CHAPTER 14

PATHOBIOLOGY OF THE PERIAPEX

presented by:
BERNALES, BESO, CABIJE, CAIRODEN, CAMONGAY, CONCEPCION
PREVALENCE

According to a survey by the American Dental Association in 1990, an estimated

14 million root canal treatments were performed in the United States alone.

Prevalence of apical periodontitis in European and Scandinavian countries

varies among patients aged 20 to 30 (33% prevalence of apical periodontitis), 30
to 40 (40%), 40 to 50 (48%), 50 to 60 (57%), and older than 60 years of age
(62%)
ETIOLOGY

Exogenous factors include microbes,mechanical irritation, foreign bodies, and trauma.

Endogenous factors include the host’s metabolic products, such as urate and cholesterol
crystals, as well as cytokines or other inflammatory mediators that activate osteoclasts.

(Kakehashi et al.)
demonstrated that pulp necrosis and periradicular inflammation developed in conventional rats
when the pulps of teeth were exposed to oral microorganisms. However, in germ-free laboratory
rats, no pulp necrosis and periradicular inflammation occurred .

In the root canal system, infection of the pulp tissue caused by caries or other pathways is
the primary cause of apical periodontitis.
FEATURES OF ADAPTIVE AND INNATE IMMUNITY
DIAGNOSIS
Correlation Between Clinical and Histologic Findings

apical periodontitis is not always symptomatic or painful.

Although many inflammatory mediators and proinflammatory cytokines, as well as

neuropeptides , are capable of sensitizing and activating nociceptive sensory nerve fibers,
other mediators such as endogenous opioids and somatostatin released by inflammatory
cells during inflammation are able to inhibit firing of sensory nerve fibers.

The complexity of these findings supports the clinical observation that there is no good
correlation between clinical symptoms and histopathologic findings of apical periodontitis
DIAGNOSIS

Correlation Between Radiographic and Histologic Findings

Using conventional radiographic and histologic methods in the same cadavers,

evidence of inflammation was often observed in the periapical tissues of
endodontically treated teeth with normal radiographic features. This finding is
supported by the fact that lesions localized in the cancellous bone may not be
visible radiographically unless they involve cortical bone.

Accordingly, radiographic findings and histopathologic features of apical

periodontitis have a poor correlation .
SYMPTOMATIC APICAL PERIODONTITIS
 Inflammatory Mediators
● derived from plasma and
cells
● cause vasodilation and
increased vascular
permeability
● recruit inflammatory cells to
the site of tissue injury
● Some mediators can also
cause tissue damage
Clinical Features
● symptomatic
● painful to bite and percussion

allodynia and hyperalgesia

● Radiographically:
slight widening of the apical periodontal ligament space loss of the

apical lamina dura

Outcomes
1) restitution of normal periapical tissues if irritants are immediately
eliminated by root canal therapy
(2)abscess formation if massive invasion of periapical tissues by
highly pyogenic bacteria occurs

(3)organization by scarring if extensive destruction of periapical tissues

results; or
(4)progression to chronic apical inflammation if irritants continue to
persist
 ASYMPTOMATIC APICAL
PERIODONTITIS: APICAL GRANULOMA,
CHRONIC APICAL PERIODONTITIS

CABIJE, ATHEA ZENN QUIELLEN F.

