Introduction : Our fascination with the marvelous machine that is our body predates Shakespeare by many, many centuries.

From earliest times, we have attempted to understand anatomy and have tried to map the body and its systems. One such system for discussion today is the salivary glands. We have pairs of ma!or salivary glands " parotid, sub#mandibular and sub#lingual besides several minor glands which are scattered through out the mouth and pharyn$. %he human salivary glands are important organs of oral cavity that produce saliva and essential fluid re&uired for normal speech, taste, mastication, swallowing and in digestions. Saliva functions in the maintainance of oral health through its anti microbial, cleansing, lubricating and buffering functions, as well as its role is digestion. %oday i will be discussing the development structure, function, and developmental anomalies of the ma!or and minor salivary gland is health. %he ma!ority of oral secretions are contributed by the sub#mandibular and parotid glands which e&ually provide '(#)(* of saliva,reminder is formed by sub#lingual and minor salivary glands. +n a day about ,((( ml " ,-(( ml of salivary is produced which contributes to the digestions of food, to the maintainance of oral hygiene and speech. %he development of these glands are principally induced to begin their characteristic branching morphogenesis through an interaction of the cells of the oral epithelium which is derived from the endoderm and the underlying mensenchyme.

DEVELOPMENT OF SALIVARY GLANDS ,. /eneral development process 0pithelial#mesenchymal interactions 1euro epithelial interactions 2. /eneral development pattern of salivary glands. . Stages of development. 1) General de elo!"ent !roce## $ i. 0pithelial#3esenchymal interactions 4 %he development of glandular tissue in mammals involves the interactions of epithelium with the underlying mesenchyme to form functional part of the gland. %hey are also defined as pro$imate tissue interactions and also secondary induction " in which the presence of mesenchyme in close pro$imity to epithelium is re&uired for normal development of epithelium. %he interactions regulate both initiation and growth of glandular tissue and cytodifferentiation of cells within salivary glands. %he mesenchyme is therefore re&uired for normal development as well as formation of supporting part of adult gland. 5awson studied rat sub#mandibular and parotid epithelium and found that both types can undergo differntiation with their own 6or. reciprocal gland7s mesenchyme. +n those cases when epithelium of one gland was combined with mesenchyme of other gland 6in vitro., growth and arrangements of acini were found to be governed by mesenchyme but not the function. +nteraction between salivary epithelium and mesencyme is provided by recent studies describing the presence of an acid mucopolysaccharide 638S. at the epithelio#mesenchymal interface. %here is an increasing concentration of this material at the distal end of growing and branching lobules. So these authors are suggesting 38S may be involved in
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morphogenesis. %his 38S is located in the basal lamina and appears to be protein#bound, permits glandular primordial branching when it is retained in vitro. 9nd if this 38S is removed, the epithelial growth produces only a spherical, unbranched structure. +n growing of salivary epithelial cords is related to the contractile ability of intra epithelial microfilaments. 0ven though microfilaments are present the budding 6clefting. will not occur unless specific salivary mesenchyme is present. ii) Me#enc%&"e : 'co"!o#ed o( cell# deri ed (ro" neural cre#t) 0$tracellular matri$ 60:3. and basal lamina. 3esenchyme consists of 4 a. ;ndifferentiated pluripotential connective tissue cells. b. 0:3 a. ;ndifferentiated pluedripotential :.% cells. # Fibroblasts # 3acrophages # 3ast cells b. 0:3 4 # /lycosaminoglycans # 8roteoglycans. Gl&co#a"ino)l&can# : # :hondroitin sulphate # <eratan sulphate # =yaluronic acid " gives gel like characteristic to 0:3. %hese glycosamino glucans 6,,2. are bound to a core protein to form proteoglycan sub units. %hese sub units are non#covalently bound to hyaluronic acid 6another /9/. " to form the bristle brush like structure of proteoglycan aggregate found in 0:3.
/ives gel like characteristic to 0:3.

Function# o( !roteo)l&can# : # Forms hydrated ground substance and also function in filtration 6eg. >enal glomerular ?.3.. # ?ind signaling molecules 6like growth factors to this target cells.. 5aminin " 0ntacin 6glycoprotein. " interact with each other and other components of 0:3 through receptors, a family of transmembrance linker proteins " known as +ntegrins. 0g. Fibronectin receptors. %hey allow intra cellular adhesive molecules 6+:93s. facilitate communication within cell cytoplasm. 60:3 to cytoskeleton.. %his communication @ linked changes " cell shape # 3otility # 3igration # 8roliferation # Aifferentiation 9ll which occurs during salivary gland development. In(luence o( E*M on de elo!"ent : %he 0:3 provides regulatory cues for # :ell proliferation # :ell differentiation # 3orphogenesis, the ma!or developmental process re&uired for the formation of adult salivary gland structure. *ell !roli(eration : +t is increased in number of cells that occurs during development as organs enlarge. :ells enter cell cycle, replicate A19 and undergo cytokinesis to form progeny 6daughter cells. *ell di((erentiation : +t describes process responsible for development of cell specificity and diversity as observed at the morphologic 6or. molecular level. +t e$presses a specific portion of genome that is characteristic of that particular cell type.
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*ell "or!%o)en#i# : +t describes those developmental process that are responsible for formation of shape and form of organ. 0g. ?randing of salivary gland. Neuro e!it%elial interaction# : 9nother study dealing with the events leading to the initiation of epithelial ingrowth has been under taken by AOC+1. %he research demonstrates formation of both the human and mouse mandibular and sublingual glands is directly related to /anglioneural recess. /anglio neural recess is term descriptive of the developing sub#mandibular ganglion cells and their location. %he further report demonstrated that both post ganglionic parasympathetic neurons as well as mesenchyme into which epithelium invagiantes are composed of ectomesenchyme, thus bringing salivary gland morphogenesis within the scope of developmental events that involve neural crest derivative cells. General de elo!"ent !attern and #ali ar& )land# : 9ll salivary glands follow similar developmental pattern. %he functional glandular tissue 6parenchyma. develops as an epithelial out growth. 6/landular bud. of the buccal epithelium that invades the underlying mesenchyma. %he connective tissue stroma 6capsule and septa. and blood vessels form from the mesenchyme. %he mesenchyme is composed of cells derived from the neural crest. +t is essential for normal differentiation of the salivary glands. 0:3 components synthesiDed by mesenchymal differentiation. +ud (or"ation and )land ori)in : 9s the epithelial bud forms during development, the portions that are close to stomodeum 6primitive and cavity. differentate into main e$cretory :.% cells provide signals to morphogenesis and

