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Systemic periodontology

Systemic Peridoontology, link between systemic health and periodontology, diabetes and periodontology, Pregnancy and Peridotology,Nutrition and periodontology

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Systemic periodontology

  2. 2. INTRODUCTION  Periodontitis is a chronic bacterial infection of the supporting structures of the teeth.  Clinical and basic research over the past several decades has lead to an improved understanding and appreciation for the complexity and pathogenesis of periodontal diseases.  Host response varies between the individuals and an altered, deficient or to bacterial pathogens may lead to more severe forms of disease.  Furthermore, Systemic disorders and conditions alter host tissues and physiology, which may impair host’s barrier function and immune defense against periodontal pathogens creating opportunities for destructive periodontal disease.  It is important to recognize that these disorders and conditions themselves do not cause periodontitis, but they may predispose, accelerate or increase its progression.
  3. 3. Hormonal changes Endocrine Influences Hematologic Disorders Immunodeficiency Disorders Genetic Disorders Stress & Psychosomatic Disorders Nutritional Influences Medications Other Systemic Conditions Various systemic factors that play role in etiology of periodontal disease are as follows:
  4. 4. ENDOCRINE DISORDERS & HORMONAL CHANGES  Endocrine disturbances and hormone fluctuations affect the periodontal tissues directly, modify the tissue response to local factors, and produce anatomic changes in the gingiva that may favor plaque accumulation and disease progression. DIABETES MELLITUS  It is a complex metabolic disease characterized by chronic hyperglycemia.  Diminished insulin production, 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 levels and excretion of sugar in the urine.  Lipid and protein metabolism are also altered in diabetes. An estimated 23.6 million individuals (children and adults), or 7.8% of the United States (US) population, have diabetes. (CDC 2008)
  5. 5. TYPE I DIABETES TYPE II DIABETES insulin-dependent diabetes mellitus (IDDM) non–insulin-dependent dia- betes mellitus (NIDDM) caused by a cell-mediated autoimmune destruction of the insulin- producing beta cells of the islets of Langerhans in the pancreas, which results in insulin deficiency. caused by peripheral resistance to insulin action, impaired insulin secretion, and increased glucose production in the liver. The insulin- producing beta cells in the pancreas are not destroyed by cell-mediated autoimmune reaction. accounts for 5% to 10% of all cases of diabetes and most often occurs in children and young adults. most common form of diabetes, accounting for 90% to 95% of all cases, and usually has an adult onset. It has a marked tendency toward ketosis and coma Ketosis and coma are uncommon. not preceded by obesity generally occurs in obese individuals requires injected insulin to be controlled controlled by diet and oral hypoglycemic agents. DIFFERENCES BETWEEN TYPE I AND II
  6. 6. CLINICAL SYMPTOMS:  The typical signs and symptoms of diabetes are polyuria, polydipsia, polyphagia, weakness and fatigue.  These features are more pronounced in type 1 than in type 2 DM, and are a result of hyperglycemia. Complications of Diabetes Mellitus  Retinopathy  Nephropathy  Neuropathy  Macrovascular disease( Cardiovascular and Cerebrovascular complications)  Altered wound healing  Periodontal disease [Loe H: Periodontal disease: The sixth complication of diabetes mellitus. Diabetes Care 1993; 16(suppl 1):329.]
  7. 7.  ORAL MANIFESTATIONS OF DIABETES:  Cheilosis, mucosal drying and cracking,  Burning mouth and tongue,  Diminished salivary flow  Alterations in the flora of the oral cavity, with greater predominance of Candida albicans, haemolytic streptococci, and staphylococci. (Adler P, 1973)  An altered rate of dental caries EFFECTS ON PERIODONTIUM:  Tendency toward enlarged gingiva  Sessile or pedunculated gingival polyps  Polypoid gingival proliferations, abscess formation, periodontitis, and loosened teeth. (Hirschfield I, J Periodontol, 1934)  The most striking changes in uncontrolled diabetes are the reduction in
  8. 8. •Periodontitis in type 1 diabetic patients appears to start after age 12 years. The prevalence of periodontitis has been reported as 9.8% in 13- to 18-year-old patients, increasing to 39% in those 19 years and older. (Park BH, JADA, 1982) •Severe gingival inflammation, deep periodontal pockets, rapid bone loss, and frequent periodontal abscesses often occur in diabetic patients with poor oral hygiene. •In juvenile diabetics, extensive periodontal destruction often occurs due to the age of these patients.
  9. 9. • Candidiasis has been reported in patients with poorly controlled DM (Ueta et al. 1993), associated with suppressed free radical release by polymorphonuclear cells (PMNs) and reduced phagocytosis. • The majority of well-controlled studies show a higher prevalence and severity of periodontal disease in individuals with diabetes than without, with similar local factors (O’Leary TM et al, 1962; Anderson JL et al, 1975; Nichols C, 1978)  Findings include a greater loss of attachment, increased bleeding on probing, and increased tooth mobility. Diabetes does not cause gingivitis or periodontal pockets, but there are indications that it alters the response of the periodontal tissues to local factors -hastening bone loss and retarding postsurgical healing of the periodontal tissues. •Approximately 40% of adult Pima Indians in Arizona have type 2 diabetes. A comparison of individuals with or without diabetes in this Native American tribe has shown a clear increase in prevalence of destructive periodontitis, as well as a 15% increase in edentulousness, in diabetic patients. The risk of developing destructive periodontitis increases threefold in these individuals. (Sheridan P, 1987)
  10. 10. Mechanisms Of Diabetic Influence On Periodontium  A number of possible mechanisms have been proposed by which diabetes may affect the periodontium.  These are primarily related to changes in: -Subgingival Microbiota -GCF glucose levels -Periodontal vasculature -Host response -Collagen Metabolism (Oliver RC, J Periodontol, 1994)
  11. 11. BACTERIAL PATHOGENS •The glucose content of gingival fluid and blood is higher in individuals with diabetes than in those without diabetes, with similar plaque and gingival index scores. (Ficara AJ, 1975) •The increased glucose in the gingival fluid and blood of diabetic patients could change the environment of the microflora, inducing qualitative changes in bacteria that could contribute to the severity of periodontal disease observed in those with poorly controlled diabetes. •Patients with type 1 diabetes mellitus and periodontitis have been reported to have a subgingival flora composed mainly of Capnocytophaga, anaerobic vibrios, and Actinomyces species. • Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, which are common in periodontal lesions of individuals without diabetes, are present in low numbers in those with the disease.
  12. 12. •Other studies, however, found scarce Capnocytophaga and abundant A. actinomycetemcomitans and black-pigmented Bacteroides, as well as P. intermedia, P. melaninogenica, and Campylobacter rectus. (Mascola RF, 1970) Black pigmented species, especially P. gingivalis, P. intermedia, and C. rectus, are prominent in severe periodontal lesions of Pima Indians with type 2 diabetes. (Genco RJ, 1987)
  13. 13. POLYMORPHONUCLEAR LEUKOCYTE FUNCTION The increased susceptibility of diabetic patients to infection has been hypothesized as being caused by polymorphonuclear leukocyte (PMN) deficiencies resulting in: • impaired chemotaxis • defective phagocytosis • impaired adherence. (Mc Mullen et al, 1981)  In patients with poorly controlled diabetes, the function of PMNs and monocytes/ macrophages is impaired. (Icapino AM, 2001) As a result, the primary defense (PMNs) against periodontal pathogens is diminished, and bacterial proliferation is more likely.  No alteration of immunoglobulin A(IgA), G (IgG), or M (IgM) has been found in diabetic patients. (Robertson HD,1974) EFFECTS ON HOST RESPONSE
  14. 14. Crevicular collagenase activity released by PMNs is increased and inhibited by invitro by tetracycline through its enzyme inhibitory effects. (Sorsa et al 1992).  B- glucoridinase and elastase in associated with diabetic angiopathy have been detected as significantly higher levels in poorly controlled DM. PIwowar et al (2000).