Asymptomatic apical periodontitis
-is a form of adaptive immune response
Granuloma
- is a focal area of granulomatous inflammation
- relatively avascular
Chronic apical periodontitis
- is very vascular
Inflammatory Mediators
• Tumor necrosis facto alpha
• Interleukin- 1
• Interleukin- 6
• Interleukin- 8
• Interleukin- 10
• Transforming growth factor beta
• Prostaglandins
• Matrix metalloproteinases (MMPs)
• RANK ligand ( RANKL)
CLINICAL FEATURES
• ill-defined or well-defined periapical radiolucent lesion.
• chronic apical abscess and associated sinus tract are usually
asymptomatic
• sinus tract from an apical abscess may drain along the root surface
and opens into the gingival sulcus.
• development of a deep, narrow pseudopocket that often mimics a
periodontal pocket or a vertical root fracture
OUTCOMES
Asymptomatic apical periodontitis may result in:
1. Regeneration or repair of the periapical tissues after root canal therapy;
2. Severe periapical tissue destruction
3. Acute exacerbation
4. Development of an abscess with an intraoral or extraoral draining sinus
tract
5. Development of a serious cellulitis.
ASYMPTOMATIC APICAL
PERIODONTITIS WITH CYST
FORMATION: RADICULAR CYST,
CHRONIC APICAL PERIODONTITIS WITH
CYST FORMATION

Report by Cairoden
 ASYMPTOMATIC APICAL PERIODONTITIS WITH CYST FORMATION: RADICULAR
CYST, CHRONIC APICAL PERIODONTITIS WITH CYST FORMATION

Inflammatory Mediators:
o Similar to those present in chronic
apical periodontitis

Clinical Features:
o Asymptomatic

Outcomes:
o Nonsurgical root canal therapy (no direct
evidence)
o Surgical biopsy or extraction of teeth with
apical periodontitis
o Pocket Cysts
o Apical True Cysts

Report by Cairoden
ASYMPTOMATIC APICAL PERIODONTITIS WITH REACTIVE
BONE FORMATION: CONDENSING OSTEITIS OR CHRONIC
FOCAL SCLEROSING OSTEOMYELITIS

Lesions are caused by a long-term, low-grade inflammation/infection or

a high resistance of local tissue to inflammation/infection

Instead of bone resorption, the inflammation induces reactive bone

formation of alveolar trabecular or spongy bone around the periapex of
endodontically involved teeth
 Cell Biology Osteoblasts appear to be stimulated to produce more bone

There is an excessive apposition of bone

Histopathology mass without bone resorption in the apical area
Clinical Features
➢ Lesion is usually observed in young patients, and the mandibular
first molar
➢ Teeth often have gross carious lesions and can be vital or nonvital
➢ Asymptomatic
➢ Radiographically, the lesion may have a well-defined or ill-defined
radiopaque mass associated with the apex of an endodontically
involved tooth
➢ The lamina dura around the root apex is usually intact

Outcomes Healing after nonsurgical root canal therapy

 PERIAPICAL LESIONS OF NONENDODONTIC ORIGIN
• Pathological condition affecting the periapical region of tooth that are not
caused by pulpal infection or inflammation

• Treatment: Surgical excision, endodontic therapy and periodontal treatment

EXTRARADICULAR ENDODONTIC INFECTION
• Bacteria have established an infectious process outside the
root canal system
• It’s development still not fully understood but usually, it
originates from the Intraradicular endodontic infection
• Can only be diagnosed after surgical biopsy
INTRARADICULAR ENDODONTIC INFECTION
• Bacteria established an infectious process within the root canal
system
• Primary – “virgin” infection
• Secondary – during treatment, between appointments or after
root canal filling
• Persistent – “recurrent infection”
APICAL PERIODONTITIS AND SYSTEMIC DISEASE
• Systemic conditions affecting the severity of
inflammatory periapical lesions

Ex: Diabetes, Smoking and hypertension

→Diabetes – more prone to infection due to nerve

damage and reduced blood flow
WOUND HEALING OF APICAL
PERIODONTITIS
• Understanding of wound healing is as important as knowing the
pathogenesis of disease

• Ultimate goal of treatment: satisfactory wound healing

• Healing begins as soon as the inflammation starts.

