Periodontal medicine the updated version.pptx

A complete update on the periodontal medicine including all aspects of pathogenesis

1. Greetings from GSL Dental College, Rajahmundry

2. The current status of periodontal medicine and its relevance in dental practice Dr Ashok K P Prof & Head Dept Of Periodontics GSL Dental College Rajahmundry

3. PERIODONTAL MEDICINE Periodontal Medicine is a rapidly emerging branch of Periodontology , focusing on the wealth of new data, establishing a strong relationship between Periodontal Health or disease and systemic health or disease. William and Offenbacher-2000

4. PERIODONTAL MEDICINE Periodontal Medicine deals with a two way relationship in which periodontal disease in an individual may be a powerful influence on an individual’s systemic health or disease or the more customarily understood role of systemic disease on influencing an individual’s Periodontal Health or disease. William and Offenbacher-2000

5. OLD WINE IN A NEW BOTTLE

6. FOCAL INFECTION THEORY Focal Infection is an idea that a local infection affecting the small area of the body can lead to subsequent infection or symptoms in other parts of the body due either to the spread of infectious agent itself or toxins produced by it. Robert Koch

7. FOCAL INFECTION CHANGING CONCEPTS Hippocrates (460-370BC) – noted a case of rheumatism cured after infected tooth extraction. Benjamin Rush (1745-1813) – recognized relation of oral infection to general health. W.D.Miller (1853-1907) – proposed oral infections as the cause of many diseases.

8. William Hunter (1861-1937) – indicated dental diseases as a cause of what he called “oral sepsis” – that caused rheumatic & other chronic diseases. For major infections oral focus was the periodontium and not periapical disease. G.V.Black – important role of dental profession in preserving general health. Frank Billings, Edward C. Rosenow , Charles H. Mayo – interested in the same concept.

9. Cecil.R (1938) – no improvement in rheumatoid arthritis patients after teeth extraction & tonsillectomy . Williams & Burkett – found no good scientific evidence to support “focal infection theory ”. Many patients with diseases presumably caused by foci of infection have not been relieved by removal of foci Patients with same diseases may not have detectable foci of infection Foci of infection can occur in healthy persons with no ill effects. Journal of the American Medical Association (1952)

10. SYSTEMS BIOLOGY It is the study of interaction between the components of biological systems and how these interactions influence the function and the behavior of that system. Snoep et al-2005

11. SYSTEMS BIOLOGY The living systems are maintained by the continuous flow of matter and energy, and thus any biological system will inevitably be a subsystem of a large one. The key feature of such a system is the interaction among the components.

12. Human organism is a single unit composed of seemingly infinite number of biological processes so intertwined that abnormalities of almost any of its parts or processes have profound effect on multiple other body areas. Vincent Friedwell and Kenneth Kornman (2009)

13. ASSOCIATION AND CAUSALITY

14. ASSOCIATION Association is defined as the concurrence of two variables more often than would be expected by chance . CAUSALITY Causality is defined as the relationship between an event (cause) and a second event (effect) where the second event is understood as a consequence of the first

15. Bradford Hill’s criteria (1971) Strength of association Plausibility Temporality Biological gradient Specificity of association Consistency of the findings

16. RISK FACTOR Risk factor – distinctive characteristics/exposures that increase the probability of disease outcome ( Albandar , 2002). Is any characteristic, behavior, or exposure with a association to a particular disease. The relationship is not necessarily causal in nature. It increases the risk of disease occurrence. It is verified to be associated with disease through longitudinal studies. eg : smoking and periodontal disease

17. Type of Study Ability to ‘prove’ causation 1) Randomised Controlled Trial STRONG 2) Cohort Study Moderate 3) Case-control study Moderate 4) Cross-sectional study WEAK 5) Ecological study WEAK STUDY DESIGN Relative ability of different types of study to ‘prove’ causation NB: Assuming study well-designed & conducted & bias etc. minimised

18. Is Periodontitis unique ? Unusual anatomy of the tooth – The crown is exposed to external environment , whereas the root is within the connective tissues. Non-shedding outer layers of the tooth – facilitates diverse microbial colonization held in proximity to soft tissues of periodontium . Periodontitis is a Biofilm-induced disease – environment very protective for colonizing organisms. Polymicrobial infection- Interplay of many putative organisms

