Introduction

The secretion of the major and minor salivary glands along with

gingival crevicular fluid form the oral fluid or the whole saliva

which provides the chemical milieu of the teeth and oral soft tissues.

In daily talk, word saliva is used to describe the combined fluids

present in the mouth. But in its strict sense of word, it denotes

secretions from submandibular, sublingual, parotid and minor

salivary glands.

A critical component of oral environment saliva bathes the teeth and

structures of oral mucosa which aids in speech mastication and

deglutition.

The term whose saliva, oral fluid, mixed saliva are commonly used.

Salivary glands

Salivary glands are exocrine glands, whose secretions flow into the

oral cavity.

Salivary glands can be divided into:

Major and minor salivary glands.

Major – There are their pair of major glands namely:

- Parotid.

- Submandibular

- Sublingual

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Minor – These are distributed in mucosa and submucosa of the oral cavity

namely:

- Labial and buccal glands.

- Glossopalatine glands.

- Palatine glands.

- Lingual glands.

Both major and minor salivary glands are composed

of parenchymal elements, (derived from oral epithelium) supported

by connective tissue.

Parenchymal elements consists of terminal secretory

units leading into ducts that open into the oral cavity.

Connective tissue forms a capsule around the glands

and extends into it, dividing groups of secretory units and ducts into

lobes and lobules.

Histology

The terminal secretory units are composed of serous, mucous and

myoepithelial cells arranged into acini or secretory tubules.

a) Serous cells:

These are specialized for synthesis storage and secretions of

proteins.

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Serous cells form a thin watery secretion containing ptylin

[salivary -amylase] which initiates digestion of starch to maltose in

the oral cavity.

Mucous cells:

These are specialized for synthesis, secretion and storage of

secretory products.

Mucous cells secrete a viscous glycoprotein called “mucin”,

a useful lubricant for food and also protects the oral mucosa.

Myoepithelial cells

These cells are closely related to the secretory and

intercalated duct cells, lying between the basal lamina and the basal

membranes of parenchymal cells.

These cells are considered to have a contractile function,

helping to expel secretions form the lumina of the secretory units and

ducts.

Both pairs of gland contains their secretory cells in acini where in

the cells are arranged around a central lumen which leads into the

‘intercalated duct’ which connects the secretory units to the larger ‘striated

ducts’. These ducts join to form interlobular ducts which leads into the

main excretory duct.

3

SALIVARY GLANDS AND THEIR MAIN FEATURES

Gland type and weight Location Route of secretory

duct Histology

Percentage of total salivary

secretion (1500ml/day)

Nerve supply

1. Parotid gland 20-30gm each

In the groove between ramus of mandible and mastoid process i.e. below the ear

Secretions pass via Stenson’s duct which opens opposite the upper second molar tooth in oral cavity

Contains purely serous cells 25% IX

Nerve

2. Submandibular or submaxillary 8-10gm each

In submaxillary triangle behind and below the mylohyoid muscle, with a small extension lying above the muscle.

Its duct i.e. Wharton’s duct opens into floor of the mouth at canancula sublingualis a papilla along the side of lingual frenum .

Mixed i.e. contains both serous and mucous cells in the ratio of 4:1

70% VII nerve

3. Sublingual glands 2-3gm each

Between floor of mouth and mylohyoid muscle

Its secretions are discharged by 5-15 small ducts Main duct is Barthobinis duct “ducts of Rivinus in floor of mouth

Mixed but mainly mucous cells

Ratio 1:4

S:M

5% VII nerve

SOURCES OF SALIVA

Saliva is a complex mixture of fluids which is derived from major

and minor salivary glands and gingival crevicular fluid. Along with this, it

contains high population of bacteria, desquamated epithelial cells, transient

residues of foods and drinks.

SALIVA

Composition:

Saliva is a dilute “hypotonic fluid” over 99.5% consisting of water.

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Saliva contains both organic and inorganic constituents which are

dissolved.

The concentration of dissolved solids are characterized by wide

variations, both between individuals and within a single individual.

Inorganic Constituents

Saliva contains both cations and Anions.

The main cations are : Sodium, potassium along with calcium and

magnesium.

The main anions are : Chloride, bicarbonate and phosphate and trace

amount of other halides.

Saliva has less of sodium and higher concentrations of potassium as

compared to extracellular fluid.

Sodium

Salivary sodium concentration are highly flow dependent. In resting

state saliva has trace amount of sodium which increases from 10mEq/L to

100mEq/L at rapid secretory rates.

Potassium

Unlike sodium, potassium level is independent of the secretory flow

rate.

5

Mixed saliva contains about 8.20 mEq/L of potassium which is

about 1.5-4.0 times its concentration in plasma.

Calcium

In resting condition 3.0mEq/L.

