#D3/S2/W1
#Endo

Aetiology of pulpal and periapical diseases

• injury or irritation -> inflammation

  • pulpitis - inflammation of the pulp
  • apical periodontitis - inflammation of paical periodontium

• reaction of pulp and periapical tissues to irritants dictated by type and duration of stimulus

• irritants classified as

  • non-microbial (mechanical, thermal, chemical)
  • microbial

Mechanical irritants

• cavity preparatoins (dentine permeability increases closer to pulp
• deep scaler/curettage
• impact injuries
  • mild/moderate trauma (extrusion) vs severe trauma (intrusion)
  • immature vs closed apices
• impact trauma
  • luxation/avulsion injuries cause direct PDL trauma
• occlusal trauma
• overinsturmentation of root canals
• root perforation
• overextension of root filling materials
• orthodontic forces beyond tolerance of PDL

Chemical irritants-pulpal

• cavity cleansers (alcohol or hydrogen peroxide)
• acids
• chemicals present in desensitisers, cavity liners, bases, temporary and permanent restorative materials

Chemical irritants-Periapical

• antibacterial irrigants
• intracanal medicaments
• some obturating materials

Microbial irritants - pulpal

• most significant cause of inflammation
• bacteria in dentine induce pulpal inflammation well before invading the pulp
  • bacterial antigen diffuses through tubules
  • localised inflammatory respopnse adjacent to affected tubules
• as caries progresses, intensity and character of infiltrate changes
• initial pulpal reaction mediated through innate immune response
  • localised acute inflammatory response
  • focal infiltration of PMNs and macrophages in sub odontoblastic tissue
• adaptive immune response develops (over time)
  • bacteria antigen captured by dendritic cells
  • focal accumulation of chronic inflammatory cells -> macrophages, lymphocytes, plasma cells
• pulpal response to bacteria constitutes first line of defence and is generally unable to clear the infection
  • increased dentinal fluid flow (dilution and flushing effect)
  • dentinal fluid components (IgG, albumin, fibrinogen, tubule occlusion)
  • sclerosis of tubules (requires vital odontoblasts)
  • production of tertiary dentine
  • immunological reaction in the pulp
• pulp can survive a mild-moderate inflammatory episode, may cause death of odontoblasts, pulp may undergo fibrosis
• pulp may undergo eventual or rapid necrosis
  • deeper damage (subodontoblastic zone) with microabscess formation is the point of no return (messer 2002)
  • formatoin of small abscesses and necrotic foci progresses to total necrosis
  • bacteria invade the entire root canal system
• what drives progression from pulpitis to necrosis
  • dental pulp is unique connective tissue -> confined
• confined within rigid dentine walls
  • self strangulation theory (old theory)
  • pulp has mechanisms to oppose increased tissue pressure
• no collateral circulation
  • effectiveness of inflammatory response depends on pulpal bloodflow
• progression to pulpal necrosis depends on
  • number and virulence of microorganisms
  • amount of circulation
  • ability to avoid marked increase in intrapulpal pressure
  • lymphatic drainage
  • host resistance
• ultimately
  • pulp is overwhelmed by increasing numbers of bacteria
  • blood flow cannot meet demands for an effective response
  • bacteria grow unopposed
  • host response cause indirect tissue damage (PMNs release lysosomal contents -> liquefaction necrosis)
• microbial irritants from infected necrotic pulp diffuse from root canal to periapical tissues
• Apical Periodontitis - inflammatory response to infection of the root canal
  • purpose is to prevent spread of infection from the root canal

Microbial irritants

• bacteria play primary aetiological role in development or pulpal and periapical pathosis

  • Kakehashi et al 1965 conventional vs germ free rats
  • Sundqvist et al 1976 traumatised intact teeth with necrotic pulps, with and without apical pathosis

• Routes of infection

  • enamel and cementum are protective barriers
  • happens via:
    • caries
    • fractures and cracks
    • restorative procedures
    • congenital anomalies of teeth
    • scaling and root plaining
    • loss of PDL attachment to apical foramen or lateral canal
  • following pulpal necrosis bacteria invade the entire root canal system