duct of gland. %he distal portions arboriDe to form the terminal portions of duct system, secretory end pieces or acini. %he origin of epithelial buds is believed to be ectodermal in the parotid and minor salivary glands and endodermal in the sub#mandibular and sub#lingual glands. %he break down of oropharyngeal 6bucco pharyngeal. membrane during Bth week of development, permits the intermingling of stomodeal ectoderm and cranial forgut endoderm, which complicates identifications of specific germ layer origin of S.glands, parotid glands originate near corners of stomodeum by E th week of prenatal life. Sub#mandibular araise from floor of mouth at the end of E th or beginning of Fth week of utero. %he sub lingual glands form lateral to sub#mandibular primordial at 'th week. 3inor S.glands form from epithelium but don7t develop until ,2th prenatal week. STAGES OF DEVELOPMENT Salivary gland development may be divided into E stages. Sta)e I : For"ation : induction o( oral e!it%eliu" ,& underl&in) "e#enc%&"a%he mesencyme underlying the buccal epithelium induces proliferation in the epithelium, which results in the thickening and formation of epithelial bud. %he growing bud is separated from the condensation of mesenchyme by basal lamina that is secreted by the epithelium. %he process of development of all salivary glands is similar e$cept the site and time of development. Sta)e II : For"ation and )ro.t% o( t%e e!it%elial cord : 9 solid cord of cells forms the epithelial bud by cell proliferation. :ondensation and proliferation occur in the surrounding mesenchyme that is closely associated with the epithelial cord. %he basal lamina is composed of /9/s, glycoproteins and collagen.

%he basal lamina, as well as surrounding mesenchyme influences morphogenesis and differentiation of salivary glands throughout their development. /%& "e#enc%&"a induce !roli(eration t%ere onl& 0 %o. 1 8resence of ,st arch ecto#mesenchyme is essential for full salivary gland development. 0g. if non#salivary gland mesenchyme is combined with salivary gland epithelium, the epithelium does not differentiate into glandular epithelium. Sta)e III : Initiation o( ,ranc%in) in ter"inal !art# o( t%e e!it%elial cord and continuation o( )landular di((erentiation %he epithelial cord proliferates rapidly and branches into terminal bulbs 6presumptive acini.. %he growth in length of solid epithelial cords and differentiation of the berry like terminal bulbs are noticed. Sta)e IV : Re!etati e ,ranc%in) o( e!i2cord and lo,ule (or"ation : %he branching continues at terminal portions of the cord, forming an e$tensive trace like systems of the bulbs. 9s the branching occurs connective tissue differetate around the branches, eventually producing e$tensive lobulation. %he glandular capsule forms from mesenchyme and surrounds the entire glandular parenchyma. Sta)e V : *anali3ation o( !re#u"!ti e duct# : :analiDation of epithelial cord, with formation of hallow tube or duct usually occurs by Eth month in all ma!or salivary glands. 5umen appear ,st in the proimal 6oral, terminal. and distal portions of the main e$cretory duct and in the branch ducts, then in the mid portion of main duct and lastly in the acini, all of which precede the formation of secretory granules. 5umen development occurs as a result of formation of tight !unctions 6Donular occludens. among the cells surrounding what was initially a simpler

intercellular space. 0$tensive branching of duct structure and growth of connective tissue septa continue at this stage of development. Sta)e VI : *&todi((erentiation : %he final morphologic stage of salivary gland development is cytodifferentation of functional acini and intercalated ducts. Auring this period, mitotic activity shifts from the entire epithelial cord to the terminal bulb portions. :ells of the bulb region are the stem cells that undergo cell proliferation and subse&uent differentiation into acinar cells as well as duct cells. 3yo epithelial cells also arise from epithelial stem cells in the terminal bulbs of the developing duct system and development in contact with acinar cytodifferentation. 3aturation of acinar cells occur in specific statges classified according to the morphology of secretory granules and cellular organells. 9cinor development differs for serous and mucous cells. %herefore, the parodid, sub#mandibular and sublingual salivary glands show variations in cuto differentiation patterns. %erminal bulb cells differentiate into intercalcated duct cells of the acdulct glands and they serve as a stem cell for acinor, myoepthelial and ductal cells. Secretogogue stimulus#secretion coupling mechanisms and innervation of the gland continue to mature following cytodifferentiation. PATIENT D4*T SYSTEM +n the formation of patient duct system of salivary glands it has been shown that 6a. the mucous membrane at the end of the duct differentiates insitu into a papilla. 6b. ducts are dilated initially by the secretion of water and of electrolytes by the cells themselves. Further, the prenatal duct cells, studies invitro, are sensitive to pharmocoliogic agents which tend to increase or decrease the transport of water and electrolytes. %he later fetal stages of human sub#mandibular salivary gland differentiations have been studied and they reported that 4 at B months of
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gestation only undifferentiated cells are present. 3ucous like cells can be seen in striated ducts at F months and serous cells are found in the terminal portions of the gland at gestation. POSTNATAL DEVELOPMENT %he postnatal developmental changes is the salivary glands was the work of Gacoby and 5eeson with light microscope and electron microscope. +n rat the sub mandibular and sub#lingual glands are more highly differentiated than the parotid at birth. +n rat acinar cells are not present at birth as they are in man and in pig. 9cinar cells are not present until F th day in the rat sub mandibular gland. %erminal ducts do not disappear and acini do not grow completely until B(th and ,2(th day. %hey 6Gacoby and 5eeson. described ultra structural changes in the terminal cells as secretory function is established. +n the mouse, also, the post natal developmental changes include the opening of the secretory lumina and secretory cell differentiation. Functional influences on the initiations of salivary secretion is a postnatal event. 9cinar transformation is induced and affected by cellular secretory activity. Secretion evokes a neural stimulation that effects acinar cyto differentiation. %he further correlation between function and glandular development is reported by >edmass and Sreebny. %hey noted two early postnatal developmental stages ,. ,st from , to ,2 days 2. 2nd from ,- to 2- days +n first enDymatic concentration in the cells increase greater than cell number or siDe. Auring 2nd phase cell siDe in particular is increased. Further ,st phase correlates with the on set of suckling 6enDymatic concentration. and 2nd phase with weaning, leading to suggestion that food substrates and

