Periodontal medicine

Periodontal medicine

1. GOOD MORNING 1

2. PERIODONTAL MEDICINE PRESENTED BY : SAHIL SHARMA MDS STUDENT 2

3. Offenbacher 1996 defines periodontal medicine as a rapidly emerging branch of periodontology which focuses on the research of new data establishing a strong relationship between periodontal health or disease and systemic health or disease. 3 INTRODUCTION

4. This means a two-way relationship in which periodontal disease in an individual may have a powerful influence on an individual’s systemic health or disease . Non specific accumulation of bacterial plaque was once thought to be the cause of periodontal destruction, but now it is recognised that periodontitis is an infectious disease associated with predominantly gram negative bacteria. Although pathogenic bacteria are necessary for periodontal disease, they are not sufficient alone to cause the disease. A susceptible host is also required. 4

5. There are many systemic conditions that can modify the host susceptibility to periodontitis . Patients with immune suppression may not be able to mount effective host response to subgingival microorganisms, resulting in more rapid and severe attachment loss. 5

6. Although the potential impact of many systemic conditions on the periodontium is well documented, recent studies done by Seymour et al suggest that periodontal infection may significantly enhance the risk for certain systemic condition or alter the course of systemic condition. 6

7. Acc. To W illiam Hunter in 1900, Oral microorganism- responsible for systemic conditions Restoration instead of extraction, trapping of infectious agents Gingivitis & periodontitis- foci of infection Connection between oral sepsis & resulting systemic condition could be shown by removal of causative sepsis through extraction & observation of improvement in systemic health 7 FOCAL INFECTION THEORY

8. This theory fell into disrepute in 1940’s & 1950’s when widespread extraction failed to reduce or eliminate the systemic conditions to which the supposedly infected dentition has been linked. 8

9. Cardiovascular/ cerebrovascular system Atherosclerosis Coronary heart disease (CHD) Angina Myocardial infarction (MI) Cerebrovascular accident (stroke) Endocrine system Diabetes mellitus 9 Organ system & conditions possibly influenced by periodontal infection

10. Reproductive system Preterm low birth weight infants Preeclampsia Respiratory system Chronic obstructive pulmonary disease Acute bacterial pneumonia 10

11. Well known relationship Study done by Matilla et al found that MI patients had significantly worse dental health than did the controls. This association between poor dental health and MI was independent of the known risk factor for heart disease such as age, hypertension, chlosterol levels, diabetes. Malthaner et al also found an increased risk of angiographically defined CAD in subjects showing greater attachment and bone loss. However after adjusting for other risk factor for the CAD the relationship between the periodontal status and CAD was no longer significant. 11 PERIODONTAL DISEASE & CORONARY HEART DISEASE/ ATHEROSCLEROSIS

12. Associated with atherogenesis & thrombogenesis 12 Ischemic heart disease

13. Increased viscosity of blood → increase risk of thrombus formation → ischemic heart disease & cerebrovascular accident Factors affecting blood viscosity Plasma fibrinogen Plasma lipoproteins White blood cell count von Willebrand factor Increased plasma fibrinigen level is considered as risk factor for cardiovascular disease (Lowe et al). 13

14. 14 Effect of infection on blood viscosity

15. Thrombogenesis Platelet aggregation plays a major role in thrombogenesis . Most cases of acute myocardial infarction are precipitated by thromboembolism Oral organisms may be involved in coronary thrombogenesis 15

16. Thromboembolism mechanism Platelet binds – Streptococcus s anguis and P. g ingivalis ↓ Platelet aggregation – Plalelet Aggregation Associated Protein ↓ Bacterial strains enters the circulation ↓ Forms thromboemboli ↓ Cardiac & pulmonary changes 16

17. It is a focal thickening of the arterial intima , the innermost layer lining the lumen of the vessel , and the arterial media, the thick layer under the arterial intima consisting of smooth muscle, collagen, and elastic fibres . Occur in large & medium sized elastic & muscular arteries Intimal lesion is called atheroma or atheromatous or fibro fatty plaques Protrude into & obstruct vascular lumina 17 Atherosclerosis

