4 Saliva (DRG Juni)

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drg. Juni Handajani, M.

Kes, PhD
Departement of Oral Biology
Faculty of Dentistry
Gadjah Mada University
Referensi:
Van Rensburg BGJ. Oral Biology. Germany:
Quintessence Publ. 1995; 469-478.
Garrant PR. Oral Cells and Tissues. Canada:
Quintessence Publ. 2003; 239-164.
- compound, tubuloacinar, merocrine, exocrine
glands whose ducts open into the oral cavity.
- “compound”  > one tubule entering the main
duct;
- tubuloacinar  the morphology of the
secreting cells;
- merocrine  only the secretion of the cell is
released;
- exocrine  a gland that secretes fluid on to a
free surface.
 essential for the maintenance of oral health.
- > 99% water, the small content of other elements
(ex as bacteriocidal agents and growth factors)
 both major and minor salivary glands, and serous,
mucous or mixed glands.
 secretion is under the control of the autonomic
nervous system
 produced by the parenchymal cells undergoes
modification within striated ducts as it passes along
the duct system.
 Reduction in salivary flow in older patients, often as
a side-effect of drugs, can give rise to dry mouth
(xerostomia)
SALIVA
is a bodily fluid secreted by three pairs of major
salivary glands

supplemented :
- constituents originate from blood serum,
- from intact or destroyed mucosal and immune cells,
- from intact or destroyed oral microorganisms that result in
a complex mixture of a variety of molecules.
ROLE SALIVA
in acquired pellicle formation on tooth surfaces,
crystal growth homeostasis, bacterial adhesion,
plaque formation, and—because of its
lubricating effect—in maintaining mucosal
integrity of the oral and upper gastrointestinal
mucosal surfaces.

in physico-chemical defense, antimicrobial


defense, and wound healing.
SALIVA
Local and systemic disorders may disturb and interrupt
these complex balanced functions, which can lead to
mucosal and tooth damages.
Systemic disorders induce salivary changes without any
significant local effects.
Many such changes are of high diagnostic interest
because they can be rather specific to the causing
conditions and can be used for screening and early
diagnosis of several local and systemic disorders.
• lubrication for mastication, swallowing and
speech
• bringing substances in solution for taste
• acting as a buffer to maintain the integrity of
enamel
• limiting the activity of bacteria
• promoting the health of the oral mucosa.
KEL. PAROTIS
 Serous and sero-mukous
Dekat M2 RA

KEL. SUB-MANDIBULARIS
 sero-mukous
Dekat frenulum lidah

KEL. SUBLINGUAL
 mucous
 tersebar
Circles  the duct system
of intralobular ducts, that
is, intercalated and
striated secretory ducts
located within the lobule.
Above  interlobular and
multicelled excretory
ducts located outside the
lobules and lobes.
• serous and is the largest of the major salivary glands.
• occupies the region between the ramus of the
mandible and the mastoid process.
• The parotid is pyramidal in shape; its apex extends
beyond the angle of the mandible and the base is
closely related to the external acoustic meatus.
• The deep surface of the gland rests anteriorly on the
ramus and masseter.
• The gland is surrounded by an unyielding tough
fibrous capsule, the parotid capsule.
• The parotid duct appears at the anterior border
of the gland and passes horizontally across the
masseter muscle before piercing the buccinator
to terminate in the oral cavity opposite the
maxillary second molar.

• Lying with the duct on the masseter may be an


accessory parotid gland.

• Within the parotid gland are found the external


carotid artery, the retromandibular vein and
the facial nerve.
• Branches of the facial nerve are seen emerging
from the anterior and inferior margins of the
gland.

• Appearing at the superior border of the gland


are the superficial temporal vessels and the
auriculotemporal nerve.

• From the inferior border of the gland may be


seen the anterior and posterior branches of the
retromandibular vein.
• Lymph nodes are also associated with the
parotid gland.

• The parasympathetic innervation : from the


lesser petrosal branch of the glossopharyngeal
nerve.

