GOOD MORNING

INTRODUCTION

• Saliva reflects the physiological state of the body including emotional, endocrinal, nutritional and metabolic variations of the body

• Saliva is a complex fluid.• Saliva circulating in mouth at any

given time is termed “whole saliva”.

Whats this

According to Stedmen’s Dictionary Saliva is a clear, tasteless, odourless

slightly acidic (pH6.8), viscid fluid, consisting of secretions from the parotid, sublingual and submandibular salivary gland and the mucous glands of the oral cavity.

Whole saliva is derived from 3 pairs of major salivary glands (90% of total saliva secretion) & Minor salivary glands

Whole saliva contains gingival crevicular fluid, micro organisms from dental plaque, food debris

• In resting phase- 2/3rd of whole saliva produced by submandibular glands

• When stimulated- atleast ½ of whole saliva by parotid

• Only small % of stimulated & unstimulated whole saliva comes from sublingual glands

SALIVARY GLANDS

CLASSIFICATION OF SALIVARY GLANDS

MAJOR SALIVARY GLANDS

Parotid Gland

Submandibular Gland

Sublingual Gland

MINOR SALIVARY GLANDS

Lingual

Retromolar

Buccal glands

Labial glands

Palatal glands

Blandin/ nuhn glands

von ebners glands

According to size and location

Based on type of secretion–Serous –Mucous –Mixed Parotid glands - Purely serous

Von Ebner’s Glands(lingual) - Purely serous Submandibular-Predominantly mucuos, MixedSublingual - Predominantly mucous , MixedLabial, Buccal, retromolar - mainly Mucous , MixedPalatine- Purely mucous.

DEVELOPMENT of salivary glands

ORAL EPITHELIAL BUDS

ECTODERM ENDODERM

PAROTID GLAND AND MINOR SALIVORY GLANDS

SUBMANDIBULAR AND SUBLINGUAL GLAND

All salivary glands show similar pattern of development

• As the salivary glands develop near the junctional area between the ectoderm of the foregut, it is difficult to determine whether they are ectodermal or endodermal.

• The outgrowth for the parotid gland arises in relation to the line along which the maxillary and mandibular process fuse to form the cheek. it is generally considered as ectodermal.

• The outgrowths for the submandibular and sublingual glands arise in relation to the linguo-gingival sulcus. They are usually considered to be of endodermal origin.

• The parotid are the first to develop, followed by the submandibular gland, and finally the sublingual gland.

• Parenchymal tissue (secretory) of the glands arises from the proliferation of oral epithelium.

• The stroma (capsule and septae) of the glands originates from mesenchyme that may be mesodermal or neural crest in origin

• Although the parotid are the first to develop, they become encapsulated after the SMG and SLG.

The Primordia of the glands of humans appear during sixth week .

The minor salivary glands begin their development during the third month.

They arise as epithelial buds in the oral cavity & extends into underlying mesenchyme(bud stage)

• The epithelial buds of each gland enlarge, elongate and branch initially forming solid structures.(cord stage)

• Branching of the glandular mass produces arborization.(a fine branching structure)

• Each branch terminates in one or two solid end bulbs.( terminal bulb stage)

• Elongation of the end bulb follows and lumina appears in their centers, transforming the end bulbs into terminal tubules. ( lobule stage)

• These tubules join the canalizing ducts to the peripheral acini. (duct canalization)

• Canalization is complete by 6th month post conception.

• Finally cytodifferentiation begins following canalization..(dev of specialized cells)

– Largest of salivary glands Wt – 15g a three sided pyramid With apex directed downwards. Has large superficial & small deep lobes- divided by

facial nerve 4 surfaces (superficial, superior, anteromedial,

posteromedial) & 3 borders( ant, post, medial). Accessory parotid – a part of forward extension,

often detached.

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Capsule of parotid gland:• The deep cervical fascia forms a capsule for a

gland• The fascia splits between angle of mandible

& mastoid process to enclose the gland

Superficial lamina: thick, adherent to gland attached above zygomatic arch

Deep lamina: thin, attached to the styloid process, tympanic plate, the angle & ramus of mandible.

A portion of deep lamina extending between the styloid process & mandible is thickened to form stylomandibular ligament.

