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Salivary glands
Objectives
• What are the functions of saliva
• Explain the anatomy, development and structure of salivary glands
• Understand the mechanism of saliva production and modulation
• Nerve and blood supply of salivary glands
• Histology of major and minor salivary glands
• Discuss Clinical nosiderations
Oral fluid
mixed or whole saliva
• secretions of the major glands, the minor glands, desquamated oral
epithelial cells, microorganisms and their products, food debris, and serum
components and inflammatory cells that gain access through the gingival
crevice.
Functions of saliva
• Protection
• Buffering
• Tooth integrity
• Antimicrobial activity
• Tissue repair
• Digestion
• Taste
Functions of saliva…
• Protection
Flushing action-water
Lubrication-mucins and glycoproteins
barrier against noxious stimuli; microbial toxins and minor traumas
Pellicle formation-proteins, glycoproteins, mucins
• Buffering action-
Bicarbonate and phosphate protect the teeth from demineralization caused by
bacterial acids produced during sugar metabolism.
metabolism of salivary proteins and peptides by bacteria produces urea and
ammonia, which help to increase the pH.
Functions of saliva…
• Tooth integrity
Post-eruptive maturation of the enamel-Calcium, phosphate, fluoride,
statherin, acidic proline-rich proteins
• Antimicrobial activity
Physical barrier-Mucins
Immune defense-Secretory IgA
Nonimmune defense-Peroxidase, lysozyme, lactoferrin, histatin, mucins,
agglutinins, secretory leukocyte
cystatin (inhibitors of harmful cysteine-proteinases produced by bacteria and dying
neutrophils), lysozyme histatin and lactoferrin (antibacterial agents), statherin
(inhibitor of mineralization)
Functions of saliva…
• Tissue repair
Wound healing, tissue growth and regeneration by growth factors
• Digestion
Amylase and lipase
• Taste
minor glands proteins- bind taste substances and present them to the taste
receptors-gustin (detection of taste).
Composition of saliva
• 99% water
• Electrolytes
Na+, K+, Cl−, Ca2+, Mg2+, and F−
• Secretory proteins/peptides
Amylase, proline-rich proteins, mucins, histatin, cystatin, peroxidase, lysozyme,
lactoferrin, defensins, and cathelicidin-LL37
• Immunoglobulins
Secretory IgA; IgG and IgM
• Small organic molecules
Glucose, amino acids, urea, uric acid, and lipid molecules
• Other components
EGF, insulin, and serum albumin
Saliva production, rate and pH
• 90% saliva production from the major salivary glands
• very small contribution to the pooled saliva is derived from gingival fluid and from
sebaceous glands.
• Sublingual gland and the minor salivary glands spontaneously secrete saliva, but the
bulk of this secretion is nerve-mediated.
• parotid and submandibular glands do not secrete saliva spontaneously and their
secretion is entirely nerve-mediated (during anaesthesia, secretion ceases)
• Resting 0.2–0.4 ml/min
• Stimulated 2.0–5 ml/min
• pH 6.7–7.4
Salivary gland
• 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
Major salivary glands
• Collection of secretory cells aggregated into large bilaterally paired extra oral
extra oral glands with extended duct system through which gland secretions
secretions reach the oral cavity
i. Parotid
ii. Submandibular
iii. Subligual
Minor salivary glands
• Collection of secretory cells scattered throughout the mucosa and
submucosa of oral cavity with short ducts opening directly into oral cavity
cavity
Serous glands of von ebner
labial, lingual, palatal, buccal, glossopalatine, and retromolar glands
• Based on type of secretory cells
1. Serous: parotid
2. Mixed: submandibular
3. Mucous: lingual
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
• A small portion of parotid forms
accessory gland associated with
stenson’s duct, ant. to the Superficial
portion of gland
• Stenson’s duct
runs forward across masseter muscle,
turns inwards at the ant. border of
masseter & opens at a papilla in oral
cavity just opp. 2nd maxillary molar
Parotid gland:
• Nerve supply:
Sensory supply –
Greater auricular and ariculotemporal nerve
Autonomic supply
Parasympathetic supply: CN IX
Preganglionic fibers (tympanic branch → plexus→nerve) synapse in the otic
Parotid gland:
• Vascular supply & Lymphatic drainage :
Arterial supply-
External carotid artery
Venous drainage-
External jugular vein
Lymphatic drainage-
Upper deep cervical lymph nodes
Parotid gland:
Submandibular gland
• 10 to 15 gm
• 2 to 30% of total saliva
• Located at Post part of floor of mouth,
medial aspect of mandible & wrap around
posterior border of mylohyoid.
• Wharton's duct runs forward above the
mylohyoid muscle and opens into the mouth
beneath the tongue( sublingual caruncle),
lateral to lingual frenum
Sensory supply –
via the lingual nerve
Autonomic supply
Parasympathetic supply: CN VII
Preganglionic fibers (facial nerve sensory root→ geniculate
ganglion→chorda tympani →lingual nerve) synapse in the submandibular
ganglion. Postganglionic fiber enter the gland through glandular branches.
Sympathetic Supply:
originates from the superior cervical ganglion → postganglioic fibers travel
along the facial artery to reach the submandibular gland
Submandibular gland
Blood supply:
Facial and lingual arteries.
Lymphatic drainage:
Submandibular lymph node & deep cervical lymph nodes.
Submandibular gland
Sublingual gland
• Smallest major salivary gland
• 2gm
• 2.5% of total saliva
• Located at ant. part of floor of the mouth, just
between mucosa & mylohyoid muscle
• Open into oral cavity either through series of
small ducts-duct of Rivinus opening along
sublingual fold or through large duct-
Bartholin’s duct, that opens with
submandibular duct at sublingual caruncle.
Sensory supply –
via the lingual nerve
Autonomic supply
Parasympathetic supply: CN VII
Preganglionic fibers (facial nerve sensory root→ geniculate
ganglion→chorda tympani →lingual nerve) synapse in the
submandibular ganglion. Postganglionic fiber enter the gland through
glandular branches.
Sympathetic Supply:
originates from the superior cervical ganglion → postganglioic fibers
travel along the facial artery to reach the sublingual gland
Sublingual gland
Blood supply
Sublingual & submental arteries
Lymphatic drainage: Submental lymph nodes
Nerve supply: Parasympathetic supply: Facial nerve reaching gland through
through the lingual nerve & submandibular ganglion. Sympathetic Supply: -
Postganglionic fibers from plexus on facial artery.
Sublingual gland
Minor Salivary glands
• 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.
• predominantly mucous glands
• 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.
Development of salivary glands
Stage I Initial Bud stage
Stage II Early pseudoglandular stage.
Stage III Late pseudoglandular stage.
Stage IV Canalization
Stage V Cytodifferentiation
Stage I (Initial Bud stage)
• proliferation of oral epithelium into underlying
ectomesenchyme (condensation occurs) form spherical
epithelial bud
• spherical bud connected to the oral epi. through a thick solid
solid epi. stalk
• Epi. stalk → the main salivary duct, whereas the terminal
bulb → intralobular parenchyma (acini, duct system).
• thin basal lamina separates the bud from underlying
mesenchyme.
• B.M not only provides structural support to the epithelium,
but it acts as a reservoir of growth factors
• surrounding mesenchymal cells become more tightly
packed and well-defined →form the capsule of the gland.