• The preganglionic fibres synapse in the otic


ganglion, and postganglionic fibres reach the
gland by travelling with the auriculotemporal
branch of the mandibular nerve.
• is a mixed gland but is primarily
serous.
• A large part it (the superficial part)
is visible just beneath the inferior
border of the mandible, where it
lies on the mylohyoid muscle.
• The gland has an important
relationship with the mylohyoid
muscle, wrapping around the free
posterior border.
• This gives rise to the smaller deep portion of
the gland that lies on the hyoglossus muscle.

• The submandibular duct appears from the


deep part of the gland and wraps around the
lingual nerve as it crosses the hyoglossus
muscle to terminate on the sublingual papilla
in the floor of the mouth
• is the smallest of the three major salivary glands.
• It is a mixed gland but has a preponderance of
mucous elements.
• Is not a single unit like the parotid and
submandibular glands
• made up of one large segment (the major
sublingual gland) with a main duct that either joins
the submandibular duct or drains directly on to the
sublingual papilla, and a group of 8–30 mixed,
minor salivary glands, each having its own duct
system emptying into the sublingual fold in the
floor of the mouth.
• The sublingual gland lies between the hyoglossus and
mylohyoid muscles and lies against the sublingual
fossa of the mandible.

• The parasympathetic innervation of both the


submandibular and sublingual glands is from the
chorda tympani branch of the facial nerve.

• Preganglionic fibres are carried via the lingual nerve to


the submandibular ganglion.

• Postganglionic fibres pass from this ganglion to the


submandibular and sublingual glands.
Function of saliva
Digestive
Antibacterial
Lubrication
Taste
Buffering action
Hygienic action
Blood coagulation and tissue repair
Inhibition of dental caries
Water balance
Fungsi ekskretoris
cairan diagnostik
Digestive function
α-amylase (α-1:4 glucan-4-glucanohydrolase):
ptialin
High concentration in parotid
Forms 30% protein fraction & in secretion
submandibular gland cells
Insignificant from sublingual & minor salivary
gland
Inactivated by gastric hydrochloric acid
Weak action is compensated for by strong
action of pancreatic amylase in duodenum
Concentration low before breakfast, rises during
morning, peak in the middle of the day
Concentration rises with an increased rate of
flow saliva
Antibacterial function
Secretory IgA
- IgA & IgM small amounts
- Most sIgA and IgM in salivary gland
- different from plasma IgA
- resistant to proteolysis by bacteria
enzyme
-conc 90% parotid saliva, 85% whole
saliva, high-minor gland but small
contribution to whole saliva
- IgA formed in plasma cells present interstitially
in the gland, taken up by glandular cells

- secretory synthesized by glandular cells


(intravesicular transport of IgA)

- prevention of bacteria colonization by binding


to specific Ag responsible for adhesion
Peroxidase
- in parotid saliva consists of H2O2 formed by
mo, thiocyanate, and lactoperoxidase

-inhibit acid prod and growth (lactobacilli,


streptococci and fungi)

-thiocyanate oxidation catalysed by


lactoperoxidase (H2O2 presence), resulting
formation hypothiocyanate anions oxidize
bacterial enzymes
Lysozyme
- active to cell walls Gram +
- conc too small
- effect resulted from concerted action with
other system (ex: thiocyanate)
- hypothiocyanate very effective in the lysis
bacteria treated with lysozyme
Lubrication

Chewing process, food bolus formation,


swallowing, speech
Protects the soft mucosal surface from
damage by coarse foods
Taste

When dissolved and the solvent action of


saliva
Buffering action

pH and buffering dependent on bicarbonate


Inorganic phosphate contribute
Hygienic action

Desquamated oral epithelial cells, clumps of


bacteria, food debris loose by cleansing
action saliva
Blood coagulation and tissue repair

Clotting time reduced by protein saliva similar to the


blood factor VII, IX, and platelet factor.