  16. 16. Hyperglycemi a Glycosylatio n of basement membrane proteins Thickening of basement membrane Altered structural and physical properties of BM Disruption of collagen fibers in BM, swelling of endothelium Impedes oxygen diffusion, metabolic waste elimination, PMN migration diffusion of serum factor including antibodies Susceptible to infection Brownlee et al 1994 Microvascular Changes
  17. 17. ALTERED COLLAGEN METABOLISM Chronic hyperglycemia adversely affects the synthesis, maturation, and maintenance of collagen and extracellular matrix. In the hyperglycemic state,numerous proteins and matrix molecules undergo a nonenzymatic glycosylation, resulting in AGEs (Advanced Glycation end products) collagen is cross linked by AGE molecules making it less soluble and less likely to be normally repaired or replaced. Cellular migration through cross-linked collagen is impeded, and tissue integrity is impaired as a result of damaged collagen remaining in the tissues for longer periods (i.e., collagen is not renewed at a normal rate). As a result, collagen in the tissues of patients with poorly controlled diabetes is older and more susceptible to pathogenic breakdown (i.e., less resistant to destruction by periodontal infections). . (Grossi SG,
  18. 18. ADVANCED GLYCATION END PRODUCTS Carbohydrate containing proteins which accumulate in patients with sustained hyperglycaemia are known as AGEs. Formation of AGEs begins with the attachment of glucose of amino groups on proteins to form an unstable schiff base adduct. Through a slow chemical rearrangement, these are converted to a more stable but still reversible glucose-protein adduct known as Amadori product. Normalization of glycaemia at this stage results in the reversal of the amadori product. If hyperglycaemia is sustained, Amadori product becomes highly stable and forms AGEs. Since AGEs are irreversible, once formed, they remain attached to proteins for lifetime. Thus, if hyperglycaemia is corrected, level of AGEs in affected tissues does not return back to normal.
  19. 19. Effects on healing and treatment response  Wound healing is impaired due to the cumulative effects on cellular functions as described above. In summary, these factors include: 1. Decreased synthesis of collagen by fibroblasts 2. Increased degradation by collagenase 3. Glycosylation of existing collagen at wound margins 4. Defective remodeling and rapid degradation of newly synthesized, poorly cross-linked collagen.
  20. 20. PERIODONTAL TREATMENT: •The treatment of well controlled DM patients would be similar to that of non-diabetic patients for most routine dental procedures. •Well controlled diabetics with regular supportive therapy have been shown to maintain treatment results 5 years after a combination of non-surgical and surgical treatment (Westfelt et al. 1996). •The short-term nonsurgical treatment response of stable diabetics has been found to be similar to that of non-diabetic controls, with similar trends in improved probing depths, attachment gain, and altered subgingival microbiota (Christgau et al. 1998).
  21. 21. FEMALE SEX HORMONES & PERIODONTIUM  The hormonal changes experienced by women during physiological and non physiological conditions (HRT and use of OCP’s) result in significant changes in the periodontium, particularly in presence of pre-existing inflammation.  Period of hormonal flux are known to occur during puberty, menstruation, pregnancy and menopause.  Changes in hormonal levels occur when the anterior pituitary secretes FSH and LH, resulting in maturation of ovary and cyclical production of estrogen and progesterone.  The gingiva is a target tissue for the actions of steroid hormones. Receptors for estrogen and progesterone have been demonstrated in the gingiva, providing evidence that this tissue can be a target organ for both sex hormones (Vittek J, 1982).  Clinical changes in the tissues of the periodontium have been identified during
  22. 22. The main potential effects of these hormones on the periodontal tissues can be summarized as: •Estrogen affects salivary peroxidases, which are active against a variety of microorganisms (Kimura et al. 1983), by changing the redox potential. • Estrogen has stimulatory effects on the metabolism of collagen and angiogenesis (Sultan et al. 1986). •Estrogen can trigger autocrine or paracrine polypeptide growth factor signaling pathways, whose effects may be partially mediated by the estrogen receptor itself (Chau et al. 1998). •Progesterone has been associated with increased permeability of the vasculature •Altering rate and pattern of collagen production in gingiva •Increasing folate metabolism •Altering the immune response. •Plays a role in the production of prostaglandins that mediate the body’s response to inflammation Estrogen and progesterone can modulate vascular responses and connective tissue turnover in the periodontium, associated with interaction with inflammatory mediators (Soory 2000b).
  23. 23. PUBERTY  occurs between the average ages of 11 to 14 in most women.  The production of sex hormones (estrogen and progesterone in females and testosterone in males) increases, then remains relatively constant during the remainder of the reproductive phase.  Also, the prevalence of gingivitis increases, without an increase in the amount of plaque.  Gram negative anaerobes, especially Prevotella intermedia, have been implicated in association with puberty gingivitis. Kornman and Loesche (1979) postulated that this anaerobic organism may use ovarian hormones (E and P) as a substitute for vitamin K growth factor (Menadione).  Levels of black-pigmented Bacteroides, especially P. intermedia (formerlyknown as Bacteroides intermedius), are thought to increase with increased levels of gonadotropic hormones in puberty.
  24. 24.  Capnocytophaga species also increase in incidence, as well as in proportion.  These organisms have been implicated in the increased bleeding tendency observed during puberty.  Recent studies associated with pubertal gingivitis indicate proportionately elevated motile rods, spirochetes, and P. intermedia. (Mombelli A, 1995)  Statistically significant increases in gingival inflammation and in the proportions of P. intermedia and P. nigrescens have been seen in pubertal gingivitis. (Nakagawa S, 1994).  A recent study of 11- to 17-year-old adolescents found higher levels of Actinobacillus actinomycetemcomitans and Fusobacterium nucleatum, which were associated with bleeding indices, probing depth, and attachment loss.
  25. 25. C/F:  During puberty, periodontal tissues may have an exaggerated response to local factors.  A hyperplastic reaction of the gingiva may occur in areas where food debris, materia alba, plaque, and calculus are deposited.  Marginal & interdental gingival enlargement found primarily on the facial surfaces, with lingual surfaces remaining relatively unaltered.  The inflamed tissues become erythematous, lobulated, and retractable.  Bleeding may occur easily with mechanical debridement of the gingival tissues.  As the adulthood approaches, severity of
  26. 26. MENSES  During menses, progesterone increases from the second week, peaks at approximately 10 days, and dramatically drops before menstruation.  Prevalance of gingivitis increases.  Gingival tissues have been reported to be more edematous during menses and erythematous before the onset of menses in some women.  Complains of bleeding gums.  Bloated or Tense feeling in the gums preceding menstrual flow.  Increased exudation from inflamed gingiva suggesting that pre-existing gingivitis in aggravated but GCF of normal gingiva not affected. Holm Pederson et al (1967).  Tooth mobility does not change significantly. Friedman LA et al (1972).  Salivary bacterial count is elevated during menstruation and at ovulation upto 14 days earlier. Prout RE et al (1970)
  27. 27.  A recent study reported higher gingival indices during ovulation and before menstruation despite reported increases in oral symptoms during menses. ( Mahler D et al, 2004)  In addition, an increase of gingival exudate has been observed during the menstrual period and is sometimes associated with a minor increase in tooth mobility. (Grant D,1988)  When the progesterone level is highest (during luteal phase of cycle), intraoral recurrent aphthous ulcers, herpes labialis lesions, and candidal infections occur in some women as a cyclic pattern. (Ferguson MM, 1984)  Because the esophageal sphincter is relaxed by progesterone, women may be more susceptible to gastroesophageal reflux disease (GERD) during this time of the cycle as well.  Symptoms of GERD include heartburn, regurgitation, and chest pain, and when reflux is severe, some patients develop
  28. 28. PREGNANCY  Pregnant women, near or at term, produce large quantities of estradiol (20 mg/day), estriol (80 mg/day) and progesterone (300 mg/day).  Gingival inflammation initiated by plaque, and exacerbated by these hormonal changes in the second and third trimester of pregnancy, is referred to as pregnancy gingivitis.  Parameters such as gingival probing depths ( Hugoson 1970, Miyazaki et al. 1991), bleeding on probing (Miyazaki et al. 1991) and crevicular fluid flow (Hugoson 1970) were found to be increased.  A study of rural population of Sri Lankan women (Tilakaratne et al. 2000a) showed increased gingivitis of varying degrees of significance amongst all the pregnant women investigated, compared with non pregnant controls.  It has also been suggested that the accentuation of gingivitis in pregnancy occurs in two peaks: -during the first trimester, when there is overproduction of gonadotropins -during the third trimester, when estrogen and progesterone levels are highest
  29. 29. Effects on the microbiota  An alteration in the compositions of subgingival plaque occurs during pregnancy. Kornman and Loesche (1979) found that during 2nd trimester, gingivitis and gingival bleeding increased without an increase in plaque levels. Bacterial anaerobic/aerobic ratios increased, in addition to proportions of B. melanogenicus and P. intermedia. Authors suggested that estradiol or progesterone can substitute for menadione (vit K) as an essential growth factor for PI but not for P gingivalis or E corrodens. During pregnancy, progesterone is less actively catabolized to its inactive products, resulting in higher levels of the active hormone (Ojanotko- Harri et al. 1991). A 55-fold increase in the proportion of P. intermedia has been demonstrated in pregnant women compared with non-pregnant controls (Jensen et al. 1981), implying a role for gestational hormones in causing a change in microbial ecology in the gingival
  30. 30. Effects on the tissues and host response The increase in severity of gingivitis during pregnancy has been partly attributed to the increased circulatory levels of progesterone and its effects on the capillary vessels (Lundgren et al. 1973).  Elevated progesterone levels in pregnancy enhance capillary permeability and dilatation, resulting in increased gingival exudate.  The elevated levels of estrogen and progesterone in pregnancy affect the degree of keratinization of the gingival epithelium and alter the connective tissue ground substance.  The decreased keratinization of the gingivae, together with an increase in epithelial glycogen, are thought to result in decreased effectiveness of the epithelial barrier in pregnant women (Abraham-Inpijn et al. 1996).  High levels of progesterone and estrogen associated with pregnancy (and the use of some oral contraceptives) have been shown to suppress the immune response to plaque (Sooriyamoorthy & Gower 1989).  Neutrophil chemotaxis and phagocytosis, along with antibody and T- cell responses have been reported to be depressed in response to high levels of gestational hormones (Raber-Durlacher et al. 1993).
