Etiology of periodontal diseases

11/19/1411/19/14 Ossama El-ShallOssama El-Shall 11

Etiology & pathogenesis of Etiology & pathogenesis of Periodontal DiseasesPeriodontal Diseases

Dr. Ossama El-ShallDr. Ossama El-Shall

Professor and Chairman; Oral Medicine, Professor and Chairman; Oral Medicine, Periodontology, Diagnosis and Radiology Periodontology, Diagnosis and Radiology

Dept.Dept.Faculty of Dental Medicine, Al-Azhar Univ. , Faculty of Dental Medicine, Al-Azhar Univ. ,

Girls Branch. Girls Branch. E-mail : [email protected] : [email protected]


The pathogenesis of periodontal The pathogenesis of periodontal disease. disease.

Periodontal diseases Periodontal diseases are the most common of are the most common of the oral inflammatory the oral inflammatory diseases and are diseases and are described as the described as the bacterially initiated bacterially initiated conversion of a healthy conversion of a healthy gingival region to one gingival region to one characterized by characterized by inflammation inflammation (gingivitis) and the (gingivitis) and the destruction of the destruction of the supporting structures of supporting structures of the teeth (periodontitis).the teeth (periodontitis).


The pathogenesis of periodontal diseases is a sequence of The pathogenesis of periodontal diseases is a sequence of processes from periodontal health to the development of processes from periodontal health to the development of

characteristic lesion of periodontal destruction.characteristic lesion of periodontal destruction.


The pathogenesis of periodontal disease. The pathogenesis of periodontal disease.

The recognition that periodontal diseases The recognition that periodontal diseases are infection process is important to are infection process is important to understand their pathogenesis.understand their pathogenesis.

InfectionInfection is defined as the process by is defined as the process by which pathogenic microorganisms penetrate which pathogenic microorganisms penetrate or invade the host tissue and cause injury or invade the host tissue and cause injury followed by reactive inflammatory followed by reactive inflammatory phenomena.phenomena.


BacteriaBacteria are the primary causative are the primary causative agents of periodontal diseases. agents of periodontal diseases.

Bacteria in dental plaque that Bacteria in dental plaque that accumulate on the tooth surface and on accumulate on the tooth surface and on the gingival margin the gingival margin induce the early induce the early forms of gingival inflammationforms of gingival inflammation..

Certain Certain productsproducts from these plaque from these plaque bacteria enter the gingival tissues and bacteria enter the gingival tissues and initiateinitiate the immuno-inflammatory the immuno-inflammatory processes.processes.


The inflammatory immune response is The inflammatory immune response is characterized by recruitment of inflammatory characterized by recruitment of inflammatory cells cells (PMNs, monocytes, and lymphocytes)(PMNs, monocytes, and lymphocytes) and and mediators (cytokines, prostagandins and matrix mediators (cytokines, prostagandins and matrix metalloproteinase)metalloproteinase) to the local area to the local area to fightto fight the the bacterial challenge. bacterial challenge.

The amount of inflammation and the severity of The amount of inflammation and the severity of destruction of periodontal disease differed destruction of periodontal disease differed widely widely among patients. among patients.

This variability in disease expression is the This variability in disease expression is the result of result of genetic and acquiredgenetic and acquired environmental environmental factors that modify the host response to factors that modify the host response to bacteriabacteria


Genetic risk factors

Environmental and acquired risk factors

Bacteria on the teeth and

gingival margin

Immuno-inflammatory response in periodontal

tissue

C.T and bone

destruction

Clinical signs of disease

AB

PMNs

Antigen

LPS,other V factors

Cytokines

Pgd

MMPs

Tissue breakdown products & ecological changes


Dental plaque induced gingivitisDental plaque induced gingivitis

It is the inflammation of the gingiva in the absence of clinical attachment loss


Chronic periodontitisChronic periodontitis

Inflammation of the gingiva and the adjacent Inflammation of the gingiva and the adjacent attachment apparatus. attachment apparatus. Loss of clinical attachment due to: Loss of clinical attachment due to:

*Destruction of the periodontal ligament.*Destruction of the periodontal ligament. *Loss of the adjacent supporting bone.*Loss of the adjacent supporting bone.


Etiology of Periodontal DiseasesEtiology of Periodontal Diseases In health there is equilibrium between In health there is equilibrium between

aggression of bacterial plaque and reparative aggression of bacterial plaque and reparative tissue capacity.tissue capacity.

bacterial plaque

Host responce


This equilibrium could be broken by increased amount or virulence of bacteria

or decreased defensive capacity of tissue.

bacterial plaque

Host responce


Etiology of periodontal disease

Primary etiology(Initiating factors)

Secondary etiology(predisposing factors)

Microbial effect

Host response

Local predisposing factor

Systemic predisposing factors


Bacterial Plaque

Reparative tissue capacity

Host response

Factors that upset the balance by

Increasing aggression

I- Initiating factorsII- Local factors

Decreasing defense Systemic factors


Initiating factors

Microbial dental plaqueMicrobial dental plaque


Local factorsCalculus.Calculus.Materia alba.Materia alba.Food debris. Food impaction. Food retention.Food debris. Food impaction. Food retention.Faulty dentistry. Faulty dentistry.

Over hanging fillingOver hanging filling Roughness of filling materialsRoughness of filling materials Over or under contoured crownsOver or under contoured crowns Inadequate located proximal contactInadequate located proximal contact Occlusal disharmonyOcclusal disharmony Orthodontic wiresOrthodontic wires

MalocclusionMalocclusion trauma. trauma.Mouth breathing.Mouth breathing.Unreplaced missing teeth.Unreplaced missing teeth.Dental wear,Dental wear, -Attrition, Physiologic loss of enamel-Attrition, Physiologic loss of enamel -Abrasion, Mechanical loss of enamel-Abrasion, Mechanical loss of enamel -Erosion, Chemical loss of enamel-Erosion, Chemical loss of enamelHabits.Habits. Bruxism, tongue thrusting,& smoking. Bruxism, tongue thrusting,& smoking.


Subgingival calculus


Crowding


Overhanging restoration


Primary EtiologyPrimary Etiology

a) Microbial effect

Dental plaque composition and types

Role of dental plaque in periodontal diseases


Microbial dental plaqueMicrobial dental plaque Dental plaqueDental plaque is a complex, is a complex, tenaciously attachedtenaciously attached

aggregations of bacteria to the tooth and other oral aggregations of bacteria to the tooth and other oral surfaces,surfaces,

Saliva, gingival fluid, and liquids from diet can penetrate through this structures depending on its

porosity.

The porosity in turn depends on the specific arrangement of bacteria and the extent to which the intercellular spaces are filled with polysaccharides and

other matrix substances synthesized by plaque bacteria.

It also contains few inflammatory and epithelial cells with intermicrobial matrix filling the spaces between them.


The intermicrobial matrix

polysaccharides

livans (5%) dextrans (95%)

formed by bacterial enzymes from sucrose

These chemical compounds hold the units of plaque together, keeping it firmly attached to each other and to tooth surface.

All these structural components of dental plaque are assembled on salivary-derived pellicle called acquired pellicle which is made up of glycoproteins derived from submandibular glands


Submandibular gland

Glycoproteins + Saliva

Acquired pellicle formation

Carbohydrates and sucrose in oral cavity

Dextrans & Levans

Bact. enzymesHold bacteria, inflammatory cells, and

other plaque components firmly attached to tooth

surfaces


Plaque may be differentiated from other Plaque may be differentiated from other deposits that may be found on the tooth deposits that may be found on the tooth surface such as asurface such as a

materia-alba and calculusmateria-alba and calculus

Materia alba;Materia alba; refer to soft accumulations of refer to soft accumulations of bacteria and tissue cells and debris that:bacteria and tissue cells and debris that:

Lack the organized structure of dental plaque Lack the organized structure of dental plaque Easily displaced with a water spray.Easily displaced with a water spray.

Calculus;Calculus; is a hard deposit that forms by is a hard deposit that forms by mineralization of dental plaque and is generally mineralization of dental plaque and is generally covered by a layer of un-mineralized plaque.covered by a layer of un-mineralized plaque.


Materia alba generalized throughout the mouth, with heaviest accumulation near the gingiva.


Supragingival plaque disclosed with an oxidation-reduction dye that indicates reduced (anaerobic) areas

of plaque.


Marginal supragingival plaque and gingivitis.


Dental plaque Dental plaque

Plaque is divided into 2 Plaque is divided into 2 distinct types based on the distinct types based on the relationship of the plaque relationship of the plaque to the gingival margin:to the gingival margin:

Supragingival plaqueSupragingival plaque Subgingival plaqueSubgingival plaque


Classification of dental PlaqueClassification of dental Plaque

Supragingival Subgingival

Coronal :Coronal : on the tooth on the tooth surfacesurface

Marginal:Marginal: in an immediate in an immediate contact with the gingival contact with the gingival margin.margin.

Tooth associatedTooth associated: : subgingival plaque; on subgingival plaque; on enamel and cementumenamel and cementum

Epithelial associatedEpithelial associated: : subgingival plaque; on subgingival plaque; on inner surface of the inner surface of the pocketpocket

Apical bacteriaApical bacteria: loosely : loosely adherentadherent


Supragingival plaqueSupragingival plaque

Supregingival plaqueSupregingival plaque

Mechanism of formationMechanism of formation

A.A.Formation of acquired pellicle.Formation of acquired pellicle.

B.B.Bacterial adherence or colonization.Bacterial adherence or colonization.

C.C.Formation of intermicrobial matrix.Formation of intermicrobial matrix.

D.D.Plaque maturation and growth.Plaque maturation and growth.


Supragingival plaqueSupragingival plaque Mechanism of formationMechanism of formation

A-Formation of acquired pellicle:A-Formation of acquired pellicle:

The first process in pellicle formation is adsorption of The first process in pellicle formation is adsorption of salivary glycoproteins to the enamel surface. salivary glycoproteins to the enamel surface.

This process involves electronic attraction between This process involves electronic attraction between opposite charges on opposite charges on (enamel)(enamel) and the and the salivary salivary macromolecules (glycoproteins).macromolecules (glycoproteins).

In the early stages , it is of small globular In the early stages , it is of small globular aggregations , and after maturation it becomes a aggregations , and after maturation it becomes a fibrellar or granular is structure. fibrellar or granular is structure.


Submandibular gland

Glycoproteins + Saliva

Acquired pellicle formation

Carbohydrates and sucrose in oral cavity

Dextrans & Levans

Bact. enzymesHold bacteria, inflammatory cells, and

other plaque components firmly attached to tooth

surfaces


B- Bacterial adherence or colonization :B- Bacterial adherence or colonization :

Bacterial colonization of the surface of the Bacterial colonization of the surface of the acquired pellicle takes place very rapidly .acquired pellicle takes place very rapidly .

Bacteria may attach directly to the salivary pellicle Bacteria may attach directly to the salivary pellicle or it may attach to the plaque aggregation.or it may attach to the plaque aggregation.

This attachment is mediated by This attachment is mediated by specific enhancers specific enhancers of colonization calledof colonization called adhesionsadhesions on the bacterial on the bacterial cell and receptors on the salivary glycoprotein ,eg . cell and receptors on the salivary glycoprotein ,eg . proline rich protein . proline rich protein .

This process is also influenced by inhibitors of This process is also influenced by inhibitors of

colonization, eg .IgA.colonization, eg .IgA.


C- Formation of intermicrobial matrix :C- Formation of intermicrobial matrix :

These are organic substances formed by These are organic substances formed by bacterial enzymes from sucrose, they are bacterial enzymes from sucrose, they are mainly polysaccharides constitute of mainly polysaccharides constitute of glucansglucans and and LevansLevans. .