Clot formed less solid than normal clot

Saliva (especially submandibular gland) accelerate the


rate of wound contraction in mice (probably EGF)
Inhibition of dental caries

mechanical action by cleansing tooth


surface
immunological action (sIgA)
Enzymatic action (peroxidase & lysozyme
system)
Fluor, Calcium & Phosphate promote
remineralization
Composition saliva

Parotid (serous) watery

Submandibular and sublingual mixed

Water (94.0%-99.5%) & solids (6.0% in


unstimulated, 0.5% in stimulated
Composition saliva cont

Organic contituents:
- urea, uric acid, free glucose, free amino
acid, lactate & fatty acid.
- Macromolecul: protein, amylase,
peroxidase, thiocyanate, lysozyme, lipid, IgA,
IgM, & IgG
Inorganic constituent : Ca, Mg, F, HCO3,K,Na,
Cl, NH4
Gases : CO2, N2, O2
Water
Constituents derived from oral cavity :
desquamated epithelial cells, PMN from cgf,
bacteria.
Modification of salivary composition by ductal
system
• Functions :mastication, swallowing, digestion,
maintenance of oral hard and soft tissues, control
of oral microbial population, and voice and
speech articulation.

• Lubrication : enhances the movement of the


tongue and lips, and aids in cleansing the oral
cavity of food debris and bacteria.
• Mastication, bolus formation and swallowing depend on
a moist, lubricated oral mucosa and fluid to wet the
bolus.

• Digestive enzymes are present in saliva and aid in the


initial process of digestion.

• Saliva has a protective function, maintaining an effective


barrier to external insults.

• Saliva calcium and phosphorus are in supersaturated


concentrations in the saliva and play a role in the
remineralization of the teeth.

• Neutral pH in the oral cavity is maintained by the


buffering capacity of the saliva.
• 99% is water, with the remaining 1% (ions and organic
constituents)
• most often hypotonic when compared with plasma;
however, it has the ability to be isotonic and even
hypertonic under physiological control mechanisms.
• The important ions in saliva are the cations Na+ and K+,
and the anions Cl− and bicarbonate (HCO3−).
• Other electrolytes : calcium phosphate, fluoride,
thiocyanate, magnesium sulphate and iodine.
• Saliva is derived from blood plasma but is not an
ultrafiltrate of plasma.
proteins, carbohydrates, lipids and small organic
molecules.
• contains a variety of proteins and glycoproteins,
including the serum proteins γ-globulins, albumin
and α/β globulins.

The proteins synthesized in the glands are:


• IgA (analogous to serum proteins)
• enzymes, including amylase, lysozyme, peroxidase,
kallikrein and small amounts of many others (e.g.
acid phosphatase, RNAase, cholinesterase, lipase)
• glycoproteins that contribute to viscosity of
saliva,enhancing and facilitating its lubricating and
agglutinating properties
• various small N-containing compounds.
• Parotid gland synthesize more protein than
glycoprotein a lower carbohydrate content

• Submandibular and sublingual glands synthesize


and secrete greater amounts of glycoprotein than
protein, and saliva from these two glands is higher
in carbohydrate content.

• histologically, where the parotid gland contains


high levels of secretory granules (protein-rich) but
no secretory droplets (mucin-rich), which are
present in the submandibular and sublingual
glands.
• The function of the salivary proteins can be related to
their structural features;

• facilitate the lubricating properties of the saliva, essential


for healthy mucosal tissue and antimicrobial protection.
• Enzymes amylase  the digestive role played by saliva,
whereby complex starch present in food can be broken
down (amylase hydrolyses α1–4 glycosidic linkages) prior
to the food bolus entering the stomach.

• Lysozyme, acid phosphatases and peroxidases may well


facilitate the protective role saliva plays in maintaining a
balanced oral microflora, as these enzymes have
antimicrobial properties.
• Lysozyme  cleaving β-N-acetylmuramic acid
residues in bacterial cell walls and aggregates
bacterial cells in suspension, also enhance the
activity of immunoglobulins.

• Salivary peroxidase catalyses the reaction of


bacterial metabolic products, hydrogen
peroxide with salivary thiocyanate to oxidized
derivatives.

• Salivary carbonic anhydrase increases the


buffering capacity of saliva by producing
bicarbonate.
• The sIgA is produced as a specific response to
contact with an antigen, synthesized by immune
cells and translocated to the surface by epithelial
cells.

• Lactoferrin binds ferric iron (Fe3+), an essential


microbial nutrient, and therefore demonstrates
some antibacterial activity (nutritional
immunity) but can have direct bactericidal
effects on some micro-organisms.
• Salivary mucins are a large family of
glycoproteins existing with differing
oligosaccharide chains and a protein core.

