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SALIVARYSALIVARY
GLANDSGLANDS
Dr AmithaDr Amitha
Dept of oral pathologyDept of oral pathology
 Definition
 Classification Of Salivary Glands
 Anatomy of salivary glands
 Development of salivary glands
 Structure Of Salivary Glands
 Histology of major salivary glands
 Saliva
 Clinical considerations
DEFINITION
 These are compound tubuloacinar exocrine glands found in oral
cavity that secrete complex fluid known as saliva.
CLASSIFICATION OF SALIVARY GLANDS
 Based on size
 Based on type of secretory cells
Based on size:
1. Major salivary glands
2. Minor salivary glands
1. Major salivary glands
 Collection of secretory cells aggregated into large bilaterally paired
extra oral glands with extended duct system through which the gland
secretions reach the mouth.
- Parotid
- Submandibular
- Sublingual
2. Minor salivary glands
Collection of secretory cells scattered
throughout the mucosa & submucosa of the
oral cavity with short ducts opening directly
onto mucosal surface.
- Serous glands of Von Ebner.
- Anterior lingual glands.
- Lingual, buccal, labial, palatal
glands, glossopalatine and
retromolar
glands
2. Based on type of secretory cells
1. Serous : Parotid
2. Mixed (seromucous):
Submandibular
3. Mucous: Minor salivary glands.
Parotid gland:
 Largest salivary gland
 60 to 65% of total saliva.
 Pyramidal in shape.
 Weighs between 14 & 28g.
 Superficial portion of gland
is located subcutaneously,
in front of the external ear
& deeper portion lies
behind ramus of mandible.
 Associated with facial
nerve.
ANATOMY OF SALIVARY GLANDS
 Stenson’s duct:
- runs forward across
masseter muscle, turns
inwards at the anterior
border of masseter &
opens at a pappilla in
oral cavity just opposite
second maxillary molar
crown.
-5cmx3cm
-A small portion of
parotid forms accessory
gland associated with
stenson’s duct, just
anterior to the Superficial
portion of gland
Nerve supply:
 Sensory supply-Greater auricular and ariculotemporal nerve
 Parasympathetic supply:
Glossopharyngial nerve (Preganglionic fibers) synapse in the otic
ganglion. Postganglionic fiber enter the gland through the
ariculotemporal nerve.
 Sympathetic Supply:
Postganglionic fibers from plexus on external carotid artery or middle
meningial arteries.
 Vascular supply & Lymphatic drainage :
Arterial supply-External carotid artery
Venous drainage-External jugular vein
Lymphatic drainage-Upper deep cervical
lymph nodes.
Submandibular gland:
 10 to 15 gm.
 2 to 30% of total
saliva.
 Located at Posterior
portion of floor of
mouth, medial
aspect of mandible
& wrapping around
posterior border of
mylohyoid.
•Wharton's duct runs
forward and opens
into the mouth
beneath the tongue,
lateral to lingual
frenum.
 Blood supply: Facial and lingual arteries.
 Lymphatic drainage: Submandibular lmph node & deep cervical
lymph nodes.
 Nerve supply:
Parasympathetic supply: Facial nerve reaching gland through the
lingual nerve & submandibular ganglion.
Sympathetic Supply:
Postganglionic fibers from plexus on facial artery
Sublingual gland:
 Smallest major salivary
gland
 2gm.
 2.5% of total saliva.
 Located at anterior part
of floor of the mouth, just
between mucosa &
mylohyoid muscle.
 Open into oral cavity
through series of small
ducts (duct of Rivinus)
opening along sublingual
fold and open through
large duct- Bartholin’s
duct, that opens with
submandibular duct at
sublingual caruncle.
 Blood supply: Sublingual & submental arteries.
 Lymphatic drainage: Submental lymph nodes
 Nerve supply:
Parasympathetic supply: Facial nerve reaching
gland through the lingual nerve & submandibular
ganglion.
Sympathetic Supply:
-Postganglionic fibers from plexus on facial
artery.
Minor Salivary gland:
 No. between 600 and 1000.
 Exist as aggregates of secretory tissue present in
submucosa throughout most of the oral cavity.
 Not seen in gingiva & anterior part of hard plate.
 Rich in mucin, antibacterial proteins and secretory immunoglobulin.
 Continuous slow secreting glands, thus have a important role in
protecting and moistening oral mucosa, especially when major
salivary glands are mostly inactive.
Von Ebners’s Lingual serous gland
 Located in tongue and open into the troughs
surrounding circumvallate papillae on the dorsum o
tongue and at the foliate papillae on the side of
tongue.
 Secrete digestive enzymes & proteins that are
thought to play role in taste process
 Fluid of their secretion cleanse the trough & prepare
the taste receptors for a new stimulus.
DEVELOPMENT OF SALIVARY GLANDS
Bud formation
Formation and growth of epithelial chord.
Initiation of branching in terminal parts of
epithelial chord.
Branching of epithelial chord and lobule
formation
Canalizatio
n
Cytodifferentiation
Stage I
Stage II
Stage III
Stage IV
Stage V
Stage VI
Stage I (Bud formation) :
 Develops as proliferation of oral epithelium
into underlying ectomesenchyme
(condensing around bud).
 A thin basal lamina separates the bud from
underlying mesenchyme.
 Interaction of the epithelium with underlying
condensing mesenchyme associated with
salivary glands provide optimum environment
for gland formation.
Stage II (Formation and growth of epithelial
chord):
• Proliferation of the epithelial
bud into the underlying
mesenchyme results in long
epithelial cords.
• The mesenchyme (MES)
around the developing
glandular epithelium also
proliferates.
• Basal lamina is believed to
play a role in influencing the
morphogenesis &
differentiation of the salivary
glands.
Stage III (Initiation of
branching in terminal
parts of epithelial chord):
 Epithelial chord
proliferates & its end
branch into bulbs.
Stage IV (Branching of epithelial chord and lobule
formation):
• Terminal ends branch extensively forming numerous
bulbs - cleft formation.
• ECM component deposition within clefts apparently serve
to stablise them.
• Connective tissue component below epithelial chord
forms capsule & surrounds entire gland.
• Hypothesis:
-Epithelial Mesenchymal Interactions.
Fibroblast growth factor family & their receptors
Transforming growth factor-b
-Differential contraction of actin filament at the basal and
apical ends of the epithelial cells
Stage V (Canalization):
 Lumen formation takes place at distal ends of chord,
then in proximal and at last in central part.
 Lumen forms within the ducts before they develop within
the terminal buds.
 Apoptosis of centrally located cells.
 Different rates of proliferation of outer and inner layers o
epithelial chord.
 Secretion of fluid by ductal cells which increases the
hydrostatic pressure within to form a canal.
Stage VI (Cytodifferentiation):
 Following lumen formation in the terminal buds, epithelium consists
of two layers of cells.
 Inner cells differentiate into mucous or serous cells depending upon
type of specific gland.
 Some of the outer cells of epithelium differentiate into myopithelial
cells that are present around secretory end piece and intercalated
ducts.
 Portion of epithelial bud close to the oral cavity forms main
excretory duct, distal portion forms secretory end piece.
 As epithelial
parenchyma increase
in size, connective
tissue component
around them
diminishes and
remains as a thin
layer.
 Thicker partition of
connective tissue
(septa), continuous
with the capsule and
within which run
nerves & blood vessels
supplying gland,
 Parotid: 4-6th
week of I.U. life.
 Submandibular :6th
week of I.U. life.
 Sublingual and minor salivary gland : 8th
week of I.U.life.
 Maturity of secretory end piece: During
last 2 months of gestation.
 Secretory component of Gland continues
to grow postnatally while as ductal,
connective tissue component and
vascular component decreases- up to
two years of age.
DEVELOPMENT OF SALIVARY GLANDS
 Comprises of
-a series of secretory end piece or
acini.
-connected to the oral cavity by a
system of ducts.
STRUCTURE OF SALIVARY GLANDS
Secretory end piece or accini:
• Consists of secretory cells, which are arranged in a roughly spherical
configuration around a central lumen or cavity.
• Show a great diversity in size, shape, and cell number.