The The glucansglucans is mainly dextran which is a is mainly dextran which is a sticky adhesive material that has a major sticky adhesive material that has a major role in colonization of bacteria role in colonization of bacteria

Livan,Livan, on the other hand, functions as a on the other hand, functions as a storage of polysaccharide, providing a storage of polysaccharide, providing a source of fermentable carbohydrate when source of fermentable carbohydrate when hydrolyzed .hydrolyzed .


The intermicrobial matrix

polysaccharides

livans (5%) dextrans (95%)

formed by bacterial enzymes from sucrose


D- Plaque maturation and growth :D- Plaque maturation and growth :

The growth and maturation of attached The growth and maturation of attached organisms occurs byorganisms occurs by multiplication multiplication, and , and the organism becomes resident of the the organism becomes resident of the plaque aggregate. plaque aggregate.

Organisms that attach but fail to grow Organisms that attach but fail to grow on the surface often do not become a on the surface often do not become a stable part, and these are termed stable part, and these are termed transient organisms.transient organisms.


Disclosed supragingival plaque covering one half to two thirds of the clinical crowns.


Supragingival plaque disclosed with an oxidation-reduction dye that indicates reduced (anaerobic) areas of plaque.


24 hour plaque growth disclosed with red dye


Supragingival plaque EcologySupragingival plaque Ecology


Supragingival plaque Ecology Supragingival plaque Ecology

In early stages of plaque accumulation In early stages of plaque accumulation (2days)(2days) the tooth surface is colonized the tooth surface is colonized primarily by primarily by

gram–positive facultative cocci , gram–positive facultative cocci , which are mainly which are mainly Streptococcus speciesStreptococcus species, , andand

gram–positive rods gram–positive rods that are mainly that are mainly Actinomyces spiecesActinomyces spieces..


Over the next Over the next 7-days7-days other early other early colonizers enter the plaque, including colonizers enter the plaque, including

gram-negative anaerobic cocci such as gram-negative anaerobic cocci such as Veillonella speciesVeillonella species in addition of some in addition of some

gram–negative rod such as gram–negative rod such as Capnocytophaga speciesCapnocytophaga species..


By time more strictly anaerobic bacterial By time more strictly anaerobic bacterial species become prominent, in particular species become prominent, in particular Fusobacterium speciesFusobacterium species and and

Prevotella intermediaPrevotella intermedia.. The morphology of the plaque at this The morphology of the plaque at this

time is primarily filamentous instead of time is primarily filamentous instead of coccoid that of early stage, and reflects coccoid that of early stage, and reflects the dominance of the dominance of ActinomycesActinomyces and and FusobacteriumFusobacterium species. species.


This ecological structure remain relatively This ecological structure remain relatively stable if undisturbed and represents the stable if undisturbed and represents the layer of plaque attached to the tooth layer of plaque attached to the tooth surface . surface .

Late colonizers appear at different times Late colonizers appear at different times on the surface of this bacterial material. on the surface of this bacterial material. Porphyromonas gingivalisPorphyromonas gingivalis, , motile rodsmotile rods, and , and SpirochetesSpirochetes are major component of the late are major component of the late colonizers. colonizers.

Mature supraingival plaque may induce Mature supraingival plaque may induce gingivitis and supragingival calculus, and may gingivitis and supragingival calculus, and may be the precursor of subgingival plaque.be the precursor of subgingival plaque.


Summary of Events Summary of Events

Initial colonisationInitial colonisation by by pioneer speciespioneer species

OutgrowthOutgrowth, microcolonies , microcolonies are formed which spread are formed which spread outwards and upwardsoutwards and upwards

Secondary colonizationSecondary colonization and and multiplication. Species multiplication. Species diversity increases. The diversity increases. The proportion of streptococci proportion of streptococci decreases as the plaque is decreases as the plaque is invaded by bacteria from invaded by bacteria from other genera other genera


Subgingival plaqueSubgingival plaque


Mechanism of formationMechanism of formation

The tooth associated subgingival plaqueThe tooth associated subgingival plaque is is dominated by gram–positive filamentous dominated by gram–positive filamentous bacteria and therefore, it nearly has same bacteria and therefore, it nearly has same mechanism of formation of mechanism of formation of supragingival supragingival plaqueplaque as discussed before. as discussed before.

The mechanism of formation of the The mechanism of formation of the epithelial associatedepithelial associated and the and the apical apical subgingival plaquesubgingival plaque will be discussed through will be discussed through the subgingival plaque ecology .the subgingival plaque ecology .

Subgingival plaque Ecology Subgingival plaque Ecology


Supragingival plaque maturation

Inflammatory changes

Swelling of gingival margin and increase

in GCF.

The supragingival plaque that is covered by the swollen gingival margin and bathed by (GCF) undergoes ecological changes that result in bacterial composition

characteristic of subgingival plaque .


The structure of The structure of epithelial associatedepithelial associated and the and the apical subgingival plaqueapical subgingival plaque is very different than is very different than that seen in supragingival areas. that seen in supragingival areas.

With the destruction of With the destruction of epithelial attachmentepithelial attachment and and formation of periodontal pocketformation of periodontal pocket, ,

some some gram–negative anaerobic speciesgram–negative anaerobic species may may become attached to the cementum and provide become attached to the cementum and provide a different basis for ecological niche that has a different basis for ecological niche that has low 0low 022 potential potential which allows for anaerobic of which allows for anaerobic of bacteria . bacteria .


Some bacteria also bind directly to Some bacteria also bind directly to the lining pocket epithelium and allow the lining pocket epithelium and allow the formation of a loose adherent the formation of a loose adherent mat on its surface mat on its surface

(epithelial associated subgingival plaque).(epithelial associated subgingival plaque).


The bottom or the apical portion of the The bottom or the apical portion of the pocket has loosely adherent and somewhat pocket has loosely adherent and somewhat unorganized filamentous gram–negative rods unorganized filamentous gram–negative rods and and spirochetesspirochetes (the apical bacteria of (the apical bacteria of subgingival plaque).subgingival plaque).

In this area , the virulent periodontal In this area , the virulent periodontal

pathogens may be found such as pathogens may be found such as PorphyromonasPorphyromonas.gingivalis, Bacteriod forsythus .gingivalis, Bacteriod forsythus and Actinobacillus actinomycetemcomitansand Actinobacillus actinomycetemcomitans. .

The bacteria in this area is sometimes The bacteria in this area is sometimes referred to as the referred to as the advancing front.advancing front.

Advancing frontAdvancing front

Porphyromonas gingivalisPorphyromonas gingivalis, , Bacteriod forsythus Bacteriod forsythus Actinobacillus actinomycetemcomitansActinobacillus actinomycetemcomitans..

Aggregatibacter actinomycetemcomitansAggregatibacter actinomycetemcomitans



Mature and undistributed subgingival Mature and undistributed subgingival

plaque may induce root caries, root plaque may induce root caries, root

resorption and different forms of resorption and different forms of

periodontal diseases, it also may be periodontal diseases, it also may be

the precursor of subgingival calculus.the precursor of subgingival calculus.

Factors that influence bacterial plaque mass

composition


Bacterial FactorsBacterial Factors A- A- Bacterial AttachmentBacterial Attachment B- Bacterial metabolism and nutritional B- Bacterial metabolism and nutritional factorsfactors

Host FactorsHost Factors A-A- Mechanical cleaningMechanical cleaning B- Periodontal pocket depthB- Periodontal pocket depth C- SmockingC- Smocking


Bacterial Factors that influence bacterial mass compositionBacterial Factors that influence bacterial mass composition

A- A- Bacterial Attachment

Bacteria may Bacteria may attach directlyattach directly to the to the salivary pellicle on the tooth surface as salivary pellicle on the tooth surface as described before, or it may adhere to described before, or it may adhere to the plaque by interbacterial aggregation the plaque by interbacterial aggregation process. These attachments are modified process. These attachments are modified by by enhancersenhancers and and inhibitorsinhibitors of of colonization. colonization.


The The enhancersenhancers of the of the attachmentattachment

are the are the adhesionsadhesions on the on the bacterial cells (Fembriae bacterial cells (Fembriae and Pili) and also by and Pili) and also by specific receptors specific receptors contained in the salivary contained in the salivary pellicle (Proline rich pellicle (Proline rich protein).protein).

The The inhibitorsinhibitors of of attachmentattachment

are the secretory are the secretory

immunoglobulin A immunoglobulin A (IgA),(IgA), Lactoperoxidase and Lactoperoxidase and Lactoferrin which are Lactoferrin which are salivary enzymes that salivary enzymes that inhibit bacterial growth.inhibit bacterial growth.

This important This important influence on bacterial influence on bacterial ecology may be most ecology may be most prominent in situations in prominent in situations in which there are which there are disturbance in the content disturbance in the content of saliva or in the of saliva or in the production of IgA.production of IgA.




B-B-Bacterial metabolism and nutritional factorsBacterial metabolism and nutritional factors

Bacterial metabolic environment is determined by:Bacterial metabolic environment is determined by:

1-1- The nature and availability of nutrients. The nature and availability of nutrients.2-2- PH of the ecological niche. PH of the ecological niche.3-3- The oxidation-reduction potential. The oxidation-reduction potential.4-4- Metabolic inhibitors. Metabolic inhibitors.


1-Nature and availability of nutrients1-Nature and availability of nutrients

This factor depends on the nature ofThis factor depends on the nature of

A-A- Host diet Host diet

B-B- Presence of bacterial species that can Presence of bacterial species that can undergo interbacterial feeding mechanism.undergo interbacterial feeding mechanism.



Nature and availability of nutrientsNature and availability of nutrients

Bacterial metabolism depends in part on the Bacterial metabolism depends in part on the chemical composition of the chemical composition of the host diethost diet, the , the smaller the molecules and the longer time it is smaller the molecules and the longer time it is retained in the oral cavity, the easier their retained in the oral cavity, the easier their degradation by bacteria.degradation by bacteria.

This factor is highly influence by the This factor is highly influence by the stickiness stickiness of foodof food and the and the frequency of intakefrequency of intake..

The nutritional interaction of bacteria is a The nutritional interaction of bacteria is a mechanism by which mechanism by which bacteria can utilize bacteria can utilize nutrients from each othersnutrients from each others. This can be . This can be illustrated, illustrated, as an exampleas an example, in the following , in the following diagramdiagram



Available nutrients in the oral cavityAvailable nutrients in the oral cavity

COH Small carbohydrate molecules (sucrose & lactose)

Oxygen Salivary glycoproteins

Streptococcus

ActinomycesLactate Formate

Veillonella

H2Menadione (vit K)

Cambilobacter rectus

Blood hemin at gingival bleeding sites

Porphyromonas gingivalis

Fusobacterium, Eubacteria, prevotella intermedia

A.actinomycetemcomitans, Capnocytophaga, Eikenella

corrodens, Bacteroid forsythus

CO2


2- PH of the ecological niche2- PH of the ecological niche

Some bacteria functions very well in low-Some bacteria functions very well in low-pH (acidic) and referred to as pH (acidic) and referred to as acidophilic bacteria e.g Lactobacillus acidophilic bacteria e.g Lactobacillus species. Some other bacteria can not species. Some other bacteria can not tolerate the low-pH, e.g.Streptococcus tolerate the low-pH, e.g.Streptococcus species.species.



3- Oxidation –reduction potential:3- Oxidation –reduction potential:

Anaerobic bacteria can not live in the Anaerobic bacteria can not live in the presence of oxygen. presence of oxygen.

