted
 Ductal Modifications of Ionic Concentrations

E
C
B A

D
D

Ductal modifications cause the final fluid to be

hypotonic (but potassium ion concentration is raised)
 General Ionic Composition of Oral Fluid
mmol/l Plasma Acinar Fluid Slow Saliva Fast Saliva

Sodium 152 136 <10 80

Potassium 4 8 21 22

Calcium 2.5 1.2 1.8

Chloride 112 112 10 40

Hydrogen Carbonate 23 30 4 35
Some Concentration Changes with Flow Rate

The rise in bicarbonate and the maintenance of the calcium

/phosphate product are both protective during mastication
Calcium Ions in Salivary Secretions
1.4 mmol/l in unstimulated saliva
Rising in stimulated saliva to 1.7 mmol/l

Only 50% is ionic with 40% complexed with other

ions and 10% bound by salivary protein

Phosphate Ions in Salivary Secretions

6.0 mmol/l in unstimulated saliva
Falling in stimulated saliva to 4.0 mmol/l

More than 90% is ionic with the remainder

present as organic phosphate
 Acid Production in Dental Plaque and the
Dissolution of Hydroxyapatite
The pH at a point in a dental plaque can be easily measured
At different teeth locations plaques show different resting pHs
Such values tend to reflect
the general activity of the plaque

The lowest resting pHs are seen

in (active) carious cavities
A sucrose or glucose rinse causes
all plaque pHs to fall to some extent
Such a fall and subsequent rise in
pH is called a Stephan Curve 17
 Hydroxyapatite Solubility Product
Salivary Ca++ and
PO4--- can be substituted
into the equation for the
solubility product of
hydroxyapatite Solubility product above that of HA

Solubility product below that of HA

The result shows
hydroxyapatite is
unlikely to dissolve
in saliva at its resting
pH of about 6.0

However the value of the product of the ions is pH-dependent

and shows that hydroxyapatite will dissolve below a Critical
pH of about 5.6 illustrated in the diagram above
 Bicarbonate Ion in Oral Fluid (Total Saliva)
Very low in unstimulated saliva from all glands

Rapidly increases at fast flow rates due to

glandular metabolic activity aided by carbonic anhydrase

The pH of stimulated saliva rises towards pH 8.0 and

resists acidogenic-driven falls to critical plaque pH of 5.6

The enamel-dissolving pH level might be avoided

The different effects of unstimulated and stimulated saliva on

plaque pH can be demonstrated experimentally

A paper strip test of patients buffering of saliva is available

 Thiocyanate Ions in Oral Fluid
Thiocyanate ion concentration lin saliva is inversely
correlated with a lower incidence of dental caries

It is oxidised to hypothiocyanite by the active oxygen

from bacterial peroxides being broken down by salivary
lactoperoxidase. Hypothiocyanite is strongly
antibacterial

Thiocyanate reaches saliva by transport in the

ducts and so decreases in concentration as flow rate
increases.

High in concentration in saliva from cigarette smokers

and can be used to identify children who smoke.
 Fluoride in Oral Fluid

Fluoride concentrations in saliva are low and very similar

to those in plasma and extracellular fluids in general.

Intake of fluoride increases plasma levels transiently

and that increase is also observed in saliva but still the
levels are not clinically significant

This emphasises that the action of fluoride ion in reducing

dental caries needs repeated local application of high
concentrations into the mouth, e.g. by fluoride dentifrices
Major Organic Constituents of Salivary Secretions
Mucins and Proline-Rich Glycoproteins
Mucins are glycoproteins with more than 40% carbohydrate, MG1 and Mg2,

Digestive Proteins
Mostly amylase, trace of lipase, traces of microbial enzymes

Antimicrobial Proteins
Sialoperoxidase, lysozyme, IgS, lactoferrin, histatins, SLPI

Calcium Binding Proteins

Statherin, Proline-Rich Proteins
The latter form the major component of the protein secreted by the
parotid glands. There is an acidic group, a basic group and a gylcylated group
Protein and Mucins in Salivary Secretions
Summary of Process
of Salivary Secretion
Mucins and Proline-Rich Glycoproteins (P-RG)
kDa % Protein Side Chain Length Gland Function

MG1 1000 15% 14-16 residues Submand Lubricate

MG2 200-250 30% 170 chains, 2-7 residues Submand Viscosity

P-RG 40% 6 oligosaccharide units Viscosity

Mucins have protein cores with oligosaccharide side-chains

Main amino acids are threonine, proline, serine and alanine.

Carbohydrate residues include fucose and large amounts of

both N-acetylglucosamine and N-acetylgalactosamine.
 Digestive Proteins
Amylase is about 30% of the protein from the parotid glands

It breaks down starch at O-glycosidic linkages to give

maltase and longer chain polysaccharides.