• When irritants are removed, inflammatory mediators are no longer

produced in the periapical tissue
PERIAPICAL WOUND HEALING OF SURGICAL
AND NONSURGICAL ROOT CANAL THERAPY
NON-SURGICAL ENDODONTIC THERAPY
- Main goal is to remove primary microbial etiology from the root
canal system by performing bacterial killing and clean up called
biological debridement

SURGICAL ENDODONTIC THERAPY

- Removal of the irritants that causes inflammation in the periapical
lesion such as necrotic cells, tissue debris and bacteria called
surgical debridement
 FACTORS INFLUENCING PERIAPICAL
WOUND HEALING
• Local and systemic factors may affect periapical wound healing.
Infection will complicate and prevent wound healing, foreign bodies can
impair wound healing, and nutrition can also affect wound healing.

• DIABETES
• IMMUNOCOMPROMISED PATIENTS
• SMOKING
• RADIOTHERAPY OF JAWS AND BISPHOSPHONATE THERAPY
 CHAPTER 15
Microbiology and Treatment
of
Endodontic Infections

presented by:
BERNALES, BESO, CABIJE, CAIRODEN, CAMONGAY, CONCEPCION
APICAL PERIODONTITIS
AS AN INFECTIOUS DISEASE

Antony van Leeuwenhoek

root canals of a decayed tooth “were stuffed with a soft matter” and
that “the whole stuff” seemed to him to be alive,but the role of
Leeuwenhoek’s “animalcules” in disease causation was
unsuspected at that time.

after almost 200 years a confirmed cause-and-effect relationship

between bacteria and apical periodontitis was suggested.
APICAL PERIODONTITIS
AS AN INFECTIOUS DISEASE

Willoughby Dayton Miller

by means of bacterioscopy of the canal samples, he found bacterial

cells in the three basic morphologies known at the time: cocci, bacilli,
and spirilla (or spirochetes)

spirochetes were found in high frequencies in abscessed cases.

the endodontic microbiota was clearly different in the coronal, middle,

and apical parts of the root canal
APICAL PERIODONTITIS
AS AN INFECTIOUS DISEASE
Kakehashi et al.
conventional and germ-free rats exposed to oral
cavities.Pulp necrosis and apical periodontitis lesions
developed in all conventional rats, the pulps of germ-free
rats not only remained vital but also repaired themselves by
hard-tissue formation.
ROUTES OF ROOT CANAL INFECTION

pulpodentin complex is sterile and isolated from oral microbiota by overlying

enamel and cementum, if this is breached, the pulpodentin complex is exposed to
the oral environment and then challenged by microorganisms present in caries
lesions, saliva bathing the exposed area, or in dental plaque.

dentinal tubules:
largest diameter -2.5mm
(located near the pulp)

smallest diameter-0.9 mm
(periphery, near the enamel
or cementum)

bacteria:
ranges from 0.2 -0.7 mm
Trauma
when teeth experience trauma and the pulp inside dies, bacteria from the
gums or pockets around the teeth can travel through the severed blood
vessels of the gums and enter the root canals. This process is called
anachoresis.

Caries
is the most common cause of pulp exposure, but bacteria may also reach the
pulp via direct pulp exposure as a result of iatrogenic restorative procedures.
Bacterias multiply and push deeper through tubules. And sometimes when you chew, it
pushes bacteria through.So even before the cavity gets deeper, the bacteria can already
reach into the pulp.
MECHANISMS OF MICROBIAL PATHOGENICITY AND VIRULENCE FACTORS

The ability of a microorganism to cause disease is regarded as pathogenicity. Virulence

denotes the degree of pathogenicity.

Some microorganisms routinely cause disease in a given host and are called
primary pathogens. Other microorganisms cause disease only when host defenses
are impaired and are called opportunistic pathogens.

