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وزارة التعليم العالي والبحث العلمي جامعة القادسية كلية طب االسنان

HISTOLOGICAL STUDY FOR SALIVARY AND COMPARESION BETWEEN ADULT AND CHILD IN SOME HISTOLOGICAL STRUCTURES

بحث مقدم الى كلية طب االسنان كجزء من متطلبات نيل شهادة البكالوريوس

تقدم به الطالبات: ندى علي حسين فرح علي عبد أطياف ماجد جميل امال عبد الكريم جريو

بأشراف: الدكتورة نهى شاكر علي

1440هـ 2019 م

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بسم هللا الرحمن الرحيم ))قالوا سبحانك ال علم لنا اإل ما علمتنا إنك انت العليم الحكيم (( صدق هللا العلي العظيم

سورة البقرة /32

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شكر وثناء : الحمد هلل الذي ذكره شرف للذاكرين وشكره فوز للشاكرين وحمده عز للحامدين وطاعته نجاة للطائعين والصالة والسالم على خاتم األنبياء والمرسلين محمد وعلى ال بيته الطيبين الطاهرين وبعد : فعن رسول هللا )صل هللا عليه واله وسلم( انه قال:من لم يشكر الناس لم يشكره هللا فبعد االنتهاء من هذا البحث يطيب لي في مقام الشكر ان اسجل بأمتنان شكري وتقديري الى دكتورتي الفاضلة )الدكتورة نهى شاكر علي ( وذلك لقبولها باالشراف على البحث . كما أتقدم بشكري وامتناني لعائلتي وأصدقائي وزمالئي في الدراسة لمساندتهم لي كما اهدي شكري لكل من اعانني في دراستي سواء بالقول او الفعل او الدعاء وأخيرا فأني وان ذكرت بعض األسماء دون األخرى فأن ذلك ال يعني عدم الوفاء والتنكر للقسم االخر بل لهم مني جميعا بعد المعذرة – أكثر مما تحويه األسطر وتقدمه الكلمات.

االهداء :

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الى بؤرة النور التي عبرت بي نحو األمل واألماني الجميلة واتسع قلبه ليحتوي حلمي حين ضاقت الدنيا فروض الصعاب من اجلي وسار في حلكة الدرب ليغرس معاني النور والصفاء في قلبي والدي الحبيب لقد عاش من اجلنا من اجل ان نحيا حياة كريمه في بيتا كريم وفي احضان علم نافع كريم ومن اجل ان انفذ امامه بشهاده التي تعترف كل قصاصة فيها بانه سبب جهدها , فقد كنت معنى الحياة لي وقد رضاني هللا فيك يا ابتي فهل رضيت عني الى من تتسابق الكلمات لتخرج معبرتا عن مكنون ذاتها الى التي تمتهن الحب وتغزل األمن في قلب عصفورايرفرف فوق ناصية االحالم فتبقى روحي متالأللة ومشرقة طالما كانت دعواتها عنوان دربي وتبقى امنياتي على وشك التحقق طالما يدها في يدي وسنارة جهدها وسهرها تصتاد لي الراحة وتخطف التعب وااللم من قلبي الى امي التي مهما كبرت سأبقى طفلتها التي تكتب اسمها على دفتر قلبهافي ساعة حزنها .

CONTENT:

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Conclusion p.7 Introduction p.8 p.12 Introduction p.12 Location p.15 Function p.15 Development p.16 p.16 Comparesion between parotid gland in child and adult p.18 p.19 Location p.20 Function p.20 Development p.21 Histology p.21 Comparesion between sublingual gland in child and adult p.21 p.23 Location p.24 Function p.24 Development p.24 Histology p.25 Comparesion between submandibular gland in child and p.26 adult Minor salivary p.27 Location p.27 Function p.27 Development p.28 Histology p.28 Comparesion between minor salivary glands in child and p.29 adult Refrences p.30

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Figures content Figure1 p.8 Figure2 p.9 Figure3 p.13 Figure4 p.14 Figure5 p.17 Figure6 p.18 Figure7 p.18 Figure8 p.19 Figure9 p.22 Figure10 p.23 Figure11 p.23

