Salivary Glands Salivary Glands Major Minor Parotid serous

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Salivary Glands

Salivary Glands

Salivary Glands Major Minor Parotid – serous Labial (lips) – mixed Sublingual – mucous

Salivary Glands Major Minor Parotid – serous Labial (lips) – mixed Sublingual – mucous Buccal (cheeks) - mixed Submandibular – mixed sero-mucous Palatine - mucous (hard/soft palate) Lingual: Anterior – mixed Middle – serous Posterior – mucous

Major salivary Glands Parotid: largest, anterior ear, serous, 25% of total saliva Submandibular: Intermediate,

Major salivary Glands Parotid: largest, anterior ear, serous, 25% of total saliva Submandibular: Intermediate, angle of mandible, 60% of total saliva Sublingual: Smallest, anterior floor of mouth, 5% of total saliva

Major glands • Parotid: watery serous saliva rich in amylase, proline-rich proteins – Stenson’s

Major glands • Parotid: watery serous saliva rich in amylase, proline-rich proteins – Stenson’s duct • Submandibular gland: more mucinous – Wharton’s duct • Sublingual: viscous saliva – ducts of Rivinus; duct of Bartholin

Minor glands • Minor salivary glands are not found within gingiva and anterior part

Minor glands • Minor salivary glands are not found within gingiva and anterior part of the hard palate • Serous minor glands=von Ebner below then sulci of the circumvallate and folliate papillae of the tongue • Glands of Blandin-Nuhn: ventral tongue • Palatine, glossopalatine glands are pure mucus • Weber glands – in posterior lateral tongue

Functions • Protection – lubricant (glycoprotein) – barrier against noxious stimuli; microbial toxins and

Functions • Protection – lubricant (glycoprotein) – barrier against noxious stimuli; microbial toxins and minor traumas – washing non-adherent and acellular debris – formation of salivary pellicle • calcium-binding proteins: tooth protection; plaque

Functions • Buffering (phosphate ions and bicarbonate) – bacteria require specific p. H conditions

Functions • Buffering (phosphate ions and bicarbonate) – bacteria require specific p. H conditions – Neutralization of acids

Functions • Digestion – neutralizes esophageal contents – dilutes gastric chyme – forms food

Functions • Digestion – neutralizes esophageal contents – dilutes gastric chyme – forms food bolus – breaks starch

Functions • Antimicrobial – lysozyme hydrolyzes cell walls of some bacteria – lactoferrin binds

Functions • Antimicrobial – lysozyme hydrolyzes cell walls of some bacteria – lactoferrin binds free iron and deprives bacteria of this essential element – Ig. A agglutinates microorganisms

Functions • Maintenance of tooth integrity – calcium and phosphate ions • ionic exchange

Functions • Maintenance of tooth integrity – calcium and phosphate ions • ionic exchange with tooth surface

Functions • Tissue repair – bleeding time of oral tissues shorter than other tissues

Functions • Tissue repair – bleeding time of oral tissues shorter than other tissues – resulting clot less solid than normal – remineralization

Functions • Taste – solubilizing of food substances that can be sensed by receptors

Functions • Taste – solubilizing of food substances that can be sensed by receptors – Maintenance of taste buds

Embryonic development • The parotid: ectoderm (4 -6 weeks of embryonic life) • The

Embryonic development • The parotid: ectoderm (4 -6 weeks of embryonic life) • The sublingual-submandibular glands: foregut endoderm • The submandibular gland around the 6 th week • The sublingual and the minor glands develop around the 8 -12 week • Differentiation of the ectomesenchyme • Development of fibrous capsule • Formation of septa that divide the gland into lobes and lobules

Individual salivary glands arise as a proliferation of oral epithelium (parotid), forming a focal

Individual salivary glands arise as a proliferation of oral epithelium (parotid), forming a focal thickening that grows into the underlying ectomesenchyme Continued growth results in the formation of a small bud connected to the surface by a trailing cord of epithelial cells, with mesenchymal cells condensing around the bud Clefts develop in the bud, forming two or more new buds; continuation of this process is called branching morphogenesis produces successive generations of buds and a hierarchic ramification of the gland

Salivary Acinus Functional unit of the salivary gland Acinus: A cluster of pyramidal cells

Salivary Acinus Functional unit of the salivary gland Acinus: A cluster of pyramidal cells (serous or mucous or both) that secretes into a terminal collecting duct Collecting duct called intercalated ducts All glands are arranged in lobules or lobes composed of many acini

Secretory Cells: Serous cells • Serous cells produce proteins and glycoproteins that have enzymatic,

Secretory Cells: Serous cells • Serous cells produce proteins and glycoproteins that have enzymatic, antimicrobial or calcium-binding activities • Usually modified by addition of sugar residues (glycosylation); therefore called glycoproteins – N-linked oligosaccahride side chains • They have all the features of a cell specialized for the synthesis, storage, and secretion of protein – Rough endoplasmic reticulum (ribosomal sites-->cisternae) – Prominent Golgi-->carbohydrate moieties are added Secretory granules-->exocytosis

