Saliva in Caries

Parotid gland

Major saliva-producing gland; located over the cheek, near the upper second molar; contributes ~20% of unstimulated saliva but >50% of stimulated saliva

Submandibular gland

Located below/on the side of the mandible; contributes the largest share (~65%) of unstimulated whole saliva

Sublingual gland

Located under the tongue; contributes ~7-8% of unstimulated saliva

Minor mucous glands

Distributed over the whole mouth; contribute ~7-8% of unstimulated saliva

Ductal saliva

Saliva produced in the serous acinus cell and collected directly from a single duct, typically via a Lashley cannula, mainly for research (no clinical use)

Lashley cannula

Device used to collect pure ductal (glandular) saliva, mainly for research purposes

Whole (mixed) saliva

The saliva normally present in the mouth; combines secretions from all major and minor salivary glands plus additional sources like GCF, epithelial cells, leukocytes, bacteria, and food debris

Gingival crevicular fluid (GCF)

Fluid that flows from the periodontal pocket and contributes to whole saliva

Normal whole saliva volume

500-750 mL per day

Two-stage model of saliva secretion

Model describing how acinar cells first produce isotonic primary saliva, which is then modified by the ductal cells as it passes through the duct

First stage of saliva secretion

Acinar cells release isotonic primary saliva containing Na+, Cl-, HCO3-, and K+, in equilibrium with surrounding tissue fluid

Second stage of saliva secretion

As primary saliva passes down the ductal tree, Na+ is actively reabsorbed, K+ is actively secreted, Cl- is passively absorbed, and HCO3- is reabsorbed

Effect of flow rate on saliva ions

As flow rate increases, pH and concentrations of protein, Na+, Cl-, and HCO3- rise, while Mg and phosphate concentrations fall; fluoride stays relatively constant

Fluoride concentration in saliva

About 0.019 ppm; relatively independent of flow rate

Most potent stimulus for salivary secretion

Acidic taste

Effect of chewing duration on flow rate

Flow rate is highest right after chewing begins and decreases the longer you chew; no need to chew sugar-free gum for long since the effect diminishes

Circadian rhythm and saliva flow

Salivary flow rate is highest at midday and lowest at night, following a 24-hour cycle like other endocrine/secretory glands

Important factors affecting salivary flow

Degree of hydration, body position, exposure to light, previous stimulation, circadian rhythms, circannual rhythms, drugs

Unimportant factors for salivary flow

Gender, age (above 15), body weight, gland size, psychic effects (thought/sight of food, appetite, mental stress)

Xerostomia

Dry mouth; caused by about 80% of prescribed drugs (e.g., anticholinergics, antihistamines, antidepressants, diuretics, antihypertensives)

Henderson-Hasselbalch equation (salivary buffering)

pH = pKa + log([HCO3-]/[H2CO3]); describes bicarbonate buffering in saliva

Bicarbonate buffering

H+ + HCO3- <-> H2CO3 -> H2O + CO2 (via carbonic anhydrase); the major buffer in saliva that raises plaque/oral pH

Phosphate buffering

PO4(3-) binds H+ to form HPO4(2-) then H2PO4-; buffers acid until pH reaches 5, after which phosphate has no further buffering capacity

Ionic product (Ip) of saliva

Ip = [Ca2+]^5 [PO4^3-]^3 [OH-]^3; used to compare saliva's calcium/phosphate/hydroxide levels to hydroxyapatite's solubility product

Ksp

Solubility product of tooth mineral (hydroxyapatite) = [Ca2+]^5 [PO4^3-]^3 [OH-]

Ip = Ksp

Saliva is saturated with respect to hydroxyapatite (HA)

Ip less than Ksp

Saliva is under-saturated with respect to HA; favors demineralization (tooth dissolves)

Ip greater than Ksp

Saliva is supersaturated with respect to HA; favors remineralization

Effects of high salivary flow rate on Ip

Calcium ion concentration increases, PO4^3- fraction increases markedly, hydroxyl ion concentration increases, all promoting remineralization

Statherin

"To stabilize" (Greek); allows saliva to become supersaturated with calcium phosphate by adsorbing to crystal growth sites, preventing unwanted crystal formation and blocking excess mineral deposition on the tooth

Acidic proline-rich proteins (PRP)

Bind calcium (release at low ionic strength, bind at high concentration, reduced binding at low pH) and inhibit hydroxyapatite deposition by blocking crystal growth sites

Acquired salivary pellicle

Protein film covering the tooth (statherin, PRPs, immunoglobulins, amylase, lysozyme, peroxidase, glycoproteins, serum proteins, mucins) that limits Ca/PO4 diffusion and reduces acid diffusion to the tooth surface

Arginine-rich proteins

Contribute to salivary buffering capacity

Urea

Inorganic salivary component that helps buffer/neutralize acid and is broken down by bacteria to release ammonia (raises pH)

Two main organic functions of salivary proteins in caries

Maintaining tooth integrity (protecting against demineralization) and controlling cariogenic microflora (antimicrobial function)

4 ways saliva maintains tooth integrity

Binding/releasing calcium, maintaining high Ca near tooth surface, preventing HA precipitation, forming the protective pellicle

Lactoferrin

Binds iron (an essential bacterial nutrient), making it unavailable and limiting microbial growth

Lysozyme

Causes direct lysis of bacterial cell membranes via enzymatic hydrolysis of cell wall polysaccharides; may also cause non-enzymatic membrane injury and promote bacterial aggregation

Salivary peroxidase (lactoperoxidase)

Converts H2O2 + thiocyanate into hypothiocyanate, a powerful oxidant that inactivates glycolytic/carbohydrate transport enzymes in bacteria; most effective against S. mutans below pH 6

Serous glycoproteins

Made in all salivary glands; includes secretory IgA, functions to block bacterial adherence, induce aggregation, and interfere with colonization enzymes

Secretory IgA

Immunoglobulin in saliva that blocks bacterial adherence determinants, induces aggregation, and interferes with colonization-associated enzymes

Basic proline-rich glycoproteins

Glycosylated and basic (unlike acidic PRPs); bind S. mitis and S. sanguis, potentially interfering with attachment to the tooth or inhibiting growth

Mucinous glycoproteins

Very viscous and hydrophilic; interact with specific microorganisms and cause bacterial aggregation, enhancing clearance by swallowing

Salivary agglutinins

Selectively agglutinate S. mutans (not other Streps); if free in saliva they promote clearance by swallowing, but if adsorbed to the tooth surface they can actually promote colonization/attachment

Histidine-rich proteins (histatins)

Growth-inhibitory and bactericidal against S. mutans

6 modes of action of salivary antimicrobial proteins

Direct lysis (lysozyme), interfering with growth (histatins), removing nutrients (lactoferrin), causing bacterial aggregation for clearance (agglutinins, basic PRP), interfering with bacterial systems (peroxidase), and providing strain-specific attachment sites (acidic PRP)

Saliva's clearance function

Clears acid from plaque and fermentable carbohydrate from the oral cavity, reducing cariogenic potential

Saliva as a caries risk indicator

Unstimulated flow rate <0.2 mL/min and stimulated flow rate <0.7 mL/min indicate high caries risk

Types of phosphate in saliva

Non-ionic phosphate and three ionic forms: PO4^3-, HPO4^2-, and H2PO4-; only the PO4^3- fraction increases with flow rate, since it's part of the ionic product equation