Abstract: Salivary glands are compound, tubuloacinar , , exocrine glands which ducts open into the oral cavity . There glands that distributed in many locations inside the oral cavity which include 800-1000 glands. Secretion of is the main function emanating from salivary glands that is depend on are three pairs of major salivary glands which are parotid gland , sublingual gland , and submandibular gland and minor salivary

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afferent stimulation ( and mastication ). Saliva is a complex fluid composed from over 99% water , yet the small amount of additional inorganic and organic compounds (such as protein ,glycoproteins , and ) allows it to perfume many important functions . A major role is related to production of , which acts as lubricant during mastication , , and speech . The mucous film protect the mucosa and keep it moist , Also it brings substances into solution so that they can tasted , and limit the activity of bacteria by causing their aggregation . Saliva contains minerals and acts as buffer , both features helps to maintain the integrity of the dental enamel . Salivary glands pass major changes during age in morphology , amount of secretions , and size , Also it may be changes due to many types of .

REVIEW

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Salivary glands Introduction:

Fig(1) Saliva is produced by three pairs of major salivary glands ... Parotid, Sublingual and Submandibular . as well as minor accessory glands found throughout the mucosa.

Fig (2)A diagram of part of a showing a serous and mixed serous-mucous acinus.

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Salivary glands are made up of secretory acini (acini - means a rounded secretory unit) and ducts. There are two types of secretions - serous and mucous. The acini can either be serous, mucous, or a mixture of serous and mucous. A serous acinus secretes proteins in an isotonic watery fluid. A mucous acinuss secretes secretesmucin – lubricant. In a mixed serous-mucous acinus, the serous acinus forms a around mucous acinus,The secretory units merge into intercalated ducts, which are lined by simple low cuboidal , and surrounded by myoepithelial cells. These ducts continue on as striated ducts. These have a folded basal membrane, to enable active transport of substances out of the . Water resorption, and ion secretion takes place in the striated ducts, to make saliva hypotonic (reduced Na,Cl ions and increased carbonate, and potassium ions).The striated ducts lead into interlobular (excretory) ducts, lined with a tall columnar epithelium.The glands are divided into lobules by connective tissue septa. Each lobule contains numerous secretory units, or acini.

Aging of salivary glands show some structural changes, such as: 1- Decrease in volume of acinar tissue. 2- Increase in fibrous tissue. 3- Increase in adipose tissue. 4- Ductal hyperplasia and dilation. 5- In addition, there are also changes in salivary contents: A- Decrease in concentration of secretory IgA. B- Decrease in the amount of mucin.

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However, there is no overall change in the amount of saliva secreted. And Salivary glands secrete saliva which has many benefits for the oral cavity and health in general. These benefits include: -Protection: Saliva consists of proteins (for example; ) that lubricate and protect both the soft and hard tissues of the oral cavity. Mucins are the principal organic constituents of , the slimy visco-elastic material that coats all mucosal surfaces. -Buffering(6): In general, the higher the saliva flow rate, the faster the clearance and the higher the buffer capacity, hence better protection from dental caries. Therefore, people with a slower rate of saliva secretion, combined with a low buffer capacity, have lessened salivary protection against microbes. -Pellicle formation: Saliva forms a pellicle on the surface of the tooth to prevent wearing. The film contains mucins and proline-rich glycoprotein from the saliva. The proteins (statherin and proline-rich proteins) within the salivary pellicle inhibit demineralization and promote remineralization by attracting calcium ions. -Maintenance of tooth integrity: Demineralization occurs when enamel disintegrates due to the presence of acid. When this occurs, the buffering capacity effect of saliva (increases saliva flow rate) inhibits demineralization. Saliva can then begin to promote the

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remineralization of the tooth by strengthening the enamel with calcium and phosphate minerals. -Antimicrobial action: Saliva can prevent microbial growth based on the elements it contains. For example, lactoferrin in saliva binds naturally with iron. Since iron is a major component of bacterial cell walls, removal of iron breaks down the cell wall, which in turn breaks down the bacteria. Antimicrobial peptides such as histatins inhibit the growth of Candida albicans and Streptococcus mutans. Salivary Immunoglobulin A serves to aggregate oral bacteria such as S. mutans and prevent the formation of dental plaque.