Mature supragingival plaque and Mature supragingival plaque and undisturbed subgingival plaque provide undisturbed subgingival plaque provide the most suitable environment for the most suitable environment for anaerobic growth of bacteria. anaerobic growth of bacteria.



4-Bacterial metabolic inhibitors:4-Bacterial metabolic inhibitors:

Some bacteria produce substance that Some bacteria produce substance that inhabit for growth of others, eg. inhabit for growth of others, eg. BacteriocineBacteriocine produced by produced by bacteroidbacteroid species can kill other bacteria.species can kill other bacteria.

Another example are the compounds Another example are the compounds produced by produced by SterptococcusSterptococcus species species that can inhibit the growth of that can inhibit the growth of A.actinomycetemcomitans.A.actinomycetemcomitans.



Bacterial FactorsBacterial Factors A- A- Bacterial AttachmentBacterial Attachment B- Bacterial metabolism and nutritional B- Bacterial metabolism and nutritional factorsfactors

Host FactorsHost Factors A-A- Mechanical cleaningMechanical cleaning B- Periodontal pocket depthB- Periodontal pocket depth C- SmockingC- Smocking


Host factors that influence bacterial mass composition Host factors that influence bacterial mass composition

A- Mechanical cleaning:A- Mechanical cleaning:

This is the most dominant influence on This is the most dominant influence on plaque mass and composition. The mechanical plaque mass and composition. The mechanical disruption of plaque forces the ecological disruption of plaque forces the ecological succession to start over after every cleaningsuccession to start over after every cleaning

The cleaner the tooth surface, the more The cleaner the tooth surface, the more immature the ecological system around it, immature the ecological system around it, and the more difficult and longer the system and the more difficult and longer the system will take to reach full maturity and produce will take to reach full maturity and produce harmful effect.harmful effect.


Host factors that influence bacterial mass compositionHost factors that influence bacterial mass composition

B- Periodontal pocket depth.B- Periodontal pocket depth.

It is likely that deeper pockets provide many It is likely that deeper pockets provide many of the ecological features that favors the of the ecological features that favors the growth of pathogenic bacteria as discussed growth of pathogenic bacteria as discussed before. Therefore the deeper the pocket the before. Therefore the deeper the pocket the most likely it can support the growth of most likely it can support the growth of fastidious bacterial speciesfastidious bacterial species. .

A deep pocket would not only provide an A deep pocket would not only provide an escape for bacteria from cleaning but also escape for bacteria from cleaning but also may be a heaven for the host derived may be a heaven for the host derived nutrients through the constant flow of gingival nutrients through the constant flow of gingival crevicular fluid. crevicular fluid.


C- SmokingC- Smoking

Smoking is one of the strongest risk Smoking is one of the strongest risk factors for periodontal diseases, it can factors for periodontal diseases, it can inhibit the host immunological response that inhibit the host immunological response that can help to control the bacterial challenge.can help to control the bacterial challenge.

Smoking also may favor bacterial Smoking also may favor bacterial

colonization through altering the tissue colonization through altering the tissue response by affecting PMNs and Antibody, response by affecting PMNs and Antibody, thus allowing easier spread and growth of thus allowing easier spread and growth of certain bacteria.certain bacteria.

Host factors that influence bacterial mass compositionHost factors that influence bacterial mass composition


The concept of plaque Biofilm : The concept of plaque Biofilm : an integrate teem an integrate teem

The ecological interactions of dental plaque The ecological interactions of dental plaque described above is better understood recently described above is better understood recently by the introduction of the concept of plaque by the introduction of the concept of plaque biofilm.biofilm.

Plaque Plaque biofilmbiofilm is defined as is defined as ““matrix–enclosed bacterial populations adherent matrix–enclosed bacterial populations adherent

to each other and /or to surface or interfaces to each other and /or to surface or interfaces ““

For many years this description was applied For many years this description was applied for adherent bacterial masses in water pipes, for adherent bacterial masses in water pipes, water tanks, and other humid structures.water tanks, and other humid structures.


• Supragingingival and subingival dental plaque exhibit Supragingingival and subingival dental plaque exhibit all the primary characteristics of biofilm according to all the primary characteristics of biofilm according to its inherent structure.its inherent structure.

• This include a primitive circulatory system and a This include a primitive circulatory system and a complex microbial community that is highly integrated in complex microbial community that is highly integrated in terms of nutritional needs and metabolic requirements.terms of nutritional needs and metabolic requirements.

• Understanding that dental plaque is biofilm is Understanding that dental plaque is biofilm is critical to clinical practice, because special attention critical to clinical practice, because special attention should be made to control bacteria that live in a should be made to control bacteria that live in a biofilm. biofilm.

• Most important, bacteria living in biofilm are not Most important, bacteria living in biofilm are not easily eradicated by antimicrobial agents. This means easily eradicated by antimicrobial agents. This means that control of bacteria living in dental plaque biofilm that control of bacteria living in dental plaque biofilm must start with physical disruption of the plaque.must start with physical disruption of the plaque.

• The golden rule is that once dental plaque has bacteria The golden rule is that once dental plaque has bacteria

can not be treated by antimicrobial agents alone.can not be treated by antimicrobial agents alone.


Bacteria Associated with periodontal Bacteria Associated with periodontal Diseases Diseases

Bacteria associated with gingivitis :Bacteria associated with gingivitis :Actinomyces viscosusActinomyces viscosusPrevotella intermediaPrevotella intermediaPorpheromonas gingivalis Porpheromonas gingivalis Fusobacterium nucleatumFusobacterium nucleatumEubacterium timidus Eubacterium timidus Treponema species Treponema species

Colonization in periodontal diseasesColonization in periodontal diseases



Bacteria associated with chronic Bacteria associated with chronic Periodontitis:Periodontitis:

1.1. Porpheromonas gingivalis.Porpheromonas gingivalis.2.2. Bacteroid forsythus.Bacteroid forsythus.3.3. Actinobacillus actinomycetemcomitans. Actinobacillus actinomycetemcomitans. 4.4. Fusbacterium nucleatum.Fusbacterium nucleatum.5.5. Prevotella intermediaPrevotella intermedia. .


Prophyromonas gingivalisProphyromonas gingivalis

A member of A member of black pigmented bacteroides.black pigmented bacteroides.

Gram Gram negative anaerobicnegative anaerobic non motile, rods ( dependent on non motile, rods ( dependent on nitrogenous substrate for its energy) with the greatest nitrogenous substrate for its energy) with the greatest proteolytic activity.proteolytic activity.

The major pathogen associated with severe, adult forms of periodontitis is Porphyromonas gingivalis.

This organism produces potent cysteine proteases known as gingipains, which have specificity for cleavage after arginine or lysine residues.

The lysine specific gingipain, Kgp, appears to be the ‑major virulence factor of this organism.



Porpheromonas gingivalisPorpheromonas gingivalis

P. gingivalis is an anaerobic motile rod that P. gingivalis is an anaerobic motile rod that has been implicated in chronic periodontisis for has been implicated in chronic periodontisis for so many years. so many years.

Virulence factors:Virulence factors: true collagenasetrue collagenase, , EndotoxinEndotoxin and and powerful proteases called gingipains powerful proteases called gingipains . In . In addition to low-molecular weight compounds addition to low-molecular weight compounds such as hydrogen sulfide and ammonia .such as hydrogen sulfide and ammonia .

The net result of these virulence factors is The net result of these virulence factors is that that P. gingivalis P. gingivalis has the ability to induce bone has the ability to induce bone resorption, destroy connective tissue, and resorption, destroy connective tissue, and inhabit host protective immune response.inhabit host protective immune response.

““As the other bacteria As the other bacteria attack and immune cells attack and immune cells counterattack, counterattack, progressively damaging progressively damaging the integrity of the the integrity of the tooth in the process, tooth in the process,

P. gingivalis P. gingivalis sits in the sits in the shadows and feasts on shadows and feasts on the inflammatory spoils,”the inflammatory spoils,”



Bacteroid forsythus Bacteroid forsythus

B.forsythusB.forsythus is a gram–negative anaerobic is a gram–negative anaerobic rod with pointed ends, due to its rod with pointed ends, due to its fastidious needs of growth, it is usually fastidious needs of growth, it is usually found in deep pockets.found in deep pockets.

And it can also be associated with And it can also be associated with

aggressive periodontitis.aggressive periodontitis.


Actinobacillus actinomycetemcomitans Actinobacillus actinomycetemcomitans

Although this microorganism is strongly Although this microorganism is strongly associated with aggressive Periodontitis, associated with aggressive Periodontitis, it was also observed occasionally in it was also observed occasionally in associated with chronic Periodontitis.associated with chronic Periodontitis.

A has an extensive collection of virulence A has an extensive collection of virulence factors comparable with factors comparable with P. gingivalis.P. gingivalis.

These include a true These include a true collagenase, collagenase, endotoxine, proteases and leukotoxins.endotoxine, proteases and leukotoxins.

Leukotoxin; kills PMNs and monocytes.Cytolethal distending toxinImmunosuppression factors that inhibit blastogenesis, antibody production and activate T-suppressor cellsInhibition of PMNs functionsResistant to complement mediated killing.LipopolysaccharidesSurface antigensHeat shock proteinsAntimicrobial resistance


http://en.wikipedia.org/wiki/Granulocyte

http://en.wikipedia.org/wiki/Monocytes

http://en.wikipedia.org/wiki/Cytolethal_distending_toxin

http://en.wikipedia.org/wiki/Antibody

http://en.wikipedia.org/wiki/Granulocyte

http://en.wikipedia.org/wiki/Complement_system


Fusbacterium nucleatumFusbacterium nucleatum

This microorganism is found in This microorganism is found in early plaque early plaque induced gingivitis induced gingivitis and increase prominently and increase prominently with the development of Periodontitis. with the development of Periodontitis.

This organism produce high concentration of This organism produce high concentration of butyric acid butyric acid and capable of initiating early and capable of initiating early inflammatory response.inflammatory response.

It is a gram–negative anaerobic rod and is It is a gram–negative anaerobic rod and is associated with chronic Periodontitis with associated with chronic Periodontitis with severe attachment loss.severe attachment loss.


Prevotella intermediaPrevotella intermedia

It has been associated with chronic It has been associated with chronic Periodontitis, aggressive Periodontitis and Periodontitis, aggressive Periodontitis and also in association with ANUG and also in association with ANUG and pregnancy gingivitis.pregnancy gingivitis.Gram negative short round ended anaerobic Gram negative short round ended anaerobic rodsrodsIt resist phagocytes (due to its capsule)It resist phagocytes (due to its capsule)It has LPS endotoxin that has marked effect It has LPS endotoxin that has marked effect on immune cells and bone cellson immune cells and bone cells


Bacteria associated with aggressive Bacteria associated with aggressive Periodontitis :Periodontitis :

A. actinomycetemcomitans A. actinomycetemcomitans Capnocytophaga species Capnocytophaga species P. intermedia P. intermedia P. gingivalis P. gingivalis when chronic periodontitis is when chronic periodontitis is superimposed on localized aggressive superimposed on localized aggressive periodontitis .periodontitis .


Bacteria associated with refractory Bacteria associated with refractory chronic periodontitis chronic periodontitis

F. nucleatum F. nucleatum P. gingivalis P. gingivalis P. intermediaP. intermediaE corodansE corodansCambylobacter rectusCambylobacter rectusB. forsyhusB. forsyhus


Bacteria associated with NUGBacteria associated with NUG

P. intermedia. P. intermedia. F. nucleatum.F. nucleatum.Spirochetes (Treponema species).Spirochetes (Treponema species).


The complexes are comprised of species thought to colonize the tooth surface and proliferate at an early stage. The orange complex becomes numerically more dominant later and is thought to bridge the early colonizers and the red complex species which become numerically more dominant at late stages in plaque development.