18. Periodontitis & atherosclerosis have many potential pathogenic mechanism in common Both have Complex causation Genetic & gender predisposition Share many risk factors, most significant is smoking status Periodontitis, which is a chronic inflammation initiated by microbial plaque can predispose to atherosclerosis. 18

19. 19 Atherosclerosis mechanism

20. 20 Figure showing pathogenesis of atherosclerosis        

21. 21 Influence of periodontal infection on atherosclerosis

22. 22 Cardiovascular & periodontal consequences of hyper responsive monocytes/ macrophage phenotype

23. Direct effects of infectious agents in atheroma formation Indirect or host mediated effects triggered by infection Common genetic predisposition for periodontal disease & atherosclerosis Common risk factors such as life style Mechanism by which infection may contribute to atherosclerosis

24. Direct effects of infectious agents in atheroma formation Studies done by Tonetti M et al, 2007 show Porphyromonas gingivalis is found in carotid and coronary atheromas . Deshpande and colleagues (1998) conducted a study and concluded that P. gingivalis can invade and may proliferate in the endothelial cells Herzberg and Meyer (1996) showing that P. gingivalis is able to induce aggregation of platelets, which is thought to be associated with thrombus formation .

25. Indirect or host mediated effects triggered by infection P eriodontitis induces an inflammatory response, production of acute-phase proteins, such as C-reactive protein and fibrinogen. C-reactive protein and fibrinogen are independent risk factors for coronary artery disease, hence if they are induced by periodontal infection , this may help explain the link between periodontal disease and heart disease .

26. A recent study by Wu and colleagues (1999) using the NHANES III database, found that C-reactive protein and plasma fibrinogen were related to poor periodontal health, which provides support for this hypothesis.

27. Common genetic predisposition for periodontal disease & atherosclerosis Beck JD and colleagues (1996) have provided a model proposing that there is a genetically determined hyper inflammatory macrophage phenotype in periodontal disease, which contributes to the susceptibility for atherosclerosis

28. 28 Potential linkage mechanisms for periodontal disease & myocardial infarction Evidence for the role of inflammatory mediators C-reactive protein (CRP) Smooth muscle cells proximal to apoptotic cells in the arterial plaque produce secretory type II phospholipase which interacts with inverted phospholipid bilayer in the membrane of an apoptotic cell, thus preparing a nidus for CRP to bind. CRP induces local proinflammatory cytokine production & may bind complement either prior to tissue localisation or in situ, thereby enhancing removal of dying cell. Complement activation in turn may precipitate collateral damage.

29. 29 Tumor Necrosis Factor-α TNF - α has been shown to increase the synthesis of triglycerides in the liver and to inhibit lipoprotein lipase. This elevated levels of triglyceride rich glycoproteins and decreased levels of high density lipoprotein cholesterol has been associated with coronary heart disease. Also macrophages and smooth muscle cells expressing TNF –α are present in atherosclerotic plaques, suggesting its role in atherogenesis .

30. 30 Fibrinogen Fibrinogen is an acute phase protein mainly synthesized in the liver in response to IL-6. Fibrinogen levels increase during infections and inflammatory conditions including Periodontitis . IL-1 is considered as one of the important mediators in the pathogenesis of periodontal disease and both fibrinogen and fibrin can stimulate production of IL-1β and protein by binding to CD18 integrin receptors on normal human monocytes .

31. 31 ICAM-1 and VCAM-1 Intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in the firm endothelial cell attachment and transendothelial migration of leucocytes, thus playing a central role in leucocyte recruitment and their function in inflammatory reactions. These molecules act as modulators of cell to cell interactions as activators of certain target cells and possibly, even as neutrophil chemoattractants . These soluble factors have been associated with various inflammatory conditions.