19. Periodontitis disturbs systemic homeostasis Chronic damage of epithelial tissues due to periodontitis may induce the periodontal pocket to ulcerate that allows access to the bloodstream Bacteria and their toxins, cytokines, mediators of inflammation disrupt homeostasis when toxins gain entry to the systemic circulation

20. IS PERIODONTITIS A RISK FACTOR FOR…….?? Cardiovascular disease Diabetes mellitus Adverse pregnancy outcomes Respiratory infections Rheumatoid arthritis Osteoporosis Renal dysfunction Alzheimer’s disease

21. ADVERSE EFFECTS OF PERIODONTAL DISEASE ON CARDIOVASCULAR SYSTEM

22. PERIODONTAL DISEASE Periodontal disease is an immuno inflammatory disease initiated by micro- organisms and characterized by the destruction of the supporting tissues of the tooth

23. CARDIO VASCULAR DISEASES Cardiovascular diseases are the class of diseases that involve the heart or blood vessels. It refers to those related to atherosclerosis (arterial diseases)

24. CARDIO VASCULAR DISORDERS Endothelial Dysfunction Hyper tension Atherosclerosis Coronary heart disease Angina Myocardial Infarction Cerebro Vasclular Accidents Peripheral arterial disease

25. Endothelial dysfunction Accumulation of foam cells Inflammatory cells Smooth muscle cells Fibrous intima Narrow lumen PATHO PHYSIOLOGY OF CVD

26. Mechanism of Atheroma formation

27. In 1989, Mattila & Colleagues found an increase in caries, Periodontal disease, Pericoronitis in patients with recent MI when compared to controls. Many Risk factors for MI were the same for Periodontitis, Mainly Smoking Older male patients Lower SES

28. Plausible theories

29. Specific pathways linking Periodontitis and CVD

30. Bacteria entering the circulation as a result of periodontal infection, dental procedures, and routine tooth care result in varying levels of bacteremia. This may enhance the progression of atherosclerotic cardiovascular disease (red arrow). Inflammatory mediators produced in infected gingival tissues or as part of the hepatic response to periodontal infection may enhance the progression of atherosclerotic cardiovascular disease (blue arrow). Dyslipidemia modulated by periodontal infection primarily affecting the hepatic response may enhance the progression of atherosclerotic cardiovascular disease (green arrow). Biological plausibility of the relationship between the development of athero-thrombotic lesions and periodontal infection.

31. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. “There is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; While in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.” Tonetti MS, Van Dyke TE; working group 1 of the joint EFP/AAP workshop.. J Periodontol . 2013 Apr;84(4 Suppl ):S24-9

32. Stroke/ Ischaemic Cerebral Infarction & Periodontitis

33. Etiology of stroke

34. Periodontitis as a risk factor for stroke

35. Indirect Systemic effects Elevated production of fibrinogen and CRP Atheroma formation

36. Platelet aggregation Platelets selectively bind with some strains of Streptococcus Sanguis and Porphyromonas Gingivalis . Aggregation of platelets is induced by Platelet aggregation associated protein (PAAP) expressed on some strains of these bacteria Thrombus formation Thromboembolism Stroke

37. Association between periodontal disease and stroke George S. Sfyroeras, MD, PhD,a Nikolaos Roussas, MD,b Vassileios G. Saleptsis, MD,b Christos Argyriou, MD,b and Athanasios D. Giannoukas, MSc, MD, PhD, FEBVS,b Athens and Larissa, Greece Conclusions: There is evidence that periodontitis is associated with increased risk of stroke. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity of the studies as well as the differences in periodontitis definition. ( J Vasc Surg 2012;55:1178-84)

38. EFFECT OF PERIODONTITIS ON DIABETES MELLITUS

39. DIABETES Diabetes mellitus is a heterogeneous group of disorders characterized by hyperglycaemia, absolute or relative insulin deficiency or resistance to action of insulin. There is a two way relationship between diabetes and periodontitis.