Immuno-inflammatory Response in Periodontal Tissue



Plaque bacteria on the teeth

Bacterial products

Activation of host immune response

2-Selective accumulation of inflammatory cells

3-Secretion of inflammatory mediators

4-Activation of antibody response.

1-Salivary and epithelial immune mechanisms


Bacterial products

Bacterial Adherence.Bacterial Adherence.Extracellular capsules.Extracellular capsules.Lipopolysaccharides (LPS). (Endotoxins)Lipopolysaccharides (LPS). (Endotoxins)ExotoxinsExotoxinsBacterial metabolities.Bacterial metabolities.Bacterial hydrolvtic and proteolytic Bacterial hydrolvtic and proteolytic

enzymes.enzymes.

virulence factorsvirulence factors

The biologic properties by which pathogenic bacteria can have the capacity to produce a disease


Role of Bacteria in Periodontal Tissue Role of Bacteria in Periodontal Tissue DestructionDestruction

Bacterial accumulations on the teeth are Bacterial accumulations on the teeth are necessary to necessary to initiateinitiate the processes that the processes that lead to periodontal destruction. lead to periodontal destruction.

As the periodontal infection process is As the periodontal infection process is initiated, the periodontal pathogenic initiated, the periodontal pathogenic bacteria, bacteria, that colonizethat colonize the periodontal the periodontal sites, process all the biologic sites, process all the biologic characteristics to establish the infection. characteristics to establish the infection.


They are equipped to be able to They are equipped to be able to

1)1) Colonize and gain access to host tissue Colonize and gain access to host tissue 2)2) Multiply in host tissue Multiply in host tissue

3)3) Evade and resistEvade and resist the host defense mechanisms the host defense mechanisms

4)4) Damage directly the host tissueDamage directly the host tissue, or , or indirectlyindirectly, by , by triggering the destructive host immune response. triggering the destructive host immune response.

Role of Bacteria in Periodontal Tissue Role of Bacteria in Periodontal Tissue DestructionDestruction


The biologic properties by which The biologic properties by which pathogenic bacteria can have the capacity pathogenic bacteria can have the capacity to produce a disease, is termed: to produce a disease, is termed:

virulence factorsvirulence factors. .

In periodontal infection, bacterial virulence In periodontal infection, bacterial virulence factors are actually the factors are actually the sumsum total of total of integrating virulence factors produced by integrating virulence factors produced by the dental plaque bacteria working the dental plaque bacteria working together to establish to disease .together to establish to disease .


Virulence Factors of Periodontopathic Bacteria

Bacterial Adherence.Bacterial Adherence.

Extracellular capsules.Extracellular capsules.

Lipopolysaccharides (LPS). (Endotoxins)Lipopolysaccharides (LPS). (Endotoxins)

ExotoxinsExotoxins

Bacterial metabolities.Bacterial metabolities.

Bacterial hydrolvtic and proteolytic enzymes.Bacterial hydrolvtic and proteolytic enzymes.


Bacterial Adherence.Bacterial Adherence.

Bacterial adherence is mediated by bacterial cell surface Bacterial adherence is mediated by bacterial cell surface structure called structure called adhesions,adhesions, which recognize specific which recognize specific receptors on the host surface. receptors on the host surface.

Adhesins are located on Adhesins are located on bacterial fembriaebacterial fembriae which is a which is a bacterial surface appendages.bacterial surface appendages.

S. sanguis, Actinomyces.viscosusS. sanguis, Actinomyces.viscosus,, and and P.gingivalisP.gingivalis process a highly specific and well characterized type of process a highly specific and well characterized type of adhesins.adhesins.

Adhesion of bacteria to the host tissue facilitates its Adhesion of bacteria to the host tissue facilitates its

penetration,penetration, and enhances the activity of toxic bacterial and enhances the activity of toxic bacterial products by delivering it in close approximation to the host products by delivering it in close approximation to the host tissue .tissue .


bacterial fembriaebacterial fembriae


Extracellular capsules.Extracellular capsules.

The presence of Extracellular polysaccharide The presence of Extracellular polysaccharide capsule increases bacterial virulence.capsule increases bacterial virulence.

Actinomyces.viscousus, Bacteroides species,Actinomyces.viscousus, Bacteroides species, and P.gingivalisand P.gingivalis are examples of bacteria with are examples of bacteria with capsules . capsules .

The polysaccharide capsule The polysaccharide capsule resists phagocytosisresists phagocytosis by by preventing opsonizationpreventing opsonization, and hinder the , and hinder the effect of antibiotics by preventing it from effect of antibiotics by preventing it from coming into direct contact with the bacterial coming into direct contact with the bacterial outer membrane or cell wall.outer membrane or cell wall.


Lipopolysaccharides (LPS).Lipopolysaccharides (LPS).

The powerful toxic effect of the gram-negative bacterial The powerful toxic effect of the gram-negative bacterial cell wall component; cell wall component; the endotoxinsthe endotoxins is attributed to its is attributed to its inherent molecular structure, which is composed of inherent molecular structure, which is composed of

lipid moietylipid moiety polysaccharide moietypolysaccharide moiety

Renders the Renders the endotoxins resistant endotoxins resistant to neutralization by to neutralization by

antibodiesantibodies

Resists Resists phagocytosis by phagocytosis by

neutrophilsneutrophils


Much of the tissue damage seen in Much of the tissue damage seen in periodontal disease may be attributed to LPS periodontal disease may be attributed to LPS function, it can function, it can

induce bone resorption, induce bone resorption, cytotoxicity to fibroblasts, cytotoxicity to fibroblasts, chemoattraction to PMNs, chemoattraction to PMNs, activation of complementactivation of complement platelet aggregation.platelet aggregation.

Periodontal pathogens that posses a relatively Periodontal pathogens that posses a relatively powerful LPS are; powerful LPS are; bacteroides species, E. bacteroides species, E. corodans , Capnocytophaga , P.gingivalis and corodans , Capnocytophaga , P.gingivalis and A. actinomycetemcomitans.A. actinomycetemcomitans.


ExotoxinsExotoxins

They represent a family of molecules with the ability to They represent a family of molecules with the ability to elicit massive activation of the immune system. elicit massive activation of the immune system.

Exotoxins may have general cytotoxic effects, or they Exotoxins may have general cytotoxic effects, or they may be targeted at a certain host cell type as may be targeted at a certain host cell type as neurotoxins, leukotoxins, or hepatotoxins neurotoxins, leukotoxins, or hepatotoxins

Ex;Ex; Aa and campylobacter rectusAa and campylobacter rectus leukotoxinleukotoxin and and PgPg epitheliotoxinepitheliotoxin

These proteins share the ability to stimulate T cell These proteins share the ability to stimulate T cell proliferation. proliferation.

The important feature of this interaction is the The important feature of this interaction is the resultant production of resultant production of IL-1, TNFIL-1, TNF, and other , and other lymphokines which appear to be the principal mediators lymphokines which appear to be the principal mediators of periodontal destruction processes associated with of periodontal destruction processes associated with these toxins.these toxins.


Bacterial metabolitesBacterial metabolites

Plaque microbial mass releases large Plaque microbial mass releases large quantities of metabolic end products. These quantities of metabolic end products. These are either are either

small molecular weight substances such assmall molecular weight substances such as , , amines (ammonia), amines (ammonia), hydrogen sulfide, hydrogen sulfide, butyric acid,butyric acid, or large molecules such asor large molecules such as peptides (FMLP).peptides (FMLP).


The small molecularThe small molecular substances can substances can diffuse diffuse through junctional epitheliumthrough junctional epithelium and produce tissue and produce tissue damage.damage.

The large moleculesThe large molecules are delivered after bacteria are delivered after bacteria gain access inside the tissue and function as gain access inside the tissue and function as potent potent chemo-attractants for leukocytes. chemo-attractants for leukocytes.

Among other periodontal pathogens, Among other periodontal pathogens, F. nucleatumF. nucleatum is an example of plaque bacteria that produce is an example of plaque bacteria that produce large amount of large amount of butyric acid butyric acid that is capable of that is capable of initiating early inflammatory changes.initiating early inflammatory changes.


Bacterial hydrolvtic and proteolytic enzymesBacterial hydrolvtic and proteolytic enzymes

Most of periodontal pathogens synthesize Most of periodontal pathogens synthesize variety of enzymes that are useful to them in variety of enzymes that are useful to them in their confrontation with the host. their confrontation with the host.

The lytic enzymes are;The lytic enzymes are;

CollagenaseCollagenase

PeptidasePeptidase

Acid and alkaline phosphatasesAcid and alkaline phosphatases

ProteasesProteases

IGA proteasesIGA proteases


Collagenase:Collagenase: that degrades that degrades collagen collagen of periodontal tissue of periodontal tissue

PeptidasePeptidase:: is active on is active on glycine–prolineglycine–proline (major unit of (major unit of

collagen of periodontal ligament)collagen of periodontal ligament)

Acid and alkaline phosphatases:Acid and alkaline phosphatases: which can degrade which can degrade bone bone protein.protein.


Proteases:Proteases: that can degrade human serum that can degrade human serum proteins such as:proteins such as:

immunoglobulins, immunoglobulins, complement and complement and cytokines. cytokines.

GingipainsGingipains of of P.gingivalisP.gingivalis are one example are one example of powerful bacterial proteases.of powerful bacterial proteases.


IgA proteasesIgA proteases:: are important and a are important and a specific type of proteases that degrade specific type of proteases that degrade secretory IgAsecretory IgA, the ability to produce IgA , the ability to produce IgA proteases is clearly an advantage for proteases is clearly an advantage for mucosal surface pathogen.mucosal surface pathogen.

P. gingivalisP. gingivalis produce IgA proteases that produce IgA proteases that are different from all other proteases in are different from all other proteases in that it results in that it results in totaltotal destruction of destruction of IgAIgA molecule.molecule.

Host Immune response of Host Immune response of periodontal tissueperiodontal tissue



Plaque bacteria on the teeth

Bacterial products

Activation of host immune response

2-Selective accumulation of inflammatory cells

3-Secretion of inflammatory mediators

4-Activation of antibody response.

1-Salivary and epithelial immune mechanisms


Host Immune response of Host Immune response of periodontal tissueperiodontal tissue

1. Salivary and epithelial immune mechanisms

2. Selective accumulation of inflammatory cells

3. Secretion of inflammatory mediators

4. Activation of antibody response.


1-Salivary and epithelial immune mechanisms:1-Salivary and epithelial immune mechanisms:

Salivary components play an important role in Salivary components play an important role in controlling the rate of plaque formation. controlling the rate of plaque formation.

Besides its important function in oral cleansing Besides its important function in oral cleansing

by by salivary flowsalivary flow, , masticationmastication, and , and movement of the tonguemovement of the tongue,, saliva exerts a major effect on metabolism and saliva exerts a major effect on metabolism and

microbial composition of plaque. microbial composition of plaque.


induce their aggregation and induce their aggregation and clearance when they are not clearance when they are not attached to the tooth attached to the tooth surface as a part of salivary surface as a part of salivary pellicle. pellicle.


Proline–rich protein plyeoproteins

Bacteria

bind

HistatinsHistatins

Are family of small basic peptides that Are family of small basic peptides that

inhibit the precipitation of inhibit the precipitation of Ca phosphateCa phosphate

salts, and display powerful antibacterial salts, and display powerful antibacterial

and antifungal properties.and antifungal properties.