It occurs in ionic (the major part) and bound form in saliva; like as

in plasma either with protein or as colloidal calcium phosphate.

High level of calcium is responsible for the resistance to dental

caries but increased level may cause salivary calculi.

Magnesium

Present in trace amount of about 0.6mEq/L.

Chloride

Chloride concentration of saliva is less than that of plasma.

It is minimal in resting condition.

Concentration increase with flow rate and may increase upto 15-

25mEq/L.

Bicarbonate

Bicarbonate is present in saliva to contribute to its osmolarity and

buffering functions.

6

Its concentration in saliva is less than that in plasma which is about

5mEq/L.

As secretion rate increases bicarbonate level rises and than becomes

stable at a concentration of about 40-60 mEq/L.

Saliva also secretes other halogens such as iodides, bromides and

fluorides.

Organic

The chief organic constituents of saliva are the complex

Group of salivary proteins, mainly comprising the

glycoprotein mucin and the enzyme amylase.

a) Glycoprotein Mucin:

These are mainly sialomucins.

These are responsible for lubricating, viscosity and buffering

properties of saliva.

Secreted by mucous-cells.

These comprise of 200mg/100ml approximately which is

only about 3% of the protein concentration of plasma.

Quantity of salivary protein increases with the flow rate.

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b) Enzymes:

1) Alpha-amylase

It is the major digestive enzyme of saliva about

30% of protein found in saliva.

It is present in parotid saliva at concentration of

60-120 mg/100ml and in submandibular saliva at

approximately 25mg/100ml.

Alpha-amylase is Ca2+ dependent and readily

inactivated by a pH of 4 or less.

The end product of amylase digestion are

mainly maltose together with oligosaccharide and some free

glucose.

The concentration of -amylase increases with

the rate of salivary secretion.

2) Lysozyme:

Is an antibacterial enzyme.

The mean concentration in whole saliva (resting) is

2.2mg/100ml and when stimulated-11mg/100ml.

Lysozyme acts on the B (1-4) bond between N-acetyl

muramic acid and N-acetyl glucosamine in the gram +ve

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bacterial cell wall leading to its subsequent disruption and

microbial death.

3) Acid phosphatase, cholinesluase, ribonuclease. -

These enzymes are present in similar concentration in parotid and

submandibular saliva with phosphatase having an optimum pH of 4.

4) Lipase : A specific lipase occurs in parotid saliva.

5) Peroxidase

An antibacterial peroxidase system occurs in parotid saliva

and comprises lacto-peroxidase, thiocyanate and H2O2.

This system inhibits growth and acid production of a variety

of micro-organisms, including streptococcus, lactobacilli,

fungi and enteric bacteria.

Lactoperoxidase also retains activity when absorbed on

hydroxyapetite and salivary sediment, thereby protecting the

enamel surface.

6) Kallikarin

It splits beta-globulin into bradykinin, which then passes

back into the gland and into B.V.’s thus causing functional

vasodilatation to supply an actively secreting gland.

7) Dextranases

8) Invertase

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Miscellaneous Enzymes

- Proteases, iminopeptidases, endopeptidases, carboxy

peptidases, aminopeptidase, urease, glucuronidase,

hyaluonidase, neuraminidases, esterases, sulphatases etc.

c) Serum proteins

These amount to about 20% and include IgG, IgM, IgA,

albumin, and - globulins.

IgA is the predominant immunoglobulin and comprises of 90%

of total parotid IgA1, IgG and IgM are present in low amounts.

IgA has 3 main functions:

a. Inhibition of bacterial colonization.

b. Binding to specific bacterial antigen.

c. Affects specific enzymes essential for bacterial

metabolism.

d) Other polypeptides:

2) Blood Group Substances:

Blood group antigens are also present in saliva namely Ag A and

AgB.

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3) Hormones

Two hormone like substance have been described in saliva

“Parotin” and a “nerve growth factor”.

Parotin – facilitates calcification and helps to maintain serum

calcium levels.

Nerve Growth Factor (NGF) – affects growth and

development of symphathetic nerve fibres.

4) Carbohydrates

Has glucose at a concentration of 0.5-1mg/100ml (parotid).

In submandibular – glucose, hexose, fructose with small

amounts of hexosamine and sialic acid.

5) Lipids

Saliva contains small amount of diglycerides, triglycerides,

cholesterol and cholesterol esters, phospholipids, corticosteroids.

Salivary lipids play a role in salivary protein binding

bacterial absorption to apatite, and plaque microbial aggregation.

6) NitrogenAmino acids – 9 type in parotid

12 in submandibular

18 in whole saliva at low concentration of about 0.1mg /100ml.

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7) UreaApproximate level 12-20mg/100ml.

8) Water soluble vitamins.

