SALIVARY GLAND, SALIVA, PATHOLOGY OF SALIVA

The salivary gland is a vital organ located in the mouth that produces saliva, a clear liquid that plays a crucial role in digestion, oral health, and overall well-being. There are three main salivary glands:

1. Parotid gland (located in front of the ear)
2. Submandibular gland (located under the jawbone)
3. Sublingual gland (located under the tongue)

The salivary gland's functions include:

- Producing saliva (up to 2 liters daily) to break down food, aid in swallowing, and maintain oral hygiene
- Regulating pH levels in the mouth
- Aiding in the digestion of carbohydrates and fats
- Helping to neutralize acid and remineralize teeth
- Supporting the immune system by producing antibodies

1. SALIVARY GLAND PRESENTED BY DR. SRI SRUTHI PREMAN FIRST YEAR POST GRADUATE ORAL MAXILLOFACIAL PATHOLOGY

2. CONTENTS: INTRODUCTION SALIVA gland AND ITS FUNCTIONS CLASSIFICATION Major and minor salivary gland embryology Acini Formation of saliva Ducts Saliva modification Connective tissue component Pattern of innervation Production of saliva Special stains Clinical significance REFERENCES

3. INTRODUCTION: The salivary glands are group of compound exocrine glands secreting saliva. Saliva is a complex fluid produced by the salivary glands. The ducts of the salivary glands carry the saliva and discharge it into the oral cavity. The saliva forms a film of fluid coating the teeth and mucosa thereby creating and regulating a healthy environment in the oral cavity.

4. Functions of salivary gland Cleanses the oral cavity due to bactericidal action of lysozyme , IgA and the constant backflow towards the esophagus. Moistening of buccal mucosa, essential for speech. Creates a feeling of oral comfort by its lubricating action Dissolve food chemicals so that they can stimulate taste sensation Food bolus formation.

5. CLASSIFICATON OF SALIVARY GLANDS BASED ON SIZE BASED ON TYPE OF Secretion

6. BASED ON SIZE 1. MAJOR SALIVARY GLANDS 2. MINOR SALIVARY GLANDS

7. MAJOR SALIVARY GLANDS The largest of the glands are the three bilaterally paired major salivary glands. They are all located extra orally and their secretions reach mouth by variably long ducts. Parotid Submandibular Sublingual

8. PAROTID GLAND LARGEST salivary gland 60 to 65% of total saliva produced Pyramid in shape Weighs between14 & 28g Location: superficial portion of the gland is located subcutaneously in front of the external ear and deeper portion lies behind ramus of the mandible.

9. Stenson’s duct: Runs forward across masseter muscle, turns inwards at the anterior border of the masseter and opens at a papilla in oral cavity ,opposite to maxillary second molar crown. Size: 5cm*3cm

10. Nerve supply: greater auricular nerve ,auriculotemporal nerve , glossopharyngeal nerve

11. Arterial supply - external carotid artery Venous drainage-external jugular vein Lymphatic drainage- upper deep cervical lymph nodes .

12. SUBMANDIBULAR GLAND 10 to 15gm 20 to 30% of total saliva Located at posterior portion of floor of mouth, medial aspect of mandible and wrapping around posterior border of mylohyoid muscle.

13. Wharton’s duct: Runs forward and opens into the mouth beneath the tongue, lateral to lingual frenum

14. BLOOD SUPPLY: facial and the lingual artery LYMPHATIC DRAINAGE: submandibular lymph nodes and deep cervical lymph nodes NERVE SUPPLY: Parasympathetic supply: facial nerve reaching gland through the lingual nerve and submandibular ganglion. Sympathetic supply: postganglionic fibers from plexus to facial nerve.

15. SUBLINGUAL GLAND Smallest major salivary gland 2gm 2.5% of total saliva. Located at anterior part of floor of the mouth ,just between mucosa and mylohyoid muscle. Opens into oral cavity through series of small ducts( ducts of rivinus )opening along sublingual fold and opens through large duct- barthon’s duct, that opens with submandibular duct at sublingual caruncle.

