3/22/20

1

Salivary Glands

1

Salivary Glands

Major Minor

Parotid – serous

Sublingual – mucous

Submandibular – mixed sero-mucous

Labial (lips) – mixed

Buccal (cheeks) - mixed

Palatine - mucous(hard/soft palate)

Lingual:Anterior – mixedMiddle – serousPosterior – mucous

2

Major salivary GlandsParotid: largest, anterior ear, serous,25% of total saliva

Submandibular: Intermediate, angleof mandible,60% of total saliva

Sublingual: Smallest, anterior floorof mouth, 5% of total saliva

3 4

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

5 6

3/22/20

2

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

7

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

8

Functions

• Buffering (phosphate ions and bicarbonate)– bacteria require specific pH conditions– Neutralization of acids

9

Functions

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

10

Functions

• Antimicrobial– lysozyme hydrolyzes cell walls of some

bacteria– lactoferrin binds free iron and deprives

bacteria of this essential element– IgA agglutinates microorganisms

11

Functions

• Maintenance of tooth integrity– calcium and phosphate ions

• ionic exchange with tooth surface

12

3/22/20

3

Functions

• Tissue repair– bleeding time of oral tissues shorter than

other tissues– resulting clot less solid than normal– remineralization

13

Functions

• Taste– solubilizing of food substances that can be

sensed by receptors– Maintenance of taste buds

14

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

embryonic life)• The sublingual-submandibular glands: foregut

endoderm• The submandibular gland around the 6th

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

15 16

Individual salivary glands arise as a proliferation of oralepithelium (parotid), forming a focal thickening thatgrows into the underlying ectomesenchyme

Continued growth results in the formation of a small budconnected 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 morphogenesisproduces successive generations of buds and a hierarchicramification of the gland

17 18

3/22/20

4

19

Salivary Acinus

Functional unit of the salivary gland

Acinus: A cluster of pyramidal cells(serous or mucous or both) that secretesinto a terminal collecting duct

Collecting duct called intercalatedducts

All glands are arranged in lobules orlobes composed of many acini

20

21

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

22

Serous cell

23

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

24

3/22/20

5

Parotid Gland

25 26

27

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

28

Mucous Cell

29

Mucous Cell

• High in Carbohydrates and low in proteins and discharge a viscousproduct called mucin

• When mucin mixes with watery oral fluids, it becomes mucous, causingthe saliva to be thick and viscous

• Mucous cell appears light and foamy because of the presence ofcarbohydrates in mucin

30

3/22/20

6

Sublingual Gland

31 32

33 34

Serous Demilune* (Mixed serous/mucous)

*This is not true! It is an artifact!

35

Submandibular gland

36

3/22/20

7

37 38

Myoepithelial CellsContratile cells that originate from the oral epithelium and remain on the outside ofthe 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 thathave a muscle function

Have long processes that wrap around the acinar and intercalated duct cells

39 40

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

41

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

42

3/22/20

8

43 44

45

Salivary Ductal SystemSmallest diameter ducts are in directcontact with salivary acini

They become larger as other aciniempty into a collecting duct, whichcontinues to increase in size until itenters the oral cavity

Duct system consists of:1. Secretory portion which lies within

the acinar cells2. Excretory portion which lies in the

connective tissue septa betweenlobules

In secretory portion substances enter and leave the cells of the secretory ductby ion exchange with the adjacent bloodvessels, whereas the excretory portion isjust a saliva-collecting tubes

46

Acinar cells drain directly intointercalated ducts (low cuboidal cells)

Intercalated ducts opens into striatedducts (slightly taller and more columnar)

Both intercalated and striated a reintralobular duct system, which meansthey are present inside the lobules

The remaining excretory ducts areinterlobular which means it is locatedwithin the connective tissue septa

47

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).

48

3/22/20

9

Intercalated duct cell

49

Intercalated ducts - intralobular

50

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

51 52

Striated duct - intralobular

53 54

3/22/20

10

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.

55

Interlobular excretory duct

56

Small excretory duct Large excretory duct

57

Main excretory ducts of major salivary glands

Parotid: Stensen’s duct

Submandibular: Wharton’s duct

58

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

59

Macromolecular component

• Synthesis of proteins• RER, Golgi apparatus• Ribosomes àRER àposttranslational modification

(N- & O-linked glycosylation) àGolgi apparatus àSecretory granules

• Exocytosis until appropriate secretory stimulus is received

• The sympathetic neurotransmitter, norepinephrine, is an effective stimulus of exocytosis (binds to b-adrenergic receptors on cell surface)

• Endocytosis of the granule membrane, which is recycled or degraded

60

3/22/20

11

Fluid and Electrolytes

• Secretion of water and electrolytes• Parasympathetic innervation• Binding of acetylcholine to muscarinic receptors

– Activation of phospholipase à IP3 à release of Ca2+ à 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 HCO3- is transported into the lumen through apical Cl-channels

• Other receptors: norepinephrine via alpha-adrenergic receptors and substance P can activate the Ca2+ -phospholipid pathway

61

Mechanisms of Salivary Secretion

Inositol Triphosphate: IP3Diacylglycerol: DAGPhospholipase C: PLCAch: AcetylcholineNE: NorepinephrineAC: Adenylyl cyclaseGs: Heterotrimeric G proteinAMP: Adenosine monophosphateATP: Adenosine triphosphatePKA: Protein Kinase APIP2: Phosphatidylinositol biphosphate

62

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

63

Modification of saliva in ducts

• Intercalated duct– Secretion of bicarbonate– Absorption of chloride

• Striated duct (Hypotonic)– 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

64

Connective tissue

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

– Glycoproteins and proteoglycans• Collagen and oxytalan fibers• Blood supply

65 66

3/22/20

12

Minor Salivary Glands

67 68

Architecture of the salivary gland ducts

69

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.

70

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

71

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

72

3/22/20

13

Age changes

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

containing many mitochondria)

73

Clinical Considerations

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

74

75 76

77 78

3/22/20

14

79 80

81