-Tissue repair(9): Saliva can encourage soft tissue repair by decreasing clotting time and increasing wound contraction. -: Saliva contains the , which hydrolyses into maltose and dextrin. As a result, saliva allows digestion to occur before the food reaches the stomach(16). -Taste(12): Saliva acts as a solvent in which solid particles can dissolve in and enter the taste buds through located on the . These taste buds are found within foliate and circumvallate papillae, where minor salivary glands secrete saliva(10) .

REVIEW

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1-Parotid gland : Introduction: The parotid gland is the largest major salivary gland. The parotid is 5.8 cm craniocaudally and 3.4cm ventrodor- sally. It weighs between 14 and 28 grams. The main excretory duct, Stensen’s duct measures 4–6cm in length and 5 mm in diameter. A small portion of the parotid generally accompanies the duct forming an accessory gland, a few millimeter anterior to the superficial portion of the gland. The parotid gland receives its blood supply from the branches of the external carotid as they pass through the gland. The parasympathetic supply is derived mainly from the ninth cranial nerve reaching the gland via the and the auriculotemporal nerve. The sympathetic innervation of all salivary glands is provided by the postganglionic fibers from the superior cervical ganglion and reaches the individual gland in association with their vascular supply. The lymphatic drainage is via paraparotid and intraparotid nodes into the superficial and deep cervical lymph nodes. The parotid gland is enclosed in a well defined connective tissue capsule which sends septa into the gland, separating it into lobes and lobules. The parotid gland is a pure ; all the acinar cells. The parotid gland is a pure serous gland ; all the acinarcells are similar in structure to the serous cells described earlier. In the infant, however, a few mucous secretory units may be found. Electron microscopic studies indicate that the serous granules may have a dense cen- tral core. The intercalated ducts of the parotid are long and branching , and the pale-staining striated ducts are numerous and stand out conspicuously against the more densely stained acini (15) Fig(3).

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Fig(3):Clusters of large, pale staining mucous cells (arrows) occasionally are present in the parotid gland but the acini are overwhelmingly of serous type; each serous acinus is composed of several pyramidal shaped cells with basal nuclei and basophilic cytoplasmic granules.

Structure: The parotid glands are a pair of mainly serous salivary glands located below and in front of each ear canal, draining their secretions into the vestibule of the through the (8) .Each gland lies behind the mandibular ramus and in front of the mastoid process of the . The gland can be felt on either side, by feeling in front of each ear, along the , and below the angle of the (7). The parotid duct, a long excretory duct, emerges from the front of each gland, superficial to the masseter muscle. The duct pierces the buccinator muscle, then opens into the mouth on the inner surface of the cheek(7), usually opposite the maxillary second molar. The parotid papilla is a small elevation of tissue that marks the opening of the parotid duct on the inner surface of the cheek. The gland has four surfaces — superficial or lateral, superior, anteromedial, and posteromedial. The gland has three borders — anterior, medial, and posterior. The parotid gland has two ends — superior end in the form of small superior surface and an inferior end (apex). A number of different structures pass through the gland. From lateral to medial, these are:

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1. (Fig.4). 2.Retromandibular . 3.External carotid artery. 4.Superficial temporal artery. 5.Branches of the great auricular nerve. 6.Maxillary artery Sometimes accessory parotid glands are found as an anatomic variation. These are close to the main glands and consist of ectopic salivary gland tissue.

Fig(4):Facial nerve branches in parotid gland: relatively large nerve lies adjacent to a lobule of parotid glandular tissue.

REVIEW 1-1-Location: Superficial or lateral relations: The gland is situated deep to the , superficial fascia, superficial lamina of investing layer of deep cervical fascia and great auricular nerve (anterior ramus of C2 and C3). Anteromedial relations: The gland is situated posterolaterally to the mandibular ramus, masseter and medial pterygoid muscles. A part of the gland may extend between the

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ramus and medial pterygoid, as the pterygoid process. Branches of facial nerve and parotid duct emerge through this surface. Posteromedial relations: The gland is situated anterolaterally to mastoid process of temporal bone with its attached sternocleidomastoid and digastric muscles, styloid process of temporal bone with its three attached muscles (stylohyoid, stylopharyngeus, and ) and carotid sheath with its contained neurovasculature (internal carotid artery, internal jugular vein, and 9th, 10th, 11th, and 12th cranial ). Medial relations: The parotid gland comes into contact with the superior pharyngyeal constrictor muscle at the medial border, where the anteromedial and posteromedial surfaces meet. Hence, a need exists to examine the in (20).