16. BLOOD SUPPLY : sublingual and submental arteries. LYMPHATIC DRAINAGE: submental lymph nodes NERVE SUPPLY: parasympathetic: facial nerve reaching the gland via submandibular ganglion and lingual nerve Sympathetic : post ganglionic fibres from plexus on facial nerve .

17. Minor salivary gland Collection of secretory cells scattered throughout the mucosa and submucosa of the oral cavity with short ducts opening directly onto mucosal surface. No. Between 600 and 1000 Not seen in gingiva and anterior part of hard palate. Rich in mucin, antibacterial proteins and secretory immunoglobins Continuous slow secreting glands, thus have an important role in protecting and moistening oral mucosa, especially when major salivary glands are mostly inactive.

18. LABIAL AND BUCCAL GLANDS Mixed Has mucous tubules with demilunes Intercellular canaliculi are seen between mucous cells Buccal glands are described as a continuation of the labial glands with a similar structure.

19. Glossopalatine glands: Pure mucous cells Location: glossopalatine fold but extends from the posterior extension of sublingual gland to glands of the soft palate.

20. Palatine glands: Mucous Consists of several hundred glandular aggregates in the lamina propria of the posterolateral region of the hard palate and uvula The excretory ducts may have an irregular contour with large distensions as they course through the lamina propria Their openings are easily recognizable

21. LINGUAL GLANDS: Two groups: anterior and posterior Anterior are located in the apex of the tongue. Chiefly mucous Posterior lingual glands are located posterior and lateral to vallate papilla and in association with the lingual tonsils. Purely mucous and their ducts open in the dorsal surface of the tongue

22. Von Ebner's gland Posterior lingual serous glands Located in tongue and open into troughs surrounding circumvallate papillae on the dorsum of the tongue and the foliate papillae on the side of the tongue. Secrete digestive enzymes and proteins that play role in taste process.

23. Development of parotid: 4-6 weeks of IU life Submandibular: 6 th week Sublingual and minor salivary glands: 8 th week Maturity: last two months EMBRYOLOGY

24. Structure of salivary glands Comprises of a series of secretory end piece or acini Connected to the oral cavity by a system of ducts

25. ACINI Consists of secretory cells, which are arranged in roughly spherical configuration around a central lumen or cavity. Show a great diversity in size, shape and cell number Two types of cells: Serous Mucous

26. SEROUS CELLS They are present in parotid and submandibular gland Secretions of serous cells are proteinaceous- usually enzymatic, antimicrobial. A main type of protein alpha- amylase is present in this type of secretion.

27. Pyramidal in shape, with broad base adjacent to connective tissue stroma and apex situated towards the central lumen. Nucleus is spherical and situated at the basal third of the cell. Sometimes binucleated.

28. Cytoplasm stains intensely with H & E Apical cytoplasm is filled with secretory granules( macromolecular component of saliva) Basal cytoplasm contains RER which coverage towards the Golgi apparatus complex located apical or lateral to nucleus Also contain cytoskeleton components.

29. The lumen of serous end piece has small extensions in the form of intercellular canaliculi( found between adjacent serous cells) The surface of the serous cell lining both the central lumen and canaliculi possess a delicate microvilli that extend into luminal and canalicular spaces. Canaliculus terminates in the form of a classic junctional complex consisting of a tight junction ( zona occludens) and desmosomes.

30. MUCOUS CELLS Predominant secretory cells type of the sublingual gland and most of the minor salivary glands. Also seen in submandibular glands. Secretion consists of large amount of mucins- lubrications , effective barrier against aggregation of microorganisms

31. Larger lumen Larger than serous cells Pyramid shape Flattened nucleus situated towards the base Apical cytoplasm is filled with mucous secretory droplets. Stain poorly in H & E PAS or Alcian blue is positive.

32. MYOEPITHELIAL Cells (BASKET CELLS) Contractile cells located around the terminal secretory units and the first portion of the duct system. Located between basal lamina and duct cells and are joined by desmosomes. They are similar to smooth muscle cells. They are stellate or spider like with a flattened nucleus surrounded by a small amount of perinuclear cytoplasm.