secretory stimuli may have indictive significance in salivary gland differatiation. PRO*ESS INVOLVED IN SALIVARY GLAND DEVELOPMENT 1) General Aevelopment of salivary glands is influenced by intrinsic and e$trinsic factors that regulate the process of cells proliferation, differentation and morphogenesis. %he intrinsic factors are defined as the programmed pattern of gene e$pression specific for each cell type. %his programmed script, with gene turned#on and turned off at appropriate times, leads to the normal development and growth of tissues and organs and the differentiation of cells. 0$trinsic factors are signals provided by cell#cell and cell#matri$ interactions, as well as by cytokines, hormones and growth factors in e$tracellular milier. %he e$trinsic factors define boundaries between groups of cells during development. 0g. 6Fruit fly. Arosaphila has been used as a model of embryonic development. %here is a shift during development between genes. 3aternal genes are e$pressed during oogenesis by the mother and act during oocyte maturation. %hey define broad regions with in the egg and regulate e$pression of the segmentation genes, that determine the number and @ or polarity of segments. Segmentation genes define smaller regions of embryo. %he last group, homeotic genes regulate development of , body part compared to other 6same as other side.. =omologous genes to those identified in drosophila are being identical in mammalian development with remarkable conservation of structure and regulatory functions. categories of

,(

5) Po#itionin) o( t%e )land# : %he formation of specialiDed structures 6salivary glands. is regulated by homeotic genes. %hese genes contain " homeobo$ domain i.e. E(#amino acid, A19 binding domain. 3uch of informations is obtained from the studies of drosophila. +n drosophila polarity is established initially along an anterior#posterior a$is 6head#tail. that establishes the segmentation of embryo. Further development within each segment establishes a doral#ventral 6back# abdomen. gradient that is translated into specialiDed structures in each segment of the larua and eventually the adult segmented fly. +n drosphila, the gene S0H :O3?S >0A;:0A 6se$. is a homeotic gene. +t encodes a transcription factor that is responsible for the location of salivary glands. Scr is uniformly transcribed in the cells of posterior head segment where the drosophila suli.gland will develop. %he dorso ventral boundaries of glands are established by genes homologous to mammalian genes, such as bone morphogenic protein " B 6?38#B. ?38#B limit the permissibility of Scr e$pression in drosophilla also involved in cascode of gene e$pression that regulates epithelial mesenchymal interactions involved in branching and other morphogenetic events. %he development of mammalian salivary glands mrophogenesis remain unclear. %he correct patterning of vertebrate embryo is based upon e$pression of =OH genes. %he e$pression and restriction of =OH genes are responsible for the differentiation of cells along the anterior#posterior a$is of all metaDoans. =OH#genes e$pression occurs in the vertebrate nervous system and its derivatives, including the neural crest cells.

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%he neural crest is instrumental in the formation of the salivary glands, teeth and over all craniofacial morphology through formation and differentiation of bronchial arches. 6) +ranc%in) o( t%e e!it%elial cord : ?ranching is the primary morphogenetic process in salivary gland development. :left formation in distal buds initiates branching process that is followed by epithelial proliferation. :ollagen type +++ accumulates at cleft points and appear to be critical for branching to occur. %ype + and +I collagen appear to be more ruportant for the maintenance and support of established branches. %ype + 4 %ype +++ collagen ratio increases at the time of branching. %ype +leads to stabiliDation while type +++ is more involved in active branching. 3ore recent studies also indicate that proteoglycan biosynthesis and deposition are re&uired for branching but not growth of the rudiments. :hondroitin sulfates are the predominant /9/S in the basal lamina of actively branching young rudiments and appear to increase during stabiliDation. %he independence of epithelial e$pansion and branding has been demonstrated by use of tunicamycin 6in vitro.. %unicamycin inhibits 1# linked glycosylation resulting in dramatically decreased protein accumulation and cell proliferation but epithelial branching is unaffected. 9fter tunicamycin treatment branching accurs and lobules form normally with inhibited cell proliferations, resulting in smaller rudiment with miniature lobes. +n contrast, the siDe and number of lobes increase in control cultures. ?ranching and proliferation must be coordinated processes for normal development. 3itotic activity is normally localiDed in the most peripheral regions of the bud. %reatment with hyaluronidase disrupts the basal lamina interfering with the signal re&uired for cleft formation. AestabiliDation of
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basal lamina there fore inhibits cleft development but also effects cell proliferation. +n the absence of normal basal lamina there is an absence of branching and generaliDed cell proliferation replaces localiDed mitotic activity. So basal lamina is important in initiation and maintenance of lobular morphology. %he basal lamina regulate morphogenetic changes by selective filtration or channeling of materials to the epithelium. For 0g 4 the regulation of the flow of ions such as :aJJ to epithelium may alter the function of micro tubules and microfilaments in cellular proliferation, migrations and arrangement. Synthesis of collagen 6collagenogentic. and selective break down of collagen 6collagenolysis. play a critical role in salivary gland development. For e$ample collagen synthesis by mesenchyme provides structural stabiliDation after branding has occurred. StabiliDation appear to be provided by type + and +I collagen fibres. +n addition, collagenolytic activity in the epithelium and mesenchyme may allow for selective breakdown of basal lamina and communicate between the epithelium, basal lamina, and surrounding mesenchyme at key stages of development. 7) Proce## in ol ed in c&to di((erentiation : %he interaction of the epithelium and mesenchyme is best stududied in a culture disb. Where epithelium can be grown in the presence of selected components of the basal lamina and specific growth factors. Salivary gland rudiments can branch invitro in the absence of mesenchymal cells, but in presence of other factors. 9 developing salivary gland rudiment have three clefts at the beginning of culture. %he epithelium is grown in serum with the use of an artificial matri$ known as 3atrigel, composed of mainly laminin, type +I collagen, heparan sulfate, entactin, and nidogen. ;sing this they abserved that different growth factors appear to regulate distinct parts of
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morphogenetic process. Fibroblast growth factor has bear shown to alter stalk elongation and epidermal growth factor 60/F. regulater branching. %he F/F and 0/F combination results in morphology similar to in vivo studies. 0:3 molecules regulate presentation and the distribution of growth factors to epithelium at appropriate time during in vivo. %here for, the 0:3 in concern with specific growth factors appears to regulate the comple$ processes involved in branching morphogenesis. :yto differentiation is believed as pre#programmed development occurring in early stages of morphogenesis. 9 period of in situ epithelial " mesenchymal contact is re&uired for cyto differentiation. 9fter this contact has taken place. 0$ocrine cell differentiation occurs without continued presence of mesenchyme. %here fore it appears there is a partial coupling of morphogenesis and cyto differentiation. Full differentiation of secretory components is apparent at birth, but is complete until the onset of a solid diet and the presence of masticatory stimuli. %his post natal development process includes the maturations of stimulus " secretion coupling that links secretagogue " membrane receptors to signal transudation pathways within the cell and control acinar cell secretion and establishment of neural connections from autonomic nervous system, the primary regulator of salivary gland function. Sali a (or"ation : ionic tran#!ort : Saliva is formed in 2 stage. First stage " is production by acinar cells. Second stage " is the ducts that change isotonic solution to the hypotonic solution. Aifferent systems involved are ,. 1aJ <J # 9%pase 2. 1aJ <J :l# co#trans port system. . ?icarbonate secretions " by 1aJ @ =J e$changer.
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B. :hloride secretions " by 1aJ @ =J and :l# @ =co e$changer. -. :aJJ regulated <J and :l# channels E. Osmotic flow of water. F. <J @ =J e$changers. '. 8aracellular transport of 1aJ and water. Saliva is primarily formed is the arrival cells and released into ducts where isotonic solution is modified into hypotonic solution by removal and addition of specific ions. 8rimary site of ionic transport is striated duct. Acinar #ecretion o( #ali a : +. On basolateral membrane 1aJ <J #9%pase e$changes 1aJ in an outward direction towards the interstitions with 2 < J moving inward. %he result is maintenance of high intracellular <J and low intracellular. ++. Aue to this action it drives 1aJ <J :l# co#transporter %his 1aJ <J :l# transporter necessary to transport :l# into acinar cells +++. 1aJ @ =J and :l# @ =:O # e$changers.o =co 9llow transport of =J 1aJ are taken by the acinar cells. On the laminal surface chloride channels allow for rapid efflu$ of :l # following cellular stimulation. 9ctivations of acetylcholine receptors Following para sympathetic nerve stimulation >esult in increased inter cellular calcium 6:aJ. %his 6:aJ. drives apical :l# channer. 9nd also activate :aJ activated <J channel on the baso lateral surface to preserve the membrane potential by giving the < J out into interstitium.
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to go outK while :l# and