9) Gases dissolved in saliva

Like all body fluids, saliva contains N2, O2 and CO2 in solutions. O2

and N2 contents are stated to be between 0.18 and 0.25 volume % and

about 0.9 volume % respectively.

FACTORS AFFECTING COMPOSITION

The composition is altered as the saliva passes in the duct system,

mainly due to reabsorption of sodium chloride and secretion of potassium

and inorganic phosphates.

A) Flow rate

As the flow rate increases the

concentration of proteins, sodium chloride, bicarbonate and

amylase rise, while the levels of phosphate, urea, amino acid,

uric acid, ammonia, serum albumin and magnesium

concentration decrease.

Calcium, protein bound

carbohydrates concentration fall at first and then slowly

increases with increasing salivary flow rates.

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For sodium and chloride, this

can be explained on the basis of two stage secretory

mechanisms.

As the amount of primary

secretion increases the time during which the fluid is passing

through the duct is reduced; at very high flow rates, the

composition of high flow therefore approaches that of the

primary acinar secretion.

With other components, this

process cannot explain the flow rate e.g. bicarbonate is secreted

by the duct and its concentration should therefore fall with

increased flow. Infact, bicarbonate level rise dramatically at high

flow rates, probably due to the secretion of the raised levels of

bicarbonate formed by metabolically active gland cells.

B) Differentiatal gland contributions:

In unstimulated whole saliva, the parotid glands contribute only

about 10% of the fluid volume where as in stimulated they

become predominant. Thus the composition of mixed saliva

approaches that of parotid gland secretion at high flow rates.

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C) Circadian Rhythm

Rhythmic variations are seen in the concentration of many

salivary constituents.

Levels of Ca2+ and PO4 ions are low in the early morning and

remain stable during day and than calcium concentration

increases at night.

Concentration of Na+ and Cl-2 are maximum in morning.

Protein concentration increase in noon.

K++ concentration is high in early afternoon.

D) Duration of the stimulus

At a constant rate of flow, the composition varies with the

duration of the stimulation. If the salivary glands are stimulated

for more than 3 months, the composition of many components is

decreased, although after for a short period bicarbonate Ca2+ and

protein concentration begin to rise again.

Mg2+, Po4 and K+ concentrations, plateau after an initial fall.

Chloride concentration fall during periods of increased

stimulation.

Whereas sodium and iodide concentration are unaffected by the

duration of stimulation after the first few months.

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E) Nature of stimulus:

If the flow rate is constant the secretions elicited with sour, sweet,

bitter stimuli are similar in electrolyte composition, however salt stimulates

a higher protein content.

F) Diet

Long term changes in diet do not appear to have much effect on

salivary composition.

It has been suggested, however that changes in plasma PO4 and

urea concentration induced by dietary alteration may be reflected

in saliva.

Functional salivary glandular activity is influenced by

mechanical and gustatory factor e.g. copious salivary flow

results from smell of food or denture insertion.

G) Hormones

In man injection of adrenocartocotrophic hormone and cortisone

decreased salivary Na2+ and little changes in concentration of K++

are seen.

A tendency of salivary Na2+ concentration to be lowered during

IInd half of menstrual cycle has been reported.

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H) Fatigue

If the salivary glands are stimulated vigorously for an hour, the

volume of saliva secreted per minute shows little tendency to fall, some

constituents such as immunoglobulins may increase whereas other such as

urea, sodium, K+ Cl- ion may remain stable for as long as three hours.

I) Plasma concentration

Salivary concentration of amino acid, calcium, glucose, potassium,

urea, Cl-, Na+ ions are co-related with those in plasma.

PROPERTIES OF SALIVA

Daily secretory volume 500-7500ml

Consistency slightly cloudy and viscous due to the presence of cells

and mucin.

Saliva is acidic in nature usually.

Saliva is colourless opalscent fluid.

Specific gravity is 1002 to 1012

Saliva is usually hypotonic but approaches isotonicity when flow

rates are high. It is rarely hypertonic.

pH 5 to 8

Mean pH 6.4

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- pH becomes alkaline with high flow rates.

- Bacterial action may also alter the pH of saliva.

Freezing point – 0.07-0.34°C.

Osmotic pressure – ½ -3/4 of blood (1400m osmol/L) i.e.

700-1000m osmol/L.

Flow rate – 0.02ml / min. – At rest

7ml / min. – In stimulated saliva.

Velocity – 0.8-8mm/min. – As estimated on tooth surface by

“Daves et al”.

- Lowest velocity films occurred on facial surfaces of upper

incisors 0.8-1.3mm/min.

- Highest velocity occurred on lingual surfaces of teeth.