  31. 31. PERIODONTAL MANIFESTATIONS  Pregnancy itself does not cause gingivitis.  Gingivitis in pregnancy is caused by bacterial plaque, just as it is in non pregnant women. Pregnancy accentuates the gingival response to plaque and modifies the resultant clinical picture During pregnancy, there is an increase in levels of both progesterone and estrogen, which by the end of the third trimester reach levels 10 and 30 times the levels during the menstrual cycle, respectively. (Amar S 1994) These hormonal changes induce changes in vascular permeability leading to gingival edema and an increased inflammatory response to dental plaque. The subgingival microbiota may also undergo changes, including an increase in Prevotella intermedia. (Kornman KS 1980)
  32. 32.  Reported incidence of gingivitis in pregnancy varies from about 50% to 100% (Loe H, 1965)  Pregnancy affects the severity of previously inflamed areas; it does not alter healthy gingiva.  Severity of gingivitis is increased during pregnancy beginning in the 2nd or 3rd month.  Gingivitis becomes more severe by the eighth month and decreases during the ninth month of pregnancy (Hayden P, 1989) Some investigators report that the greatest severity is between the second and third trimesters. (Carranza FA Jr, 1965)  Partial reduction in the severity of gingivitis occurs by 2 months postpartum, and after 1 year the condition of the gingiva is comparable to that of patients who have not been pregnant. However, the gingiva does not return to normal as long as local factors are present.
  33. 33.  Pronounced ease of bleeding is the most striking clinical feature.  Gingiva is inflamed and varies in color from a bright red to bluish red.  Marginal and interdental gingivae are edematous, pit on pressure, appear smooth and shiny, are soft and pliable, and sometimes present a raspberry-like appearance.  Extreme redness results from marked vascularity, and there is an increased tendency to bleed .  Gingival changes are usually painless unless complicated by acute infection.  In some cases the inflamed gingiva forms discrete “tumorlike” masses,
  34. 34. PREGNANCY GRANULOMA OR EPULIS These are discrete ‘tumor-like masses’.  A combination of the vascular response induced by progesterone and the matrix stimulatory effects of estradiol contributes to its development.  The vascular effects result in a bright red, hyperemic, and edematous presentation.  The lesions often occur in the anterior papillae of the maxillary teeth and usually do not exceed 2 cm in diameter.  They can bleed when traumatized and their removal is best deferred until after parturition, when there is
  35. 35. HORMONAL CONTRACEPTIVES  Hormonal contraceptives aggravate the gingival response to local factors in a manner similar to that seen in pregnancy and, when taken for more than 1.5 years, increase periodontal destruction. (Knight GM et al, 1974)  Mullally et al (2007) found that current users of OCs had poorer periodontal health.80 An exaggerated response to local irritants occurs in gingival tissues.  Inflammation ranges from mild edema and erythema to severe inflammation with hemorrhagic or hyperplasic gingival tissues.  It has been reported that more exudate is present in inflamed gingival tissues of OC users than in pregnant women. (Sooriyamoorthy M, 1989)  Kalkwarf KL (1978) reported that the response may be caused by an altered microvasculature, increased gingival permeability, and increasing
  36. 36.  Jensen J et al (1981) found dramatic microbial changes in pregnant and OC groups compared with a non pregnant group. A sixteen fold increase in Bacteroides species was noted in the OC group versus the non pregnant group, despite no statistically significant clinical differences in gingival index or GCF flow. The authors stated that the increased female sex hormones substituting for the naphthoquinone requirement of certain Bacteroides species were most likely responsible for this increase.  The OC-associated gingival inflammation may become chronic (versus the acute inflammation of pregnancy) because of the extended periods that women are exposed to elevated levels of estrogen and progesterone.  Some have reported that the inflammation increases with prolonged
  37. 37. MENOPAUSAL GINGIVOSTOMATITIS (SENILE ATROPHIC GINGIVITIS)  During menopause, usual rhythmic hormonal fluctuations of female cycle are ended as estradiol ceases to be the major circulating estrogen. As a result, females can develop gingivostomatitis.  It is not a common condition.  The gingiva and remaining oral mucosa are dry and shiny, vary in color from abnormal paleness to redness, and bleed easily.  Fissuring occurs in the mucobuccal fold in some cases.  The patient complains of a dry, burning sensation throughout the oral cavity, associated with extreme sensitivity to thermal changes; abnormal taste sensations described as "salty," "peppery" or "sour"; and difficulty with removable partial prostheses. (Massler M et al, 1950).
  38. 38. MENOPAUSE AND OSTEOPOROSIS  During menopause there is a decline in hormonal levels due to decreased ovarian function.  This is characterized by tissue changes such as desquamation of gingival epithelium and osteoporosis which may be attributed to hormone deficiency.  It has been demonstrated that women with early onset of menopause have a higher incidence of osteoporosis and significantly lower bone mineral density (Kritz-Silverstein & Barrett-Connor 1993).  A third of women over age 60 are affected by postmenopausal osteoporosis (Baxter 1987).  The changes involved are a reduction in bone density, affecting its mass and strength without significantly affecting its chemical composition.  An alteration in the calcium- phosphate equilibrium due to deficient absorption of dietary calcium and increased excretion due to diminished estrogen levels can account for some of the bone changes seen in
  39. 39. HYPER PARATHYRODISM  Parathyroid hyper secretion produces generalized demineralization of skeleton, increased osteoclastic activity with proliferation of connective tissue in the enlarged marrow spaces and formation of bone cysts and giant cell tumors.  Also known as brown tumors.  Also called ostitis fibrosa cystica or von Recklinghausen’s bone disease.  Oral changes malocclusion, tooth mobility, radiographic evidence of anterior osteoporosis with closely meshed trabeculae.  Widening of PDL space, absence of lamina dura, radiolucent cystic like spaces.  A relationship between periodontal diseases in dogs and hyperparathyroidism secondary calcium deficiency. (Hemrickson PA et al 1968).