32. Presence of systemic infection before stroke ↓ G reater ischemia & more severe post ischemic neurologic defect . 32 PERIODONTAL DISEASE & STROKE Stroke patients with a preceding infection had a slightly higher levels of plasma fibrinogen & CRP than those without infection

33. Syrjagen et al 1989, found a statistically significant poor level of oral health in patients with ischemic cerebral infarction as compared to controls. Grau & colleagues 1997, reported that poor dental status was associated with cerebral ischemia. Beck & colleagues 1996, provided first longitudinal data relating stroke to oral infections. They found that high mean alveolar bone loss was predictive of subsequent stroke. 33

34. Complex metabolic disorder characterised by chronic hyperglycemia. Diminished insulin secretion, impaired insulin action or a combination of both result in the inability of glucose to be transported from the bloodstream into the tissues which in turn results in high blood glucose level. Alteration in lipid or protein metabolism 34 DIABETES MELLITUS

35. Type 1 diabetes (insulin dependent) Type 2 diabetes (non insulin dependent) Gestational diabetes Others Genetic defects in beta cell function Genetic defects in insulin action 35 Classification

36. Food digestion ↓ ↑ blood glucose ↓ ↑ Insulin secretion ↓ Muscle increases uptake of glucose Muscle & liver store glucose as glycogen Liver prevents glycogen from breaking down into glucose ↓ ↓ blood glucose 36 Insulin control of blood glucose

37. Type 1 diabetes Type 2 diabetes Age of onset Generally < 30 years Generally in adult hood Most common body type Thin or normal stature Obese Race White African American, American Indian Family history Common More common Rapidity of clinical onset Abrupt Slow Pathogenesis Autoimmune beta cell destruction Insulin resistance, impaired insulin secretion, increased liver glucose production Endogenous insulin production None Decreased, normal or elevated Susceptibility to ketoacidosis High Low Treatment may include Diet, exercise, insulin Diet, exercise, oral agents, insulin 37 Characteristic of Type 1 & Type 2 diabetes

38. It is clear from epidemiologic research that diabetes increases risk for & severity of periodontal disease. The increased prevalence and severity of periodontitis typically seen in patients with diabetes, especially those with poor metabolic control led to the designation of periodontal disease as sixth complication of diabetes ( Loe et al ). 38 Periodontal disease & Diabetes mellitus

39. Complications of diabetes mellitus 39 Retinopathy Nephropathy Neuropathy Macrovascular disease Altered wound healing Periodontal disease

40. Taylor et al conducted a study amongst type 2 diabetes patients and concluded that severe periodontitis was associated with significant worsening of the glycemic control over time. He concluded that individual with severe periodontitis at baseline examination were associated with a greater incidence of worsening glycemic control over a period of 2 to 4 years as compared to those without periodontitis at baseline examination. Macrovascular complications were also found to be more amongst individual with severe periodontitis at baseline. 40

41. In diabetic patients with periodontitis , periodontal therapy may have beneficial effect on glycemic control. This is true for patients with with relatively poor glycemic control and advanced periodontal destruction before treatment. Hiltunen et al conducted a study amongst 65 subjects with type 1 diabetes and chronic periodontitis and found that although there was overall improvement in periodontal health after therapy , 35 % of subjects had an improvement in glycemic control after therapy, 37 % had no significant change and 28 % showed worsening of glycemic control. 41

42. 42 Effects of periodontal infection on glycemia Bacterial infections decrease insulin-mediated glucose uptake by skeletal muscle and produce whole-body insulin resistance. Acute endotoxemia and cytokine production, mostly TNF-α and IL- lß , induce insulin resistance and decreased insulin action. The insulin receptor tyrosine kinase , and the action of protein kinase C may, either individually or in combination, mediate some of the insulin effects such as translocation and activation of glucose-transporting proteins.

43. 43 TNF-α has been suggested as the mediator of insulin resistance in infection by suppressing insulin induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), thus impairing insulin action.

