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Endodontic infection is recognized as a major etiologic agent of apical periodontitis. This infection of the root canal system commonly follows pulp necrosis due to a myriad of causes such as caries, trauma, periodontal disease or operative procedures, which provide a pathway for oral micro-organisms to infiltrate it. Though chemical and physical factors have been implicated in the induction of peri-radicular inflammation, there is compelling evidence that micro-organisms are essential in progression and perpetuation of apical periodontitis.
Microbial Causation of Apical Periodontitis
Guidelines for establishing specific microbial causation
Several guidelines have emerged over the years to identify pathogenic micro-organisms. Koch's postulates and several variants have been commonly used to establish microbial etiology for many diseases. With the advent of genomics, molecular biology has also provided us with useful tools to identify these pathogens.
Current evidence suggests that a consortium rather than a single species is involved in apical periodontitis and that different compositions of root canal microbiota can cause equal destruction. Unfortunately, the specifics are still unknown though a handful of species (20 to 40) have been frequently detected in such infections and may be responsible for the majority of apical periodontitis lesions.
Requirements for endodontic pathogens
For a micro-organism to be involved in the pathogenesis of apical periodontitis, it must fulfil the following criteria:
1) It must be present in sufficient quantity for initiation & maintenance of disease
2) It must possess an array of virulence factors
3) It must be located such that it or its virulence factors can access the peri-radicular tissues
4) The root canal environment must permit its survival and growth and stimulate its virulence genes
5) Inhibiting micro-organisms must be absent or present in low numbers
6) Host response occurs to limit the spread of infection but with resultant tissue damage
Mechanisms of microbial pathogenicity
Bacteria can cause disease by direct and indirect mechanisms.
The direct mechanism involves bacteria secreting products eg. enzymes, exotoxins and other metabolites. Bacterial components may invoke a host response which causes tissue destruction by secretion of cytokines, prostaglandins and other inflammatory mediators. These cause bone resorption seen in chronic apical periodontitis.
The indirect mechanism for example, involves indirect damage caused by bacteria due to pus formation in the case of chronic apical abscess.
Genetic control of virulence
Virulence of bacteria is controlled by pathogenicity islands found in their DNA (chromosome or plasmid).
Bacterial cell components as well as their released products make up virulence factors. These act synergistically to cause disease, by attaching to host surfaces, invading tissues and host cells, spreading in the host, causing direct and indirect tissue damage, as well as evading host response.
Lipopolysaccharides (LPS) present in the cell walls of Gram-negative bacteria, are well-known virulent factors for causing disease. Its toxic component is Lipid A while its carrier is known as LPS binding protein (LBP). CD 14 on the macrophage recognizes the LPS and the signal transducer involved is TLR-4. LPS can stimulate macrophages to produce proinflammatory cytokines such as IL-1Î², IL-6, IL-8, TNFÎ±), PGE2, nitrogen oxide, and oxygen-derived free radicals, which in turn lead to inflammation and bone resorption. LPS also activates the complement system via both the alternative and classical pathway. They stimulate the expression of leukocyte adhesion molecules in endothelial cells , as well as osteoclast differentiation and bone resorption via RANKL expression in osteoblasts. At low concentrations, they can cause specific antibody production but at high concentrations, they cause unspecific polyclonal activation of B cells. Teeth with symptomatic apical periodontitis, periradicular bone destruction, and persistent exudation have demonstrated higher levels of LPS. LPS of porphyromonas endodontalis has been tracked down in infected canals and acute abscesses.
Many other virulent factors have similar action as bacterial LPS - stimulation of macrophages to release cytokines, and activating the complement system. These include peptidoglycan, teichoic and lipoteichoic acids (LTA), outer membrane proteins, lipoproteins, and bacterial DNA. It has been suggested that outer membrane proteins (OMP) are implicated in apical periodontitis while bacterial DNA also modulates osteoclastogenesis.