  40. 40. Secondary hyperparathyroidism- Ground glass appearance. Periapical And Occlusal Radiographic appearance of browns tumor
  41. 41. HEMATOLOGIC DISORDERS & IMMUNE DEFICIENCIES  WBCs : Involved in the inflammatory reactions.  RBCs : Responsible for gas exchange and nutrient supply to the periodontal tissues.  Platelets : Normal haemostatic as well as recruitment of cells during inflammation and wound healing.  Disorders of any blood cells or blood forming organs have profound effect on periodontium.  Deficiency of host immune response may also lead to the severe destructive periodontal diseases
  42. 42. LEUCOCYTE (NEUTROPHIL) DISORDERS  Majority of haematological disorders affecting the periodontium are related to WBC function or numbers.  Quantitative PMN deficiencies (Neutropenia, Agranulocytosis) are accompanied by generalised periodontal destruction.  Qualitative/Functional defects (Lazy Leukocyte Syndrome, Chediak Hegashi syndrome) are often associated with localised destruction affecting only the periodontium of certain teeth. NEUTROPENIA • Blood disorder that results from low levels of circulating neutrophils. • Serious condition caused by diseases, medications, chemicals, infections, idiopathic conditions or hereditary disorders. • May be chronic or cyclic, severe, or benign. • Mild neutropenia: ANC of 1000-1500 cells/l ( Absolute neutrophil count) • Moderate: ANC of 500-1000 cells/l • Severe : ANC less than 500 cells/l
  43. 43. AGRANULOCYTOSIS  Characterized by a reduction in the number of circulating granulocytes and results in severe infections, including ulcerative necrotizing lesions of the oral mucosa, skin, and gastrointestinal and genitourinary tracts.  Less severe forms of the disease are called neutropenia or granulocytopenia.  Drug idiosyncrasy is the most common cause of agranulocytosis, but in some cases, its cause cannot be explained.  Agranulocytosis has been reported after the administration of drugs such as aminopyrine, barbiturates and their derivatives, benzene ring derivatives, sulfonamides, gold salts, or arsenical agents. (Greenberg MS, Cohen SG et al, 1987)  It generally occurs as an acute disease. It may be chronic or periodic with
  44. 44.  The onset of disease is accompanied by fever, malaise, general weakness, and sore throat.  Ulceration in the oral cavity, oropharynx, and throat is characteristic.  The mucosa exhibits isolated necrotic patches that are black and gray and are sharply demarcated from the adjacent uninvolved areas.  The absence of a notable inflammatory reaction caused by lack of granulocytes is a striking feature.  The gingival margin may or may not be involved.  Gingival hemorrhage, necrosis, increased salivation, and fetid odor are accompanying clinical features.  In cyclic neutropenia the gingival changes recur with recurrent exacerbation of the disease.The occurrence of aggressive (formerly termed “rapidly progressive”) periodontitis has been described in cyclic Ulceration on palate in agranulocytosis patient
  45. 45. LEUKAEMIA  The leukemias are "malignant neoplasias of WBC precursors, characterized by: (1) Diffuse replacement of the bone marrow with proliferating leukemic cells. (2) Abnormal numbers and forms of immature WBCs in the circulating blood (3) Widespread infiltrates in the liver, spleen, lymph nodes, and other sites throughout the body. CLASSIFICSTION  According to the type of WBC involved:  Lymphocytic  Myelocytic or Myelogenous  According to their evolution:  Acute  Subacute,  Chronic.
  46. 46. All leukemias tend to displace normal components of bone marrow elements with leukemic cells Anaemia Leukopenia Thrombocytopenia resulting in reduced production of RBCs WBCs Platelets leading to results in poorer Tissue oxygenation, making tissues more friable and susceptible to breakdown. leads to an increased susceptibility to infections. leads to bleeding tendency, which can occur in any tissue . Some patients may have normal blood counts while leukemic cells are present in the bone marrow; this type of disease is called “aleukemic leukemia." Several factors are implicated in the aetiology of leukaemia – radiation,
  47. 47. A classification for the aetiology of gingival lesions in leukaemic patients has been proposed by Barrett (1984). Category 1- is caused by direct leukaemic infiltration and includes gingival enlargement. Category 2- deals with direct drug toxicity caused by chemotherapeutic agents. The immunosuppressive drug cyclosporin, used to prevent graft rejection after transplantation, can contribute to gingival hyperplasia.Category 3- comprises the detrimental effects of graft-versus- host reactions. In this disease, the transplanted lymphocytes react against host antigens. Mucosal lesions include lichenoid striae, epithelial detachment, erosions and ulceration can be useful markers of graft-versus-host activity. Category 4- involves secondary effects from the depression of marrow/lymphoid tissue and includes haemorrhage, neutropenic ulceration and an increased susceptibility to
  48. 48. Periodontium in Leukemic Patients Oral and periodontal manifestations of leukemia consist of: Oral ulcerations & infections Gingival enlargemen t Expression of these signs is more common in acute and subacute forms than in
  49. 49. Leukemic Infiltration • Leukemic cells can infiltrate the gingiva and, less frequently, the alveolar bone. • Gingival infiltration often results in leukaemic gingival enlargement. • Leukemic gingival enlargement consists of a basic infiltration of the gingiva by leukemic cells that creates gingival pockets where bacterial plaque accumulates, initiating a secondary inflammatory lesion that contributes also to the enlargement of the gingiva. • It may be localized to interdental papilla or expand to include marginal gingiva and partially cover the crowns of teeth. Leukemic infiltration causing localized gingival swelling of the interdental papillae between the maxillary CI and LI
  50. 50.  The abnormal accumulation of leukaemic cells in dermal & subcutaneous CT is called Leukaemia Cutis and forms elevated and flat macules and papules.  Gingiva appears initially bluish red and cyanotic, with a rounding and tenseness of the gingival margin; then it increases in size, most often in the interdental papilla and partially covering the crowns of the teeth.
  51. 51.  Microscopically:  Gingiva exhibits a dense, diffuse infiltration of predominantly immature leukocytes in the attached and marginal gingiva.  The normal connective tissue components of the gingiva are displaced by the leukemic cells.  The cellular accumulation is denser in the entire reticular connective tissue layer.  In almost all cases the papillary layer contains comparatively few leukocytes.  The blood vessels are distended and contain predominantly leukemic cells, and the RBCs are reduced in number.  The epithelium presents a variety of changes and may be thinned or hyperplastic.  Common findings include: degeneration associated with intercellular and intracellular edema and leukocytic infiltration with diminshed surface
  52. 52.  The periodontal ligament may be infiltrated with mature and immature leukocytes.  The marrow of the alveolar bone exhibits localized areas of necrosis, thrombosis of the blood vessels, infiltration with mature and immature leukocytes, occasional RBCs, and replacement of the fatty marrow by fibrous tissue.  In leukemic mice, the presence of infiltrate in marrow spaces and the periodontal ligament results in osteoporosis of the alveolar bone with destruction of the supporting bone and disappearance of the periodontal fibers. (Brown LR, 1969)  A study of 1076 adult patients with leukemia showed that 3.6% of the patients with teeth had leukemic gingival proliferative lesions, with the highest incidence in patients with acute monocytic leukemia (66.7%), followed by acute myelocytic-monocytic leukemia (18.7%) and acute myelocytic leukemia (3.7%) (Dreizen S et al, 1983)
  53. 53. BLEEDING  Gingival hemorrhage is a common finding in leukemic patients, even in the absence of clinically detectable gingivitis.  Bleeding gingiva can be an early sign of leukemia.  It is due to the thrombocytopenia that results from replacement of the bone marrow cells by leukemic cells and also from the inhibition ofnormal stem cell function by leukemic cells or their products.  Bleeding tendency can also manifest itself in the skin and throughout the oral mucosa, where petechiae are often found, with or without leukemic infiltrates. More diffuse submucosal bleeding manifests as Ecchymosis.  Oral bleeding has been reported as a presenting sign in 17.7% of patients with acute leukemia and in 4.4% of patients with chronic leukemia. Spontaneous bleeding from the gingival sulcus in patient with thrombocytopenia.
  54. 54. ORAL ULCERATION & INFECTION  In leukemia the response to bacterial plaque or other local irritation is altered.  The cellular component of the inflammatory exudate differs both quantitatively and qualitatively from that in nonleukemic individuals.  There is pronounced infiltration of immature leukemic cells in addition to the usual inflammatory cells.  As a result, the normal inflammatory response may be diminished.  Granulocytopenia (diminished WBC count) results from the displacement of normal bone marrow cells by leukemic cells, which increases the host susceptibility to opportunistic microorganisms and leads to ulcerations and infections.  Discrete, punched-out ulcers penetrating deeply into the submucosa and covered by a firmly attached white slough can be found in the oral mucosa.
  55. 55.  These lesions occur in sites of trauma such as the buccal mucosa in relation to the line of occlusion or the palate.  A gingival (bacterial) infection in leukemic patients can be the result of an exogenous bacterial infection or an existing bacterial infection (e.g., gingival or periodontal disease).  Acute gingivitis and lesions of necrotizing ulcerative gingivitis are more frequent and severe in terminal cases of acute leukemia.
  56. 56.  The inflamed gingiva in patients with leukemia differs clinically from that in nonleukemic individuals.  Gingiva is a peculiar bluish red, is sponge like and friable, and bleeds persistently on the slightest provocation or even spontaneously in leukemic patients.  This greatly altered and degenerated tissue is extremely susceptible to bacterial infection, which can be so severe as to cause acute gingival necrosis and pseudomembrane formation or bone exposure. Opportunistic bacterial infection of gingiva in patient with leukemia Opportunistic bacterial infection in immuno- suppressed patient caused complete destruction of gingiva, exposing underlying alveolar bone.