REVIEW 1-2-Function: When we are at rest, or not eating, the parotid glands account for about ten percent of the saliva in our mouth. It is essential to keep our mouth lubricated at all times to protect the delicate linings of our alimentary canal as dryness can lead to broken skin through which pathogens can enter. However, once activated they will secrete upwards of twenty-five percent of the saliva in our . This increase is imparted by the body’s need for amylase to start the digestion of . The main function of parotid glands, like salivary glands in general, lies in facilitating the digestion of food by secreting saliva. There are various cell types within the gland that allow saliva secretion. For example, acinar cells are berry-lobed cells that will expel enzymes. Though salivary glands are always working – especially the parotids as they are the largest and biggest producers of saliva – they are prone to infections and are even affected by our water intake.

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REVIEW 1-3-Development: The parotid salivary glands appear early in the sixth week of prenatal development and are the first major salivary glands formed. The epithelial buds of these glands are located on the inner part of the cheek, near the labial commissures of the primitive mouth (from ectodermal lining near angles of the stomodeum in the 1st/2nd pharyngeal arches; the stomodeum itself is created from the rupturing of the oropharyngeal membrane at about 26 days (11). These buds grow posteriorly toward the oticplacodes of the ears and branch to form solid cords with rounded terminal ends near the developing facial nerve. Later, at around 10 weeks of prenatal development, these cords are canalized and form ducts, with the largest becoming the parotid duct for the parotid gland. The rounded terminal ends of the cords form the acini of the glands. Secretion by the parotid glands via the parotid duct begins at about 18 weeks of gestation. Again, the supporting connective tissue of the gland develops from the surrounding mesenchyme(3).

REVIEW 1-4-Histology : The gland has a capsule of its own of dense connective tissue, but is also provided with a false capsule by investing layer of deep cervical fascia. The fascia at the imaginary line between the angle of mandible and mastoid process splits into the superficial lamina and a deep lamina to enclose the gland. The risorius is a small muscle embedded with this capsule substance. The gland has short, striated ducts and long, intercalated

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ducts(3). The intercalated ducts are also numerous and lined with cuboidal epithelial cells, and have lumina larger than those of the acini Fig(5). The striated ducts are also numerous and consist of simple columnar epithelium, having striations that represent the infolded basal cell membranes and mitochondria (13) Fig(6,7). Though the parotid gland is the largest, it provides only 25% of the total salivary volume. The serous cell predominates in the parotid, making the gland secrete a mainly serous secretory product (3). The parotid gland also secretes salivary alpha-amylase (sAA), which is the first step in the decomposition of starches during mastication. It is the main to secrete this. It breaks down amylose (straight chain starch) and amylopectin (branched starch) by hydrolyzing alpha 1,4 bonds. Additionally, the alpha amylase has been suggested to prevent bacterial attachment to oral surfaces and to enable bacterial clearance from the mouth (2).

Fig(5):Striated duct is larger than an acinus and much larger than the intercalated duct; ductal cells are eosinophilic columnar cells with central nuclei and vertical cytoplasmic striations due to folds in the basal plasma membranes.

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Fig(6):This small, interlobular excretoryduct is lined by pseudostratifiedcolumnar epithelium and embedded in dense fibrous con

Fig(7):sebaceouscellsinparotidgland:cells in 2 foci of sebaceous differentiation (arrows) are large with central nuclei and clear reticulated cytoplasmthat is unreactive with mucicarmine stain; small foci of sebaceous cells occur frequently in the parotid gland (mucicarmine stain).