Serous cell

Serous cell

Serous cells • Zymogen granules (precursors to enzyme amylase) • The secretory process is

Serous cells • Zymogen granules (precursors to enzyme amylase) • The secretory process is continuous but cyclic • There are complex foldings of cytoplasmic membrane • The junctional complex consists of: – Tight junctions (zonula occludens)-->fusion of outer cell layer – Intermediate junction (zonula adherens)-->intercellular communication – Desmosomes-->firm adhesion

Parotid Gland

Parotid Gland

Mucous cells • Production, storage, and secretion of proteinaceous material; smaller enzymatic component -more

Mucous cells • Production, storage, and secretion of proteinaceous material; smaller enzymatic component -more carbohydrates-->mucins=more prominent Golgi -less prominent (conspicuous) rough endoplasmic reticulum, mitochondria -less interdigitations

Mucous Cell

Mucous Cell

Mucous Cell • High in Carbohydrates and low in proteins and discharge a viscous

Mucous Cell • High in Carbohydrates and low in proteins and discharge a viscous product called mucin • When mucin mixes with watery oral fluids, it becomes mucous, causing the saliva to be thick and viscous • Mucous cell appears light and foamy because of the presence of carbohydrates in mucin

Sublingual Gland

Sublingual Gland

Serous Demilune* (Mixed serous/mucous) *This is not true! It is an artifact!

Serous Demilune* (Mixed serous/mucous) *This is not true! It is an artifact!

Submandibular gland

Submandibular gland

Myoepithelial Cells Contratile cells that originate from the oral epithelium and remain on the

Myoepithelial Cells Contratile cells that originate from the oral epithelium and remain on the outside of the secretory end pieces and intercalated ducts Function as muscle cells to contract and squeeze the acinus, facilitating secretion Therefore myoepithelial cells is used to refer cells of epithelial origin that have a muscle function Have long processes that wrap around the acinar and intercalated duct cells

Myoepithelial cells • The myoepithelial cells of the intercalated ducts are more spindled-shaped and

Myoepithelial cells • The myoepithelial cells of the intercalated ducts are more spindled-shaped and fewer processes • Ultrastructurally very similar to that of smooth muscle cells • Functions of myoepithelial cells – Support secretory cells – Contract and widen the diameter of the intercalated ducts – Provide signals to the acinar secretory cells to maintain cell polarity and structural organization

Myoepithelial cells • One, two or even three myoepithelial cells in each salivary end

Myoepithelial cells • One, two or even three myoepithelial cells in each salivary end pieces and intercalated ducts • Four to eight processes • Desmosomes between myoepithelial cells and secretory cells • Myofilaments frequently aggregated to form dark bodies along the course of the process

Salivary Ductal System Smallest diameter ducts are in direct contact with salivary acini They

Salivary Ductal System Smallest diameter ducts are in direct contact with salivary acini They become larger as other acini empty into a collecting duct, which continues to increase in size until it enters the oral cavity Duct system consists of: 1. Secretory portion which lies within the acinar cells 2. Excretory portion which lies in the connective tissue septa between lobules In secretory portion substances enter and leave the cells of the secretory duct by ion exchange with the adjacent blood vessels, whereas the excretory portion is just a saliva-collecting tubes

Acinar cells drain directly into intercalated ducts (low cuboidal cells) Intercalated ducts opens into

Acinar cells drain directly into intercalated ducts (low cuboidal cells) Intercalated ducts opens into striated ducts (slightly taller and more columnar) Both intercalated and striated a re intralobular duct system, which means they are present inside the lobules The remaining excretory ducts are interlobular which means it is located within the connective tissue septa

Intercalated Ducts • • Small diameter Lined by small cuboidal cells Nucleus located in

Intercalated Ducts • • Small diameter Lined by small cuboidal cells Nucleus located in the center Well-developed RER, Golgi apparatus, occasionally secretory granules, few microvilli • Myoepithelial cells are also present • Intercalated ducts are prominent in salivary glands having a watery secretion (parotid).

Intercalated duct cell

Intercalated duct cell

Intercalated ducts - intralobular

Intercalated ducts - intralobular

Striated Ducts • • • Largest portion of the duct system Columnar cells Centrally

Striated Ducts • • • Largest portion of the duct system Columnar cells Centrally located nucleus Eosinophilic cytoplasm Prominent striations – Indentations of the cytoplasmic membrane with many mitochondria present between the folds • Some RER and some Golgi, short microvilli • Modify the secretion – Hypotonic solution=low sodium and chloride and high potassium • Basal cells

Striated duct - intralobular

Striated duct - intralobular

Terminal excretory ducts • Near the striated ducts they have the same histology as

Terminal excretory ducts • Near the striated ducts they have the same histology as the striated ducts • As the duct reaches the oral mucosa the lining becomes stratified • Goblet cells, basal cells, clear cells. • Alter the electrolyte concentration and add mucoid substance.

