Salivary Glands

Ten Cate, Chapter 11

What are the three pairs of major salivary glands?

1. Parotid

2. Submandibular

3. Sublingual

What are the functions of saliva?

1. Wetting

2. Lubricating

3. Digestive

4. Mineralization

5. Protective

What do parotid glands produce?

A serous (watery) secretion and produces only 20% of daily saliva volume (but includes SIgA and other defense chemicals)

What do submandibular glands produce?

A mixed serous and mucous secretion, produce 65% of daily saliva volume (dsv)

What do sublingual glands produce?

Secrete a predominantly mucous saliva, = 5% of daily saliva volume

Describe the salivary gland structure

• Has lots of lobules within each lobe

• The connective tissue capsule is rich in collagen fibers and continuous with the connective tissue septa within the gland

• Blood vessels, nerves, and excretory ducts run within the connective tissue septa

What components make up salivary glands?

A capsule surrounding a branched duct system ending in acini or compound acinar gland (serous) or in tubules (mucous)

What are some artifacts of preparation in salivary glands?

Secretory end pieces called demilunes

What are serous cells?

• pyramidal in shape

• broad base attached to basal lamina

• narrow apical end towards lumen

• polarized cells

• protein secreting cells

• round nuclei

What do serous cells secrete that begin to digest dietary starch into maltose?

Alpha-amylase

What is the function of alpha-amylase?

Digest dietary starch into maltose

Serous cells always stain

Dark purple

What do serous cells secrete?

A watery fluid with proteins, and are devoid of mucus cells

What are mucous cells?

1. Pyramidal in shape

2. Have flattened nuclei

3. Polarized cell (nuclei near basal end)

Mucous cells stain

Light pink

What do mucous cells produce?

A very mucus-rich secretion (mucin) stored in large, light-colored vesicles

What are myoepithelial cells?

They are present between serous cells and their basal lamina in the serous acini as branched “basket cells”

They are part of the epithelium that has constructed the gland

What is the function of the myoepithelial cells?

Because of the star shape, they are going to squeeze the serous gland

What is the origin of myoepithelial cells?

The intercalated ducts resemble smooth muscle cells, but they are ectodermal in origin

Where are myoepithelial cells located?

At the acini and intercalated ducts where they cover 25-50% of their surface area

What is the duct system

The secretory end pieces that empty into intercalated ducts

What are intercalated ducts?

It serves as a stem cell for both the secretory end piece cells and for the ductal cells

Both the secretory and ductal cells are considered

Intralobular ducts - intercalated and striated

What are striated ducts?

They connect to several intercalated ducts and are “striated” due to the infoldings of the basal plasma membrane (for ion transport)

Excretory ducts are considered

Interlobular and have their own stem cells

What are intercalated duct cells?

• Nonpolar

• Small diameter and drain individual secretory units

• Synthesis and secretion of lysozyme and lactoferrin

• Source of salivary gland stem cells

What are striated duct cells?

• Mainly in Parotid and Submandibular glands

• Polarized cells

• Striated appearance in basal plasma membrane with many mitochondria

• Role in the assembly and transcytosis of SIgA

What are excretory ducts?

• They are stratified and bilayered

• Two layers of cuboidal cells

• Generally are passive conducting tubes

• Maybe pseudostratified to stratified

• Contain both goblet cells and stem cells

What is the Parotid Gland?

• 100% serous acini

• A well developed duct system

• highest amount of amylase of all salivary glands

• Defensive chemicals

• Stimulated saliva (produces little saliva during resting = not eating)

Parotid gland with the amylase producing serous cells storing enzyme in secretory granules

The granules also contain defensive proteins as well

What are submandibular salivary gland?

• Mixed gland with both serous and mucous cells

• Branched tubuloacinar gland composed of serous and mucous cells

• 70% of the ducts end in serous acini, 30% mucous acini

• Serous cells secrete lysozyme to kill bacteria

• Saliva produced is mostly resting saliva

Sublingual salivary gland

• Predominately a mucous salivary gland

• 50% mucous acini and 50% serous acini

• Branched tubuloacinar glands

• Resting saliva

What is this, and what does it contain?

Sublingual gland containing lighter areas of mucous cells (large and take up most of the space),
Some serous cells

Minor salivary glands

• Mucous

• Serous

• Mixed

What are the minor mucous salivary glands?

• Palatine glands

• Posterior lingual glands

What are the minor serous salivary glands?