II Sta)e o( #ali ar& #ecretion : =ere the isotonic saliva produced by acinar cells is modified into hypotonic saliva. %he duct cells reobsorb 1a J and :l# and secrete <J and =co # with out water reobsorption resulting in hypotonic saliva. %he basolateral membrane of duct cells process high # 1aJ # <J # 9%pase # 1aJ @ =J # e$changer # :l# @ <J channels %he luminal surface processes # 1aJ channels # :l# channels # 1aJ @ =J # :l# @ =:o # # =J @ <J e$change 9 genetic mutation in cystic fibrosis 6:F. gene alters :l # and other channels in salivary glands and leads to following symptoms. Seen commonly among :aucasian children is characteriDed by general dysfunction of salivary and other e$ocrine glands and results in pulmonary, digestive and nutritional difficulties. 9ccumulations of glycoproteinaceous material in the acinar cells and ducts leading to eventually obstructions of the ducts. Auring salivary secretion there is a rapid movement of water following stimulation. Since acinar cells shrink dramatically following secretions, it appears that most of water moves by osmosis in response to 1aJ in primary saliva. %here is also evidence for paracellular and transcellar movement of water. 9&uaporins are membrane proteins that function as high selective water channels in fluid transporting epithelum. 9&ua porins 69L8S. , and - are predominant inhuman salivary glands and mainly in serous acini.
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*LASSIFI*ATION OF SALIVARY GLANDS %he glands of the body may be classified into two general types 4 ,. 0$ocrine 2. 0ndocrine 1) E8ocrine : /lands are those glands with a duct system to transport secretion from the glands. 5) Endocrine : /lands are those duct less glands dependent on blood supply for delivery of their secretary products. Salivary glands are classified as e$ocrine glands, but these glands are associated with a number of biologically active substances 60g4 nerve growth factor and epidermal growth factor. that may be secreted by an endocrine mechanism. %hey are classified as compound tubulo acinar glands, which indicates the presence of a branched duct system and secretory units with both tubular and acinar portions. I) %he salivary glands of mammalian species may be divided into ,. 3a!or salivary glands 2. 3inor salivary glands. 1) Ma9or #ali ar& )land# : %hese glands produce ma!or part of salivary secretion most of the 6(.to (.F- lit.. saliva produced daily. %hese glands are located apart from oral cavity, they communicate with large e$cretory ducts. %here are three pairs of ma!or salivary glands 4 ,. 8arotid 2. Sub mandibular 6formely sub#ma$illary. . Sub lingual 5) Minor #ali ar& )land# : %hey are found in the oral cavity and are named according to their location. # ?uccal
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# 5abial # 5ingual # 8alative # /lasso palatine II) Salivary glands may also be classified by types of secretion. ,. Serous 2. 3ucous . 3i$ed 1) Serou# : serous secretion contains water, enDymes 6primarily salivary amylase and some maltase., a variety of salts, and organic ions. i. 8arotid gland ii. 5ingual glands " circumvallate papillar 6Ion 0bner7s glands. 5) Mucou# : 3ucous secretion produces mucins, which act as lubricant to aid in mastication, deglutition and digestin. i. /losso palatine "9nterior faucial pillar, and glasso palatine fold. ii. 8alatine glands iii. posterior lingual glands 6) Mi8ed )land# : i. ii. iii. iv. v. Sub#mandibular gland Sub lingual gland 5abial gland ?uccal glands 9nterior lingual glands

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GROSS ANATOMY OF SALIVARY GLANDS I- MA:OR SALIVARY GLANDS : 1) Parotid )land : 8arotid gland is the largest of the salivary glands. +t weight about ,-gm. Situation : +t is situated below e$ternal acoustic meatus, between the ramus of the mandible and the sternomastoid. 9 part of this forward e$tention is often detached, and is known as the accessory parotid. +t lies between the Dygomatic arch and parotid duct. Parotid ca!#ule : %he investing layer of the deep cervical fascia forms a capsule for the gland. %he fascia splits to enclose the gland. %he superficial lamina is thick and adherent to the gland is attached above to the Dygonatic arch. %he deep lamina is thin and is attached to the styloid process, the mandible and tympanic plate. 9 portion of deep lamina e$tending between styloid and mandible is thickened to form stylomandibular ligament which separate parotid from sub#mandibular gland. E8ternal (eature# : %he gland resembles a three sided pyramid with its ape$ down wards. %he gland has B surfaces. ,. Superior 6base of the pyramid. 2. Superficial . 9nteromedial B. 8osteriomedial. %he surfaces are separated by i. ii. 9nterior 8osterior
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borders 4

iii.

