Salivary Glands and Saliva

Report
Salivary Glands and Saliva
Oral cavity
•
•
•
•
Entrance door of the gastrointestinal tract;
Beginning of the digestive function;
Provides security of the body against food and drink;
Prior to the adoption act two strong evolutionary verified sensory
systems:
– Appearance;
– Flavor;
• When they enter in the mouth triggers the umbrella of the immune
system:
– Cell-associated protection:
– Phagocytes and lymphocytes;
• Secretory immunity system mainly protects mucous with secretory
IgA.
Additional protection in the mouth
• Taste - taste buds;
• Tactile sense - proprioception ;
• Saliva.
Liquid oral environment
• This is the liquid into the oral cavity, washing
mucosa and dental enamel;
• It consists of:
– Saliva;
– Gingival sulcus fluid;
– Peeling epithelial cells and their degradation
products;
– Microorganisms and their products.
Saliva
• Saliva is a complex fluid that in health almost
continually bathes the parts of the tooth
exposed within the oral cavity;
• Consequently, saliva represents the
immediate environment of the tooth.
Production
• Saliva is produced by three paired sets of
major salivary glands:
– Parotid;
– Submandibular;
– Sublingual glands;
– and by the many minor salivary glands scattered
throughout the oral cavity.
Account of the composition
• A precise account of the composition of saliva
is difficult because not only are the secretions
of each of the major and minor salivary glands
is different, but their volume may vary at any
given time.
• In recognition of this variability, the term
mixed saliva has been used to describe the
fluid of the oral cavity.
Saliva has several functions
•
•
•
•
•
•
Saliva moistens the mouth;
Facilitates speech;
Lubricates food;
Helps with taste by acting as a solvent for food molecules;
Saliva also contains a digestive enzyme (amylase);
Saliva dilutes noxious material mistakenly taken into the
mouth;
• Cleanses the mouth;
• Furthermore, it contains antibodies and antimicrobial
substances;
• Its buffering capacity plays an important role in
maintaining the pH of the oral cavity.
There are three major pairs of salivary glands that differ
in the type of secretion they produce:
• parotid glands - produce a serous, watery
secretion.
• submaxillary (mandibular) glands - produce a
mixed serous and mucous secretion.
• sublingual glands - secrete a saliva that is
predominantly mucous in character.
Three pairs of major salivary glands
• They are located outside the oral cavity, with
extended duct systems through which the
gland secretions reach the mouth.
Numerous
smaller minor salivary glands
• They are located in
various parts of the oral
cavity
–
–
–
–
–
the labial,
lingual,
palatal, buccal,
glossopalatine,
and retromolar glands—
• They are typically located
in the submucosal layer
with short ducts opening
directly onto the mucosal
surface.
- Minor mucous salivary gland, located in the
submucosa below the epithelium of the oral cavity.
Composition of Saliva
PARAMETER
• Volume
• Electrolytes
CHARACTERISTICS
• 600-1000 mL/day
• Na+, K+, Cl, HCO3−, Ca2+, Mg2+,
HPO42−, and F–
• Secretory proteins/Peptides
• Amylase, proline-rich proteins,
mucins,histatin, cystatin, peroxidase,
lysozyme, lactoferrin, defensins, and
cathelicidin-LL37
• Immunoglobulins
• Secretory immunoglobulin A;
immunoglobulins G and M;
• Small organic
• Glucose, amino acids, urea, uric acid,
and lipid molecule
• Other components
• Epidermal growth factor, insulin, cyclic
adenosine monophosphate–binding
proteins, and serum albumin
FLOW RATE
(ML/MIN)
WHOLE
PAROTID
SUBMANDIBULAR
Resting
0.2-0.4
0.04
0.1
Stimulated
2.0-5.0
1.0-2.0
0.8
pH
6.7-7.4
6.0-7.8
• The basic secretory units of salivary glands are
clusters of cells called an acini;
• These cells secrete a fluid that contains water,
electrolytes, mucus and enzymes, all of which
flow out of the acinus into collecting ducts.
Acinar epithelial cells
• Two basic types of acinar epithelial cells exist:
– serous cells, which secrete a watery fluid, essentially
devoid of mucus.
– mucous cells, which produce a very mucus-rich
secretion.
• Small collecting ducts within salivary glands lead
into larger ducts, eventually forming a single large
duct that empties into the oral cavity.
Superficial
temporal vessels
Transverse facial artery
Parotid duct
Parotid
gland
Branches of facial nerve
Great
auricular
nerve
Facial artery
Anterior
facial vein
Submandibular gland
Masseter muscle
Sternocleidomastoid muscle
The parotid gland is the largest salivary
gland.
• The superficial portion of the
parotid gland is located
subcutaneously, in front of the
external ear, and its deeper
portion lies behind the ramus of
the mandible.
• The parotid gland is associated
intimately with peripheral
branches of the facial nerve;
• The parotid gland receives its
blood supply from branches of
the external carotid artery as
they pass through the gland.
The duct
(Stensen’s duct) of
the parotid gland
runs forward
across the
masseter muscle,
turns inward at
the anterior
border of the
masseter, and
opens into the
oral cavity at a
papilla opposite
the maxillary
second molar.
Submandibular duct
Tongue
Sublingual ducts
Sublingual gland
Submandibular gland
The major glands are bilaterally paired and
have long ducts that convey their saliva to the
oral cavity.
• The submandibular gland is
situated in the posterior part of the
floor of the mouth, adjacent to the
medial aspect of the mandible and
wrapping around the posterior
border of the mylohyoid muscle;
• The excretory duct (Wharton’s
duct) of the submandibular gland
runs forward above the mylohyoid
muscle and opens into the mouth
beneath the tongue at the
sublingual caruncle, lateral to the
lingual frenum.