• infections classified as intra-radicular or extra radicular

  • intraradicular
    • primary
    • secondary: m/o not present in primary infection but introducing during or after initial treatment
    • persistent: m/o from primary infection resist intracanal antimicrobial procedures

• persistent and secondary

  • responsible for clinical problems: persistent exudation, persistent symptoms, interappointment flare-ups, failure of treatment
  • due to
    • poor aseptic technique
    • leaking restorations, caries not addressed
    • untreated/inadequately cleaned canals
    • inaccessible anatomy (isthmus etc.)
    • procedural errors (ledging)
    • inadequate obturation
    • tooth/root fractures
  • extra-radicular infections
    • usually host defences in form of AP are effective at confining microorganisms to root canal
    • situations where they do occur
      • acute apical abscess
      • periapical actinomycosis
      • infected periapical cysts
      • periapical biofilms
      • displaced infected dentine pieces

host response to pulpal disease

• pulpal inflammatory response involves cellular and molecular changes
• degree of irritation stimulates a corresponding level of inflammation
• at some point inflammation changes from reversible to irreversible
  • which is important distinct -> determines treatment
• cellular response
  • increase in inflammatory cells (neutrophils, lymphocytes, macrophages, plasma cells, mast cells, dendritic cells)
  • intensity of inflammatory response correlates to depth of carious lesion (Torabinejad et al 2021)
  • 
• Bacterial ingress into the pulp (severe pathosis) only occurred in cases diagnosed clinically as irreversible pulpitis (ricucci et al 2014)
• molecular mediators of pulpal inflammation
  • some inflammatory mediators correlate with pulpal pain and diganosis of irreversible pulpitis
  • PGE, neuropeptides, bradykinin, cytokines, chemokines, MMPs (mente et al 2016)
• increased mineralisation
  • tertiary dentine, pulp stones
  • pulp canal obliteration following dental trauma
  • not considered pathologic in the absence of symptoms of apical pathosis
• internal resorption defects
  • initiated by osteoclasts and odontoclasts (not normally present in a healthy pulp)
  • arise from monocytes and are normally present in PDL and alveolar bone
  • considered pathologic even in absence of symptoms

Classification of pulpal conditions

• pulpal diagnosis determined clinically by reliance on
  • signs and symptoms of disease
  • clinical tests
  • radiographic imaging
• diagnosis must be obtained prior to contemplating endodontic procedure
• histologic examination of pulp at various stages of disease reveals that different areas of the pulp may have different stages of normalcy, inflammation or necrosis
• progression from reverible to irreversible to necrosis is gradual and occurs in small compartments of the pulp - can complicate diagnosis

Normal Pulp

• histologic features
  • intact odontoblast layer
  • cell-free zone
  • cell rich zone
  • absence of inflammation or necrosis (sporadic inflammatory cells located in central pulp)
• 

Reversible Pulpitis

• irritant
• inflammatory response in close proximity to area of irritation
• clinical features: no symptoms of mild hyperalgesia (sharp transient pain) in response to stimulus
• removal of irritant results in healing and resolution of symptoms (e.g. desensitisation of exposed dentine)
• histologically
  • odontoblast layer may be reduced or flattened
  • thick tertiary dentine, islands of calcification
  • moderate chronic inflammation not disrupting architecture
  • no necrosis, no bacterial invasion
• 

Irreversible Pulpitis

• transition from reversible to irreversible pulpitis is gradual
• may or may not be associated with changes in symptoms
• clinical features
  • may be associated with severe spontaneous and lingering pain, or milder symptoms or no pain
  • inconsistent association of pain with irreversible pulpitis -> potentially for challenging diagnosis
• histologically
  • foci of pulpal necrosis (liquefaction) surrounded by severe inflammation
  • bacterial invasion of the pulp
  • 
• additional conditions
  • internal resorption with a vital (responsive) pulp
  • hyperplastic pulpitis (pulp polyp)
    • proliferative response occasionally seen in children
    • pulp exposed to oral cavity and covered in desquamated oral epithelium

