"INFLUENCE OF SYSTEMIC FACTORS(CONDITIONS) ON PERIODONTIUM"

GOOD MORNING

INFLUENCE OF SYSTEMIC

CONDITIONS ON THE

PERIODONTIUM

CONTENTS

• Endocrine Disorders and hormonal changes• Hematologic disorders and immune

deficiencies• Genetic disorders• Stress and psychosomatic disorders• Nutritional influences• Medications• Other Systemic Conditions.

ENDOCRINE DISORDERS AND HORMONAL CHANGES.DIABETES MELLITUS

• Diabetes mellitus is a clinically and genetically heterogeneous group of metabolic disorders

manifested by abnormally high levels of glucose in the blood.

• The hyperglycemia is the result of a deficiency of insulin secretion caused by pancreatic Beta cell dysfunction or of resistance to the action of insulin in liver and muscle

or a combination of these. (Brian L Mealey 2007)

CLINICAL SIGNS & SYMPTOMS AND DIABETIC COMPLICATIONS

• Polyuria (excessive urination)• Polydipsia ( excessive thirst)• Polyphagia (excessive hunger)• Unexplained weight loss• Changes in vision• Fatigue, weakness• Irritability• Nausea• Dry mouth

COMPLICATIONS RetinopathyNephropathyNeuropathyMacrovascular diseaseAltered wound healingPeriodontal disease( Loe H. Periodontal disease is the sixth complication of diabetes mellitus. Diabetes Care,1993).Ketoacidosis (usually associated with severe hyperglycemia in Type I diabetes)Hyperglycemic hyperosmolar stateHypoglycemia

ORAL MANIFESTATIONS OF DIABETES

• Xerostomia• Greater susceptibility of oral tissues to trauma• More opportunistic infections (e.g., Candidiasis)• Greater accumulation of plaque, greater risk of caries• Greater susceptibility to periodontal disease• Greater risk of developing periodontal abscesses when

periodontitis is present• Delayed healing• Oral paraesthesia, including burning mouth or tongue• Altered taste sensations

DIABETES: DIAGNOSTIC CRITERIA AND EVALUATION OF GLYCEMIC CONTROL

Three ways in diagnosis• Symptoms of diabetes + casual glucose

concentration>200mg/dl(>11.1 mmol/l).

• Fasting plasma glucose ≥126 mg/dl (≥7.0 mmol/l)

• 2 -hour postload glucose ≥200 mg/dl (≥11.1 mmol/l) during an oral glucose tolerance test.

GLYCATED HEMOGLOBIN(HB A1c)

Formed in erythorocytes by non-enzymatic reactions between hemoglobin protein and glucose. This binding is highly stable.

Hemoglobin remains glycated for life span of RBC’s

Accurately reflects mean blood glucose concentration over last 1-3 months.

Normal is less than 6%

Measurement of glycated proteins • Alternative to the HbA1c for assessment of

glycemic control over time.

• The fructosamine test measures glycated albumin.

• Reflects glycemic control over a shorter interval (weeks), than the HbA1c test (months).

• The normal range for the fructosamine test is between 200 and 300 µmol/l.

EFFECTS OF DIABETES ON THE PERIODONTIUM

GINGIVITIS •Erythema, oedema, •Bleeding on probing,•Gingival exudates.

PERIODONTITIS•Greater attatchment loss & bone loss (Emrich LJ 1991, Shlossman M 1990).•Multiple periodontal abscess•Loosened teeth

PATHOGENESIS OF PERIODONTAL DISEASE IN DIABETIC SUBJECTS

Bacterial flora• Although bacteria are necessary for periodontal

diseases to occur, few differences in the subgingival microflora between diabetic and non-diabetic patients with periodontitis (Zambon JJ1988,Sastrowijoto S 1989).

HOST DEFENSE ALTERATIONS• The function of immune cells, including neutrophils,

monocytes, and macrophages, is altered in diabetes (American Academy of Periodontology 1999).

