The Fundamentals of Saliva, Xerostomia, Clinical Features

1. Fundamentals of saliva
DENT 5302
Topics in Dental Biochemistry
Dr. Joel Rudney

2. Foundation knowledge
DENT 5315 Oral Histology
Dr. Koutlas’ salivary gland lectures
Ten Cate’s Oral Histology
Chapter on Salivary Glands

3. General attributes of saliva
Clear fluid
Slightly alkaline pH (from the glands)
Viscous
Multiple contributions from:
Major (parotid, SM/SL) and minor glands
Extraneous contributors
Gingival crevicular fluid
• Serum proteins, WBC and their products
Oral epithelial cells and their proteins
Oral bacteria and their proteins
Food debris and dissolved food components

4. General composition
Saliva is hypotonic - 99.5% water
Remaining 0.5%
Ions
K+
, Na+
, Ca2+
, Mg2+
, H+
Cl-
, HCO3
-
, I-
, F-
, HPO4
2-
Small organic molecules
Urea, hormones, lipids, DNA, RNA
An extremely complex “proteome”
106
D glycoproteins to 1000 D peptides
pI range from 11.5 - 3.0
Secretory products of salivary gland cells
Products of B cells, PMNs, epithelial cells, bacteria

5. Protective functions of saliva
Deduced from our knowledge of saliva components
Mechanical cleansing (water/flow)
Lubrication of tissues and teeth (secreted proteins)
Buffering of acids (HCO3
-
, HPO4
2-
, peptides)
Maintaining tooth integrity
Post-eruptive maturation (Ca2+
, F-
, HPO4
2-
)
Mineralization equilibrium (Ca2+
, F-
, HPO4
2-
)
Pellicle (proteome components)
Maintaining tissue integrity (proteome components)
Regulation of the oral flora (proteome components)

6. Saliva and oral functions
Food processing (water)
Taste solute
Bolus formation and swallowing (secreted proteins)
Digestion (secreted proteins)
Speech (water, secreted proteins)
Lubrication and rehydration
Excretion (the long way around)
Small molecules (nitrate, thiocyanate. etc.)
May interact with salivary proteins, oral bacteria

7. Complications
Saliva from different glands differs in composition
Parotid - dominated by serous secretory cells
SM/SL minor - mixed serous or mostly mucous
Qualitative and quantitative differences in output
Composition is affected by level of gland activity
Spontaneous (baseline) activity (during sleep)
Unstimulated/”resting” (awake, but mouth at rest)
Stimulated (eating or talking)
Qualitative and quantitative differences in output

8. Stimulation and flow rate
Cumulative daily flow rates for whole saliva
Spontaneous (asleep): 8 hr at 0.05/ml/min = 25 ml
Unstimulated (awake): 12 hr at 0.7/ml/min = 504 ml
Stimulated (eating,talking) 4 hr at 2.0ml/min = 480 ml
24 hour total = 1009 ml
These are average values
Individual flow rates vary widely in healthy persons
Variation at each level of stimulation
At each level of stimulation
Variation in flow rate affects saliva composition
There is circadian variation during the day

9. Changes with stimulation
P, K, duct cell proteins,
immunoglobulins decrease
Ca, Na, Cl, Bicarbonate,
secretory cell proteins increase

10. Stimulation and gland output
Level of stimulation
Low Moderate High
Parotid 25% 35% 44%
Submandibular 62% 53% 44%
Sublingual 5% 4% 4%
Minor 8% 8% 8%

11. Whole (mixed) saliva
The actual fluid present in the mouth
Mixture from all the glands
Plus GCF, cells, bacteria, debris
The mixture is uneven at different oral sites
Varies according to duct locations
Lecomte and Dawes, J. Dent. Res. 66:1614

12. Research design issues
Collect glandular or whole saliva?
Glandular - harder to get, “purer”?, which gland(s)?
Whole - easy to get, messier, more representative?
Stimulated or resting?
Stimulated - faster - what level of stimulation?
Resting - slower - more representative?
What time of day? - standardization needed
How to control for variation in flow rate?

13. Xerostomia - dry mouth
Range of dryness
Profound - saliva flow absent or greatly reduced
The subjective perception of dry mouth
Difficult to define normal flow rate
Normal for one person may be too low for another
Causes of profound xerostomia
Head and neck radiotherapy for cancer
Absence or surgical removal of salivary glands
Inflammatory disease of salivary glands
Sjogren's syndrome
Other autoimmune diseases
Parotitis

14. Medication and xerostomia
1800 drugs in 80 drug classes report this as a side effect
www.drymouth.info
Great variation in frequency and severity
Opiates, anti-cholinergics, anti-depressives, anti-
hypertensives, anti-histamines, bronchodilators
• Variation within drug classes
Multiple medications increase risk
No direct correlation with aging
In unmedicated healthy adults
Parotid flow does not decrease with age
SM/SL, minor glands may decrease with age
Very difficult to disentangle effects of aging and meds

15. Clinical strategies
Drugs to stimulate flow
Depend on presence of functional gland tissue
Artificial salivas
Poor substantivity
Need for constant replenishment
Can replace water and ions
The protein component is much harder to replace
Gland repair or replacement
Gene therapy and tissue engineering