3edial.

Structure# .it%in !arotid )land : 1) Arterie# : %he e$ternal carotid artery enters the gland through its postero medial surface. %he ma$illary artery leaves the gland through its anteromedial surface. %he superficial temporal vessels emerge at the anterior part of the superior surface. %he posterior auricular artery may araise with in the gland. 5) Vein# : %he retromandibular vein is formed with in the gland by the union of the superficial temporal and ma$illary veins. +n the lower part of gland the vein divides into anterior and posterior divisions which emerge at ape$. 6) Ner e# : %he facial nerve enter the gland through the upper part of its posteriomedial surface and divides into its terminal branches with in the gland. %he branches leave the gland through anteriomedial surface temporal, Dygomatic, 6upper buccal and lower buccal., buccal, mandibular and cervical branch. Parotid duct : +t is thick walledand is about - cm long emerges form the middle of the anterior border of the gland. +t runs forward and down wards on masseter. =ere its relations are " Su!eriorl& : a. 9ccessory parotid gland b. ;pper buccal branch of facial nerve c. %ransverse facial vesels. 9t the anterior border of the masseter it turns medially and pierces a. ?uccal pad of fat b. ?uccal pharyngeal fasia c. ?uccinator.
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%he duct runs forward for a short distance between buccinator and oral mucosa. Finally the duct turns medially and opens into the vestibule of the mouth opposite the crown of the upper second molar tooth. +lood #u!!l& : 8arotid gland is supplied by the e$ternal carotid artery and its branches that araise near the gland. %he veins drain into the e$ternal Gugular vein. Ner e #u!!l& : ,. 8ara sympathetic nerves are secretomotor. %hey reach the gland through the auriculotemporal nerve. %he pre ganglionic fibres begins in the inferior salivary nucleus, pass through the ) th nerve, its tympanic branch, the tympanic ple$us, and the lesser petrosal nerve and relay in the otic ganglion. %he post ganglionic fibres pass through the auriculotemporal nerve and reach the gland. 2. Sympathetic nerve supply 4 sympathetic nerves are vasomotor and are derived from the ple$us around e$ternal carotid artery. . Sensory nerve Supply 4 Sensory nerve supply to gland comes from the auriculo temporal nerve, but parotid fascia is innervated by the sensory fibres of the greater auricular nerve 6:2.. L&"!%atic draina)e : 5ymph drains first to parotid nodes and from there to the upper deep cervical nodes. 5) Su, ; "andi,ular #ali ar& )land : %his is large salivary gland. +t is about siDe of a walnut. +t is roughly MG7 shaped. Situation 4

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+t is situated in the anterior part of the digastric triangle. +t is roughly MG7#shaped being indented by the posterior border of mylohyoid which divides it into large part superficial to the muscle, and a small part lying deep to muscle. Superficial part 4 %his part e$tends upwards deep to the mandible upto the mylohyoid line. +t has a. +nferior b. 5ateral c. 3edial surfaces. %he gland is partially enclosed between two layers of deep cervical fascia. %he superficial layer of fascia covers the inferior surface of the gland and is attached to the base of the mandible. %he deep layer covers the medial surface of the gland and is attached to mylohyoid line of the mandible. Relation# : A) In(erior #ur(ace : +nferior surface is covered by a. Skin. b. 8latysma c. :ervical branch of facial nerve d. Aeep fascia e. Facial vein f. Sub#mandibular lymph nodes. +) Lateral #ur(ace : +s related to a. Sub mandibular fossa on the mandible b. +nsertion of medial pterygoid c. Facial artery

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*) Medial #ur(ace : %his surface is divided into a. 9nterior part b. 3iddles part c. 8osterior part a) Anterior !art : +s related to ii. iii. iv. i. ii. iii. iv. v. i. ii. iii. iv. 3ylohyoid muscle 1erves Iessels =yoglossus Styloglossus 5ingual nerve Sub mandibular ganglion =ypoglossal nerve Styloglossus Stylohyoid ligament 1inth nerve Wall of pharyn$ parts.

,) Middle !art : +s related to

c) Po#terior !art : +s related to

9nd inferiorly it overlaps stylohyoid and the posterior belly of digastric. Dee! !art : %his part is small in siDe. +t lies deep to mylohyoid and superficial to the hyoglossus and the styloglossus. 8osteriorly it continues with superficial part round the posterior border of mylohyoid. 9nteriorly it e$tends upto the posterior end of sub lingual gland. Su, "andi,ular duct : +t is thin walled and is about - cm long. +t emerges at the anterior end of the deep part of the gland.
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 >uns between the lingual and hypoglossal nerves. 9t the anterior border of hyoglossus the duct is crossed by lingual nerve. +t opens on the floor of the mouth on the summit of the sub lingual papilla at the side of the francium of the tor&ue. +lood #u!!l& : +t is supplied by the facial artery. %he veins drain into the common facial or lingual vein. L&"!%atic draina)e : 5ymph passes to sub mandibular lymph nodes. Ner e #u!!l& : Supplied by the branches of submandibular ganglion. %hese branches convey a. Secretomotor fibres. b. Sensory fibres fromlingual nerve c. Iasomotor sympathetic fibres from the ple$us of facial artery. Secretomotor pathway begins in superior salivarynuclers 8reganglionic fibres pass through the sensory root of facial " nerve, /eniculate ganglion, Farial nerve, :horda tympani and lingual nerve to reach sub#mandibular ganglion %hen port ganglionic fibres enter the sub mandibular gland.
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6) Su,2lin)ual #ali ar& )land : %his is the smallest of the three ma!or salivary glands. +t is almond shaped and weighs about #Bgm. Situation : +t lies#above mylohyoid, below mucoso of the floor. ?ehind is deep art of sub mandibular gland. 3edial to the sub lingual fossa of mandible and lateral to the genioglosses. 9bout ,- ducts emerge from the gland. 3ost of these ducts 6ducts of >inivus.. Open directly into the floor of the mouth on the summit of the sub#lingual fold. 9 few of them !oin sub mandibular duct. +lood #u!!l& : ?lood supply is from lingual and sub mental arteries. Ner e #u!!l& : +t is similar to sub mandibular gland. II) MINOR SALIVARY GLANDS : La,ial )land# : 9 large percentage of substance of the lips is glandular tissue. =ere multiple small glands lie between the mucosa of the lip and orbicularies muscle. %hey open directly by many small ducts directly onto lip mucosa. +uccal )land# : +n a similar, diffuse fashion, to that labial glands, the buccal glands are located in the cheek, between the mucosa and the buccinator muscle. Palatine )land# : %he posterior one third of the hard palate is covered with palatine glands. %hese glands are sparsely found anterior to the bicuspid region of the plate. %hey are also found in the soft palate. %hey are &uite numerous here.