• The submandibular gland receives
its blood supply from the facial and
lingual arteries.
• The parasympathetic nerve supply
is derived mainly from the facial
nerve, reaching the gland through
the lingual nerve and
submandibular ganglion.
Submandibular
gland
Submandibular
gland
• The sublingual gland is the smallest of the
paired major salivary glands;
• The gland is located in the anterior part
of the floor of the mouth between the
mucosa and the mylohyoid muscle;
• The secretions of the sublingual gland
enter the oral cavity through a series of
small ducts (ducts of Rivinus) opening
along the sublingual fold and often
through a larger duct (Bartholin’s duct)
that opens with the submandibular duct
at the sublingual caruncle.
• The sublingual gland receives its blood
supply from the sublingual and submental
arteries.
• The facial nerve provides the
parasympathetic innervation of the
sublingual gland, also via the lingual
nerve and submandibular duct at the
sublingual caruncle
Sublingual
gland
Sublingual gland
The minor salivary glands
• They are estimated to number
between 600 and 1000, exist as
small, discrete aggregates of
secretory tissue present in the
submucosa throughout most of
the oral cavity.
• The only places they are not found
are the gingiva and the anterior
part of the hard palate.
• They are predominantly mucous
glands, except for the lingual
serous glands (Ebner’s glands) that
are located in the tongue and
open into the troughs surrounding
the circumvallate papillae on the
dorsum of the tongue and at the
foliate papillae on the sides of the
tongue.
Salivary gland showing its lobular
organization.
Lobule
Connective
tissue
septum
• Thicker partitions of
connective tissue
(septa), continuous
with the capsule and
within which run the
nerves and blood
vessels supplying the
gland, invest the
excretory ducts and
divide the gland into
lobes and lobules.
A salivary gland may be likened to a
bunch of grapes.
• Each “grape” is the acinus or
terminal secretory unit, which
is a mass of secretory cells
surrounding a central space;
• The spaces of the acini open
into ducts running through the
gland that are called
successively the intercalated,
striated, and excretory ducts
analogous to the stalks and
stems of a bunch of grapes.
• These ducts are more than
passive conduits, however
their lining cells have a
function in determining the
final composition of saliva.
• The ducts and acini constitute
the parenchyma of the stroma
carrying blood vessels and
nerves.
• This connective tissue
supports each individual
acinus and divides the gland
into a series of lobes o lobules,
finally encapsulating it.
Diagrammatic illustration of the ductal system of a
salivary gland.
Main
excretory duct
Excretory duct
Striated duct
Intercalated duct
Canaliculus
between cells
Tubular secretory
end piece
Spherical secretory and piece
• The main excretory duct, which
empties into the oral cavity, divides
into progressively smaller interlobar
and interlobular excretory ducts that
enter the lobes and lobules of the
gland.
• The predominant intralobular ductal
component is the striated duct, which
plays a major role in modification of
the primary saliva produced by the
secretory end pieces.
• Connecting the striated ducts to the
secretory end pieces are intercalated
ducts, which branch once or twice
before joining individual end pieces.
• The lumen of the end piece is
continuous with that of the
intercalated duct.
Intercellular canaliculi
Lu
N
• In some glands, small
extensions of the lumen,
intercellular canaliculi, are
found between adjacent
secretory cells;
• These intercellular
canaliculi may extend
almost to the base of the
secretory cells and serve to
increase the size of the
secretory (luminal) surface
of the cells.
Acini - the basic histologic structure of
the major salivary glands is similar
• Acini in the parotid glands
are almost exclusively of
the serous type, while
those in the sublingual
glands are predominantly
mucous cells.
• In the submaxillary
glands, it is common to
observe acini composed
of both serous and
mucous epithelial cells.
SECRETORY CELLS
• Serous and mucous cells differ in structure
and in the types of macromolecular
components that they produce and secrete.
Serous cells
• In general, serous cells produce
proteins and glycoproteins
(proteins modified by the
addition of sugar residues
[glycosylation]), many of which
have well-defined enzymatic,
antimicrobial, calciumbinding,
or other activities.
• Typically, serous glycoproteins
have N-linked (bound to the βamide of asparagine)
oligosaccharide side chains.
Serous cell
Intercellular canaliculi are seen in
longitudinal (right) and cross section (left).
• Secretory end pieces that are
composed of serous cells are
typically spherical and consist of 8
to 12 cells surrounding a central
lumen;
• The cells are pyramidal, with a
broad base adjacent to the
connective tissue stroma and a
narrow apex forming part of the
lumen of the end piece.
• The lumen usually has fingerlike
extensions located between
adjacent cells called intercellular
canaliculi that increase the size of
the luminal surface of the cells.
• The spherical nuclei are located
basally, and occasionally,
binucleated cells are seen.
• Numerous secretory granules, in
which the macromolecular
components of saliva are stored,
are present in the apical cytoplasm
Mucous cells
• The main products of
mucous cells are mucins,
which have a protein core
(apomucin) that is
organized into specific
domains and is highly
substituted with sugar
residues.
• Mucins are therefore also
glycoproteins, but they
differ from most serous cell
glycoproteins in the
structure of the protein
core.
• Mucins function mainly to
lubricate and form a barrier
on surfaces and to bind and
aggregate microorganisms.
• Mucous cells secrete few, if
any, other macromolecular
components.
Mucous Cells
Lu
The nuclei (arrowheads) are flattened and
compressed against the basal surfaces of the cells
The lumina (Lu) are large compared with those
of serous acini.