Interlobular excretory duct

Interlobular excretory duct

Small excretory duct Large excretory duct

Small excretory duct Large excretory duct

Main excretory ducts of major salivary glands Parotid: Stensen’s duct Submandibular: Wharton’s duct

Main excretory ducts of major salivary glands Parotid: Stensen’s duct Submandibular: Wharton’s duct

Formation and Secretion of Saliva Two stages • Primary saliva: Isotonic and contains mostly

Formation and Secretion of Saliva Two stages • Primary saliva: Isotonic and contains mostly organic component and water – Serous and mucous cells – Intercalated ducts • Modified saliva – Striated and terminal ducts – Reabsorption and secretion of electrolytes – End product is hypotonic

Macromolecular component • Synthesis of proteins • RER, Golgi apparatus • Ribosomes RER posttranslational

Macromolecular component • Synthesis of proteins • RER, Golgi apparatus • Ribosomes RER posttranslational modification (N- & O-linked glycosylation) Golgi apparatus Secretory granules • Exocytosis until appropriate secretory stimulus is received • The sympathetic neurotransmitter, norepinephrine, is an effective stimulus of exocytosis (binds to adrenergic receptors on cell surface) • Endocytosis of the granule membrane, which is recycled or degraded

Fluid and Electrolytes • Secretion of water and electrolytes • Parasympathetic innervation • Binding

Fluid and Electrolytes • Secretion of water and electrolytes • Parasympathetic innervation • Binding of acetylcholine to muscarinic receptors – Activation of phospholipase IP 3 release of Ca 2+ opening of channels K+ (basolateral membrane), Cl- (apical) Cl- and Na+ in the lumen creates an osmotic gradient results in net movement of water into the lumen through aquaporins in apical membrane and tight junctions – Also HCO 3 - is transported into the lumen through apical Clchannels • Other receptors: norepinephrine via alpha-adrenergic receptors and substance P can activate the Ca 2+ phospholipid pathway

Mechanisms of Salivary Secretion Inositol Triphosphate: IP 3 Diacylglycerol: DAG Phospholipase C: PLC Ach:

Mechanisms of Salivary Secretion Inositol Triphosphate: IP 3 Diacylglycerol: DAG Phospholipase C: PLC Ach: Acetylcholine NE: Norepinephrine AC: Adenylyl cyclase Gs: Heterotrimeric G protein AMP: Adenosine monophosphate ATP: Adenosine triphosphate PKA: Protein Kinase A PIP 2: Phosphatidylinositol biphosphate

Ductal modification • Autonomic nervous system • Striated and terminal ducts • Modification via

Ductal modification • Autonomic nervous system • Striated and terminal ducts • Modification via reabsorption and secretion of electrolytes • Final product is hypotonic due to a net reabsorption of Na+ and Cl • Rate of salivary flow affects composition of saliva – High flow rate: Na+ and Cl- high; K+ low – Low flow rate: Na+ and Cl- low; K+ high

Modification of saliva in ducts • Intercalated duct • Striated duct (Hypotonic) – Secretion

Modification of saliva in ducts • Intercalated duct • Striated duct (Hypotonic) – Secretion of bicarbonate – Absorption of chloride – Reabsorption of sodium • More sodium – Secretion of potassium and bicarbonate • Less potassium However, when the secretion is rapid the system cannot keep up and more sodium appears than potassium so the solution becomes isotonic or even hypertonic

Connective tissue • • • Fibroblasts Inflammatory cells Mast cells Adipose cells Extracellular matrix

Connective tissue • • • Fibroblasts Inflammatory cells Mast cells Adipose cells Extracellular matrix – Glycoproteins and proteoglycans • Collagen and oxytalan fibers • Blood supply

Minor Salivary Glands

Minor Salivary Glands

Architecture of the salivary gland ducts

Architecture of the salivary gland ducts

Nerve supply • No direct inhibitory innervation • Parasympathetic and sympathetic impulses • Parasympathetic

Nerve supply • No direct inhibitory innervation • Parasympathetic and sympathetic impulses • Parasympathetic are more prevalent. • Parasympathetic impulses may occur in isolation, evoke most of the fluid to be excreted, cause exocytosis, induce contraction of myoepithelial cells (sympathetic too) and cause vasodilatation.

Nerve supply • There are two types of innervation: Epilemmal and hypolemmal • beta-adrenergic

Nerve supply • There are two types of innervation: Epilemmal and hypolemmal • beta-adrenergic receptors that induce protein secretion • L-adrenergic and cholinergic receptors that induce water and electrolyte secretion

Hormones can influence the function of the salivary glands. They modify the salivary content

Hormones can influence the function of the salivary glands. They modify the salivary content but cannot intiate salivary flow.

Age changes • Fibrosis and fatty degenerative changes • Presence of oncocytes (eosinophilic cells

Age changes • Fibrosis and fatty degenerative changes • Presence of oncocytes (eosinophilic cells containing many mitochondria)

Clinical Considerations • • • Obstruction Role of drugs Systemic disorders Bacterial or viral

Clinical Considerations • • • Obstruction Role of drugs Systemic disorders Bacterial or viral infections Therapeutic radiation Formation of plaque and calculus