Development of salivary glands…
Stage II (Early pseudoglandular stage) epithelial chord formation,
Initiation of branching in terminal parts of epithelial chord
cell proliferation
• epithelial bud solid cord of cells i.e., epi. cord
• mesenchyme around the epithelial cord Condense and
and proliferate
• arborization of salivary gland epi. produced by
branching morphogenesis
clefting
• Single primary epithelial bud 2 to 3 buds.
• Buds expand, elongate, and cleft again and again
extensive network of epithelial stalks and end buds.
• Basal lamina is believed to play a role in influencing the
morphogenesis & differentiation of the salivary glands
Stage III (Late pseudoglandular stage) epithelial chord
branching and lobule formation
• Complex network of epithelial stalks and end buds
multilobed gland.
• branching continues at the terminal portion of the cord
cord extensive treelike system of bulbs.
• C. tissue differentiates around the branches
extensive lobulation.
• glandular capsule forms from mesenchyme and
surrounds the entire glandular parenchyma
• The basement membrane is secreted by the epithelial
cells located at the periphery of the salivary epithelial
bud and the adjacent mesenchymal cells, whereas the
stromal elements of the extracellular matrix are
produced by the mesenchymal cells.
Stage IV (Canalization)
• Lumen formation takes place at distal ends of
chord, then in proximal and at last in central part.
Stage V (Cytodifferentiation)
• histodifferentiation of the acini and
intercalated ducts
• Epi. cells lining the ducts, tubules, and acini
proceed to differentiate both morphologically
morphologically and functionally
• Following lumen formation in the terminal
buds, epithelium consists of two layers of
cells.
1. Inner cells differentiate into mucous or
serous cells depending upon type of
specific gland.
2. Some of the outer cells of epithelium
differentiate into myopithelial cells that are
are present around secretory end piece and
and intercalated ducts.
• Portion of epithelial bud close to the oral
• 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
Development of salivary glands…
• 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.
• Gland continues to grow postnatally with the volume proportion of acinar
tissue increasing and the volume proportions of ducts, connective tissue, and
vascular elements decreasing— up to 2 years of age
Development of salivary glands…
Structure of salivary glands
• Comprises of a series of secretory end piece or acini
• connected to the oral cavity by a system of ducts.
On the basis of location, ducts are of two
types:
• Intralobular ducts
within the lobule (intercalated and striated
ducts)
• Interlobular ducts:
lie within the connective tissue within the
lobules of the gland (excretory ducts)
Intercellular canaliculi are extensions of the
lumen between adjacent secretory cells-
increase the luminal surface area available for
secretion.
Structure of salivary glands…
Salivary gland showing its lobular
organization.
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 cell
Serous cells
• Secretory end pieces that are composed of serous
cells are typically spherical and consist of 8 to 12
cells surrounding a central lumen
• pyramidal in shape
• broad base on the basement membrane, and
narrow apex faces the lumen
• spherical nucleus placed at the basal region of the
cell
• lumen usually has finger-like extensions located
between adjacent cells called intercellular
canaliculi that increase the size of the luminal
surface of the cells.
• secretory granules-macromolecule components of
saliva are stored in the apical cytoplasm.
• granules are zymogen granules-eosinophilic and are formed by
glycosylated proteins which are released into a vacuole.
• serous cells produce proteins and glycoproteins (enzymatic,
antimicrobial, calcium-binding)
• serous glycoproteins have N-linked (bound to the β-amide of asparagine)
oligosaccharide side chains.
Organelles include
• RER (basal)
• Golgi complex (lateral or apical)
• Mitochondria
• lysosomes
• peroxisomes. cytoskeletal components,
Serous cells
several specializations
• luminal surface have intercellular canaliculi and
few short microvilli
• lateral surfaces have occasional folds that
interdigitate with similar processes from the
adjacent cells
• Basal surface has regular folds
• folding of the cell membranes greatly increases
the surface area of the cell.
Serous cells-plasma membrane
Serous cell-Cell junctions
• Cells joined to one another-intercellular junctions
• junctional complex
A tight junction
an adhering junction
desmosome
• cells attached to the basal lamina and the underlying
C. tissue by hemidesmosomes.
• Gap junctions along
the lateral cell surfaces.
separates the luminal
surface from the basolateral
surfaces of the cell, selective
permeability to ions, hold
cells together
allow the passage of small
molecules e.g., ions,
metabolites, and cAMP.
Mucous cell
• secretory endpieces that are composed of mucous
cells typically have a tubular configuration
• these tubules appear as round profiles with mucous
cells surrounding central lumen of larger size than
that of serous endpieces.
• nucleus is oval or flattened located above the basal
plasma membrane
• Mucous end pieces have serous cells associated with
them in the form of a demilune or crescent
• large amounts of secretory product (mucus)
accumulates in the apical cytoplasm such that
nucleus and ER compressed against the basal cell
mem.
• Mucus unstained in histologic preparations-giving an
empty appearance to the supranuclear cytoplasm.
• Special stains: periodic acid–Schiff stain or Alcian
blue reveal sugar residues or acidic groups in the
the secretory material
Mucous cell
• Mucous cells have a large Golgi complex
• Small granules form at the trans face of the
Golgi complex, stored in the apical cytoplasm.
• The ER and other organelles are limited
mainly to the basal cytoplasm of the cell
• mucous cells are joined by a variety of
intercellular junctions.
• Mucous cells lack intercellular canaliculi,
except for those covered by Demilune cells.
Mucous cell
• products of mucous cells are mucins (glycoproteins which have a protein
core called apomucin)
• mucous glycoproteins have O-linked (bound to the hydroxyl groups of
serine or threonine) oligosaccharide side chains
• Mucins function mainly to lubricate and form a barrier on surfaces and to
bind and aggregate microorganisms.
Mucous cell
Myoepithelial Cells (Basket cells):
• Contractile cells located around the
terminal secretory units and intercalated
duct
• Located between basal lamina and
secretory or duct cells and are joined by
desmosomes
• Similar to smooth muscle cells but are
derived from epithelium
• 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.
• Other Cellular organelle are located in
perinuclear cytoplasm
SEM of myoepithelial cells
Myoepithelial Cells
• Myoepithelial cells related to intercalated ducts are more spindle shaped and
have fewer processes
• processes are filled with filaments of actin and myosin
• cell membrane characterized by the presence of pinocytic vesicles- later
named caveolae
• Caveolae are a special type of lipid rafts, small invaginations of the plasma
membrane involved in signal transduction pathways
Myoepithelial Cells-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 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
• Cells may act as effective invasive barrier against epithelial neoplasms
DUCTS
• varied network of tubules that progressively increase in diameter, beginning
at the secretory end pieces and extending to the oral cavity
• 3 classes of ducts
Intercalated
Striated
Excretory
• participates in the production and modification of saliva.
1. Intercalated Ducts
• 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.
• intercalated ducts are lined by a simple cuboidal
epi., and myoepithelial cell bodies and their
processes typically are located along the basal
surface of the duct.
• overall diameter of the intercalated ducts is
smaller than that of the end pieces, and their
lumina are larger than those of the end pieces.
• Several ducts draining individual end pieces join
to form larger intercalated ducts, which may join
again before emptying into the striated ducts
Intercalated Ducts- cells
• Low cuboidal in shape
• centrally placed nuclei and a small amount of
cytoplasm containing RER and a small Golgi complex
• 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
• lateral surfaces are joined by junctional complexes,
desmosomes and gap junctions
• lateral surfaces have folded processes that
interdigitate with similar processes of adjacent cells.
• Because of their small size and lack of distinctive
features, intercalated ducts often are difficult to
identify in routine histologic sections.
• secrete macromolecular components (lysozyme and lactoferrin) in the
saliva, stored in their secretory granules.