• Neutrophil adherence, chemotaxis, and phagocytosis are often impaired (Manouchehr-Pour M 1981).

• Monocytes from diabetic subjects produce elevated levels of TNF-α in response to antigens from Porphyromonas gingivalis (Salvi GE 1997).

HOST DEFENSE ALTERATIONS• Subjects with HbA1c levels over 8% had crevicular

fluid levels of interleukin-1 beta (IL-1β) almost twice as high as subjects with HbA1c levels <8% (Engebretson SP 2005).

• The net effect of these host defense alterations in diabetes is an increase in periodontal inflammation, attachment loss, and bone loss.

ALTERATIONS IN CONNECTIVE TISSUE METABOLISM

• Impaired osseous healing and bone turnover (Loder RT 1988, Tisdel CLn 1995, White CB 2003).

• Inhibition of osteoblastic cell proliferation and collagen production -reduced bone formation - poor newly formed bone (Gooch HL 2000, Beam HA 2002, Lu H,2003).

• Increased rate of apoptosis of fibroblasts & osteoblasts (He H, Liu R 2004).

More severe periodontal attachment loss

Impaired wound healing

Elevated gingival crevicular fluid glucose levels in diabetic individuals (Ficara AJ 1975).

Inhibiting attachment and spreading of fibroblasts (Nishimura F 1998).

Impaired wound healing and tissue turnover

Formation of AGE (advanced glycation end-products )

AGE’shave multiple effects on cell-to-cell and cell-to-matrix interactions and are commonly thought to be a major link between the various diabetic complications.

Higher levels of periodontal AGE accumulation are found in those with diabetes than in non-diabetic subjects (Schmidt AM 1997).

AGEs often form on collagen, increasing collagen cross-linking

formation of highly stable collagen macromolecules

resistance to normal enzymatic degradation

AGE-modified collagen accumulates in the walls of larger blood vessels

macrovascular complications of diabetes

• AGE-modified collagen macromolecules accumulate and resulted in increased basement membrane thickness in the microvasculature, altering normal homeostatic transport across the membrane (Frantzis 1991).

• AGE formation - increased production of vascular endothelial growth factor (VEGF), plays a major role in microvascular complications of diabetes.

• Also present in gingival tissues of diabetic subjects ( Gurdal 2003).

AGE- RAGE interaction

• ‘‘receptor for AGEs’’ (RAGE) found on the surface of smooth muscle cells, endothelial cells, neurons, and monocytes/ macrophages (Schmidt AM1997).

• A 50% increase in mRNA for RAGE in gingival tissues of type 2 diabetic subjects (Katz J, Bhattacharyya I, 2005).

AGE- RAGE interaction

• AGE-RAGE interaction on the endothelium, causing an increase in vascular permeability and thrombus formation.

• The AGE-RAGE interaction on monocytes increases cellular oxidant stress and activates the transcription factor nuclear factor kappa B (NF-kB)- results in the increased production of proinflammatory cytokines.

Altered collagen metabolism in diabetes

AGE altered collagen- highly stable

Glycation in bone collagen appear to affect bone turnover, bone formation is reduced (Gunczler P,2001)

Altered osteoblastic differentiation and extracellular matrix production (McCarthy 2001, Santana RB 2003)

Increased levels of osteoclast numbers, resorptive markers, and bone resorption (Takagi M 1997, Valerio G 1999)

Alter wound healing responses to chronic microbial wounding of the periodontium.

FEMALE SEX HORMONESGingival alterations during Puberty ,pregnancy

and menopause are associated with physiologic hormonal changes in the female patient.

Gingiva in PUBERTY• Pronounced inflammation,bluish-red

discolouration,edema and enlarged gingiva.

• There is increased prevalence of gingivitis,bleeding,exudation from inflammed gingiva,but the crevicular fluid is not affected.

