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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-, HPO42Small 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
