Pathogenesis of Periodontal Disease PDF

13/01/2022 Pathogenesis of Periodontal Disease – Part 2 Intended Learning Outcomes By the end of this session students should be able to:  Recap previous knowledge of gingival histology, immunology and pathogenesis.  Revise the different types of chemical mediators relevant to periodonta...

13/01/2022 Pathogenesis of Periodontal Disease – Part 2 Intended Learning Outcomes By the end of this session students should be able to:  Recap previous knowledge of gingival histology, immunology and pathogenesis.  Revise the different types of chemical mediators relevant to periodontal disease and their role in the host response.  Describe bacterial, cellular, tissue level & clinical features of disease and host response in the four stages of gingivitis to periodontitis; 1. Initial lesion 2. Early lesion 3. Established lesion 4. Advanced lesion  Explain what contributing factors impact the progression of disease 2 1  13/01/2022 GDC Learning Outcomes  1.1.2 Describe oral diseases and their relevance to prevention, diagnosis and treatment  1.1.4 Explain the aetiology and pathogenesis of oral disease  1.1.6 Describe relevant and appropriate physiology and explain its application to patient management  1.11.1 Assess and manage the health of periodontal and soft tissues taking into account risk and lifestyle factors  1.11.2 Explain and take account of the impact of the patient’s periodontal and general health on the overall treatment plans and outcomes 3 Recall of knowledge Gingival histology Immunology Biofilm Virulence factors Gingivitis & Periodontitis Pathogenesis of periodontal disease 4 2 13/01/2022 6 3  13/01/2022 What is the role of host immune system? To defend from initial aspect from disease in health to destruction 7 Histological Stages of Periodontitis 8 4  13/01/2022 We need to consider Bacterial Cellular features features Impacting Clinical Tissue level features features factors Host response Factors affecting periodontitis: Smoking Dry mouth Poor oral hygiene 9 Diet rich in cards Hormonal shift Crowded teeth 4 stages/lesions Initial Early Established Advanced 10 5  13/01/2022 INITIAL LESION – commences 2-4 days after plaque accumulation Bacterial features Cellular features Tissue level features Clinical features Host response 11 12 6  13/01/2022 EARLY LESION – commences 4-7days after plaque accumulation Bacterial features Cellular features Tissue level features Clinical features Host response 13 14 7 Initial lesion 2-4 days after plaque acculimation Bacteria present - in acclimated plaque release toxins that make way to underlying connective tissue through intracellular gaps present in cells of junctional epithelium. Initiate inflammatory process but stimulating immune cells within connective tissue - mast cells and neutrophils Release pro inflammatory cytokines (mediators) - histamine and interleukins - they increase vascular permeability and allow plasma fluids to exerdate within sulcus - gingival crevicular fluid Chemotaxis - neutrophil observes to leave blood cells and enter junctional epithelium and gingival sulcus. No obvious changes detected on clinical level - only histological changes - mild vasodilation of blood vessels adjacent to junctional epithelium which is followed by plasma fluids and inflammatory cells within gingival sulcus and increasing gingival crevicular fluid. Early lesion 4-7 days after plaque acculimation Exaggeration of all events that started in initial phase Vascular permeability is increased even more - migration of more inflammatory cells at site of insult Inflammatory cells- Neutrophils, T lymphocytes and macrophages - predominant cells; T lymphocytes and neutrophils Huge number of neutrophils are observed in the connective tissues within the junctional epithelium and gingival sulcus - Neutrophils release cytotoxic enzymes - attempt to kill evading bacteria and destruct nearby tissues such as the collagen fibre bundles of the gingivae. Spaces left behind by destruction of collagen fibres are soon filled by proliferation of junctional epithelium Fibroblasts also show alterations in structure with decreased capacity for collagen production Lymphocytes and macrophages promote development of new blood vessels Gingivae becomes slightly inflammed, bleeding on probing due to increased blood vessel proliferation, plaque present, slothed papilla, gingival sulcus becomes slightly deeper due to destruction of gingival fibres. Established lesion 21 days after plaque acculimation Huge number of infiltrating immune cells within gingival tissues - plasma cells, B lymphocytes and neutrophils - predominant cells: plasma cells and B lymphocytes Neutrophils release matrix metalloproteins and collagenase enzymes as they migrate through dense collagen fibre bundles Collagenase enzymes cause further destruction of collagen fibre bundles Leakage of plasma proteins from blood vessels cause an increased viscosity of blood - reduces blood flow in region - blueish look in esthablished phase Destruction of gingival collagen fibres and intense acclimation of immune cells within junctional and sulcular epithelium contains a large number of immune cells and more permeable to substances in and out of underlying connective tissue. Only loss of collagen - no bone loss present at this stage All stages above are reversible Advanced lesion - irreversible Destruction of collagen fibres further extends into periodontal ligament and alveolar bone Junctional epithelium migrates apically to fill the collagen depleted areas - periodontal pocket formation Deeper periodontal pocket is a great place for further plaque acculimation which is not reachable with normal oral hygiene measures - favourable environment for pathogenic bacteria involved in periodontal disease. Neutrophils predominate in the junction epithelium and periodontal pockets However macrophages, T and B lymphocytes dominate in underlying connective tissue B lymphocytes mature into plasma cells to produce antibodies which work along the complement system to kill bacteria but end up destructing normal periodontal tissues. Tissue destruction results from 2 main sources: inflammatory mediators derived from sub gingival microbes and those derived from host immune response. Although the presence of plaque biofilm is important to initiate an inflammatory response, the majority of tissue destruction comes from severe immune response of the host itself. Inflammatory mediators related to individuals immune system and involved in periodontal breakdown = matrix matalloproteins (MMPs), PGE2 and cytokines. MMPs = are proteolytic enzymes or collagenases that degrade collagen fibres of periodontium, produces buy osteoclasts and fibroblasts. PGE2 = lipid compound primarily derived from plasma membranes from most cells - significantly macrophages and fibroblasts in periodontal disease. Causes vasodilation and induced cytokine production from variety of cells. Results in induction of MMPs, stimulates macrophages to turn into osteoclasts - bone dissolving cells. Cytokines = Interleukin-1 beta and tnf-alpha most important cytokine produced by T lymphocytes and macrophages- they are key inflammatory mediators in periodontal disease. They act as messengers and transmit signals from one cell to another, aid in further recruitment of immune cells in the area of insult. They indirectly promote bone destruction by stimulating sustained inflammation of periodontal tissues. Causes vasodilation and increase recruitment of immune cells, activate neutrophils. Individuals with periodontitis elevated levels of pro inflammatory cytokines and increasing numbers of infiltrating T cells, result in activation of osteoclasts, results in alveolar bone loss. Clinical: Bone loss present Mobility, furcations Periodontal pocketing - true  13/01/2022 ESTABLISHED LESION – 21 days after plaque biofilm accumulation Bacterial features Cellular features Tissue level features Clinical features Host response 15 16 8  13/01/2022 ADVANCED LESION Bacterial features Cellular features Tissue level features Clinical features Host response 17 18 9  13/01/2022 Pathogenesis model of Periodontal Risk factors, genetics, smoking, Disease – Page and systemic health Korman 1997 Antibodies Cytokines PMN’s / Tcells Connective tissue / bone destruction LPS Virulence factors Antigens MMPS, PGE2, TNFa 19 A model of periodontitis pathogenesis (adapted from Meyle & Chapple) 20 10