VISCOSITY-‘SPINN BARKEIT PHENOMENA’

Viscosity of secretions of various glands depends on their

glycoprotein content as described by Gottschalk 1961. Viscosity of

saliva is non-newtonian.

Saliva exhibits different viscosities at different rate of shear and has

viscoelastic properties.

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Ability to draw out a thread of saliva is typical of a viscoelastic fluid

and is known “Spinn Barkeit”.

The relative viscosity of the three main secretions after acetic acid

stimulation were found by Schneyer (1955).

Parotid - 1.5

Submandibular - 3.4

Sublingual - 13.4

Buffering action of saliva

Ericsson (1959) on studying the diurnal clinical variation in the

buffering power of slaiva found that:

a. It was immediately high on rising in the morning but rapidly

decreases.

b. It increased about a quarter to a half hour after meals but usually fell

within ½ -1hour after meal.

c. There was an upward trend in the buffering power throughout the

day until evening when it usually tends to fall.

Reducing power of saliva

In addition to bacterial reduction saliva contains a complex misture

of substances which possess reducing properties.

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These include carbohydrates split off from glycoproteins, nitrites

and some unidentified substance of low molecular weight.

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BUFFERING POWER OF SALIVA

Solutions containing both weak acids and their salts are referred to

as ‘buffer solutions’. These solutions have the capacity of resisting changes

of pH where either acids or alkalies are added to them. For the buffering

properties of saliva two terms “buffer capacity” and buffer effect are used

synonymously. The buffer capacity express the resistance to pH changes at

an arbitrary point. The term “buffer effect” refers to amount of acid

required to change the pH of the saliva sample from one value to another.

The buffer capacity of human saliva is regulated by three buffer

systems:

a. The carbonic acid / bicarbonate system.

b. Phosphate system.

c. The proteins – mucin.

In stimulated saliva it is largely due to the bicarbonate ion which

provides 85% of the total buffering capacity of about 10m-equiv/liter.

1) Carbonic acid/bicarbonate system

It is based on the equilibrium

H2CO3 HCO3-+H+

When an acid is added, the bicarbonate releases the weak carbonic

acid. Carbonic acid is readily decomposed into H2O and CO2 which leaves

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the solution. In contrast to most buffers, the net result is therefore not an

accumulation of a weaker acid but a complete removal of acid. This change

of phase for CO2 from dissolved states to gas phase for which the term

“phase buffering” is used is essential for the buffer action of bicarbonate

system. Bicarbonates are therefore very effective buffer against acid and

are important in reducing pH changes in plaque after meals. The

bicarbonate ion concentration of resting saliva is low and therefore its

buffering capacity is provided by histidine-rich peptides, PO4 and amino

acids together with ammonia generated from amino acids.

2) Phosphate buffer system

This system functions basically by the same general principle as the

HCO3- system except for the fact that no phase change is involved. At

physiological pH, the system operates according to the following

equilibrium.

H2PO4- HPO4

2-+H+

Thus the two buffer system described act together to keep the

salivary pH above 6.

3) Salivary proteins

These are usually not considered to have any significant buffer

capacity at pH values involved in the oral cavity. It is possible, however,

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that carbamino compounds or carbonate will contribute to the acid

buffering of saliva.

It is possible that cigarette smoking may influence the salivary

buffer capacity. In a comparison of smokers and non-smokers the buffer

capacity of resting and stimulated saliva was significantly lower in

smokers. Reason for an impaired salivary buffer capacity in smokers are

not readily apparent.

Functions of saliva

1. Digestion of polysaccharides

Salivary amylase acts on the polysaccharides startch, dextrin and to

some extent on glycogen. Major steps in digestion are:

Cooked starch + saliva soluble starch Erythodextein

archcodextun maltose.

But due to rapid ingestion of food digestion of starch continues in

the stomach.

2. Diluent and cooling effect

Acidic solutions or spicy foods evoke marked salivation and this

seems to dilute their effects. Hot foods and drinks may be cooled in the

mouth before they are swallowed.

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3. Buffering action

The three buffering system of saliva are:

a. Bicarbonates.

b. Phosphates.

c. Protein mucin.

About 85% of total buffer capacity of saliva comes from

bicarbonate system Walleung1989.

Among the three; bicarbonates along with the dissolved CO2, acts as

a major buffer pair. As the salivary flow increases during a meal the

concentration of bicarbonate also increases thus increasing the buffering

capacity of saliva.

Importance

The buffering action of saliva helps to keep the

reaction of the fluids in the oral cavity with a range optimum for

activity of salivary amylase.

pH of oral fluids is also critical for survival of the

bacterial flora of the mouth and influences the development of

dental caries.

4. Moistening, cleansing and antibacterial function:

Saliva keeps the oral and pharyngeal mucosa moist.

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This helps in speech, swallowing, thirst etc.