• 2 types of cells
- Serous cells
- Mucous cells
Serous Cells:
 Parotid & submandibular gland.
 Serous cells are also present in demilune formations at the blind ends
of mucous secretory tubules (submandibular and sublingual glands).
 Secretions of serous cells are proteinaceous -usually enzymatic,
antimicrobial, calcium-binding.
 Secretory end piece consisting of serous cells are typically spherical
and consist of 8 to 12 cells surrounding a central lumen.
 Pyramidal in shape, with broad base adjacent
to connective tissue stroma & apex situated
towards the central lumen.
 Nucleus is spherical & situated at the basal third
of the cell. Sometimes binucleated.
 Cytoplasm stains
intensely with H and E.
 Apical cytoplasm is
filled with secretory
granules( macromolec
ular component of
saliva).
 Basal cytoplasm
contains RER, which
converge towards the
golgi complex located
just apical or lateral to
nucleus.
 Also contain
cytoskeleton
components,
Lumen and intercellular
canaliculi in a serous end piece
• The lumen of serous end
piece has small extensions
in the form of intercellular
canaliculi (found between
adjacent serous cells).
Plasma membrane exhibits several specializations:
 The surface of the seromucous cell lining both
the central lumen & canaliculi possess a delicate
microvilli that extend into luminar and
canalicular spaces.
 Space between basement membrane and
basal plasma membrane may be increased by
complex foldings (0.5 microns) of the basal
plasma membrane.
 Canaliculus terminates in the form of a classic
junctional complex consisting of a tight junction
(zona occludens), an adherent junction & a
desmosome.
Mucous cells:
 Predominant secretory cell type of the sublingual gland & most of
minor salivary glands.
 Also occur in submandibular gland.
 Secretion consists of large amount of mucins -lubrication, effective
barrier, aggregation of microorganisms.
 Secretory component of mucous cell accini
consists of round or tubular configuration.
 Larger lumen.
 Larger than serous cells.
 Pyramidal in shape.
 Broader luminal surface.
 Flattened nucleus situated towards its base
 Apical cytoplasm is filled with mucous secretory droplets.
 Stain poorly in H & E.
 PAS or Alcian blue +ve
 Mucous droplets are larger
and more irregular in shape
- Electron lucent droplets
 More prominent Golgi
complexes.
 Also contain cytoskeleton
components, RER,
mitochondria, lysosomes
and peroxisomes but less
prominent.
 Like serous cells , mucous
cells are joined by
intercellular junctions.
 Lack intercellular canaliculi.
Demilunes Of Gianuzzi
 Mucous cells accini may be capped at the blind end by crescents of
several serous cells.
 Their secretion reach the lumen of the end piece through intercellular
canaluculi between mucous cells at the end of the tubule.
Myoepithelial Cells
(Basket cells):
 Contractile cells
located around the
terminal secretory
units and the first
portion of the duct
system, intercalated
duct.
 Located between
basal lamina and
secretory or duct
cells and are joined
by desmosomes.
 Similar to smooth
muscle cells but are
 They are stellate or spider like, with a flattened nucleus surrounded by
a small amount of perinuclear cytoplasm, & long branching process
that embrace the secretory duct cells.
 The processes are filled with filaments of actin and soluble myosin.
Salivary gland immunostained to demonstrate
actin in the contractile myoepithelial cells.
 Cell membrane has numerous caveolae - initiation of contraction.
 Cellular organelle are located in perinuclear cytoplasm.
 Only their nuclei is visible in ordinary H & E section.
 Myoepithelial cells related to intercalated ducts are more spindle
shaped and have fewer processes.
Functions:
 Expulsion of saliva from secretory end piece to
ductal system.
 Contraction of myoepithelial cells of
intercalated ducts may shorten or widen the
ducts , helping in maintaining their patency.
 Maintaining cell polarity and structural integrity
of secretory end piece.
 Produce proteins that have tumour suppressor
activity, such as proteinase inhibitors (e.g., tissue
inhibitors of metalloproteinases) and
antiangiogenesis factors and that cell may act
as effective invasive barrier against epithelial
neoplasms.
DUCTS:
 3 classes of ducts
- Intercalated
- Striated
- Terminal
 Terminal secretory units opens into a small
duct called the intercalated duct. These
ducts join to form larger striated ducts
which finally empty into a larger excretory
duct.
Ductal system of a salivary
gland:
Main excretory duct opens into the
oral cavity. Excretory ducts are
mostly located in the interlobular
connective tissue.
Striated ducts are the main
intralobular ductal component.
Intercalated ducts vary in length
and connect the secretory end
pieces with the striated ducts.
Intercellular canaliculi are
extensions of the lumen of the end
piece between adjacent secretory
cells that serve to increase the
luminal surface area available for
secretion.
Intercalated Ducts:
 Small ducts into
which secretory end
piece empties.
 Lined by a single
layer of low cuboidal
cells and
myoepithelial bodies
and their processes.
 Overall diameter is
less than secretory
end piece but their
lumen is larger than
secretory end piece.
•Centrally placed nucleus
•Little cytoplasm – RER and Golgi
apparatus.
•A few secretory granules may be
found in the apical cytoplasm,
especially cells located near end
pieces.
•Few microvilli projecting into
lumen.
•Joined to adjacent cells by apical
junctional complexes and scattered
desmosomes & gap junctions and
have folded processes that
interdigitate with similar processes
of adjacent cells.
 Long intercalated duct : Parotid
 Shorter : Submandibular
 Poorly developed in : sublingual
Function:
• Channel for salivary flow
• Contributes to the salivary secretion –
lysozymes & lactoferrin.
• Reservoir of undifferentiated cells that may
undergo proliferation & differentiation to
replace damaged or dying cells in the end
pieces and striated ducts.
Striated ducts:
 Larger duct into which the intercalated ducts
empty.
 Main ductal component in intralobular portion
of gland.
 Lined by tall columnar cells.
 Centrally placed
spherical nucleus.
 Pale acidophillic
cytoplasm
 Basal striation
perpendicular to the
base of the cells
-Mitochondria are lying
in cytoplasmic partitions
produced by infoldings
of the basal plasma
membrane.
 RER and Golgi
apparatus and few
secretory granules and
 Short stubby microvilli at the luminal surface.
 Joined to adjacent cells by junctional complexes and tight junction
but lack gap junctions.
 Function:
-Modify the salivary secretion-Changes from isotonic to hypotonic.
-Na+ reabsorption & K+ excretion.
Terminal Excretory
Ducts:
 As the striated ducts
leave the individual
glandular lobules and
enter the inter lobular
connective tissue,
they join to form
excretory ducts.
 Larger than striated
ducts
 Main excretory ducts
leading from the
gland to the oral
cavity is formed by
the continued
confluence of the
 Near the striated ducts they are lined by
pseudostratified with columnar cells admix with
small basal cells and goblet cells.
 As the smaller duct join to form larger duct, no. of
basal cells increase & goblet may also be present.
• As they approach oral cavity epithelium changes to a
stratified epithelium.
• Function: Modify the final saliva by altering its electrolyte
concentration.
CONNECTIVE TISSUE:
 Capsule –demarcate
gland from adjacent
structures.
 Septa –divide gland into
lobes and lobules
-Carry the nerves and
blood vessels and
excretory ducts.
 Fibroblast, Macrophages,
Dendritic cells, Mast cells,
Plasma Cells, Adipose
tissue.
 Collagen fibers and elastic
fibers along with
glycoprotein and
proteoglycans of the
Nerve Supply:
 Follow the course of vessels
 2 patterns :
I. Intraparietal type : Axons leaves the nerve bundle, looses its schwann
cell investment, penetrate the basal lamina and form an expanded
swelling or varicosity in close contact(10 to 20 nm) to basolateral
membrane or between epithelial cells.
e.g., submandibular gland & minor salivary gland of lip.
II. Extraparietal Type: Axons remain associated with the nerve bundle in
the connective tissue-100 to 200 nm from epithelial cells.
e.g., parotid gland
Histology of major salivary
glands
Parotid gland:
 All serous
 Fat cells may be seen.