• Secretory end pieces
that are composed of
mucous cells typically
have a tubular
configuration;
• When cut in cross
section, these tubules
appear as round profiles
with mucous cells
surrounding a central
lumen.
Mucous cell.
• The most prominent
feature of mucous cells is
the accumulation in the
apical cytoplasm of large
amounts of secretory
product (mucus), which
compresses the nucleus an
endoplasmic reticulum
against the basal cell
membrane.
Distinction between serous cells and
mucous cells
• In recent years the distinction between serous
cells and mucous cells has become somewhat
blurred.
• Serous cells of some salivary glands are known
to produce certain type of mucins, and some
mucous cells are thought to produce certain
nonglycosylated proteins.
Submandibular gland
• Contain mucous cells
coated with serous
cells called – crescent;
• Serous fluid passes
down through the
channels between
terminal mucinous
cells to the lumen of
the alveoli.
Ducts
• Within the ducts, the
composition of the
secretion is altered.
• Much of the sodium is
actively reabsorbed,
potassium is secreted,
and large quantities of
bicarbonate ions are
secreted.
Striated duct
DUCTS
• The ductal system of salivary
glands is a varied network of
tubules that progressively
increase in diameter, beginning at
the secretory end pieces and
extending to the oral cavity;
• The three classes of ducts are:
– intercalated,
– striated,
– and excretory, each with differing
structure and function.
• The ductal system is more than
just a simple conduit for the
passage of saliva;
• It actively participates in the
production and modification of
saliva.
Excretory duct
striated,
intercalated
• The primary saliva produced by
the secretory end pieces passes
first through the intercalated
ducts;
• The first cells of the
intercalated duct are directly
adjacent to the secretory cells
of the end piece, and the lumen
of the end piece is continuous
with the lumen of the
intercalated duct.
• The intercalated ducts are lined
by a simple cuboidal
epithelium,and myoepithelial
cell bodies and their processes.
• The intercalated ducts
contribute macromolecular
components, which are stored
in their secretory granules, to
the saliva.
• These components include
lysozyme and lactoferrin;
Intercalated Ducts
• The intercalated duct cells have
centrally placed nuclei and a
small amount of cytoplasm
containing some rough
endoplasmic reticulum and a
small Golgi complex
• A few small secretory granules
may be found in the apical
cytoplasm, especially in cells
located near the end pieces.
• The apical cell surface has a few
short microvilli projecting into
the lumen;
• The lateral surfaces are joined by
apical junctional complexes and
scattered desmosomes and gap
junctions and have folded
processes that interdigitate with
similar processes of adjacent
cells.
Intercalated duct
cell
Striated Ducts
• The striated ducts, which
receive the primary saliva
from the intercalated
ducts, constitute the
largest portion of the
duct system.
• These ducts are the main
ductal component located
within the lobules of the
gland, that is, intralobular
striated ducts
Lu
SD
• The ducts have large
lumina (Lu) and are
lined by a pale-staining,
simple columnar
epithelial cells with
centrally placed nuclei
and faint basal
striations.
Striated duct
cells
• The basal striations of the duct cells
are result from the presence of
numerous elongated mitochondria,
separated by highly infolded and
interdigitated basolateral cell
membranes;
• The apical cytoplasm may contain small
secretory granules and electron-lucent
vesicles;
• The granules contain kallikrein and
perhaps other secretory proteins;
• The presence of vesicles suggests that
the cells may participate in endocytosis
of substances from the lumen;
• The duct cells contain numerous
lysosomes and deposits of glycogen
frequently are present in the
perinuclear cytoplasm.
• Adjacent cells are joined by tight
junctions and junctional complexes but
lack gap junctions.
Excretory Ducts
• The excretory ducts are
located in the connective
tissue septa between the
lobules of the gland, that is, in
an extralobular or interlobular
location.
• These ducts are larger in
diameter than striated ducts
and typically have a
pseudostratified epithelium
with columnar cells extending
from the basal lamina to the
ductal lumen and small basal
cells that sit on the basal
lamina but do not reach the
lumen.
Larger excretory duct
• As the smaller ducts join
to form larger excretory
ducts, the number of
basal cells increases, and
scattered mucous cells
may be present;
• A large excretory duct is
surrounded by dense
connective tissue.
• The pseudostratified
epithelium contains
several mucous goblet
cells (arrowheads).
FORMATION AND SECRETION OF
SALIVA
• The formation of saliva occurs in
two stages.
• In the first stage, cells of the
secretory end pieces and
intercalated ducts produce
primary saliva, which is an isotonic
fluid containing most of the
organic components and all of the
water that is secreted by the
salivary glands.
• In the second stage, the primary
saliva is modified as it passes
through the striated and excretory
ducts, mainly by reabsorption and
secretion of electrolytes.
• The final saliva that reaches the
oral cavity is hypotonic.
DUCTAL MODIFICATION OF SALIVA
Interstitum
Na+
H+ K+ Cl−
Na+
ATP
K+
Striated duct cell
Na+
Cl−
Na+
Cl−
H+
H2O
HCO3−
Lumen
TJ
• An important function of the
striated and excretory ducts is the
modification of the primary saliva
produced by the end pieces and
intercalated ducts occurring
principally through reabsorption
and secretion of electrolytes.
• The luminal and basolateral
membranes have abundant
transporters that function to
produce a net reabsorption of Na+
and Cl– resulting in the formation
of hypotonic final saliva.
• The ducts also secrete K+ and
HCO3 but little if any secretion or
reabsorption of water occurs in
the striated and excretory ducts.