Saliva helps to maintain oral hygiene when salivation is suppressed

as during fever, post-operatively or as seen in mouth breathers lips,

teeth, oral mucosa dry up and thus mucosa gets coated with food

particles. Dried mucosa sheds epithelium which harbours bacteria.

Thus a constant flow of saliva has a cleansing effect on the mouth

and the teeth.

Saliva also has antibacterial activity. Its bacteriostatic properties are

due to the presence of lysozyme and related antibacterial substance

such as leukocytes and opsonins.

5. Lubrication for mastication, swallowing and speech.

6. Saliva as a solvent: Its role in taste sensation. The sensation of taste

is produced only by substances in solution. Some foods such as fruits,

contains increased proportion of H2O that probably all the substances

which have a taste may be perceived as soon as they are released by

mastication, some foods containing less amount of H2O and before their

taste becomes, apparent saliva must dissolve out the flavoured

constituent. Thus saliva helps in taste perception.

7. Role in thirst mechanisms Canon in 1937 observed, drying of

mouth due to evapration of saliva , Mucosa of mouth and pharynx dry

up when salivary secretion is suppressed. This persistent dryness results

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in constant stimulation of afferent nerves of the mouth and evokes

sensation of thirst. Thus, salivation plays an important role in

maintenance of water balance of body.

8. Saliva in temperature regulation

In animals like dogs, sweat glands are absent and salivation along

with panting, constituents a part of physiological responses to increase in

body temperature.

The secretory rate is proportional to rise in body temperature.

Salivation thus helps to dispose the excess heat and is concerned

with temperatures regulation of the body.

9. Excretory function

Several substances like lead, mercury iodides, alkaloids like

morphine, urea, uric acid, ammonia are excreted in the saliva.

The excretion of ethyl alcohol by salivary gland has promoted this

test to be used for medicolegal purposes.

10. Middle ear pressure adjustment

Helps to equalize pressure on either side of tympanic membrane.

SECRETION OF SALIVA

Total volume – 500-750ml/day

Submandibular – 60%

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Parotid – 30%

Sublingual 3-5%

Minor salivary glands – 7%

These proportions vary with intensity and type of stimulation.

In Sleep

Parotid - 0%

Submandibular - 72%

Sublingual - 8%

Resting stage:Submandibular – 72%

Parotid – 21%

Sublingual -1-2%

Minor salivary glands – 7%

Acidic stimulationSubmandibular – 46%

Parotid – 45%

Sublingual – 1.5%

Mechanical stimulationParotid – 58%

Submandibular – 33%

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Control of salivary secretion

Salivary glands differ from other glands of digestive system as they

are purely under nervous control; hormonal influence can alter its

composition but not its secretion.

Nerve supply to major glands is via sympathetic and

parasympathetic branches of Autonomic nervous system.

Sympathetic causes release of secretory proteins such as amylase

and vasoconstrictors.

Parasympathetic – are secretomotor and vasodilator. Nerves

innervate acinar cells, duct cells, blood vessels and myoepithelial

cells.

Controlled by three mechanisms:

Afferent pathway.

Central control.

Efferent pathway.

Afferent pathway

Includes :

- Resting flow

- Psychic flow

- Unconditional reflexes

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1) Resting flow

Under resting

conditions, there is a slow flow of saliva which keeps the mouth

moist and lubricates the mucous membrane and thus is very

important for health and well being of oral cavity.

The unstimulated

flow rate varies considerably during the day and is influenced by

these factors.

a. Circadian variation

Unstimulated flow peaks at appropriate 5pm with a minimum

flow during night. This variation is independent of eating and

sleeping behaviour.

b. Light and arousal

In dark unstimulated flow rates decrease. This is associated

with the effect of visual input in maintaining a state of

arousal.

c. Hydration

A loss of 8% of body water results in a cessation of saliva

flow. The resultant drying of oral cavity is a feature of thirst,

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although thirst and water intake are under hypothalamic

control and not dependent upon oral dryness.

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d. Exercise and stress

A dry mouth is a feature of ‘fright and flight’ response.

This is probably not a direct action of sympathetic supply to

the gland, but rather it is due to inhibitory influences on the

salivary nuclei arising from hypothalamus.

2) Psychic flow

A ‘mouthwatering’ sensation is a universal experience on the

anticipation or sight of food.

However, although the sensation is of a sudden flow of saliva into

the mouth, it has not proved possible to demonstrate a large increase

in flow rate in man arising from such psychic stimuli.

This is in contrast to the well-established conditioned reflex effect in

dogs as demonstrated by “Pavlov”, who noted that animal

associated ringing bells with meal times and thus salivated on

hearing of bells through food was not sight.

In man a slight increase in flow occurs on thinking or seeing food,

but is not related to amount of salivation.