33. These processes are filled with filaments of actin and soluble myosin that helps in contractile action. Cellular organelles are located in perinuclear cytoplasm

34. Functions: Expulsion of saliva from secretory end piece to ductal system Contraction of myoepithelial ducts may shorten or widen the ducts, help in maintaining their patency. Maintaining cell polarity and structural integrity Produce proteins that have tumor suppressor activity, such as proteinase inhibitors and antiangiogenic factors and that act as effective invasive barrier against epithelial neoplasms.

35. ducts 3 classes Intercalated Striated Terminal secretory units opens into a small duct called the intercalated duct. These ducts joins to form larger straited ducts which finally empty into larger excretory duct

36. INTERCALATED DUCTS Small ducts into which secretory end piece empties Lined by single layer of low cuboidal cells and myoepithelial bodies and their processes Overall diameter is less than secretor end piece but their lumen is larger than secretory

37. Centrally placed nucleus Few secretory granules may be found in the apical cytoplasm especially cells located near end pieces Few microvilli projecting into the lumen Desmosomes and gap junctions present Long intercalated duct- parotid Shorter-submandibular Poorly developed- sublingual

38. STRAITED DUCTS: Larger ducts into which the intercalated ducts empties Main ductal component in intratubular portion of gland Lined by tall columnar cells

39. Centrally placed spherical nucleus. Pale acidophilic cytoplasm Basal striations perpendicular to the base of the cells Mitochondria are lying in the cytoplasmic partitions Golgi complex, RER and secretory granules are seen Desmosomes and gap junctions seen Functions: Modify the salivary secretion- changes from isotonic to hypotonic Na+ reabsorption and k+ excretion

40. TERMINAL EXCRETORY DUCTS : As the striated ducts leaves the individual glandular lobules and enter the interlobular connective tissue, they join to form excretory ducts Larger than straited ducts Main excretory ducts leading from the gland to the oral cavity.

41. They are lined by pseudostratified columnar cells admix with goblet cells and small basal cells. As they approach the oral cavity epithelium changes to stratified epithelium Function : modify the final saliva by altering its electrolyte concentration

42. Salivary glands are composed of highly differentiated epithelial cells. The salivary glands consist of two functional and anatomical regions, acinar and ductal . Acinar cells are salt secreting and are considered to be exclusive site of fluid movement in these glands. Ductal cells reabsorb Na and Cl transcellularly and secrete K and HCO3. For primary saliva formation , the transcellular movement of Cl is the key step . SALIVA MODIFICATION

43. Cl is taken up basolaterally via NKCCL channels and thereafter leaves the acinar cell through Ca activated Cl channel into the luminal surface. Large amount of NaCl rich fluid is collected into the acinar lumen compartment The major task of salivary gland epithelia is to modify the primary saliva in the acinar compartment.. NaCl reabsorption exceeds the secretion of K and HCO3 the final saliva becomes hypotonic. striated duct cells also secrete kallikrein and epidermal growth factor. Thus, saliva secreted into the oral cavity is hypotonic as compared to serum.

44. Connective tissue component The connective tissue includes capsules that separates from adjacent structures, septa that divide the gland into lobes &lobules and carries blood vessel and nerves that supply the parenchymal components and excretory ducts. Connective tissue includes fibroblasts, macrophages , dendritic cells, mast cells, plasma cells , adipose cells, granulocytes and lymphocytes. Collagen and elastin fibers along with the glycoproteins and proteoglycans of the ground substance constitutes the matrix of the connective tissue.