• A portion of the fluid component of the primary saliva is also added
• Undifferentiated cells (salivary gland stem cells) are believed to be
present in the intercalated ducts--proliferate and undergo
differentiation to replace damaged or dying cells in the end pieces and
striated ducts.
Intercalated Ducts-function
2. Striated ducts
• constitute the largest portion of the duct system.
• located within the lobules of the gland-intralobular
• In well-preserved tissue, faint radially oriented lines or striations may be
observed in the basal cytoplasm of the ducts.
• overall diameter of the duct is greater than secretory end pieces, and the
lumen is larger than those of the secretory end pieces and intercalated ducts.
• basal lamina encloses the striated duct, and a capillary plexus is present in
the surrounding connective tissue.
H and E stained micrograph of human
submandibular gland. Striated ducts (arrowheads)
stain lightly with eosin. The serous acini stain with
hematoxylin.
Light micrograph of striated ducts (SD) in the
human submandibular gland.
• duct cells are columnar, with a centrally placed nucleus
and pale, acidophilic cytoplasm
• duct cells show basal striations due to presence of
numerous elongated mitochondria in narrow cytoplasmic
partitions, separated by highly infolded basolateral cell
membranes
• apical cytoplasm contain small secretory granules
(kallikrein) and electron-lucent vesicles (endocytosis of
substances) .
• duct cells also contain lysosomes and peroxisomes, and
glycogen deposits (present in the perinuclear cytoplasm)
• Adjacent cells are joined by well-developed tight
junctions and junctional complexes but lack gap
junctions.
• The structure of the duct cells reflects an important
2. Striated ducts-cells
3. Excretory ducts
• located in the connective tissue septa between the
lobules of the gland, named as extralobular or
interlobular ducts.
• ducts are larger in diameter than striated ducts
• Ducts 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
• As the smaller ducts join to form larger excretory ducts,
the number of basal cells increases, and scattered
mucous (goblet) cells may be present
• The epithelium of the main excretory duct may become
stratified near the oral opening.
• smaller excretory duct cells structure (columnar cells) is similar to that
of the striated duct cells.
• As the ducts increase in size, the number of mitochondria and the extent
of infolding of the basolateral membranes decrease.
• basal cells have
intermediate filaments (tonofilaments),
actin filaments
elongated processes similar to myoepithelial cells
attached to the basal lamina by prominent hemidesmosomes.
• experimental research suggest that the columnar cells and the basal
cells have a high rate of proliferation.
3. Excretory ducts-cells
Other cell types include
• Tuft (caveolated or brush) cells, with long stiff microvilli and apical
vesicles → believed to be receptor cells, nerve endings occasionally are
found adjacent to the basal portions of these cells
• lymphocytes and macrophages-with pale cytoplasm and dense nuclear
chromatin
• dendritic cells, or antigen presenting cells with long branching processes
that extend between the epithelial cells→involved in immune
surveillance and the processing and presentation of foreign antigens to T
lymphocytes.
3. Excretory ducts-cells
Formation and Secretion of Saliva
• Two Stages 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
First stage of saliva secretion
• Formation of macromolecular component
• Fluid and Electrolytes secretion
Sympathetic or parasympathetic
stimulation
Ribosomes-
mRNA→protein
RER-
Protein Folding and
post-translational
modification
(glycosylation)
Golgi complex-
Further
modification,
condensation and
packaging
Secretory
granules-
Stored in apical
cytoplasm
Contents released
into lumen in
response to
stimulus
Mechanisms of salivary secretion
1. Norepinephrine, acting via Îą-adrenergic receptors, activate the
phospholipid-Ca2+ pathway
2. Substance P, VIP, neuropeptide Y and calcitonin G-RP (peptides
released from autonomic nerve terminals) exert effects on the
glandular vasculature to regulate blood flow
3. Nitric oxide (produced by PS nerves, VEC, and GSC) stimulates the
production of cyclic GMP, release of Ca2+ from intracellular storage
sites in secretory cells
4. Extracellular ATP activates the P2X and P2Y receptors on secretory and
duct cells→ P2X receptors allow EC Ca2+ to enter the cell
→ P2Y receptors cause release of Ca2+ from intracellular storage
sites
Other Mechanisms Modulating Saliva
Secretion
Ductal Modification of Saliva
1. reabsorption of Na+ and Cl−
2. Secretion of K+ and HCO³¯
little or no secretion or reabsorption of water occurs in the striated and
excretory ducts.
• depends on the salivary flow rate
At high flow rates, saliva in contact with ductal epithelium for a shorter
time
Low flow rates the electrolyte concentrations change in the opposite
direction
reabsorption of Na+ and Cl−↓, Secretion of K+ ↓
Na+ and Cl− conc ↑, K+
conc↓
Innervation of ducts
• Electrolyte reabsorption and secretion is regulated by
autonomic nervous system
mineralocorticoids
• The sympathetic innervation has a more important role in regulating
electrolyte transport in the ducts than in the acini because of a larger number
of cAMP regulated Cl− channels in the luminal cell membrane.
Connective Tissue component
• a surrounding capsule that demarcates the gland from adjacent
structures
• Septa extend inward from the capsule divide the gland into lobes and
lobules
• Cells include
fibroblasts, macrophages, dendritic cells, mast cells, plasma cells,
adipose cells, granulocytes and lymphocytes.
• ECM has
Proteins (Collagen and elastic fibers) and ground substance
(glycoproteins and proteoglycans)
• Septa carry the blood vessels and nerves that supply the parenchymal
components and the excretory ducts that convey saliva to the oral cavity
• partitions carry the arterioles, capillaries, and venules of the
microcirculation and the finer branches of the autonomic nerves that
innervate the secretory and ductal cells.
Connective Tissue component
• Plasma cells located adjacent to the secretory end pieces and intralobular
ducts produce immunoglobulins
• IgA- main immunoglobulin-synthesized as a dimer complexed with an
additional protein called J chain.
• epithelial cells have receptors for dimeric IgA on their basolateral
membranes
• IgA-secretory vesicles move from the basolateral cytoplasm to the apical
cytoplasm, translocated into the saliva by transcytosis.
• Small amounts of IgG and IgM also are secreted into the saliva.
Connective Tissue component
Nerve Supply
• Within the gland lobules, branches of the nerves follow the blood
vessels, eventually forming a plexus of unmyelinated fibers adjacent to
arterioles, ducts, and secretory end pieces
• axons of each nerve bundle are invested by cytoplasmic processes of
Schwann cells.
• Several varicosities may be present along the length of an axon
containing neurotransmitter vesicles and mitochondria
• These varicosities are believed to be the site of innervation of the gland
cells and thus the site of neurotransmitter release.
• a single nerve may innervate more than one epithelial cell.
• no specializations of the axonal or epithelial cell membranes occur at
these sites as occur at synapses in the CNS.
Intraparenchymal Extraparenchymal
axon leaves the nerve bundle, loses its
its Schwann cell investment,
penetrates the epi basal lamina, and
forms an expanded swelling/ varicosity
varicosity
the axon remains associated with the
nerve bundle, and forms a varicosity
but the Schwann cell covering is
absent over the varicosity.
Axonal Varicosity is in close contact
(10 to 20 nm) with the basolateral
membrane of the epithelial cell.
the axonal varicosity is separated from
from the epithelial cells and the basal
laminae by 100 to 200 nm
Hypolemmal Neuroeffector
relationship
Epilemmal Neuroeffector relationship
submandibular gland and in the minor
glands of the lip,
Parotid gland.