 Long intercalated ducts are seen.
Submandibular gland:
 Consists of serous end pieces & mucous tubules
capped with serous demilunes.
 Serous cells significantly outnumber the mucous
cells (pale staining).
 The intercalated & striated ducts are less
numerous than those in parotid but structurally
similar.
Sublingual salivary gland :
 Mixed, with mucous cells more.
 Intercalated ducts are short & difficult to
recognise.
 Intralobular ducts are fewer in no. than in the
parotid or submandibular gland
 Some ducts may lack the infoldings
characteristics of striated ducts.
Minor salivary glands:
 Consists of aggregates of secretory
end pieces and ducts, organised
into lobule like structure in the
submucosa or between muscle
fibers of tongue.
 Mostly mucous
 Occasional demilunes.
SALIVA
Thin, watery, slightly viscid fluid secreted by the salivary
glands.
•Composition
• Functions
•Formation & Secretion Of Saliva
Water: 94 to 99.5%
Solids: 0.5 to 0.6%
Organic:
Glycoproteins
Enzymes: α- amylase
Lysozyme
Lactoperoxidase
Kallikrein
Esterase
Acid phosphatase
Mucins
Lactoferrin
Blood clotting factors
Hormones - Parotin
Secretory Immunoglobulin-
Composition
Inorganic Substances:
Sodium
Calcium
Chloride
Bicarbonate
Phosphate
Potassium
Less Amounts:
Fluoride
Magnesium
Iodides
 More than a litre of saliva is secreted per day.
 Specific Gravity : 1.002 to 1.008
 pH: 6.2 to 7.6 (6.7)
 Water : 99.4% (unstimulated) & 99.5% (stimulated)
Solids: 0.6% (unstimulated) & 0.5% (stimulated)
Salivary flow rate
• Normal salivary flow
rate:
0.3ml/min(unstimulated)
2.0 – 5.0 (stimulated)
• Exhibit diurnal and
seasonal variations
Peak : Mid afternoon
Spring
• Negligible: During sleep
flow
No
sleep
sle
ep
12
am
6
am
12
pm
6
pm
12
am
6
am
12
pm
6
pm
12
am
30
20
10
 Time of day
CIRCAIDIAN RHYTHM OF
SALIVA FLOW
CIRCAIDIAN RHYTHM OF
SALIVA FLOW
Effect of feeding on
salivary secretion
0
0.005
0.01
0.015
0.02
0.025
0.03
0.035
Volumeofsalivacollectecdeach10min
10 min collection periods
Meal
during
this
period
• Unstimulated flow
– Whole 0.2 – 0.4 ml/min
– Submandibular g. 0.1
ml/min
– Parotid g. 0.04 ml/min
• Stimulation
– Whole 2.0 – 5.0 ml/min
– Submandibular g. 0.8
ml/min
– Parotid g. 1.0 – 2.0
ml/min
 Parotid glands:
-Watery saliva.
-Rich in enzymes such as amylase, proteins
such as proline rich proteins and other glycoproteins.
 Submandibular glands:
-In addition to above component, contains highly glycosalated
substance called mucins
 Sublingual glands:
-Viscous rich in saliva
Mucins:
 Glycoproteins - protein core with many
oligosacharide side chains attached by O-
glycosidic bond.
Two major mucins (MG1 and MG2).
 Lubrication
Hydrophillic-resists dehydration.
Amylases:
 30% of total protein in parotid saliva
 Hydrolyzes α(1-4) bonds of starches such as
amylose and amylopectin
Organic components
Lingual Lipase:
• Secreted by lingual glands and parotid.
• Involved in fat digestion-Important in digestion of milk
fat in new-born.
 Statherins:
 Statherins prevent
precipitation or
crystallization of
supersaturated calcium
phosphate in ductal
saliva and oral fluid.
 Also an effective
Lactoferrin:
Iron-binding protein
Lysozyme:
• Also called muramidase
• Hydrolysis of α(1-4) bond between N-acetylmuramic acid
and N-acetylglucosamine in the peptidoglycan layer of
bacteria.
Proline-rich Proteins (PRPs):
• Inhibitors of calcium phosphate crystal growth
• Subdivided into three groups
Acidic 45%
Basic 30%
Glycosylated 25%
Salivary peroxidase systems
 Sialoperoxidase (SP, salivary peroxidase)
 Produced mainly by parotid gland
 Myeloperoxidase (MP)
 From leukocytes entering via gingival crevice
Histatins
• Potent inhibitors of Candida albicans growth
Cystatins:
• Considered to be protective against unwanted proteolysis
caused by bacteria - inhibit proteases in periodontal tissues
• Also have an effect on calcium phosphate precipitation
Inorganic Content
Calcium and phosphate:
 Help to prevent dissolution of dental enamel
 Calcium
 1.4 mmol/l (unstimulated saliva)
 1.7 mmol/l (stimulated saliva)
 50% in ionic form
 sublingual > submandibular > parotid
 Phosphate
 6 mmol/l (unstimulated saliva)
 4 mmol/l ( stimulated saliva)
 90% in ionic form
Bicarbonate:
 Buffer - Defence against acids produced by
cariogenic bacteria
 Derived actively from CO2 by carbonic anhydrase
Thiocyanate:
 Antibacterial
 Higher conc. => lower incidence of caries
 Smokers - increased conc.
Lead, cadmium, copper:
 May reflect systemic concentrations - diagnostics
FUNCTIONS
1.PROTECTION:
 Mechanical washing action:
- Flushes away non-adherent bacterial and acellular
debris from the mouth.
-Clearance of sugars from the mouth limits their
availability to acidogenic plaque microorganisms.
 Lubricant: (mucin)
- Protects the lining mucosa by forming a barrier
against noxious stimuli, microbial toxins and minor
trauma.
- Allows the oral surface to move one another with
minimal friction during function.
2.BUFFERING:
 Bicarbonate ,phosphate, some salivary proteins.
Metabolism of salivary proteins and peptides produce
ammonia and urea which help in increase of pH.
3.Pellicle formation:
 Salivary proteins bind to surface of the teeth and
oral mucosa, thus forming salivary pellicle which
behaves as a protective membrane .
 Binding site for bacteria – plaque.
4.MAINTAINENCE OF TOOTH INTEGRITY:
 Saliva is saturated with Ca+
& PO4- : acidic prolein
rich proteins & statherin
 High concentration of these ions ensures that
ionic exchange with the tooth surface results in
post eruptive enamel maturation, increase in
surface hardness, decrease in permeability and
increase in resistance to demineralization.
5.ANTIMICROBIAL ACTION:
 Lysozyme is an enzyme that can hydrolyse the
cell wall of some bacteria.
 Lactoferrin binds free iron & in doing so
deprives bacteria of this essential element.
 Antibodies present in saliva (IgA)
-has the capacity to agglutinate
microorganisms that are swallowed.
-prevent their agglutination to oral tissue.
 Mucin and specific agglutins: aggregate
microorganisms.
 Histatin and peroxidase
6.ROLE OF SALIVA IN TISSUE REPAIR:
 Bleeding time of oral tissues is shorter than other
tissues.
 Experiment have shown that wound healing is
faster & wound contraction is also increased in
the presence of saliva.
7.DIGESTION:
 Forms the food bolus-preparation of the ingested
food for deglutition.
 Breaks down starch (Amylase).
 Lipase
 Dilutes gastric chyme.
8.TASTE:
 Saliva is required to dissolve substance to be
tasted & carry them to the taste buds.
 It also contains a protein called gustin that is
8.Salivary anticaries activity:
 Carbohydrate & microbial clearance from
the oral cavity.
 Buffering action - Salivary bicarbonates.