Structures within parotid glandArteries: external

carotid arterymaxillary arterysuperficial

temporal artery transverse facial

artery

Veins: retromandibular vein is formed by union of superficial temporal & maxillary veinsIn the lower part of gland the vein divides into ant & post divisons & emerges

Nerve : facial nerve divides into its terminal branches facial nerve lies in relation to isthmus of the gland

Parotid duct:• It is thick walled • 5cm long • Emerges from the middle

of the ant border of gland • The duct runs forward for a

short distance between buccinator and oral mucosa

• Then the duct turns medially and opens into the vestibule of mouth

• Blood supply: parotid gland

supplied by the external carotid artery & its branches

Veins drain into ext & internal jugular veins• Lymphatic drainage:

Lymph drains first to parotid nodes then upper deep cervical nodes

Parotid lymph nodes lie partly in the superficial fascia and partly deep to the deep fascia

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Nerve supply:

Parasympathetic nerves- are secreto motor, reach gland through the auriculotemporal nerve. Sympathetic nerve supply – Plexus around middle meningeal arterySensory nerves to the gland- auriculotemporal nerve

to the parotid fascia- sensory fibers of the greater auricular nerve

Tympanic

branch

Tympanicplexus

Foramen ovale

Leser petrosal nerve

Inf sn

• Situated in the anterior part of digastric triangle

• Size of walnut• Roughly J shape• Two parts by mylohoid muscle• larger superficial and small deep part• Partially Enclosed between 2 layers of deep

cervical fascia• Superficial layer of fascia covers inferior

surface of gland & attached to base of mand• Deep layer cover medial surface of gland & is

attached to mylohoid line of mand

Submandibular duct

Superficial part

Deep part

Superficial part: • fills digastric triangle• Extends upwards deep the mandible upto

mylohoid line• It has 3 sufarces inf, lat & medial• Medial surface- mylohyoid, hyoglassus,

styloglossus mus• Inferiorly overlaps stylohyoid & post belly of

digastric• Lateral surface- facial artery,

Submandibular fossa on mandinsertion of medial pterygoid

Deep part- small in size. anteriorly extends upto the post end of sublingual gland.Deep to the mylohyoid, & superficial to hyoglossus & styloglossus muscle

SUBMANDIBULAR DUCT / WHARTON’S DOCT: • Thin walled & 5 cm

long• Emerges at ant end

of deep part of the gland

• Runs between lingual & hypoglossal nerves

• Opens on the floor of the mouth on the summit of sublingual papilla, at the side of frenulum of tongue.

Blood and lympatic drainageArterial supply• Cervical part of facial artery

from external carotid art• The artery makes an s-bend

(two loops) first winding down over the sub mand gland then up over the base of mandible

Veins: vein drain into common facial or lingual vein

Lymph passes to submandibular lymph nodes.

• Lies in the sublingual fossa on the base of the mandible

• Smallest of the 3 paired salivary glands

• Weighs about 3 to 4 gms• Not enclosed by fascia• Mainly mucus secreting• About 15 ducts emerge from

the gland – most of them open directly on the summit of sublingual fold. Few of them join the submandibular gland

Relations :• Front – meet with opp side gland• Behind- comes in contact with deeper part of

sub mand gland• Above- mucous membrane of mouth• Below mylohyoid muscle• Lateral- sublingual fossa• Medial – genioglossus muscle• Blood supply-

lingual & submental arteries

Nerve supply: similar for both submand & sub lingual glands• Supplied by branches from

submandibular ganglion • These branches conveya. Parasympathetic fibers are

Secretomotor, post ganglionic fibers reach gland through 5 or 6 branches from submandibular ganglion

b. Sensory fibers reach ganglion through the lingual nerve

c. Vasomotor sympathetic fibers from plexus on the facial artery. It contains post ganglionic fibers arising in the superior cervical ganglion

Superior salivatory nucleus

Nervus intermedius

Facial nerve

Chorda tympani

Joins lingual nerve, branch of mand nerve

Submandibular ganglion

Sub mand & sub ling glands

Post ganglionic fibers

Sublingual gland

Submandibular gland

Minor Salivary gland:• Continuous slow secreting glands, thus have

a important role in protecting and moistening oral mucosa.