Glands of von Ebner

What are the minor mixed salivary glands?

• Anterior lingual glands

• Buccal glands

• Labial glands

How many minor salivary glands do we have in the oral cavity?

600-1000

What is the new minor human salivary gland discovery made?

Two predominantly mucous glands with multiple draining ducts near the torus tubarius, superior the the eustachian tube

“tubarial glands”

What are tubarial salivary glands?

• Primarily mucous glands with minor serous output

• Location in the submucosa, diffuse nature of the glandular tissue and lack of capsule suggest a minor salivary gland designation

• The gland is comparable to the mucous glands in the soft palate and assist in swallowing

What do minor salivary glands look like?

Individual lobules that don’t grow any more extensive

What is the role of the minor salivary glands in the submucosa?

• Only 10% of the salivary secretion, but 70% of the mucous secretion

• Important contributors to unstimulated or resting saliva

• Have shorter excretory ducts

• Have poorly developed intercalated and striated ducts

• They are not surrounded by a connective tissue capsule

What are the Glands of von Ebner?

Serous glands on our tongue associated with papillae that have lots of taste buds with them

• Posterolingual in the tongue

• Secretions are released in areas with significant number of taste buds

• Near the troughs and clefs of circumvallate and foliate papille

What do von Ebner glands secrete?

Serous fluid with digestive enzymes and other proteins which assist in the perception of taste, they are associated with Weber’s glands (mucous glands)

What does the development of a salivary gland compare to?

The development of a tooth bud in regards to beginning in a similar structure, and using the same signaling molecules

What are the developmental steps of salivary glands?

What are some differences between facial exocrine glands and exocrine glands located elsewhere in the body?

1. Ectomesenchyme reacts differently than mesenchyme

2. There is less reciprocal induction signals received from ectomesenchyme

3. Teeth and sweat glands are more affected by hypohidrotic ectodermal dysplasia

4. Higher degree of epithelial interactions in salivary glands

5. Very few mesenchyme locations will support development of salivary glands from oral ectoderm

What is hypohidrotic ectodermal dysplasia?

Abnormal development of structures including the skin, hair, nails, teeth, and sweat glands

62% of people have reduced salivation

What is the only other place that we can see mesoderm that can cause salivary glands?

Mesoderm associated with mesenchyme from urogenital ridge

Skin vs. oral ectoderm-derived organs

Reciprocal inductive signals originating from Oral Ectoderm and Neural Crest derived Ectomesenchyme

What dictates what kind of cell you’re going to be? (gland shape/product)

The recombination of mammary epithelium with salivary gland mesenchyme gives rise to salivary glands that secrete milk proteins instead of salivary proteins

What designates the product of the gland (serous or mucous)?

The epithelia

What designates the shape of the gland?

Mesenchyme

Salivary Gland Development

What is ectodysplasin A (EDA)?

A signaling molecule that is necessary to go from a placode to a beginning bud. It is necessary for our salivary glands and tooth buds. There is a receptor that the epithelial cells have to have

What mades EDA?

Underlying mesenchyme that works with the receptor on the epithelia to make a bud form

What is sonic hedgehog?

Epithelial cell proliferation, survival and differentiation, creating branching

What is elongation?

Fibroblast growth factor, secretion of collagen- cleft formation

What is epidermal growth factor?

Stimulates epithelial proliferation and differentiation

People with Hypohidrotic ectodermal dysplasia are (HED)

1. Deficient in producing EDA from the mesenchymal cells

2. the epithelial cells are deficient in making receptors

3. Often tend to lack production of fibroblast growth factor to cause the elongation of the bud

What happens during Bud Formation (1)?

1. Human development late 4th week

2. EDA is produced by the underlying mesenchymal

3. Receptors are on epithelial cells causing growth of placode down into a bud shape

4. Fibroblast growth showing development of salivary glands

What happens during Cord Growth (2)?

1. Using fibroblast growth factors as a signaling molecule, there is a lot more condensation of ectomesenchyme

2. Early week 5

3. Bud growing into ECM because of FGF from ECM

4. Parotid, submandibular and sublingual gland growth

5. Extracellular matrix of ectomesenchyme (NCCs) growth

Development of various portions of salivary glands

What happens during Branching of Cords (3)?