GINGIVAL DISEASES IN PREGNANCY

• Pronounced base of bleeding

• Gingiva is bright red to bluish red

• Marginal and interdental gingiva is edematous,pits on pressure and sometime presents rasberry like appearance

• There is depression of maternal T-lymphocyte response.

• Aggravation of gingivitis has been attributed principally to increased levels of progesterone

• Increased crevicular fluid,pocket depth,mobility.

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.

MENOPAUSE• Females can develop gingivostomatitis• Oral mucosa is dry and shiny,vary in color from abnormal

paleness to redness,and bleed easily.• Dry burning sensation throughout the oral cavity• Extreme sensitivity to thermal changes;abnormal taste

sensations described as salty,peppery or sour.

HYPERPARATHYROIDISM• 25% to 50% of patients hyperparathyroidism has

associated oral changes• Malocclusion• Tooth mobility• Radiographic evidence of alveolar osteoporosis

with closely meshed trabeculae• Widening periodontal space• Absence of the lamina dura• radiolucent cystlike spaces.

HEMATOLOGIC DISORDES AND IMMUNE DEFICIENCIES

WBC• Involved in inflammatory

reactions for cellular defense• Proinflammatory cytokine

release

RBC• Gas exchange • Nutritional supply to the periodontal

tissues and platelets.• Normal hemostasis• Recruitment of cells during inflammations

and wound healing

• Abnormal bleeding from the gingiva or other areas of the oral mucosa that is difficult to control is an important clinical sign.

• Petechiae• Ecchymosis(Soft palate)

• Deficiencies in the host immune response may lead to severely destructive lesions.

LEUCOCYTE DISORDERS.• Disorders that affect production or function of leukocytes

may result in severe periodontal destruction.

• Neutropenia: Results in low levels of circulating neutrophils.

• Agranulocytosis:is more severe neutropenia involving not only neutrophil but also basophils and eosinophils.

Anug Drug idiosyncrasy-most common cause

• Gingival margin may or may not be involved.• Gingival hemorrhage,necrosis,increased

salivation,and fetid odor• In cyclic neutropenia- gingival changes recur

with recurrent exacerbation of the disease• generalized aggressive periodontitis.

LEUKEMIA• Periodontal manifestationsLeukemic infiltrationBleedingOral ulcerationsInfections.

ANEMIA

• Pernicious anemia and Iron deficiency anemia- marked pallor changes in gingiva

• Sickle cell anemia--Generalized osteoporosis of the jaws,with a peculiar stepladder alignment of the trabeculae of the interdental septa,along with pallor and yellowish dicoloration of oral mucosa.

• Periodontal infections precipitate sickle cell crisis.

• Aplastic anemia--Pale discoloration of the oral mucosa and increased susceptibility to infection because of the concomitant neutropenia.

THROMBOCYTOPENIC PURPURA

• Gingivae are swollen,soft and friable.• Bleeding occurs spontaneously or on slight

provocation and is difficult to control.• Gingival changes represent an abnormal

response to local irritation.

ANTIBODY DEFICIENCY DISORDERS

• Agammaglobulinemia• Recurrent bacterial infections• Patients are susceptible to periodontal

infections • Aggressive periodontitis in children.

GENETIC DISORDERS• Primary neutrophil disorders Chediak Higashi Syndrome Lazy leucocyte syndrome• Secondary netrophil disorders Papillon lefevere syndrome Down syndrome.

STRESS AND PSYCHOSOMATIC DISORDERS

• Psychological stress might play a role as an aetiological agent of periodontal disease (Dean and Dean 1945 and Schluger 1949).

Genco et al. (1998)

Genco et al. (1998)

• 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.

PSYCOSOMATIC DISORDERS

• It affects the oral cavity by 1) development of habits that are injures to the

periodontium as grinding or clenching the teeth, nibbing on foreign objects as pencils, nail biting of excessive use of tobacco.