40. Effect of Diabetes on periodontium Poor periodontal outcomes result from hyperglycemia in diabetes due to changes in : Host response Blood vessels Wound healing Micro-organisms

41. Change in oral Microorganisms SALIVARY FLUX REDUCTION HIGH GLUCOSE CONC IN SALIVA & GCF DEVELOPMENT OF PERIODONTOGENIC FLORA Thus susceptibility of diabetics to periodontal disease is increased

42. Changes in Immune response

43. a)The fibroblast , does not function properly in high-glucose environments. b) The collagen produced by these fibroblasts is susceptible to rapid degradation by MMP enzymes which are elevated in diabetes. Wound healing responses to chronic microbial insult may be altered in those with sustained hyperglycemia, resulting in increased bone loss and attachment loss. Altered wound healing

44. Change in microvascular Integrity

45. Infection Acute systemic Endotoxemia TNF- α +IL- β FFA, LDL,TRG hyperlipidemia Increased serum pro-inflammatory cytokines Diabetes Altered lipid metabolism Insulin resistance Monocyte hyper response Chronic localized Bacteremia Effect of infection on glycemic control

46. Gram negative periodontal infection   Increased insulin resistance Worsened glycemic control Improved glycemic control Improved insulin sensitivity Periodontal treatment Potential effects of periodontal infection and periodontal therapy on glycemia in patients with diabetes.  

47. MECHANISM BY WHICH PERIODONTAL DISEASE MAY INFLUENCE DIABETES

48. Diabetes and periodontal diseases : consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases Overall , there is consistent and robust evidence that severe periodontitis, adversely affects blood glucose levels expressed as HbA1C in individuals with and without diabetes . Moderate-to-severe periodontitis is associated with an increased risk for the development of diabetes . Evidence supports a dose-dependent role for periodontitis and diabetes complications .” Chapple ILC, Genco R, and on behalf of working group 2 of the joint EFP/ AAPworkshop . Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol 2013;40 (Suppl. 14): S106–S112 .

49. Guidelines Good glycemic control, an HbA1c value of less than 6% for most patients, significantly reduces the risk for the serious complications of diabetes, including periodontal disease. Treating periodontal infection in people with diabetes is an important component in maintaining oral health . It may also play an important role in establishing and maintaining glycemic control, and possibly in delaying the onset or progression of diabetes and its complications . Therefore , dental health professionals might fulfill an important role in maintaining or improving the health, and ultimately the quality of life, of individuals with diabetes and GDM, as well as aiding in lessening the immense burden of diabetes and periodontal diseases.

50. When gum disease goes untreated in patients with diabetes, they are put at greater risk for developing long-term complications associated with diabetes, such as CVD and kidney disease. There is a great need for dental and medical practitioners to communicate and partner to facilitate the care of patients with diabetes. The physicians can assist in assessing if their patients are being evaluated by oral healthcare providers, and if not, they should make the appropriate referral.

51. Periodontitis and Adverse Pregnancy Outcome

52. For centuries. dental profession was aware of effect of pregnancy on periodontal health. In recent years due to the work of Offenbacher and associates, it is realized that pregnancy and periodontal disease have a bidirectional relationship and periodontitis can be a risk factor for adverse pregnancy outcome

53. PERIODONTITIS & ADVERSE PREGNANCY OUTCOMES Preterm birth – one of the most complicated and challenging issues in perinatal medicine Spontaneous preterm birth – social (maternal race/ethnicity, poverty) and individual risk factors (underweight, tobacco use, maternal infection). Periodontal disease occurs in 40% of pregnant women ( Lieff et al.,2004)

54. PRE-TERM BIRTH LATE PRE-TERM BIRTH birth <37wks gestational age birth at 34-36wks gestational age VERY PRE-TERM (Martin et al.,2007) Birth <32wks of gestational age EXTREMELY PRE-TERM (Martin et al.,2007) Birth <28wks gestational age LOW BIRTH WEIGHT (WHO 2005) <2500g VERY LOW BIRTH WEIGHT (WHO 2005) <1500g

55. PHYSIOLOGY OF NORMAL LABOUR

56. ABNORMAL LABOUR

57. Landmark study Greg Collins (1994) conducted series of experiments in pregnant hamster animal model. Demonstrated that chronic exposure to oral pathogens like Porphyromonas gingivalis in a chamber model amplifies enhanced fetal-placental toxicity of exposure during pregnancy. Offenbacher et al., (1996) (human study) conducted a case-control study on 124 pregnant or postpartum women. Significant association was observed between periodontal disease and low birth weight.