It is suggested that salivation occurs due to a sudden awareness of

saliva present in mouth, or a momentary contraction of

myoepithelial elements.

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3) Unconditional Reflexes

The most important stimulation to salivation are those associated

with feeding, masticatory movements and taste stimuli.

a. Mastication

Chewing a flavourless bolus such as wax or chewing gum

base leads to an increase in saliva three-fold.

This is a reflex response : receptors in the muscles of

mastication, TMJ, PDL and mucosa detect the presence of

bolus and its mastication, and stimulate the salivary nuclei to

increase the parasympathetic secretomotor discharge.

b. Gustatory stimuli

The reflex effects of stimuli gives rise to a ten-fold increase in saliva

flow sour stimuli are most effective, followed by sweet, salt, bitter.

c. Other stimuli

The connections between salivary nuclei and the vomiting center in

medulla, have been demonstrated.

Just before vomiting increased salivation and nausea takes place as

an attempt to dilute or neutralize the irritant which gives rise to

nausea.

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Hypersalivation also occurs in pregnancy, in motor disturbances of

the orofacial musculature.

Central Control

The afferent stimuli are finally integrated in the cell bodies of

preganglionic secretomotor neurons. The cell bodies of the sympathetic

nervous system appear to lie in the lateral columns of first thoracic nerves.

The nuclei of the facial and glossopharyngeal nerve contain cell

bodies of parasympathetic system. The nucleus salivatorius consists of 2

components:

a. Nucleus salivation superior stimulates ipsilateral submandibular

gland.

b. Nucleus salivatorius inferior stimulates ipsilateral parotid gland.

Efferent Pathway

Pharmacological agents such as pilocarpine can cause salivation by

mimicking the action of transmitter substance such as acetyl and

noradrenaline.

Five possible effects in glands can occur as a result of nervous

stimulation a) initiation of secretory act, b) increase in blood flow to

maintain secretion, c) synthesis of new secretory products d) changes in

activity of duct cells, e) contraction of ME cells (myoepithelial cells).

32

Secretory activity is stimulated by sympathetic/parasympathetic or

both together.

These neurons innervate serous and mucous cells stimulate different

receptor site on effector cells and hence activate different secretory

pathways.

Formation of Saliva

Saliva is formed in two stages:

a. Primary secretion occurs in the acini.

b. Than modified as it passes through the ducts.

c. Primary secretion : formed actively by movement of Na+ and Cl-

ions into the lumen, creating an osmotic gradient which leads to the

passive movement of water. Before the fluid enters the duct, the Na+

ion are actively reabsorbed, Cl- ions move passively to maintain

electrical equilibrium and K+ and bicarbonate ions are secreted.

The macromolecules components like amylase, mucous,

glycoproteins are formed in acinar cells by endoplasmic reticulum which

are processed into Golgi apparatus and exported from the cells by

exocytosis.

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SECRETION OF SALIVA – MECHANISM

Signal Transduction

When a nerve to the salivary gland is stimulated, the transduction of

this signal is brought about first by the release of neurotransmitter

substances such as Nor-adrenalin (from sympathetic supply), acetyl

choline, substance P, vasointestinal peptide (from parasympathetic supply).

When a Neuro-transmitter arrives at a secretory cell membrane, it

binds to and activates receptor ( or ) on the external surface of cell

membrane. This activates an intermediate guanine neuclotide dependent

membrane protein known as ‘G’ protein which in turn activates a

regulating enzymes (phospholipase/adenyl cyclase) on the inner

cytoplasmic surface of the cell.

Thus, we have two pathways:

i) Phosplipase C pathway.

ii) Adenyl cyclase pathway.

PHOSPHOLIPASE C

The enzyme PLC is activated on binding of:

a. Acetyl choline at muscuramic receptors.

b. Substance p at peptidergic receptor or

c. Nor adrenaline at adrenergic receptors on cell membrane.

34

It controls the intracellular pathway leading to the secretion

of water and electrolytes.

The pathway is rather complex, phospholipase C is

responsible for hydrolyzing a membrane phospholipid (P1P2) to form

diaceyl glycerol and Inositol triphosphate (IP3).

IP3 stimulates release of calcium ions from the endoplasmic

reticulum. This increased cytoplasmic Ca2+ ion concentration causes the

opening of K+ channels in the acinar cell membrane which allow K+

ions to diffuse out of the cell down a concentration gradient established

by a Na+ K+ membrane pump.

The K+ ions now outside the cells stimulate 2 membrane

transport system.

i) Na, Cl, K co-transport system which permits the

coupled entry of three ions into the cell.

ii) Na/K exchange in the membranes of intercellular

canaliculi.

