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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.
2
 Serous cells form a thin watery secretion containing ptylin
[salivary α-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. Submandi
bular 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. Sublingua
l 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.
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 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.
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 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 α-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, α and β - 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) Nitrogen
Amino 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) Urea
Approximate 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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B) 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.
C) 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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C) 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.
D) 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.
E) 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.
15
F) 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.
G) 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.
17
 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.
18
 These include carbohydrates split off from glycoproteins, nitrites
and some unidentified substance of low molecular weight.
19
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,
21
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.
23
 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
24
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 stimulation
Submandibular – 46%
Parotid – 45%
Sublingual – 1.5%
Mechanical stimulation
Parotid – 58%
Submandibular – 33%
26
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,
28
although thirst and water intake are under hypothalamic
control and not dependent upon oral dryness.
29
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.
30
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.
33
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 (α or β) 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 β-
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).
36
 Minor salivary glands  Dawe’s and Wood’s method
(1973).
37
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.
38
 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
39
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.
40
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.
41
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.
42
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
43
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,
44
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:
45
 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.
46
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.
47
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
48

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Saliva (2)

  • 1. 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 1
  • 2. 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. 2
  • 3.  Serous cells form a thin watery secretion containing ptylin [salivary α-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
  • 4. 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. Submandi bular 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. Sublingua l 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. 4
  • 5.  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
  • 6.  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
  • 7.  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. 7
  • 8. 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 α-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 8
  • 9. 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 9
  • 10. 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, α and β - 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. 10
  • 11. 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) Nitrogen Amino acids – 9 type in parotid 12 in submandibular 18 in whole saliva at low concentration of about 0.1mg /100ml. 11
  • 12. 7) Urea Approximate 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. 12
  • 13.  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. 13
  • 14. B) 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. C) 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. 14
  • 15. C) 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. D) 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. E) 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. 15
  • 16. F) 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. G) 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 16
  • 17. - 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. 17
  • 18.  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. 18
  • 19.  These include carbohydrates split off from glycoproteins, nitrites and some unidentified substance of low molecular weight. 19
  • 20. 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 20
  • 21. 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, 21
  • 22. 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. 22
  • 23. 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. 23
  • 24.  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 24
  • 25. 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% 25
  • 26. 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 stimulation Submandibular – 46% Parotid – 45% Sublingual – 1.5% Mechanical stimulation Parotid – 58% Submandibular – 33% 26
  • 27. 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 27
  • 28. 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, 28
  • 29. although thirst and water intake are under hypothalamic control and not dependent upon oral dryness. 29
  • 30. 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. 30
  • 31. 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. 31
  • 32.  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
  • 33. 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. 33
  • 34. 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 (α or β) 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
  • 35.  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
  • 36. 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 β- 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). 36
  • 37.  Minor salivary glands  Dawe’s and Wood’s method (1973). 37
  • 38. 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. 38
  • 39.  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 39
  • 40. 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. 40
  • 41. 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. 41
  • 42. 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. 42
  • 43. 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 43
  • 44. 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, 44
  • 45. 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: 45
  • 46.  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. 46
  • 47. 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. 47
  • 48. 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 48