13. Etiopathogenesis of Perio Disease I.pptx

The main etiological factor of periodontal disease is the bacteria, which are capable of activating the innate immune response of the host inducing an inflammatory response. The evolution of this inflammatory response ends in the destruction of periodontal tissues. For this reason, it is important to understand the different molecular and cellular mechanisms of the pathogenesis of periodontal disease, with the purpose of making an opportune diagnosis and appropriate treatment
and prognosis.
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1. Good Morning

2. ETIOPATHOGENESIS OF PERIODONTAL DISEASE Presented by : DR. AISHWARYA S. IKHAR Post Graduate Student DEPARTMENT OF PERIODONTOLOGY AND IMPLANT DENTISTRY

3. Contents Etiology of periodontal disease Factos associated in the etiology Local factor Sytemic Fcator Pathogenesis of periodontal disease Histopathalogy of periodontal disease Clinically healthy gingiva Hisopathology of gingivitis and periodontitis Inflamatory response in periodontal disease Microbial Virulence factor Host immun - inflammatory response Immune responses in periodontal pathogenesis Linking of periodontal disease to clinical signs Conclusion

4. Introduction The two common diseases affecting the periodontium: The first is gingivitis, which is defined as inflammation of the gingiva in which the connective tissue attachment to the tooth remains at its original level . The disease is limited to the soft-tissue compartment of the gingival epithelium and connective tissue. The second is periodontitis, which is an inflammation of the supporting tissues of the teeth with progressive attachment loss and bone destruction.

5. Etiology of periodontal disease The clinical manifestations of periodontal disease result from a complex interplay between bacteria found in dental plaque and the host tissues. Etiological factors in periodontal disease are classified into two broad categories, depending on their specific origin.

6. Local Factors

7. WHO in 1978 defined “dental plaque as specific but highly variable structural entitiy resulting from sequential colonization and growth of microorganism on the surface of teeth and restoration consisting of microorganism of various strain and species are embedded in extracellular matrix, composed of bacterial metabolic products and substance from saliva and blood.” It can be also defined as soft tissue that form the biofilm adhering to the tooth surface or other hard surface in the oral cavity, including removable and fixed restoration. 1 . Dental Plaque

8. Plaque Composition Dental plaque is composed primarily of micro-organism (85% gram positive amd 15% gram negative ) Organic and inorganic component in the intercellular matrix Organic constituents: polysaccharides, proteins, glycoproteins and lipid material. Inorganic component: calcium, phosphorus and other minerals such as sodium, potassium and fluoride.

9. Nonspecific plaque hypothesis:- Proposed by Walter J Loesche . Periodontal disease results from the elaboration of noxious products by the entire plaque flora. b. Specific Plaque Hypothesis:- Only certain plaque is pathogenic and its pathogenicity depends on the presence or increase in specific microorganisms. Association between plaque microorganisms and Periodontal Diseases

10. c. Ecological plaque hypothesis :- In 1991 PD Marsh proposed ecological concept of plaque formation . Periodontitis is an opportunistic endogenous infection due to ecological shift in the plaque biofilm involving predominant transition of gram positive facultative anaerobic bacteria to gram negative obligate anaerobic bacteria.

11. 2. Dental Calculus Albucasis , Arabian physician and surgeon (986-1013 AD) put forth the significant association between calculus and dental disease. According to current knowledge, dental plaque is considered as the precursor of calculus which exist in the form of mineralized plaque.

12. Role of Calculus in disease Calculus may be harmful both physically and chemically. It causes periodontal destruction in following manner: Bring bacterial overlay closer to the supporting tissue. In interferes with local self cleansing mechanism. It provides nidus for continuous plaque accumulation. It makes plaque removal difficult.

13. Deficiencies in the quality of dental restorations or prostheses are contributing factors for gingival inflammation and periodontal destruction. Restorative dentistry: Laceration of gingiva due to improper use of rubber dam clamps, matrix band and bur causing varying degree of mechanical trauma and inflammation. Prosthesis: Poorly designed clasp, prosthesis saddle and pontics can directly traumatized periodontal tissue. Orthodontic procedure: It directly injures gingiva due to use of extended bands, chemical irritation by exposed cement and by creating extensive unfavourable forces. 3. Iatrogenic Factors

14. 4. Malocclusion Crowded/ malaligned teeth are always difficult to clean as compared to properly aligned teeth. In deep bite maxillary incisors impinge on mandibular labial gingiva or on palatal leading to gingival inflammation

15. 5. Tobacco/smoking The smokers had more sites with: Deep pockets, greater attachment loss and severe periodontal disease. Effects of tobacco use: Diminish host response and increase disease susceptibility. Less numbers of T- lymphocytes and less antibody production and serum levels of IgG. Reduce serum IgG antibobies to P. intermedia and F. nucleatum . Diminish neutrophils chemotaxis, phagocytosis or both. Nicotina decrease gingival blood flow.