• 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.

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LINGUAL MINOR GLANDSVon Ebners’s Lingual serous gland:• Located in tongue open into the troughs

surrounding circumvallate papillae on the dorsum of 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.

Blandin or nuhn glands mucous gland: situated on the under surface of the apex of the tongue on either side of frenulum.

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Nerve supply of minor salivary glands• Palatinal – facial nerve• Buccal – facial nerve• Labial are supplied by facial nerve• Lingual are supplied by

glossopharyngeal nerve• Retro molar supplied by both facial & IX

nerves

Structure of salivary glands• The working parts of the salivary

glandular tissue consist of the secretory end pieces (acini) and the branched ductal system.

• In serous glands (e.g. the parotids) the cells in the end piece are arranged in a roughly spherical form.

• In mucous glands, they tend to be arranged in a tubular configuration with a larger central lumen.

• In both types of gland the cells in the end piece surround a lumen and this is the start of the ductal system.

• There are three types of duct present in all salivary glands.– Intercalated duct– Striated duct– Excretory duct

The fluid first passes through the intercalated ducts which have low cuboidal epithelium and a narrow lumen.

From there the secretions enter the striated ducts which are lined by more columnar cells with many mitochondria.

Finally, the saliva passes through the excretory ducts where the cell type is cuboidal until the terminal part which is lined with stratified squamous epithelium.

• End pieces may contain mucous cells, serous cells or a mixture of both.

• A salivary gland can consist of a varied mixture of these types of end pieces.

• In mixed glands, the mucous acini are capped by a serous demilune. (secrete proteins that digest cell membrane of bacteria)

• In addition, myoepithelial cells surround the end piece, their function being to assist in propelling the secretion into the ductal system.

• The gland and its specialised nerve and blood supply are supported by a connective tissue stroma.

Serous acini

1. Samller in size,rounded in shape.

2. Lumen hardly visible.

3. Lining cells pyramidal in shape and relatively more in number.

4. Nuclie are round and basal.

5. Cytoplasm depicts basal basophilia and apical eosinophilia.

6. May present as demilunes on one aspect of some mucous acini

Mucous acini

1. Larger in size , more variable in shape.

2. Lumen mostly visible.

3. Lining cells truncated columnar in shape. Cells relatively fewer in number.

4. Nuclie are flattened and peripheral.

5. Cytoplasm is pale and vacuolated.

6. Mucous acini only present as complete acini.

Types of Saliva

• salivary glands, their cells and ducts are greatly responsible for the modification and kind of saliva being secreted

• It is of three types:–Serous Saliva–Viscous Saliva–Mixed Saliva

Serous Saliva• Content:

–Amylase protein–polysaccharides

• Cell: Serous Cells• “watery saliva”• Glands that secrete this type:

–Parotid Gland–Von Ebner’s glands

MUCOUS SALIVA• Content:

–Mucins (glycoproteins)–Carbohydrates

• Cell: Mucous Cells• Thick and viscous• Glands that secrete this type:

• Sub lingual salivary gland, palatine , retromolar minor salivary glands

MIXED SALIVA• simply the combination of the

aforementioned types of saliva • Secreted by: Submandibular Gland (mainly mucous)Retro molar (mainly mucous)Buccal , labial are seromucoussCells:

–Serous Cells–Mucous Cells

Secretion of saliva

• Although fluid secretion occurs only through the acini, proteins are produced and transported into the saliva through both acinar and ductal cells.

• The primary saliva within the acinar end pieces is isotonic with serum but undergoes extensive resorption of sodium and chloride and secretion of potassium within the duct system.

• The saliva, as it enters the oral cavity, is a protein-rich hypotonic fluid.• Blood supply & nerve control of salivary glands is important for saliva

production

Fluid in saliva originates from the capillaries & interstitial fluid• This blood supply is organised

as portal system with two capillary networks, a dense one around duct system, & another around secretory end piece

• Blood vessels of the SG are controlled by sym NS, which makes them constrict

• However parasympathetic stimulation induces formation of

Vaso active intestinal polypeptideNitric oxide that are released by SGs

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BLOOD SUPPLY OF SALIVARY GLANDS

• The secretion of saliva is regulated by Autonomic NS.