 Remineralization of incipient carious lesion-
Ca+
, PO4
+
, Fl-
 Increase enamel resistance to acid
decalcification- Fl-
 Salivary urea and bicarbonate can increase
rate of glycolysis, thus leading to faster
carbohydrate metabolization, which inturn
leads to reduced duration of the enamel
Multifunctionality
Salivary
Functions
Anti-
Bacterial
Buffering
Digestion
Mineral-
ization
Lubricat-
ion &Visco-
elasticity
Tissue
Coating
Anti-
Fungal
Anti-
Viral
Carbonic anhydrases,
Histatins
Amylases,
Mucins, Lipase
Cystatins,
Histatins, Proline-
rich proteins,
Statherins
Mucins, Statherins
Amylases,
Cystatins, Mucins,
Proline-rich proteins, Statherins
Histatins
Cystatins,
Mucins
Amylases, Cystatins,
Histatins, Mucins,
Peroxidases
FORMATION & SECRETION OF
SALIVA
Two Stage Hypothesis Of Saliva Formation:
First stage:
 Primary saliva is produced by secretory end
piece & intercalated ducts.
 Isotonic - most of the organic components &
water.
Second stage:
 Primary saliva is modified as it passes striated &
excretory ducts - reabsorption & secretion of
electrolyte.
TWO STAGE HYPOTHESIS
OF SALIVA FORMATION
Water &
electrolytes
Isotonic
primary saliva
Most proteins
Some proteins electrolytes
Na+
Cl-
resorbed
K+
secreted
Hypotonic
final saliva
into mouth
First stage:
 Formation of macromolecular component
 Fluid & Electrolyte release
Formation of macromolecular component
Proteins synthesis in ribosomes associated with RER
Translocated to lumen of RER
Folding of protein & Posttranscriptional modification such
as disulphide bond formation & N- and O-glycosylation.
Transferred as small vesicles to golgi complex
Further modification followed by condensation & packing
into secretory granules (stored in apical cytoplasm).
Secretory signals (via sympathetic neurotransmitters)
Fused to luminal surface [Exostosis]
Released to external surface
The binding of the sympathetic transmitter norepinephrine (NE) to (β-
adrenergic (β) receptors on the basolateral membrane activates adenylyl
cyclase (AC)
Catalyzes the formation of cyclic adenosine monophosphate
(cAMP) from adenosine triphosphate (ATP)
Cyclic adenosine monophosphate activates protein kinase A (PKA)
Phosphorylates other proteins in a cascade
Exocytosi
s
Fusion of secretory granules with the luminal surface to
release their contents into the lumen
Role of Secretory signals in exostosis
Fluid & Electrolyte
Parasympathetic stimulation, Noradrenaline, and substance P
ER releases Ca++
Free cytoplasm Ca++
Opens Cl-
channel in apical & K+channel in basolateral membrane
Apical Efflux of Cl-
Extracellular Na+ draws into lumen probably through tight
junction to balance the electrochemical gradeint
Efflux of water-aquaporin & tight Junction
Binding of the parasympathetic transmitter, acetylcholine (ACh), to muscarinic
cholinergic (MC) receptors, and by norepinephrine binding to (α-adrenergic receptors
(α).
Activate phospholipase C (PlC),
Converts phosphatidylinositol bisphosphate (PIP2) to inositol trisphosphate (IP3) and
diacylglycerol (DAG).
Inositol trisphosphate causes the release of Ca2+ from intracellular stores, probably
the endoplasmic reticulum.
The increased Ca2+ concentration opens Cl– channels in the luminal membrane and
K+ channels in the basolateral membrane, and activates the basolateral Na+/K+/2Cl–
cotransporter.
The increased luminal Cl– is balanced by the movement of extracellular Na+ across
the tight junctions (TJ), and the resulting osmotic gradient pulls water into the lumen
through the cell and probably through the tight junction.
Role of Stimulatory signals in Fluid & Electrolyte release
• Calcium also modulates the activity of protein kinase A
and protein kinase C (PKC). Protein kinase C, in turn,
modulates exocytosis and intracellular Ca2+ concentrations.
Ductal Modification of saliva:
 Net reabsorption of Na+
and Cl-
by luminal & basolateral
membranes-hypotonic final saliva.
 Secretion of K+
and HCO3
-.
 Flow rate is directly related to Na+
and Cl-
in saliva and inversely
related to K+
in saliva
 Flow rate is directly related to HCO3
-
in saliva.
Neural control of Salivation:
 The afferent pathways: via the facial &
Glossopharyngeal nerves to a solitary nucleus in
the medulla.
 There is also an input from higher centers in
response to smell, sight etc.
 Efferent pathways:
 The Parasympathetic efferent pathways
-for the S.L&S.M. from the Facial nerve (chord
tympani to reach the lingual nerve) via S.M.
ganglion;
-the parotid gland from the glossopharyngeal N
which pass through the tympanic and lesser
superficial petrosal nerves to reach the otic
ganglion where they synapse with post ganglionic
fibres of the auriculotemoral nerve which supply
Clinical considerations
Xerostomia:
 Drugs- central or peripheral inhibition of salivary
secretion.
 Destruction of salivary gland:
-Radiotherapy to H & N region
-Chemotherapy
-Bone marrow transplant
-Autoimmune diseases (sjogren’s syndrome)-
invasion of
lymphocytes & destruction of epithelial cells.
 Psychological factors
 Loss of protective effect of salivary buffers, proteins, and mucins-
increased susceptibility to infections.
 Difficulty & pain on eating, speech and swallowing.
 Temporary saliva
Oral pharmacosympathomimmetic drugs like
Pilocarpine.
Sialorrhea:
Refers to excess saliva production.
Causes:
-Gastrointestinal irritants
-Drugs (Pilocarpine)
-Cerebro vascular accident
-Pt. with a severe neurologic deficit
-Pt. who have undergone extensive oral
surgical procedures.
Blockage of duct:
1.Sialolith (stones)
Mostly in submandibular gland
2.Mucous plugging in minor salivary glands due to trauma.
Age changes:
 Parenchymal cells are replaced by adipose tissue.
 Decreased saliva production
 Resting saliva (unstimulated) is in normal range, while stimulated
saliva is less.
Diseases:
 Viral( mumps) & bacterial infections- painful swelling .
Endocrine:
 Diabetes :
Parotid gland swelling may occur
Salivary flow is reduced.
Changes in salivary proteins.
Autoimmune diseases may cause destruction of salivary glands &
reduced salivary flow.
 Sjogren’syndrome
 Rheumatoid arthritis
 Graft-verus host diseases
Patients with adrenal disease may have altered electrolyte composition.
Immune deficiency syndrome:
 Decreased flow rates.
 Lower levels of immunoglobulins in saliva
 Parotid enlargement – lympathedenopathy and lymphoepithelial
cysts
Genetic diseases:
 Cystic fibrosis: Na+ & Cl-
conc. are increased and mucous secreting
glands may develop mucous plugs.
Benign & malignant tumours.
Saliva as a diagnostic aid:
 Oral diseases
High risk caries patient, Patient susceptible to
candidiasis
 Diagnostic aid for clinical problems
Psychological problems, smoking, poisoning
 Systemic diseases affecting saliva
Sjogren’s syndrome, Cystic fibrosis
 Steroid hormone determination:
Functional efficiency of corpus luteum in case
of defect in hypothalamic-pituitary-ovarian axis,
Pregnant status, Ovulation time
 Monitoring of certain drugs that exhibit consistent
saliva : plasma ratio. e.g., phenytoin,
carbamazine, theophyline
References:References:
• Ten Cate’s Oral histology, Development, Structure, and function.Ten Cate’s Oral histology, Development, Structure, and function.
Sixth Edition.Sixth Edition.
• Orban’s Oral Histology and Embryology. Tenth Edition.Orban’s Oral Histology and Embryology. Tenth Edition.
• Bhalajhi SI. Dental anatomy, histology and development. FirstBhalajhi SI. Dental anatomy, histology and development. First
Edition.1998.Edition.1998.
• Berkovitz, Holland GR, Moxham BJ. A colour atlas and textbook ofBerkovitz, Holland GR, Moxham BJ. A colour atlas and textbook of
oral anatomy and embryology. Second Edition.oral anatomy and embryology. Second Edition.
• W.M. Edgar, D.M.O’ Mllane. Saliva and Oral health. (1996), 2nd .W.M. Edgar, D.M.O’ Mllane. Saliva and Oral health. (1996), 2nd .