DUCTAL
MODIFICATION OF
SALIVA
Interstitum
•
•
Na+
H+ K+ Cl−
Na+
•
ATP
•
K+
Striated duct cell
Na+
Cl−
Na+
Cl−
H+
H2O
HCO3−
Lumen
•
TJ
•
Release of water by the cells of the
secretory end pieces is regulated
principally by the parasympathetic
innervation.
The next step – Ca2+ is released from
intracellular stores.
The increased Ca2+ concentration opens
Cl– channels in the apical cell membrane
and K+ channels in the basolateral
membrane.
The apical Cl– efflux draws extracellular
Na+ into the lumen,through the tight
junctions, to balance the electrochemical
gradient.
It results in the movement of water into
the lumen via water channels in the apical
membrane and through the tight
junctions.
Thus fluid secretion by the salivary glands
is driven by the active transport of
electrolytes.
Electrolyte composition of saliva and
salivary flow rate
• The final electrolyte composition of saliva varies, depending on the
salivary flow rate.
• At high flow rates, saliva is in contact with the ductal epithelium for
a shorter time, and Na+ and Cl– concentrations rise and the K+
concentration decreases.
• At low flow rates the electrolyte concentrations change in the
opposite direction.
• The HCO3− concentration, however, increases with increasing flow
rates, reflecting the increased secretion of HCO3− by the acinar cells
to drive fluid secretion.
• Electrolyte reabsorption and secretion by the striated and excretory
ducts is regulated by the autonomic nervous system and by
mineralocorticoids produced by the adrenal cortex.
Macromolecular Components
• The cells of the secretory end pieces have abundant rough
endoplasmic reticula and a large Golgi complex, and they store
their products in membrane-bound granules in the apical
cytoplasm.
• The secretory granules are stored in the apical cytoplasm until
the cell receives an appropriate secretory stimulus.
• The granule membranes fuse with the cell membrane at the
apical (luminal) surface, and the contents are released into the
lumen by the process of exocytosis;
• The fusion of the granule membrane with the cell membrane is
mediated by the formation of a protein complex involving
proteins of the granule membrane, proteins of the cell
membrane, and proteins in the cytoplasm.
• Following release of the granule content, the granule
membrane is internalized by the cell as small vesicles, which
may be recycled or degraded.
MYOEPITHELIAL
CELLS
• Myoepithelial cells are
contractile cells
associated with the
secretory end pieces and
intercalated ducts of the
salivary glands;
• These cells are located
between the basal lamina
and the secretory or duct
cells and are joined to the
cells by desmosomes;
• Myoepithelial cells have
many similarities to
smooth muscle cells but
are derived from
epithelium.
MYOEPITHELIAL CELLS
Intercalated
duct
Basal lamina
Secretory
end piece
Myoepithelial
cell
Secretory cell
Myoepithelial cells
• Myoepithelial cells
present around the
secretory end pieces have
a stellate shape;
• Numerous branching
processes extend from
the cell body to surround
and embrace the end
piece ;
• The processes are filled
with filaments of actin
and soluble myosin.
Control of the secretion
• Secretion of saliva is under control of the
autonomic nervous system, which controls both
the volume and type of saliva secreted.
• This is actually fairly interesting: a dog fed dry
dog food produces saliva that is predominantly
serous, while dogs on a meat diet secrete saliva
with much more mucus.
• Parasympathetic stimulation from the brain, as
was well demonstrated by Ivan Pavlov, results in
greatly enhanced secretion, as well as increased
blood flow to the salivary glands.
• Potent stimuli for increased salivation include
the presence of food or irritating substances in
the mouth, and thoughts of or the smell of
food.
• Knowing that salivation is controlled by the
brain will also help explain why many psychic
stimuli also induce excessive salivation - for
example, why some dogs salivate all over the
house when it's thundering.
Composition of the saliva
organic elements
–
–
–
–
–
–
–
–
–
–
–
proteins;
amino acids;
enzymes;
immunoglobulins;
glucose;
lactates;
citrate;
ammonia;
urea;
creatinine;
Cholesterol.
inorganic elements
•
•
•
•
•
•
•
•
•
calcium;
phosphorus;
sodium;
potassium;
magnesium;
fluorine;
chlorides;
bicarbonates;
Phosphates.
Saliva
• Human saliva is 99.5% water, while the other
0.5% consists of electrolytes,
mucus, glycoproteins, enzymes,
and antibacterial compounds such as
secretory IgA and lysozyme.
Electrolytes:
•
•
•
•
•
•
•
•
2–21 mmol/L sodium (lower than blood plasma);
10–36 mmol/L potassium (higher than plasma);
1.2–2.8 mmol/L calcium (similar to plasma);
0.08–0.5 mmol/L magnesium;
5–40 mmol/L chloride (lower than plasma);
25 mmol/L bicarbonate (higher than plasma);
1.4–39 mmol/L phosphate;
Iodine - usually higher than plasma, but
dependent variable according to dietary iodine
intake.
Organic components of Saliva
• Enzymes:
– Amylase – converting starch into glucose and
fructose;
– Lyzozymes – prevents bacterial infection in the
mouth;
– Histatins – prevents fungal infections;
– Secretory IgA – immunity mediator.
Mucus
• Mucus in saliva mainly consists
of mucopolysaccharides and glycoproteins;
Glycoprotein (Mucins)
•
•
•
•
Lubricant;
Types – MG1 and MG2;
Polypeptide chain that stick together;
Low solubility, high viscosity, strong
adhesiveness;
• Aids in mastication, speech, swallowing by
lubrication.