Nerve–epithelial cell relationship
Blood supply
• an extensive blood supply-Rapid and sustained secretion of saliva
• One or more arteries enter the gland and give rise to smaller arteries and
arterioles that tend to follow the path of the excretory ducts.
• arterioles break up into capillaries that are distributed around the secretory
end pieces and striated ducts.
• In some species the capillaries supplying the secretory end pieces and ducts
arise from separate arterioles (i.e., a parallel arrangement), whereas in other
species a venous portal system connects the capillary network around the
end pieces with that around the ducts.
• An extensive capillary plexus exists around the excretory ducts.
• The endothelium of the capillaries and postcapillary venules is fenestrated.
Blood supply
• The venous return follows the arterial supply
• arteriovenous anastomoses occur in some glands.
Blood flow↑
more blood is diverted
through AV
anastomoses
↑ fluid filtration across
the capillary
endothelium
↑ venous and capillary
pressures
Histology of the Major Salivary Glands
PAROTID GLAND
• spherical secretory end pieces are all serous
• pyramidal shaped acinar cells have a spherical, basally situated nucleus and
and surround a small, central lumen.
• Basal cytoplasm stains with basophilic dyes, and the secretory granules in
in the apical cytoplasm usually stain with acidophilic dyes.
• Fat cell spaces often are seen in sections of the parotid gland.
• Intercalated ducts are
numerous and long
lined with cuboidal epithelial cells
lumina are larger than that of the acini.
myoepithelial cells sometimes present at the basal surface of the ducts
• Striated ducts are
Simple columnar epithelium, with round, centrally placed nuclei
Numerous in number
slightly acidophilic
round or elongated tubules of larger diameter than the end pieces.
Faint striations, representing the infolded basal cell membranes and
mitochondria, may be visible below the nucleus.
H and E micrograph of Parotid gland
Submandibular gland
• Mixed gland contain serous end pieces and mucous tubules capped with
serous demilunes
• Although the proportions of serous and mucous secretory end pieces may
vary from lobule to lobule and among individual glands, serous cells
significantly outnumber the mucous cells.
• serous end pieces are similar in structure to those found in the parotid gland
• mucous secretory cells
pale-staining secretory material
little cytoplasm is usually visible,
nucleus is compressed against the basal cell membrane and contains
densely stained chromatin.
• intercalated and striated ducts are less numerous than those in the parotid
gland
H and E micrograph of Submandibular gland
Sublingual gland
• mixed gland, but mucous secretory cells
predominate
• The mucous tubules and serous demilunes
resemble those of the submandibular gland.
• The intercalated ducts are short and difficult to
recognize.
• Intralobular ducts are fewer in number than in the
parotid or submandibular glands
• some ducts may lack the infolded basolateral
membranes characteristic of striated ducts.
Histology of Minor salivary glands
• consist of aggregates of secretory end pieces and ducts, organized into small
lobule-like structures located in the submucosa or between muscle fibers of
the tongue
• ducts open directly onto the mucosal surface.
• The secretory end pieces of most minor glands are mostly mucous or have a
small serous component arranged as occasional demilunes.
• Intercalated ducts often are poorly developed, and the larger ducts may lack
the typical infolded basolateral membranes of the striated ducts of the major
glands.
lingual serous glands (of Ebner) present in the tongue below the
circumvallate papillae are pure serous glands.
• secretions are released in regions with significant numbers of taste buds
e.g., troughs surrounding the vallate papillae, and clefts between the
foliate papillae on the sides of the tongue.
• They secrete digestive enzymes and proteins believed to play a role in
the taste process.
• The fluid component of their secretions is presumed to cleanse the
trough and prepare the taste receptors for a new stimulus.
• Minor gland saliva typically is rich in mucins, various antibacterial
proteins, and secretory immunoglobulins.
• minor glands exhibit a continuous, slow secretory activity, and thus have
an important role in protecting and moistening the oral mucosa,
especially at night when the major salivary glands are mostly inactive
H and E stained micrographs of human minor salivary glands.
A, Mucous gland (Muc) in the lateral portion of the hard
palate. B, Lingual serous (Ebner's) glands and mucous glands
located between muscle fibers in the post part of the tongue.
Clinical Considerations
Age changes
• With age, a generalized loss of salivary gland parenchymal tissue
tissue occurs i.e., 30% to 60% reduction in acinar volume of the
the major salivary glands has been observed.
• lost salivary cells are replaced by adipose tissue.
• increase in fibrous c. tissue and vascular elements
• Changes of the duct system, including an increase in nonstriated
Age changes
• Although decreased production of saliva often is observed in older
older persons, whether this is related directly to the reduction in
in parenchymal tissue is not clear.
• Some studies of healthy older individuals, in which the use of
medications was controlled carefully, revealed little or no loss of
of salivary function, suggesting a large functional reserve capacity.
capacity.
• Other studies suggest that although resting (unstimulated)
salivary secretion is in the normal range, the volume of saliva
produced during stimulated secretion is less than normal.
Clinical Considerations
Xerostomia
• Dry mouth caused by loss of salivary function or a reduction in the volume of
volume of secreted saliva
Xerostomia
Medication Increasing
age
Radiotherapy Chemotherapy
Autoimmune
diseases
Clinical Considerations
Loss of salivary function
• Oral dryness
• loss of the protective effects of salivary buffers, proteins, and mucins.
• oral tissues are more susceptible to infections
• Difficulty in speech, mastication, and swallowing
• teeth are highly susceptible to caries
Rx
• frequent sipping of water or artificial saliva (temporary relief)
• therapy with oral parasympathomimetic drugs, such as pilocarpine, to
increase salivary flow
• genetic modification of salivary gland cells to increase fluid and protein
secretion.
Diseases
Clinical Considerations
Diseases that affect salivary
gland function
Endocrine Autoimmune
diseases
Infectious Genetic
SjĂśgren's syndrome,
Rheumatoid
arthritis Graft-
versus-host disease,
acquired immune
deficiency
Diabetes Viral (CMV, EBV,
HSV-6 & 7)
Bacterial
Cystic fibrosis
Sialoliths
• Blockage may occur of the main collecting duct of a major salivary gland
(usually the submandibular, but occasionally the parotid)
• Cause is usually the sialolith (stone or calculus) but sometimes is a stricture
or an inflammatory exudate.
• At mealtimes, lack of saliva access to the mouth caused by the blockage
results in swelling of the gland, together with pain and subsequent discharge.
Clinical Considerations
Mucoceles and ranulas
• Damage to the ducts of minor and sublingual salivary
glands result in the extravasation of mucus into the
surrounding soft tissues
• When the extravasation persists, mucocele is formed
• In the case of the sublingual gland, it is also termed a
ranula because the swelling it causes to the floor of the
mouth somewhat resembles the belly of a frog.
• When a ranula is situated above the mylohyoid muscle (oral
ranula), it produces a painless swelling that may displace
the tongue
• If it penetrates the mylohyoid (cervical ranula), it produces a
swelling in the neck.
• Treatment of these conditions may necessitate the surgical
removal of the affected sublingual gland.
Staphne’s cavity (cyst)
• A portion of the submandibular gland may
invaginate into the lingual surface of the
mandible, typically in the region of the ramus
ramus below the mandibular canal, near the
the angle of the ramus.
• On a radiograph, this will give the appearance
appearance of a circumscribed, unilateral
radiolucent lesion with a radiopaque border
Clinical Considerations
References
• Nanci, A. 2017 (9th Edition). Ten Cate's Oral Histology-e-book:
development, structure, and function, Elsevier Health Sciences.
