Transcript Fundamentals of saliva

Fundamentals of saliva
DENT 5302
Topics in Dental Biochemistry
Dr. Joel Rudney
Foundation knowledge
 DENT 5315 Oral Histology
Dr. Koutlas’ salivary gland lectures
 Ten Cate’s Oral Histology
Chapter on Salivary Glands
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
General composition
 Saliva is hypotonic - 99.5% water
 Remaining 0.5%
Ions
K+, Na+, Ca2+, Mg2+, H+
Cl-, HCO3-, I-, F-, HPO42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
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-, HPO42-, peptides)
 Maintaining tooth integrity
Post-eruptive maturation (Ca2+, F-, HPO42-)
Mineralization equilibrium (Ca2+, F-, HPO42-)
Pellicle (proteome components)
 Maintaining tissue integrity (proteome components)
 Regulation of the oral flora (proteome components)
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
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
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
Changes with stimulation
P, K, duct cell proteins,
immunoglobulins decrease
Ca, Na, Cl, Bicarbonate,
secretory cell proteins increase
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%
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
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?
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
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, antihypertensives, 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
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