ETIOLOGY OF PERIODONTAL DISEASES
DENTAL PLAQUE = PERIODONTITIS?
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dental plaque → gingivitis (Loe 1965)
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dental plaque → periodontitis
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dental plaque → no periodontitis
PERIODONTITIS – PATOGENESIS
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participation of many genetic and environmental factors (multi-factorial disease)
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presence of different species of bacteria (polymicrobial infection)
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a susceptible host
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the presence of pathogens
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absence of beneficial bacteria
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a conductive environment in the pocket
DENTAL PLAQUE - MATRIX
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bacterial components (polysaccharides)
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host components (saliva glycoproteins, dead cells, serum proteins)
DENTAL PLAQUE - BACTERIA
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approximatly 500 species
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1010 – 1012 of bacteria per gram of plaque
HOW DO BACTERIA CAUSE PERIODONTAL DISEASE?
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acquisition
→ at birth (from mother)
→ later (from partner)
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adherence/retention
→ glycoprotein pellicle
→ mucopolysaccharides (Gram-positive streptococci)
→ lipoteichoic acids (Gram-negative bacteria)
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survival
→ presence of glucose and iron
→ biofilm – a complex structure (bacteria, matrix, bacterial antigens and toxins)
→ avoidance of elimination by host defense system
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multiplication
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elaboration of virulence factors
→ enzymes (collagenase, elastase, hyaluronidase)
→ metabolic waste products (ammonia, cytotoxic amines, volatile fatty acids)
→ toxins (endotoxins – LPS, exotoxins – leucotoxin)
MATURATION OF PLAQUE BIOFILM
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immature plaque
Gram-positive aerobic and facultative bacteria→ rods and cocci (S. sanguis, Actinomyces sp.)
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matured plaque
Gram-negative anaerobic bacteria → rods, spirochetes
WHICH ORGANISMS CAUSE PERIODONTAL DISEASE
1. THE SPECIFIC PLAQUE HYPOTHESIS (Loesche 1976)
Specific microorganisms are necessary for the development of periodontal disease
Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia
2. THE NON-SPECIFIC PLAQUE HYPOTHESIS (Thielade 1986)
Periodontal disease results from the shear mass of bacteria present and once this exceeds a
certain threshold, disease will occur
3. THE ENVIROMENTAL PLAQUE HYPOTHESIS (Haffajee 1991)
The entire subgingival microbial environment is the key to periodontal disease developing
Condition
Organism
Healthy gingivae
Streptococcus sanguis
Actinomyces viscosus
Streptococcus oralis
Gingivitis
Fusobacterium nucleatum
Porphyromonas gingivalis
Necrotising ulcerative gingivitis
Treponema vincentii
Fusobacterium nucleatum
Prevotella intermedia
Condition
Organism
Localised aggressive periodontitis
Aggregatibacter actinomycetemcomitans
Generalised aggressive periodontitis
Porphyromonas gingivalis
Chronic periodontitis
Porphyromonas gingivalis
Tannnerella forsythia
Treponema denticola
Fusobacterium nucleatum
Campylobacter rectus
Eikenella corrodens
Peptostreptococcus micros
Prevotella intermedia
THE ENVIROMENTAL PLAQUE HYPOTHESIS (Haffajee 1991)
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Bacteria must be of a virulent clonal type
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The host must be susceptible to the pathogen
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The number of pathogens within a clone must exceed a threshold for the host
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Bacteria must be located at correct site
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Other species must support or at least not inhibit the pathogen
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The local environment must be conductive the the production of virulence factors
SUBGINGIVAL BIOFILM (Socransky 1998)
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certain organisms cluster together in discrete micro-environments
Complex
Bacteria
Purple
Veillonella parvula
(gram-positive rods and cocci)
Actinomyces odontolyticus I
Yellow
Streptococcus sanguis
(gram-positive facultative cocci)
Streptococcus godonii
Streptococcus intermedius
Streptococcus oralis
Streptococcus mitis
Green
Eikenella corrodens
(gram-positive and gram-negative rods/ cocci non-motile)
Aggregatibacter actinomycetemcomitans
Capnocytophagia ochracea
Capnocytophagia sputigena
Capnocytophagia gingivalis
Complex
Bacteria
Orange
Fusobacterium nucleatum
(gram-positive and gram-negative rods/ cocci some motility)
Fusobacterium periodonticum
Prevotella intermedia
Prevotella nigescens
Streptococcus constellatus
Eubacterium nodatum
Campylobacter gracilis
Campylobacter rectus
Campylobacter showae
Peptostreptococcus micros
Red
Porphyromonas gingivalis
(gram-negative, anaerobic, motile)
Tannerella forsythia
Treponema denticola
Porphyromonas gingivalis
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Gram-negative anaerobic rod
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dark pigmentation on media containing lysed blood
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Black pigmentation due to accumulated hemin used as an iron source for growth
Virulence factors
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IgA proteases
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Collagenases
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Hemagglutinins - mediate the binding of Pg to epithelial cells and erythrocytes
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LPS – endotoxin
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Gingipain(cystein proteases)
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Trypsin-like protease
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Fimbriae - mediate the binding of Pg to epithelial cells
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Cytotoxic metabolic end products - butyrate, propionate, have low molecular weights which
allows them to easily penetrate periodontal tissue and disrupt the host cell activity
Tannerella forsythia
Virulence factors
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LPS - endotoxin
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Trypsin-like protease
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cell-wall lipoproteins -induction of apoptosis
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Cytotoxic metabolic products– fatty acids
Treponema denticola
Virulence factors
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Major outer membrane protein (Msp) - 53-kDa adhesin with pore forming activity, cytotoxic