Glycoprotein (Mucins)
• Preserve mucosal integrity;
• Protective barrier by excessive wear;
• Antibacterial action by selective adhesion of
microbes to oral tissue surface;
• Barrier against acid penetration.
MG1
• High molecular wt;
• Adsorbs tightly to the tooth surface – enamel;
• Pellicle formation – protection from acid
challenges;
• High in caries susceptible patients.
MG2
• Low molecular wt;
• Binds to enamel but get displaces easily;
• Promotes the aggregation and clearance of
oral bacteria (S. mutans);
• High in caries resistant cases.
Antibacterial compounds and growth
factor
• Antibacterial compounds
(thiocyanate, hydrogen peroxide, and
secretory immunoglobulin A);
• Epidermal growth factor or EGF.
Antimicrobial enzymes that kill
bacteria
•
•
•
•
Lysozyme;
Salivary lactoperoxidase;
Lactoferrin;
Immunoglobulin A.
There are three major enzymes found
in saliva:
• α-amylase or ptyalin, secreted by the acinar cells
of the parotid and submandibular glands, starts
the digestion of starch before the food is even
swallowed. It has a pH optima of 7.4;
• Lingual lipase is secreted by the acinar cells of
the sublingual gland, has a pH optimum ~4.0 so it
is not activated until entering the acidic
environment of the stomach;
• Kallikrein is a vasodilator. It is secreted by the
acinar cells of all three major salivary glands.
ά-Amylase
• Present in parotid saliva at conc. of 60-120
mg/100ml; in submandibular saliva at approx.
25 mg/100 ml;
• Very little amylase activity in the sublingual
and minor glandular secretions;
• 6 isoenzyme forms exist. Alpha-amylase is Ca
dependent and readily inactivated by a pH of
4 or less’;
• The enzyme hydrolyses the alpha 1:4
glycosidic bond between glucose units in the
polysaccharide chain of starch.
Enzymes
• Lactoperoxidase – stimulation of minor
salivary glands;
• RNA and DNA – cellular maintenance;
• Lipase – iniciates digestion of fat;
Lyzozyme
• An antibacterial enzymes;
• The mean concentration in whole saliva:
– Resting – 22 mg/100ml;
– Stimulated – 11 mg/100 ml;
• Lyzozyme acts on the B(1-4) bond between Nacetyl-muramic acid and N-acetyl glucosamin in
the Gram+ bacterial cell wall component;
• Lyzozyme may also be bactericidal;
• Inhibits mucosal colonization by microbial
aggregation.
Enzymes
• Kallikrein
– Splits serum beta-globulin into bradykinin;
– Functional vasodilatation to supply an actively
secreting gland;
• Dextranases
– Increased whole saliva dextranase levels may be
associated with impaired oral hygiene and over
consumption of sucrose and related fermentable
carbohydrates which support the growth of
organisms producing dextranases.
Invertases
• High invertase activity is based on the
involvement of several enzymes chiefly
derived from dental plaque S. Mutans and S.
Salivarius;
• High invertase activity – consume high sucrose
and it usually parallels with high lactobacillus
and streptococcus count of plaque.
Prolin-rich proteins
• Proline-rich proteins have function
in enamel formation, Ca2+-binding, microbe
killing and lubrication.
Minor enzymes
• Include:
– salivary acid phosphatases A+B;
– N-acetyl-alanine amidase;
– NAD(P)H dehydrogenase;
– superoxide dismutase;
– transferase;
– aldehyde dehydrogenase;
– glucose-6-phosphate isomerase,
– and tissue kallikrein (function unknown).
Cells:
• Possibly as many as 8 million human and 500
million bacterial cells per mL;
• The presence of bacterial products (small
organic acids, amines, and thiols) causes saliva
to sometimes exhibit foul odor.
Cellular Composition
• The cellular composition consists of:
– Epithelial cells;
– Neutrophils;
– Lymphocytes;
– Bacterial flora.
Opiorphin
• Opiorphin, a newly researched pain-killing
substance found in human saliva
Haptocorrin
• a protein which binds to Vitamin B12 to
protect it against degradation in the stomach,
before it binds to Intrinsic Factor
Individual Hydration
• The degree of individual hydration is the most
important factor that interferes in salivary
secretion;
• When the body water content is reduced by
8%, salivary flow virtually diminishes to zero,
whereas hyperhydration causes an increase in
salivary flow.
• During dehydration, the salivary glands cease
secretion to conserve water.
Factors Influencing Salivary Flow and
Composition
• Several factors may influence salivary flow and
its composition.
• As a result, these vary greatly among
individuals and in the same individual under
different circumstances.
Body Posture, Lighting, and Smoking
• Patients kept standing up or lying down present
higher and lower SF, respectively, than seated
patients.
• There is a decrease of 30% to 40% in SF of people
that are blindfolded or in the dark. However, the
flow is not less in blind people, when compared
with people with normal vision.
• This suggests that blind people adapt to the lack
of light that enters through the eyes.
• Olfactive stimulation and smoking cause a
temporary increase in unstimulated SF.
The Circadian and Circannual Cycle
• SF attains its peak at the end of the afternoon but goes
down to almost zero during sleep.
• Salivary composition is not constant and is related to the
Circadian cycle.
• The concentration of total proteins attains its peak at the
end of the afternoon, while the peak production levels of
sodium and chloride occur at the beginning of the morning.
• According to Edgar, the circannual rhythm also influences
salivar secretion.
• In the summer lower volumes of salivary flows from the
parotid gland, while in the winter there are peak volumes
of secretion.
Thinking of Food and Visual
Stimulation
• Thinking of food or looking at food are weak
salivation stimuli in humans.