Bab et al1 realized that LTA leads to a cascade of events that causes tissue damage. Ciardi et al 2 also found that it plays a role in adhesion and colonization. Card et al3 later found that LTA induces inflammation.
In addition to stimulation of macrophages to release cytokines, fimbriae allow the adhesion of bacteria onto host surfaces via specific receptors. Exo-polysaccharides may also be involved in bacterial adhesion. They hinder phagocytosis, inhibit the complement system as well as complement-mediated killing. It has been shown that bacteria encapsulated in exopolysaccharides are more capable of causing abscesses.
Rakita et al4 found that aggregation substance (AS), a bacterial adhesion, gives the bacteria resistance to host response.
Enzymes are another group of virulence factors that degrade extracellular components of the connective tissue and allow bacterial invasion. Proteinases such as those in P. endodontalis allow bacterial evasion from phagocytosis. Hyaluronidase has been isolated from canals exhibiting acute or sub acute clinical symptoms.
Takao et al5 proved that hyaluronidase causes tissue damage.
Metabolic end products are toxic to host cells and they induce degradation processes. They can accumulate to reach toxic levels in periradicular tissues. Flagella on the other hand, gives the bacteria its motility and hence virulence.
Relevance in the root canal system
The root canal system with a necrotic pulp, with its moist, warm, nutritious, and anaerobic environment, provides a desirable environment for microbial colonization. The intracanal location and lack of micro-circulation within the necrotic pulp tissue further confers protection to these micro-organisms from host defenses.
Nonetheless, during the dynamic process of root canal infection, the root canal system is only colonized by restricted species of microorganisms, with dominance of different bacterial species in different parts, due to selective pressures from various ecological factors.
For instance, an intracanal temperature of about 30-38 degrees celcius may select against bacteria which are thermophiles and psychrophiles. An intracanal pH of 6.4-7.0 (or slightly higher pH due to protein metabolism) may favour neutralophiles or other putative endodontic pathogens which usually thrive under such pH range.
Facultative bacteria predominating the initial phases of pulpal infection are gradually replaced by obligate anaerobic bacteria as the disease progresses. Oxygen depletion from pulp necrosis and consumption by facultative bacteria, exacerbated by the loss of blood circulation within the necrotic pulp, creates an anaerobic environment with low oxygen tension and low redox potential, favouring colonization of the latter.
Competition for and utilization of nutrients either from the host (necrotic pulp tissue, tissue fluids, exudate, and saliva) or other species in the infected site (metabolites) also affects the type of bacteria colonizing the canal. Initially, saccharolytic species predominate. Shortly after, the carbohydrates are depleted and nutrients are now supplied by exudate from periradicular inflammation in the form of protein and glycoproteins. This results in a shift to asaccharolytic or weakly saccharolytic species, as they are able to ferment peptides and amino acids to obtain energy. Some strongly proteolytic endodontic pathogens, such as porphyromonas, dominate and assist non-proteinase and peptidase -producing bacteria by degrading macromolecular protein compounds to produce polypeptides.
Intracanal variation in oxygen and nutrition levels also affects bacterial colonization at different parts of the root canal system. The coronal region is mainly colonized by facultatives and aero-tolerant anaerobes which utilize carbohydrate for metabolism. The apical region, however, is mainly colonized by obligate anaerobes which utilize protein and glycoprotein-rich tissue fluid and exudate.
The abovementioned microbial interactions within the densely populated root canal system can be either positive or negative. Positive interactions such as mutualism (e.g. T.denticola, a strongly proteolytic pathogen, degrades glycoproteins and proteins for its own catabolism. The polypeptides produced can also be utilized by non-proteinase and peptidase-producing bacteria such as F. nucleatum for energy) and commensalism (e.g. Veillonella utilizes the metabolite lactate secreted by streptocci) enhance survival capacity of interacting microorganisms, and they are usually found together in the habitat. On the other hand, negative interactions such as competition (e.g. Pioneer species inhibiting establishment of competitive latecomers) and amensalism (e.g. Accumulation of metabolites such as short-chain fatty acids and sulfur compounds inhibiting growth of some species) help to limit population densities. Such organisms are usually found independent of each other in the habitat.