Thus the extrusion of K triggers the entry of Na+, Cl ions into

the cell and than allows Na+ to enter intercellular canaliculi.

Cl- ions diffuse across the luminal membrane via a Ca2+

sensitive channel. The arrival of Cl- ions trigger the movement of Na+

35

ions from the canaliculi across tight junction between cells to establish

the osmotic gradient for movement of water into lumen.

Adenyl Cyclase Pathway:

This pathway is activated when Nor-adrenalin binds to -

adrenergic acinar receptors or vasoactive intestinal peptide binds to

peptidergic receptors.

Activation leads to exocytosis of secretory protein.

Acetylcholene cause the intracellular formation of 3,5 cyclic

AMP from ATP.

GAMP activates a second enzyme, GAMP dependent protein

kinase which exists in four subunits when these sub-units bind with

GAMP, they liberate other two catalytic subunits to activate effector

proteins (Pr) by phosphorylation. This protein stimulates exocytosis.

Methods of collection of saliva

Individual methods

Parotid secretion

a. Carlson Crittenden cannula also known as Lashley canula.

b. Curby’s canula.

Submandibular and sublingual Schneyer’s device (1965).

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Minor salivary glands Dawe’s and Wood’s method

(1973).

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Whole saliva collection method:

Resting saliva

a. Draining method.

b. Spitting method.

c. Suction method.

d. Swab method.

Stimulated saliva

a. Masticatory method.

b. Gustatory method.

ROLE OF SALIVA IN ORAL DISEASE

a. Pellicle and plaque deposition

Both pellicle and plaque matrix contain protein predominantly

derived from saliva.

Pellicle formation is a physico-chemical process involving

selective adsorption of salivary glycoproteins, proteins from bacteria

(Glycosyl transferase and gingival crevicular fluid [IgG Albumin]) on

to the tooth surface.

Pellicle protects tooth against chemical and mechanical

insult.

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It acts as a substrate for colonization of bacteria which attach

by means of adhesive which bind to oligosaccharide group of mucous

glycoproteins other organisms appear to attach by means of glucans

synthesized by cell bound as well as pellicle bound glycol transferase

enzymes.

Plaque formation involves incorporation of salivary proteins

but their characterization is difficult because they are extensively

degraded in plaque.

Once the initial layer of bacteria attaches to the pellicle

surface, plaque build up can progress at a rapid rate depending on the

influence of self cleansing mechanisms, salivary proteins and

carbohydrates serve as substrate for metabolic activity of bacteria.

b. Plaque mineralization and calculus formation:

Salivary calcium and phosphate are the source of minerals for

calculus formation.

Saliva contains certain inhibitors of precipitation such as statherin

and proline-rich proteins which present excessive calcification in the

mouth.

But in plaque matrix these proteins cannot penetrate due to their

large molecular size or due to proteolysis by oral bacteria (as they

become unavailable). Thus they are unable to prevent seeding and

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growth of calcium phosphate crystal forming calculus. Deposits of

calculus is rapid and heaviest against orifice of salivary glands.

c. Saliva and Dental Caries

There is general agreement that saliva may be one of innate

mechanisms against dental caries. A number of potential mechanisms may

be involved:

i) Increased salivary flow, increase carbohydrate

and microbial clearance from oral cavity.

ii) Acid formed by carbohydrate fermentation are

reduced due to buffering action of bicarbonates.

iii) The rate of glycolysis could be increased by

salivary urea, bicarbonate or sialin, so that plaque carbohydrate

would be metabolized faster, thus reducing the duration of

enamel exposure to critical pH levels.

iv) Salivary components, could increase resistance to

acid decalcification due to its component fluoride activity.

v) Salivary components such as fluorides could

promote subsurface remineralization of carious lesion.

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d. Halitosis

Saliva plays a central role in oral malodor such formation has as its

basis bacterial putrefaction, degradation of protein and the resulting amio-

acids by micro-organisms. Saliva provides substrates that are readily

oxidized and in the process facilitate oxygen depletion, This favours the

decreased condition condusive to reduction of oderiferous volatiles.

CLINICAL CONSIDERATION

An understanding of anatomy, histology and

physiology of the salivary glands is essential for good dental practices.

Salivary glands occurs everywhere in the oral

cavity except in the anterior palatine region. Thus lesion of salivary

glands including tumours can occurs anywhere in the mouth.

Thus in a differential diagnosis, salivary gland

origin should be kept in mind always.

Salivary glands are subject to a number of

pathologic conditions such as:

i) Inflammation diseases – viral, bacterial or allergic

sialadenitis.

ii) Variety of benign and malignant tumours.

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iii) Autoimmune disease such as Sjogren’s syndrome –

decreased salivary secretion.

iv) Genetic disease – cystic fibrosis.

v) Mucocele.

