Pathobiology of CariesMajor conceptsUnderstanding the processEquilibrium at normal pHDemineralizationRemineralizationAlternating cycles of de/re-minEnamel cariesSlide 9Dentinal cariesRisk factorsCariogenicity of microbesMicrobes as risk factorsAntimicrobial strategiesHost factors - teethHost factors - no salivaHost factors - normal salivaDiet and behavior“Social demineralization”Pathobiology of CariesDENT 5301Introduction to Oral BiologyDr. Joel RudneyMajor conceptsCaries is a process, not a diseaseDriven by biofilm, but initiated by the hostClosely linked to specific microenvironmentsThe process is dynamic and reversibleOral ecological shifts are normal and cyclicalMany factors influence the outcomeMicrobes are necessary, but not sufficientUnderstanding the processEnamel is a unique hard tissueEnamel is 95% mineralizedMinimal protein contentEnamel is acellular and non-vitalCannot repair itselfEnamel is permeableWater and small moleculesEnamel is in dynamic chemical equilibrium with the oral environmentEnamel caries is primarily a chemical processhttp://dentistry.uic.edu/CraniofacialGenetics/ResearchTED.htmEquilibrium at normal pHSaliva is supersaturated with respect to enamelSalivaEnamelCa10(PO4)6OH2[Ca] [PO4] [Ca] [PO4]Ca+statherinCa+aPRPDemineralizationSalivaEnamelCa10(PO4)6OH2[Ca] [PO4] [Ca] [PO4]Ca+statherinCa+aPRPDietary CHO + biofilm = lactic acid; diffusion into enamel = local pH dropEnamelsolubilityincreases[Ca][PO4]exit tosalivaCHO CHOCHO[H+][H+][H+][H+][H+]RemineralizationSalivaEnamelCa10(PO4)6OH2[Ca] [PO4] [Ca] [PO4]statherinCa+aPRPSaliva flow clears CHO; salivary HCO3 returns pH to normal Enamel becomeslesssoluble[Ca][PO4]move intoenamelCHOCHO[HCO3][HCO3][HCO3]Alternating cycles of de/re-minBreak even - sound enamel or arrested cariesNet lossSubsurface demineralizationNew cariesProgression of old lesionsNet gain - remineralization of existing lesionshttp://www.uiowa.edu/~ocrdent/crown%20model.htmEnamel cariesBegins as discrete lesions in the enamel of specific sites (reservoirs) Occlusal pits and fissures of Interproximal contacts molars and premolars between adjacent teeth (usually posterior)Caries risk varies greatly between tooth sitesMicro-environments account for this variationhttp://www.dentsply.de/products/esthet_x/ http://www.dent.ucla.edu/ce/cariesEnamel carieshttp://www.dent.ohio-state.edu/radiologycariehttp://www.st-andrews.ac.uk/~amc/research/medical.htmhttp://www.uic.edu/classes/peri/peri343/WsptPrev02/wspt7.htmWhite spot lesions• Intact surface• Subsurface demineralizationAdvanced enamel caries• Intact surface• “Sticky” fissures• Visible in radiographs• Dentin defensive reactionEnamel caries can be remineralizedDentinal carieshttp://www.st-andrews.ac.uk/~amc/research/medical.htmhttp://www.dent.umich.edu/research/loeschelabsLove et al. Infect. Immun. 68:1359• Cavitation• Demineralization + proteolysis• Bacteria move down tubules• Pulpal involvement• Major damage if uncheckedCan be arrested, but generallymust be restoredRisk factorshttp://wwwsam.brooks.af.mil/af/files/fsguide/HTML/Graphics/fig_12-06.gifThe initiation and progression of caries is the outcome of interaction between:• Microbial factors• Host factors• Behavioral/dietary/environmental factors• Institutional factorsCariogenicity of microbesStreptococcus mutans/sobrinusMajor source of demineralizationCariogenic propertiesHighly acidogenicHighly aciduricExtracellular polysaccharide from sucrose - insolubleAdheres to pellicle•So do most oral strepTransmisible - mother/caregiver to child•So are all oral bacteriaMicrocolonies - localized zones of high acidity in protected sitesOcclusal pits and fissures; interproximal contactshttp://www.dokidoki.ne.jp/home2/saishika/caries01.htmMicrobes as risk factorsNecessary, but not sufficientHigh S. mutans levels in saliva/plaque increase riskLongitudinal studiesMost people who get new lesions will have “high” levels BUTMany people with “high” levels won’t get new lesionsThe majority of oral streptococci belong to non-mutans speciesS. mutans is a minority streptococcus - not a good competitorHigh % of acidogenic/aciduric non-mutans = increased risk?Low % of acidogenic/aciduric non-mutans = decreased risk?Other species may moderate riskAre high levels of Veillonella related to lower lactate levels?Antimicrobial strategiesTargeted attacks on mutans streptococciFundamental concept - S. mutans is the main demineralizerCaries vaccines - results not impressiveSecretory immune system (S-IgA) is tolerant of oral microbesTopical antibodies - results not impressiveNEW Antimicrobial peptides combines w/ S. mutans pheromonesBroad-spectrum attempts to eliminate/limit biofilmAllows for the possibility of other acidogenic speciesSystemic antibiotics (fungal overgrowth)Chlorhexidine rinses or varnishes (recolonization from reservoirs)NEW Antimicrobial peptides (a “natural” defense system)NEW Quorum sensing inhibitorsReplacement with “probiotics”, natural or genetically engineeredAll approaches have limitations, possible risksHost factors - teethGenetics (twin studies)Occlusal morphologyPredisposing•Complexity (e.g. buccal pits)Simplicity may be protectiveEnvironment (diet, prevention)Resistance to demineralizationReplacement ions in hydroxyapatiteFluoride, strontium - protectiveSelenium - predisposinghttp://www.zahntechnik-online.deHost factors - no salivaSaliva is an important regulator of the caries processXerostomia due to radiation therapy or Sjogren’s syndromeVery high S. mutans levels + rampant cariesDecay in unusual sites in multiple teethhttp://www.eastman.ucl.ac.uk/climages/ © Eastman Dental InstituteHost factors - normal salivaWhat is the effect of individual variation in saliva?Variation in flow rateHigh flow rate - protective; low (normal) flow rate - predisposingNot considered a major risk factor by itselfVariation in salivary buffering capacity (HCO3)High HCO3 - protective; Low HCO3 - predisposingNot considered a major risk factor by itselfVariation in antimicrobial protein concentrationsS-IgA, peroxidase, lysozyme, lactoferrin and othersExpectation: High [ ] - protective; Low [ ] - predisposingStudies
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