Some microbial of different oral species also interact via co-aggregation, as it favours colonization of host surfaces and facilitates metabolic interactions.
Overtime, driven by mutual nutritional and functional interests, the microorganisms may organize and achieve a certain degree of stability, resulting in the formation of a climax community. Equilibrium is established between the microorganisms and between them and the environment. Such cases are associated with larger peri-radicular bone destruction, and correspondingly poorer treatment prognosis.
Patterns of colonization
The knowledge of the pattern of microbial colonization allows understanding of the disease process and establishment of effective antimicrobial treatment. Although, theoretically any bacterial species may invade the root canal system, evidences suggest that some bacterial species are related to certain forms of apical periodontitis.
Studies using light and/or electron microscopy identified, morphologically, the root canal microbiota consists of cocci, rods, filaments and spirochetes with fungal cells sporadically found. Most of them remain suspended in the fluid phase of the main root canal, sometimes forming multilayered bacterial condensations that resemble biofilm like communities. A common observation is that the pattern of colonization is not uniform among different teeth, not even in the same root canal. The degree of colonization is independent of the root canal third and can be a reflex of diverse ecological factors operating in each area.
Bacteria forming dense accumulations on the root canal walls are often seen penetrating the dentinal tubules. Most of the bacteria invading the dentinal tubules are cocci, but rods are seen occasionally. Since most bacteria that have been identified in tubules are non-motile species, motility is not a necessary bacterial attribute to dental invasion. Microorganisms located into tubules may pose a treatment problem, because of difficulties in their elimination during intracanal procedures.
Dividing cells in-situ indicates that bacteria can derive nutrients within tubules, probably from degrading odontoblastic processes, denatured collage, bacterial cells that die during the course of infection and intracanal fluids that enter the tubules by capillarity.
Primary Endodontic Infections
With the advent of new microbiological methods, new pathogens related to endodontic infections have been elucidated. Meanwhile, higher prevalence of a polymicrobial mix of known pathogens such as obligate anaerobic bacteria has been noted with the use of these methods and this has strengthened their association with apical periodontitis.
Previously known as Bacteroides melaninogenicus, these anaerobic Gram negative rods have been reclassified into the Prevotella species consisting of P. tannaerae, P. Multissacharivorax, P denticola and the Porphyromonas species consisting of P. endodontalis and P. gingivalis. T. forsythia has been detected for the first time with the use of PCR techniques. Dialister species consisting of D. pneumosintes and D. invisus have been associated with primary endodontic infections with the use of new molecular biology techniques. F. Nucleatum with its five subspecies of fusiforme, nucleatum, polymorphum, vincentii and animalis has been frequently detected in infected root canals and abscesses. Spirochetes such as Treponema consisting of T. pectinovorum, T. socranskii,T. amylovorum, T. lecithinolytum,T. maltophilum and T. parvum together with T. denticola, T. medium, T. putidum and T. vincentii have been detected with T denticola and T socranskii being most prevalent amongst the treponemes in endodontic infections.
Gram positive rods are also detected as part of the endodontic microflora and include P. alactolyticus, Filifactor alocis, Slackia exigua, Mogibacterium timidum, E saphenum and Eubacterium infirmum. Actinomyces gerencseriae, Actinomyuces israelii and P. propionicum have been associated with endodontic failure by causing apical actinomycosis.
Gram positive cocci such as peptostreptococci and streptococci including P. micros and S. anginosus are commonly detected although other streptococci such as S. gordonii, S. mitis and S. sanguinis can also be detected.
Gram negative rods such as those of the Campylobacter species like C. rectus and C. gracilis have been detected in low to moderate prevalence. Whilst P. aeruginosa and E. coli are more commonly found in secondary endodontic infections, a breach in the aseptic chain may result in their introduction into the root canal system. Capnophilic species such as A. actinomycetemcomitans are not favored in the root canal environment and are not found in primary endodontic infections.