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Lin)ual )land# : %here are two groups of lingual glands. 9nteriorly, on the ventral surface of the tongue, is anterior lingual gland 6of ?landin and 1uhn.. On the dorsal surface of tongue are the glands surrounding the trough of the circumvallate papillae. 9lso, on the dorsal surface are glands around the lingual crypts at the base of the tongue. <ISTOLOGY OF SALIVARY GLANDS Serou# cell# : %he parotid gland is the largest of the salivary glands. %he acine of the gland are serous although mucous cells have occasionally been reported. %he cells have characteristic granular appearance with rouine haemoto$ylin and eosin staining. :onnective tissue septa can be seen sub dividing the secretory parenchyma into lobes and lobules. %he connective tissue contain blood vessels, nerves and collecting ducts. %he lumina of acini are very hallow, unless distended by the accumulation of secretions. %he prominent nuclei are round and located in the basal third of the cell which is basophilic 6due to presence of roFugh endoplasmic reticulum.. +n the ultra structural appearance of serous acini, the cells have wedge shaped outline and surround the central lumen %he basal part of each serous cell is delineated from the surrounding connective tissue by a basal lamina. %his region of cell contains the nucleus and rough endoplasmic reticulum and capillaries are in close appro$imations to this surface. %he leminal part of the cell contain dense round symogen granules. 3any narrow canaliculi run between the cells and !oin the lumen. ?oth the canaliculi and lumen are lined by short microvilli. 9d!acent cells membranes contact at desmosomes, gap !unctions and tight !unctions.

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Mucou# cell# : +n routine microscopy the collections of mucous acini are readily distinguished in the resting gland because the mucous acini are paler since their mucinous content does not readily take up routine stains or is lost during preparation. %he nucli are compressed into the basal part of the cell. small crescent shaped collections of serous cells may be found in routine sections at the most distal ends of the mucous acini. %hese are referred to as serous demilunes. 3ucous acini can be specifically differentiated from serous cells by staining with alcian blue 6or. 89S 6periodoe acid " schiff.. %he distentions caused by mucous granules with in each cell results in a flattering and displacement of the nucleus into the basal cyto plasm. +n the early stages of synthesis of its secretory products, large amounts of rough endoplasmic reticulum and few mucous droplets are present. :ompared with serous cells, the mucous cells have more golgo apparatus. 9s carbohydrates at the later stage of its secretion round pale granules are e$hibited. M&oe!it%elial cell# : 3yoepithelial cells lie between the basal lamina and the basal membranes of the acinar secretory cells and intercalated duct cells. 3yoepithelial cells around acini are dendritic cells consisting of a stellate " shaped body containing the nucleus and a number of tapering processes radiating from it. 3yoepithelial cells in the intercalated ducts are elongated, run longitudinally along the duct and have few short processes. 9round the acini, the processes lie in gathers on the surface of the secretory cells, so the out line of the acinus remains smooth. 9round the intercalated ducts, the cells lie more superficially and produce a bulge in the out line of the duct. 3yoepithelial cells contract as a result of activity of both parasympathetic
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and sympathetic stimulations. ;ltrastructurally, the nucleus tends to be flattened and intra cellular organelles associated with protein synthesis are not abundant. :ell contains numerous contractile actin microfilaments B #'m in diameter. 3yo epithelial cells have desmoromal attachment with under lying parenchymal cells, gap !unctions and remidesmoromal attachment with the basal lamina. 3yoepithelial cells contain cytokeratin inter mediate filament ,B and contractile acine filaments. %he presence of cyto keratin confirms the epithelial origin of myoepithelial cell. pincytotic vesicles and dense attachment areas are associated with that part of plasma membrance of the myoepithelial cell covered by basal lamina. Functional role o( "&oe!it%elial cell# in #ali ar& #ecretion#,. 9ccelerate the initial out flow of saliva. 2. >educe leminal volume . :ontribute to the secretory pressure. B. Support the underlying parenchyma and reduce back permeation of fluid. -. =elp salivary flow to overcome increases in peripheral resisitance " but of this is e$cessive of may lead to sialectatic damage of striated ducts, thereby increasing over all permeability. 9nd also include assistance for some parenchymal cells to e$pel their contents. <ISTOLOGY OF T<E SALIVARY D4*TS Duct : %he duct differs in each of ma!or salivary glands. %he duct system has 2 main structural parts4 +ntra lobular and the interlobular portions. +ntra lobular ducts are of two types 4 ,. +nter calated ducts 2. Striated ducts.
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+nter lobular portion ducts are termed the e$cretory ducts. Intercaled duct# : +ntercaled ducts are lined by low cuboidal epithelium and drain secretory end pieces. %hey contain few secretory granules, rough endo plasmic reticulum, mitochondria, round @ oval centrally placed nucleus. Striated duct# : 9re ne$t largest ducts located between the e$cretory and intercalated ducts. %hey carry ion#transport functions that occur along the route of the saliva from the acinar lumen to the oral cavity. %hey are lined by tall columnar epithelial cells, with distinct eosnophillic cytoplasm, special, centrally or ecentrally placed nuclei. %he term striated refers to light microscopic appearance of the basal cytoplasm that has well developed striations perpendicular to the base of the cells. Striated duct cells are present around lumen. Sodium reabsorption and potassium e$cretion occur within these cells and effect the change of level of adrenal cortical steroid hormone mainly aldosterone. Sodium reabsorption changes saliva from an isotonic to a hypotonic osmolarity. E8cretor& duct# : %hese e$cretory ducts empty the secretions into the oral cavity. 9s the e$cretory ducts become larger the epithelium lining of these ducts change from simple columnar to psuedo stratified or stratified columnar epithelium. 9t or near the entrance of oral cvity these ducts become lined with stratified s&uamous epithelium continued with buccal epithelium. *ONGENITAL ANOMALIES Sali ar& )land <eteroto!ia : 8resence of salivary gland tissue outside the ma!or salivary glands and the upper aerodigestive tract is called as hypertopia. Etiolo)& : 0mbryonic migration of salivary gland. +t is congenital anomaly due to developmental defect.
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+t may be intalymphatic @ e$tralymphatic. Intra l&"!%atic %&!e : +n lymph nodes 3ost lymph nodes was to parotid than S.3. 6or. upper cervical nodes. :onsist " +nter collated, interlobular ducts, acini. E8tra l&"!%atic i. ii. =igh form " limited to parotid 5ow form