Salivary peroxidases (loctoperoxidase)Salivary peroxidases (loctoperoxidase)

which in combination with which in combination with salivary salivary thiocyanatethiocyanate and and H2O2H2O2, , generate generate hypothiocyanatehypothiocyanate which is toxic to bacteria which is toxic to bacteria

LactoferrinLactoferrin is an iron-binding protein is an iron-binding protein

present in saliva, present in saliva,

this iron-binding capacity may deprive this iron-binding capacity may deprive

plaque microorganisms of iron affecting plaque microorganisms of iron affecting

their growth. their growth.



LysozymeLysozyme splits the bond between splits the bond between N-acetyleglucosamine N-acetyleglucosamine andand N- acetyle mumeric acid N- acetyle mumeric acid in the bacterial wall. in the bacterial wall.




1-Salivary and epithelial immune mechanisms:1-Salivary and epithelial immune mechanisms: Finally, there are Finally, there are twotwo main categories of host immune main categories of host immune

components present in the oral cavity. components present in the oral cavity. Those contained in Those contained in salivasaliva and those contained in the and those contained in the GCFGCF.. The first category involves

IgA, secreted by salivary glands, which act mainly in supragingival plaque by coating bacterial surfaces preventing their attachment, and by interacting with the specific receptors on oral surfaces and on other bacteria, thus competing with their adherence.

The second category, involves antibodies, complement and leukocytes, which function predominantly in subgingival plaque to fight a large antigenic challenge.



On the other hand, mucosal epithelium plays a On the other hand, mucosal epithelium plays a

crucial role in controlling bacterial penetration. crucial role in controlling bacterial penetration.

This function is mediated by the This function is mediated by the rapid cell rapid cell

turnover, turnover, which leads to constant shedding of which leads to constant shedding of

mucosal surfaces with bacteria.mucosal surfaces with bacteria.

Keratinocytes can respond to Keratinocytes can respond to inflammatory stimuli via production of inflammatory stimuli via production of proinflammatory mediatorsproinflammatory mediators such as such as cytokinescytokines. .

Such ability to "sense" inflammation Such ability to "sense" inflammation acts locally to transmit the acts locally to transmit the inflammatory massage inwards to the inflammatory massage inwards to the subepithelial microvessels subepithelial microvessels and induce and induce inflammatory reaction. inflammatory reaction.



IL-8,IL-8, an inflammatory an inflammatory chemokinechemokine that is that is responsible for attraction of leukocytes is responsible for attraction of leukocytes is found in junctional epithelium.found in junctional epithelium.

In addition, epithelial cells in general are In addition, epithelial cells in general are known to produce a board range of known to produce a board range of cytokines, including cytokines, including IL-1 alphaIL-1 alpha and and beta,beta, interferon beta (INF-B), tumor necrosis interferon beta (INF-B), tumor necrosis alpha (TNF), IL-6, and transforming alpha (TNF), IL-6, and transforming growth factor beta (TGF-B).growth factor beta (TGF-B).




The cytokines produced by the stimulated The cytokines produced by the stimulated epithelial cells can also stimulate epithelial cells can also stimulate endothelial endothelial cellscells to produce adhesion molecules to produce adhesion molecules (ICAM, (ICAM, VCAM, and E and P-selectins).VCAM, and E and P-selectins).

These adhesion molecules will produce stickiness These adhesion molecules will produce stickiness properties to blood vessels, thus attaching properties to blood vessels, thus attaching circulating leukocyte via circulating leukocyte via leukocyte function – leukocyte function – associated antigen (LFA-1)associated antigen (LFA-1) and facilitate their and facilitate their entrance to the site of inflammation inside the entrance to the site of inflammation inside the tissue.tissue.


2- Selective accumulation of 2- Selective accumulation of inflammatory cellsinflammatory cells

Second step in Host Immune Second step in Host Immune response of periodontal tissueresponse of periodontal tissue


2- Selective accumulation of inflammatory cells2- Selective accumulation of inflammatory cells

In response to direct microbial In response to direct microbial stimulation, junctional epithelial cells are stimulation, junctional epithelial cells are now activated and produce wide range of now activated and produce wide range of inflammatory mediators inflammatory mediators

(IL-1, TNF, and IL-8).(IL-1, TNF, and IL-8).

It is here, where prostaglandin It is here, where prostaglandin (PGE2)(PGE2) and matrix metaloproteinases and matrix metaloproteinases (MMPs(MMPs)) are firstly detected. are firstly detected.


It is via these It is via these mediatorsmediators the gingival the gingival vessels become inflamed and leukocytes vessels become inflamed and leukocytes

(PMNs) (PMNs) are guided to the location of the are guided to the location of the microbial plaque and even may reach the microbial plaque and even may reach the gingival sulcus.gingival sulcus.




As As endothelial cellsendothelial cells become activated and become activated and blood vessels become inflamed,blood vessels become inflamed, their their permeability increases allowing these permeability increases allowing these inflammatory substances to traverse the inflammatory substances to traverse the junctional epithelium and enter the junctional epithelium and enter the connective tissue.connective tissue.



While, While, PMNsPMNs emigrate out to gingival sulcus, emigrate out to gingival sulcus, the majority of the majority of mononulclear cellsmononulclear cells persist in persist in the perivascular connective tissue and form the the perivascular connective tissue and form the local inflammatory infiltrate. local inflammatory infiltrate.

Specific monocyte attracting substance called Specific monocyte attracting substance called monocyte chemotactic protein-1 (MCP--l)monocyte chemotactic protein-1 (MCP--l) is is responsible for this selective recruitment of responsible for this selective recruitment of monocytes. monocytes.



In summary, the topographical distribution of inflammatory In summary, the topographical distribution of inflammatory cells in periodontal tissue can be divided into two regions:cells in periodontal tissue can be divided into two regions:

1-The junctional 1-The junctional

epithelium and epithelium and epithelial-connective epithelial-connective tissue interface tissue interface regionregion

This region, is the This region, is the

area, where the PMN area, where the PMN plays the central role plays the central role

2- connective tissue 2- connective tissue region.region.

This region is the This region is the grounds for grounds for mononuclear cells mononuclear cells (macrophages and (macrophages and lymphocytes). lymphocytes).

Ossama El-ShallOssama El-Shall 138138

Direct Microbial stimulation

Activation of junctional epithelial

Production of a wide range of

inf. Mediators..IL1, TNF,

IL8

Inflammation of gingival vessels

Guided of PMNs to the location of microbial

plaque at the sulcus

Activation of endothelial cells and increase

permeability leads to more Inf. Med. To cross J.Epith

to C.T



Polymorph Nuclear Neutrophils (PMNs)Polymorph Nuclear Neutrophils (PMNs)

Neutrophils represent about 70% of Neutrophils represent about 70% of circulating nucleated cells. circulating nucleated cells.

The unique cell characteristics of PMN are The unique cell characteristics of PMN are the basis on which it gained its reputation the basis on which it gained its reputation as a powerful defense cell in acute as a powerful defense cell in acute inflammation. inflammation.



After their emigration through the blood After their emigration through the blood vessel wall vessel wall (diapedesis),(diapedesis), PMNs exerts their PMNs exerts their major function major function (phagocytosis).(phagocytosis).

This role is highly enhanced by expression of This role is highly enhanced by expression of two important receptors on their surface; the two important receptors on their surface; the receptor that bind to the receptor that bind to the fragment crystallinefragment crystalline portion of antibody, the portion of antibody, the FcFc receptor, and the receptor, and the receptor that bind complement component receptor that bind complement component (C3b), the (C3b), the CR3 CR3 receptorreceptor


http://physiologyonline.physiology.org/content/vol16/issue1/images/large/014624A.jpeg



This This oxygen- non dependent killingoxygen- non dependent killing with with the help of antibody and/or complement the help of antibody and/or complement (opsonization), PMNs can have the central (opsonization), PMNs can have the central role in protection against microbial role in protection against microbial infectioninfection

PMNs armed with two types of PMNs armed with two types of intracellular granules, intracellular granules,


Primary or azurophilic granules.

The secondary granules

myeloproxidase, lysosomal proteases such as elastase and collgenase and cathapsin D and G,

interacellular of microorganisms and

degradation of proteins,

function predominantly extracellularv,

lactoferrin and vit.B12 binding

protein



On activation, PMNs have increased 02 consumption, a On activation, PMNs have increased 02 consumption, a process known as the process known as the respiratory burst,respiratory burst, oxygen is oxygen is reduced to reduced to superoxide anion (HO2-),superoxide anion (HO2-), which, by the which, by the action of action of superoxide dismutasesuperoxide dismutase is converted to is converted to superoxide(H202).superoxide(H202).

H202 interacts with myeloperoxidase, stored in the H202 interacts with myeloperoxidase, stored in the azorophilic granules, to produce azorophilic granules, to produce hypochlorous acidhypochlorous acid, which , which is metabolized to is metabolized to hypochlorite and chlorinehypochlorite and chlorine. .

The hypochlorite produced by these reaction (oxygen The hypochlorite produced by these reaction (oxygen metabolism) is thought to be important in kill bacteria metabolism) is thought to be important in kill bacteria phagocytosed by the neutrophil. phagocytosed by the neutrophil.

This mechanism which is mediated by oxygen metabolism This mechanism which is mediated by oxygen metabolism is know as is know as oxygen-dependent killingoxygen-dependent killing..


Oxygen-dependent killing mechanismOxygen-dependent killing mechanism

O2

Superoxide Superoxide anionanion

Superoxide Superoxide HH22oo22

Myeloper-Myeloper-oxidaseoxidase

hypochlorite hypochlorite and chlorineand chlorine

hypochlorous hypochlorous acidacid

Reduction Superoxide dismutase

Halaide group



Monocytes and macrophages :Monocytes and macrophages :

Circulating monocytes migrate into various Circulating monocytes migrate into various

tissues by passing through endothelial tissues by passing through endothelial

lining of the blood vessels lining of the blood vessels (diapedsis)(diapedsis) and and

become tissue macrophages. become tissue macrophages.



This cells have important characteristic factures include; 1) the capability of phagocytosis, specially particles

coated with antibody and complement protein.

2) expression of several membrane receptors include receptors for antibody molecule (Fc receptor) and for the complement C3b (CR3 receptor).

3) the ability to secrete a wide range of cytokins (IL-l and TNF) and inflammatory mediators ( PGE2 )

4)the ability for processing and presenting antigens for subsequent B lymphocyte development and antibody synthesis.


2- Selective accumulation of inflammatory cells2- Selective accumulation of inflammatory cellsT and B Lymphocytes:T and B Lymphocytes: T LymphocytesT Lymphocytes: are associated with two : are associated with two

main immunological functions effectors main immunological functions effectors and regulatory. and regulatory.

The effectors functionsThe effectors functions include killing include killing activities of infected cells and tumors. activities of infected cells and tumors.



The regulatory functionsThe regulatory functions are represented by their are represented by their ability to amplify or suppress inflammatory reaction ability to amplify or suppress inflammatory reaction either by cytokines or by other T lymphocyte subsets either by cytokines or by other T lymphocyte subsets which are which are T helperT helper and and T suppressorT suppressor..

These T cell subsets are involved inThese T cell subsets are involved in 1) Regulation of immune response, 1) Regulation of immune response, 2) Cooperating with B cells to induce antibody, 2) Cooperating with B cells to induce antibody, 3) Releasing certain lymphokines ( IL-2 , IFN gamma, 3) Releasing certain lymphokines ( IL-2 , IFN gamma,

IL-4 and IL- IL-4 and IL- 4) Activate macrophages 4) Activate macrophages 5) Induce cytotoxic effect on intracellulalr and viral 5) Induce cytotoxic effect on intracellulalr and viral

pathogens . pathogens .



