L12

Question 1

Hyposalivation

Answer 1

xerostomia, mucosal changes, enamel erosion, increased caries, difficulty swallowing and chewing, change in taste

Question 2

hyposalivation as unstimulated salivary flow rates of

Answer 2

< 0.1ml/min (Dawes, 2008), which would correspond to at least a 2/3 reduction from normal levels. The various symptoms that occur include (1) “xerostomia” which is the unpleasant, subjective feeling of dry mouth, (2) pathologic changes in the oral mucosa- here you can see a patient with a fissured tongue, (3)erosion of the enamel and an (4) increase in the incidence of caries, (5) difficulty in chewing and especially swallowing, and (6) changes in taste perception.

Question 3

Hyposalivation can result from a genetic mutation,

Answer 3

although this is quite rare.
Medications are a much more common cause. Of course, anticholinergic drugs have a marked effect on salivary flow; one such drug that is given fairly commonly would is ipratropium bromide (“Atrovent”), used for COPD (chronic obstructive pulmonary disease). Other drugs that inhibit salivary flow are diuretics like furosemide [Lasix], a diuretic used for congestive heart failure, antidepressants, antihistamines, and antihypertensives.
Systemic diseases can also give rise to dry mouth.

Question 4

Actually a prodromal symptom of mumps is

Answer 4

xerostomia; however, fortunately, this is temporary.

Question 5

Other diseases that present more chronic problems are the

Answer 5

autoimmune disease, Sjogren’s syndrome, diabetes mellitus, and HIV.

Question 6

Finally, we should mention that hyposalivation can be a side-effect of

Answer 6

medical treatment; i.e., it can be iatrogenic. One common iatrogenic cause of hyposalivation is radiotherapy of the head and neck.

Question 7

Von ebner’s gland

Answer 7

lingual lipase

Question 8

normal resting daytime salivary flow rates are

Answer 8

.3-.4ml/min & the volume of saliva in the mouth, 0.8-1.1ml; most of it is in a thin (~100um) film that coats the mucosa & teeth.

Question 9

During sleep, flow rates

Answer 9

decrease very markedly (~.1ml/min), making pre-bedtime oral hygiene especially important.

Question 10

The parotid gland contributes the most,

Answer 10

~60% by volume, to the entire volume of saliva that is in the mouth (called whole mouth saliva),

Question 11

the submandibular accounts for

Answer 11

25%, and the submandibular and

Question 12

minor glands each contribute

Answer 12

7-8%.

Question 13

The parotid gland is a pure

Answer 13

serous gland; it secretes a watery saliva & is the main source of the enzyme, amylase, which initiates the breakdown of starch.

Question 14

Submandibular and sublingual glands are

Answer 14

mixed serous/mucous glands.

Question 15

Von Ebner’s glands are pure

Answer 15

serous glands and the source of lingual lipase, an enzyme which breaks down triglycerides into free fatty acids.

Question 16

The other minor glands, which are pure

Answer 16

mucous glands, are the major source of mucins, glycosylated proteins critical for lubrication.

Question 17

Lubrication, swallowing:

Answer 17

mucins

Question 18

Mucins are

Answer 18

highly glycosylated glycoproteins that are viscous and largely responsible for lubricating the mucosal surface & providing a protective barrier. Mucins are also important for trapping bacteria and sugar and therefore providing for their clearance.

Question 19

The Bicarbonate is also

Answer 19

secreted in saliva and serves an important function in buffering acids in the mouth

Question 20

In addition, there are calcium-binding proteins present in

Answer 20

saliva: these include the Proline-rich proteins and statherin that allow saliva to be super-saturated with calcium and thus contribute to enamel maturation and remineralization.

Question 21

Several molecules, including **lysozyme, peroxidase, the defensins and histatins, along with IgA contribute to the

Answer 21

direct antimicrobial functions of saliva; the are capable of anti-bacterial, anti-fungal and anti-viral actions…

Question 22

There is also some evidence that saliva can actively participate in

Answer 22

tissue repair by secreting **growth factors like epidermal growth factor and nerve growth factor (NGF).