• Reflex pathway is unilateral• Stimulation on one side induces ipsilateral

salivation• The act of chewing & sensation of taste

initiate action potentials in various receptors1. Masticatory salivary reflex involves sensory

inputs mainly from mechanical receptrs in mouth

These include mechanoreceptors in PDL, proprioceptors in the trigeminal innervation including muscle spindles in the masticatory muscles & oral nociceptive stimuli2. The gustatory salivary reflex utilizes sensory signals from taste activated chemoreceptors in the taste buds

NERVOUS CONTROL OF SALIVARY SECRETION

• These signals are conducted along VII, IX, X nerves to salivatory nuclei

• Here the signals activate secretomotor pathways of reflex that consist of sym & para sym nerve bundles

• They travel along separate pathways to the salivary glands

• Selective parasympathetic or sym stimulation of SGs elicit secretion

• the autonomic nerve endings release neurotransmitters

• These include Ach, noradrenaline, adenosine triphosphate, substance P, vaso active intestinal polypeptide, neuropeptide Y.

•

• These neuro transmitters activates specific cell surface membrane receptors on the salivary gland

• They also have modulatory effect on formation of saliva, there by determining flowrate & composition of saliva

• The parasympathetic branch provides the main stimulus for salivation giving rise to high flow rate of watery saliva

• Sympathetic stimulation leads to lower flow rate , much more viscous (high mucin)

• All the reflexes mentioned above are unconditioned reflexes

• Salivary secretion can also be initiated by cond.reflexes that are programmed in higher centers in brain

Factors effecting salivary flow rate:• Emotional state( anxiety- inhibition)• Salivation can also be diminished in

untreated depression• Acidic taste- max stimu, sweet- less

stimulation• During sleep- salivary secretion from major

glands very low• Positive experiences with food in the past-

increases salivationTherefore many signals from variety of peripheral receptors & from higher centers of brain are being constantly integrated in salivatory nuclei, the result of which may either facilitate or inhibit salivation

Flow rate (ml/min) of salivaWHOLE PAROTID SUBMANDIBULAR

RESTING 0.2-0.4 0.04 0.1STIMULATED 2.0-5.0 1.0-2.0 0.8

pH 6.7-7.4 6.0-7.8

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20-39 yr 40-59 yr > 60 yr0.0

0.2

0.4

Flow Rate of Salivaunstimulatedstimulated

Age

ml /

min

• Thaysen & colleagues- secretion model for formation of saliva

• Saliva is formed basically in 2 steps

1. Secretory end piece produces primary saliva(isotonic)

2. Fluid is then modified in the duct system

a) selective reabsorption of NA & CL

b) certain secretion of K & HCO3• Thus Secretion rate and

volume of the final saliva is determined by the formation of primary saliva by the acinar cells

Formation of saliva

Stimulus – secretion coupling:• The secretion of electrolytes, water &

exocytotic release of proteins from the acinar cells depends upon stimulation, involving multitude of biochemical signalling processes

• The key event is the rise in the free intra cellular Ca conc in the acinus

• This is initiated by specific activation of receptors in the plasmamembrane by neurotransmitters.

• This receptor induced rise in ca conc involves different signalling routes

AchMuscarinic cholinergic receptors

NA

Alpha1 cholinergic receptors

Binding induces phospholipase C- mediated hydrolysis of phosphatidylinositol 4,5 bisphosphate(PIP2)

Inositol 1,4,5 triphosphate (IP3)(watersoluble)

Diacylglycerol(DAG)

Binds to IP3 receptors on endoplasmic reticulum

Induces ca release from this store within cell

1

Activates protein kinaseC

Protein synthesis and secretion

2Noradrenaline (Gs protein & adenylate cyclase)

Synthesis of cAMP

Activates protein kinase A

Protein synthesis in the rough ER

Exocytosis of protein containing secretory granules across

cell membranerise in intracellular ca

• Protein secretion from the SG tissue is continuous so called constitutive exocytosis of protein vesicles• Constitutive exocytosis can be accelerated to regulatory exocytosis by appropriate firing impulse frequency & specific receptor activation of salivary gland• This regulatory exocytosis is controlled by sym & para sym secretomotor innervation• Minor glands secrete a protein rich (mucin ) secretion continuously.