• It may seem that people salivate simply
because of thinking of food, but in reality they
become more conscious of the saliva in the
floor of the mouth between swallows.
• Some researchers observed a small increase in
SF in the face of visual stimuli, while others
observed no effect whatever.
Medications
• Many classes of drugs, particularly those that
have anticholinergic action (antidepressants,
antipsychotics, antihistaminics, and
antihypertensives) may cause reduction in SF
and alter its composition.
Regular Stimulation of Salivary Flow
• There is evidence regular stimulation of SF
with the use of chewing gum leads to an
increase in stimulated SF.
Size of Salivary Glands and Body
Weight
• Stimulated SF is directly related to the size of
the salivary gland, contrary to unstimulated SF
which does not depend on its size;
• Unstimulated SF appears to be independent of
body weight;
• On the other hand, obese boys presents
significantly lower salivary amylase
concentration in comparison with controls.
Salivary Flow Index
• The main factor affecting salivary composition is the flow
index which varies in accordance with the type, intensity,
and duration of the stimulus.
• As the SF increases, the concentrations of total protein,
sodium, calcium, chloride, and bicarbonate as well as the
pH increases to various levels, whereas the concentrations
of inorganic phosphate and magnesium diminish.
• Mechanical or chemical stimulus is associated with
increased salivary secretion.
• The action of chewing something tasteless itself stimulates
salivation but to a lesser degree than the tasty stimulation
caused by citric acid.
• Acid substances are considered potent gustatory stimuli.
Physical Exercise
• Physical exercise can alter secretion and induces
changes in various salivary components, such as:
– immunoglobulins, hormones, lactate, proteins, and
electrolytes.
• In addition to the determined intensity of the
exercise, there is a clear rise in salivary levels of
α-amylase and electrolytes (especially Na+).
• During physical activities sympathetic stimulation
appears to be strong enough to diminish or
inhibit salivary secretion.
Systemic Diseases and Nutrition
• In some chronic diseases such as: pancreatitis,
diabetes mellitus, renal insufficiency, anorexia,
bulimia, and celiac disease, the amylase level is
high;
• Alterations in the psycho-emotional state may
alter the biochemical composition of saliva.
• Depression is accompanied by diminished salivary
proteins.
• Nutritional deficiencies may also influence
salivary function and composition.
Fasting and Nausea
• Although short-term fasting reduces SF it does
not lead to hyposalivation, and the flow is
restored to normal values immediately after
the fasting period ends.
• Stimulated SF increases when preceded by
gustatory stimulation in less than one hour
before saliva collection.
• Saliva secretion increases before and during
vomiting
Age
• Despite numerous studies on salivary
secretion the effect of aging on SF remains
obscure;
• However, functional studies among healthy
individuals indicate aging itself does not
necessarily lead to diminished capacity to
produce saliva.
Gender
• The differences in salivary secretion between
men and women have been attributed to two
theories: women present smaller salivary
glands in comparison with men and the
female hormonal pattern may contribute to
diminished salivary secretion.
Contributions of Different Salivary
Glands
• Other factors that influence total salivary
composition are the relative contribution of the
different salivary glands and the type of
secretion.
• The percentage of contribution by the glands
during unstimulated SF is as follows:
–
–
–
–
20% by the parotid glands;
65%-70% submandibular glands;
7% to 8% sublingual glands;
<10% by the minor salivary glands.
Glands contribution of Stimulated SF
• When SF is stimulated, there is an alteration in
the percentage of contribution of each gland
with the parotids contributing over 50% of the
total salivary secretion.
Sales
<10%
minor
20%
parotid
7-8%
sublingu
al
65-70%
Subman
dibular
Unstimulated flow
• Resting salivary flow – no external stimulus:
– Typically – 0.2ml – 0.3ml per min;
– Less then 0.1 ml per minute means the person has
hyposalivation;
– Hyposalivation – non produsing enough saliva.
Stimulated saliva
• Response to the stimulus, usually taste,
shewing, or medication, at mealtime;
– Tipically – 1,5 ml – 2,0 ml per minute;
– Les then 0,7 ml per minute is considered
hyposalivation
Stimulated Salivary Flow
• Saliva passes through the salivary duct very
rapidly;
– It impedes the exchange of sodium and chloride
for potassium and bicarbonate;
Unstimulated Salivary Flow
• Has high content of potassium and
bicarbonate;
– The quality of unstimulated saliva will change
when flow increases because of a stimulus
(chewing gum, thinking about lemons, looking at a
food you crave).
Average amount of saliva
• The average person produces approximately
• 0.5 to9 1,5 L per day.
Secretory leukocyte proteinase
inhibitor (SLPI)
• Proteinase inhibitory property;
• Antimicrobial and antiviral;
• Important role in wound healing
Tissue inhibitors of metalloproteinase
• Remodeling of extracellular matrix in
inflamation;
• Growth promoting activity;
• Stimulation of osteclastic bone resorption.
Immunoglobulins
• Secretory IgA is the predominant immunoglobulin –
20mg/100ml;
• 90% of the total parotid IgA;
• 85% of whole saliva IgA;
• 30-35% of which is derived from minor glands, IgG
(1.5mg/100ml)& IgM (0,2mg/100ml);
• Secretory IgA is syntesized by plasma cells within the
glands in addition to the mucosal epithelial cells;
• Secretory IgA – non-lymphoid-derived glycoprotein
designated as the secretory component.
Immunoglobulins
• This IgA exhibits 3 possible functions:
– Inhibition of bacterial colonization ,probably by
agglutination;
– Binding to specific bacterial antigens involved with
adherence;
– Affecting specific enzymes essential for bacterial
metabolism.
