1 Pathogenesis of Pulp and Periapical Diseases CHRISTINE SEDGLEY, RENATO SILVA, AND ASHRAF F. FOUAD CHAPTER OUTLINE Histology and Physiology of Normal Dental Pulp, 1 Normal Pulp, 11 Etiology of Pulpal and Periapical Diseases, 2 Reversible Pulpitis, 11 Microbiology of Root Canal Infections, 5 Irreversible Pulpitis, 11 Endodontic Infections Are Biofilm Infections, 5 Pulp Necrosis, 12 The Microbiome of Endodontic Infections, 6 Clinical Classification of Periapical (Apical) Conditions, 13 Pulpal Diseases, 8 Nonendodontic Pathosis, 15 LEARNING OBJECTIVES After reading this chapter, the student should be able to: 6. Describe the histopathological diagnoses of periapical lesions of 1. Describe the histology and physiology of the normal dental pulpal origin. pulp. 7. Identify clinical signs and symptoms of acute apical periodon- 2. Identify etiologic factors causing pulp inflammation. titis, chronic apical periodontitis, acute and chronic apical 3. Describe the routes of entry of microorganisms to the pulp and abscesses, and condensing osteitis. periapical tissues. 8. Discuss the role of residual microorganisms and host response 4. Classify pulpal diseases and their clinical features. in the outcome of endodontic treatment. 5. Describe the clinical consequences of the spread of pulpal 9. Describe the steps involved in repair of periapical pathosis after inflammation into periapical tissues. successful root canal treatment. palisading layer that lines the walls of the pulp space, and their Histology and Physiology of Normal Dental tubules extend about two thirds of the length of the dentinal Pulp tubules. The tubules are larger at a young age and eventually become more sclerotic as the peritubular dentin becomes thicker. The dental pulp is a unique connective tissue with vascular, lym- The odontoblasts are primarily involved in production of mineral- phatic, and nervous elements that originates from neural crest ized dentin. They are connected by gap junctions that allow them cells. It resides inside the tooth in a chamber with rigid walls. to form a semipermeable membrane. In addition, odontoblasts The pulp contains odontoblasts, highly specialized cells with a play an important role in defense as they express Toll-like recep- secretory function, which not only form dentin, but also interact tors (see later), cytokines, and defensins, among other immuno- with dental epithelium early in tooth development to initiate the logic mediators. formation of enamel. The pulp also contains fibroblasts, undiffer- Two main types of sensory fibers innervate the pulp: δA -fibers entiated mesenchymal cells, collagen type I and II, proteoglycans, in the periphery and C-fibers in the central pulp. Theδ A -fibers glycoproteins, and water1 (Fig. 1.1). are responsible for the sharp response to thermal changes. They The histologic structure of the pulp is important, because it extend between the odontoblasts, lose their myelin sheath, and reflects a unique architecture suited for the formation of dentin extend to a distance of 100 to 200 μm into the dentinal tubules. and defense against invading pathogens. Odontoblasts form a The C-fibers are unmyelinated and are responsible for the dull 1 2 CHAPTER 1 Pathogenesis of Pulp and Periapical Diseases A B BV PD * OD C OD FB PD D • Fig. 1.1 Histologic section of (A) rat molar tooth showing coronal (B) and (C) radicular dental pulp in higher magnification. Masson-Goldner trichrome staining. BV, Blood vessels; D, dentin; FB, fibroblasts; OD, odontoblasts in odontoblastic layer; PD, predentin. An artifact (*) separating the predentin from the odontoblastic layer. (Courtesy Dr. Claudia Biguetti.) ache that affects patients with symptomatic irreversible pulpitis. Pulpal damage can occur because of impact injuries. Teeth The pulp may also have Aβ-fibers and sympathetic fibers in the undergoing mild to moderate trauma and those with immature walls of arterioles. apices have a better chance of pulpal survival in comparison with The pulp vasculature plays a critical role in its response to irrita- those suffering severe injury or those with closed apices. Intrusion tion. When the tooth first erupts into the oral cavity, the root apex is injuries are more likely to lead to pulp necrosis than are lateral or immature, and there is ample blood supply to the pulp. Eventually, extrusion injuries4 (Fig.1.3). the apex matures, and the ability of the pulp to withstand external Periapical tissues can be mechanically irritated and inflamed by irritation, such as from trauma or caries, diminishes. However, the impact trauma, hyperocclusion, overinstrumentation of root canals, pulp of the mature tooth has mechanisms to cope with increased perforation of the root, and overextension of root canal filling materi- blood flow