Only active above pH 6 so stops working in the stomach

and therefore the amylase of the pancreatic gland is much
more effective in carbohydrate digestion

So the function of salivary amylase is rather obscure

The other enzymes in saliva include several of bacterial

origin and a lipase
 Antimicrobial Proteins (One)
Immunoglobulin A - IgA
Made as a monomer by plasma cells in the glandular lymphatic
tissue together with a small protein termed the J-protein, which
forms a dimer of two IgA molecules

It binds to a cell membrane receptor on the ductal epithelium,

transported to the luminal surface and released into
the saliva, still bound to a part of the receptor molecule.

The receptor fragment is called the secretory piece, and the

dimeric IgA configuration with the secretory piece protects the
antibody from breakdown in the oral fluids.

sIgA may be active against cariogenic bacteria

 Antimicrobial Proteins (Two)
Sialoperoxidase already noted as part of the thiocyanate
antibacterial mechanism

Lysozyme (muraminidase) Breaks microbial cell walls

Lactoferrin Deprives microrganisms of essential iron

Histidines six in number, these peptides may be active

against candidal organisms

Salivary Leucocyte Proteinase Inhibitor (SLPI) is thought

responsible for the inability of saliva to transmit HIV
 Calcium Binding Proteins

Statherin is a small protein which can bind calcium and may

help prevent stones (calculii) in the salivary glands

Proline-rich proteins are the largest organic component of

parotid saliva

They also can bind calcium and therefore may be involved

In helping to prevent stones (calculii) in the salivary glands
Miscellaneous Organic Components

1. Blood Group Substances

2. Sugars
3. Lipids
4. Nitrogenous Compounds
 Blood Group Substances

This property of saliva is of some importance forensically. Note however

that parotid saliva does not contain blood group substances.

About 80% of people in Western communities secrete A and B blood

group substances of the ABO blood groups into their saliva. Group O
people produce H substance.

Other blood group antigens, except Lewis A and Lewis B, are not
secreted, although Lewis A is also secreted by subjects of otherwise
non-secretor status.
 Nitrogenous Compounds

Saliva contains amino acids, a tetrapeptide named

sialin with the composition GCKR (gly-gly-1ys-arg),
urea, uric acid, ammonia and creatinine.

Urea is readily broken down by plaque ureases to yield

ammonia, sialin is also converted into ammonia in
plaque, and ammonia is itself present.

The pH of dental plaque is raised by ammonia from

these three sources: this provides a means of
combating plaque acid production and maintains a
more alkaline plaque during fasting periods.
 Use of Saliva as a Diagnostic Fluid
The possibility that saliva samples can replace blood tests
for diagnosis have so far be largely disappointing.

For example glucose or blood sugar levels are not reflected

in saliva as glucose is metabolised during the secretory
process

However free lipid levels in blood are reflected in saliva.

Those levels include steroid hormones, especially
oestrogen and testosterone

So saliva can be used for tests and has the benefit that
protein-bound steroid hormones in blood which are not of
interest are not reflected in saliva samples
Effects Causing to the Sensation of Dry Mouth
1. Subjective Sensations
In some people dry mouth without detectable change in flow
May be an alteration to the nature of the oral mucosa

2. Pharmacological Side Effects

Anti cholinergic drugs and other affecting the autonomic system
Include diuretics and some anti-depressantant drugs
Elderly people taking medications gives an age-related effect

3. Sjogren's Syndrome
A connective tissue disease. Often involves reduced lachrymal secretion.
Diagnosis by biopsy of minor salivary glands

4. Age Inherent Effects

Degenerative changes well established with aging
Many studies fail to correlate this with reduced flow
 Proposed Caries Risk Assessment Systems
CAMBRA California, USA 2003 - Featherstone

Caries Management By Risk Assessment

1. Is there existing or has there been new untreated cavities in the past two years?

2. Has there been orthodontic appliances or removable partial dentures?

3. Is there reduced salivary function as measured by stimulated saliva flow less than
0.7 ml/minute?

4. Is there use of hypo-salivatory medications?

5. Is there frequent ingestion of fermentable carbohydrates (by questioning)?

6. Is current use of fluoride products inadequate?

7. Is there high caries bacterial challenge as measured by testing mutans

streptococci and lactobacilli?
 Caries Management By Risk Assessment
Management Protocols Suggested for CAMBRA
1. Four Risk Groups, Low Risk, Moderate Risk, High Risk, Extreme Risk
2. Patients with one or more cavitated lesions are High Risk patients
3. High-risk criteria & extreme hyposalivation are Extreme Risk patients

Recommended Management Protocol Headings

1. Frequency of Radiographs
2. Frequency of Recall for Caries Coding
3. Saliva Testing (Flow and Bacterial Counts)
4. Antibacterials/Chlorhexidine/Xylitol
5. Fluoride Supplementation
6. pH Control System
7. Calcium Phosphate Topical Supplements
8. Sealants(Resin-Based or Glass-Ionomer)
End of Oral Physiology Four
Saliva in Health and Disease

End of Oral Physiology Lectures for Semester One