Strucural features of salivary proteins
•
•
•
•
Proline – rich proteins;
Statherins;
Cystatins;
Histatins
Prolin-rich protein (Glycoprotein)
•
•
•
•
•
70% of total secretory proteins;
Acidic (Large), Basic (Small);
Present in enamel pellicle;
Larger PRP promote bacterial attachment;
Smaler reduces the initial bacterial
attachment;
• Actinomyces viscosus, S. mutans, S.Gordoni.
Staterin (Phosphoprotein)
• Is a small phosphoprotein (12 000 daltons)
relatively rich in tyrosine and proline which
has the property of inhibiting Hydroxyapatite
crystal growth;
• Potential precursor of enamel pellicle;
• Inhibit spontaneous precipitation of Ca,
phosphate in saturated solution.
Cystatins
• Several cystatins are phosphorylated and bind
to HA;
• Inhibit crystal growth of Ca Phosphate salt.
Histatin
•
•
•
•
•
Parotid and Submandibular saliva;
Bind to HA, precursor of acquired pellicle;
Kills C. Albican in yeast form and mycelia form;
Bacteriostatic;
Inhibit hem agglutination and thereby
colonization.
Other organic compounds
• Free Amino acids – (Below 0,1mg/100ml)
– Too low to provide nutrient source for bacterial
growth;
• Urea (12-20 mg/100ml)
– Hydrolized by bacteria with the release of
Ammonia – Rise in pH;
• Glucose (0,5-1,0mg/100ml)
– Too low for bacterial growth;
– Increase in DM
Lipids
– Cholesterol, fatty acid glycerides, phospholipids;
– Corticosteroids;
– Cortisol and cortisine;
– 1-2 mg/100ml
• Vitamins
– Water soluble vitamins.
Salivary Amylase Alpha Antibody
Functions of Saliva
Protection
EFFECT
• Clearance
• Lubrication
• Thermal/chemical insulation
ACTIVE CONSTITUENTS
• Water
• Mucins, glycoproteins
• Mucins
• Pellicle formation
• Proteins, glycoproteins,
mucins;
• Basic proline-rich proteins,
histatins
• Tannin binding
PROTECTION
• Saliva protects the oral cavity in many ways.
• The fluid nature of saliva provides a washing action
that flushes away non-adherent bacteria and other
debris.
• In particular, the clearance of sugars from the mouth
limits their availability to acidogenic plaque
microorganisms.
• The mucins and other glycoproteins provide
lubrication, preventing the oral tissues from adhering
to one another and allowing them to slide easily over
one another.
• The mucins also form a barrier against noxious stimuli,
microbial toxins, and minor trauma.
Lubrication
• Coat the food, the oral soft and hard tissues;
• Allows food to travel through the digestive
system surfaces with minimal infection;
• Without appropriate lubrication, food is
retained and impacted around the teeth;
• Both, mg1 and mg2 can provide fluid layers
with high-film strength.
Maintenance of mucous membrane
integrity
• Salivary mucins possess rheological properties
that include low solubility, high viscosity,
elasticity, and adhesiveness;
• Provide an effective barrier against desiccation
and environmental factors;
• Protect the underlying cells from sudden
changes in osmotic pressure;
• Second line of defense against protease
activity-cysteine containing phosphoprotein.
Tissue repair
EFFECT
ACTIVE CONSTITUENTS
• Wound healing, epithelial
• Growth factors, trefoil
proteins, regeneration
TISSUE REPAIR
• A variety of growth factors and other biologically
active peptides and proteins are present in small
quantities in saliva.
• Under experimental conditions, many of these
substances promote tissue growth and
differentiation, wound healing, and other
beneficial effects.
• However, the role of most of these substances in
protection of the oral cavity is presently
unknown.
Dilution and clearance
• Saliva dilutes and eliminates dietary sugars
and acids;
• This process is dependent on flow rate and
swallowing frequency;
• Oral sugar clearance extensively prolonged
when unstimulated whole saliva flow rate is
below 2ml/min.
EFFECT
Antimicrobial
activity
• Physical barrier
• Immune defense
• Nonimmune defense
ACTIVE CONSTITUENTS
• Mucins
• Secretory immunoglobulin A
• Peroxidase, lysozyme,
lactoferrin, histatin, mucins,
agglutinins, secretory leukocyte
protease inhibitor, defensins,
and cathelicidin-LL 37
ANTIMICROBIAL ACTION
• Saliva has a major ecologic influence on the microorganisms that
colonize oral tissues.
• In addition to the barrier effect provided by mucins, saliva contains a
spectrum of proteins with antimicrobial activity such as the lysozyme,
lactoferrin, peroxidase, and secretory leukocyte protease inhibitor.
• A number of small peptides that function by inserting into membranes
and disrupting cellular or mitochondrial functions are present in saliva.
• In addition to antibacterial and antifungal activities, several of these
proteins and peptides also exhibit antiviral activity.
• The major salivary immunoglobulin, secretory immunoglobulin A (IgA),
causes agglutination of specific microorganisms, preventing their
adherence to oral tissues and forming clumps that are swallowed.
• Mucins, as well as specific agglutinins, also aggregate microorganisms.
Aggregation
• Inhibit bacterial attachment;
• Inhibits the adherence of these cariogenic
organisms to teeth and protection against
caries.
• Histadine-rich peptide has growth-inhibitory
and bactericidal effects on oral bacteria:
– Clumping of bacteria;
– Hinder effective adherence;
– Expectorated or swallowed.