Question 23

Saliva contributes to the digestive process in 2 very important ways-

Answer 23

the lubrication provided by the mucins already mentioned is critical to both chewing and swallowing food- just think of what it is like trying to eat when you have a dry mouth! Secondly, saliva contains enzymes, including amylase which begins to dissolve starch & lipase which breaks down fats into free fatty acids and glycerol.

Question 24

Like all glands, salivary glands are made up of

Answer 24

stroma and parenchyma– stroma serve a supporting role and parenchyma do the characteristic work of a given gland.

Question 25

In the salivary gland, *stroma provide

Answer 25

structural support to the gland, forming the capsule and organizing the gland into lobes

Question 26

whereas the *parenchyma make the

Answer 26

whereas the *parenchyma make the saliva and take care of discharging it to its final destination. In the salivary gland, stroma is made up of connective tissue, whereas parenchyma is made up of epithelium.

Question 27

Stroma includes:

Answer 27

capsule that encompasses the salivary gland and separates it from surrounding tissue & *septa

Question 28

Like many other types of connective tissue the major cell type in salivary gland stroma is the

Answer 28

fibroblast which makes collagen, the major component of the extracellular matrix. The stroma also contains a number of other types of cells and tissues listed above.

Question 29

The parenchyma are comprised of 2 main components,

Answer 29

the secretory portion, called secretory endpieces or “acini” (from the latin for grapes) AND the ducts.

Question 30

The acini are composed of

Answer 30

individual acinar or secretary cells (sometimes also called secretory units) and these are the cells that make saliva.

Question 31

There are 2 main types of acinar cells,

striated = secretory

Answer 31

serous and mucous, which in turn make up 3 types of endpieces… (spotlight)

Question 32

These acini open into a

Answer 32

series of ducts, which get progressively larger- *intercalated… *striated (also known as secretory)… *excretory . We will consider the detailed anatomy of the different acinar cells and ducts in the next module.

Question 33

Glands begin dev’t in

Answer 33

6th week (what other important oral structures begin dev’t at this time?)

Question 34

Parotid gland dev’t is initiated in the

Answer 34

1st part of the 6th wk, followed by dev’t of submandibular gland- the sublingual & minor glands develop later, between 2 & 3 months.

Question 35

Consistent with the fact that they are epithelial structures, the

Answer 35

parenchyma, both the acini & ducts, develop from ectoderm or endoderm whereas the connective tissue stroma develop from the neural crest.

Question 36

The initiation of salivary gland dev’t starts out with a

Answer 36

thickening of the ectoderm or endoderm, then the formation of an epithelial “bud” somewhat similar to the initial stage of odontogenesis.

Question 37

Also similar to odontogenesis, important signals are exchanged between the

Answer 37

epithelial and mesenchymal compartments.

Question 38

Although e-m interactions continue to be important, morphologically, the next stages of salivary gland dev’t

Answer 38

depart markedly from odontogenesis, although they bear a striking resemblance to development of other branched structures, such as the mammary glands, lung, kidney, and pancreas.
The single bud branches, then branches again and again & then the part of the branching structure that will ultimately become the ducts “hollows out” in a process known as cavitation

Question 39

How does this branching come about?

Answer 39

Before branching occurs, each cell is joined to its neighbors by cell adhesion molecules expressed on adjoining cell surfaces- an important cell adhesion molecule in this case is e-cadherin… here stained in red… as the cleft begins to form you can see evidence that cadherin staining is beginning to break up… and as the clefting progresses it disappears at the base of the cleft. Finally the e cadherin is gone on the surfaces of all the cells that face the cleft

Question 40

A very interesting aspect of this regulation is that the adhesion molecule remains on

Answer 40

other surfaces of the very same cells- so the process is very specific- the cell is not simply turning off the adhesion molecule but redirecting its expression.