# 1eoplastic transformation is rare. De elo!"ental a,nor"alitie# = di#tur,ance o( #ali ar& )land# 2. 9plasia @ 9genesis . =yper plasia of palatal glands B. 9tresia -. 9berrancy E. 9nterior lingual depression. 1) A!la#ia = A)ene#i# : 9plasia is congenital absence of any of the ma!or salivary gland. 9ny of the gland may be missing unilaterally or bilaterally. Etiolo)& : 0tiology is unknown and is not necessarily associated with othe rectodermal dysplasias. 3ay be familial 6or. hereditary. %wo such cases, accruing in father and son have been reported by smith. *linical (eature# : i. ii. iii. iv. v. vi. Herostomia @ dry mouth. Oral mucosa becomes dry and smooth. 9ccumulation of debris over oral mucosa is seen. :racking of lips Fissuring at corners of mouth >arupant caries
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Treat"ent : # Oral hygienes maintenance # Flouride treatment 5) <&!er!la#ia o( !alatal )land# : # +t appears as small localiDed swelling in palatal mucosa has been described by /iansanti and associates. # %hey are , cm 6or. more in siDe. # %hese are of normal in colour. *au#e# : :ause is unknown. %he following may result in salivary gland enlargement.
9ging 9lcoholism /out Aiabetes +nflammation ?enign lympho epithelial lesions

Starvation 3enopause =epatic disease 0ndocranial disturbances S!ogrens disease

9diposity =yperthermia Oligomenorrhae 8arotid swelling

9glossi#adactyla syndrome Wald enstrom7s macroglobulinemia ;veo parotid fever Felty7s syndrome :ertain drugs 9ging process

*linical (eature# : # +t presents a small localiDed swelling, measuring from several mm to , cm in diameter, usually on hard palate or at the !unction of the hard and soft palates. # %he lesion has intact surface and is firm, sessile and normal in colour. # +t is usually asymptomatic and patient may be un aware of the lesion. <i#tolo)ical (eature# :

3ass appears microscopically as closely packed collections of normal appearing mucous acini with the usual intermingling of normal ducts. %here is no inflammation, no spillage of mucous, no florosis. Treat"ent : %hey should be e$cised as these cannot be differentiated from neoplasm at palatal mucosa. 6because malignant palatal neoplasms also don7t ulcerate.. 9nd no further treatment is necessary and the condition is not reported to recur. 6) Atre#ia : :ongenital occlusion 6or. absence of one 6or. more of the ma!or salivary ducts in termed as atresia. 9s the salivary duct is absent it may lead to the retention cyst and $erostomia. Such a case has been reported by forotich and his associates. 7) A,eranc& : %he situations at which the salivary glands found other than there usual locations. 0g. Static ?one :yst @ Stafne7s cyst +t is well circumscribed lesion. *au#e# : +t is formed due to developmental inclusion of salivary gland tissues within 6or. ad!acent to the site, where it is formed. Radio)ra!%ic (eature# : # Ovoid area of radiolucency between mandibular canal and inferior border of !aw 6below mandibular canal.. Di((erential dia)no#i# : # =aemorrhagic bone cyst. # %raumatic bone cyst. >) Anterior lin)ual de!re##ion : # +t is poorly circumscribed depression on the anterior part of lingual aspect of mandible. # +t is present between central incisor and ,st premolar area. %his anterior radiolucency also represents a cavity 6or. depression on lingual surface of the mandible.
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5angalis and his co#workers e$amined ,2 dried mandibles and revealed that either anatomic variants related to the digastric 6or. sub# lingual fossa or developmental anomalies caused by impingement of the sublingual gland. *au#e : +t is formed due to inclusion or impingment of salivary gland tissues. *o"!lication# : 9 complications occasionally reported is the development of true central salivary gland neoplasm from the included salivary gland tissue, but this is rare. *linical con#ideration# 1) <&!er (unction Sali ar& #ecretion i# increa#ed : Etiolo)& : # 3entally retarted children # ;nderlying neurological disease like cerebral palsy # Side effect of the neuroleptic drugs like fluphenaD %riflupro maDine # +ll#fitting dentures # Optics ulcers # >abies # =eavy metal poisoning *linical (eature# ; 8atient present with hyper salivation noticed clinically. # Arooling of saliva in mentally retarted children # :erebral palsy # 3ental retardations # 3acerated sores around mouth # :onstant soling of cloths and beds Idio!at%ic !aro8&#"al #ialorr%ea :

# 2 " - 3inutes # :ause is unknown # 0pisodes of nausea @ epigastria pain is noticed. Treat"ent : # +f mild treatment is not method # +ncreased saliva with gastro esophageal reflu$,,st that reflu$ should be corrected and saliva decreased. # 9nticholinergic medications " Scopolamine # 0$cision of sub mandibular and ligations of parotid duct # Sectioning of chordac tympanic. Sometimes relocations of parotid @ sub mandibular duct positioned posteriorly to tonsillarfossa. 5) <&!o#ali ation : Aecrease in the salivary flow Etiolo)& : 6i. 6ii. 6iii. 6iv. 6v. +atrogenic " 3edicaments 1eurological " ?ells palsy 3etabolic disease# 3ental depression,malnutrition, Iitamin deficiency dehydrations. =ormonal diseases " Aiabetes mellitus. +nfections " ?acterial Iiral =+I 6vi. 9uto immune# S!ogren7s syndrome 6non specific parotitis.. %umors :arcinomas. 6vii. 5ocal salivary disease " Sialolithiasis 8orotitis 3umps