1. Clefts develop in the bud forming two+ buds

2. Growth factors like Shh and TGFb (transforming or tumor growth factor) from mesenchyme result in clefts from changes in epithelial cell shape

3. Fibronectin and Collagen III (reticular fibers) in the ECM are important to cleft formation, as In non-muscle myosin

What is Lobule Formation (4)?

The result of repeated branching and budding along major branches of the cord stimulated by FGF and EGF (epidermal growth factor).

E-cadherin is important in acinar formation

What is this

In the cleft, there is a lot of expression for collagen III/I being on the outside.

There is an original bulb and there are clefts starting to develop along with branching

Fibronectin is important because it holds all of it together

What is important for branching and cleft formation?

Collagen III and Fibronectin

What is Collagen IV important for?

Basement membrane

Branching acinar morphogenesis)

What are proteoglycans and GAGs important for?

Branching

What are Laminins important for?

Basement membrane assembly of

• Lumen formation

• FGFR signaling

• Acinar formation

How can branching be inhibited?

If treated with collagenase so no clefts with form

Antibodies against collagen for the basement membrane will result in

No terminal end buds forming

What is the Canalization of Cords (5)?

Creating space (making them hollow) using water and apoptosis.

All ducts (lumens) form before the formation of secretory granules within the acinar cells

Lumens appear first at the distal end of main cord and in the branches, then at the proximal end and finally in the central portion of the main cord

Lamina form in the ducts before they form in the acini

Canalization of Cords

What is Cytodifferentiation (6)?

Signaling molecules come out to designate what are going to be serous, mucous, intercalated duct, striated duct, excretory cells, etc

Cells of the bulb region are the stem cells that undergo cell proliferation and differentiation Into acinar and ductal cells

Myoepithelial cells also arise from the stem cells of the terminal bulbs and develop in concert with acinar cells

What is the development of minor salivary glands?

They develop in the same way as the major salivary glands but they stop development early.

Formation of minor salivary glands (1-3)

What is saliva?

A complex oral biofluid

A mixture of components derived from multiple sources (different salivary glands)

What is the secretion of saliva?

1. Water

2. Proteins and glycoproteins

3. Electrolytes

What is saliva production stimulated by?

Unconditioned reflexes (things that stimulate saliva)

Conditioned reflexes (such as hearing, thinking about or looking at food, things that you associate with eating that then generate saliva)

What are the unconditioned reflexes?

1. Gustatory Stimulus- Taste

   1. Taste receptors on tongue, soft palate, pharynx and epiglottis

2. Masticatory Stimulus- Chewing

   1. Sensory receptors within the periodontal ligaments

3. Olfactory stimulus - smelling (lamina cribrosa)

What is the nerve input for unconditioned reflexes?

Taste buds (neuroepithelial cells)

• Gustatory salivary reflex- neurons are located in lower brainstem

  • Lateral hypothalamus modulates this center

• Mechanoreceptor fibers are sensitive when pinching the tongue

What are the afferent pathways?

Taste- facial (VII) and glossopharyngeal (IX) nerves

• To solitary tract nucleus in the medulla

• Plus input from higher centers of brain in response to smell

What are the efferent pathways?

Parasympathetic nerves

• To sublingual and submandibular glands

• From facial nerve (VII) via submandibular ganglion

• Parotid gland from glossopharyngeal (IX) via otic ganglion

• Sympathetic postganglionic nerve from cervical ganglion

What is the separation between the superior and inferior salivatory nuclei?

There is none

What do preganglionic fibers innervate from the superior salivatory nucleus?

1. Submandibular salivary glands

2. Sublingual salivary glands

Efferent fibers travel with which nerve to the submandibular and sublingual salivary glands?

Chorda tympani nerve (facial nerve, VII)

What do preganglionic fibers innervate from the inferior salivatory nucleus?

1. Parotid glands

2. von Ebner’s glands

Efferent fibers travel with which nerve to the parotid and von Ebner’s glands?

Glossopharyngeal nerve (IX)

Fluid and electrolytes present in saliva are derived from blood plasma in

Ion and water channels

What surrounds acini and salivary ducts?

Capillary networks

What is needed in order to maintain a rapid and sustained secretion of saliva into oral cavity?

An extensive blood flow

What are the components of unstimulated saliva (resting)

• Basal Production

• Confers most protection

• Importance of Minor Salivary and Submandibular Glands

• Low output during sleeping hours

What are the components of stimulated saliva (resting)

• Protection during mastication

• Rich in digestive enzymes

• Importance of Parotid Gland output