B lymphocytes,B lymphocytes, when activated, is when activated, is transformed into an antibody secreting transformed into an antibody secreting Plasma cells. Plasma cells. They are committed to produce the They are committed to produce the heavy chains or major antibody classes heavy chains or major antibody classes (IgM, IgG, IgA' IgE and IgD)(IgM, IgG, IgA' IgE and IgD)

3- Secretion of 3- Secretion of inflammatory mediators:inflammatory mediators:


1. Salivary and epithelial immune mechanisms

2. Selective accumulation of inflammatory cells

3. Activation of antibody response.


3- Secretion of inflammatory mediators:3- Secretion of inflammatory mediators:The hallmark of periodontal inflammation is the The hallmark of periodontal inflammation is the presence of wide range of inflammatory presence of wide range of inflammatory mediators.mediators.

These inflammatory mediators are produced by These inflammatory mediators are produced by activated resident gingival cells activated resident gingival cells and and infiltrating infiltrating leukocytesleukocytes, as well as by the , as well as by the complement complement cascadecascade. .

MonocytesMonocytes of individuals who are susceptible to of individuals who are susceptible to or who have severe periodontitis produce or who have severe periodontitis produce elevated amounts of mediators. This elevated elevated amounts of mediators. This elevated concentration of mediators decreases following concentration of mediators decreases following successfully therapy. successfully therapy.


IL-1

IL-2

IL-3

IL-5

IL-4

IL-6 IL-8

TNF Alpha

Prostaglandins Ieukotriens B4

Matrix metaloproteinasesMatrix metaloproteinases (MMPs)(MMPs)

Complement


3- Secretion of inflammatory mediators:3- Secretion of inflammatory mediators:IL-1:IL-1: is a major mediator in periodontal inflammation.is a major mediator in periodontal inflammation.

IL-1 betaIL-1 beta IL-1 alphaIL-1 alpha

activated macrophages activated macrophages and PMNsand PMNs

keratinocytes of junctional or keratinocytes of junctional or pocket epitheliumpocket epithelium

induced by bacterial LPS and other bacterial componentsinduced by bacterial LPS and other bacterial componentsIL-1, is auto stimulatoryIL-1, is auto stimulatory

Up regulates complement and Fc receptors on PMNs and MonocytesUp regulates complement and Fc receptors on PMNs and MonocytesUp regulates adhesion molecules on fibroblasts. leukocytes and Up regulates adhesion molecules on fibroblasts. leukocytes and endothelial cellsendothelial cellsInduces homing receptor for lymphocytes, osteoclast formation and Induces homing receptor for lymphocytes, osteoclast formation and bone resorptionbone resorptionEnhances production of itself, MMPs, and prostaglandins by Enhances production of itself, MMPs, and prostaglandins by macrophage, fibroblasts, and PMNs,macrophage, fibroblasts, and PMNs,


3- Secretion of inflammatory mediators:3- Secretion of inflammatory mediators:

lL-2, lL-3, lL-4 and lL-5 lL-2, lL-3, lL-4 and lL-5 are involved in are involved in lymphocyte lymphocyte colonal expansioncolonal expansion and the and the differentiation of B cellsdifferentiation of B cells into antibody- into antibody-producing plasma cells.producing plasma cells.

They also They also Induce expression of specific clones of T cells, Induce expression of specific clones of T cells,

Regulate IgG and IgE, Regulate IgG and IgE, Suppress activated macrophages and causes Suppress activated macrophages and causes their apoptosis (programmed cell death) their apoptosis (programmed cell death)



lL-6 lL-6

macrophagesmacrophages

fibroblastsfibroblasts

endothelial cellsendothelial cells

lymphocyteslymphocytesinduced' by IL1 and LPSinduced' by IL1 and LPS

is involved in is involved in osteoclast recruitment osteoclast recruitment

by its action on by its action on monocytes.monocytes.



lL-8lL-8


keratynocyteskeratynocytes

endothelial cellsendothelial cells

PMNsPMNs

Responsible for leukocyte Responsible for leukocyte attraction to the site of attraction to the site of

inflammationinflammation



TNF-alphaTNF-alpha has a similar pro-inflammatory has a similar pro-inflammatory function as function as IL-I,IL-I, which is the activation of which is the activation of various types of inflammatory cells and various types of inflammatory cells and secretions. secretions.

TNF-alpha has a special role on endothelial TNF-alpha has a special role on endothelial cells amplifying their expression to cells amplifying their expression to adhesion adhesion moleculesmolecules thus allowing leukocyte emigration thus allowing leukocyte emigration from the vasculature. from the vasculature.



ProstaglandinsProstaglandins

Ieukotriens B4 (LB4)Ieukotriens B4 (LB4)

FibroblastsFibroblasts

PMNsPMNs


basophilsbasophils

mast cellsmast cells

eosinophilseosinophils

They are the most They are the most prominent arachidonic prominent arachidonic acid metabolites in acid metabolites in inflamed periodontal inflamed periodontal

tissue.tissue.


AffectAffect blood vessel toneblood vessel tonePromote smooth muscle Promote smooth muscle contractioncontraction,,Increase collagenase Increase collagenase productionproduction by monocytes.by monocytes.

PGE2, in particular, make up PGE2, in particular, make up the primary pathway of the primary pathway of alveolar bone resorptionalveolar bone resorption in in Periodntitis. Periodntitis.

ProstaglandinsProstaglandins Ieukotriens B4

Is a potent Is a potent chemoattractants chemoattractants

for PMNs for PMNs

3- Secretion of inflammatory mediators



MMPs can digest all the components of the MMPs can digest all the components of the extracellular matrix. extracellular matrix.

These enzymes are tightly controlled by IL-1 These enzymes are tightly controlled by IL-1 and TGf·alpha and beta (trasformed growth and TGf·alpha and beta (trasformed growth factor), epidermal growth factor and factor), epidermal growth factor and IFN·gamma (interform).IFN·gamma (interform).

FibroblastsFibroblasts


activated activated keratinocyteskeratinocytes

Matrix metaloproteinasesMatrix metaloproteinases (MMPs)(MMPs) They are a large family of zinc dependent They are a large family of zinc dependent enzymesenzymes


Complement:Complement: The classical, complex system of complement contains11 The classical, complex system of complement contains11

interacting blood proteins and glycoprotein found in human interacting blood proteins and glycoprotein found in human serum.serum.

(C I, C2, C4, C3-a and b,C5,C6,7, C8 and C9)(C I, C2, C4, C3-a and b,C5,C6,7, C8 and C9) The The alternative pathwayalternative pathway comprises six serum components comprises six serum components

(C3-a and b, C5----C9). (C3-a and b, C5----C9).

The primary function of these complements are The primary function of these complements are induction induction of inflammation, facilitate phagocytosis (opsonization)of inflammation, facilitate phagocytosis (opsonization) and and direct direct toxicitytoxicity of various cells and microorganisms. of various cells and microorganisms.

The primary difference between the classical and the The primary difference between the classical and the alternative pathways is that C3b is alternative pathways is that C3b is immediately activatedimmediately activated upon contact with the pathogen, while upon contact with the pathogen, while specific immune specific immune (response is required to activate the classical pathway(response is required to activate the classical pathway . .



4- Activation of antibody Response


4- Activation of antibody Response :

As the bacterial challenge increases, protection As the bacterial challenge increases, protection of the host tissue is achieved by PMN activity of the host tissue is achieved by PMN activity in the sulcus, facilitated by a specific antibody in the sulcus, facilitated by a specific antibody that is produced systemically and in the local that is produced systemically and in the local tissues. tissues.

Circulating antibody may be more abundant and Circulating antibody may be more abundant and important than locally produced antibody.important than locally produced antibody.

Patients of aggressive, and chronic Periodontitis Patients of aggressive, and chronic Periodontitis mount a systemic antibody response to infecting mount a systemic antibody response to infecting bacteria.bacteria.


Immunoglobulins (antibodies) Immunoglobulins (antibodies) are glycoproteins present in human are glycoproteins present in human serum and fluids, These molecules bind-serum and fluids, These molecules bind-specifically to foreign antigens (bacteria, specifically to foreign antigens (bacteria, viruses. parasites. and toxins). viruses. parasites. and toxins).

There are five immunoglobulin (Ig) classes There are five immunoglobulin (Ig) classes as follow:as follow: IgM, IgG, IgA, IgD, IgE IgM, IgG, IgA, IgD, IgE




IgM,IgM, is the first Ig class to appear in is the first Ig class to appear in the immune response, it is the the immune response, it is the antibody of the antibody of the primary immune primary immune responseresponse. .

The pentameric nature of IgM The pentameric nature of IgM molecule results in a high capacity for molecule results in a high capacity for agglutination/ aggregation of bacteria.agglutination/ aggregation of bacteria.

IgM is also the antibody most IgM is also the antibody most observed in autoimmune response. observed in autoimmune response.



IgG.IgG. makes up 75% of serum Igs makes up 75% of serum Igs IgG is the most important, And most of antibody IgG is the most important, And most of antibody activity during bacterial infection is attributed to activity during bacterial infection is attributed to IgG. IgG. It is the predominant Ig in the It is the predominant Ig in the secondary immune secondary immune response.response.

The functions of IgG The functions of IgG 1)neutralization of bacterial toxins 1)neutralization of bacterial toxins 2)IgG bind surface of bacteria can produce 2)IgG bind surface of bacteria can produce

complement fixation and mediate cell lysis.complement fixation and mediate cell lysis. 3)Opsonization3)Opsonization 4)Antibody dependent cell mediated cytotoxic reaction, 4)Antibody dependent cell mediated cytotoxic reaction,

which is mediated by' Fc receptors on leukocytes. which is mediated by' Fc receptors on leukocytes.



IgA.IgA. is the predominant Ig in is the predominant Ig in external secretions, existing as a external secretions, existing as a dimeric molecule with a J chain and dimeric molecule with a J chain and Sc (secretory component).Sc (secretory component).

Its major function is preventing Its major function is preventing bacterial colonization and adherence bacterial colonization and adherence to oral surfacesto oral surfaces



IgD.IgD. in association with IgM, is found on in association with IgM, is found on the surface of B lymphocytes the surface of B lymphocytes

Its suggested that it is important in Its suggested that it is important in B-cell differentiation. B-cell differentiation.



IgEIgE Is the Ig predominant in allergic Is the Ig predominant in allergic reaction. reaction.

Mast cells and basophils Mast cells and basophils have a have a specific receptor (Fc) for IgE causing specific receptor (Fc) for IgE causing their' degranulation and release or their' degranulation and release or their contentstheir contents


Repair and regeneration of Repair and regeneration of periodontal tissueperiodontal tissue


Repair of damaged tissue is a major biologic Repair of damaged tissue is a major biologic response in human body. However. the nature response in human body. However. the nature of the repair process often leads to of the repair process often leads to compromised function. compromised function. In this respect, periodontium is no exception. In this respect, periodontium is no exception.

Tissue affected by Tissue affected by gingivitisgingivitis usually usually regenerate regenerate to their complete form and functionto their complete form and function; however, ; however, this may not be true with periodontitis. this may not be true with periodontitis. Once the Once the destructive phase reaches the destructive phase reaches the deeper periodontal structuredeeper periodontal structure, clinical , clinical predictable predictable regeneration is less likely.regeneration is less likely.

Repair and regeneration of periodontal tissueRepair and regeneration of periodontal tissue



Typically, a wound healing response is Typically, a wound healing response is initiated by initiated by inflammationinflammation when PMNs when PMNs migrate Into the wound site that has migrate Into the wound site that has been filled with fibrous clot. been filled with fibrous clot.