Bacterial virulence factors comprise structural cellular components and released

products.Virulence is described by the extent of how our tissue is either directly
and indirectly harmed.
BIOFILM AND COMMUNITY-BASED MICROBIAL
PATHOGENESIS

ECOSYSTEM
COMMUNITY - unified assemblage of populations that coexist and interacts
POPULATION - maintains ecological balance of the ecosystem
INDIVIDUAL
 BIOFILM AND BACTERIAL INTERACTIONS
Biofilm is a sessile multicellular microbial community characterized by cells that
are firmly attached to a surface and enmeshed in a self-produced matrix of
Extracellular Polymeric Substance (EPS), usually polysaccharide.

- Structurally and dynamically organized complex substance

- Microcolonies usually shaped as ‘towers’ or ‘mushrooms’
- Biofilms can reach up to 300 or more cell layers in thickness
 BIOFILM COMMUNITY LIFESTYLE
● A BROADER HABITAT RANGE FOR GROWTH
○ Early colonizers alters the local environment for the latecomers.
○ Diversity of the microbiota increases over time because of bacterial succession

● INCREASED METABOLIC DIVERSITY AND EFFICIENCY

○ Byproducts of the degradation of complex nutrients are trapped in the biofilm matrix
and shared with other community members

● PROTECTION FROM COMPETING MICROORGANISMS, HOST

DEFENSES, ANTIMICROBIALAGENTS, AND ENVIRONMENTAL STRESS
○ Cells of different species produce enzymes such as beta-lactamase, catalase, and
proteinases, metabolites and bacteriocins
● GENETIC EXCHANGES
○ Cell-cell associations and related to the acquisition and dissemination of virulence
and antibiotic-resistance genes

● ENHANCED PATHOGENICITY
○ Diverse range of virulence traits are required for a particular stages of the disease
process, concerted action of bacterias in a community.
 RESISTANCE TO ANTIMICROBIAL AGENTS
● Biofilm structure
● Altered growth rate of biofilm bacteria
○ In stationary phase represent a general mechanism of antibiotic resistance in the biofilm
● Presence of ‘Persister’ Bacteria
○ Persisters are subpopulation of specialized survivor cells
QUORUM SENSING-BACTERIAL INTERCOMMUNICATION

● Cell-cell communication that regulate gene

expression in a cell density-dependent manner.
● Involves the production, release of signaling molecules
called autoinducers.
● Regulate virulence, competence for DNA uptake, entry into
stationary phase and biofilm formation.
 METHODS FOR MICROBIAL
IDENTIFICATION

BY: CABIE, ATHEA ZENN QUIELLEN F.

WHAT IS CULTURE?
- is the process of propagating microorganisms in the laboratory

Steps Involved:
• Sample collection and transport
• Dispersion
• Dilution
• Cultivation
• Isolation
• Identification
 ADVANTAGES LIMITATIONS
• Widely available • Impossibility of culturing a large
number of extant bacterial species
• Allow quantification of all major • Not all viable bacteria can be
viable cultivable microorganisms recovered
• Allow determination of antimicrobial • Once isolated, bacteria require
susceptibilities of isolates identification using a number of
techniques
• Physiologic studies are possible • Takes several days to weeks to
identify most anaerobes

• Pathogenicity studies are possible • Samples require immediate

processing
ADVANCEMENT IN MOLECULAR BIOLOGY

- Molecular biology technique is widely used to directly identify

microorganisms without the need of cultivation
- Utilization of specific gene:
o16S rRNA gene (bacteria) can be amplified by polymerase
chain reaction (PCR) using broad range (or universal)
primers
o18S rRNA gene ( fungi and other eukaryotes)
Impact of Molecular Methods in Endodontic Microbiology