58. Proposed hypothetical model of the association between periodontal disease and adverse pregnancy outcomes (Ann Acad Med Singapore 2005) Infection (bacterial vaginosis , Periodontitis) Endotoxin/microbiological products Inflammation Pro-inflammatory mediator activation IL-1,TNF-alpha,MMPs Fetal toxicity Pre-term low birth weight Fetal growth restriction

59. Schematic summary of the effects of pro-inflammatory cytokine/matrix metalloproteinases ( MMPs) from periodontal tissues on pregnancy outcomes ( CRP = C reactive protein ; GDM = gestational diabetes mellitus; IUGR = intrauterine growth restriction; PGE2 = prostaglandin E ; PTB = preterm birth).

60. Effect of Periodontal therapy on Adverse Pregnancy outcome

61. Significant Effect of Periodontal Treatment on APO No Significant Effect of Periodontal treatment on APO Lopez et al 2002,2005) Michalowicz et al., (2013) Offenbacher et al., (2006) Alcione Maria Soares Dutra Oliveira (2010) Sadatmansouri et al., (2006) Tarannum & Faizuddin (2007) Nikolaos P Polyzos (2010) Jeffcoat et al (2003)

62. “Although periodontal therapy has been shown to be safe and leads to improved periodontal conditions in pregnant women, case-related periodontal therapy, with or without systemic antibiotics does not reduce overall rates of pre-term birth and low birthweight .” Sanz M, Kornman K; Working group 3 of joint EFP/AAP workshop. Periodontitis and adverse pregnancy outcomes: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol .  2013 Apr;40 Suppl 14:S164-9.  Periodontitis and adverse pregnancy outcomes: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases.

63. PERIODONTAL DISEASE AND PRE-ECLAMPSIA

64. Pre- eclampsia Pre- eclampsia is a maternal multi-organ disease that clinically manifests in the second half of pregnancy by the appearance of hyper-tension and protein urea. Pre- Eclampsia is a disorder unique to pregnancy with prevalence of 2- 3%. It is one of the leading cause of maternal morbidity and mortality in the western world. In recent years a number of studies have explored the relationships between pre- eclampsia and periodontal disease.

65. Pathogenesis Pathogenesis of pre- eclampsia is not completely understood but it is generally accepted that endothelial dysfunction of maternal vascular system plays a key role in the clinical manifestation of disease. It is believed that pre- eclampsia is most likely the result of generalized inflammatory response including activation of inflammatory and endothelial cells. Saftlas et al-1990 Women with diseases associated with chronic low grade inflammation such as diabetes mellitus, hypertension, obesity and arterial diseases are at an increased risk of developing pre- eclampsia . Rodie et al-2004

66. The Periodontal disease is also associated with low grade inflammation. It is hypothesized that patients with periodontal disease have an increased risk of developing pre-eclampsia.

67. Systematic review on periodontal disease & pre- eclampsia ( Alina Kunnen et al.,2010) A generalized inflammatory response plays an important role in the pathogenesis of pre- eclampsia ; periodontal disease might contribute to its pathogenesis. Questionable role of periodontal disease None of RCTs till date reported reductions in pre- eclamptic rate after periodontal therapy during pregnancy. Larger RCTs – required to explore causuality and biologic mechanism.

