1. Orofacial structures

2. Salivary glands three pairs of major salivary glands + multiple minor glands minor glands located in the labial, lingual, palatal, buccal, glossopalatine and retromolar glands –these are typically located in the submucosal layer

3. Salivary glands compound tubuloacinar merocrine exocrine

4. Saliva 600-1000ml/day over 99% water product of an active secretion process – NOT the filtration of blood multiple electrolytes: sodium, postassium, chloride, calcium, magnesium amylase, mucins, peroxidase, lyzozyme, proline-rich proteins –composition can vary from gland to gland –parotid gland: watery fluid rich in amylase, proline-rich proteins and glycoproteins –submandibular gland also contains higher levels of mucins secretory Igs – IgM and IgE and IgA glucose, amino acids, urea, uric acid and lipids EGF, insulin, cAMP-binding proteins, albumin oral fluid is mixed or whole saliva – includes secretions from all three major glands + minor glands plus desquamated epithelial cells, microorganisms, food, debris, inflammatory cells and serum components

5. Saliva functions: –1. buffering – bicarbonate, phosphate ions protection against demineralization caused by bacterial acids resulting from the breakdown of sugars the metabolism of proteins and peptides by bacteria also results in the production of urea and ammonia (increases pH) –2. Pellicle formation many salivary proteins bind to the surface of the teeth and oral mucosa – forms a thin film = salivary pellicle several of these proteins bind calcium to protect the tooth other proteins bind bacteria – initial attachment of organisms that produce plaque –3. maintenance of tooth integrity saliva is saturated with calcium and phosphate ions at the tooth surface the high concentration of calcium and phosphate results in maturation of the enamel – increases surface hardness remineralization of lesions upon caries can also be induced by saliva – enhanced by fluoride in the saliva

6. Saliva –4. antimicrobial action barrier function provided by mucins saliva also contains a spectrum of proteins with antimicrobial activity – histatins, lysozyme, lactoferrin and peroxidase also the presence of antibodies – IgA is the major salivary Ig (results in agglutination of microbes and prevents their adherence to oral tissues) –5. tissue repair variety of growth factors are present in saliva many promote tissue growth and differentiation –6. digestion amylase and lipase –7. taste solubilizes food substances – allows binding to taste receptors located in taste buds

7. Saliva secretion average flow rate of 0.3ml/min spontaneously secreted by the sublingual and minor glands –bulk of sublingual secretion is nerve-mediated bulk of parotid and submandibular is nerve-mediated two methods of protein secretion involved in saliva production –regulated cells synthesize, store and then secrete protein by exocytosis upon receipt of neuronal signal – about 3.5 hours from synthesis to exocytosis storage within immature granules in the cytoplasm until secreted –constitutive cells continually synthesize then immediately secrete the products some products can be secreted into the blood rather than the gland’s lumen other products (IgA) can pass from blood into the lumen through transcytosis

8. Salivary glands - Anatomy Parotid Gland – development at 4 to 6 weeks –duct = Stensen’s duct –blood supply – external carotid artery –parasympathetic nerve supply from IX –sympathetic innervation by superior cervical ganglion Submandibular gland – development at 6 weeks –duct = Wharton’s duct –opens lateral to the lingual frenulum –blood supply from facial and lingual arteries –parasympathetic supply – facial nerve Sublingual gland – development at 8 to 12 weeks –small ducts = ducts of Rivinus –larger duct = Bartholin’s duct –empty with the SM duct at the sublingual caruncle –blood supply – sublingual and submental arteries –facial nerve innervation minor salivary glands –600 to 1000 glands –small aggregates of secretory tissue present in the submucosa –not found in the gingiva and anterior hard palate –predominantly mucus glands –except the lingual glands (von Ebner’s glands) found on the tongue – open into troughs surrounding the circumvallate papilla

9. Structure of Salivary glands consist of two main elements –glandular secretory tissue = parenchyma –supportive connective tissue = stroma divides the gland into lobes and lobules as connective tissue septa these septa carry blood vessels,lymphatics and nerves each lobe contains secretory units consisting of grape-like clusters of parenchyma called acini positioned around a lumen these secretory acini may be serous, mucous or mixed based on what they secrete serous – protein and watery, source of amylase mucus – mucins and viscous mixed – serous cells form a “cap” on top of the mucus acinus

10. Structure of Salivary glands main excretory duct empties into the oral cavity – divides up into progressively smaller ducts –comprised of interlobular and intralobular ducts which enter the lobes and lobules of the gland –main excretory duct connects to collecting ducts (excretory duct) which are considered interlobular –the collecting ducts divide into striated ducts –connecting the striated ducts to the acini are intercalated ducts – branch once or twice and end up entering the acini –within the acini, the lumen forms small extensions between the secretory cells called intercellular canaliculi (increase the secretory/luminal surface of the cells)

11. Acini & secretory cells two main types –serous & mucus differ in structure serous cells – e.g. parotid gland –produce proteins and glycoproteins – enzymatic, antimicrobial and calcium-binding activities –acini are typically spherical –8 to 12 cells with a central lumen –the fingerlike extensions of the intercellular canaliculi are located between adjacent cells –basally located spherical nuclei –numerous secretory granules containing its components of saliva present in the apical cytoplasm – granular appearance –luminal surface studded with microvilli –cells are held together by numerous tight junctions and gap junctions at the lateral surface– help regulate the passage of materials from the lumen into the intercellular spaces –the permeability of these junctions can be increase by specific NTs Lumen and intercellular canaliculi in a serous end piece. The lumen (L) and intercellular canaliculi were filled with India ink. Arrowheads indicate intercellular canaliculi extending between adjacent cells. N, Nuclei of serous cells.