45. Arterioles, capillaries, autonomic nerves that innervates the secretory and ductal cells passes through the finer partitions. Plasma cells located adjacent to the secretory end pieces and the intralobular ducts produce immunoglobulins that are translocated into the saliva by transcytosis. Like IgG,IgA,IgM

46. The secretory cells receive their innervation by two patterns: INTRAEPITHELIAL(INTRAPARENCHYMAL) the axons split off from the nerve bundle and penetrates the basal lamina , lying adjacent or between the secretory the cells. As they pass through the basal lamina , the schwann cell covering is lost . The site of innervation ( neuroeffector site) is considered to be varicosities of axon which contain small vesicles and mitochondria. The vesicles contain neurotransmitters like norepinephrine and acetylcholine and presumably release them by exocytosis.. The membrane of axons and secretory cells are separated by 10 to 20nm Seen in submandibular and minor salivary glands of lip PATTERN OF INNERVATION

47. 2. SUBEPITHELIAL(EXTRAEPITHELIAL)- i nstead of penetrating the axons remain associated with the nerve bundle in the connective tissue . Some of the axonal varicosities which contains small neurotransmitter vesicles , lose their coverings of Schwann cell cytoplasm. These bared axonal varicosities are the sites of transmitter release . The axon remain separated from secretory cells by 100 to 200nm. They are seen in parotid gland.

48. CONTROL OF SECRETION The postganglionic fibers of both sympathetic and parasympathetic divisions innervates the secretory cells. The neurotransmitter stimulates to discharge the secretory granules, water, electrolytes, and contraction of myoepithelial cells. This molecular events are known as stimulus secretion coupling. Sympathetic Norepinephrine activates α and β adrenergic receptors. Parasympathetic transmitters activates cholinergic receptors. Receptor activation results in increase in intracellular concentration of “second messenger” which triggers additional cellular response.

49. In case of α - adrenergic,cholinergic , and substance P receptors activation,the membrane permeability to Ca++ is increased, cytoplasmic Ca++ concentration is increased. It causes K++ efflux , water and electrolyte decreases and low level of exocytosis Stimulation of β -adrenergic receptor, results in the formation of cyclic AMP The increased intracellular concentration of cyclic AMP activates cyclic AMP dependent protein kinase , an enzyme that phosphorylates other proteins, which in turn involved in the process of exocytosis.

50. MACROMOLECULAR COMPONENTS formation: The nucleus sends an encoded message and an amino acid with specific sequence is synthesized. These preproteins have NH2 terminal extensions of 16 to 30 amino acids called signal sequence RER recognizes the signal along with certain proteins and crosses the RER membrane along with the growing polypeptide chain. A proteolytic enzyme, signal peptidase removes the signal and sends the protein to the cisternal space of RER. From here the protein is sent to Golgi apparatus. Golgi apparatus has several stacks of 4 to 6 smooth surfaced saccules . Production of saliva:

51. It is connected to RER through budding vesicles at the end of RER. Each GA has a cis face and a trans face. budding vesicles enter the cis face where the vesicles fuse with Golgi saccules emptying its contents. The proteins migrate from cis to trans face where they are packed into vacuoles of variable density & size. These are the secretory / immature/ presecretory granules These have irregular surface and fuse with themselves and increases its size and matures.

52. During this process they undergo structural modification prior to secretion like addition of carbohydrate side chains to amino acids asparagine,serine and threonine in the protein. Glycosylation is a process that begins in RER and ends in GA.

53. These zymogen granules are stored in the apical cytoplasm until the cell receives appropriate secretory stimulus. The granule membrane fuse with cell membrane and the contents are released by the process of exocytosis. After the release of the granule content, the membrane is internalized by the cell as small vesicles, which may be recycled or degraded.

54. Mucous secretion The mucous cell shows accumulations of large amounts of secretory products at the apical cytoplasm.This pushes the nucleus and the endoplasmic reticulum against the basal cell membrane. The mucous secretion differs from serous by these two aspects: 1. little or no enzymatic activity, serve mainly for lubricating activity& protection of oral cavity. 2. ratio of carbohydrate to protein is greater and larger amounts of salicylic acid and occasionally sulfated sugars are present.

55. The mucous droplet secretion is different from serous. When a single droplet is discharged, its membrane fuses with apical plasma membrane , resulting in single membrane. This membrane may then fragmented or get lost with the discharge of mucous, or the droplet may be discharged with the membrane intact.