PMNs, and later monocyte-macrophages, PMNs, and later monocyte-macrophages, remove damaged tissueremove damaged tissue and foreign and foreign matter through phagosytosis and by matter through phagosytosis and by enzymes secreted by these cells. enzymes secreted by these cells.


• Regeneration:Regeneration: Reproduction or Reconstruction of a Reproduction or Reconstruction of a lost or injured part in such a way lost or injured part in such a way that the that the architecture and function architecture and function of of the lost or injured tissues are the lost or injured tissues are completely restored. completely restored.

• Periodontal regeneration:Periodontal regeneration: Implies formation of new cementum Implies formation of new cementum with inserting collagen fibers and bone with inserting collagen fibers and bone


• Periodontal repair:Periodontal repair: Healing that does not completely Healing that does not completely restore the architecture or function restore the architecture or function of the partof the part


RegenerationRegeneration

Is the replacement of old damaged tissue Is the replacement of old damaged tissue by by new tissue identicalnew tissue identical to normal healthy to normal healthy tissue. tissue.

Regeneration occurs when the Regeneration occurs when the "labile""labile" undifferentiated pluripotential cells undifferentiated pluripotential cells ( mesenchymal) carry out the healing ( mesenchymal) carry out the healing process. process.


RepairRepair

Is the replacement of damaged tissue Is the replacement of damaged tissue by scar tissue. by scar tissue.

Repair occurs when the Repair occurs when the “permanent “permanent cellscells with less division capacity with less division capacity (fibroblasts and osteblasts) carry out (fibroblasts and osteblasts) carry out the healing process. the healing process.


Organization of granulation tissue follows when Organization of granulation tissue follows when endothelial cells activity divide to form new endothelial cells activity divide to form new capillaries, and fibroblasts begin to synthesize capillaries, and fibroblasts begin to synthesize matrix components. matrix components.

This process requires the participation of a This process requires the participation of a variety of cell types and molecules. These variety of cell types and molecules. These molecules include molecules include degradation products of fibrin degradation products of fibrin clotclot and and host tissuehost tissue, along with , along with

growth factorsgrowth factors,, cytokines, and lymphokinescytokines, and lymphokines secreted by platelets, macrophages and other secreted by platelets, macrophages and other cells. cells.




Growth factorsGrowth factors and inflammatory and inflammatory mediators function in healing by influencingmediators function in healing by influencing

1) migration of reparative cells, 1) migration of reparative cells, 2) attachment to tissue matrix. 2) attachment to tissue matrix. 3) growth of reparative cells,3) growth of reparative cells, 4) synthesis activities4) synthesis activities


Growth factorsGrowth factors and inflammatory and inflammatory mediators as a healing adjunctivemediators as a healing adjunctive


Growth factorsGrowth factorsThey are polypeptide molecules released by They are polypeptide molecules released by

cells in the inflamed area, that regulates cells in the inflamed area, that regulates events in wound healingevents in wound healing

Platelet derived growth factorPlatelet derived growth factorTransforming growth factor BTransforming growth factor BBone morphogenic proteinBone morphogenic proteinHeparin- Binding Growth FactorsHeparin- Binding Growth FactorsInsulin-Like growth factorsInsulin-Like growth factors


Platelet derived growth factorPlatelet derived growth factor

PDGFPDGF is the major mitogen of periodontal is the major mitogen of periodontal tissue mesenchymal cells, which are tissue mesenchymal cells, which are pluripotential cells that have unlimited division pluripotential cells that have unlimited division capacity. capacity.

PDGF PDGF can induce these cells to differentiate can induce these cells to differentiate into several cell lines including, fibroblast for into several cell lines including, fibroblast for connective tissue collagen formation connective tissue collagen formation cementoblast for cementogensis, osteblast cementoblast for cementogensis, osteblast for bone formation, and endothelial cells for for bone formation, and endothelial cells for angiogenesis angiogenesis


Transforming growth factor BTransforming growth factor B

TGF-B activates the synthesis of TGF-B activates the synthesis of collagen and other matrix components collagen and other matrix components by fibroblast. by fibroblast.


Bone morphogenic proteinBone morphogenic protein

BMP triggers inflammatory and wound- BMP triggers inflammatory and wound- healing response in injured bone, and healing response in injured bone, and accomplish accomplish total healing of bone.total healing of bone.

It induce It induce new bone formation new bone formation by help by help differentiation of mesenchymal cells to differentiation of mesenchymal cells to osteoblast instead of changing the osteoblast instead of changing the growth rate of pre-existing bone growth rate of pre-existing bone (osteoinduction) (osteoinduction)


Heparin- Binding Growth FactorsHeparin- Binding Growth Factors

Heparin-Binding Growth Factors (HBGFs) Heparin-Binding Growth Factors (HBGFs) are a family of 7 related heparin-binding are a family of 7 related heparin-binding

proteins, which interact with heparin, proteins, which interact with heparin, enhancing their effect on bone cell enhancing their effect on bone cell replication. replication.

Among other members in this family are, Among other members in this family are,

Acidic fibroblast growth factor (aFGF)Acidic fibroblast growth factor (aFGF) Basic fibroblast growth factor (bFGF)Basic fibroblast growth factor (bFGF) Important in bone protein synthesisImportant in bone protein synthesis


Insulin-Like growth factorsInsulin-Like growth factors

Insulin-Like growth factors ( IGFs), Insulin-Like growth factors ( IGFs), derived its name from its ability to derived its name from its ability to function as an autoecrine, it functions function as an autoecrine, it functions as a regulator of bone formation. as a regulator of bone formation.

It can be produced either locally in It can be produced either locally in the tissue by fibroblasts and the tissue by fibroblasts and osteblasts. or systemically by liver osteblasts. or systemically by liver


Risk factors of periodontal diseaseRisk factors of periodontal disease


Risk Factors of Periodontal Diseases Risk Factors of Periodontal Diseases

Risk factors Risk factors affecting prevalence affecting prevalence

of disease among of disease among populations.populations.

Risk factors Risk factors affecting severity affecting severity and progression of and progression of

the diseasethe disease


Risk factors affecting the prevalence Risk factors affecting the prevalence of diseases of diseases

1.1. Gender:Gender: Men experiencing greater level of the Men experiencing greater level of the disease incidence than women.disease incidence than women.

2.2. Socioeconomic:Socioeconomic: Individuals with higher education and Individuals with higher education and income are associated with lower levels of disease income are associated with lower levels of disease prevalenceprevalence

3.3. Number of teeth:Number of teeth: Individuals with more are Individuals with more are associated with greater level of diseases (numerical associated with greater level of diseases (numerical associated only)associated only)

4.4. Smoking:Smoking: Individuals, with heavy smoking are Individuals, with heavy smoking are associated with greater prevalence of the disease.associated with greater prevalence of the disease.

5.5. Age:Age: Older adults exhibit more incidence of the Older adults exhibit more incidence of the diseases. diseases.


Risk factors affecting the severity Risk factors affecting the severity and progression of diseases and progression of diseases

Local risk factorsLocal risk factors 1- Specific bacterial 1- Specific bacterial

pathogenpathogen2- Patient’s compliance 2- Patient’s compliance

with oral hygienewith oral hygiene3- Past history of severe 3- Past history of severe

generalized diseasesgeneralized diseases4- Poor clinical response to 4- Poor clinical response to

initial therapyinitial therapy

Systemic risk factorsSystemic risk factors1- Diabetes mellitus1- Diabetes mellitus2- Smoking2- Smoking3- Genetic factors3- Genetic factors4- Menopause4- Menopause


Risk factors affecting the severity and progression of diseasesRisk factors affecting the severity and progression of diseases

Local risk factorsLocal risk factors

1- 1- Specific bacterial pathogen:Specific bacterial pathogen: The The presence of specific bacterial species presence of specific bacterial species including Aa,P.g,B.. forsythus and including Aa,P.g,B.. forsythus and spirochetes are associated with spirochetes are associated with increased severity and progression increased severity and progression disease. disease.



2- Patient's compliance with oral hygiene:2- Patient's compliance with oral hygiene: In general individuals who follow In general individuals who follow suggested oral hygiene and maintenance suggested oral hygiene and maintenance schedules have less disease, compared schedules have less disease, compared to those who do not comply. to those who do not comply.



3- Past history of severe generalized disease:3- Past history of severe generalized disease: The majority of individuals will develop The majority of individuals will develop

only mild to localized moderate disease in only mild to localized moderate disease in response to moderate plaque accumulation. response to moderate plaque accumulation. Sever generalized destruction suggests a Sever generalized destruction suggests a problem with the patient's host response. problem with the patient's host response.



4- Poor clinical response to initial therapy:4- Poor clinical response to initial therapy:

After plaque removal and regular plaque After plaque removal and regular plaque control, diseased sites accessible for cleaning control, diseased sites accessible for cleaning should demonstrate a predictable clinical should demonstrate a predictable clinical improvement. improvement.

If the majority of such sites do not respond If the majority of such sites do not respond as described, it may indicate either something as described, it may indicate either something of concern in the biologic response or in of concern in the biologic response or in patient's compliance with home care.patient's compliance with home care.


Systemic risk factorsSystemic risk factors

1- Diabetes mellitus1- Diabetes mellitus2- Smoking2- Smoking3- Genetic factors3- Genetic factors4- Menopause4- Menopause



Diabetes MellitusDiabetes Mellitus

individuals with diabetes who do not adhere individuals with diabetes who do not adhere to medical regimen for diabetes control, or to medical regimen for diabetes control, or do not comply with periodontal treatment, do not comply with periodontal treatment, have more severe diseases. have more severe diseases.


Diabetes may exert its effect on periodontal tissue due to Diabetes may exert its effect on periodontal tissue due to increased glucose levels in serumincreased glucose levels in serum and tissues. and tissues.

Hyperglycemia can affects inflammatory cells and the Hyperglycemia can affects inflammatory cells and the tissue response to inflammatory mediators through the tissue response to inflammatory mediators through the production of production of advanced–glycation end products (AGE)advanced–glycation end products (AGE)

There are receptors present on PMNs' and monocytes that There are receptors present on PMNs' and monocytes that

interact with interact with AGEAGE called called receptors of advanced-glycation receptors of advanced-glycation end products (RAGE).end products (RAGE).

When AGE bind to RAGE on inflammatory cells, these cells When AGE bind to RAGE on inflammatory cells, these cells will be activated and produce more inflammatory mediators will be activated and produce more inflammatory mediators (PGE2 and MMPs) or hyper-responsive to inflammatory (PGE2 and MMPs) or hyper-responsive to inflammatory cytokines (IL-l B, IL-6, and TNF-alpha) and bacterial cytokines (IL-l B, IL-6, and TNF-alpha) and bacterial products (LPS). products (LPS).

The net result will be more destruction of periodontal The net result will be more destruction of periodontal tissues. tissues.


Un-controlled DiabetesUn-controlled Diabetes

HyperglycemiaHyperglycemia

advanced–glycation end products advanced–glycation end products (AGE)(AGE)

PMNs

receptors of receptors of advanced-glycation advanced-glycation

end products end products (RAGE).(RAGE).

more inflammatory mediators more inflammatory mediators (PGE2 and MMPs) or (PGE2 and MMPs) or

hyperresponsive to inflammatory cytokines hyperresponsive to inflammatory cytokines (IL-l B, IL-6, and TNF-alpha) and bacterial (IL-l B, IL-6, and TNF-alpha) and bacterial

products (LPS).products (LPS).

more destruction of periodontal tissuesmore destruction of periodontal tissues



2- Smoking2- Smoking has a strong relationship with severity and has a strong relationship with severity and

progression of periodontal diseases. progression of periodontal diseases. It can interfere with the host immunological It can interfere with the host immunological

response by increasing production of response by increasing production of PGE2PGE2 and, and, MMPsMMPs from from PMNs and monocytes.PMNs and monocytes.