Electrolyte transport of acinar cells:The plasma membranes of the acinar cells are freely permeable to water and to lipid soluble substances, but not to ions• Thus electrolyte transport across the plasma

membrane must occur through specific transport mechanism such as ion channels, pumps, cotransporters & exchange systems

• The general principle behind the formation of primary saliva is the increase in intracellular free Ca by losing

K to interstitium &CL to lumen via activated ca

regulated K & CL channels.

• The accumulation of CL in lumen creates negative intracellular potential

• This drives interstitial Na into the lumen ( via cation selective tight junctions) to preserve elecroneutrality.

• A transepithelial water flux occurs probably by trans & paracellular pathways, due to net movement of salt into the lumen osmotically

• This results in acinar cell shrinkage ( by water loss via water channels aquaporins) & formation of isotonic, plasma like primary saliva.

initial receptor activation of acinar cell

Loss of K , CL, water from acinar cells

Increase in na conc by downhill influx

Activation of Na/ H exchange

Na/ K/ 2CL cotransporer

or

Activates cell membrane element, Na/K pump (ATPase)

This active mechanism then utilizes energy in the form of ATP, then re-estlabish the

Original Prestimlatory(unstimulated) ion gradients across the acinar plasma membrane by

active uphill extrusion of Na & influx of K

• Similarly the prestimulatory acinar CL conc is re-established by uphill influx of the Cl ion

• This influx of CL occurs through CL/ HCO3 exchangers ( parallel with Na/H exchange) & Na/K/2CL Cotransporters

• Osmosis causes water to follow the inward movement of ions & cell swells back to its prestimulatory volume

When stimulus removed, the free intracellular ca conc, the cytoplasmic PH, the cell volumes, the activity of Transporters including ion channels return the their original prestimulatory levels &

the acinus is again ready to produce substantial amounts of primary saliva.

Ductal modification of electrolyte• Sym & para sympathetic nerve fibers control

the activity of salivary ducts in the secretory end piece

• The membrane transporters and the cell signalling mechanisms of the duct cells are similar to those of acinar cells.

• These transporters are most important for the modification of primary saliva in ducts

• Stimulation of receptors in the duct cells by neurotransmitters and peptides induce rise in intracellular free Ca concentration & cyclic AMP

• Most of the Na reabsorption from primary saliva occurs across the luminal membrane in the infoldings of the striated duct by ATP- consuming Na / K pumps

• The pump mechanism maintains extrusion of Na from duct cell to the interstitium and ductal uptake of K

• This creates an inwardly directed Na gradient allowing Na to pass into duct cell from primary saliva.

• The uptake of Na is balanced by parallel uptake of CL via CL channels & CL/HCO3 exchange mechanisms

• Secrection of K into saliva occurs to preserve electro neutrality.

• Because of low water permeability of the duct , the final saliva secreted into mouth becomes hypotonic to plasma with much lower conc of Na & CL than primary saliva

Composition of salivaThe final composition of saliva arising from major

salivary glands secreted into mouth is hypotonic relative to plasma

More than 99% water and less than 1% dry matterDepending on flow rate

Whole saliva – 3-6 times less electrolytes than plasma

As flow rate inc – dramatic inc in NA+, CL-, HCO3-

Stimulated saliva is less hypotonic than unstimulated saliva

Stimulated saliva contains more higher conc of HCO3- than unstimulated saliva.

Solid present in saliva consists:-• Cellular constituents – consist of yeast,

bacteria, protozoa, polymorpho nuclear leukocytes and desquamated epithelial cells.

• Inorganic ions- major(Na + ,k+ ,Cl-,HCO3-) and Minor (Ca++ ,Mg++ ,HPO4-, bromide and F-)

• Secretory proteins and glycoproteins – various enzymes, large carbohydrate rich protein or mucin, antibacterial substance, group of protein's involved in enamel.

• Serum constituents- albumin, blood clotting factor , B2 microglobulin and immunoglobulin.