44. 44 Effects of periodontal infection on glycemia

45. 45 Effects of periodontal therapy on glycemia Decreased inflammation

46. Treatment with scaling & root planing, surgery, selected tooth extraction & systemic antibiotics resulted in decreased insulin demand. Miller et al 1992, evaluated that scaling & root planing combined with systemic doxycycline therapy for 2 weeks , when given in type I diabetic patients with improved periodontal health also had significant improvement in glycemic control. 46

47. Tetracycline can also be given as tetracycline is known to suppress glycation of proteins & to decrease activity of tissue- degrading enzymes such as MMPs. Diabetes is associated with greatly elevated production of collagenase, low dose doxycycline has been used in treatment of periodontitis in diabetic subjects. Al-Ghazi et al 2003 & Engerbretson et al 2003, reported short term improvements in glycemic control with combination therapy, whereas no change was seen with mechanical therapy alone. 47

48. The international definition of low birth weight adopted by the Twenty-ninth World Health Assembly in 1976 is a birth weight of ‘‘less than 2500 g ’’ Low birth weight can be as a result of both a short gestational period and retarded intrauterine growth . 48 LOW BIRTH WEIGHT (LBW) INFANTS

49. Causes Preterm labor or premature rupture of membranes Smoking, alcohol or drugs use during pregnancy Inadequate prenatal care Race, low socioeconomic status Hypertension, diabetes High or low maternal age Genitourinary tract infection Maternal stress & genetic background Periodontal disease 49

50. Labor is characterized by coordinated uterine contractions leading to cervical dilatation, and finally expulsion of the fetus . In term (‘‘normal’’) labor , rupture of the membranes occurs after initiation of contractions. 50 Mechanism involved in preterm labor & premature rupture of the membranes:

51. 51 The earliest identified events in labor are increases in the bioavailability of prostaglandin E 2 , and in the concentration of receptors for the hormone oxytocin . The increase in oxytocin receptors during labor induces the stretching of the cervix and myometrium which is thought to initiate a neurogenic reflex to the neurohypophysis of the pituitary gland, which acts as positive feedback for oxytocin production.

52. Remote gram- negative infection may play a role in LBW infants Periodontopathic organisms & their products may mediate host cytokine production in target tissues. Collins et al 1994, reported that P.gingivalis during gestation causes significant increase in TNF- a & PGE2. 52 Periodontal disease & Pregnancy outcome

53. Significant correlation between both TNF- a & PGE2 levels, as well as fetal death & growth retardation. Collins et al also evaluated that there was decreased fetal birth weight & increased fetal death after intravenous injections with LPS derived from P.gingivalis. Offenbacher et al 1996 found that women having LBW infants had greater clinical attachment loss than women having NBW infants. 53

54. In a cross sectional study, women having LBW infants had significantly higher levels of A.A, Bacteroides forsythus , P. gingivalis and Treponema denticola in their subgingival plaque . Lopez et al 2002 found that women who received SRP before 28 weeks of gestation, followed by prophylaxis every 2 weeks until parturition, had a LBW rate of 1.8% as compare to women who did not receive periodontal therapy who had LBW rate of 10.1% 54

55. 55 Periodontal infections, serve as reservoirs for Gram-negative anaerobic organisms, lipopolysaccharide (LPS, endotoxin ), and inflammatory mediators. Exposure to oral LPS down-regulates E- selectin expression on endothelial cells and thereby prevents the normal leukocytic margination and diapedesis which would occur in response to a secondary enteric LPS challenge. This raises the possibility that systemic challenge with oral LPS may inhibit normal neutrophil clearance of enteric organisms that may permit a selective overgrowth or invasion of Gram-negative organism within the genitourinary tract. including PGE2 and TNF-α, may pose a potential threat to the fetal -placental unit.

56. 56   Bacterial Vaginosis   Caused by changes in the vaginal microflora in which normally predominant facultative lactobacilli are replaced by Gardnerella vaginalis ; anaerobic organisms, including species of the genera Prevotella , Bacteroides , Peptostreptococcus , Porphyromonas , and others.   Bacterial vaginosis is a known risk factor for preterm labor, premature rupture of membranes, and LBW.   .  

57. 57 The primary mechanism has traditionally been thought to be ascending infection from the vagina and endocervix .   Endotoxin & bioactive enzymes by many organisms associated with vaginosis may directly injure tissue, as well as induce release of proinflammatory cytokines and prostaglandins.  