Smoking also may favor bacterial colonization Smoking also may favor bacterial colonization through altering the tissue response by affecting through altering the tissue response by affecting antibody production and leukocyte phagocytosisantibody production and leukocyte phagocytosis, , thus allowing easier spread and growth of thus allowing easier spread and growth of periodontal pathogens. periodontal pathogens.



3-Genetic Factors3-Genetic Factors• There are several genetic markers that There are several genetic markers that

may predispose to periodontal disease, may predispose to periodontal disease, that are still under investigations. that are still under investigations.

• Among these markers, IL-f genotype- Among these markers, IL-f genotype- (poleomorphesim) and IL-l genotype-(poleomorphesim) and IL-l genotype-positive smokers in their genes, render positive smokers in their genes, render the individuals to have higher levels of the individuals to have higher levels of bacterial pathogens, and tend to bacterial pathogens, and tend to overproduce inflammatory mediators. overproduce inflammatory mediators.



4- Menopause4- Menopause • Estrogen influences bone metabolism Estrogen influences bone metabolism directlydirectly

by its effect on osteoclastic activitiesby its effect on osteoclastic activities• oror indirectlyindirectly, by inhibiting IL6 production , by inhibiting IL6 production

(a mediator of bone resorption).(a mediator of bone resorption).• In postmenopausal women, osteoporosis may, In postmenopausal women, osteoporosis may,

develop affecting bone metabolism in the develop affecting bone metabolism in the maxilla and the mandible. maxilla and the mandible.


Dental CalculusDental Calculus



Calculus is primarily a mineralized Calculus is primarily a mineralized bacterial plaque, results from bacterial plaque, results from calcification of salivary proteins and calcification of salivary proteins and bacteria.bacteria.



Supra-gingival calculusSupra-gingival calculus is clinically is clinically visible coronal to the gingival margin. visible coronal to the gingival margin.

The presence and amount of supra-The presence and amount of supra-gingival calculus are the result of the gingival calculus are the result of the level of level of bacterial depositsbacterial deposits on the teeth, on the teeth, but are also influenced by but are also influenced by salivary salivary secretionsecretion. .


As a result, the greatest quantity of As a result, the greatest quantity of supragingival calculus is usually seen on the supragingival calculus is usually seen on the buccal surface of the maxillary morals buccal surface of the maxillary morals adjacent to the parotid gland duct adjacent to the parotid gland duct (Stennson's duct), and on the lingual surface (Stennson's duct), and on the lingual surface of the madibular anterior teeth opposite to of the madibular anterior teeth opposite to the submanibular gland duct (Warton's the submanibular gland duct (Warton's duct).duct).

Supragingivil calculus may range in color Supragingivil calculus may range in color from from white to dark brownwhite to dark brown. depending on . depending on stain from food and beverage.stain from food and beverage.


Dental calculusDental calculus

Supragingival calculus is depicted on the buccal surfaces of maxillary molars adjacent to orifice

for Stenson’s duct.


Extensive supragingival calculus on the lingual surfaces of lower

anterior teeth.


Subgingival calculusSubgingival calculus forms apical to the forms apical to the gingival margin and gingival margin and is usually not visible.is usually not visible.

It may be detected by tactile exploration It may be detected by tactile exploration

with a periodontal probe or fine explorer, with a periodontal probe or fine explorer, and is usually evident as a roughened and is usually evident as a roughened surface. surface.


If the gingival margin is retracted by a If the gingival margin is retracted by a blast of air or dental instrument, blast of air or dental instrument, subgingival calculussubgingival calculus may be evident at and may be evident at and just apical to the cementoenamel junction. just apical to the cementoenamel junction.

Subgingival calculus frequently appears Subgingival calculus frequently appears brown or black, brown or black, which reflects the which reflects the presence of bacterial and blood products. presence of bacterial and blood products.


Supragingival calculusSupragingival calculus consists of 70% to 90% consists of 70% to 90%

inorganic salts, which are mainly in the from of inorganic salts, which are mainly in the from of calcium phosphate (Ca3(PO4)2).calcium phosphate (Ca3(PO4)2).

Calculus also contains varying amounts of Calculus also contains varying amounts of calcium calcium carbonate and magnesium phosphatecarbonate and magnesium phosphate. .

The inorganic part of the calculus is chemically The inorganic part of the calculus is chemically similar to the inorganic portion on bone, dentin, similar to the inorganic portion on bone, dentin, and cementum.and cementum.

The organic component of calculus involves The organic component of calculus involves proteins and polysaccharide complex derived proteins and polysaccharide complex derived from dental plaque, saliva, and desquamated from dental plaque, saliva, and desquamated epithelial cells and white blood cells.epithelial cells and white blood cells.


Subgingival calculus presents as a black-brownish hard mass if the gingival margin is retracted or

reflectedduring a surgical procedure (a). Healing of the site

following removal of all hard deposits (b).


The composition of The composition of subgingival plaquesubgingival plaque is similar to supragingival plaque in the is similar to supragingival plaque in the hydroxyapatite content, hydroxyapatite content,

but it contains but it contains more magnesium more magnesium as well as well as higher as higher ca to phosphate ratio ca to phosphate ratio . .


Mechanism of calculus formation Mechanism of calculus formation

As stated before, calculus is dental As stated before, calculus is dental plaque that has undergone mineralization plaque that has undergone mineralization Calcification begins by binding of Calcification begins by binding of calcium ions to the carbohydrate-calcium ions to the carbohydrate-protein complex of saliva. protein complex of saliva. Crystals of calcium phosphate initially Crystals of calcium phosphate initially forms in the intercellular matrix and on forms in the intercellular matrix and on bacterial surfaces .and finally within bacterial surfaces .and finally within the bacteria. the bacteria.


This reaction varies from person to This reaction varies from person to person and at different times at the person and at different times at the same person, Accordingly, individuals same person, Accordingly, individuals can said to be, can said to be,

heavy calculus formers, heavy calculus formers, moderately formers, and moderately formers, and light calculus formers. light calculus formers.

This tendency to form variable amounts This tendency to form variable amounts of calculus may depend on the of calculus may depend on the followings: followings:


Increased salivary pH due toIncreased salivary pH due to A)A) loss of C02 by bacteria, shifting plaque loss of C02 by bacteria, shifting plaque

to an alkaline pH, which in turn increases to an alkaline pH, which in turn increases the precipitation of calcium phosphate the precipitation of calcium phosphate crystals crystals

B)B) formation of ammonia by bacteria , formation of ammonia by bacteria , which increase the alkalinity of plaque pH which increase the alkalinity of plaque pH and increase the formation of calcium and increase the formation of calcium phosphate crystals .phosphate crystals .


Increased the degree of saturation of Increased the degree of saturation of calcium and phosphate ions,calcium and phosphate ions,

this can be induced by this can be induced by A) A) Protein degradation during stagnation of Protein degradation during stagnation of

salivasaliva which will affect the degree of which will affect the degree of saturation of saliva and facilitate the saturation of saliva and facilitate the precipitation of calcium phosphate crystals precipitation of calcium phosphate crystals from this saturated solution (saliva). from this saturated solution (saliva).

B) Enzyme liberation from bacteria.B) Enzyme liberation from bacteria. Phosphatases and esterases from bacteria Phosphatases and esterases from bacteria

liberate increased amount of phosphate liberate increased amount of phosphate molecules that can bind to calcium and form molecules that can bind to calcium and form calcium phosphate crystals. . calcium phosphate crystals. .


It is clear from the previous discussion that It is clear from the previous discussion that bacteria not only can act as a seeding agent bacteria not only can act as a seeding agent for calculus deposition (seeding theory) for calculus deposition (seeding theory)

but also can modulate the local environment but also can modulate the local environment for precipitation of calcium phosphate crystals for precipitation of calcium phosphate crystals . .

It is also important to note that calculus It is also important to note that calculus may also be formed as a result of increased may also be formed as a result of increased saturation of calcium and/or phosphate in saturation of calcium and/or phosphate in saliva due to alteration of salivary saliva due to alteration of salivary constituents. constituents.


Clinical significance of calculus Clinical significance of calculus

There is certainly a proven association There is certainly a proven association between calculus and periodontal between calculus and periodontal diseases but there is diseases but there is no evidenceno evidence to to implicate calculus as a primary cause. implicate calculus as a primary cause. This conclusion is the result of the This conclusion is the result of the following observations: following observations:


Mineralized surface of calculus is always Mineralized surface of calculus is always covered by unmineralized bacterial plague, covered by unmineralized bacterial plague, and therefore calculus itself does not contact and therefore calculus itself does not contact the gingival tissues. the gingival tissues.

When bacteria are eliminated from calculus When bacteria are eliminated from calculus surfaces, in animals treated with antimicrobial surfaces, in animals treated with antimicrobial agents, calculus may actually come in direct agents, calculus may actually come in direct contact with gingival tissues. In such contact with gingival tissues. In such artificially induced situation, calculus was not artificially induced situation, calculus was not able to induce gingival inflammation. able to induce gingival inflammation.

Calculus may amplify the effect of bacteria Calculus may amplify the effect of bacteria and act as a reservoir for bacterial toxins and and act as a reservoir for bacterial toxins and nutrients. It also serves to keep the bacteria nutrients. It also serves to keep the bacteria in direct contact with gingival tissues. in direct contact with gingival tissues.


The End


Advanced Readings

11/19/1411/19/14 Ossama El-ShallOssama El-Shall 227227The natural history of inflammation


Figure 1.


Potential therapeutic strategies to treat bone resorption: agents that block the differentiation oractivity of osteoclasts are potential therapeutic agents. Osteoprotegerin (OPG) inhibits thedifferentiation of osteoclasts through its action as a decoy receptor that blocks receptor activatorof nuclear factor-kappa B (NF-kB) ligand (RANKL) and RANK juxtacrine interaction. Non-steroidalanti-inflammatory drugs (NSAIDs) and other anti-inflammatory molecules (including p38

Figure 1.


mitogen-activated protein kinase inhibitors, c-jun N-terminal kinase inhibitors, NF-kB inhibitors,

and the specific, high-affinity IL-1 inhibitor IL-1 [TRAP]) can inhibit the formation of hematoprogenitor

cells to preosteoclasts. Antibodies to RANKL can also block this interaction. MMP

inhibitors reduce the protease degradation of the organic matrix, and anti-integrins block the initial


osteoclast adhesion to the matrix. Bisphosphonates and MMP inhibitors work at the site of the

osteoclast adhesion zone to the mineralized matrix in blocking bone resorption. M-CSF =

macrophage colony-stimulating factor; sRANKL = soluble RANKL; TNFsRC = TNF soluble receptor.

Adapted with permission from Blackwell Publishing.


Figure 2.


Figure 2.

Overview of the key biomarkers related to periodontal disease progression.

Initial events are triggered by LPS from Gram -ve plaque biofilms on the periodontal tissues.

As a first line of defense, PMNs are recruited to the site. Monocytes and activated macrophages respond to endotoxin by releasing cytokines (TNF and IL-1) that direct further destruction processes.


MMPs, which can act as powerful collagen-destroying enzymes, are produced by fibroblas and PMNs. TNF, IL-1, and receptor activator of nuclear factor-kappa B legend (RANKL) are elevated in active sites and mediate osteoclastogenesis and bone breakdown.

Bone-specific markers, such as ICTP, are released into the surrounding area and transported by way of gingival crevicular fluid into the sulcus or pocket and serve as potential biomarkers for periodontal disease detection.

Etiology of periodontal diseases

Health & Medicine

Transcript of Etiology of periodontal diseases