  57. 57. ANAEMIA  It is a deficiency of quantity and quality of blood, as manifested as reduction in circulating erythrocytes and in the amount of hemoglobin.  Results from the :  Blood loss.  Defective blood formation.  Increase RBCs destrction. Classified based on the cellular morphology and hemoglobin content:  Macrocytic hyperchromic ( Pernicious Anaemia)  Microcytic hypochromic ( Iron deficiency Anaemia)  Sickel cell Anaemia  Normocytic-Normochromic anaemia ( Hemolytic or aplastic anaemia)
  58. 58. PERNICIOUS ANEMIA: o results in tongue changes in 75% of cases. o The tongue appears red, smooth, and shiny, owing to atrophy of the papillae. o There is also marked pallor of the gingiva. IRON DEFICIENCY ANEMIA: o Induces similar Tongue and gingival changes. o A syndrome consisting of glossitis and ulceration of the oral mucosa and oropharynx, inducing dysphagia (Plummer-Vinson syndrome), has been described in patients with iron deficiency anemia.
  59. 59. SICKLE CELL ANEMIA: • It is a hereditary form of chronic hemolytic anemia that occurs exclusively in blacks. • There is a defect in adult haemoglobin of RBC and the cell appears as sickle or crescent shaped erythrocyte .The haemoglobin is genetically altered, as a result the RBC undergoes destruction quickly resulting anemia.  Characterized by: Pallor, jaundice, weakness, rheumatoid manifestations, leg ulcers.  Oral changes include generalized osteoporosis of jaws, with a peculiar stepladder alignment of trabeculea of the interdental septa alongwith pallor and yellowish discoloration of mucosa.  Periodontal infections may precipitate sickle cell crisis. APLASTIC ANEMIAS:  result from a failure of the bone marrow to produce erythrocytes.  Their etiology is usually the effect of toxic drugs on the marrow or displacement of RBCs by leukaemic cells.  Oral changes include pale discoloration of the oral mucosa and increased susceptibility to infection.
  60. 60. THROMBOCYTOPENIA  Condition of reduced platelets count result from either lack of platelet production or increased loss of platelet production.  “Purpura” refers to purplish appearance of skin or mucous membranes where bleeding has occurred as a result of decreased platelets.  Thrombocytopenic purpura may be idiopathic ( Unknown etiology as in Werlhof’s disease) or secondary to some known etiological factors responsible for reduced amount of functioning marrow & a resultant reduction in the number of circulating platelets. These factors include:  Aplasia of bone marrow  Displacement of megakaryocytes in the marrow  Replacement of marrow by tumor.  Destruction of marrow by irradiation or radium or by drugs.
  61. 61.  C/F:  Characterized by low platelet count, prolonged clot retraction & BT & normal or slightly prolonged CT.  Spontaneous bleeding into skin or from mucous membrane.  Petechiae and Hemorrhagic vesicles in the oral cavity particularly in palate, tonsillar pillars & buccal mucosa.  Gingiva- soft , swollen and friable.  Bleeding occur spontaneously and is difficult to control. Petechiae on palate Echymosis
  62. 62. GENETIC DISORDERS Many systemic conditions associated with or predisposing to periodontal destruction include genetic disorders that result in an inadequate number or function of circulating neutrophils. Severe periodontitis has been observed in individuals with primary neutrophil disorders such as neutropenia, agranulocytosis, Chédiak-Higashi syndrome, and lazy leukocyte syndrome. In addition, severe periodontitis has also been observed in individuals who exhibit secondary neutrophil impairment, as seen in Down syndrome, Papillon-Lefèvre syndrome, and inflammatory bowel disease.
  63. 63. Chediak- Higashi syndrome: Rare diseases that affects the production of organelles found in almost every cells. It affects the melanocytes, Platelets, Phagocytes. Causes Partial albinism, mild bleeding disorders, recurrent bacterial infections. Neutrophil ability to release their contents is impaired. Aggressive form of periodontitis has been Lazy Leukocyte syndrome: Characterized by : susceptibility to severe microbial infections. Neutropenia. Defective chemotatctic response by neutrophils Abnormal inflammatory response. Patient susceptibility to aggressive form periodontitis with destruction of bone and early tooth loss.
  64. 64.  Rare genetic disorder. Because it is an inherited disease, it is categorized as a Primary immunodeficiency most often diagnosed at birth. Results from the inability to produce or failure to normally express an important cell surface integrin( CD18).  Rare periodontal diseases are noticed : Begin during or immediately after eruption of primary teeth. Extremely acute inflammation. Proliferation of gingival tissue with rapid destruction of bone found.  Profound defects in peripheral blood neutrophils, monocytes, and absence of neutrophils in the gingival tissue noticed. Both permanent and primary teeth are affected, often resulting in early tooth loss. LEUKOCYTE ADHESION DEFICIENCY:
  65. 65. Papillon- lefevre syndrome  Inherited disease, autosomal recessive pattern.  Frequency 1-4 cases/ million individual.  Characterized by:  Hyperkeratotic skin lesions.  Severe destruction of periodontium.  Calcification of dura. Hyperkeratotic and scaly lesions on palm Hyperkerototic and scaly lesions on knees Periodontal Destruction
  66. 66.  PERIODONTAL INVOLVEMENT:  Early inflammatory changes that lead to bone loss and exfoliation of teeth.  Primary teeth loss by 5-6 years.  Permanent dentition erupt normally, but within few years lost because of destructive periodontal diseases.  At a very early age, usaually15- 20 years, patients are often edentulous except for the third molars.  Tooth extraction heal uneventfully. MICROSCOPIC CHANGES:  Marked chronic inflammation of the lateral wall of the pockets with predominant plasma cell infiltration, considerable osteoclastic activity and apparent lack of osteoblastic activity and extremely thin cementum. Martinez lalis RR ( 1965)  Bacterial flora similar to chronic periodontitis.  Spirochete-rich zone in the apical portion of the pockets and adhere to the cementum.  Microcolony formation of mycoplasma species have been reported.Firatli et al (1996) reported depressed chemotaxis of peripheral neutrophils and suggested that it explained the pathogenesis of papillon-lefevre syndrome.
  67. 67. Down syndrome  Mongolism, trisomy 21  Caused by Chromosomal abnormality and characterized by mental deficiency and growth retardation.  Prevalence of periodontitis is high (occurring in almost 100% of patients younger than 30 years). (Mackey SA, 2003)  Although plaque, calculus, and local irritants (e.g., diastema, crowding of teeth, high frenum attachments, and malocclusion) are present and oral hygiene is poor, the severity of periodontal destruction exceeds that explainable by local factors alone. (Cohen DW, 1961)  Periodontial Disease is characterized by:  Deep periodontal pockets associated with substantial plaque accumulation and moderate gingivitis.  Generalized form but more severe in lower anteriors.  Moderate recession seen.  High prevalence and increased severity of periodontal destruction associated with Down syndrome is most likely explained by poor PMN chemotaxis, phagocytosis, and intracellular killing. Cutler CW (1994).
  68. 68.  Psychophysiological response of the organism to a perceived challenge or threat.” (Breivik et al 1996).  A state of physiological or psychological strain caused by adverse stimuli, physical, mental, or emotional, internal or external, that tend to disturb the functioning of an organism and which the organism naturally desires to avoid. (Boyapati et al, 2007)  All individuals experience stress, but these events do not invariably result in destructive periodontitis. The types of stress that lead to periodontal destruction appears to be more chronic or long term and less likely to be controlled by the individual.  A systematic review has documented a positive relationship between stress and chronic forms of periodontal disease.
  69. 69.  Psychologic conditions, particularly psychosocial stress, have been implicated as risk indicators for periodontal disease. (Genco RJ, 1996)  Increasing evidence suggest that emotional stress may also influence the extent and severity of chronic periodontitis. (Glaser et al 2002)  Stress and psychosomatic disorders most likely impact the periodontal health through changes in the individual’s behaviour and through complex interactions among the nervous, endocrine and immune systems.  Individuals under stress may have poorer oral hygiene, may start or increase clenching and grinding of their teeth and may smoke frequently.  All these behavioral changes increase their susceptibility to periodontal disease destruction.  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 (ie stress alone does not cause or lead to periodontitis in the absence of
  70. 70.  Genco et al (1999) found that individuals with high levels of financial stress and poor coping skills had twice as much as those with minimal stress and good coping skills.  Financial Stress is an example of long-term, constant pressure that may exacerbate periodontal destruction in susceptible individuals.  Researchers also found that chronic stress and inadequate coping could lead to changes in daily habits, such as poor oral hygiene, clenching and grinding as well as physiologic changes such as decreased saliva flow and suppressed immunity  Wimmer et al (2002) found that pateints with periodontal disease were less likely to refuse responsibility and downplay their condition.  Studies support the concept that one of the most important aspects related to the influence of stress on periodontal disease destruction is the manner in which the individual copes with the stress.