Ed. BDA LONDON.Ed. BDA LONDON.
• Arther c Guyton, John E Hall. Text Book of Medical physiology,Arther c Guyton, John E Hall. Text Book of Medical physiology,
(2001)10th. Ed. W.B. Saunders company.(2001)10th. Ed. W.B. Saunders company.
• Mandel ID. The diagnostic uses of saliva. J Oral Pathol Med 1990;Mandel ID. The diagnostic uses of saliva. J Oral Pathol Med 1990;
19: 119-25.19: 119-25.
• www.sciencephoto.comwww.sciencephoto.com
THANK YOU

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Salivary glands

  • 1. SALIVARYSALIVARY GLANDSGLANDS Dr AmithaDr Amitha Dept of oral pathologyDept of oral pathology
  • 2.  Definition  Classification Of Salivary Glands  Anatomy of salivary glands  Development of salivary glands  Structure Of Salivary Glands  Histology of major salivary glands  Saliva  Clinical considerations
  • 3. DEFINITION  These are compound tubuloacinar exocrine glands found in oral cavity that secrete complex fluid known as saliva.
  • 4. CLASSIFICATION OF SALIVARY GLANDS  Based on size  Based on type of secretory cells
  • 5. Based on size: 1. Major salivary glands 2. Minor salivary glands 1. Major salivary glands  Collection of secretory cells aggregated into large bilaterally paired extra oral glands with extended duct system through which the gland secretions reach the mouth. - Parotid - Submandibular - Sublingual
  • 6. 2. Minor salivary glands Collection of secretory cells scattered throughout the mucosa & submucosa of the oral cavity with short ducts opening directly onto mucosal surface. - Serous glands of Von Ebner. - Anterior lingual glands. - Lingual, buccal, labial, palatal glands, glossopalatine and retromolar glands
  • 7. 2. Based on type of secretory cells 1. Serous : Parotid 2. Mixed (seromucous): Submandibular 3. Mucous: Minor salivary glands.
  • 8. Parotid gland:  Largest salivary gland  60 to 65% of total saliva.  Pyramidal in shape.  Weighs between 14 & 28g.  Superficial portion of gland is located subcutaneously, in front of the external ear & deeper portion lies behind ramus of mandible.  Associated with facial nerve. ANATOMY OF SALIVARY GLANDS
  • 9.  Stenson’s duct: - runs forward across masseter muscle, turns inwards at the anterior border of masseter & opens at a pappilla in oral cavity just opposite second maxillary molar crown. -5cmx3cm -A small portion of parotid forms accessory gland associated with stenson’s duct, just anterior to the Superficial portion of gland
  • 10. Nerve supply:  Sensory supply-Greater auricular and ariculotemporal nerve  Parasympathetic supply: Glossopharyngial nerve (Preganglionic fibers) synapse in the otic ganglion. Postganglionic fiber enter the gland through the ariculotemporal nerve.  Sympathetic Supply: Postganglionic fibers from plexus on external carotid artery or middle meningial arteries.
  • 11.  Vascular supply & Lymphatic drainage : Arterial supply-External carotid artery Venous drainage-External jugular vein Lymphatic drainage-Upper deep cervical lymph nodes.
  • 12. Submandibular gland:  10 to 15 gm.  2 to 30% of total saliva.  Located at Posterior portion of floor of mouth, medial aspect of mandible & wrapping around posterior border of mylohyoid.
  • 13. •Wharton's duct runs forward and opens into the mouth beneath the tongue, lateral to lingual frenum.
  • 14.  Blood supply: Facial and lingual arteries.  Lymphatic drainage: Submandibular lmph node & deep cervical lymph nodes.  Nerve supply: Parasympathetic supply: Facial nerve reaching gland through the lingual nerve & submandibular ganglion. Sympathetic Supply: Postganglionic fibers from plexus on facial artery
  • 15. Sublingual gland:  Smallest major salivary gland  2gm.  2.5% of total saliva.  Located at anterior part of floor of the mouth, just between mucosa & mylohyoid muscle.  Open into oral cavity through series of small ducts (duct of Rivinus) opening along sublingual fold and open through large duct- Bartholin’s duct, that opens with submandibular duct at sublingual caruncle.
  • 16.  Blood supply: Sublingual & submental arteries.  Lymphatic drainage: Submental lymph nodes  Nerve supply: Parasympathetic supply: Facial nerve reaching gland through the lingual nerve & submandibular ganglion. Sympathetic Supply: -Postganglionic fibers from plexus on facial artery.
  • 17. Minor Salivary gland:  No. between 600 and 1000.  Exist as aggregates of secretory tissue present in submucosa throughout most of the oral cavity.  Not seen in gingiva & anterior part of hard plate.
  • 18.  Rich in mucin, antibacterial proteins and secretory immunoglobulin.  Continuous slow secreting glands, thus have a important role in protecting and moistening oral mucosa, especially when major salivary glands are mostly inactive.
  • 19. Von Ebners’s Lingual serous gland  Located in tongue and open into the troughs surrounding circumvallate papillae on the dorsum o tongue and at the foliate papillae on the side of tongue.  Secrete digestive enzymes & proteins that are thought to play role in taste process  Fluid of their secretion cleanse the trough & prepare the taste receptors for a new stimulus.
  • 20. DEVELOPMENT OF SALIVARY GLANDS Bud formation Formation and growth of epithelial chord. Initiation of branching in terminal parts of epithelial chord. Branching of epithelial chord and lobule formation Canalizatio n Cytodifferentiation Stage I Stage II Stage III Stage IV Stage V Stage VI
  • 21. Stage I (Bud formation) :  Develops as proliferation of oral epithelium into underlying ectomesenchyme (condensing around bud).  A thin basal lamina separates the bud from underlying mesenchyme.  Interaction of the epithelium with underlying condensing mesenchyme associated with salivary glands provide optimum environment for gland formation.
  • 22. Stage II (Formation and growth of epithelial chord): • Proliferation of the epithelial bud into the underlying mesenchyme results in long epithelial cords. • The mesenchyme (MES) around the developing glandular epithelium also proliferates. • Basal lamina is believed to play a role in influencing the morphogenesis & differentiation of the salivary glands.
  • 23. Stage III (Initiation of branching in terminal parts of epithelial chord):  Epithelial chord proliferates & its end branch into bulbs.
  • 24. Stage IV (Branching of epithelial chord and lobule formation): • Terminal ends branch extensively forming numerous bulbs - cleft formation. • ECM component deposition within clefts apparently serve to stablise them. • Connective tissue component below epithelial chord forms capsule & surrounds entire gland. • Hypothesis: -Epithelial Mesenchymal Interactions. Fibroblast growth factor family & their receptors Transforming growth factor-b -Differential contraction of actin filament at the basal and apical ends of the epithelial cells
  • 25. Stage V (Canalization):  Lumen formation takes place at distal ends of chord, then in proximal and at last in central part.  Lumen forms within the ducts before they develop within the terminal buds.  Apoptosis of centrally located cells.  Different rates of proliferation of outer and inner layers o epithelial chord.  Secretion of fluid by ductal cells which increases the hydrostatic pressure within to form a canal.
  • 26. Stage VI (Cytodifferentiation):  Following lumen formation in the terminal buds, epithelium consists of two layers of cells.  Inner cells differentiate into mucous or serous cells depending upon type of specific gland.  Some of the outer cells of epithelium differentiate into myopithelial cells that are present around secretory end piece and intercalated ducts.  Portion of epithelial bud close to the oral cavity forms main excretory duct, distal portion forms secretory end piece.
  • 27.  As epithelial parenchyma increase in size, connective tissue component around them diminishes and remains as a thin layer.  Thicker partition of connective tissue (septa), continuous with the capsule and within which run nerves & blood vessels supplying gland,
  • 28.  Parotid: 4-6th week of I.U. life.  Submandibular :6th week of I.U. life.  Sublingual and minor salivary gland : 8th week of I.U.life.  Maturity of secretory end piece: During last 2 months of gestation.  Secretory component of Gland continues to grow postnatally while as ductal, connective tissue component and vascular component decreases- up to two years of age.