REVIEW Comparesion between parotid gland in child and adult: 1.Inanatomy:the facial nerve in children lies much more laterally than in adults, as the mastoid cells are not yet fully developed. In young children, the nerve is even a little larger in proportion to the surrounding structures.

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2.Insalivation:Persistent dry mouth is a common symptom in aged individuals, although the mechanisms involved are not well understood. Dry mouth in the elderly is frequently associated with the increased use of medications and the functional disturbances associated with these medications . Examples of such differences include a decrease in gland size and weight , decreased saliva flow rate, and an increased concentration of immunoglobulin A (IgA). In humans, decreases in protein synthesis and salivary flow rate have been reported. 3. In amount of adipose tissue :The amount of intra glandular adipose tissue in parotid gland is change over age from no tissue to moderate then large amounts Fig (8).

Fig(8):Intraglandular adipose tissue in parotid gland:(A) parotid glandfrom neonate contains no discernible adipose tissue;(B) moderate amountof intralobular adipose tissue in parotid tissue from middle aged adult;(C)intraparotid adipose tissue is quite prominent in gland from elderly person.

REVIEW Sublingual gland:

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The sublingual glands are a pair of major salivary glands located inferior to the tongue, anterior to the submandibular glands The secretion produced is mainly mucous in nature; however, it is categorized as a mixed gland Unlike the other two major glands, the ductal system of the sublingual glands does not have intercalated ducts and usually does not have striated ducts either, so saliva exits directly from 8-20 excretory ducts known as the Rivinus ducts Approximately 5% of saliva entering the oral cavity comes from these glands.

REVIEW 2-1-Location: Sublingual gland Sublingual gland is the smallest of the major salivary glands which is almond shaped. The sublingual gland lies between the floor of the mouth, below the mucosa and above the mylohyoid muscle. It is composed of one main gland with sev- eral small glands((5). The main duct; Bartholin’s duct opens with or near the . Several smaller ducts; duct of Rivinus, open independently along the sublingual fold. The sublingual is also a mixed gland, but the mucous secre- tory units greatly outnumber the serous units. The mucous cells are usually arranged in a tubular pattern; serous demilunes may be present at the blind ends of the tubules. Pure serous acini are rare or absent. The interca- lated and striated ducts are poorly developed; mucous tubules may open directly into ducts lined with cuboid or columnar cells without typical basal striations. The sublingual gland receives its blood supply from the sublin- gual and the submental . The parasympathetic nerve supply ,is also derived from the VII cranial nerve. It reaches the gland via the lingual nerve after synapsing in the . The lymphatic drainage is to the submandibular lymph nodes.

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REVIEW

2-2-Function: Function of sublingual gland: The salivary glands produce saliva, which keeps the mouth(especially the area of the floor of the mouth) and other parts of the digestive system moist. It also helps break down carbohydrates (with salivary amylase, formerly known as ptyalin) and lubricates the passage of food down from the oro- to the to the stomach.The sublingual gland gland estimated to contribute only by 2% to 5% of the salivary gland flow rate, which act as cleansing action for the lower anterior teeth by equalization of the PH level and so prevention or decreasing of caries in these teeth.

REVIEW 2-3-Development: The sublingual salivary glands appear in the eighth week of prenatal development, two weeks later than the other two major salivary glands. They develop from epithelial buds in the sulcus surrounding the sublingual folds on the floor of the mouth, lateral to the developing submandibular gland. These buds branch and form into cords that canalize to form the sublingual ducts associated with the gland. The rounded terminal ends of the cords form acini (4) .

REVIEW

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2-4-Histology: The sublingual gland consists mostly of mucous acini capped with serous demilunesand is therefore categorized as a mixed with a mucous product predominating. Striated and intercalatedductsare also present (4).

REVIEW 2-5-Comparesion between sublingual in child and adult: In child:The human sublingual gland is not a single unit like the parotid and sub- mandibular glands, but is made up of a posterior part (the greater sublin- gual gland) and an anterior part (the lesser sublingual gland) of 8–30 small salivary glands, each having its own duct system emptying into the sub- lingual fold . The sublin gual gland has been conventionally considered to be a mixed gland but with a preponderance of mucous elements. Although with routine staining at the light microscope level, it is seen to consist of many groups of pale staining mucous cells with darker staining so-called serous acini and demilunes there is evidence that the so-called serous cells in this gland are immature mucous cells. The histological structure of the greater and lesser sublingual glands is identical to that of the mucous minor salivary glands(16). In adult:The sublingual glands showed age-related decreases in size, with approximately 25% of the thickness present in the second decade of life being lost by the seventh decade. T1- weighted signal intensity of theparotid gland increased with age, but the signal intensity of thesublingual and submandibular glands did not.