68. Principles guiding dental treatment during pregnancy Women should be advised to seek oral health care prior to becoming pregnant and throughout gestation. Oral health care is safe and effective during pregnancy First trimester diagnosis (including dental x-rays) is safe. Acute infection, abscess and conditions predisposing to bacteremia and sepsis require prompt intervention regardless of the stage of pregnancy. Necessary treatment can be provided throughout pregnancy. However, the period between the 12 th and 22nd weeks represents the best time to provide oral services, especially scaling and root planning. Elective treatment for conditions considered not progressive may be deferred until after delivery Delay in necessary treatment could result in significant risk to the mother and fetus

69. PERIODONTAL DISEASE AND RESPIRATORY DISORDERS

70. Pneumonia is the inflammation of lung tissues followed by the accumulation of blood cells, fibrin & exudates in the alveoli COPD is characterized by chronic obstruction to airflow with excess production of sputum resulting from chronic bronchitis (CB) and or emphysema. Chronic bronchitis is defined as a condition associated with excessive tracheo -bronchial mucus production to cause cough with expectoration for at least 3 months of the year, for more than 2 consecutive years. Emphysema is defined as the distention of the air spaces distal to the terminal bronchiole with destruction of the alveolar septa

71. VAP – pneumonia developing in 48hrs or more after initiation of mechanical ventilation HAP – pneumonia with an onset 48hrs or more after admission to the hospital

72. Scannapieco’s report (1992) – oral and/or periodontal infection may increase the risk for bacterial pneumonia or COPD

73. Etiopathogenesis Four important mechanisms have been proposed to explain, how oral bacteria can participate in the pathogenesis of respiratory infection. 1. Oral pathogens may be aspirated into the lung. 2. Enzymes in the saliva, which are associated with periodontal disease, may modify mucosal surfaces to promote adhesion and colonization by respiratory pathogens 3. Periodontal disease associated enzymes may destroy salivary pellicles on pathogenic bacteria . 4. Cytokines released during periodontal disease process may alter respiratory epithelium to promote infection by respiratory pathogens Scannapieco FA ,Role of Oral Bacteria in Respiratory Infection, J Periodontol 70, 1999, 793-802 .

74. Aspiration of bacteria from oral cavity Entry into upper airway & lungs Failure of host defense to clear bacteria Lung infection VAP Bacteria adhere to endotracheal tube surface Growth of biofilm Biofilm dislodged & embolize distally to set up foci of infection

75. Systematic reviews AUTHOR FINDING Scannapieco et al., (2003) No sufficient evidence to say there is an association between periodontal disease and COPD Azarpazhooh & Leake (2006) No sufficient evidence to say there is an association between periodontal disease and COPD

76. Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

77. COPD “An association with periodontitis is suggested based on analyses of the NHANES data sets. There appears to be a dose effect, whereby greater periodontal disease is associated with increasing loss of lung function. The primary aetiological factor is smoking as modified by underlying inflammation. Studies of the association between periodontal disease and exacerbations of COPD would be valuable .”

78. Pneumonia “ The association between dental plaque and pneumonia appears to be stronger than for plaque and COPD. The improved oral hygiene reduces the risk of health care-associated pneumonia as suggested by several meta-analyses. The relationship with periodontitis however is not known.” Linden JG ,Herzberg MC, Periodontitis and systemic diseases:a record of discussion of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases , J Periodontol , 84(4 suppl.), 2013, S20-3 .

79. Guidelines 1. remove all dental appliances upon admission to the critical care unit 2. Conduct oral examination initially and daily by a nurse 3. Brush teeth two or three times per day; also floss if possible . 4. Rinse all oral surfaces with antimicrobial rinses. 5. Perform frequent deep suction of oral and pharyngeal secretions as needed,as well as prior to repositioning the tube or deflating the cuff . 6. Remove hard deposits (e.g., tartar/ calculus ) from the teeth, if possible . 7. Request that teeth be professionally cleaned before admission to the hospital for elective procedures

80. Suggestions to health care providers 1.Place the patient’s head to the side or place in semi-reclined body position. 2. Provide deep suction, as needed, in intubated patients to remove oropharyngeal secretions that can migrate down the tube and settle on top of the cuff. 3. Brush teeth using a wet soft toothbrush for approximately one to two minutes. 4. Brush tongue and vestibular surfaces. 5. Apply mouth moisturizer inside mouth and lip balm if needed to reduce risk of oral ulceration.

