1.
INFLUENCE OF
SYSTEMIC CONDITIONS
ON PERIODONTIUM
Presented by:
SURBHI KAPOOR
MDS 2nd YEAR
DEPT. OF PERIODONTOLOGY
AND ORAL IMPLANTOLOGY

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.
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.
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.
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.
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.
 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.
•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.
• 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.
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.
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.
•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.
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.
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).

15.
CYTOKINES, MONOCYTES AND MACROPHAGES

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.
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.
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.
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.
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.
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.
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.
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.
 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.
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.
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.
 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.
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.
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.
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.
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.
 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.
 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.
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.
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.
 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.
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.
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.
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.
Secondary
hyperparathyroidism- Ground
glass appearance.
Periapical And Occlusal Radiographic appearance of
browns tumor

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.
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.
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.
 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.
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.
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.
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.
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.
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.
 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.
 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.
 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.
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.
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.
 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.
 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.
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.
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.
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.
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.
 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.
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.
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.
 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.
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.
 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.
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.
 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.
 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.
 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.
Stress
Induced
Immuno-
suppression
Boypati et al 2007

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.
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.
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.
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.
 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.
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.
 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
 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.
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.
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.
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.
 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.
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.
 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.
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.
 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.
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.
 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.
 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.
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.
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.
 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.
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.
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.
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.
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.
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.
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