Pathogenesis of periodontitis

D R G A B R I E L D O E K E T E M E P I , G C P S I I

PATHOGENESIS OF PERIODONTITIS

OUTLINE• Introduction• Theories

• Biofilm• Complexes• Microbial Virulence

• Clinically Healthy GINGIVA• Stages of Periodontitis• HOST RESPONSE• Host Innate Defense• Adaptive Defense

• Modifying Factors• Summary• References

PERIODONTITIS

• Periodontitis, also known as pyorrhea, is a set of inflammatory diseases affecting the periodontium, i.e., the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth.

• Inflammatory and immune reactions to microbial plague are the predominant features of gingivitis and periodontitis.

THEORIES

BIOFILM

• Cooperating community of various types of microorganisms

• Microorganisms are arranged in microcolonies with channels between the microcolonies

• Microcolonies are surrounded by protective matrix• Differing environments within the microcolonies in the

biofilm• Microbial gene expression differs when microorganisms

are in a biofilm• Microorganisms have primitive communication system• Microorganisms in biofilm are resistant to antibiotics,

antimicrobials, and host response

MICROBIAL COMPLEXES

• Multiple bacterial spp are implicated at various stages of disease.• Bacterial species relevant at a stage of the

disease may not be important at other stages• The pathogenicity of micro-organism relates to

interplay between:• Individuals host innate capability• Adaptive response• Virulence of the bacteria

MICROBIAL VIRULENCE

• Microbial invasion• Enzymes- Protease• Endotoxin – lipopolysaccharide• Microbes and their products can directly or

indirectly harm the host. However, the main detrimental effect may be the host’s own innate, inflammatory and immune response to the foreign molecules and antigens of the microbe

CLINICALLY HEALTHY GINGIVA

• Clinically healthy gingiva is associated with small infiltrate of inflammatory cells that involves both junctional epithelium and subjacent Connective Tissue.• Subclinical inflammatory reactions occur in

response to the continuous presence of bacterial pdts in the crevice.• Present in a healthy gingiva are:• Leucocyte; PMN• lymphocyte• Macrophages

STAGES OF PERIODONTAL DISEASE

• Four stages - Page and Shroeder (1976), • Initial• Early• Established• Advanced

INITIAL

• 24hrs of plaque accumulation changes in dentogingival plexus• Increased blood flow (vascular dilatation)• Increased hydrostatic pressure• Formation of inter cellular gaps between Endothelial cells• Increased Gingivo crevicular Fluid• Chemotaxis of PMNWithin 2-4 days of days of plaque, there is an established response but gingiva still looks healthy clinically

EARLY LESION

• There is marginal redness of the gingiva- characteristic clinical symptom.

• Lymphocytes and PMNs are predominant leukocytes in the infiltrate at this stage

• Very few plasma cells• Degeneration of fibroblasts via apoptosis• Breakdown of collagen fibers providing space for

inflammatory cells• Basal cells of junction and sulcular epith proliferate. • Biofilm may now form

ESTABLISHED LESION

• Exposure to plaque continues leading to enhancement of the inflammatory response of the gingiva

• Plasma cells predominate• Increased proliferation of epithelium and rete pegs

extend deeper into the connective tissue• Junction epithelium is substituted by pocket epithelium.

Enhancing further apical migration of the biofilm• Ulceration of pocket epithelium • 2 types of established lesion appear to exist;• Stable• Progressive

ADVANCED LESION

• As the pocket deepens, the biofilm continues its apical down growth and flourishes in this anaerobic ecological niche. • There is further loss of connective tissue and

bone• The lesion is not localized to gingiva but extends

apically and laterally into CT with Plasma cells dominant.

HOST RESPONSE

• How an individual responds to the bacterial attack, greatly determines the disease progression.

Host Innate DefenseAdaptive Defense

INNATE DEFENSE SYSTEMS

Does not require any previous contact with the micro-organismIncludes: Barrier function of oral epitheliumVascular and Cellular aspects of inflammatory responseMechanical washing effects of Saliva and GCFAntibodies, proteases, complement, cytokines, salivary lactoferrin found in saliva and GCFToll-like receptors

• The immune system generally elicits a vigorous inflammation response against pathogens aimed at eliminating them, whereas it normally tolerates commensals.