  71. 71. Stress Induced Immuno- suppression Boypati et al 2007
  72. 72. • Psychologic conditions, such as stress and depression, may also influence the outcome of periodontal therapy. Elter et al (2002) concluded that depression might have a negative effect on periodontal treatment outcomes. • A recent study investigating the relationship between psychologic stress and wound repair in patients after routine surgery revealed that stress impairs the inflammatory response and matrix degradation. • Greater psychologic stress was significantly associated with lower levels of IL-1 and MMP-9, as well as significantly more painful, poorer, and slower recovery. (Broadbent E et al, 2003) • studies suggest that both stressful life events and the individual’s personality and coping skills are factors to consider in assessing the risk of periodontal disease destruction and the potential for successful periodontal therapy. • If patients are identified with emotional or defensive coping skills, care should be taken to ensure that they receive information in a manner that does not elicit a“defensive” reaction. Influence of Stress on periodontal therapy outcomes
  73. 73. NUTRITION & PERIODONTAL DISEASE  Diet is total oral intake of substance that provides nourishment and energy. (Nizel,1989)  Nutrition is science of food and its relationship to health. It is concerned primarily with part played by nutrients in body growth, development and maintenance.( WHO 1971) MACRONUTRIENTS  Carbohydrates-65 to 80%  Proteins- 7 to 15%  Lipids -10 to 30% MICRONUTRIENTS  Vitamins  Minerals  Trace elements Recommended Dietary Allowances- Quantities of nutrients to be provided daily in the diet for maintaing good health. Adult Man weighing 70 Kg  Proteins 56 g  Fats 70 g  Carbohydrates 400 g  Calcium 800 mg  Iron 10 mg  Vit A 1000 g  Vit D 5 mg or 200 IU  Vit E 10 mg  Thiamine 1.5 mg  Riboflavin 2 mg  Niacin 20 mg  Pyridoxine 2 mg  Folic acid 150 g  Cobalamin 2 g  Ascorbic acid 60 mg
  74. 74. NUTRITIONAL INFLUENCES Effects of Nutrition on Oral and Periodontal Tissues. There are nutritional deficiencies that produce changes in the oral cavity. These changes include alterations of the lips, oral mucosa, and bone, as well as the periodontal tissues. These changes are considered to be periodontal or oral manifestations of nutritional disease. There are no nutritional deficiencies that by themselves can cause gingivitis or periodontal pockets. Nutritional deficiencies can affect the condition of the periodontium and thereby can aggravate the deleterious effects of plaque-induced inflammation in susceptible individuals.
  75. 75. Physical character of the diet Physical character of the diet may play some role in the accumulation of plaque and the development of gingivitis. Soft diets, although nutritionally adequate, may lead to plaque and calculus formation. Hard and fibrous food provides surface cleaning action and stimulation, which result in less plaque and gingivitis, even if the diet is nutritionally inadequate. A strong link between obesity and periodontal diseases has been reported. Indeed, a higher body fat content has been associated with increased gingival bleeding in older patients. (Ritchie C et al, 2001) Polyunsaturated fats (such as omega-3s) have been observed to have a positive effect on periodontal health. (El-Sharkawy et al, 2010)  A study conducted on Japanese young adults also found an association between high body mass index (BMI) and high risk of periodontal disease. (Ekuni D et al 2008)
  76. 76.  In addition, vitamin-B supplementation results in higher clinical attachment following flap surgery. (Neiva, R.F. Et al, 2005)  Vitamin D deficiency contributes to negative outcomes following periodontal surgery. (Bashutski, J.D et al, 2011)  Animal studies have found a positive correlation between Vitamin D3 supplementation and osseointegration of dental implants. (Liu, W et al, 2014)  A higher intake of vitamins A, B, C, and E along with omega-3 fatty acids results in improved healing after non-surgical periodontal therapy . (Sullivan, P.J et al, 2015)
  77. 77. NUTRITIONAL MECHANISMS OF INFLAMMATION • In health a fine balance exists between, on one the hand oxidants and on the other antioxidants which are found in all tissues of the body. • If this fine balance is disturbed by excess production of oxidants and/or depletion of local antioxidants the resulting oxidant excess causes oxidative stress and is associated with the local tissue damage seen in periodontitis. (MR Milward, ILC Chapple, THE ROLE OF DIET IN PERIODONTAL DISEASE,2013)
  78. 78.  Oxidative stress is defined as “an imbalance between oxidants & antioxidants in favour of the oxidants, leading to a disruption of redox signalling & control and/or molecular damage. (Sies & Jones 2007)  Oxidative stress is a key driver of chronic inflammation and as a result has a central role in the pathogenesis of a wide range of chronic inflammatory diseases.  It can cause direct tissue damage by altering molecules, such as proteins, lipids and DNA, thus damaging cells directly, or by activating redox- sensitive transcription factors within the cell that leads to downstream gene expression changes and production of pro-inflammatory molecules.
  79. 79. How can diet cause oxidative stress?  If dietary levels of simple sugars and fat are increased this further enhances oxidative stress levels. Firstly, excess glucose in the blood (hyperglycemia) results in the formation of advanced glycation end products (AGE), when glucose binds to proteins in tissues and the bloodstream. Neutrophils have receptors for AGE called RAGE and their ligation by AGEs activates the NADPH-oxidase enzyme complex (called the “respiratory burst”) to generate oxygen radicals. Secondly, metabolism of excess saturated fats generates elevated low density lipoprotein (LDL) cholesterol, which when oxidized forms oxidized LDL, this in turn binds to complementary receptors found on the cell membrane of neutrophils (Toll-like receptors), activating NADPH-oxidase and oxygen radical formation, further adding to the oxidative stress burden.
  80. 80. FAT-SOLUBLE VITAMIN DEFICIENCY VITAMIN A DEFICIENCY. • Dermatologic, mucosal, and ocular manifestations. • Degenerative changes occur in epithelial tissues resulting in keratinizing metaplasia. Periodontal changes • Animal studies: Hyperplasia and hyperkeratinization of the gingival epithelium with proliferation of the junctional epithelium and retardation of gingival wound healing. In the presence of local factors, vitamin A-deficient rats develop • VITAMIN E DEFICIENCY • Vitamin E serves as an antioxidant to limit free- radical reactions and to protect cells from lipid peroxidation.  Cell membranes, which are high in polyunsaturated lipids, are the major site of damage in vitamin E deficiency.  No relationship has been demonstrated between deficiencies in vitamin E and oral disease, but systemic vitamin E appears to accelerate gingival wound healing in the rat. (Kim JE,1983)
  81. 81. VITAMIN D DEFICIENCY.  Deficiency results in rickets in the very young and osteomalacia in adults.  The effect of such deficiency on the periodontal tissues of young dogs results in: 1. Osteoporosis of alveolar bone; 2. Osteoid that forms at a normal rate but remains uncalcified; 3. Failure of osteoid to resorb, which leads to its excessive accumulation; 4. Reduction in the width of the periodontal ligament space; 5. A normal rate of cementum formation, but defective calcification and some cementum resorption; and distortion of the growth pattern of alveolar bone. (Becks H et al, 1946) •Studies have suggested that a deficiency of dietary vitamin D leads to periodontal inflammation and a delay in post-surgical periodontal healing. (Stein S.H, 2011) •However, other clinical trials have found no significant link between serum vitamin D levels and periodontal health. (Lee H et al, 2015) • Nevertheless, when the correlation between serum vitamin D levels and disease progression was studied in individuals over 60 years of age, an inverse relationship was observed. (Kaye E.K et al, 2013)
  82. 82. WATER-SOLUBLE VITAMIN DEFICIENCY B-COMPLEX DEFICIENCY Oral changes common to B complex deficiencie s Gingivitis Glossitis Glossodyn ia Angular Cheilitis Inflammation of the entire oral mucosa
  83. 83. VITAMIN B1 (Thiamin) Oral disturbances:  Hypersensitivity of the oral mucosa.  Minute vesicles (simulating herpes) on the buccal mucosa, under the tongue, or on the palate.  Erosion of the oral mucosa • Glossitis; angular cheilitis; seborrheic dermatitis; and superficial vascular keratitis. • Glossitis is characterized by a magenta discoloration and atrophy of the papilla. • In mild to moderate cases, dorsum exhibits a patchy atrophy of the lingual papilla and engorged fungiform papilla, which project as pebble like elevations. • In severe deficiency, the entire dorsum is flat, with a dry and often fissured • surface. VITAMIN B2 (Riboflavin)
  84. 84. VITAMIN B3 (Niacin)  Oral manifestations in experimental animals : ◦ Black tongue ◦ Gingival inflammation with destruction of gingiva, periodontal ligament and alveolar bone. ◦ Necrosis of the gingiva and other oral tissues and leucopenia are the terminal features of niacin deficiency. (Becks H, 1943; Denton J, 1928)  Pellagra characterized by dermatitis, gastrointestinal disturbances, neurologic and mental disturbances (Dermatitis, diarrhea or dementia), glossitis, gingivitis and generalized stomatitis.  Glossitis and stomatitis may be the earliest signs of niacin deficiency. Gingiva may be involved in ANIACINOSIS with or without tongue changes. Most common finding is NUG usually in areas of local irritation.