  • 30.  Comprises of -a series of secretory end piece or acini. -connected to the oral cavity by a system of ducts. STRUCTURE OF SALIVARY GLANDS
  • 31. Secretory end piece or accini: • Consists of secretory cells, which are arranged in a roughly spherical configuration around a central lumen or cavity. • Show a great diversity in size, shape, and cell number. • 2 types of cells - Serous cells - Mucous cells
  • 32. Serous Cells:  Parotid & submandibular gland.  Serous cells are also present in demilune formations at the blind ends of mucous secretory tubules (submandibular and sublingual glands).  Secretions of serous cells are proteinaceous -usually enzymatic, antimicrobial, calcium-binding.
  • 33.  Secretory end piece consisting of serous cells are typically spherical and consist of 8 to 12 cells surrounding a central lumen.
  • 34.  Pyramidal in shape, with broad base adjacent to connective tissue stroma & apex situated towards the central lumen.  Nucleus is spherical & situated at the basal third of the cell. Sometimes binucleated.
  • 35.  Cytoplasm stains intensely with H and E.  Apical cytoplasm is filled with secretory granules( macromolec ular component of saliva).  Basal cytoplasm contains RER, which converge towards the golgi complex located just apical or lateral to nucleus.  Also contain cytoskeleton components,
  • 36. Lumen and intercellular canaliculi in a serous end piece • The lumen of serous end piece has small extensions in the form of intercellular canaliculi (found between adjacent serous cells).
  • 37. Plasma membrane exhibits several specializations:  The surface of the seromucous cell lining both the central lumen & canaliculi possess a delicate microvilli that extend into luminar and canalicular spaces.  Space between basement membrane and basal plasma membrane may be increased by complex foldings (0.5 microns) of the basal plasma membrane.  Canaliculus terminates in the form of a classic junctional complex consisting of a tight junction (zona occludens), an adherent junction & a desmosome.
  • 38.
  • 39. Mucous cells:  Predominant secretory cell type of the sublingual gland & most of minor salivary glands.  Also occur in submandibular gland.  Secretion consists of large amount of mucins -lubrication, effective barrier, aggregation of microorganisms.
  • 40.  Secretory component of mucous cell accini consists of round or tubular configuration.  Larger lumen.  Larger than serous cells.  Pyramidal in shape.  Broader luminal surface.
  • 41.  Flattened nucleus situated towards its base  Apical cytoplasm is filled with mucous secretory droplets.  Stain poorly in H & E.  PAS or Alcian blue +ve
  • 42.  Mucous droplets are larger and more irregular in shape - Electron lucent droplets  More prominent Golgi complexes.  Also contain cytoskeleton components, RER, mitochondria, lysosomes and peroxisomes but less prominent.  Like serous cells , mucous cells are joined by intercellular junctions.  Lack intercellular canaliculi.
  • 43. Demilunes Of Gianuzzi  Mucous cells accini may be capped at the blind end by crescents of several serous cells.  Their secretion reach the lumen of the end piece through intercellular canaluculi between mucous cells at the end of the tubule.
  • 44. Myoepithelial Cells (Basket cells):  Contractile cells located around the terminal secretory units and the first portion of the duct system, intercalated duct.  Located between basal lamina and secretory or duct cells and are joined by desmosomes.  Similar to smooth muscle cells but are
  • 45.  They are stellate or spider like, with a flattened nucleus surrounded by a small amount of perinuclear cytoplasm, & long branching process that embrace the secretory duct cells.
  • 46.  The processes are filled with filaments of actin and soluble myosin. Salivary gland immunostained to demonstrate actin in the contractile myoepithelial cells.
  • 47.  Cell membrane has numerous caveolae - initiation of contraction.  Cellular organelle are located in perinuclear cytoplasm.  Only their nuclei is visible in ordinary H & E section.  Myoepithelial cells related to intercalated ducts are more spindle shaped and have fewer processes.
  • 48. Functions:  Expulsion of saliva from secretory end piece to ductal system.  Contraction of myoepithelial cells of intercalated ducts may shorten or widen the ducts , helping in maintaining their patency.  Maintaining cell polarity and structural integrity of secretory end piece.  Produce proteins that have tumour suppressor activity, such as proteinase inhibitors (e.g., tissue inhibitors of metalloproteinases) and antiangiogenesis factors and that cell may act as effective invasive barrier against epithelial neoplasms.
  • 49. DUCTS:  3 classes of ducts - Intercalated - Striated - Terminal  Terminal secretory units opens into a small duct called the intercalated duct. These ducts join to form larger striated ducts which finally empty into a larger excretory duct.
  • 50. Ductal system of a salivary gland: Main excretory duct opens into the oral cavity. Excretory ducts are mostly located in the interlobular connective tissue. Striated ducts are the main intralobular ductal component. Intercalated ducts vary in length and connect the secretory end pieces with the striated ducts. Intercellular canaliculi are extensions of the lumen of the end piece between adjacent secretory cells that serve to increase the luminal surface area available for secretion.
  • 51. Intercalated Ducts:  Small ducts into which secretory end piece empties.  Lined by a single layer of low cuboidal cells and myoepithelial bodies and their processes.  Overall diameter is less than secretory end piece but their lumen is larger than secretory end piece.
  • 52. •Centrally placed nucleus •Little cytoplasm – RER and Golgi apparatus. •A few secretory granules may be found in the apical cytoplasm, especially cells located near end pieces. •Few microvilli projecting into lumen. •Joined to adjacent cells by apical junctional complexes and scattered desmosomes & gap junctions and have folded processes that interdigitate with similar processes of adjacent cells.
  • 53.  Long intercalated duct : Parotid  Shorter : Submandibular  Poorly developed in : sublingual Function: • Channel for salivary flow • Contributes to the salivary secretion – lysozymes & lactoferrin. • Reservoir of undifferentiated cells that may undergo proliferation & differentiation to replace damaged or dying cells in the end pieces and striated ducts.
  • 54. Striated ducts:  Larger duct into which the intercalated ducts empty.  Main ductal component in intralobular portion of gland.  Lined by tall columnar cells.
  • 55.  Centrally placed spherical nucleus.  Pale acidophillic cytoplasm  Basal striation perpendicular to the base of the cells -Mitochondria are lying in cytoplasmic partitions produced by infoldings of the basal plasma membrane.  RER and Golgi apparatus and few secretory granules and
  • 56.  Short stubby microvilli at the luminal surface.  Joined to adjacent cells by junctional complexes and tight junction but lack gap junctions.  Function: -Modify the salivary secretion-Changes from isotonic to hypotonic. -Na+ reabsorption & K+ excretion.
  • 57. Terminal Excretory Ducts:  As the striated ducts leave the individual glandular lobules and enter the inter lobular connective tissue, they join to form excretory ducts.  Larger than striated ducts  Main excretory ducts leading from the gland to the oral cavity is formed by the continued confluence of the
  • 58.  Near the striated ducts they are lined by pseudostratified with columnar cells admix with small basal cells and goblet cells.  As the smaller duct join to form larger duct, no. of basal cells increase & goblet may also be present. • As they approach oral cavity epithelium changes to a stratified epithelium. • Function: Modify the final saliva by altering its electrolyte concentration.
  • 59. CONNECTIVE TISSUE:  Capsule –demarcate gland from adjacent structures.  Septa –divide gland into lobes and lobules -Carry the nerves and blood vessels and excretory ducts.  Fibroblast, Macrophages, Dendritic cells, Mast cells, Plasma Cells, Adipose tissue.  Collagen fibers and elastic fibers along with glycoprotein and proteoglycans of the
  • 60. Nerve Supply:  Follow the course of vessels  2 patterns : I. Intraparietal type : Axons leaves the nerve bundle, looses its schwann cell investment, penetrate the basal lamina and form an expanded swelling or varicosity in close contact(10 to 20 nm) to basolateral membrane or between epithelial cells. e.g., submandibular gland & minor salivary gland of lip. II. Extraparietal Type: Axons remain associated with the nerve bundle in the connective tissue-100 to 200 nm from epithelial cells. e.g., parotid gland
  • 61. Histology of major salivary glands Parotid gland:  All serous  Fat cells may be seen.  Long intercalated ducts are seen.
