Fundamentals of saliva

DENT 5302

Topics in Dental BiochemistryDr. 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 proteinsOral bacteria and their proteinsFood debris and dissolved food components

General composition Saliva is hypotonic - 99.5% water Remaining 0.5%

IonsK+, Na+, Ca2+, Mg2+, H+

Cl-, HCO3-, I-, F-, HPO4

2-

Small organic moleculesUrea, hormones, lipids, DNA, RNA

An extremely complex “proteome”106 D glycoproteins to 1000 D peptidespI range from 11.5 - 3.0Secretory products of salivary gland cellsProducts 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-, HPO4

2-)

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 compositionThere 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 glandsPlus 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 syndromeOther autoimmune diseasesParotitis

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 ageSM/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