  85. 85. VITAMIN B9 (FOLIC ACID)  Macrocytic anemia with megaloblastic erythropoeisis, accompanied by oral changes , gastrointestinal changes, diarrhea and intestinal malabsorption.  Folic acid deficient animals demonstrate necrosis of gingiva, periodontal ligament and alveolar bone without inflammation. The absence of inflammation is due to deficiency induced granulocytopenia.  In humans with sprue and other folic acid deficient states, generalized stomatitis occur, accompanied by ulcerated glossitis and cheilitis.  Ulcerative stomatitis is an early indication of the toxic effect of folic acid antagonists used in the treatment of leukemia. Vogel et al (1976,78) reported significant reduction of gingival inflammation after systemic or local use of folic acid compared with placebo. Reduction occurred with no change in plaque accumulation. Authors also postulated that gingival changes associated with pregnancy and OCPs may be partly related to suboptimal levels of folic acid in gingiva.
  86. 86. VITAMIN B12 DEFICIENCY  A deficiency of vitamin B12 is rarely caused by insufficient dietary sources unless strict vegetarian diets are followed.  Lack of intrinsic factor is the primary cause of deficiency.  Pernicious anemia ( megaloblastic anemia) occurs frequently in the elderly relative to achlorhydria and decreased synthesis of intrinsic factor by the parietal cells. • Deficiency symptoms develop very slowly. Initial oral symptoms develop with Glossopyrosis followed by swelling and pallor with eventual disappearance of the filiform and fungiform papilla. • The tongue may be completely smooth, shiny and deeply reddened with loss or distortion of taste. • Stomatitis or a pale or yellowish mucosa, cheilosis, hemorrhagic gingiva and bone loss. • Neurological symptoms like numbness or tingling, occur as a consequence of demyelination of nerves.
  87. 87. VITAMIN C  Severe Vitamin C deficiency in humans result in scurvy, a disease characterized by hemorrhagic diathesis and delayed wound healing.  Scurvy results in:  Defective formation and maintenance of collagen  Impairment or cessation of osteoid formation  Impaired osteoblastic function (Folis R, 1948)  Vitamin C deficiency is also characterized by:  Increased Capillary permeability.  Susceptibility to traumatic hemorrhages.  Hyporeactivity of contractile elements of peripheral blood vessels  Sluggishness of blood flow. (Lee R et al, 1947)
  88. 88.  Hemorrhagic lesions into muscles of extremities, joints & sometimes nail beds. Petechial hemorrhages often around hair follicles. Increased susceptibility to infections. Impaired wound healing. Bleeding and swollen gingiva. Loose teeth. CLINICAL MANIFESTATIONS
  89. 89. POSSIBLE ETIOLOGIC RELATIONSHIPS Low levels of ascorbic acid influence the metabolism of collagen within the peridontium. Thereby affecting the ability of the tissue to regenerate and repair itself. Ascorbic acid deficiency interferes with bone formation( failure of the osteoblasts to form osteoid) leading to loss of periodontal bone. (Glickman I, 1948) Ascorbic acid deficiency increases the permeability of oral mucosa to tritiated endotoxin and tritiated inulin and of normal human crevicular epithelium to tritiated dextran. (Alfano MC et al, 1975) Increasing levels of ascorbic acid enhance both the chemotactic and the migratory action of leukocytes without influencing their phagocytic activity. (Wasserman SI, 1974) An optimal level of ascorbic acid is apparently required to maintain the integrity of the periodontal microvasculature & vascular response to bacterial plaque & wound healing. (Cabrini RL, 1963) Depletion of Vitamin C may interfere with the ecologic equilibrium of
  90. 90. PERIODONTITIS Acute Vit C deficiency results in:  Oedema & Hemorrhage in PDL.  Osteoporosis of alveolar bone.  Tooth mobility  Hemorrhage, oedema & degeneration of collagen fibers occurs in gingiva.  Gingival healing is impaired.  PDL fibers that are least affected by Vit C deficiency are those just below the JE and above alveolar crest.  A case report by Charbeneau & Hurt (1983) showed worsening of preexisting moderate periodontitis with the development of scurvy.  Nishida M et al (2000) found that there was weak but statistically significant dose-response relationship between levels of dietary vitamin C intake & periodontal disease in current & former smokers as measured by clinical attachment. Gingivitis with enlarged, hemorrhagic, bluish red gingiva is described as one of the classic signs of vitamin C deficiency, Gingivitis is not caused by vitamin C deficiency. It is caused by bacterial plaque. Deficiency may aggravate the gingival response to plaque and worsen the edema, enlargement and bleeding. GINGIVITIS
  91. 91. MEDICATIONS 1) BISPHOSPHONATES  Bisphosphonate medications are primarily used to treat cancer (intravenous [IV] administration) and osteoporosis (oral administration).  They act by inhibiting osteoclastic activity, which leads to less bone resorption, less bone remodeling, and less bone turnover. (Russel RG 2007)  The use of bisphosphonates in cancer treatment is aimed at preventing the often lethal imbalance of osteoclastic activity.  In the treatment of osteoporosis, the goal is simply to harness osteoclastic activity to minimize or prevent bone loss and in many cases, to increase bone mass by creating an advantage for osteoblastic activity.  The ability of bisphosphonates to increase bone mass was discovered after animal studies in 1966, but the potential advantage of using bisphosphonates in humans with low bone mass was not appreciated until 1984. (Wade ML et al, 2007)
  92. 92.  Bisphosphonates have a high affinity for hydroxyapatite and are rapidly absorbed in bone, especially in areas of high activity, which may explain why bisphosphonate-induced osteonecrosis is only found in the jaws. (Wade ML,2007)  The bisphosphonate molecule gets incorporated into bone without being metabolized or modified.  During osteoclastic resorption of bone, the trapped bisphosphonate is released and able to affect osteoclasts again.  As a result, the halflife of bisphosphonates in the bone is estimated to be 10 years or more.