• Two main mucin subfamilies : MG1 (high


molecular weight and high carbohydrate
content) and MG2 (lower molecular weight and
lower carbohydrate content).

• These mucins form superstructures through


electrostatic bonds and formation of covalent
disulphide bonds.
The main functions of salivary mucins relate to:
• lubrication (due to the high negative charge of
salivary mucin, superstructures adopt an
expanded structure aiding lubrication)
• hydration (as mucins exhibit negative charges
that help bind water)
• pellicle formation and remineralization (MG1
helps in binding Ca2+ and hydroxyapatite)
• facilitating the direct removal of bacteria (MG2
can interact with bacteria).
• a number of small molecular weight proteins
that are generally phosphorylated and non-
glycosylated.

• proline-rich peptides, which have a negatively


charged amino terminal that is phosphorylated
and a positively charged carboxy terminal.
• These function by inhibiting calcium phosphate
crystal growth; they may also have a role in
remineralization of enamel.
• They also exhibit selective interaction with oral
bacteria and other pellicle proteins,
demonstrating a role in pellicle formation.
• Statherin, a tyrosine-rich protein, has a negative
amino terminal (phosphorylated) and
hydrophobic carboxy terminal.

• These molecules function by maintaining


supersaturated levels of Ca2+ and PO4– whilst
inhibiting mineral formation in the salivary
glands and oral cavity.

• The histatins are histidine-rich proteins and are


inhibitors of Candida albicans and Streptococcus
mutans growth in the oral cavity.
• epidermal growth factor and nerve growth
factor
• other regulatory peptides are also present in
saliva, though the precise role of these has
not been determined with certainty
• saliva is mostly a hypotonic secretion.
• formation is dependent upon the stimuli
mediated by both the parasympathetic and
sympathetic parts of the autonomic nervous
system.
• Parasympathetic cholinergic stimuli provide
the principal stimulus for fluid secretion;
• It is most likely that under reflex control
mechanisms, cholinergic, adrenergic and
peptidergic neurotransmitters are involved in
the secretion of saliva.
• formed in the acinar cells of the glands and is
delivered into the mouth through a series of
ductal trees.
• Salivary secretion is essentially a two-stage
process.
• The primary stage of salivary secretion results
in the formation of an isotonic primary
secretion by the acinar cells; this is later
rendered hypotonic by the removal of Na+ and
Cl− as it flows through the ductal system with
little loss of fluid volume.
• When the parasympathetic nerves are
stimulated, acetylcholine (ACh) binds to the
muscarinic ACh receptors and causes an
increase in inositol trisphosphate (IP3) levels.

• This rise in IP3 levels leads to an increase in


Ca2+ release from intracellular stores and, in
turn, these higher Ca2+ levels lead to an
increase of fluid secretion from the cells.
The mechanisms brought into play by this
increase in Ca2+ are as follows:
• Cl−, which is concentrated within the acinar
cells, is released across the apical membrane of
the acinar cell.
• This leads in turn to a secretion of Na+.
• The combined NaCl secretion takes water
across the cells by osmosis.
Water crosses the epithelium by two possible
routes, moving:
• through the tight junctions between the cells
via paracellular transport
• through the acinar cells through both the
apical and basolateral membranes via
transcellular transport.
• involves the modification of the isotonic saliva
secreted by the acini into the hypotonic saliva
secreted from the salivary ducts into the
mouth.
• This ductal modification of the primary, acinar
derived isotonic solution is effected by apical
Cl− and Na+ channels, along with Cl−/HCO3 −
and Na+/H+ exchanges.
• These allow movement of Na+ and Cl− along a
concentration gradient into the striated duct
cells and then drive them out of the cell
across the basolateral membrane.
• As the striated duct cells are impermeable to water,
there is no osmotically driven reabsorption of water
and so the saliva in the duct becomes hypotonic.

• Since the fluid secretory process in the acinar cells


has a greater capacity than the electrolyte
reabsorption process in the ductal cells, there can be
large composition changes of the saliva entering the
mouth.