16. Smokers have significantly elevated risks of all‑cause mortality and developing a variety of pathological conditions. A direct causal relationship between smoking exposure and the prevalence and the severity of periodontal disease has been firmly established

17. Systemic Factors

18. DIABETES MELLITUS Diabetes mellitus is a clinically and genetically heterogeneous group of metabolic disorders manifested by abnormally high levels of glucose in the blood. The hyperglycemia is the result of a deficiency of insulin secretion caused by pancreatic Beta cell dysfunction or of resistance to the action of insulin in liver and muscle or a combination of these . ENDOCRINE DISORDERS AND HORMONAL CHANGES.

19. CLINICAL SIGNS & SYMPTOMS • Polyuria (excessive urination) • Polydipsia ( excessive thirst) • Polyphagia (excessive hunger) • Unexplained weight loss • Changes in vision • Fatigue, weakness • Irritability • Nausea COMPLICATIONS Retinopathy Nephropathy Neuropathy Macrovascular disease Altered wound healing Periodontal disease( Loe H 1993 Periodontal disease is the sixth complication of diabetes mellitus.). Ketoacidosis (usually associated with severe hyperglycemia in Type I diabetes) Hyperglycemic hyperosmolar state Hypoglycemia

20. ORAL MANIFESTATIONS OF DIABETES Xerostomia Greater susceptibility of oral tissues to trauma More opportunistic infections (e.g., Candidiasis) Greater accumulation of plaque Greater susceptibility to periodontal disease Greater risk of developing periodontal abscesses when periodontitis is present Delayed healing Oral paraesthesia, including burning mouth or tongue Altered taste sensations

21. EFFECTS OF DIABETES ON THE PERIODONTIUM GINGIVITIS •Erythema, oedema, •Bleeding on probing, •Gingival exudates. PERIODONTITIS •Greater attatchment loss & bone loss ( Emrich LJ 1991, Shlossman M 1990). •Multiple periodontal abscess •Loosened teeth

22. HOST DEFENSE ALTERATIONS The function of immune cells, including neutrophils, monocytes, and macrophages, is altered in diabetes (American Academy of Periodontology 1999). Neutrophil adherence, chemotaxis, and phagocytosis are often impaired (Manouchehr-Pour M 1981). Monocytes from diabetic subjects produce elevated levels of TNF- α in response to antigens from Porphyromonas gingivalis (Salvi GE 1997). ALTERATIONS IN CONNECTIVE TISSUE METABOLISM Impaired osseous healing and bone turnover ( Loder RT 1988, Tisdel CLn 1995, White CB 2003). Inhibition of osteoblastic cell proliferation and collagen production -reduced bone formation - poor newly formed bone (Gooch HL 2000, Beam HA 2002, Lu H,2003). Increased rate of apoptosis of fibroblasts & osteoblasts (He H, Liu R 2004). More severe periodontal attachment loss

23. Diabetes affects osteoclast and osteoblasts in the periodontium in different ways, such as by increasing the expression of inflammatory mediators and RANKL/ osteoprotegerin (OPG) ratios and by enhancing the levels of AGEs and ROS.

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25. FEMALE SEX HORMONES

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27. HYPERPARATHYROIDISM 25% to 50% of hyperparathyroidism patients has associated oral changes, Malocclusion. Tooth mobility Radiographic evidence of alveolar osteoporosis with closely meshed trabeculae Widening periodontal space Absence of the lamina dura Radiolucent cyst like spaces.

28. WBC Involved in inflammatory reactions for cellular defence Proinflammatory cytokine release RBC Gas exchange Nutritional supply to the periodontal tissues and platelets. Normal hemostasis Recruitment of cells during inflammations and wound healing HEMATOLOGIC DISORDES AND IMMUNE DEFICIENCIES

29. Abnormal bleeding from the gingiva or other areas of the oral mucosa that is difficult to control is an important clinical sign. Petechiae Ecchymosis(Soft palate) Deficiencies in the host immune response may lead to severely destructive lesions.

30. GENETIC DISORDERS T here are challenges to develop clinically relevant diagnostic or screening tests for chronic periodontal diseases, as genetic polymorphisms that contribute to disease susceptibility are individually not deterministic of disease. Single genes may contribute to susceptibility, but since we have many interactions at the gene-gene and the gene-environmental levels, the real contribution to disease outcome might not be decisive.