  • 62. Submandibular gland:  Consists of serous end pieces & mucous tubules capped with serous demilunes.  Serous cells significantly outnumber the mucous cells (pale staining).  The intercalated & striated ducts are less numerous than those in parotid but structurally similar.
  • 63. Sublingual salivary gland :  Mixed, with mucous cells more.  Intercalated ducts are short & difficult to recognise.  Intralobular ducts are fewer in no. than in the parotid or submandibular gland  Some ducts may lack the infoldings characteristics of striated ducts.
  • 64. Minor salivary glands:  Consists of aggregates of secretory end pieces and ducts, organised into lobule like structure in the submucosa or between muscle fibers of tongue.  Mostly mucous  Occasional demilunes.
  • 65. SALIVA Thin, watery, slightly viscid fluid secreted by the salivary glands. •Composition • Functions •Formation & Secretion Of Saliva
  • 66. Water: 94 to 99.5% Solids: 0.5 to 0.6% Organic: Glycoproteins Enzymes: α- amylase Lysozyme Lactoperoxidase Kallikrein Esterase Acid phosphatase Mucins Lactoferrin Blood clotting factors Hormones - Parotin Secretory Immunoglobulin- Composition Inorganic Substances: Sodium Calcium Chloride Bicarbonate Phosphate Potassium Less Amounts: Fluoride Magnesium Iodides
  • 67.  More than a litre of saliva is secreted per day.  Specific Gravity : 1.002 to 1.008  pH: 6.2 to 7.6 (6.7)  Water : 99.4% (unstimulated) & 99.5% (stimulated) Solids: 0.6% (unstimulated) & 0.5% (stimulated)
  • 68. Salivary flow rate • Normal salivary flow rate: 0.3ml/min(unstimulated) 2.0 – 5.0 (stimulated) • Exhibit diurnal and seasonal variations Peak : Mid afternoon Spring • Negligible: During sleep flow No sleep sle ep 12 am 6 am 12 pm 6 pm 12 am 6 am 12 pm 6 pm 12 am 30 20 10  Time of day CIRCAIDIAN RHYTHM OF SALIVA FLOW CIRCAIDIAN RHYTHM OF SALIVA FLOW
  • 69. Effect of feeding on salivary secretion 0 0.005 0.01 0.015 0.02 0.025 0.03 0.035 Volumeofsalivacollectecdeach10min 10 min collection periods Meal during this period • Unstimulated flow – Whole 0.2 – 0.4 ml/min – Submandibular g. 0.1 ml/min – Parotid g. 0.04 ml/min • Stimulation – Whole 2.0 – 5.0 ml/min – Submandibular g. 0.8 ml/min – Parotid g. 1.0 – 2.0 ml/min
  • 70.  Parotid glands: -Watery saliva. -Rich in enzymes such as amylase, proteins such as proline rich proteins and other glycoproteins.  Submandibular glands: -In addition to above component, contains highly glycosalated substance called mucins  Sublingual glands: -Viscous rich in saliva
  • 71. Mucins:  Glycoproteins - protein core with many oligosacharide side chains attached by O- glycosidic bond. Two major mucins (MG1 and MG2).  Lubrication Hydrophillic-resists dehydration. Amylases:  30% of total protein in parotid saliva  Hydrolyzes α(1-4) bonds of starches such as amylose and amylopectin Organic components
  • 72. Lingual Lipase: • Secreted by lingual glands and parotid. • Involved in fat digestion-Important in digestion of milk fat in new-born.  Statherins:  Statherins prevent precipitation or crystallization of supersaturated calcium phosphate in ductal saliva and oral fluid.  Also an effective
  • 73. Lactoferrin: Iron-binding protein Lysozyme: • Also called muramidase • Hydrolysis of α(1-4) bond between N-acetylmuramic acid and N-acetylglucosamine in the peptidoglycan layer of bacteria. Proline-rich Proteins (PRPs): • Inhibitors of calcium phosphate crystal growth • Subdivided into three groups Acidic 45% Basic 30% Glycosylated 25%
  • 74. Salivary peroxidase systems  Sialoperoxidase (SP, salivary peroxidase)  Produced mainly by parotid gland  Myeloperoxidase (MP)  From leukocytes entering via gingival crevice Histatins • Potent inhibitors of Candida albicans growth Cystatins: • Considered to be protective against unwanted proteolysis caused by bacteria - inhibit proteases in periodontal tissues • Also have an effect on calcium phosphate precipitation
  • 75. Inorganic Content Calcium and phosphate:  Help to prevent dissolution of dental enamel  Calcium  1.4 mmol/l (unstimulated saliva)  1.7 mmol/l (stimulated saliva)  50% in ionic form  sublingual > submandibular > parotid  Phosphate  6 mmol/l (unstimulated saliva)  4 mmol/l ( stimulated saliva)  90% in ionic form
  • 76. Bicarbonate:  Buffer - Defence against acids produced by cariogenic bacteria  Derived actively from CO2 by carbonic anhydrase Thiocyanate:  Antibacterial  Higher conc. => lower incidence of caries  Smokers - increased conc. Lead, cadmium, copper:  May reflect systemic concentrations - diagnostics
  • 77. FUNCTIONS 1.PROTECTION:  Mechanical washing action: - Flushes away non-adherent bacterial and acellular debris from the mouth. -Clearance of sugars from the mouth limits their availability to acidogenic plaque microorganisms.  Lubricant: (mucin) - Protects the lining mucosa by forming a barrier against noxious stimuli, microbial toxins and minor trauma. - Allows the oral surface to move one another with minimal friction during function. 2.BUFFERING:  Bicarbonate ,phosphate, some salivary proteins. Metabolism of salivary proteins and peptides produce ammonia and urea which help in increase of pH.
  • 78. 3.Pellicle formation:  Salivary proteins bind to surface of the teeth and oral mucosa, thus forming salivary pellicle which behaves as a protective membrane .  Binding site for bacteria – plaque. 4.MAINTAINENCE OF TOOTH INTEGRITY:  Saliva is saturated with Ca+ & PO4- : acidic prolein rich proteins & statherin  High concentration of these ions ensures that ionic exchange with the tooth surface results in post eruptive enamel maturation, increase in surface hardness, decrease in permeability and increase in resistance to demineralization.
  • 79. 5.ANTIMICROBIAL ACTION:  Lysozyme is an enzyme that can hydrolyse the cell wall of some bacteria.  Lactoferrin binds free iron & in doing so deprives bacteria of this essential element.  Antibodies present in saliva (IgA) -has the capacity to agglutinate microorganisms that are swallowed. -prevent their agglutination to oral tissue.  Mucin and specific agglutins: aggregate microorganisms.  Histatin and peroxidase
  • 80. 6.ROLE OF SALIVA IN TISSUE REPAIR:  Bleeding time of oral tissues is shorter than other tissues.  Experiment have shown that wound healing is faster & wound contraction is also increased in the presence of saliva. 7.DIGESTION:  Forms the food bolus-preparation of the ingested food for deglutition.  Breaks down starch (Amylase).  Lipase  Dilutes gastric chyme. 8.TASTE:  Saliva is required to dissolve substance to be tasted & carry them to the taste buds.  It also contains a protein called gustin that is
  • 81. 8.Salivary anticaries activity:  Carbohydrate & microbial clearance from the oral cavity.  Buffering action - Salivary bicarbonates.  Remineralization of incipient carious lesion- Ca+ , PO4 + , Fl-  Increase enamel resistance to acid decalcification- Fl-  Salivary urea and bicarbonate can increase rate of glycolysis, thus leading to faster carbohydrate metabolization, which inturn leads to reduced duration of the enamel
  • 82. Multifunctionality Salivary Functions Anti- Bacterial Buffering Digestion Mineral- ization Lubricat- ion &Visco- elasticity Tissue Coating Anti- Fungal Anti- Viral Carbonic anhydrases, Histatins Amylases, Mucins, Lipase Cystatins, Histatins, Proline- rich proteins, Statherins Mucins, Statherins Amylases, Cystatins, Mucins, Proline-rich proteins, Statherins Histatins Cystatins, Mucins Amylases, Cystatins, Histatins, Mucins, Peroxidases
  • 83. FORMATION & SECRETION OF SALIVA Two Stage Hypothesis Of Saliva Formation: First stage:  Primary saliva is produced by secretory end piece & intercalated ducts.  Isotonic - most of the organic components & water. Second stage:  Primary saliva is modified as it passes striated & excretory ducts - reabsorption & secretion of electrolyte.