81. PERIODONTAL DISEASE AND RHEUMATOID ARTHRITIS

82. Rheumatoid arthritis is a chronic destructive inflammatory disease characterized by the accumulation and persistence of an inflammatory infiltrate in the synovial membrane that leads to synovitis and the destruction of the joint architecture resulting in impaired function. RA is a disabling condition, and can lead to long-term joint damage resulting in persistent pain and loss of function in affected areas

83. RHEUMATOID ARTHRITIS AND PERIODONTAL DISEASE The relationship between rheumatoid arthritis (RA) and the progression of inflammatory conditions elsewhere in the body, such as periodontitis, is controversial. While a number of studies have presented conflicting results regarding a relationship between periodontitis and RA, there have been recent reports suggesting a significant association between these two common chronic inflammatory conditions.

84. A. . Clinical appearance of chronic periodontitis C. Clinical appearance of rheumatoid arthritis B. Radiographic appearance of chronic periodontitis D. Radiographic appearance of rheumatoid arthritis

85. Clinically, this condition is characterized by joint swelling, joint tenderness to palpation, morning stiffness, severe motion impairment, progressive degeneration of synovial-lined joints, and radiographic evidence of joint changes.

86. Periodontitis has very similar cytokine profiles to RA, consisting of persistent high levels of pro-inflammatory cytokines, including IL-1 β and tumor necrosis factor-alpha (TNF- α ), and low levels of cytokines which suppress the immuno-inflammatory response such as IL-10 and transforming growth factor- β (TGF- β ). These cytokines, together with low levels of tissue inhibitors of metalloproteinases(TIMPs) and high levels of MMPs and prostaglandin E2 (PGE2), are associated with the active stages of periodontitis.

87. Periodontitis has very similar cytokine profiles to RA, consisting of persistent high levels of pro-inflammatory cytokines, including IL-1 β and tumor necrosis factor-alpha (TNF- α ), and low levels of cytokines which suppress the immuno-inflammatory response such as IL-10 and transforming growth factor- β (TGF- β ). These cytokines, together with low levels of tissue inhibitors of metalloproteinases(TIMPs) and high levels of MMPs and prostaglandin E2 (PGE2), are associated with the active stages of periodontitis.

88. Periodontitis has very similar cytokine profiles to RA, consisting of persistent high levels of pro-inflammatory cytokines, including IL-1 β and tumor necrosis factor-alpha (TNF- α ), and low levels of cytokines which suppress the immuno -inflammatory response such as IL-10 and transforming growth factor- β (TGF- β ). These cytokines, together with low levels of tissue inhibitors of metalloproteinases (TIMPs) and high levels of MMPs and prostaglandin E2 (PGE2), are associated with the active stages of periodontitis.

89. In both rheumatoid arthritis and periodontitis, inflammation is likely initiated by antigen stimulation (in the form of peptide or virulence factors), and the subsequent cascade of acute and chronic inflammation leads to a vicious cycle of continuous release of pro-inflammatory mediators perpetuated by the host’s own cells. Both the resident cells (synovial cells and keratinocytes in rheumatoid arthritis , fibroblasts and osteoblasts in periodontitis ) and the migrating inflammatory cells are active players responsible for the destruction observed in these two chronic inflammatory diseases

90. Emerging evidence suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa. Hence, the possibility exists that both conditions result from a common underlying dysregulation of the host inflammatory response.

91. Reports of an epidemiological association with periodontal disease , including the NHANES data set and case-control studies, are inconsistent. Animal studies provide biological plausibility. (Kinloch et al. 2011). In human rheumatoid arthritis, antibodies against citrullinated proteins and peptides are often detected in the blood reflecting the enzymic conversion of arginine residues to citrulline in certain proteins. Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

92. Biological plausibility for an association with periodontitis is also reflected in the detection of citrullinated proteins in inflamed gingiva, which may be associated with elevated auto-antibodies to self-antigens (Nesse et al 2012)

93. The Humoral Immune Response to Oral Bacteria Provides a Stimulus for Development of Rheumatoid Arthritis Periodontal infection ▼ Citrullination of proteins by P. gingivalis ▼ Production of autoantibodies to citrullinated proteins ▼ Cross reactivity with cartilage components ▼ Auto-immunity to self-antigens ▼ Rheumatoid arthritis