31. 36 Although it is possible to perform genetic testing for several syndromic forms of periodontitis, there is no evidence that mutations in the genes responsible for these conditions are responsible for the more prevalent forms of non- syndromic aggressive or chronic periodontitis . A number of genetic polymorphisms have been studied for their association with chronic periodontitis, including several interleukin (IL) genes; the vitamin D receptor; the FcγRIIIb-NA1 gene; the tumor necrosis factor-β gene; and several human leukocyte antigen (HLA) variants. However , none have proven to be strongly predictive as diagnostic or prognostic markers to identify patients within the general population who are at risk, hampered by population heterogeneity and different disease criteria.

32. Psychological stress might play a role as an aetiological agent of periodontal disease. (Dean and Dean 1945 and Schluger 1949). STRESS AND PSYCHOSOMATIC DISORDERS

33. It is important to remember that although stress may predispose an individual to more destruction from periodontitis, the presence of periodontal pathogens remains as the essential etiologic factor. It affects the oral cavity by 1) Development of habits that are injures to the periodontium as grinding or clenching the teeth, nibbing on foreign objects as pencils, nail biting of excessive use of tobacco. 2) Direct effect to the autonomic nervous system on the psychologic tissue balance.

34. 1.There are no Nutritional deficiencies that by themselves may cause Gingivitis or Periodontitis 2. There are Nutritional deficiencies that produce changes in oral cavity. Changes include alterations of tissue of lips, oral mucosa, gingiva and bone. Vitamin Deficiency Fat soluble : A,D,E,K Water soluble: B,C NUTRITIONAL DEFICIENCIES

35. Vitamin A Major function is to maintain health of epithelial cells of skin & mucous membrane. Prevent microbial invasion by maintaining epithelial integrity Deficiency leads to – Hyperkeratosis, Hyperplasia of gingiva, Increased pocket formation, Proliferation of Junctional epithelium, Retardation of wound healing

36. Vitamin D Essential for absorption of Ca from GIT and maintenance of Ca- P balance Deficiency Rickets in children, osteomalcia in adults Animals – Osteoporosis of alveolar bone Vitamin E Serves an Antioxidant to prevent free radical reactions Protect cells from Lipid Peroxidation Cell membranes which contain highest content of Polyunsaturated Fatty Acids are major site of Vitamin E deficiency No direct relation have been found between Vitamin E deficiency and Oral Disease . Systemic Vitamin E have been shown to accelerate gingival wound healing .

37. Vitamin C or Ascorbic acid Deficiency Defective formation and maintenance of collagen Impairment or cessation of Osteoid formation Impaired Osteoblastic function Increased capillary permeabilty Susceptiblity to traumatic hemorrhages Hyperactivity of contractile element of peripheral blood vessels

38. CLINICAL MANIFESTATION Hemorrhagic lesions into muscles & extremities, joints, nail beds Petechial hemorrhages around hair follicles Susceptibilty to infections Impaired healing Bleeding, swollen gums and loosened teeth Vitamin C deficiency may aggravate the gingival response to dental plaque and worsen the edema , enlargement and bleeding. Acute vitamin C deficiency does not cause or increase the incidence of gingival inflammation, but it does increases its severity.

39. Pathogenesis of periodontal disease

40. Understanding periodontal pathogenesis is key to improve management strategies for this common to complex disease. According to Merrian Websters collegiate dictionary the word pathogenesis is defined as: “the origination and the development of the disease.” It is a step-by-step process that leads to the development of a disease, resulting in a series of changes in the structure and function. It is the process by which the etiologic factor causes the disease. Carranza 13 th edition

41. Histopathalogy of periodontal disease Clinically healthy tissues 47 Inflamed gingival and periodontal tissues.

42. 1. Clinically Healthy Gingival Tissues Clinically healthy gingival tissue is not inflamed, pink in appearance, not swollen and firmly attached to the underlying tooth/bone, with minimal bleeding on probing. Dento -gingival junction Epithelial portion Connective tissue portion

43. “The epithelial portion” Gingival Epithelium Stratified squamous keratinized epithelium. Continuous with the sulcular epithelium at the gingival crest/gingival margin. Covers the gingiva and forms the clinically visible gingival tissues. Covers both the free and attached gingival tissues.

44. Sulcular Epithelium Stratified squamous epithelium and Nonkeratinized. Faces the tooth surface but is not attached to it. Forms the soft tissue lining of the gingival sulcus or periodontal pocket.

45. Junctional Epithelium Forms the epithelial attachment between the gingiva and the tooth. Nonkeratinized and forms the floor of the sulcus/pocket. Wraps around the tooth like a collar, in health following the morphology of the cementoenamel junction (CEJ). Wider at the floor of the sulcus (15-30 cells thick) and tapers apically to 3-4 cells thick. Comprised of layers of flattened squamous cells oriented parallel to the tooth surface. The surface cells attach to the tooth surface via hemidesmosomes. The basal lamina differs from other basal laminae that oppose connective tissue in that type IV collagen is absent.