Thank you

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Salivary glands.pptx

  • 2. Objectives • What are the functions of saliva • Explain the anatomy, development and structure of salivary glands • Understand the mechanism of saliva production and modulation • Nerve and blood supply of salivary glands • Histology of major and minor salivary glands • Discuss Clinical nosiderations
  • 3. Oral fluid mixed or whole saliva • secretions of the major glands, the minor glands, desquamated oral epithelial cells, microorganisms and their products, food debris, and serum components and inflammatory cells that gain access through the gingival crevice.
  • 4. Functions of saliva • Protection • Buffering • Tooth integrity • Antimicrobial activity • Tissue repair • Digestion • Taste
  • 5. Functions of saliva… • Protection Flushing action-water Lubrication-mucins and glycoproteins barrier against noxious stimuli; microbial toxins and minor traumas Pellicle formation-proteins, glycoproteins, mucins • Buffering action- Bicarbonate and phosphate protect the teeth from demineralization caused by bacterial acids produced during sugar metabolism. metabolism of salivary proteins and peptides by bacteria produces urea and ammonia, which help to increase the pH.
  • 6. Functions of saliva… • Tooth integrity Post-eruptive maturation of the enamel-Calcium, phosphate, fluoride, statherin, acidic proline-rich proteins • Antimicrobial activity Physical barrier-Mucins Immune defense-Secretory IgA Nonimmune defense-Peroxidase, lysozyme, lactoferrin, histatin, mucins, agglutinins, secretory leukocyte cystatin (inhibitors of harmful cysteine-proteinases produced by bacteria and dying neutrophils), lysozyme histatin and lactoferrin (antibacterial agents), statherin (inhibitor of mineralization)
  • 7. Functions of saliva… • Tissue repair Wound healing, tissue growth and regeneration by growth factors • Digestion Amylase and lipase • Taste minor glands proteins- bind taste substances and present them to the taste receptors-gustin (detection of taste).
  • 8. Composition of saliva • 99% water • Electrolytes Na+, K+, Cl−, Ca2+, Mg2+, and F− • Secretory proteins/peptides Amylase, proline-rich proteins, mucins, histatin, cystatin, peroxidase, lysozyme, lactoferrin, defensins, and cathelicidin-LL37 • Immunoglobulins Secretory IgA; IgG and IgM • Small organic molecules Glucose, amino acids, urea, uric acid, and lipid molecules • Other components EGF, insulin, and serum albumin
  • 9. Saliva production, rate and pH • 90% saliva production from the major salivary glands • very small contribution to the pooled saliva is derived from gingival fluid and from sebaceous glands. • Sublingual gland and the minor salivary glands spontaneously secrete saliva, but the bulk of this secretion is nerve-mediated. • parotid and submandibular glands do not secrete saliva spontaneously and their secretion is entirely nerve-mediated (during anaesthesia, secretion ceases) • Resting 0.2–0.4 ml/min • Stimulated 2.0–5 ml/min • pH 6.7–7.4
  • 10. Salivary gland • Compound tubuloacinar exocrine glands found in oral cavity that secrete complex fluid known as saliva
  • 11. Classification of salivary glands • Based on size • Based on type of secretory cells
  • 12. • Based on size 1. Major salivary glands 2. Minor salivary glands Major salivary glands • Collection of secretory cells aggregated into large bilaterally paired extra oral extra oral glands with extended duct system through which gland secretions secretions reach the oral cavity i. Parotid ii. Submandibular iii. Subligual
  • 13. Minor salivary glands • Collection of secretory cells scattered throughout the mucosa and submucosa of oral cavity with short ducts opening directly into oral cavity cavity Serous glands of von ebner labial, lingual, palatal, buccal, glossopalatine, and retromolar glands
  • 14. • Based on type of secretory cells 1. Serous: parotid 2. Mixed: submandibular 3. Mucous: lingual
  • 15. 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 • A small portion of parotid forms accessory gland associated with stenson’s duct, ant. to the Superficial portion of gland
  • 16. • Stenson’s duct runs forward across masseter muscle, turns inwards at the ant. border of masseter & opens at a papilla in oral cavity just opp. 2nd maxillary molar Parotid gland:
  • 17. • Nerve supply: Sensory supply – Greater auricular and ariculotemporal nerve Autonomic supply Parasympathetic supply: CN IX Preganglionic fibers (tympanic branch → plexus→nerve) synapse in the otic Parotid gland:
  • 18. • Vascular supply & Lymphatic drainage : Arterial supply- External carotid artery Venous drainage- External jugular vein Lymphatic drainage- Upper deep cervical lymph nodes Parotid gland:
  • 19. Submandibular gland • 10 to 15 gm • 2 to 30% of total saliva • Located at Post part of floor of mouth, medial aspect of mandible & wrap around posterior border of mylohyoid. • Wharton's duct runs forward above the mylohyoid muscle and opens into the mouth beneath the tongue( sublingual caruncle), lateral to lingual frenum
  • 20. Sensory supply – via the lingual nerve Autonomic supply Parasympathetic supply: CN VII Preganglionic fibers (facial nerve sensory root→ geniculate ganglion→chorda tympani →lingual nerve) synapse in the submandibular ganglion. Postganglionic fiber enter the gland through glandular branches. Sympathetic Supply: originates from the superior cervical ganglion → postganglioic fibers travel along the facial artery to reach the submandibular gland Submandibular gland
  • 21. Blood supply: Facial and lingual arteries. Lymphatic drainage: Submandibular lymph node & deep cervical lymph nodes. Submandibular gland
  • 22. Sublingual gland • Smallest major salivary gland • 2gm • 2.5% of total saliva • Located at ant. part of floor of the mouth, just between mucosa & mylohyoid muscle • Open into oral cavity either through series of small ducts-duct of Rivinus opening along sublingual fold or through large duct- Bartholin’s duct, that opens with submandibular duct at sublingual caruncle.
  • 23. Sensory supply – via the lingual nerve Autonomic supply Parasympathetic supply: CN VII Preganglionic fibers (facial nerve sensory root→ geniculate ganglion→chorda tympani →lingual nerve) synapse in the submandibular ganglion. Postganglionic fiber enter the gland through glandular branches. Sympathetic Supply: originates from the superior cervical ganglion → postganglioic fibers travel along the facial artery to reach the sublingual gland Sublingual gland
  • 24. Blood supply Sublingual & submental arteries Lymphatic drainage: Submental lymph nodes Nerve supply: Parasympathetic supply: Facial nerve reaching gland through through the lingual nerve & submandibular ganglion. Sympathetic Supply: - Postganglionic fibers from plexus on facial artery. Sublingual gland
  • 25. Minor Salivary glands • 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. • predominantly mucous glands • 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.