  • 84. TWO STAGE HYPOTHESIS OF SALIVA FORMATION Water & electrolytes Isotonic primary saliva Most proteins Some proteins electrolytes Na+ Cl- resorbed K+ secreted Hypotonic final saliva into mouth
  • 85. First stage:  Formation of macromolecular component  Fluid & Electrolyte release
  • 86. Formation of macromolecular component Proteins synthesis in ribosomes associated with RER Translocated to lumen of RER Folding of protein & Posttranscriptional modification such as disulphide bond formation & N- and O-glycosylation. Transferred as small vesicles to golgi complex Further modification followed by condensation & packing into secretory granules (stored in apical cytoplasm). Secretory signals (via sympathetic neurotransmitters) Fused to luminal surface [Exostosis] Released to external surface
  • 87. The binding of the sympathetic transmitter norepinephrine (NE) to (β- adrenergic (β) receptors on the basolateral membrane activates adenylyl cyclase (AC) Catalyzes the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) Cyclic adenosine monophosphate activates protein kinase A (PKA) Phosphorylates other proteins in a cascade Exocytosi s Fusion of secretory granules with the luminal surface to release their contents into the lumen Role of Secretory signals in exostosis
  • 88. Fluid & Electrolyte Parasympathetic stimulation, Noradrenaline, and substance P ER releases Ca++ Free cytoplasm Ca++ Opens Cl- channel in apical & K+channel in basolateral membrane Apical Efflux of Cl- Extracellular Na+ draws into lumen probably through tight junction to balance the electrochemical gradeint Efflux of water-aquaporin & tight Junction
  • 89. Binding of the parasympathetic transmitter, acetylcholine (ACh), to muscarinic cholinergic (MC) receptors, and by norepinephrine binding to (α-adrenergic receptors (α). Activate phospholipase C (PlC), Converts phosphatidylinositol bisphosphate (PIP2) to inositol trisphosphate (IP3) and diacylglycerol (DAG). Inositol trisphosphate causes the release of Ca2+ from intracellular stores, probably the endoplasmic reticulum. The increased Ca2+ concentration opens Cl– channels in the luminal membrane and K+ channels in the basolateral membrane, and activates the basolateral Na+/K+/2Cl– cotransporter. The increased luminal Cl– is balanced by the movement of extracellular Na+ across the tight junctions (TJ), and the resulting osmotic gradient pulls water into the lumen through the cell and probably through the tight junction. Role of Stimulatory signals in Fluid & Electrolyte release
  • 90. • Calcium also modulates the activity of protein kinase A and protein kinase C (PKC). Protein kinase C, in turn, modulates exocytosis and intracellular Ca2+ concentrations.
  • 91. Ductal Modification of saliva:  Net reabsorption of Na+ and Cl- by luminal & basolateral membranes-hypotonic final saliva.  Secretion of K+ and HCO3 -.  Flow rate is directly related to Na+ and Cl- in saliva and inversely related to K+ in saliva  Flow rate is directly related to HCO3 - in saliva.
  • 92.
  • 93. Neural control of Salivation:  The afferent pathways: via the facial & Glossopharyngeal nerves to a solitary nucleus in the medulla.  There is also an input from higher centers in response to smell, sight etc.  Efferent pathways:  The Parasympathetic efferent pathways -for the S.L&S.M. from the Facial nerve (chord tympani to reach the lingual nerve) via S.M. ganglion; -the parotid gland from the glossopharyngeal N which pass through the tympanic and lesser superficial petrosal nerves to reach the otic ganglion where they synapse with post ganglionic fibres of the auriculotemoral nerve which supply
  • 94.
  • 95. Clinical considerations Xerostomia:  Drugs- central or peripheral inhibition of salivary secretion.  Destruction of salivary gland: -Radiotherapy to H & N region -Chemotherapy -Bone marrow transplant -Autoimmune diseases (sjogren’s syndrome)- invasion of lymphocytes & destruction of epithelial cells.  Psychological factors
  • 96.  Loss of protective effect of salivary buffers, proteins, and mucins- increased susceptibility to infections.  Difficulty & pain on eating, speech and swallowing.  Temporary saliva Oral pharmacosympathomimmetic drugs like Pilocarpine.
  • 97. Sialorrhea: Refers to excess saliva production. Causes: -Gastrointestinal irritants -Drugs (Pilocarpine) -Cerebro vascular accident -Pt. with a severe neurologic deficit -Pt. who have undergone extensive oral surgical procedures.
  • 98. Blockage of duct: 1.Sialolith (stones) Mostly in submandibular gland 2.Mucous plugging in minor salivary glands due to trauma. Age changes:  Parenchymal cells are replaced by adipose tissue.  Decreased saliva production  Resting saliva (unstimulated) is in normal range, while stimulated saliva is less.
  • 99. Diseases:  Viral( mumps) & bacterial infections- painful swelling .
  • 100. Endocrine:  Diabetes : Parotid gland swelling may occur Salivary flow is reduced. Changes in salivary proteins. Autoimmune diseases may cause destruction of salivary glands & reduced salivary flow.  Sjogren’syndrome  Rheumatoid arthritis  Graft-verus host diseases Patients with adrenal disease may have altered electrolyte composition.
  • 101. Immune deficiency syndrome:  Decreased flow rates.  Lower levels of immunoglobulins in saliva  Parotid enlargement – lympathedenopathy and lymphoepithelial cysts Genetic diseases:  Cystic fibrosis: Na+ & Cl- conc. are increased and mucous secreting glands may develop mucous plugs. Benign & malignant tumours.
  • 102. Saliva as a diagnostic aid:  Oral diseases High risk caries patient, Patient susceptible to candidiasis  Diagnostic aid for clinical problems Psychological problems, smoking, poisoning  Systemic diseases affecting saliva Sjogren’s syndrome, Cystic fibrosis  Steroid hormone determination: Functional efficiency of corpus luteum in case of defect in hypothalamic-pituitary-ovarian axis, Pregnant status, Ovulation time  Monitoring of certain drugs that exhibit consistent saliva : plasma ratio. e.g., phenytoin, carbamazine, theophyline
  • 103. References:References: • Ten Cate’s Oral histology, Development, Structure, and function.Ten Cate’s Oral histology, Development, Structure, and function. Sixth Edition.Sixth Edition. • Orban’s Oral Histology and Embryology. Tenth Edition.Orban’s Oral Histology and Embryology. Tenth Edition. • Bhalajhi SI. Dental anatomy, histology and development. FirstBhalajhi SI. Dental anatomy, histology and development. First Edition.1998.Edition.1998. • Berkovitz, Holland GR, Moxham BJ. A colour atlas and textbook ofBerkovitz, Holland GR, Moxham BJ. A colour atlas and textbook of oral anatomy and embryology. Second Edition.oral anatomy and embryology. Second Edition. • W.M. Edgar, D.M.O’ Mllane. Saliva and Oral health. (1996), 2nd .W.M. Edgar, D.M.O’ Mllane. Saliva and Oral health. (1996), 2nd . Ed. BDA LONDON.Ed. BDA LONDON. • Arther c Guyton, John E Hall. Text Book of Medical physiology,Arther c Guyton, John E Hall. Text Book of Medical physiology, (2001)10th. Ed. W.B. Saunders company.(2001)10th. Ed. W.B. Saunders company. • Mandel ID. The diagnostic uses of saliva. J Oral Pathol Med 1990;Mandel ID. The diagnostic uses of saliva. J Oral Pathol Med 1990; 19: 119-25.19: 119-25. • www.sciencephoto.comwww.sciencephoto.com