Action of lactoferrin
• Lactoferrin, the exocrine gland secretion;
• The bacteriostatic properties are attributed to
the ability of the unstimulated protein to bind
two iron atoms per molecule;
• Lactoferrin is capable of both a bacteriostatic
and a bactericidal effect on S. mutans that
distinct from simple iron deprivation.
Action of salivari peroxidase
• The antimicrobial effect of salivary peroxidase
against S. mutans is significantly enhanced by
interaction with high molecular weight mucin;
• This mucin serve to concentrate a defense
force on the mucosa against the external
environment, entrapping and incapacitating
microorganisms.
Antifungal activity
• Parotid fluid has an antifungal capacity, reflecting
properties of both the neutral and the basic
histidine rich peptides;
• Basic peptides could cause 99% loss of viability of
Candida albicans at level of 25mg/ml;
• Oppenheim found that the neutral histidine rich
peptide was a potent inhibitor of C. Albicans
germination at levels as low as 2 mg/ml.
Antiviral activity
• Antibody (secretory IgA) can directly
neutralize viruses;
• Mucins are also effective antiviral molecules;
• A major function of saliva is to prevent the
establishment of unwonted species in the first
place.
Buffering capacity
• Resistance to pH changes at an arbitrary point;
• There are three buffer systems:
– Carbonic acid, bicarbonate;
– Phosphate;
– Protein;
– CO2 + H2O Ca H2CO3 Ca HCO3
– Concentration of bicarbonates is highest in parotid
saliva.
Buffering
ACTIVE CONSTITUENTS
EFFECT
• pH maintenance
• Neutralization of acids
• Bicarbonate, phosphate,
basic proteins, urea,
ammonia
Buffering capacity
pH
Secretion
rate
Buffer
capacity
BUFFERING
• The bicarbonate and, to some extent, phosphate,
ions in saliva provide a buffering action that helps
to protect the teeth from demineralization
caused by bacterial acids produced during sugar
metabolism.
• Some basic salivary proteins also may contribute
to the buffering action of saliva.
• Additionally, the metabolism of salivary proteins
and peptides by bacteria produces urea and
ammonia, which help to increase the pH.
Tooth integrity
EFFECT
ACTIVE CONSTITUENTS
• Enamel maturation,
• Enamel repair
•
•
•
•
•
Calcium,
Phosphate,
Fluoride,
Statherin,
Acidic proline-rich proteins
MAINTENANCE OF TOOTH INTEGRITY
• Saliva is supersaturated with calcium and phosphate
ions.
• The solubility of these ions is maintained by several
calcium binding proteins, especially the acidic prolinerich proteins and statherin.
• At the tooth surface the high concentration of calcium
and phosphate results in a posteruptive maturation of
the enamel, increasing surface hardness and resistance
to demineralization.
• Remineralization of initial caries lesions also can occur;
• This is enhanced by the presence of fluoride ions in
saliva.
Maintenance of tooth integrity
• Physical flow of saliva coupled with muscular
activity;
• Small decrease in the resting salivary flow rate
can greatly prolong sugar clearance time;
• Interaction with saliva provides a post
eruptive maturation through the diffusion of
ions.
• This enrichment of the crystal structure
increases hardness decreases permeability,
increases resistance to caries;
• The original pellicle is replaced by a constantly
replenished salivary film
selectively
absorbed proteins with a high affinity for
hydroxyapatite provides a protective barrier.
DIGESTION
• Saliva also contributes to the digestion of
food.
• The solubilization of food substances and the
actions of enzymes such as amylase and lipase
begin the digestive process.
• The moistening and lubricative properties of
saliva also allow the formation and swallowing
of a food bolus.
Initiates starch digestion:
• in most species, the serous acinar cells
secrete an alpha-amylase which can begin to
digest dietary starch into maltose.
Digestion
ACTIVE CONSTITUENTS
EFFECT
• Bolus formation
• Starch, triglyceride digestion
Amylase, lipase
• Water, mucins
• Amylase, lipase
PELLICLE FORMATION
• Many of the salivary proteins bind to the
surfaces of the teeth and oral mucosa,
forming a thin film, the salivary pellicle.
• Several proteins bind calcium and help to
protect the tooth surface.
• Others have binding sites for oral bacteria,
providing the initial attachment for organisms
that form plaque.
Taste
ACTIVE CONSTITUENTS
EFFECT
• Solution of molecules;
• Maintenance of taste buds.
• Water and lipocalins;
• Epidermal growth factor
and carbonic anhydrase VI
TASTE
• Saliva functions in taste by solubilizing food
substances so that they can be sensed by taste
receptors located in taste buds.
• Saliva produced by minor glands in the vicinity
of the circumvallate papillae contains proteins
that are believed to bind taste substances and
present them to the taste receptors.
• Additionally, saliva contains proteins that have
a trophic effect on taste receptors.
What then are the important functions of saliva?
Actually, saliva serves many roles, some of which are
important to all species, and others to only a few:
• Lubrication and binding: the mucus in saliva is
extremely effective in binding masticated food
into a slippery bolus that (usually) slides easily
through the esophagus without inflicting
damage to the mucosa. Saliva also coats the
oral cavity and esophagus, and food basically
never directly touches the epithelial cells of
those tissues.
• Solubilises dry food: in order to be tasted, the
molecules in food must be solubilised.
Oral hygiene:
• The oral cavity is almost constantly flushed
with saliva, which floats away food debris and
keeps the mouth relatively clean. Flow of
saliva diminishes considerably during sleep,
allow populations of bacteria to build up in
the mouth -- the result is dragon breath in the
morning. Saliva also contains lysozyme, an
enzyme that lyses many bacteria and prevents
overgrowth of oral microbial populations.

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