  • 26. Development of salivary glands Stage I Initial Bud stage Stage II Early pseudoglandular stage. Stage III Late pseudoglandular stage. Stage IV Canalization Stage V Cytodifferentiation
  • 27. Stage I (Initial Bud stage) • proliferation of oral epithelium into underlying ectomesenchyme (condensation occurs) form spherical epithelial bud • spherical bud connected to the oral epi. through a thick solid solid epi. stalk • Epi. stalk → the main salivary duct, whereas the terminal bulb → intralobular parenchyma (acini, duct system). • thin basal lamina separates the bud from underlying mesenchyme. • B.M not only provides structural support to the epithelium, but it acts as a reservoir of growth factors • surrounding mesenchymal cells become more tightly packed and well-defined →form the capsule of the gland. Development of salivary glands…
  • 28. Stage II (Early pseudoglandular stage) epithelial chord formation, Initiation of branching in terminal parts of epithelial chord cell proliferation • epithelial bud solid cord of cells i.e., epi. cord • mesenchyme around the epithelial cord Condense and and proliferate • arborization of salivary gland epi. produced by branching morphogenesis clefting • Single primary epithelial bud 2 to 3 buds. • Buds expand, elongate, and cleft again and again extensive network of epithelial stalks and end buds. • Basal lamina is believed to play a role in influencing the morphogenesis & differentiation of the salivary glands
  • 29. Stage III (Late pseudoglandular stage) epithelial chord branching and lobule formation • Complex network of epithelial stalks and end buds multilobed gland. • branching continues at the terminal portion of the cord cord extensive treelike system of bulbs. • C. tissue differentiates around the branches extensive lobulation. • glandular capsule forms from mesenchyme and surrounds the entire glandular parenchyma • The basement membrane is secreted by the epithelial cells located at the periphery of the salivary epithelial bud and the adjacent mesenchymal cells, whereas the stromal elements of the extracellular matrix are produced by the mesenchymal cells.
  • 30. Stage IV (Canalization) • Lumen formation takes place at distal ends of chord, then in proximal and at last in central part.
  • 31. Stage V (Cytodifferentiation) • histodifferentiation of the acini and intercalated ducts • Epi. cells lining the ducts, tubules, and acini proceed to differentiate both morphologically morphologically and functionally • Following lumen formation in the terminal buds, epithelium consists of two layers of cells. 1. Inner cells differentiate into mucous or serous cells depending upon type of specific gland. 2. Some of the outer cells of epithelium differentiate into myopithelial cells that are are present around secretory end piece and and intercalated ducts. • Portion of epithelial bud close to the oral
  • 32. • 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 Development of salivary glands…
  • 33. • 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. • Gland continues to grow postnatally with the volume proportion of acinar tissue increasing and the volume proportions of ducts, connective tissue, and vascular elements decreasing— up to 2 years of age Development of salivary glands…
  • 34. Structure of salivary glands • Comprises of a series of secretory end piece or acini • connected to the oral cavity by a system of ducts.
  • 35. On the basis of location, ducts are of two types: • Intralobular ducts within the lobule (intercalated and striated ducts) • Interlobular ducts: lie within the connective tissue within the lobules of the gland (excretory ducts) Intercellular canaliculi are extensions of the lumen between adjacent secretory cells- increase the luminal surface area available for secretion. Structure of salivary glands…
  • 36. Salivary gland showing its lobular organization.
  • 37. 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 cell
  • 38. Serous cells • Secretory end pieces that are composed of serous cells are typically spherical and consist of 8 to 12 cells surrounding a central lumen • pyramidal in shape • broad base on the basement membrane, and narrow apex faces the lumen • spherical nucleus placed at the basal region of the cell • lumen usually has finger-like extensions located between adjacent cells called intercellular canaliculi that increase the size of the luminal surface of the cells. • secretory granules-macromolecule components of saliva are stored in the apical cytoplasm.
  • 39. • granules are zymogen granules-eosinophilic and are formed by glycosylated proteins which are released into a vacuole. • serous cells produce proteins and glycoproteins (enzymatic, antimicrobial, calcium-binding) • serous glycoproteins have N-linked (bound to the β-amide of asparagine) oligosaccharide side chains. Organelles include • RER (basal) • Golgi complex (lateral or apical) • Mitochondria • lysosomes • peroxisomes. cytoskeletal components, Serous cells
  • 40. several specializations • luminal surface have intercellular canaliculi and few short microvilli • lateral surfaces have occasional folds that interdigitate with similar processes from the adjacent cells • Basal surface has regular folds • folding of the cell membranes greatly increases the surface area of the cell. Serous cells-plasma membrane
  • 41. Serous cell-Cell junctions • Cells joined to one another-intercellular junctions • junctional complex A tight junction an adhering junction desmosome • cells attached to the basal lamina and the underlying C. tissue by hemidesmosomes. • Gap junctions along the lateral cell surfaces. separates the luminal surface from the basolateral surfaces of the cell, selective permeability to ions, hold cells together allow the passage of small molecules e.g., ions, metabolites, and cAMP.
  • 42. Mucous cell • secretory endpieces that are composed of mucous cells typically have a tubular configuration • these tubules appear as round profiles with mucous cells surrounding central lumen of larger size than that of serous endpieces. • nucleus is oval or flattened located above the basal plasma membrane • Mucous end pieces have serous cells associated with them in the form of a demilune or crescent
  • 43. • large amounts of secretory product (mucus) accumulates in the apical cytoplasm such that nucleus and ER compressed against the basal cell mem. • Mucus unstained in histologic preparations-giving an empty appearance to the supranuclear cytoplasm. • Special stains: periodic acid–Schiff stain or Alcian blue reveal sugar residues or acidic groups in the the secretory material Mucous cell
  • 44. • Mucous cells have a large Golgi complex • Small granules form at the trans face of the Golgi complex, stored in the apical cytoplasm. • The ER and other organelles are limited mainly to the basal cytoplasm of the cell • mucous cells are joined by a variety of intercellular junctions. • Mucous cells lack intercellular canaliculi, except for those covered by Demilune cells. Mucous cell
  • 45. • products of mucous cells are mucins (glycoproteins which have a protein core called apomucin) • mucous glycoproteins have O-linked (bound to the hydroxyl groups of serine or threonine) oligosaccharide side chains • Mucins function mainly to lubricate and form a barrier on surfaces and to bind and aggregate microorganisms. Mucous cell
  • 46. Myoepithelial Cells (Basket cells): • Contractile cells located around the terminal secretory units and intercalated duct • Located between basal lamina and secretory or duct cells and are joined by desmosomes • Similar to smooth muscle cells but are derived from epithelium • 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. • Other Cellular organelle are located in perinuclear cytoplasm
  • 48. Myoepithelial Cells • Myoepithelial cells related to intercalated ducts are more spindle shaped and have fewer processes • processes are filled with filaments of actin and myosin • cell membrane characterized by the presence of pinocytic vesicles- later named caveolae • Caveolae are a special type of lipid rafts, small invaginations of the plasma membrane involved in signal transduction pathways
  • 49. Myoepithelial Cells-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 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 • Cells may act as effective invasive barrier against epithelial neoplasms
  • 50. DUCTS • varied network of tubules that progressively increase in diameter, beginning at the secretory end pieces and extending to the oral cavity • 3 classes of ducts Intercalated Striated Excretory • participates in the production and modification of saliva.
  • 51. 1. Intercalated Ducts • 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. • intercalated ducts are lined by a simple cuboidal epi., and myoepithelial cell bodies and their processes typically are located along the basal surface of the duct. • overall diameter of the intercalated ducts is smaller than that of the end pieces, and their lumina are larger than those of the end pieces. • Several ducts draining individual end pieces join to form larger intercalated ducts, which may join again before emptying into the striated ducts
  • 52. Intercalated Ducts- cells • Low cuboidal in shape • centrally placed nuclei and a small amount of cytoplasm containing RER and a small Golgi complex • 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 • lateral surfaces are joined by junctional complexes, desmosomes and gap junctions • lateral surfaces have folded processes that interdigitate with similar processes of adjacent cells. • Because of their small size and lack of distinctive features, intercalated ducts often are difficult to identify in routine histologic sections.