2) direct effect to the autonomic nervous system on the psychologic tissue balance.

NUTRITIONAL DEFICIENCIES

1. There are no Nutritional defencies that by themselves may cause Gingivitis or Periodontitis (Carranza 11t edi)

2. There are Nutritional defencies that produce changes in oral cavity. (Carranza 11th edi)

Changes include alterations of tissue of lips, oral mucosa,gingiva and bone

Vitamin Deficiency • Fat soluble : A,D,E,K • Water soluble: B,C

Vitamin A• Major function is to maintain health of epithelial cells of skin &

mucous membrane.• Prevent microbial invasion by maintaining epithelial integrity • Deficiency leads to – Hyperkeratosis, Hyperplasia of gingiva, increased pocket formation, proliferation of Junctional epithelium, Retardation of wound healing

Vitamin D

• Essential for absorption of Ca from GIT and maintenance of Ca- P balance

• Deficiency Rickets in children, osteomalcia in adults

• Animals – Osteoporosis of alveolar bone

Vitamin E• Serves an Antioxidant to prevent free radical reactions

• Protect cells from Lipid Peroxidation

• Cell membranes which contain highest content of Polyunsaturated Fatty Acids are major site of Vitamin E deficiency

• No direct relation have been found between Vitamin E deficiency and Oral Disease .

• Systemic Vitamin E have been shown to accelerate gingival wound healing .

Oral Changes associated • Gingivitis • Glossitis • Glossodynia • Angular Cheilitis • Inflammation of entire oral mucosa • Oral disease is rarely caused by a deficiency in just one

component of the B-complex group, the deficiency is generally multiple Vitamin B Complex Deficiencies.

• Gingivitis in vitamin deficiencies is non- specific because it is caused by bacterial plaque rather than by deficiency but deficiency can have modifying effect.

• B1 or Thiamine Deficiency Characterised by • Paralysis • CVS symptoms including Edema • Loss of Apetite Oral symtoms • Hypersenstivity of Oral Mucosa, • Minute vesicles on oral mucosa, buccal vesicles on buccal mucosa, under the

tongue or on palate

B2 Riboflavin Deficiency • • Glossitis-Magenta Discoloartion • • Angular Cheilitis • • Seborrheic Dermatitis • • Superficial Vascularising Keratitis • • Atrophy of Papillae • • Angular Chelitis-Perleche

B3 Niacin Deficiency • Pellagra characterised by • 3Ds – Dermatitis – Diarrhea – Dementia • 3Gs – Glossitis – Gingivitis – Generalised Stomatitis

Glossitis and Stomatitis are the earliest signs of

Niacin Deficiency • Gingiva may be involved with or without tongue

changes

Folic acid Deficiency • Results in Macrocytic Anemia with

Megaloblastic Erythropoiesis • Oral Changes • GI lesions • Diarrhea • Intestinal Malabsorption

• Ulcerative stomatitis is an early indication of toxic effect of Folic acid antagonist (Methotrexate) used in treatment of leukemia.

• Gingival changes associated with pregnancy and OCP may be partly related to suboptimal levels of Folic acid in Gingiva.

• Phenytoin induced gingival growth and folic

acid, based on interference of folic acid absorption and utilization of Phenytoin.

Vitamin C or Ascorbic acid Deficiency • Defective formation and maintenance of

collagen • Impairment or cessation of Osteoid formation • Impaired Osteoblastic function • Increased capillary permeabilty • Susceptiblity to traumatic hemorrhages • Hyporeactivity of contractile element of

peripheral blood vessels

CLINICAL MANIFESTATION • Hemorrhagic lesions into muscles &

extremities,joints, nail beds • Petechial hemorrhages around hair follicles • Susceptibilty to infections • Impaired healing • Bleeding, swollen gums and loosened teeth

• Vitamin C deficiency may aggravate the gingival response to dental plaque and worsen the edema, enlargement and bleeding

• Acute vitamin C deficiency does not cause or increase the incidence of gingival inflammation, but it does increases its severity

Protein Deficiency

Degeneration of gingival& Periodontal connective tissue

Osteoporosis of Alveolar bone Impaired deposition of cementum Delayed wound Healing Atrophy of Tongue Epithelium.