46. 52 “Connective Tissue” The connective tissue component of the dentogingival unit contains densely packed collagen fiber bundles (mixture of type I and III collagen fibers ) that are arranged in distinct patterns that maintain the functional integrity of the tissues and tight adaptation of the soft tissues to the teeth. 52

47. It is important to note that even in clinically healthy gingiva, the gingival connective tissue contains at least some inflammatory cells, particularly neutrophils. Neutrophils continually migrate through the connective tissues and pass through the junctional epithelium to enter the sulcus/pocket . Page and Schroeder in 1976 .

48. Histopathology of Gingivitis and Periodontitis Vasodilatation and increased vascular permeability leads to increased leakage of fluid out of the vessels, and facilitates the passage of defense cells from the vasculature into the tissues which appear erythematous and edematous . Infiltration of the connective tissues occurs by numerous defense cells, particularly neutrophils, macrophages, plasma cells, and lymphocytes. As a result of accumulation of defense cells and the extracellular release of their destructive enzymes There is disruption of the normal anatomy of the connective tissues resulting in collagen depletion and subsequent proliferation of junctional epithelium

49. The landmark studies of Page and Schroeder 1976 Initial Lesion • Slightly elevated vascular permeability and vasodilation. • GCF flows out of the sulcus. • Migration of leukocytes, primarily neutrophils, in relatively small numbers through the gingival connective tissue, across the junctional epithelium, and into the sulcus.

50. Early Lesion Increased vascular permeability, vasodilation, and GCF flow. Large numbers of infiltrating leukocytes (mainly neutrophils and lymphocytes) Degeneration of fibroblasts. Collagen destruction, resulting in collagen depleted areas of the connective tissue. Proliferation of the junctional and sulcular epithelium into collagen-depleted areas.

51. Established Lesion Dense inflammatory cell infiltrate (plasma cells, lymphocytes, neutrophils). Accumulation of inflammatory cells in the connective tissues. Elevated release of MMPs and lysosomal contents from neutrophils. Significant collagen depletion and proliferation of epithelium. Formation of pocket epithelium containing large numbers of neutrophils.

52. Advanced Lesion Predominance of neutrophils in the pocket epithelium and in the pocket. Dense inflammatory cell infiltrate in the connective tissues (primarily plasma cells). Apical migration of junctional epithelium to preserve intact epithelial barrier. Continued collagen breakdown resulting in large areas of collagen depleted connective tissue. Osteoclastic resorption of alveolar bone.

53. 59 INFLAMMATORY RESPONSES IN THE PERIODONTIUM

54. 62 COMPLEMENT SYSTEM

55. 63

56. COMPLIMENT FUNCTION

57. C1q C2 C4 2a 2b 4b 4a C3-convertase C3 C3a C3b C5-Convertase C3a binds to receptors on basophils and mast cells triggering them to release there vasoactive compounds (enhances vasodilation and vasopermeability) - ANAPHYLATOXIN C5 C5a C5b C5a is a: Potent anaphylatoxin Chemoattractant for neutrophils C6 C7 C8 C9 Classical Pathway

58. C3 C3b C3a Anaphylatoxin B D Bb Ba C3 C3a C3b C5-Convertase C3-Convertase C5 C5a C5b Alternative Pathway C6 C7 C8 C9

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60. 70 Periodontal diseases are inflammatory diseases in which microbial etiologic factors induce a series of host responses that mediate inflammatory events. In susceptible individuals, dysregulation of inflammatory and immune pathways leads to chronic inflammation, tissue destruction and disease .

61. 71 Physiologic inflammation is a well orchestrated network of cells, mediators and tissues. It is very important to consider the inflammatory⁄immune response as a whole, rather than many different modules working separately . As disease appears to be the result of loss of regulation and a failure to return to homeostasis , it is important to achieve a more complete understanding of the molecular and cellular events in this complex system.

62. 72 Carranza’s Clinical Periodontology; 10th Ed., Chapter 12 Immunity and Inflamamtion : Basic Concepts 209-227 Textbook Of Periodontics By Shalu Bathla . Jalaluddin , Mohammad. (2016). Textbook of medical physiology: 11th Ed., Arthur C. Guyton, John E. Hall, Chapter 34, Resistance of the Body to Infection: II. Immunity and Allergy Int. J. Mol. Sci. 2012, 13, 4295-4320; doi:10.3390/ijms13044295 Yan X, Wu Z. Evidence-Based Complementary and Alternative Medicine ; 2020, Article ID 4517587, 9 pages https:// doi.org/10.1155/2020/4517587 Ali cekici , alpdogan kantarci , hatice hasturk & thomas e. Van dyke. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 2000, Vol. 64, 2014, 57–80 REFERENCES