56. SPECIAL STAINS The die mucicarmine is frequently used for nonspecific staining of mucins PAS technique is used to identify neutral mucins and they are resistance to diastase Alcian blue, toluidine blue, colloidal iron, and aldehyde fuchsin methods are used to localize acid mucins. A combinations of alcian blue/pas is used to differentiate acidic and neutral mucins These reveals differences in the mucins of different salivary gland

57. Clinical significances

58. mucocele Mucous retention cyst 70% In the lower lip third decades of life Men>women Small dome shaped swelling Size: 0.2-1.0cm Can be larger also

59. RANULA Mucous extravasation phenomenon and mucous retention cyst occurs specifically in the floor of the mouth Etiology: trauma Ductal obstruction Sialolith Clinical features: it is fluctuant, unilateral soft tissue mass in the floor of the mouth

60. XEROSTOMIA

61. Xerostomia is the term used for the subjective sensation of dry mouth. This syndrome is a combination of signs and symptoms associated with a decrease in the secretion of saliva . CAUSES: medication, systemic diseases, pathologies of the salivary glands, head and neck radiotherapy .

62. Negative effects on oral-dental tissue are: demineralization of tooth enamel rampant decay super-infections caused by fungal diseases (candidiasis), reactive gingival enlargement due to dehydration loss of salivary antimicrobial properties . swallowing and speech difficulty

63. SJOGREN SYNDROME: Sjogren syndrome (SS) is a multisystem autoimmune disease which causes lymphocytic infiltration in the exocrine glands, particularly the salivary and lacrimal ones leading to the characteristic features of dry eye and salivary dysfunction (xerostomia). In addition, approximately one third of the patients present systemic extra-glandular manifestations .

64. SIALORRHEA AND DROOLING Salivary hypersecretion/sialorrhea and drooling, may be caused by medication, systemic diseases, psychiatric disorders, oral pathologies, and toxic substances. In patients with persistent drooling salivary incontinence may even be accompanied by perioral and/or chin dermatitis, cheilitis and on occasions, they may experience fungal infection. In severe cases of salivary hypersecretion or sialorrhea, muscular fatigue may arise caused by continuous forced swallowing due to excess saliva. Sialorrhea may functionally affect phonation and gustative perception.

65. NECROTIZING SIALOMETAPLASIA clinically it is a reactive inflammatory condition of the salivary glands male predominance -2:1 Palatal location preference deep crater-like ulcer, develops rapidly & slow to heal size 1-5 cm.

66. ETIOLOGY : ischemic necrosis or infarction traumatic injury dental injection denture use adjacent tumour & cyst surgery upper respiratory infection or allergy

67. MUMPS: It is an infectious , acute viral sialadenitis Primarily affects the parotid glands it is the most common salivary gland diseases E tiology : paramyxovirus 2-3 weeks incubation period Transmission by direct contact with salivary droplets. F ever , malaise , headache , chills , preauricular pain , parotid swelling . male = female Young adults & children Complications: oophoritis , orchitis ,widespread involvement can include ,liver , pancreas , kidney ,nervous system

68. SIALADENOSIS It is non-neoplastic & non-inflammatory salivary gland enlargement . it is related to metabolic factor or secretory dysfunction painless bilateral swellings peak incidence: 5th & 6th decades of life . Slight female predominance swelling develops slowly, painless & accompanied by decreasing salivary secretion

69. It is usually associated with systemic conditions: Diabetes mellitus Malnutrition Liver cirrhosis (chronic alcoholism) Hyperlipidaemia

70. REFERENCES Orban's Oral Histology & Embryology by G. S. Kumar · Ten Cate's Oral Histology - E-Book: Development, Structure, by Antonio Nanci Shafer'S Textbook Of Oral Pathology by R. Rajendran Histology, Salivary Glands Brett Brazen , Joseph Dyer Alhajj M, Babos M. Physiology, Salivation. 2021 Jul 26. In: StatPearls . Treasure Island (FL) Carsons SE, Patel BC. Sjogren Syndrome. 2021 Nov 2. In: StatPearls . Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 28613703.

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