Fungi are rarely found in the root canal system although a study found the presence of C. Albicans in 21% of primary root canal infections. Methanogenic archaea, a diverse group of prokaryotes, are found in approximately 25% of teeth with chronic apical periodontitis. HIV has been reported in non-inflamed pulp of infected patients but HCMV and EBV have been reported in apical periodontitis lesions and have been implicated in the overgrowth of pathogenic bacteria due to their impairment of host immune response.
Factors that influence the development of symptoms include the presence of virulent clonal types, microbial synergism or additism, number of microbial cells, environmental cues, host resistance and concomitant herpes virus infection. The development of symptoms is not well understood and there is a possibility of microbial succession resulting in a shift in structure of microbial community has been postulated as a likely cause.
Persistent endodontic infection
Persistent endodontic infections usually result from bacteria that remain in the canal even after cleaning and shaping. There are several possible situations in which this could result. One of which is that during cleaning and shaping, parts of the root canal surface remain untouched. These could be due to the presence of irregularities in the surface of the canal or even lateral canals. Furthermore, micro leakage can occur, either via the restoration or root fill as there is no guarantee that an absolute apical and coronal seal can be obtained. These residual microbes can then get their necessary nutrient supply from necrotic tissue remnants or via saliva which may have leaked in.
However, having bacteria left in the canal does not always equate to treatment failure. This is because, in a filled root canal, nutrients may not be available all the time or in large amounts. Hence, bacteria need to be relatively resistant in order to endure such an environment and most bacteria are not able to do so. One of the bacteria that have shown potential to do so would be Enterococcus faecalis. On the other hand, even if bacteria such as E. faecalis can survive the environment, it must also be able to overcome the host response in order to result in a persistent endodontic infection.
Prevention of inter-appointment flare ups
To prevent the occurrence of inter-appointment flare-ups, the following steps could be taken. The treatment should be carried out in an aseptic condition, with good rubber dam isolation and sterilized endodontic instruments. Instruments and irrigant solutions should be uncontaminated. Complete cleaning and shaping of the root canal system should be carried out, with the avoidance of over instrumentation of the apical foramen. This will ensure that all potential microbial irritants are removed from the root canal, such as dental plaque, calculus, caries, and traces of necrotic pulp. As root canal treatment sometimes cannot be completed in one visit, it is essential that the temporary restorative material be placed securely to avoid dislodgement. The restoration or the tooth structure should be adjusted such that there is no occlusion, to avoid fracture or loss of the temporary restoration or tooth. The patients also ought to be informed of the possible symptoms that might occur after the appointment, and that they should call should they notice any adverse signs and symptoms.
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Bab IA, Sela MN, Ginsburg I, Dishon T (1979). Inflammatory lesions and bone resorption induced in the rat periodontium by lipoteichoic acid of Streptococcus mutans. Inflammation 3:345-358.
Ciardi JE, Rölla G, Bowen WH, Reilly JA (1977). Adsorption of Streptococcus mutans lipoteichoic acid to hydroxyapatite. Scand J Dent Res 85:387-391.
Card GL, Jasuja RR, Gustafson GL (1994). Activation of arachidonarachidonic acid metabolism in mouse macrophages by bacterial amphiphiles. J Leukoc Biol 56:723-728.
Rakita RM, Vanek NN, Jacques-Palaz K, Mee M, Mariscalco MM, Dunny GM, et al. (1999). Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation. Infect Immun 67:6067-6075.
Takao A, Nagashima H, Usui H, Sasaki F, Maeda N, Ishibashi K, et al. (1997). Hyaluronidase activity in human pus from which Streptococcus intermedius was isolated. Microbiol Immunol 41:795-798.
British Dental Journal 197, 603 - 613 (2004) Subject Category: Endodontics. Endodontics: Part 7 Preparing the root canal. P Carrotte1