• At low, resting flows, saliva moves slowly through the


ducts and the striated epithelium cells are able to
modify the composition of the saliva substantially by
absorbing Na+ and Cl−.
• However, at high, stimulated flows the saliva
passes rapidly through the ducts with much
less alteration of electrolyte concentrations.

• Thus, the electrolyte concentrations of saliva


at high rates of flow are more similar to the
primary saliva concentrations produced by the
acinar cells.
• Salivary bicarbonate ions (HCO3−) are important in
buffering plaque acid within the mouth.

• HCO3 − can pass through Cl− channels and so are


secreted along with Na+ and Cl− into the ductal
lumen by the acinar cells and possibly the
intercalated duct cells close to the acinar cells.

• At low salivary flow rates HCO3 − is reabsorbed by the


striated duct cells and so very little will get into the
mouth; however, at high flow rates there is less
reabsorption of HCO3− and therefore higher
concentrations reach the mouth when needed during
eating.
• secretions of water and electrolytes are a
secretory modality called ‘hydrokinetic’
• secretion of proteins is termed ‘proteokinetic’.
• Both these functions do not occur synchronously
but are influenced by which nerves are firing, the
impulse frequency and also the type of cell that is
being stimulated.
• In general, the bulk of the fluid flow is generated
by parasympathetic nerve activity.
• The amount of protein secreted tends to be low
when impulse frequencies are low and higher
when the stimulus is greater.
Proteins are secreted in two possible ways:
• Firstly, by ‘exocytosis’ of pre-packaged proteins
from secretory granules in specialized exocrine
cells.
• Secondly, by a process called ‘constitutive
secretion’ from the movement of Golgi-derived
vesicles to the surface of the cells in all glandular
cells.
It has been shown that similar-looking cells in
different glands produce quite different proteins,
and similar mucins may be differently glycosylated in
different glands
Transport
Water and electrolyte in the intercalated ducts.
Striated ducts are responsible for electrolyte
(secretion of potassium and reabsorption of
sodium ions)
Proteins like IgA, lysozyme, and kallikrein [and
may be Hsp70 exists in the striated duct.
An electrolyte transport in the excretory
(collecting) ducts is also suspected
• However, in human beings large increases in
secretion over short periods of time are seen
during eating and these increases are attributed,
in varying degrees, to stimulation of a number
• Whole-mouth saliva flow rates vary from resting
with a mean of 0.3 ± 0.22 ml min−1.
• When stimulated, the whole mouth salivary flow
will rise to a mean of 1.7 ± 2.1 ml min−1.
• The daily flow rates lie between 500 and 1000 ml
per day.
The contribution to the whole-mouth saliva made by
the different glands varies according to whether the
gland is at rest or stimulated:
• The parotid gland provides only 20% of the saliva
when rested and as much as 50% when
stimulated.
• The submandibular gland provides over 65% of
resting whole-mouth saliva, but only 30% of
stimulated saliva.
• The sublingual and minor salivary glands supply
the remaining saliva equally in both rest and
stimulated conditions.
Antibacterial function
Secretory IgA
- IgA & IgM small amounts
- Most sIgA and IgM in salivary gland
- different from plasma IgA
- resistant to proteolysis by bacteria
enzyme
-conc 90% parotid saliva, 85% whole
saliva, high-minor gland but small
contribution to whole saliva
- IgA formed in plasma cells present interstitially
in the gland, taken up by glandular cells

- secretory synthesized by glandular cells


(intravesicular transport of IgA)

- prevention of bacteria colonization by binding


to specific Ag responsible for adhesion
 Peroxidase
- in parotid saliva consists of H2O2 formed by
mo, thiocyanate, and lactoperoxidase

-inhibit acid prod and growth (lactobacilli,


streptococci and fungi)

-thiocyanate oxidation catalysed by


lactoperoxidase (H2O2 presence), resulting
formation hypothiocyanate anions oxidize
bacterial enzymes
Lysozyme
- active to cell walls Gram +
- conc too small
- effect resulted from concerted action with
other system (ex: thiocyanate)
- hypothiocyanate very effective in the lysis
bacteria treated with lysozyme

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