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Fig(9) Sublingual glands are composed primarily of mucous cells. The mucous aciniare capped by serous demilunes that secrete lysozyme.

Fig(10):. Mucous acini predominate. Note that the gland contains occasional adipocytes, a feature found in older individuals. The proportion of fat (A, adipocyte) in the gland generally increases with age.

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Fig.(11): Sublingual salivary gland lying beneath oral mucosa shows pre- dominantly pale staining mucous acini with serous demilunes

. REVIEW 3-Submandibular gland: The paired submandibular glands (historically known as submaxillaryglands) are major salivary glands.

The submandibular gland produces saliva with mixed mucous and serous components. The serous cells are arranged in aciniwhereas the mucous cells are capped with serous demilune cells, similar to the sublingual gland.

REVIEW 3-1-Location: located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimulation their contribution decreases in proportion as the parotid secret ion rises to 50%.

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REVIEW 3-2-Function: The submandibular gland and the other salivary glands are essential for digestioDXn and for maintaining a healthy mouth. Saliva contains enzymes that begin to break down food before it passes to your stomach, and it moistens food so that it slips easily down the esophagus. What's more, saliva contains minerals that reduce the levels of harmful acids in the mouth. Without this protective effect, the acids eat away at tooth enamel and cause cavities. Even though your saliva does a great job protecting your enamel, it doesn't hurt to further bolster your enamel health! Consider swishing with a mouthwash like Colgate Enamel Health Mouthwash, Alcohol-Free, which strengthens enamel to help prevent cavities, even where brushing may miss

REVIEW 3-3-Development : The submandibular salivary glands develop later than the parotid glands and appear late in the sixth week of prenatal development. They develop bilaterally from epithelial buds in the sulcus surrounding the sublingual folds on the floor of the primitive mouth. Solid cords branch from the buds and grow posteriorly, lateral to the developing tongue. The cords of the submandibular gland later branch further and then become canalized to form the ductal part. The submandibular gland acini develop from the cords’ rounded terminal ends at 12 weeks, and secretory activity via the submandibular duct

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begins at 16 weeks. Growth of the submandibular gland continues after birth with the formation of more acini. Lateral to both sides of the tongue, a linear groove develops and closes over to form the submandibular duct(2).

REVIEW 3-4-Histology: Normal submandibular salivary gland is shown at medium power, with both serous and mucinous acini. The serous cells contain dark granules from which enzymes such as amylase and maltase are released. The mucinous cells contain pale mucin. The secretions drain into ducts. Lobes contain smaller lobules, which contain adenomeres, the secretory units of the gland. Each adenomere contains one or more acini, or alveoli, which are small clusters of cells that secrete their products into a duct. The acini of each adenomere are composed of either serous or mucous cells, with serous adenomeres predominating. Some mucous adenomeresmay also be capped with a serous demilune, a layer of lysozyme-secreting serous cells resembling a half moon. Like other exocrine glands, the submandibular gland can be classified by the microscopic of its secretory cells and how they are arranged. Because the glands are branched, and because the tubules forming the branches contain secretory cells, submandibular glands are classified as branched tubuloacinar glands. Further, because the secretory cells are of both serous and mucous types, the submandibular gland is a mixed gland, and though most of the cells are serous, the exudate is chiefly mucous. It has long striated ducts and short intercalated ducts. The secretory acinar cells of the submandibular gland have distinct functions. The mucous cells are the most active and therefore the major product of the submandibular glands is saliva which is mucoid in nature.