94. While causality between the two diseases is very unlikely, the fact that both diseases can impact each other is becoming apparent. Thus , it is proposed that these two diseases can exist as a manifestation of generalized dysregulation of the immune and inflammatory responses . E arly evidence has suggested that treatment of periodontitis can reduce the clinical symptoms of rheumatoid arthritis . Therefore , early intervention to prevent periodontal destruction occurring in individuals with rheumatoid arthritis should be considered

95. Periodontitis and Chronic Renal Disease

96. CKD is associated with many physiologic changes that might contribute to the development of periodontal disease. There are several documented physiologic changes in oral tissues that have been associated with CKD . These include xerostomia , decreased salivary pH levels, decreased mineralization,and loss of the lamina dura . Additionally, some of the medications commonly prescribed to CKD patients may increase the risk of developing periodontal disease

97. Oral manifestations of CKD

98. Effect of Periodontitis on CKD 1. Systemic inflammation due to periodontitis can affect the kidneys 2. Bacteria from plaque can invade the endothelium of kidney forming atheromatous lesions, thus decreasing blood flow to the organ 3. CRP Levels ↑ and levels of albumin in blood ↓ The authors demonstrated that periodontal disease was associated with an increased risk of all-cause death in CKD patients. Zhang , J., Jiang, H., Sun, M.  et al.  Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies.  BMC Nephrol   18,  269 (2017). https:// doi.org/10.1186/s12882-017-0680-9 Arsalan Wahid, Saima Chaudhry, Afifa Ehsan , Sidra Butt, Ayyaz Ali Khan Bidirectional Relationship between Chronic Kidney Disease & Periodontal Disease . Pak J Med Sci . 2013 Jan-Mar; 29(1): 211–215

99. Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases The association between chronic kidney disease (CKD) and periodontitis in several studies is statistically significant and consistent. Although hypertension and diabetes are the primary aetiological factors, periodontitis is hypothesized to modify both these aetiological factors and consequently the presentation of CKD.

100. Treatment Guidelines A primary objective of periodontal therapy is the local elimination of Gram-negative bacteria and their products. In patients with moderate to severe periodontitis , decreased Gram-negative bacterial load through periodontal therapy will also decrease systemic inflammation. Antibiotic prophylaxis before the dental appointment may be considered. Dental appointments should be scheduled the day after hemodialysis sessions in view of the heparin used during hemodialysis . Among analgesics, postoperative use of acetaminophen is considered safe but nonsteroidal anti- inflammatory drugs should be avoided.

101. Periodontitis and Alzheimer’s disease

102. AD was named after Alois Alzheimer, a German psychiatrist and pathologist working in Frankfurt. Alzheimer’s disease (AD) is one of the leading causes of dementia. Two types of AD are recognized. Early onset AD is present in less than 5 % of the population and is genetically determined. Late onset or sporadic AD(LOAD ) is the most prevalent type of AD and is believed to result from the interaction of multiple genetic and environmental factors. The risk factors recognized are : cerebrovascular disease,hypertension , diabetes, obesity, smoking, depression, psychological stress, and history of head trauma. Clinical features include loss of memory, difficulty in planning and executing tasks, inability to recognize faces and orient objects, difficulty in communicating, and behavior changes.

103. Pathogenesis of AD The pathologic hallmarks of AD are the presence of senile plaques, neurofibrillary tangles , neuronal and synaptic dysfunction, and neuronal loss. The senile plaques found in the brain parenchyma contain extracellular aggregates of amyloid β-peptide (A β ) . Macroscopically, neuronal loss and brain atrophy occurs in several sites including the hippocampus and temporal and parietal lobes resulting in the thinning of the cortex and enlargement of the ventricles . The misfolded proteins hyperphosphorylated tau ( ptau ) and amyloid β (Aβ) in the brain progressively sequester their native counterparts, leading to a breakdown in neuronal structure and function.

104. Periodontal disease & Alzheimer’s -the connection ? Bacteremia can occur during manipulations of the oral tissues and daily procedures such as flossing,brushing and mastication particularly when periodontitis is present. Under normal physiologic conditions, bacteremia lasts approximately 30 min until cleared by the immune system. However , if the immune response is weakened, keystone pathogens such as P. gingivalis and T. denticola can evade, subvert the immune system, and metastasize at distant sites such as the brain and induce local inflammation. Several periodontal species can invade proximal tissue. By invading monocytes, bacteria can use these cells as transport mechanisms to reach the brain. Riviere et al. detected six different periodontal treponemes in the brains in more than 90 % of the 16 AD cases analyzed.

