Pathogenesis of periodontal

disease
 Understanding periodontal pathogenesis is key to
improving management strategies for this
common, complex disease.
 The first challenge is to understand exactly what
is meant by the term pathogenesis.
 pathogenesis is defined as the origination and
development of a disease.
 Essentially, this means the step-by-step processes
that lead to the development of the disease,
resulting in a series of changes in the structure and
function of, in this case, the periodontium.
 In broad terms, the pathogenesis of a disease is the
mechanism by which an etiologic factor (or factors)
causes the disease.
 The word derives from the Greek pathos
(suffering, which is a now obsolete translation of
pathos) and genesis (generation/ creation).
 Periodontal disease does not occur as long as balance
between plaque bacteria and host defense is maintained
 Junctional epithelium is tissue most directly challenged
by pathogenic plaque bacteria
 The microbial mass release large quantities of
metabolites like butyric and propanoic acid which are
toxic to periodontal tissues
 Peptides like N- formyl-methionyl-leucyl-phenyl alanine
which is a potent chemo attractant for poly
morphonuclear leuckocytes (PMNL) and endotoxin
are also released by plaque bacteria
 Conti…
 Keratinocytes respond to this bacterial products by releasing
cytokines and proinflamatory mediators
interleukin –I
prostaglandin E2
matrix metalloproteinases
 are released from junctional epithelium.
 these products pass through junctional connective tissue to initiate
inflammation .
 PMN (Polymorphonuclear) are commonly present in junctional
epithelium as part of host defense system
As result of microbial challenge break down products of of PMNL
antibody and compliment system are seen in the gingiva activation of
compliment system is one of earliest host response in gingival crevices
 Antibacterial action of
neutrophils
 Neutrophils deliver antimicrobial factors in four
stages
1.Respiratory burst
2. Secretion of cytosolic and granules components
3. Phagocytosis
4. Lysis apoptosis
 1.Respiratory burst

 When phagocytes come in contact with

organised bacteria they consume dioxygen by
transfering 1 or 2 electrons from cytosolic
nicotinamide adenine dineuclotide phosphate
(NADPH)to extracellular dioxygen via the
NADPH oxidase system releasing potentially
toxic super oxide ion ( o2- ) and hydrogen
perioxide (H2O2).
 This process is called respiratory burst , o2- and
H2O2 are toxic to many microorganisms.
 2.Secretion of cytosolic and granule
components
 Extracellular secretion involves the mobilization of
cytoplasmic granules fusion between granules and
plasma membranes and discharge of granules content
into external environment
 Factors secreted are cal protectin , lysosome ,
defensins , cathepsin G elastase and azurocidin.
 Calprotectin is bacteriostatic at low conce. And
bacteriocidal at high conce.
 Lysozyme has ability to hydrolise the bacterial cell
wall against gram- + ve organisms
 Lactoferin has ability of bactriostatic as well as
bacteriocidal activity
 Defensins are against fungi ,virus and other bacteria.
 3. Phagocytosis
 Bacteria are engulfed by neutrophils forming
phagosome , inside the neutrophils fusion between the
bacteria cytoplasmic granules , lysosome , occurs
resulting in phagolysozome formation .antimicrobial
products are realeased at high conce. And organisms is
killed
 4. lysis or aptosis
 The neutrophils under go aptosis and releases the anti
microbial factors into the envirnment . The anti
microbial products not only destroy microorganisms
but also destroy the host tissues.
 Role of cytokines

 The term cytokines meaning cell protein ,is used for

molecules which transmit information or signals to
another .e.g .
 Interleukins -----carry messages between leukocytes
 Growth factors ----------initiate anabolic activity
 Chemokines ---------cell recruitment to sites
 Interferon ----------are lymphocyte activating
molecules
 Cytokines are produced as well as degraded locally .
 Cytokines act very specifically on target cells
 The importance of cytokines associated
with periodontal disease
1. IL-1 is produced predominantly by macrophages
and lymphocytes and also released by fibroblast ,
platelets , keratinocytes and endo thelial cells .it
activates T & B lymphocytes and promotes antibody
production
2. IL-2 produced by monocytes and lymphocytes it
stimulates T-cells and enhances clonal expansion of B
cells into plasma cells
3. IL -6 released by lymphocytes it stimulates fibro blast
and monocytes , lipopoly sachrides , and tumor necrosis
factors up regulates the secretion of it .
 Conti…..
4.IL-8 it is secreted by monocytes , keratinocytes , endothelial
cells and fibroblast . It is srong chemo attractant of PMNL at
low conce. It activates the PMNL to undergo metabolic burst.
 5.( TNFα tumor necrosis factor α and TNF tumor necrosis
factor β= “lymphotoxin”) Tumor necrosis factors (TNF) and
lymphotoxins Macrophages produces and lymphocytes
release lymphotoxins they stimulates proliferations of
osteoclasts precursors cells and also activates the mature
oseoclasts to resorb bone
TNF also augments leukocytes chemotaxis degranulation ,
adherance to the endothelial cells and its ability to kill
bacteria , also increases vascular permebility.
 6.Prostaglandin E2

 Major sources are macrophages and fibroblast

 Arachidonic acid is converted via cylooxygenase
pathway thromboxane a2 , prostacyclin and
prosta gladin , while the lipoxygenase pathways
gives rise to a family of molecules known as
leukotrienses .
 They contribute to vasodilation and neutrophil
chemotaxis , prostaglandin E2is potent mediator
of osteoclastic resorption.
 7.Matrix metalloprotienases(MMP)

 They are family of enzymes capable of degrading

connective tissue matrix .
 These enzymes are secreted in latent form by
fibroblast , macrophages , keratinocytes and
PMNL
 Collagenases, gelatinize stromalysin matrly sin
and elastase are examples.
 Anabolic cytokines

 They promote tissue repair and regeneration

 Growth factors are secreted by monocytees,
platelets , fibroblasts etc.during repair process
 Platelet derived growth factors , fibroblastic
growth factors , insulin like growth factors and
transforming growth factors are commonly seen in
periodontal tissues during repair and regeneration
 Monocytes play a very important role in tissue
destruction as well as repair.
 Conti……
 Macrophages help in debridement of the wound .

 In the case of an aseptically created wound as in

surgery the monocytes are drawn to the site by
clotting factors .
 Alveolar bone resorption in
periodontal disease
 Alveolar bone resorption leads to periodontal
attachment loss .
 Prostaglandin E2 produced by host cells in
response to bacteria and bacterial cells products,
mediates most of tissue damages in periodontal
tissue damage (disease).
 NSAID has also effective in controlling
periodontal disease progression .
Bone resorption
 summery
 Tissues respond to plaque by the process of inflammation
 Bacteria in plaque release biologically active substances,
s.a. organic acids, endotoxins and chemotactic peptides
 Host tissue responds by leukocyte infiltration releasing
cytokines, s.a. interleukin-1β, interleukin-8,
prostaglandins and TNF-α, as well proteolytic enzymes
(collagenase) and metalloproteinases (MMP-8)
 These substances are responsible for the destruction of
pathogenic bacteria, however, when produced in very high
concentrations they also destroy periodontal tissues.
The Periodontal Disease
Process
END

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