- confirmed and strengthened the association of many cultivable

bacterial species with apical periodontitis
- Identified new potential endodontic pathogens.
- The list of candidate pathogens has expanded to include
culture-difficult or previously uncultivated bacteria.
- Molecular studies have remarkably increased knowledge of
bacterial diversity, detecting over 400 species.
- about 45% molecular biology studies, compared to 32%
detected by culture studies alone
 ADVANTAGES AND LIMITATIONS OF MOLECULAR
BIOLOGY METHODS
ADVANTAGES LIMITATIONS
High specificity and accurate identification Can be very expensive
of strains
Can be used during antimicrobial Hybridization assays using whole genome
treatment probes detect only cultivable species
Samples can be stored frozen for later Most assays detect only the target species
analysis and fail to detect unexpected species
(exception: broad-range PCR)
DNA can be transported easily between Some assays can be laborious and costly
laboratories (e.g., broad-range PCR)
TYPES OF ENDODONTIC INFECTIONS
• INTRADICULAR INFECTION
- is caused by microorganisms colonizing the root canal system.
3 CATEGORIES:
✓Primary infection
-caused by microorganisms that initially invade and colonize
necrotic pulp tissue (initial or “virgin” infection)
✓Secondary infection
- caused by microorganims not present in the primary infection but
introduced in the root canal at some time after professional intervention
(i.e., secondary to intervention)
✓Persistent infection
- caused by microorganisms that were members of a primary or
secondary infection
• EXTRARADICULAR INFECTION
- is characterized by microbial invasion of the inflamed peri radicular
tissues and is a sequel to the intraradicular infection.
PRIMARY INTRARADICULAR
INFECTION
Microbial Composition and Diversity
• PRIMARY INTRARADICULAR INFECTION
- infection of the necrotic pulp tissue
-characterized by a mixed community conspicuously
dominated by anaerobic bacteria.
-number of bacterial cells may vary from 103 to 108 per
root canal.
-Molecular studies have disclosed a mean of 10 to 20
species/phylotypes per infected canal
-Canals of teeth with sinus tracts exhibit a mean number of
species
• number of taxa per canal was clearly in direct proportion to the
lesion size:
small lesions (<5mm)= 12 taxa
lesions from 5 to < 10mm = 16 taxa
lesions over 10 mm =20 species
PRIMARY INTRARADICULAR INFECTION

SYMPTOMATIC INFECTIONS
• Acute Apical Periodontitis
Pulpal necrosis
o Location: canal, reached the peri-radicular tissues
o Common inflammatory condition
o Caused by bacterial infection of the dental pulp Cracked tooth

Bacteria

Defensive
Mechanism

Report by Cairoden
PRIMARY INTRARADICULAR INFECTION

SYMPTOMATIC INFECTIONS

• Acute Apical Abscesses

o Spread to other anatomic spaces
o Severe form of acute apical periodontitis (AAP)
o Purulent collection of fluid (abscesses)

Report by Cairoden
PRIMARY INTRARADICULAR INFECTION

GEOGRAPHIC INFLUENCE
o Refers to how the prevalence, characteristics, and outcomes of these infections
can vary based on geographical factors

❑ PREVALENCE
❑ MICROBIAL FLORA
❑ TREATMENT OUTCOMES

SPATIAL DISTRIBUTION OF MICROBIOTA --- ANATOMY OF

INFECTION
B
A Pulp Chamber
C ABSCESS
T infection Dentinal Tubules infection Peri-radicular Tissues infection
E Root Canal FORMATION
R Space
I
A

Report by Cairoden
 PRIMARY INTRARADICULAR INFECTION

MICROBIAL ECOLOGY AND THE ROOT CANAL ECOSYSTEM

o Root canal with necrotic pulp
❑ moist
❑ Warm
❑ nutritious anaerobic environment
❑ Considered a fertile environment for bacterial growth and colonization
❑ About 100-200: bacterial species
❑ About 10-40: limited assortment

o The major ecological factors that determine the o The main sources of nutrients for bacteria
composition of the root canal microbiota include: colonizing the root canal system include
▪ Oxygen tension ▪ Necrotic pulp tissue
▪ Type and amount of available nutrients ▪ Proteins and glycoproteins from tissue fluids and
▪ Bacterial interactions. exudate that seep into the root canal system via
▪ Others: temperature, pH, and receptors for apical and lateral foramens
adhesins ▪ Components of saliva that may coronally penetrate
into the root canal
▪ Products of the metabolism of other bacteria
Report by Cairoden
PRIMARY INTRARADICULAR INFECTION