12. mucus cells – e.g. submandibular gland –acini are tubular –either serous end pieces or mixed end pieces –mixed end pieces often have serous cells associated with them – form a crescent around the mucus cells = demilune –this demilune structure may NOT exist but may be the result of the histologic procedure –accumulation of mucus in the apical cytoplasm –this compresses the nucleus –this material does not stain using conventional stains – gives an empty appearance to the cytoplasm surrounding the nucleus –these acini lack intercellular canaliculi

13. Myoepithelial cells myoepithelial cells –associated with the acini and the intercalated ducts –located between the basal lamina and secretory cells –similar to smooth muscle cells – but they are derived from epithelium –numerous cellular processes that surround the acini contain actin and myosin filaments plus keratin –contraction expels primary saliva from the acini into the duct system and help shorten and widen the intercalated ducts –may also be involved in organizing the structure of the acini, may produce compounds with tumor suppressing activity and anti-angiogenic capacity, may provide a barrier against invasive neoplasms

14. Development of Salivary Glands arise as a proliferation of oral epithelial cells – forms a focal thickening continued growth results in the formation of a small bud connected to the oral surface by a trailing cord of epithelial cells mesenchymal cells condense around the bud clefts develop in the bud forming two or more new buds – branching morphogenesis this branching morphogenesis continues during development – requires interactions between the epithelial tissues of the gland and the surrounding mesenchyme a development of a lumen follows branching – occurs first in the distal ends of the gland and then ends finally in the proximal ends of the branch cords after lumen formation – the epithelium is composed of two layers of cells –inner layer becomes the secretory cells either mucus or serous cells –outer layer develops into contractile myoepithelial cells Developing salivary gland. Lumen formation (arrows) has begun in the ducts. Branching of the distal ends of the epithelial cords is evident (arrowheads).

15. Histology parotid: spherical acini (serous) made up of pyramidal acinar cells

16. sublingual glands: mixed gland –mucus cells predominate –with small areas of associated serous cells –fewer number of intralobular ducts, short and hard to identify intercalated ducts Light micrograph of human sublingual gland, stained with hematoxylin and eosin. Mucous tubules are abundant; many have serous demilunes (arrows).

17. submandibular gland: mixed gland –serous acini + mucous tubules –numerous striated ducts Serous Acini Mixed Acini

18. Xerostomia dry mouth decreased secretion of saliva leading to drying of oral tissues more susceptible to infection and disease painful swallowing certain disease states – Sjogren’s syndrome also in patients undergoing chemotherapy if functional gland tissue remains – stimulate salivary production using drugs also gene therapy as a possible approach – insertion of gene for saliva production

19. Lymphatics bean-shaped, grouped in clusters flow of lymph in via afferent vessels and flow of lymph out through efferent vessels either primary or secondary nodes –primary – drains a tissue or organ directly –secondary – drains multiple primary nodes

20. Lymph node histology surrounded by a connective tissue capsule bands of connective tissue extend from the capsule into the node – trabeculae separates the node into masses of lymphocytes = lymphatic nodules or follicles lymph flows between these nodules and through the sinus of the node at the center of each nodule is a germinative center of many immature lymphocytes –as the lymphocytes mature they move from the GC into the area surrounding the GC or into the lymph B cells develop from blood vessels through a process of budding and fusion of groups of mesenchymal cells peripheral mesenchymal cells form the nodules

21. Palatine tonsils intraoral tonsillar tissues non-encapsulated lymphoid tissue located in the lamina propria of oral tissues covered by stratified squamous epithelium that is continuous with the surrounding oral mucosa palatine tonsils –two masses of variable size –located between the anterior and posterior pharyngeal arches or tonsillar pillars –similar in structure to lymph nodes – nodules with germinal centers –but the nodules fuse together –each tonsil also has 10 to 20 invaginations or grooves which penetrate the tonsil deeply to form the tonsillar crypts – contain mature lymphocytes and bacteria lingual tonsil: –indistinct layer of diffuse lymphoid tissue –located on the dorsal surface of the tongue, posterior to the circumvallate papillae –many lymphatic nodules each with a germinal center –only one tonsillar crypt The palatine tonsil possesses numerous primary crypts (A) surrounded by lymphoid nodules (B). Surface epithelium (C). The palatine tonsils differ from the lingual tonsils in that secondary crypts (D) may arise as branches from the primary invaginations. In addition, no mucous glands secrete into the crypts which tend to fill with debris and defense cells (lymphocytes, macrophages, and PML's). Lymphoid nodules (A) aggregating around a pit or primary crypt (B) that opens onto the free surface of the mucosa. Typically the surface would be lined by non- keratinizing stratified squamous epithelium that continues down into the crypts. Mucous glands (C) secrete into the bottom of the crypts. The posterior aspect of the tonsil is surrounded by a connective tissue capsule (D).