'i)

Medica"ent# : Aiuretics 4 :aJ blockers " 1eifedepine Ierapmil 9rtery dialators

+sosorbide dinitrate " Ienal dialator 9:0 inhibitors 0nalopril :aptorpil =ydrochlorthiaDide Frusemide 9miloride Aiuretics 3i$ed dialators

9ntihypertensive drugs ?0%9#adrenergic blockers. Aiuretics :aJ channel blockers 9:0 inhibitors. # blockers " phenotalanine ?# ?lockers " 9tenolol 8ropronal 3etaprolol 9lpha beta blockers#labetolol
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Antide!re##ant 2adrener)ic ,loc?er# # +mipramine # Aesipramine # Ao$epin # 9mo$apine Anti!ar?in#oni#"# 'c%olener)ic) # 5euodopa # :arbidopa Anti%i#ta"ine# 'c%olener)ic) # 8romethaDine # :hlorpheniramine # :imitidine # >anitidine # Famotidine # %hioperamide # +mpromidine # 9tropone # Scopolamine Anti!#&c%otic# 2adrener)ic # :hlorparaDine # %hioridaDine # Aental caries # 9trophy of mucosal surfaces # +ncrease chance for oral infections # ?urning sensation of tongue
E 8henothiames = =2 =,

Antic%oliner)ic 'c%oliner)ic)

*linical (eature# o( %&!o#ali ation = 8ero#to"ia :

# Aifficulty in swallowing # 9ltered taste perception S9o)ren@# #&ndro"e : 9utoimmune disease involving salivary and lacrimal glands with lymphatic infiltration in the ducts. Etiolo)& : # 9utoimmune # 9t the time of viral @ bacterial infection it may lead to e$pression of foreign molecular species at cell surface of salivary epithelial cells triggering an immune response. Treat"ent : # /lecerin # 5emon mouth wash # 9rtificial saliva Sailolit%ia#i# 'calculi = #tone#) Sialolioths calcified structures that develop within salivary ductal system. 9raise from the deposition of :aJ salts around nidus of debris within duct lesion. Aebris may include # ?acteria # Foreign bodies # Auctal epi cells *linical (eature# : # 3ostly sub#mandibular # 8ain, swelling mostly in meal time # Seviority depends on obstruction @ back pressure # +f stone located at terminal portion of duct a hard mass may be palpated beneath the mucosa.
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# Dia)no#i# : # 1ot all stones are visible on standard radiographic e$amination. # %erminal portions of ducts " by occlusal radiograph # +n panaromic @ periapical $#rays " super imposed on mandible # Sailography # :% scan#computeriDed tomography # ;ltrasound Treat"ent : # 3assaging the gland " terminal ductal # +ncrease fluid intake # Sailogogues Surgical removal including gland # Salivary gland endoscopy " newer method i. ii. +ntrocorporeal lithotripsy to help fragment the stone. 0$tracorporeal shock wake lithotripsy have been used successfully in 0urope and Gapan Treat"ent o( 8ero#to"ia : # 9rtificial saliva # :ontinuous water through out the day # Sugar less candy " stimulate salivary flow # ?iotene o 5actoferrin o 5actopero$idase o 5ysoDyme # Aicontinuation of the medications # Sailogogue " pilocarpone " parasymptomatic against pilocarpine -# ,(mg " thrice @ four times a day.
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# :erimeline hydrochloride 6acetyl chloride derivative. 6recently approved in ;S9. # cevimelius, pilocorpine " avoided in glaucoma. # Fluoride applications # 3outh rinses # ?ethanechol F-#2((mg @day # 9mifostine " +I before radiotherapy

REFEREN*ES : ,. 8ediatric developmental pathol 2((B 3ay#Gune F 6 . 2E2#2EF +1%>9%=N>O+A95 ?>91:=+95 :50F% 5+<0 :NS% W+%= =0%0>O%O8+: S95+I9>N /591A#%N80 %+SS;0 %he patient was a Fyr old girl with growing mass in the left lateral neck. %he ultrasonography revealed a cystic lesion in left thyroid. =istologically, the cyst was lined by s&uamous @ respiratory type epi. %he cyst was intimately associated with hypertropic tissues including lobules of well differentiated seromucinous salivary glands, mature fat tissue, and islands of the cartilage. 2. O.S.O.3.O.8.O. >adio 0ndod 2((B Aec )' 6E. F,2#F,B. ;1+59%0>95 9/010S+S OF %=0 89>O%+A /591A. %hey reported a case of unilateral agenesis of parotid gland without involvement of other ma!or glands together with a compensatory hypertrophy of the contralateral parotid gland. . ?ritish !our Oral ma$illo Fac Surg 2((2 Oct B( 6-. 4 B--. :O1/01+%95 9%>0S+9 OF %=0 O>+F+:0 OF %=0 S9%# 391A+?;59> A;:%.

2 infants presented with unilateral cystic swelling in the floor of the mouth as a result of imperforate sub#mandibular ducts. %his is thought to result from a congenital failure of canaliDation of the terminal end of the duct. ?oth cases responded to simple incision and decompression of the fluid#filled duct. 0arly treatment is important to avoid feeding difficulties and to prevent later complications such as ranula or sialadenitis. B. G Oral 8athol 3ed. 2((B 1ov K 0:%OA0>395 ANS859S+9 6,(.4 E B#E. 9859S+9 OF S;?391A+?;59> S95+I9>N /591AS 9SSO:+9%0A W+%=

*ON*L4SION : %he harshness of the process of chewing is mellowed down by the secretions of salivary glands i.e. and saliva. %o put in a nut#shell, all salivary glands are a collection of secretory acini which empty their secretion into intercalated ducts. %he secretion from several intercalated ducts converges into larger ducts and the process of convergence continues until finally the secretion is poured into the mouth. %hus, the salivary glands and saliva acts as a foundation for the garden of the oral cavity to maintain the natural form of soft and hard components.

B(