Perio Lecture 3 - Pathogenesis PDF

Introduction to Periodontal Surgery Ryan Schure, DDS, MSc (Perio), FRCDC Clinical Assistant Professor, Department of Periodontics and Endodontics School of Dental Medicine, University at Buffalo The unauthorised use of any form of device to audiotape,...

Introduction to Periodontal Surgery Ryan Schure, DDS, MSc (Perio), FRCDC Clinical Assistant Professor, Department of Periodontics and Endodontics School of Dental Medicine, University at Buffalo The unauthorised use of any form of device to audiotape, photograph, video-record or otherwise reproduce lectures, course notes or teaching materials provided by instructors is covered by US Copyright Law and is prohibited. Students must obtain prior written consent to such recording. Reproducing and posting lecture recordings and/or handouts to publicly-accessible website is prohibited. Dr. Ryan Schure 1 Introduction to Periodontal Surgery Periodontal Disease Models Very old concept: Periodontal Bacteria Diseases Periodontal Disease Models Very old concept: Periodontal Bacteria Diseases Specific causative agent, like in some other diseases: − Anthrax (bacillus anthracis) − Syphilis (treponema pallidum) − Leprosy (mycobacterium leprae) − Tuberculosis (mycobacterium tuberculosis) Dr. Ryan Schure 2 Introduction to Periodontal Surgery not linear Periodontal Disease Models In fact, it is a bacterial jungle Generally, a mixed infection Some aggressive strains Complexes of associated bacteria Subgingival environments Gram (-ve) anaerobes Spirochetes and motile rods Many uncultivable species (unknown) Periodontal Disease Models Classical concept: Page & Kornman Dr. Ryan Schure 3 Introduction to Periodontal Surgery Periodontal Disease Models Modern concept: Host Immunological External and Inflammatory Internal Factors Response Factors Bacterial Challenge Genetics Connective Tissue and Bone Metabolism Systemic / Environment Medical Influences Periodontal Diseases Periodontal Disease Models Modern concept: External Bacterial Factors: Factors Bacterial species Virulence Bacterial Challenge Invasiveness Evasiveness Resistance Plaque quantity Distribution Plaque maturity Dr. Ryan Schure 4 Introduction to Periodontal Surgery Periodontal Disease Models Modern concept: Environmental Factors: External Restorations Factors Occlusion Calculus Bacterial Challenge Oral hygiene Smoking Diet Saliva Environment pH Oral habits Stress Periodontal Disease Models Modern concept: Internal Factors Systemic/ Medical Influences : Pregnancy Medications Diabetes Systemic / HIV Medical Influences 2 way arrow Dr. Ryan Schure 5 Introduction to Periodontal Surgery Periodontal Disease Models Modern concept: Host Immunological External and Inflammatory Internal Factors Response Factors Bacterial Challenge Genetics Connective Tissue and Bone Metabolism Systemic / Environment Medical Influences Periodontal Diseases Periodontal Disease Models DAMPs, damage-associated molecular patterns; fMLP, N-formylmethionyl- leucyl-phenylalanine; GCF, gingival crevicular fluid; LPS, lipopolysaccharide; MMPs, matrix metalloproteinases; PMNs, polymorphonuclear neutrophils. Meyle & Chapple. Molecular aspects of the pathogenesis of periodontitis. Periodontol 2000. 2015 Oct;69(1):7-17. exaggerated host response leads to tissue breakdown Dr. Ryan Schure 6 Introduction to Periodontal Surgery Periodontal Disease Models Pathogenic biofilm - necessary prerequisite for periodontitis but insufficient to cause the disease on its own Disease results from complex interactions between the biofilm and inflammatory immune responsefrom thehost Periodontal Disease Models Clinical Health: Health-promoting biofilm Symbiotic relationships between microorganisms and host response: Host ! provides key nutrients through GCF Bacteria ! release proteins and peptides to trigger a host response that is proportionate and resolving disease no Dr. Ryan Schure 7 Introduction to Periodontal Surgery Periodontal Disease Models Gingivitis: Accumulation of bacteria Incipient dysbiosis, favours quorum-sensing bacteria Inflammation Elicits stronger host response In a non-susceptible host ! does not progress beyond gingivitis Periodontal Disease Models Periodontitis: In a susceptible host ! incipient dysbiosis triggers an inappropriate and exaggerated host response tissue damage it i oxygen species Dr. Ryan Schure 8 Introduction to Periodontal Surgery Periodontal Disease Models Oral