OTHER MICROORGANISMS IN ENDODONTIC INFECTIONS

o FUNGI o VIRUSES
✓ Eukaryotic microorganisms ✓ Human Cytomegalovirus (HCMV)
✓ Relatively rare ✓ Epstein-Barr Virus (EBV)
✓ Candida species
o ARCHAEA
✓ Highly diverse group of prokaryotes
✓ Not considered primary pathogen of
endodontic infections
✓ Methanobrevibacter oralis

Report by Cairoden
PERSISTENT/SECONDARY ENDODONTIC INFECTIONS
Caused by microorganisms that resisted intracanal antimicrobial
procedures and survived in the treated canal

SECONDARY ENDODONTIC INFECTIONS PERSISTENT ENDODONTIC INFECTIONS

Secondary/Persistent Infections
and Treatment Failure
Regardless of treatment quality, persistent or secondary intraradicular
infections are the main causative agents of endodontic treatment failure

Bacteria at the Root Canal–Filling Stage

Diligent antimicrobial treatment may still fail to completely eliminate
bacteria from the infected root canal system. This is because persisting
bacteria are either resistant or inaccessible to treatment procedures
EXTRARADICULAR INFECTIONS
THE FOCAL INFECTION THEORY

In 1900 William Hunter, a English physician first developed the idea that oral
microorganisms were responsible for a wide range of systemic conditions.

Focal infection consists of an infectious disorder caused by microorganisms or their

products that have disseminated from a distant body site (focus of infection).

Microorganisms from an infected oral site might spontaneously or after dental

procedures gain entry into the blood circulation and cause disease in remote sites.
TREATMENT OF ENDODONTIC
INFECTIONS - RATIONALE
ULTIMATE GOALS OF ENDODONTIC TREATMENT

• Prevent development of apical periodontitis

• If diseases are present, create adequate conditions for periradicular
tissue healing
• Eliminate or reduce the microbial population within the root canal
system
• Prevent microorganism form infecting and reinfecting the root canal
or the periradicular tissues
THE MAIN STEPS OF ENDODONTIC TREATMENT
INVOLVED WITH INFECTION CONTROL
• CHEMOMECHANICAL PREPARATION → process of using
both chemical solutions and mechanical instruments.

• Sodium hypochlorite (NaOCl) → most widely used solution

• INTERAPPOINTMENT MEDICATION → complement the

antibacterial effects of chemomechanical procedures and
eliminate persisting bacteria

• Calcium hydroxide is the most used intracanal medication

MANAGEMENT OF ABSCESSES AND
CELLULITIS

AND SYSTEMIC ANTIBIOTICS FOR

INFECTIONS
Important elements of effective patient
management:
• 1.) CORRECT DIAGNOSIS OF THE LESION OR DISEASE
• 2.) REMOVAL OF THE CAUSE OF THE INFECTION

Antibiotics are not recommended for: Irreversible pulipits, acute apical

periodontits, draining sinus tracts, after endodontic surgery, to prevent flare
ups, or after incision for drainage of a localized swelling

Analgesics: they are not antibiotics and it is indicated for the treatment of
pain
Antiobitics are appropriate for:
• progressive or persistent infections with systemic signs and
symptoms such as fever, malaise, cellulitis , unexplained trismus, and
progressive or persistent swelling

Why is it that antibiotics are effective debridement for the root canal
system?

Overuse and misuse of antibiotics has been considered the major

cause for the emergence of multi drug-resistant strains
INCISION FOR DRAINAGE

• is indicated whether the cellulitis is indurated or fluctuant

• An incision for drainage allows decompression of the increased tissue

pressure associated with edema and provides significant pain relief