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Mucous cells secrete mucin which aids in the lubrication of the food bolus as it travels through the esophagus. In addition, the serous cells produce salivary amylase, which aids in the breakdown of starches in the mouth. The submandibular gland's highly active acini account for most of the salivary volume, The parotid and sublingual glands account for the remaining. The submandibular duct or Wharton duct or submaxillaryduct, is one of the salivary excretory ducts. It is about 5 cm. long, and its wall is much thinner than that of the parotid duct. It drains saliva from each bilateral submandibular gland and sublingual gland to the sublingual caruncle at the base of the tongue.

REVIEW 3-5-Comparesion between Submandibular gland in child and adult: At birth Sub mand. Gland consist of a terminal system of tubules and these gradually are replaced by a ciner structure in adult Embryonic development of submandibular gland during week 7 and 8 based upon Streeter. Carnegie stage 19 - Short, club-like duct entering mesenchymalprimordium of gland. Carnegie stage 20 - Longer, knobby duct well in gland. Duct beginning to form knob-like branches. Carnegie stage 21 - Simple, stubby primary branching of duct. Carnegie stage 22 - Secondary branching of duct. Practically solid duct; suggestion of lumen in distal part. Definite lumen in oral part of duct. Carnegie stage 23 - Long duct, much branched. Lumen deep in gland. Lumina in many terminal branches of ducts. Beginning orientation of epithelial tree. Angiogenesis beginning around epithelium. Mesoblast begins to form layer around gland.

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REVIEW 4-Minor salivary gland : There are over 600 minor salivary glangs in the oral cavity.

REVIEW

4-1-Location: Minor salivary glands are found in large numbers on the on all side of the oral cavity which cannot be pointed out , and there are minor salivary glands located on the following location in small numbers: 1-Superior portion of tonsils (Webers glands). 2-Tonsillar pillars. 3-Base of tongue. 4-paranasal sinuses . 5-Larynx and bronchi.

REVIEW 4-2-Function: Minor salivary gland Secrete lingual ; beginning the process of lipid in the mouth. Serous secretion presumably flushesmaterial from the base of the papillae to enable the taste buds to respond rapidly to changing stimuli.

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REVIEW 4-3-Development : The formation of salivary glands entails the proliferation of epithelial cells from the stomatodeum into the underlying ectomesenchyme, culminating in a complex network of ducts and acinar bulbs. The extent to which mucins regulate this process is unknown, but they appear to mediate luminal space formation and maturation. Our aim was to examine mucin expression patterns during the morphogenesis of human salivary glands. Mucin expression - MUC1, 2, 3, 4, 5AC, 5B, 6, and 16 - was analyzed in specimens of developing human salivary glands, obtained from fetuses at 4-24 weeks' gestation, and fully developed salivary glands by immunohistochemistry. Expression patterns were analyzed qualitatively according to the development stage of the salivary glands. Mucins 1, 3, 4, 5B, and 16 were expressed during salivary gland development - being stronger in all ductal segments by the final phases of branching morphogenesis and in mature glands. Acinar cells were negative for most mucins, including MUC1 in mature salivary glands. Mucins 2, 5AC, and 6 were not expressed. Mucins MUC1, 3, 4, 5B, and 16 are expressed in developing human salivary glands and in mature glands, suggesting important roles in the maturation and maintenance of the ductal network(19).

REVIEW 4-4-Histology : The minor salivary glands are important components of the oral cavity, present in most parts of the mouth, and

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their secretions directly bathe the tissues. Individual glands are usually in the between muscle fibres, and consist of groups of secretory endpieces made up of mucous acinar cells and serous or seromucousdemilune cells. The ductal systems comprise intercalated ducts, intralobular ducts usually lacking basal striations, and excretory ducts opening directly through the mucosa Minor glands secrete highly glycosylated mucins, containing blood group determinants, and probably active in tissue lubrication and bacterial aggregation. They also secrete several antimicrobial proteins and immunoglobulins, and the lingual serous (von Ebner's) glands secrete digestive enzymes and proteins with possible taste perception functions. Minor gland morphology and function can conveniently be studied in the rat. There are substantial differences between major and minor salivary glands, as well as among the minor glands, in the nature and composition of their mucous and serous secretory products.