Salivary glands may also be affected by a

variety of systemic and metabolic disturbances.

Salivary gland disorders may result in:

a. Decrease of saliva – hyposalivation.

b. Increase of saliva – hypersalivation.

c. Absence of saliva – xerostomia / aptylism.

a) Hyposalivation is seen in:

Fear and anxiety, Sjogren’s syndrome.

Fever.

Oral infections.

Following administration of drugs salivary

antihistamines, phenothiazine, atropine, barbiturates.

Mouth breathing.

Facial nerve paralysis i.e. Bell’s palsy.

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Hypersalivation / Sialorehea

Cancer.

Ill-fitting denture.

Drugs : sa-cholinergic, adrenergic and histamine like

drug.

In Parkinsonism disease.

Administration of iodides and Hg.

Xerostomia / Aptylism

Due to obstruction of salivary duct by calculi.

Atrophy of acini.

Reduction in gland size.

Congenital aplasia.

Radiation therapy – as much as 10-fold increase in

enamel and root caries (radiation caries) has been reported in patients

whose salivary glands have been irradiated to reduce tumour growth

(Driezen et al 1977).

Salivary Gland Dysfunction

The importance of saliva in oral health is dramatically revealed in

patients with salivary gland dysfunction, leading to a subjective complaint

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of xerostomia (dry mouth), which includes difficulty with speech and

mastication, a tendency towards mucositis often associated with candilal

infection, atrophic changes in the mucosa of the tongue, and a tendency to

rapid carious destruction as well as periodontal disease. Diagnosis of

salivary gland dysfunction can be made in the first instance by sialometry

(measurement of salivary flow), followed later by more sophisticated

radiological investigation.

The most common cause of salivary gland dysfunction is as a side

effect of drugs. The commonly associated drugs are:

Anorectics - Amphetamine

Anticholinergic - Atropine

Antidepressants - Amitryptyline

Antipsychotics - Phenothiazine

Antihypertensive - Clonidine

Antiparkinsonism - Benztropine

Other causes are associated with local/systemic

disease e.g. surgery / irradiation of the salivary glands, diabetes and

especially the autoimmune condition Sjogren’s syndrome.

Emotional states like anxiety and depression are also

well recognized as causes of reduced basal flow. In addition,

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xerostomia has also been reported in Parkinson’s disease, cystic

fibrosis, sarcoidosis, Mikulicz’s disease, hypertension etc.

Treatment – Is principally focused on the relief of symptoms by saliva

substitutes and where relevant the prevention of caries and periodontal

disease by intensive fluoride therapy and oral hygiene. If functional gland

tissue remains, can be stimulated by chewing non-cariogenic foods such as

raw vegetables or sugar free chewing gum (sorbitor).

Alternatively, parasympathomimetic drugs e.g.

- Pilocarpin.

- Bromhoxine (which is a mycolytic agent used in the

treatment of chronic bronchitis).

- Anethole-trithione (a newly developed agent) have been used

in mucous is selected patients under medical supervision.

Excessive salivary flow-sialorrhea or ptyalism is

most commonly seen following the insertion of new prosthodontics /

orthodontics appliances increased salivary flow rates may also occur in

cerebral palsy and epilepsy. Excessive salivation may be one of the

manifestations of primary herpetic and other infections but usually

disappares on resolution of the problem.

Age changes:

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In salivary gland, prominent in parotid gland

include:

a. Gradual replacement of parenchyma with fatty

tissue.

b. With advancing age patient c/o dryness of

mouth and increase in viscosity of saliva.

c. Flow of saliva is reduced in resting condition

but stimulated saliva is similar.

Conclusion

Determination of quantity and composition of the saliva of

sialochemistry is often of value in the diagnosis of glandular or systemic

disease.

References

1. Concise Medical Physiology – Choudhary.

2. Text book of human physiology by S.

Subramanyan and H.D. Singh.

3. Human physiology by E. Barbsky B. Whodaol

et al.

4. Physiological basis of medical practicer by

John B. West.

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5. Human Physiology by A.K. Jain.

6. Godron NikiForuk – Saliva and dental caries.

7. British dental journal 1992, 172 : 305 – Saliva :

its selection, composition and functions by W.H. Edgar.

8. Oral Histology and Embryology – Orban’s.

9. Text book of oral pathology – William G.

Shafers.

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SALIVA

Contents

2. Introduction

3. Salivary Glands

4. Saliva – Composition

5. Factors affecting composition

6. Properties of saliva

7. Function of saliva

8. Secretion of saliva- Control of salivary secretion

- Formation of saliva

- Mechanism of salivary secretion

9. Methods of collection of saliva

10.Role of saliva in oral disease

11.Applied physiology / Clinical consideration

12.Conclusion

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