Pulp Necrosis

• pulp degenerates completely + infection with microbial biofilms
• 40% cases - irreversible le pulpitis transitions to necrosis without symptoms
• pulpal necrosis is asymptomatic but may be associated with apical conditions that are symptomatic
• why may a patient still feel instruments exploring a necrotic pulp space
  • surviving pulpal nerve fibres
  • fluid pressures that stimulate apical nociceptors

Periapical Disease

Host Response

• PA inflammatory response starts soon after initiation of pulpal inflammation
  • PA inflammatory cell infiltrate + bone resorption occur in advance of total pulp necrosis, with vital pulp still resent in RC
• bone resorption occurs to accommodate formation of soft tissue lesion within which immunologic reactions occur to stop advancing infection
• microbial factors
  • lead to development of periapical lesion
  • LPS, lipteichoic acid, bacterial enzymes, adhesion factors, toxins etc.
  • 
• bacterial components stimulate innate and adaptive immune responses, involving cells, molecular mediators, effector molecules and antibodies
• innate immune response
  • dominates initial stages of pulpitis and AP
  • complement activation (opsonisation, chemotaxis, inflammation)
  • chemotaxis of neutrophils
  • LPS stimulates endothelial cells adhesion molecules) and macrophages (produced IL-1 and TNF -> pro inflammatory effects)
  • production of AA metabolites (leukotrienes, prostaglandins ->inflammation)
  • neurogenic inflammation (neuropeptides)
• Adaptive immune response
  • large load of virulent bacterial, critical in preventing disseminated infection
  • activation of T and b lymphocytes bearing complementary antigen binding receptors
    • proliferation and cytokine production by T cells
    • T cell regulated macrophage activation
    • proliferation of B cells with differentiation to plasma cells and antibody production
• bone resorption
  • critical component of host response
  • periapical bone loss correlates with degree of advancing microbial irritation and balance of pro inflammatory and anti-inflammatory factors
  • modulation of bone resorption
    • cytokines
      • Activate resorption: IL-1, IL-6, IL-11, IL-17, TNF-alpha
      • Limit resorption: IL-4, IL-10
    • RANK-L / RANK / OPG interaction
      • RANK-L (osteoclast differentiation factor) binds to its receptor (RANK)
      • RANK-L / RANK Integration inhibited by OPG (osteoprotegerin)
      • Levels of RANK-L peak at 2-3 weeks, tapering off at 4-8 weeks as OPG production increases, limiting bone loss.
    • T-reg Lymphocytes
      • Exert significant control over the size of periapical lesions
• PA host response is unable to eradicate the source of infection
• chronic inflammatory response usually effective at preventing microbial invasion into PA tissues
  • mixed inflammatory cell infilitrate of T and B lymphocytes, PMNs, macrophages, plasma cells
• course of disease and structural components of the lesion depend largely on equilibrium between bacteria and host defence

Lesions and Histology

• PA lesions classified into
  • granulomas
  • cysts
  • apical abscesses

Granuloma

• chronic inflammatory cell infiltrate (lymphocytes, plasma cells, macrophages, mast cells) arranged in a granular manner
• multinucleate giant cells (osteoclasts) and foam cells (engorged macrophages)
• 

Periapical cysts

• arise from long-standing granulomas
• proliferation of epithelial cell rests of malassez (remnants of embryonic hertwigs epithelial root sheath)
• contain fluid or semi solid material and may contain cholesterol crystals, lined by stratified squamous epithelium, surrounded by connective tissue containing all the elements of a PA granuloma
• 
• less than 20% of all AP lesions (nair et al 2004)
• two types of apical cysts
  • true cysts - do not communicate directly with apical foramen
  • pocket cysts - root apex opens directly into cyst lumen
  • 
  • 
• was previous hypothesis that true cysts would not repsond to nonsurgical RCT and would require surgical enucleation (no direct evidence)
• differentiation of cysts and granulomas is not possible clinically
• large cyst-like periapical lesions can heal after non-surgical RCT