REVIEW 4-5-Comparesion between minor salivary gland in child and adult: The minor salivary glands are of great importance in the physiology and pathology of the oral cavity. So far, studies of the minor glands have concentrated on adults. In the present study, minor salivary gland secretionwas studied in the buccal and labial mucosa of 3-year-old children, adolescents and young adults. In addition, the number of glands per surface area was assessed in the labial mucosa. A total of 90 individuals were included, 30 in each age- group. Saliva was collected on filter paper discs and the

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salivary secretion rate was measured using a Periotron 8000. The number of secreting was assessed on PAS-stained filter paper discs under a microscope. Salivary secretion in the buccal mucosa was found to be age-related, with a statistically significant lower rate of secretion (P=0.003) in the 3-year-olds (mean 7.7 μl cm−2 min−1) compared with the young adults (11.9 μl cm−2 min−1). No significant differences between the sexes were noted. For the labial glands, no age- or sex- related differences were found. In all age-groups, salivary secretion was significantly higher in the buccal than in the labial mucosal area. A statistically significant difference in number of secreting glands was found between all age- groups, with a decreasing number of glands per surface unit with age. The number of glands was significantly lower in males compared with females in the group of adults. The lower rate of buccal salivary secretion in the young children may imply that the oral mucosa is more vulnerable to external injury and that caries protection on the buccal molar surfaces is lower. Previous studies indicate that adults with a reduced rate of minor salivary gland secretion are more susceptible to caries.

REVIEW References: 1.Aqrawi LA, Jensen JL, Jordsbakken G, RuusAk, Nygard S, Holden M, Jonsson R, Galtung HK &Skarstein K. (2018). Signalling pathways identified in salivary glands from primary Sjögren syndrome patients reveal enhanced adipose tissue development 2.ArhakisA, KaragiannisV, Kalfas S(2013)

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3. Bath-Balogh M. FehrenbachMJ(2011). Illustrated dental embryology, histology, and anatomy (3rd ed.). Elsevier. P. 135. 4. Bath-Balogh and Fehrenbach, Elsevier, (2011). Illustrated dental Embryology, Histology, and Anatomy. P. 136-137. 5.Bialek EJ, JakubowskiW ,Zajkowski P , Szopinski KT , Osmolski A ( 2006) . US of the major salivary glands :anatomy and spatial relation ships , pathologic conditions , and pitfalls''. Radiographics. 26(3):745-63. 6. Comba, Allegra. Fipper e nuvola. Retreived 25 February 2018 7.Fehrenbach MJ , Herring SW(2012). Illustrated anatomy of the head and neck (4th ed.).St. Louis , Mo:. Elsevier/Saunders .p. 154. 8. JacobsS(2008). Chapter7: Head and Neck : Human Anatomy. Elsevier. P. 193. 9.Mandel, ID(February 1987). "The functions of saliva "Joumalof Dental Research. 66 Spec No (66) : 623-7. 10. Matsuo. R(2000). "Role of saliva in the maintenance of taste sensitivity ". Critical Reviews in Oral and Medicine. 11(2) : 216-29. 11. Moore P(2003). The Developing Human (7th ed.). Saunders. pp. 203,220 . 12. Nanci A (2003). Ten cate's oral histology : development, structure, and function (6th ed.). St. Louis: Mosby. pp. 300-1. 13. NanciA(2013). Ten cate's oral histology, development, structure, and function(8th ed.). St. Louis, Mo. Elsevier. 14. Ono Minagi H, Sarper SE, Kurosaka H, Kuremoto KI, Taniuchi I, Sakai T & Yamashiro T. (2017). Runx1 mediates the

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development of the granular convoluted tubules in the sub mandibular glands. 15. Orbans oral Histology and Embryology :chapter 11. P. 303. 16. Science Daily. Retrieved 24 February 2018. . 17. Taylor, John. "Immunity in the oral cavity ". British Society for Immunology. Retrieved 25 February 2018 18. Ten cate's Oral Histology, Nanci, Elsevier, 2013,p. 255 . 19. The Authors(2011). Journal of Anatomy 2011. Anatomical Society of Great Britain and Irelan. 20."The parotid gland" Teach Me Anatomy. Retrieved 11 November 2015 .

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