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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 conceptsCaries is a process, not a diseaseDriven by biofilm, but initiated by the hostClosely linked to specific microenvironmentsThe process is dynamic and reversibleOral ecological shifts are normal and cyclicalMany factors influence the outcomeMicrobes are necessary, but not sufficientUnderstanding the processEnamel is a unique hard tissueEnamel is 95% mineralizedMinimal protein contentEnamel is acellular and non-vitalCannot repair itselfEnamel is permeableWater and small moleculesEnamel is in dynamic chemical equilibrium with the oral environmentEnamel 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-minBreak even - sound enamel or arrested cariesNet lossSubsurface demineralizationNew cariesProgression of old lesionsNet gain - remineralization of existing lesionshttp://www.uiowa.edu/~ocrdent/crown%20model.htmEnamel cariesBegins 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 sitesMicro-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 microbesStreptococcus mutans/sobrinusMajor source of demineralizationCariogenic propertiesHighly acidogenicHighly aciduricExtracellular polysaccharide from sucrose - insolubleAdheres to pellicle•So do most oral strepTransmisible - mother/caregiver to child•So are all oral bacteriaMicrocolonies - localized zones of high acidity in protected sitesOcclusal pits and fissures; interproximal contactshttp://www.dokidoki.ne.jp/home2/saishika/caries01.htmMicrobes as risk factorsNecessary, but not sufficientHigh S. mutans levels in saliva/plaque increase riskLongitudinal studiesMost people who get new lesions will have “high” levels BUTMany people with “high” levels won’t get new lesionsThe majority of oral streptococci belong to non-mutans speciesS. mutans is a minority streptococcus - not a good competitorHigh % of acidogenic/aciduric non-mutans = increased risk?Low % of acidogenic/aciduric non-mutans = decreased risk?Other species may moderate riskAre high levels of Veillonella related to lower lactate levels?Antimicrobial strategiesTargeted attacks on mutans streptococciFundamental concept - S. mutans is the main demineralizerCaries vaccines - results not impressiveSecretory immune system (S-IgA) is tolerant of oral microbesTopical antibodies - results not impressiveNEW Antimicrobial peptides combines w/ S. mutans pheromonesBroad-spectrum attempts to eliminate/limit biofilmAllows for the possibility of other acidogenic speciesSystemic antibiotics (fungal overgrowth)Chlorhexidine rinses or varnishes (recolonization from reservoirs)NEW Antimicrobial peptides (a “natural” defense system)NEW Quorum sensing inhibitorsReplacement with “probiotics”, natural or genetically engineeredAll approaches have limitations, possible risksHost factors - teethGenetics (twin studies)Occlusal morphologyPredisposing•Complexity (e.g. buccal pits)Simplicity may be protectiveEnvironment (diet, prevention)Resistance to demineralizationReplacement ions in hydroxyapatiteFluoride, strontium - protectiveSelenium - predisposinghttp://www.zahntechnik-online.deHost factors - no salivaSaliva is an important regulator of the caries processXerostomia due to radiation therapy or Sjogren’s syndromeVery high S. mutans levels + rampant cariesDecay in unusual sites in multiple teethhttp://www.eastman.ucl.ac.uk/climages/ © Eastman Dental InstituteHost factors - normal salivaWhat is the effect of individual variation in saliva?Variation in flow rateHigh flow rate - protective; low (normal) flow rate - predisposingNot considered a major risk factor by itselfVariation in salivary buffering capacity (HCO3)High HCO3 - protective; Low HCO3 - predisposingNot considered a major risk factor by itselfVariation in antimicrobial protein concentrationsS-IgA, peroxidase, lysozyme, lactoferrin and othersExpectation: High [ ] - protective; Low [ ] - predisposingStudies


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U of M DENT 5301 - Pathobiology of Caries

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