Periapical Abscess

• intense inflammatory response surrounding areas of tissue necrosis
• bacteria may be present in necrotic areas
• extra-radicular bacteria are rare in asymptomatic apical lesions, but may be more frequent in cases of persistent disease after RCT
• occasionally actinomyces spp. may form extra radicular bacterial colonies
• 

Clinical Classification of periapical conditions JOE 2009

• normal periapex

  • no evidence of apical pathosis clinically or radiographically
  • asymptomatic to percussion and apical palpation
  • 

• symptomatic apical periodontitis

  • inflammation of apical periodontium producing symptoms
  • tooth is tender to percussion and or palpation
  • may be primary or secondary
  • 
  • primary
    • initiated in a healthy periodontium
    • etiology: inflammatory mediators from an irreversibly inflamed pulp, bacteria invading apical root canal, mechanical and chemical irritatnts
    • histology: acute inflammation limited to apical PDL and adjacent cancellous bone, inflammatory exudate with infiltration of neutrophils
    • clinically: pain, tooth elevation, TTP, pulp may be irreversibly inflamed or necrotic, slight widening of apical PDL space
  • secondary
    • acute inflammation which occurs in an already established chronic apical periodontitis lesion
    • etiology: changed intracranial microbiota (increased load, virulent strains) or disruption of host response
    • histology: focus of acute inflammation located within an otherwise chronic lesion
    • Clinically: non vital, TTP, radiographic lesion, possibly rapid enlargement of the radiolucent area

• asymptomatic apical periodontitis

  • periapical radiolucent lesion
  • necrotic pulp
  • 
  • etiology: bacterial infection of root canal contained by host response
  • histologically: chronic inflammation - granulation tissue infiltrated with lymphocytes, plasma cells, and macrophages. May be epithelialised or non epithelialised. Nay be granulomas or cysts (cannot determine clinically)
  • clinically: non vital tooth, periapical radiolucency, bone loss may occur at any portal of exit

• acute apical abscess

  • most serious clinicaly diagnosis in endo
  • virulent bacteria from an infected root canal invade the periapical tissues causing pain and swelling
  • subsides once the intracanal infection is treated
  • 
  • histologically: intense PMN infiltrate, liquefaction necrosis surrounded by granulation tissue, rapid bone resorption may occur
  • clinically: intense pain, swelling, TTpercussion TTpalpation, increased mobility, non-vital tooth.
    • may range from small localised swelling to a large swelling that invades fascial spaces and may cause severe morbidity
    • systemic signs include fever, malaise, lymphadenopathy, leucocytosis
  • Radiographically widened PDL to obvious radiolucent lesion

• chronic apical abscess

  • virulent bacteria from an infected root canal invade the periapical tissues to cause purulent drainage through a sinus tract
  • 
  • sinus tract follows pathway of least resistance
    • attached gingiva/oral mucosa
    • via PDL space (isolated periodontal probing depth to root apex
    • to skin of the face
  • usually asymptomatic because drainage exists
  • heals once the infected root canal system is treated
  • histology: similar to asymptomatic apical periodontitis, sinus tract may be lined partialyl or totally by epithelium surrounded by granulation tissue

• condensing osteitis

  • variant of asymptomatic apical periodontitis resulting in an increase in trabecular bone
  • 
  • etiology" chronic inflammation of pulp (reversible to irreversible) or necrotic infected pulp, result of low grade bone irritation
  • histology: dense mass of bony trabeculae with few marrow spaces
  • clinically: does not require treatment unless pulpal condition is irreversible, expected to resolve after endodontic treatment

• non-endodontic pathosis

  • other lesions of the jaws may mimic apical periodontitis
  • ddx
    • periodontal disease
    • occlusal trauma
    • benign and malignant lesions
  • usually (not always) lamina dura intact and pulp tests normal
  • final diagnosis based on surgical biopsy and histopathologic examination
  •