• Normal stimulated flow of saliva- for different ages can be calculated by the equation:-

0.78 * age + 5.6 = stimulated flow / 15 min5.6 – it is stimulated flow of the infants

Functions of salivaFunction Action

Fluid/Lubricant Saliva contains mucins that are glycoproteins, contains more than 40% carbohydrate. They have lubricating functions on oral tissues. Coats hard and soft tissue which helps to protect against mechanical, thermal and chemical irritation and tooth wear. Assists smooth air flow, speech and swallowing.

Ion reservoir Saliva is supersaturated with respect to hydroxyapatite, the main composition of teeth. This facilitates remineralisation of the teeth. Statherin and acidic proline-rich proteins in saliva inhibit spontaneous precipitation of calcium phosphate salts.

Buffer The ability of saliva to maintain the PH when exposed to food(acid) is termed buffer capacity. thus reducing time for demineralisation. The bicarbonate buffer system has highest contribution. Other include phosphate Bsys, protein Bsys,

Cleansing The clearance is mainly due to flushin effect of salivaClears food and aids swallowing.

Antimicrobial actions Specific (e.g. sIgA) and non-specific (e.g. Lysozyme,Lactoferrin and Myeloperoxidase) anti-microbial mechanisms help to control the oral microflora. The secretory salivary IgA is a specific defence factor i.e stimulated in the presence of bacteria. Some studies have shown protective effect of IgA against dental caries

Agglutination Agglutinins in saliva aggregate bacteria, resulting in accelerated clearance of bacterial cells. Examples are mucins and parotid saliva glycoproteins.

Pellicle formation Thin protective diffusion barrier formed on enamel from salivary and other proteins. The proteins include in formation of pellicle includes acidic proline rich protein, Ig-a, cystatin, lactoferrin, lysozyme & amylase. This acquired pellicle may favour non harmful colonization pattern & further protect teeth.

Digestion The enzyme α-amylase is the most abundant salivary enzyme; this enzyme hydrolyses the alpfa-1,4-glycosidic linkages of starch. These are secreted from serous cells. Amylase is active above PH 6. it splits starchy foods into maltose, malto-triose and dextrins. In infants and pancreatic dysfunction it is of major importance

Taste Saliva acts as a solvent, thus allowing interaction of foodstuff with taste buds to facilitate taste

Excretion As the oral cavity is technically outside the body, substances which are secreted in saliva are excreted. This is a very inefficient excretory pathway as reabsorption may occur further down the intestinal tract.

Water balance Under conditions of dehydration, salivary flow is reduced, dryness of the mouth and information from osmo-receptors are translated into brain. This causes decreased urine production and increased drinking.

Wound healing effect Epidermal growth factor is a small protein found in SMG, parotid gland, whose output increases during mastication. EGF enhances healing of ulcers & plays imp role in esophageal mucosal protection

� APPLIED PHYSIOLOGYHYPOSALIVATION• Reduction in the secretion of saliva is called

hyposalivation.• It is of two types, namely temporary hyposalivation

and permanent hyposalivation.1. Temporary hyposalivation occurs in:

i. Emotional conditions like fear.ii. Fever.

iii. Dehydration. . Permanent hyposalivation occurs in:

i. Sialolithiasis (obstruction of salivary duct).ii.Congenital absence or hypoplasia of salivary

glands.iii. Bell palsy (paralysis of facial nerve).

HYPERSALIVATION• Excess secretion of saliva is known as

hypersalivation.• Physiological condition when hypersalivation

occurs is pregnancy. Hypersalivation in pathological conditions is called ptyalism, sialorrhea, sialism or sialosis.

• Hyper salivation occurs in the following pathological conditions:

1. Decay of tooth or neoplasm (abnormal new growth or tumor) in mouth or tongue due to continuous irritation of nerve endings in the mouth.

2. Disease of esophagus, stomach and intestine.

3.Neurological disorders such as cerebral palsy, mental retardation, cerebral stroke and parkinsonism.

4.Some psychological and psychiatric conditions.

5.Nausea and vomiting.

OTHER DISORDERS1. Xerostomia2. Drooling3. Chorda tympani syndrome4. Paralytic secretion of saliva5. Augmented secretion of saliva6. Mumps7. Sjögren syndrome.

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