  • 53. • secrete macromolecular components (lysozyme and lactoferrin) in the saliva, stored in their secretory granules. • A portion of the fluid component of the primary saliva is also added • Undifferentiated cells (salivary gland stem cells) are believed to be present in the intercalated ducts--proliferate and undergo differentiation to replace damaged or dying cells in the end pieces and striated ducts. Intercalated Ducts-function
  • 54. 2. Striated ducts • constitute the largest portion of the duct system. • located within the lobules of the gland-intralobular • In well-preserved tissue, faint radially oriented lines or striations may be observed in the basal cytoplasm of the ducts. • overall diameter of the duct is greater than secretory end pieces, and the lumen is larger than those of the secretory end pieces and intercalated ducts. • basal lamina encloses the striated duct, and a capillary plexus is present in the surrounding connective tissue.
  • 55. H and E stained micrograph of human submandibular gland. Striated ducts (arrowheads) stain lightly with eosin. The serous acini stain with hematoxylin.
  • 56. Light micrograph of striated ducts (SD) in the human submandibular gland.
  • 57. • duct cells are columnar, with a centrally placed nucleus and pale, acidophilic cytoplasm • duct cells show basal striations due to presence of numerous elongated mitochondria in narrow cytoplasmic partitions, separated by highly infolded basolateral cell membranes • apical cytoplasm contain small secretory granules (kallikrein) and electron-lucent vesicles (endocytosis of substances) . • duct cells also contain lysosomes and peroxisomes, and glycogen deposits (present in the perinuclear cytoplasm) • Adjacent cells are joined by well-developed tight junctions and junctional complexes but lack gap junctions. • The structure of the duct cells reflects an important 2. Striated ducts-cells
  • 58. 3. Excretory ducts • located in the connective tissue septa between the lobules of the gland, named as extralobular or interlobular ducts. • ducts are larger in diameter than striated ducts • Ducts 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 • As the smaller ducts join to form larger excretory ducts, the number of basal cells increases, and scattered mucous (goblet) cells may be present • The epithelium of the main excretory duct may become stratified near the oral opening.
  • 59. • smaller excretory duct cells structure (columnar cells) is similar to that of the striated duct cells. • As the ducts increase in size, the number of mitochondria and the extent of infolding of the basolateral membranes decrease. • basal cells have intermediate filaments (tonofilaments), actin filaments elongated processes similar to myoepithelial cells attached to the basal lamina by prominent hemidesmosomes. • experimental research suggest that the columnar cells and the basal cells have a high rate of proliferation. 3. Excretory ducts-cells
  • 60. Other cell types include • Tuft (caveolated or brush) cells, with long stiff microvilli and apical vesicles → believed to be receptor cells, nerve endings occasionally are found adjacent to the basal portions of these cells • lymphocytes and macrophages-with pale cytoplasm and dense nuclear chromatin • dendritic cells, or antigen presenting cells with long branching processes that extend between the epithelial cells→involved in immune surveillance and the processing and presentation of foreign antigens to T lymphocytes. 3. Excretory ducts-cells
  • 61. Formation and Secretion of Saliva • Two Stages 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
  • 62. First stage of saliva secretion • Formation of macromolecular component • Fluid and Electrolytes secretion Sympathetic or parasympathetic stimulation Ribosomes- mRNA→protein RER- Protein Folding and post-translational modification (glycosylation) Golgi complex- Further modification, condensation and packaging Secretory granules- Stored in apical cytoplasm Contents released into lumen in response to stimulus
  • 64. 1. Norepinephrine, acting via Îą-adrenergic receptors, activate the phospholipid-Ca2+ pathway 2. Substance P, VIP, neuropeptide Y and calcitonin G-RP (peptides released from autonomic nerve terminals) exert effects on the glandular vasculature to regulate blood flow 3. Nitric oxide (produced by PS nerves, VEC, and GSC) stimulates the production of cyclic GMP, release of Ca2+ from intracellular storage sites in secretory cells 4. Extracellular ATP activates the P2X and P2Y receptors on secretory and duct cells→ P2X receptors allow EC Ca2+ to enter the cell → P2Y receptors cause release of Ca2+ from intracellular storage sites Other Mechanisms Modulating Saliva Secretion
  • 65. Ductal Modification of Saliva 1. reabsorption of Na+ and Cl− 2. Secretion of K+ and HCO³¯ little or no secretion or reabsorption of water occurs in the striated and excretory ducts. • depends on the salivary flow rate At high flow rates, saliva in contact with ductal epithelium for a shorter time Low flow rates the electrolyte concentrations change in the opposite direction reabsorption of Na+ and Cl−↓, Secretion of K+ ↓ Na+ and Cl− conc ↑, K+ conc↓
  • 66.
  • 67. Innervation of ducts • Electrolyte reabsorption and secretion is regulated by autonomic nervous system mineralocorticoids • The sympathetic innervation has a more important role in regulating electrolyte transport in the ducts than in the acini because of a larger number of cAMP regulated Cl− channels in the luminal cell membrane.
  • 68. Connective Tissue component • a surrounding capsule that demarcates the gland from adjacent structures • Septa extend inward from the capsule divide the gland into lobes and lobules • Cells include fibroblasts, macrophages, dendritic cells, mast cells, plasma cells, adipose cells, granulocytes and lymphocytes. • ECM has Proteins (Collagen and elastic fibers) and ground substance (glycoproteins and proteoglycans)
  • 69. • Septa carry the blood vessels and nerves that supply the parenchymal components and the excretory ducts that convey saliva to the oral cavity • partitions carry the arterioles, capillaries, and venules of the microcirculation and the finer branches of the autonomic nerves that innervate the secretory and ductal cells. Connective Tissue component
  • 70. • Plasma cells located adjacent to the secretory end pieces and intralobular ducts produce immunoglobulins • IgA- main immunoglobulin-synthesized as a dimer complexed with an additional protein called J chain. • epithelial cells have receptors for dimeric IgA on their basolateral membranes • IgA-secretory vesicles move from the basolateral cytoplasm to the apical cytoplasm, translocated into the saliva by transcytosis. • Small amounts of IgG and IgM also are secreted into the saliva. Connective Tissue component
  • 71. Nerve Supply • Within the gland lobules, branches of the nerves follow the blood vessels, eventually forming a plexus of unmyelinated fibers adjacent to arterioles, ducts, and secretory end pieces • axons of each nerve bundle are invested by cytoplasmic processes of Schwann cells. • Several varicosities may be present along the length of an axon containing neurotransmitter vesicles and mitochondria • These varicosities are believed to be the site of innervation of the gland cells and thus the site of neurotransmitter release. • a single nerve may innervate more than one epithelial cell. • no specializations of the axonal or epithelial cell membranes occur at these sites as occur at synapses in the CNS.
  • 72. Intraparenchymal Extraparenchymal axon leaves the nerve bundle, loses its its Schwann cell investment, penetrates the epi basal lamina, and forms an expanded swelling/ varicosity varicosity the axon remains associated with the nerve bundle, and forms a varicosity but the Schwann cell covering is absent over the varicosity. Axonal Varicosity is in close contact (10 to 20 nm) with the basolateral membrane of the epithelial cell. the axonal varicosity is separated from from the epithelial cells and the basal laminae by 100 to 200 nm Hypolemmal Neuroeffector relationship Epilemmal Neuroeffector relationship submandibular gland and in the minor glands of the lip, Parotid gland. Nerve–epithelial cell relationship
  • 73. Blood supply • an extensive blood supply-Rapid and sustained secretion of saliva • One or more arteries enter the gland and give rise to smaller arteries and arterioles that tend to follow the path of the excretory ducts. • arterioles break up into capillaries that are distributed around the secretory end pieces and striated ducts. • In some species the capillaries supplying the secretory end pieces and ducts arise from separate arterioles (i.e., a parallel arrangement), whereas in other species a venous portal system connects the capillary network around the end pieces with that around the ducts. • An extensive capillary plexus exists around the excretory ducts. • The endothelium of the capillaries and postcapillary venules is fenestrated.