MEDICATIONS

• Bisphosphonates –associated with Osteoradionecrosis of jaws.

• Corticosteroids-adverse effect by diminishing the immune response to periodontal bacteria.

OTHER SYSTEMIC CONDITIONS

HYPOPHOSPHATASIA Familial skeletal disease characterized by • Rickets,Poor Cranial Bone Formation, Premature loss of primary

teeth • Low level of Serum Alkaline Phosphatase

• Phosphoethanolamine present in serum and urine

• Teeth are lost with no clinical evidence of gingival inflammation

• Reduced cementum formation

• Early exfoliation of primary incisors in Hypophosphatasia.

CONGENITAL HEART DISEASE • Cyanosis of Lips & Oral Mucosa • Delayed eruption of both decidious and

permanent dentition •More severe Periodontal disease seen in

Cyanotic Congenital Heart Disease patients

TERATOLOGY OF FALLOT ORAL CHANGES: • Purplish Discoloration of lips and Gingiva • Severe marginal Gingivitis and Periodontal

Destruction

EISENMENGER’S SYNDROME

Oral Manifestations:• Cyanosis of Lips, Cheeks, • Buccal Mucosa Severe Generalised

Periodontitis have been reported in Eisenmengers syndrome

BISMUTH INTOXICATION

• GIT disturbances, • Ulcerative gingivostomatitis with pigmentation.• Metallic taste.• Burning sensation of the mucosa .• Inflamed sore tongue .• Narrow bluish black discoloration of the gingival

margin due to precipitation of bismuth sulfide associated with vascular changes in inflammation of the gingiva .

LEAD IN TOXICATION • pallor of face and lips .

• Peripheral neuritis, psychologic disorders and encephalitis .

• Excessive salivation .

• Coated tongue .

• Sweetish taste.

• Gingival ulceration and pigmentation (Linear pigmentation in burtonian line, Steel gray )

MERCURY INTOXICATION

• Headache • C.V.S. symptoms .• Increase salivation .• Metallic taste .• Gingival pigmentation in linear pattern due to

mercuric sulfide.• Gingival ulceration and destruction of the

underlying bone.

Other chemicals :• Phosphorus .• Arsenic .• Chromium

Inflammation and ulceration of the gingiva . Necrosis of alveolar bone and loosening of

teeth .

CONCLUSION

Dentists need to appreciate the wide range of systemic conditions that have periodontal implications to modify the treatment of affected patients,and in some cases,the dentist may be the first doctor to diagnose systemic disease based on its oral presentation.

REFERENCES1. Carranza, clinical periodontology 11th edition2. Ainamo J,Lahtinen A,Uitto VJ:Rapid periodontal destruction in adult humans

with poorly controlled diabestes.Areport of 2 cases,J Clinical Periodontal 17:22-28,1990.

3. Barett AP:Gingival lesions in leukemia.A Classification,J Periodontology 55:585-588,1984Carranza, clinical periodontology 10th edition.

4. Brain l mealey. Diabetes melitus and periodontal disease. Periodontol 2000 – vol 44, 2007 page – 127-153.

5. Elalla, I B lamster. Hypoglycemia , glycoxidation and receptor for AGE . potential mechanism underlying diabetic complications including diabetis associated periodontitis.Periodontol 2000, vol 23, 2000, 50-62.

6. Terry d. Rees. Periodontal management of the patient with diabetes mellitus. Periodontology 2000, vol. 23, 2000, 63–72.

7. Joseph p. Fiorellini&marc l. Nevins. Dental implant considerations in the diabetic patient. Periodontology 2000, vol. 23, 2000, 73–77.