58. 58 Throughout normal gestation, amniotic prostaglandin levels rise steadily until a sufficient threshold is reached that induces labor and delivery. Maternal infection may cause increased prostaglandin production and may result in labor- inducing levels being achieved before full gestation V arious pro-inflammatory cytokines such as IL-1, IL-6, and TNF α have been found in the amniotic fluid of women with preterm labor. Women with preterm labor often have culture-positive amniotic fluid, even in the absence of clinical infection. Of culture-positive patients, the most commonly isolated species is Fusobacterium nucleatum .

59. Airflow obstruction resulting from chronic bronchitis or emphysema. Bronchial mucosal gland enlarge & inflammatory process occurs in which neutrophils & mononuclear inflammatory cells accumulate within the lung tissue . 59 CHRONIC OBSTRUCTIVE PULMONARY DISEASE

60. Risk factors of COPD Cigarette smoking Genetic conditions Presence of defective alpha-1 antitrypsin Variant alpha-1 antichymotyrpsin Alpha-2 macroglobulin Vitamin D- binding protein 60

61. Share similar pathogenic process Host inflammatory response mounted in response to chronic challenge By bacteria in periodontal disease By factors like cigarette smoke in COPD Neutrophil influx → release of oxidative & hydrolytic enzymes → tissue destruction directly. 61 Periodontal disease & Chronic obstructive pulmonary disease

62. Recruitment of monocytes & macrophages leads to further release of proinflammatory cytokines. Hayes et al (1998) found a positive correlation between advanced alveolar bone loss and COPD. Scannapieco et al 1998 , individuals with poor oral hygiene have been found to be at increased risk for chronic respiratory diseases such as bronchitis & emphysema. 62

63. Infection of the lungs caused by 63 Pneumonia

64. 64

65. Caused by Inhalation of infectious aerosol Aspiration of oropharyngeal organism Streptococcus pneumoniae & H.influenzae Antibiotic therapy is highly successful in resolution of the cases of community acquired pneumonia. Till now no association between periodontal disease & community acquired pneumonia has been found 65 Community acquired bacterial pneumonia

66. Nosocomial pneumonia Gram- negative aerobic organism Many cases by anaerobic bacteria, subgingival environment It is usually caused by the aspiration of oropharyngeal contents, potential respiratory pathogens (PRPs) 66 Hospital acquired bacterial pneumonia

67. Selective decontamination to eradicate PRPs- systemic antibiotics + orally administered nonabsorbable antibiotics PRPs may also originate in oral cavity, dental plaque serve as a reservoir Subgingival plaque harbor PRPs & periodontal pathogens, associated with nosocomial pneumonia. Furthermore, anaerobic organisms from periodontal pocket may serve as a inoculum for suppurative respiratory diseases. 67

68. Scannapieco et al 2003 , concluded that interventions used to improve oral hygiene, such as mechanical tooth brushing & chemical antimicrobials rinses, have a potential to decrease the risk of nosocomial pneumonia in high-risk patients, such as those in intensive care units or those on ventilators. 68

69. Oral pathogens may be aspirated into lung to cause infection Periodontal disease- associated enzymes in saliva may modify mucosal surfaces to promote adhesion & colonization by respiratory pathogens Periodontal disease- associated enzymes may destroy salivary pellicles on pathogenic bacteria Cytokines originating from periodontal tissues may alter respiratory epithelium to promote infection by respiratory pathogens 69 Potential mechanism of action of oral bacteria in pathogenesis of respiratory infection

70. Periodontal disease may affect the host’s susceptibility to systemic disease through subgingival biofilms, acting as reservoirs of Gram negative bacteria, transient bacteremia, release of microbial toxins & as a reservoir of inflammatory mediators. More research is needed to these systemic diseases, & then develop appropriate interventions More research is needed before recommendations can be made to treat periodontal disease as a strategy to prevent or treat CVD, diabetes mellitus, pre-term birth & other adverse pregnancy outcomes & also respiratory diseases. 70 CONCLUSION

71. THANK YOU