for epithelial cells and erythrocytes
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Proteases - involved in cell attachment, tissue destruction, tissue invasion
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Hemin- /lactoferrin-binding proteins - iron acquisition and utilizes lactoferrin from the saliva
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Immunosuppressive activity - suppressed lymphocyte proliferative responses to antigens
and mitogens
Aggregatibacter actinomycetemcomitans
Virulence factors
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Leukotoxin - binds monocytes, neutrophils and lymphocytes, forms pores and leakage of
contents
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LPS – endotoxin
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Collagenases
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IgA proteases
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Fc-binding proteins -proteins that bind the Fc region of Igs, can compete with neutrophils
for binding to the Fc and therefore inhibit phagocytosis
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Fimbriae
CONCLUSIONS OF CLINICAL IMPORTANCE
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Gingivitis is a disease caused by the progressive accumulation of plaque at the gingival
margin - plaque removal results in resolution
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The majority of patients may suffer from gingivitis
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Specific bacteria cause chronic periodontitis, they exist in a subgingival biofilm, where selfsupport and protection provide resistance to elimination
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Only a small number of patients appear susceptible to aggressive periodontitis
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Physical disruption of the biofilm is essential to eliminate anaerobic pathogens
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Pathogens can be transmitted within families
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Failure of therapy me be due to factors peculiar to the patient, but may also be due to reinfection from a partner or family member
HOST RESPONSE
innate immunity
→ intact epithelial barriers
→ anti-bacterial factors present in saliva or GCF
→ neutrophils and macrophages
→ complement cascade
→ chemokines i cytokines
acquired immunity
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T cells
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B cells
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immunoglobulins
CYTOKINES ADN PERIODONTITIS
Cytokine
Source
Effect
IL-1
IL-6
TNF
PGE2
macrophages
activation of osteoclasts
fibroblasts
activation of neutrophils
epithelial cells
production of PGE2, TNF and IL-6
macrophages
production of acute phase proteins
fibroblasts
bone resorption
epithelial cells
activation of T and B cells
macrophages
production of IL-1 and PGE2
epithelial cells
activation of neutrophils
macrophages
blood vessel permeability
neutrophils
activation of neutrophils
mast cells
bone resorption
epithelial cells
CONCLUSIONS OF CLINICAL IMPORTANCE
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In clinical health, PMNs are the predominant defence cells. Innate immunity functions at a
low level, without causing significant tissue damage
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As plaque builds up, complement activation leads to a greater inflammatory response and
gingival tissue damage
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With time, T and B lymphocytes appear, providing specific and controlled killing of bacteria
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If left untreated in disease-susceptible patients, the size of inflammatory response exceeds a
threshold, and the host tissue damage occurs as a side-effect of the defence strategy
RISK ASSESSMENT
Risk factor – a factor that increases the probability that a disease may develop in an individual
1. systemic (subject-based) risk factor (smoking)
2. local (site-based) risk factor (overhanging restorations occlusal forces)
Risk marker (predictor) – is not linked to ‘causation’, but is a consequence of the disease being
present (bleeding on probing)
RISK FACTORS
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genetic (inherited syndromes, polymorphism of cytokines, FcR, MMPs)
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behavioural (poor oral hygiene, smoking, stress, malnutrition)
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metabolic disorders (diabetes mellitus, pregnancy, oral contraceptive, osteoporosis)
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haematological (leukaemia, myelodysplasia syndrome, agranulocytosis)
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drugs (phenytoin, calcium channel blockers, cyclosporine)
MOST IMPORTANAT RISK FACTORS FOR PERIODONTAL DISEASE
Increased plaque amount
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improper oral hygiene
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overhanging restorations or crowns
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caries cavities
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teeth crowding
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xerostomia
Improper host defence
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innate or acquired host immune deficiency
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hyperreactivity of host immune system (IL-1) and other genetic factors
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general diseases (diabetes)
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environmental factors (stress, smoking, unbalanced diet, certain medications)
GENE POLYMORPHISMS AND PERIODONTITIS IN THE CAUCASIAN POPULATION
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IL-1α (-899), (+4845)C>T
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IL-1β (+3953/4)C>T
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IL-6(-572)G>C
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IL-10 (-819)C>T, (-592)C>A
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IL-18 (-607)A>C, (-137)G>C
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FCGR2A, FCGR3A
SMOKING AS A RISK FACTOR
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3-6 times higher risk of periodontitis
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one cigarette per day increases attachment loss by 0,5%
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 prevalence of T. forsythia
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harder to eradicate A.a., P.g. and T.f.
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 level of salivary IgA
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 release of TNF, IL-1, i IL-6 by monocytes when stimulated by LPS
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 destruction of extra-cellular matrix proteins
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 gingival keratosis and fibrosis
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 gingival blood flow