Fundamentals of saliva

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 Cates 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-, 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

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-, 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)

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
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. 661614
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