105. The influences of genetic, proteinaceous , environmental and inflammatory factors that may contribute to the initiation and progression of Alzheimer disease (AD).

106. Periodontal disease and the risk of Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Xin HU,1 Jing ZHANG , 1 Yulan QIU1 and Zhaonan LIU 2021 Thirteen eligible studies, of which eight reported AD (291 114 participants) and eight reported MCI (4805 participants), were included in this meta-analysis. PD was related to an elevated risk of AD and cognitive impairment, and that it should receive early intervention.

107. Management Currently, two groups of drugs are used, acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Acetylcholinesterase inhibitors act by preventing acetylcholine degradation, thus increasing the concentration of acetylcholine in the synaptic cleft and prolonging cholinergic neurotransmission. N-methyl-D-aspartate (NMDA) receptor antagonists interfere with the sustained activation of NMDA receptors thus facilitating neuronal function . Oral complications are not commonly encountered for acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Due to cognitive decline and associated functional deficits, dental plaque control progressively deteriorates in those who have AD.

108. Periodontitis and stress

109. Chronic stress is unpleasant, decreases performance and can lead to mental and physical problems, the intensity of which depends on the perception, processing and coping behaviour of the individual. stress has been shown to affect the hormones’ ability to regulate the inflammatory response . In chronic stress conditions, under the effect of stress hormones such as cortisol, there is simultaneous enhancement and suppression of the immune system via alterations on cytokine secretion by T-helper ( Th ) 1 and Th2 cells.

110. In the late 1990s, Genco et al , in a cross-sectional study, reported that stress associated with financial difficulties and poor coping mechanisms, is a significant risk indicator for more severe periodontitis.

111. Periodontitis and Stress

112. SYSTEMIC DISEASES ASSOCIATED WITH PERIODONTAL DISEASE Alzheimers disease Aneamia Atheroschlerosis Auto-immune disease Cancer Chronic obstructive pulmonary disease Colon cancer Crohns disease Death Dementia Diabetes Dry mouth Endometriosis Erectile dysfunction Fatigue Fever Fibromyalgia Gastro- oesophageal reflux disease Hypertension Infertility Inflammatory bowel disease Intellectual function Leukemia Low birth weight Lung cancer Lupus Metabolic syndrome Miscarriage Mouth cancer Multiple sclerosis Obesity Obstructive sleep apnea Osteoporosis Pneumonia Polycystic ovaries Pre-eclampsia Premature birth Psoriasis Renal disease Rheumatoid arthritis Stroke Stomach ulcers Mark Bartold Editor, Australian Dental Journal ,2012

113. Conclusion Both dental and nondental healthcare practitioners, such as physicians, nurses, and allied healthcare providers , share in the responsibility to educate the public regarding the significance of oral health in achieving and sustaining whole-body health. Although there is much that is still inconclusive about certain oral-systemic relationships , there does exist sufficient evidence of the relationship between periodontal disease and its role in amplifying systemic inflammation and increased risk for heart disease, stroke , adverse pregnancy outcomes, complications of diabetes, and increased risk for respiratory infections in institutionalized patients. Patients need to be counseled to provide information about oral health—especially when gum disease has been diagnosed—to their other medical providers.

114. Thanks to Dr Meenu Merry C Paul Principal, Malabar Dental College

115. Dr Shabeer Ahamed Professor & Head Dr Jeethu John Jerry Professor Dr Hasbeena and Dr Ann

116. References 1. Periodontitis and systemic diseases Clinical evidence and biologic plausibility. J Hirschfield and Ian LC Chapple 2021. 2. A Clinician’s guide to systemic effects of periodontal diseases by Ronald C Craig And Angela Kramer 3 . Periodontal disease and overall health A Clinician’s Guide by Robert Genco 4. Oral signs of systemic disease by Nasim Fazel 5. Periodontics, Medicine, Surgery and Implants by Louis F Rose

117. Thank you