gingival epithelium = barrier: Keratinocytes release proinflammatory cytokines (IL-1a, IL-1b, IL-6, IL-8, TNF-a, defensins) Bacterial attack Bacterial proteinases (gingipains) downregulate host response Antigens Lipopolysaccharides Other virulence factors Periodontal Disease Models The body’s defense: Antibodies Neutrophils Plasma cells In a susceptible host, this response is disproportionate and exaggerated, creating a non-effective hyper- inflammatory response, leading to a state of frank dysbiosis where there is unbalance between the bacteria and host Dr. Ryan Schure 9 Introduction to Periodontal Surgery Frank 1 disbiosis Periodontal Disease Models The inflammatory response leads to high levels of: Cytokines Prostanoids Matrix metalloproteinases Oxidative stress Hyperactivated PMNs overproduce reactive oxygen species Reactive oxygen species help kill microorganism during health but become cytotoxic to host cells when overactivated …All lead to connective tissue and bone damage Periodontal Disease Models Innate immune system relies heavily on pattern recognition receptors (PRRs) e.g. membrane-bound toll- like receptions PRRs Expressed by macrophages, neutrophils, monocytes, epithelial cells Recognize various pathogens or their components Damage-associated molecular patters (DAMPs) are molecules released from damaged/dying cells and activate the innate immune system by interacting with PRRs While they contribute to the host defence, they also promote pathological inflammatory responses Dr. Ryan Schure 10 Introduction to Periodontal Surgery Periodontal Disease Models Haem (iron protoporphyrin IX) Produced through proteolytic degradation of hemoglobin and other haem-carrying plama proteins Growth factors and virulence regulator of the periodontal pathogens Porphyromonas gingivalis and Prevotella intermedia from broken down cells Periodontal Disease Models Periodontitis: In susceptible host: Incipient dysbiosis trigger an inappropriate and excessive host response Excess cytokines, reactive oxygen species, matrix metalloproteinases which overwhelm their respective antagonist Collateral periodontal tissue damage Damaged associate molecular peptides released – further propagate inflammatory response. Failure of innate inflammation resolving mechanisms Chronicity of inflammatory lesions Dr. Ryan Schure 11 Introduction to Periodontal Surgery In periodontitis, what is happening within the pocket? Gullus Dr. Ryan Schure 12 Introduction to Periodontal Surgery ICAM intercellular adhesion molecule Dr. Ryan Schure 13 Introduction to Periodontal Surgery Dr. Ryan Schure 14 Introduction to Periodontal Surgery inflammatory lytokines pro Dr. Ryan Schure 15 Introduction to Periodontal Surgery DISEASE HEALTH Higher Higher amounts of amounts of IL-1b, TNF-a, IL-10, TGF-b, PGE2, MMPs IL-1ra, TIMPs Pro-inflammatory Anti-inflammatory Destructive Protective Periodontal Risk Asses ment Dr. Ryan Schure 16 Introduction to Periodontal Surgery Pathogenesis of Periodontdal Diseases Environmental and acquired risk factors Host Immuno- Connective Clinical signs Microbial of disease inflammatory tissue and Challenge initiation and response bone metabolism progression Genetic risk factors Periodontal Risk Assessment Risk factor – environmental exposure which is associated with disease (identified in longitudinal studies) and implies modifiable condition (i.e. smoking) Determinants are risk factors than cannot be modified (i.e. genetics) puilrount Risk indicator – identified in cross sectional studies. May not always confirmed as risk factors in longitudinal studies we don't fully understand the mechanism ex age Dr. Ryan Schure 17 Introduction to Periodontal Surgery Risk indicator As age increases, prevalence, extent, & severity increase Rate of progression or likelihood of progression NOT related to age Poor predictor of future disease AGE Risk indicator Males tend to have more periodontal disease in industrialized nations Not consistent May be related to behavioural difference GENDER Dr. Ryan Schure 18 Introduction to Periodontal Surgery Risk indicator Lower SES, less education, limited access to dental care all related to higher levels of periodontal diseases socioeconomic status SocioECONOMIC STATUS Risk indicator Prevalence, extent, & severity of periodontal diseases greatest among ethnic minorities RACE/ ETHNICITY Dr. Ryan Schure 19 Introduction to Periodontal Surgery Risk factor HIV+, CD4+