  93. 93. Bisphosphonate-induced Osteonecrosis of Jaw (BIONJ)  Avascular necrosis/bisphosphonate-related or -associated ONJ (BRONJ)  First reported in 2003 by Marx in a report of 36 cases of patients with avascular necrosis of the jaws who were treated with IV bisphosphonate for malignant tumors.  The condition of BIONJ has been defined as exposure/necrosis of portions of the jaw bone in patients exposed to bisphosphonates that has persisted more than 8 weeks with no past history of radiation therapy to the jaws. (Ruggiero SL, 2009) Stage 0 is defined as patients at risk who have been treated with IV or oral bisphosphonates but have no apparent exposed/necrotic bone. Stage 1 is exposed/necrotic bone in patients who are asymptomatic with no infection. Stage 2 is exposed/necrotic bone in patients with pain and clinical evidence of infection. Stage 3 is exposed/necrotic bone in patients with pain, infection, and one or more of the following: pathologic fracture, extraoral fistula, or osteolysis
  94. 94.  Clinically, BIONJ presents as exposed alveolar bone occurring spontaneously or after a dental procedure.  The sites may be painful with surrounding soft tissue induration and inflammation. Infection with drainage may be present.  Radiographically, lesions appear radiolucent with sclerosis of lamina dura, loss of lamina dura, or widening of periodontal ligament in areas where teeth are present.  In advanced cases, pathologic fracture may be present through the area of exposed/necrotic bone.  Patients being treated for cancer with IV bisphosphonates are at greater risk than patients being treated for osteoporosis with oral
  95. 95. 2) Corticosteroids  In humans, systemic administration of cortisone and ACTH appears to have no effect on the incidence or severity of gingival and periodontal disease.  However, renal transplant patients receiving immunosuppressive therapy (prednisone or methylprednisone, azathioprine, or cyclophosphamide) have significantly less gingival inflammation than control subjects with similar amounts of plaque. (Been V et al, 1982)  Exogenous cortisone may have an adverse effect on bone quality and physiology.  The systemic administration of cortisone in experimental
  96. 96.  There was capillary dilation and engorgement with hemorrhage into the periodontal ligament and gingival connective tissue, as well as a degeneration and reduction in the number of collagen fibers in the periodontal ligament and increased destruction of the periodontal tissues associated with inflammation.  Stress increases circulating endogenous cortisol levels through stimulation of the adrenal glands (hypothalamic-pituitary-adrenal axis).  This increased exposure to endogenous cortisol may have adverse effects on the periodontium by diminishing the immune response to periodontal bacteria.
  97. 97. OTHER SYSTEMIC CONDITIONS  OSTEOPOROSIS  Osteoporosis is a disease characterized by low bone mass andstructural deterioration leading to an increased risk of bone fracture  affects approximately 10 million people in the US with a higher predilection for females (80%) as compared to males (20%).  An additional 34 million individuals in the US are estimated to have osteopenia or low bone density.  Loss of bone mass and the incidence of osteoporosis increases with age for both men and women, with women affected earlier than men.  The rate of bone loss is greatest for women during the perimenopausal years when estrogen levels decrease.  A bone mineral density (BMD) test is used to measure an individual’s bone mass.
  98. 98.  WHO defines osteoporosis and osteopenia by measures of “standard deviations” as compared to that of a normal healthy young adult.  One of the most significant consequences of osteoporosis is increased risk of bone fracture.  Gender, genetic predisposition, inactivity, deficient diets (deficient in calcium or vitamin D), alcohol,smoking, hormones, and medications put individuals at risk for osteoporosis, with some of these putting them at risk for the progression of periodontitis as well.  Several studies have reported greater tooth loss, more alveolar bone loss and edentulism in individuals with osteoporosis. ( Daniel HW, 1983)  others have suggested that tooth loss is not correlated to osteoporosis or BMD. (Bollen AM, 2004)
  99. 99.  Some studies have concluded that osteoporosis contributes to the progression of periodontitis, (Mohommad AR, 2003) whereas others refute this conclusion. (Lundstrom 2001)  The effect of estrogen deficiency and osteopenia/osteoporosis on periodontitis is not known but may be an important factor to consider.  Lerner UH (2006) also proposed that estrogen deficiency might play a significant role in the progression of periodontitis in osteopenic/osteoporotic women citing that the cytokines believed to be involved in inflammation-induced remodeling are very similar to those suggested to play crucial roles in postmenopausal osteoporosis.  In patients with periodontal disease and concomitant postmenopausal osteoporosis, the possibility exists that the lack of estrogen influences the activities of bone cells and immune cells in such a way that the progression of alveolar bone loss will be enhanced
  100. 100. CONGENITAL HEART DISEASES Occurs in about 1% of live birth.  Striking Feature: Cyanosis, caused by the shunting of deoxygenated blood from the right to left resulting in a return of poorly oxygenated blood to systemic circulation.  Chronic hypoxia causes the impaired development, compensatory polycethemia and clubbing of and edema of toes and fingers.  Oral changes : Cyanosis of lips and oral mucosa, delayed eruption of both deciduous and permanent teeth. Increased positional abnormalities of teeth.  Enamel hyperplasia, teeth are bluish white appearance with increased pulp vascular volume.  More severe caries and periodontal diseases are noticed Congenital heart diseases Tetralogy of Fallot Eisenmenge r’s Syndrome
  101. 101. Tetralogy of Fallot  Characterized by 4 cardiac defects:  VSD ( Ventricular Septal Defect)  PS ( Pulmonary Stenosis)  Malposition of aorta to right.  Compensatory right ventricular enlargement. Clinical Features: Cyanosis Audible heart murmurs Breathlessness
  102. 102.  Oral Changes  Purplish red discoloration of lips and gingiva.  Severe marginal gingivitis and periodontitis  Discoloration returns after cardiac surgery.  Tongue appears coated, fissured, and edematous, and there is extreme reddening of the fungiform and filiform papillae.  The number of subepithelial capillaries is increased but will return to normal after heart surgery. Extensive marginal inflammation-ulcerative necrotic lesions- periodontal destruction Clubbing Of Fingers
  103. 103. Eisenmenger’s Syndrome  Among patients with VSD, about half with large defects (>1.5 cm in diameter) develop this syndrome.  It is distinguished by a greater blood flow from stronger left ventricle to right ventricle (backward flow) through the septal defect causing increased pulmonary blood flow which in turn leads to progressive pulmonary fibrosis, small-vessel occlusion and high pulmonary vascular resistance.  With increased pulmonary resistance, right ventricle hypertrophies shunt becomes bidirectional ultimately blood flow is reversed (right to left) ORAL MANIFESTATIONS  Cyanosis of lips, cheeks and buccal mucosa is observed but it is less severe than those in TOF.  Severe generalized periodontitis has been reported. (Chung
  104. 104. HYPOPHOSPHATASIA  Rare familial skeletal diseases.  Characterized by : • Rickets • Poor cranial bone formation • Craniostenosis • Premature loss of primary teeth particularly primary incisors.  Low level of serum alkaline phosphatase.  Phosphoethnolmine present in the serum and urine.  Teeth are lost with no clinical evidence of gingival inflammation and shows reduced cementum formation. Beumer J (1973).  In aldoscents disease resembles localized aggressive periodontitis.
  105. 105. METAL INTOXICATION  The ingestetion of metals such as mercury, lead and bismuth in medical compounds and through industrial contact may result in oral manifestations caused by either intoxication or absorption without evidence of toxicity. BISMUTH TOXICITY Chronic GI disturbances, nausea, vomiting Jaundice Ulcerative gingivostomatitis, with pigmentation and accompanied by a metallic taste and burning sensation of the oral mucosa. Tongue may be sore and inflamed. SKIN: Urticaria, exanthematous eruptions , herpes zoster like eruptions, pigmentation of the skin and mucous membranes Acute Methemoglobin formation Cyanosis Dyspnoea
  106. 106. Bismuth pigmentation in the oral cavity • narrow, bluish-black discoloration of the gingival margin in areas of preexistent gingival inflammation. • Such pigmentation results from the precipitation of particles of bismuth sulfide associated with vascular changes in inflammation; it is not evidence of intoxication but simply indicates presence of bismuth in the bloodstream. • Bismuth pigmentation in the oral cavity also occurs in cases of intoxication. It assumes a linear form if the marginal gingiva is inflamed.
  107. 107. LEAD INTOXICATION • Pallor of the face and lips & GI symptoms consisting of nausea, vomiting, loss of appetite, and abdominal colic. • Peripheral neuritis, psychologic disorders, and encephalitis have been reported. • Oral signs- salivation, coated tongue, a peculiar sweetish taste, gingival pigmentation, and ulceration. • The pigmentation of the gingiva is linear (burtonian line), steel gray, and associated with local irritation. • Characterized by headache, insomnia, cardiovascular symptoms, pronounced salivation (ptyalism), and a metallic taste. • Gingival pigmentation in linear form results from the deposition of mercuric sulfide. • The chemical also acts as an irritant, which accentuates the preexistent inflammation and commonly leads to notable ulceration of the gingiva and adjacent mucosa and destruction of the underlying bone. MERCURY INTOXICATION
  108. 108. CONCLUSION  The manifestation and progression of periodontitis is influenced by a variety of determinants and factors including subject characteristics, social and behavioral factors, systemic factors, genetic factors, tooth level factors, microbial composition of dental plaque, and other risk factors.  In general, these factors do not initiate chronic destructive periodontitis, but they may predispose, accelerate, or otherwise increase its progression toward periodontal tissue destruction. With the large array of factors that influence the development and progression of periodontitis understanding what the relationships of these factors and determinants are to the initiation and progression of periodontal disease is very