during inflammation, such as arteriovenous anastomoses als (Fig. 1.4). Inaccurate determination of root canal length is usually and loops that can circulate and increase volume of blood when the the cause of overinstrumentation and subsequent inflammation. In need arises. The pulp also contains an elaborate network of arteri- addition, lack of an adequate apical resistance form created during oles and capillaries around the odontoblasts, which are high-meta- cleaning and shaping can cause overextension of filling materials into bolic-rate cells, commonly known as the terminal capillary network. the periapical tissues, causing physical and chemical damage (Fig. 1.5). Application of forces beyond the physiologic tolerance of the Etiology of Pulpal and Periapical Diseases periodontal ligament (PDL) during orthodontic tooth movement results in disturbance of the blood and nerve supply of the pulp Injury or irritation of pulpal or periapical tissues can result in tissue.5,6 In addition, orthodontic movement may initiate resorp- inflammation. The reactions of the dental pulp to irritants are tion of the apex, usually without a change in vitality. largely dictated by the type and duration of a stimulus. These irri- tants can be broadly classified as nonliving (mechanical, thermal, Chemical Irritants or chemical) or living (microbial) (Video 1.1). Antibacterial agents, such as silver nitrate, phenol with and without Mechanical Irritants camphor, and eugenol, have been used to “sterilize” dentin after cavity preparations. The effectiveness of many of these products The potential for pulp irritation increases as more dentin is is questionable,7 and their cytotoxicity can cause inflammatory removed during deep cavity preparations because dentinal per- changes in the underlying dental pulp.8 Other irritating agents meability is greater closer to the pulp2 (Fig. 1.2). The removal include cavity cleansers, such as alcohol, chloroform, hydrogen of tooth structure without proper cooling may also cause pulp peroxide, and various acids; chemicals present in desensitizers, inflammation. Deep scaling and curettage may injure apical ves- cavity liners and bases; and temporary and permanent restorative sels and nerves, resulting in pulpal damage.3 materials. CHAPTER 1 Pathogenesis of Pulp and Periapical Diseases 3 A B • Fig. 1.2 Scanning Electron Microscopy of Human Dentin. Dentinal permeability is greater closer to the pulp (A) than near the dentinoenamel junction (B) or the cementodentinal junction due to the higher number of tubules per unit and bigger tubule diameter. Therefore the potential for pulp irritation increases as more dentin is removed. 12 X 10 XXX 8 6 Perfusion units 4 2 • Fig. 1.4 Periapical radiograph showing overextension of root canal filling 0 material. Splint rem 12 wks 24 wks 36 wks Intrusion Extrusion Lat lux X Control • Fig. 1.3 Graphic representation of pulpal circulation subsequent to vari- ous types of luxation injuries to teeth. Pulp circulation is measured in perfu- sion units over a 36-week observation period. Antibacterial irrigants used during cleaning and shaping of root canals, intracanal medications, and some compounds pres- ent in obturating materials are examples of potential chemical irritants to periapical tissues.9,10 When testing the effects of anti- microbial medications on dental pulp cells, researchers showed that calcium hydroxide and lower concentrations of antibi- otic pastes are conducive to cell survival and proliferation, but more concentrated forms of antibiotic pastes have detrimental • Fig. 1.5 Improper instrumentation and extrusion of filling materials into effects.11 the periapical tissues causes periradicular inflammation (arrows). 4 CHAPTER 1 Pathogenesis of Pulp and Periapical Diseases 18 Microbial Irritants identified as pattern recognition receptors (PRRs). PRRs recog- nize PAMPs and initiate host defenses. G-protein coupled recep- Although mechanical and chemical irritations are predominantly tors and Toll-like receptors (TLRs) are part of the innate immune transient in nature, the most significant cause of inflammation is response and activate phagocytic functions to allow microbial microbial. Studies have shown that even superficial carious lesions ingestion. G-protein coupled receptors bind to chemokines, lipid in enamel are capable of attracting inflammatory cells in the mediators (e.g., platelet-activating factor, prostaglandin E2, and 12,13 pulp. The initial reaction of the pulp to these irritants is medi- leukotriene B4) or bacterial proteins, causing extravasation of ated through the innate immune response. This early response to leukocytes and production of bactericidal substances. TLRs are caries results in focal accumulation of chronic inflammatory cells, transmembrane