Question 41

So one aspect of clefting is the

Answer 41

suppression of e-cadherin expression in a certain region of the cell. But, of course that begs the ? In turn of how this comes about in the first place…

Question 42

It turns out that the expression of Cleftin in developing salivary gland cells is induced by the

Answer 42

well-known extracellular matrix molecule, fibronectin. Fibronectin in the ECM interacts with fibronectin receptors that are located on membranes of salivary gland cells.

Question 43

Cleftin expression (BTBD7) has

Answer 43

2 actions and both take place within the cell (cleftin is not a secreted molecule)- it acts to suppress the expression of e-cadherin expression & but it upregulates expression of another molecule called “snail2”.

Question 44

Snail2 is a well-known

Answer 44

transcription factor important in many aspects of dev’t and also cancer. Exactly what it does in the developing salivary gland is unclear- but the current hypothesis is that it promotes a change in cell shape, and that change in shape coupled with the loss of e-cadherin, this allows gaps to form, promoting clefting.

Question 45

The overall picture is that the acini

Answer 45

SECRETE saliva & that the ducts SECRETE but also RESORB certain components present in the salivary secretion.

Question 46

More specifically the acinar cells secrete =

Answer 46

water, a host of proteins and ions, including both sodium and chloride. This is called the “primary secretion or primary saliva” and it is ISOTONIC. It is important to note that acinar cells are water permeable.

Question 47

The duct cells, in contrast, are NOT

Answer 47

water permeable. These cells resorb both sodium and chloride. The duct cells also secrete a few proteins and importantly, the bicarbonate ion. After these actions in duct cells, the fluid is called the “secondary secretion or secondary saliva and it is HYPOTONIC.

Question 48

Salivary secretion is almost entirely under

Answer 48

neural control. This contrasts with secretion by many other glands, such as the secretion of thyroxin by the thyroid, which is controlled instead by blood-borne hormones.

Question 49

The salivary glands are supplied by both

Answer 49

branches of the autonomic nervous system, *parasympathethic and *sympathetic.

Question 50

As you most likely remember from anatomy. The cell bodies of pre-ganglionic parasympathetic neurons are located in the

Answer 50

*brainstem and send their axons out of the brain in the 7th and 9th cranial nerves. In turn, axons in the 7th and 9th nerves synapse on post-ganglionic neurons near each of the glands.

Question 51

The sympthetic supply originates in

Answer 51

cell bodies in the IML * of the spinal cord which send axons out of the cord to synapse in the superior cervical ganglion, and axons arising from post-ganglionic neurons in the superior cervical ganglion in turn supply the glands.

Question 52

The sympathetic nervous system is responsible for

Answer 52

protein secretion *(spot). The post-ganglionic neuron releases NE which binds to a beta-adrenergic receptor on the salivary acinar cell. This is a GCPR which is coupled to the enzyme adenyl cyclase (AC). Activation of AC - upregulates cAMP - which activates PKA. spot) Protein kinase A in turn, phosphorylates the secretory granules that contain synthesized proteins, facilitating their release. Activation of the sympathetic ns alone produces a protein-laden, viscous secretion that is not voluminous.

Question 53

The parasympathetic nervous system is mainly responsible for

Answer 53

fluid secretion and therefore accounts most for the volume of saliva. When the parasympathetic ns is activated, the post-ganglionic neuron releases acetylcholine (abbreviated Ach) which binds to a (* spot) muscarinic type receptor on the salivary acinar cell. This is also a GCPR, but in this case it is coupled to phospholipase C, which liberates IP3 from membrane phopholipids, and subsequently liberates Ca++ from the ER (endoplasmic reticulum).

Question 54

The increase in Ca++ opens a

Answer 54

chloride channel, and the conc gradient drives chloride from the cell. This increase in Cl- in the lumen creates electrical & osmotic gradient - which draws sodium & water via a paracellular (between-cells) pathway.

Question 55

• Note that, in salivary gland cells, chloride is

Answer 55

maintained at a high concentration intracellularly by an energy-requiring ion pump