ADAPTIVE DEFENSE SYSTEMS

• Adaptive response unlike Innate, utilizes features like recognition, memory and binding to support the effector system (via Innate) in the elimination of psthogens.• It is the SECOND line of defense• Hallmarks of adaptive immunity are immune

memory and clonal expansion• Consists of Cell mediated immunity and Humoral

response

• Cells involved:• Plasma cells• B cells• T helper cels• T cytotoxic cells• PolyMorphonuclear leucocytes• Macrophages

Antigen presenting Cells also play a role

MODIFYING FACTORS

• Diabetes,

• Puberty, Pregnancy and Menopause

• Tobacco smoking

• Drugs

Microbial Challenge

Host Immuno-inflammatory response

Connective tissue and bone metabolism

Clinical signs of disease initiation and progression

Environmental and acquired risk factors

Genetic risk factors

Page, Ann Periodontol 1998

Summary of Pathogenesis of Periodontitis

Pathogenesis of Periodontitis

Microbial Challenge




Bacteria attacking the body• Antigens• Lipopolysaccharides• Other virulence factors

Microbial Challenge




Bacteria attacking the body• Antigens• Lipopolysaccharides• Other virulence factors

The body defense:• Antibodies• Neutrophils

Microbial Challenge





Inflammatory response releases:• Cytokines• Prostanoids• Matrix Metalloproteinases

In Patient A, who is NOT susceptible to periodontitis:

Microbial Challenge





Tissue and bone repair/healing

In Patient B, who is susceptible to periodontitis:

Microbial Challenge





Tissue destruction and bone loss

Microbial Challenge





Deepening of periodontal pockets, furcation involvement, contaminated cementum…

In Patient B, who is susceptible to periodontitis:

Microbial Challenge




Environmental and acquired risk factors

Genetic risk factors


Pathogenesis of Periodontitis

In periodontitis, what is actually occurring in a periodontal pocket…

Periodontal Pathogens has invaded:

• Periodontal pocket• Cementum• Gingival tissue

In a patient susceptible to periodontitis, how does the body react?

1. Epithelial Cells produce IL-8 and ICAM-1 in response to bacteria & antigens

IL-8/ICAM-1

2. IL-8 and ICAM-1 are chemotactic signals for neutrophils, which are recruited to the sulcus

Neutrophils

Bacteria/Antigens

3. Neutrophils control bacterial assault by phagocytosis but also secrete matrix metalloproteinases or collagenases (MMP-8) which results in collagen degradation MMP-

8

4. Interaction of antigens with B cells lead to production of antibodies and complements, which contribute to phagocytosis

B-cell

Plasma Cell

T-cell

5. In response to bacterial LPS, various cells produce IL-1, TNF-, and PGE2

Activated B-Cell

LPSMacrophage

Fibroblast

IL-1TNF-

PGE2

Activated B-Cell

Macrophage

Fibroblast

IL-1TNF-

Osteoclast activation

PGE2

6. Production of IL-1, TNF-, and PGE2 leads to osteoclast activation, proliferation and differentiation

Higher amounts of IL-

1, TNF-, PGE2, MMPs

Disease Health

Lower amounts of IL-10, TGF-, IL-1ra, TIMPs

Major Mediators

• Proinflammatory• Destructive

Lower amounts of IL-

1, TNF-, PGE2, MMPs

Disease Health

Higher amounts of IL-10, TGF-, IL-1ra, TIMPs

• Anti-inflammatory• Protective

• Thanks

1. Karring T., Lang NP., Lindhe J., Clinical periodontology and Implant dentistry, (2008) 5th ED.

2. Pathogenesis of Periodontitis, Lecture notes, School of Medicine and Dentistry, University of Ghana.

3. Pathogenesis of Periodontitis, Lecture notes, University of Toronto

4. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr., Microbial complexes in subgingival plaque. J Clin Periodontol. 1998 Feb;25(2):134-44.

Pathogenesis of periodontitis

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