  • 74. Blood supply • The venous return follows the arterial supply • arteriovenous anastomoses occur in some glands. Blood flow↑ more blood is diverted through AV anastomoses ↑ fluid filtration across the capillary endothelium ↑ venous and capillary pressures
  • 75. Histology of the Major Salivary Glands PAROTID GLAND • spherical secretory end pieces are all serous • pyramidal shaped acinar cells have a spherical, basally situated nucleus and and surround a small, central lumen. • Basal cytoplasm stains with basophilic dyes, and the secretory granules in in the apical cytoplasm usually stain with acidophilic dyes. • Fat cell spaces often are seen in sections of the parotid gland. • Intercalated ducts are numerous and long lined with cuboidal epithelial cells lumina are larger than that of the acini. myoepithelial cells sometimes present at the basal surface of the ducts
  • 76. • Striated ducts are Simple columnar epithelium, with round, centrally placed nuclei Numerous in number slightly acidophilic round or elongated tubules of larger diameter than the end pieces. Faint striations, representing the infolded basal cell membranes and mitochondria, may be visible below the nucleus.
  • 77. H and E micrograph of Parotid gland
  • 78. Submandibular gland • Mixed gland contain serous end pieces and mucous tubules capped with serous demilunes • Although the proportions of serous and mucous secretory end pieces may vary from lobule to lobule and among individual glands, serous cells significantly outnumber the mucous cells. • serous end pieces are similar in structure to those found in the parotid gland • mucous secretory cells pale-staining secretory material little cytoplasm is usually visible, nucleus is compressed against the basal cell membrane and contains densely stained chromatin. • intercalated and striated ducts are less numerous than those in the parotid gland
  • 79. H and E micrograph of Submandibular gland
  • 80. Sublingual gland • mixed gland, but mucous secretory cells predominate • The mucous tubules and serous demilunes resemble those of the submandibular gland. • The intercalated ducts are short and difficult to recognize. • Intralobular ducts are fewer in number than in the parotid or submandibular glands • some ducts may lack the infolded basolateral membranes characteristic of striated ducts.
  • 81. Histology of Minor salivary glands • consist of aggregates of secretory end pieces and ducts, organized into small lobule-like structures located in the submucosa or between muscle fibers of the tongue • ducts open directly onto the mucosal surface. • The secretory end pieces of most minor glands are mostly mucous or have a small serous component arranged as occasional demilunes. • Intercalated ducts often are poorly developed, and the larger ducts may lack the typical infolded basolateral membranes of the striated ducts of the major glands.
  • 82. lingual serous glands (of Ebner) present in the tongue below the circumvallate papillae are pure serous glands. • secretions are released in regions with significant numbers of taste buds e.g., troughs surrounding the vallate papillae, and clefts between the foliate papillae on the sides of the tongue. • They secrete digestive enzymes and proteins believed to play a role in the taste process. • The fluid component of their secretions is presumed to cleanse the trough and prepare the taste receptors for a new stimulus.
  • 83. • Minor gland saliva typically is rich in mucins, various antibacterial proteins, and secretory immunoglobulins. • minor glands exhibit a continuous, slow secretory activity, and thus have an important role in protecting and moistening the oral mucosa, especially at night when the major salivary glands are mostly inactive
  • 84. H and E stained micrographs of human minor salivary glands. A, Mucous gland (Muc) in the lateral portion of the hard palate. B, Lingual serous (Ebner's) glands and mucous glands located between muscle fibers in the post part of the tongue.
  • 85. Clinical Considerations Age changes • With age, a generalized loss of salivary gland parenchymal tissue tissue occurs i.e., 30% to 60% reduction in acinar volume of the the major salivary glands has been observed. • lost salivary cells are replaced by adipose tissue. • increase in fibrous c. tissue and vascular elements • Changes of the duct system, including an increase in nonstriated
  • 86. Age changes • Although decreased production of saliva often is observed in older older persons, whether this is related directly to the reduction in in parenchymal tissue is not clear. • Some studies of healthy older individuals, in which the use of medications was controlled carefully, revealed little or no loss of of salivary function, suggesting a large functional reserve capacity. capacity. • Other studies suggest that although resting (unstimulated) salivary secretion is in the normal range, the volume of saliva produced during stimulated secretion is less than normal. Clinical Considerations
  • 87. Xerostomia • Dry mouth caused by loss of salivary function or a reduction in the volume of volume of secreted saliva Xerostomia Medication Increasing age Radiotherapy Chemotherapy Autoimmune diseases Clinical Considerations
  • 88. Loss of salivary function • Oral dryness • loss of the protective effects of salivary buffers, proteins, and mucins. • oral tissues are more susceptible to infections • Difficulty in speech, mastication, and swallowing • teeth are highly susceptible to caries Rx • frequent sipping of water or artificial saliva (temporary relief) • therapy with oral parasympathomimetic drugs, such as pilocarpine, to increase salivary flow • genetic modification of salivary gland cells to increase fluid and protein secretion.
  • 89. Diseases Clinical Considerations Diseases that affect salivary gland function Endocrine Autoimmune diseases Infectious Genetic SjĂśgren's syndrome, Rheumatoid arthritis Graft- versus-host disease, acquired immune deficiency Diabetes Viral (CMV, EBV, HSV-6 & 7) Bacterial Cystic fibrosis
  • 90. Sialoliths • Blockage may occur of the main collecting duct of a major salivary gland (usually the submandibular, but occasionally the parotid) • Cause is usually the sialolith (stone or calculus) but sometimes is a stricture or an inflammatory exudate. • At mealtimes, lack of saliva access to the mouth caused by the blockage results in swelling of the gland, together with pain and subsequent discharge. Clinical Considerations
  • 91. Mucoceles and ranulas • Damage to the ducts of minor and sublingual salivary glands result in the extravasation of mucus into the surrounding soft tissues • When the extravasation persists, mucocele is formed • In the case of the sublingual gland, it is also termed a ranula because the swelling it causes to the floor of the mouth somewhat resembles the belly of a frog. • When a ranula is situated above the mylohyoid muscle (oral ranula), it produces a painless swelling that may displace the tongue • If it penetrates the mylohyoid (cervical ranula), it produces a swelling in the neck. • Treatment of these conditions may necessitate the surgical removal of the affected sublingual gland.
  • 92. Staphne’s cavity (cyst) • A portion of the submandibular gland may invaginate into the lingual surface of the mandible, typically in the region of the ramus ramus below the mandibular canal, near the the angle of the ramus. • On a radiograph, this will give the appearance appearance of a circumscribed, unilateral radiolucent lesion with a radiopaque border Clinical Considerations
  • 93. References • Nanci, A. 2017 (9th Edition). Ten Cate's Oral Histology-e-book: development, structure, and function, Elsevier Health Sciences.

Editor's Notes

  1. A=Darkly staining serous acini B = intercalated duct; C = striated duct; D = plasma cell; E = fat cell
  2. Submandibular gland showing (A) darker serous and (B) lighter mucous acini. serous demilunes (arrows) C = intercalated duct; D = striated duct; E = plasma cells; F = fat cell