L8 Bone and Joint Disease

• Principles of Pathology
• Bone and Joint Disease
• Dr Braeden Donaldson
• Lecture Objectives


  By the end of this lecture, you should be able to:

  Describe the aetiology and pathogenesis of osteoarthritis, and rheumatoid arthritis, recognising the clinical, radiological, and morphological (gross and microscopic) changes in joints

  Explain the pathogenesis of an autoimmune disease, using rheumatoid arthritis as an example

  Identify the clinical presentation of gout, explaining its pathogenesis and outlining the principles of treatment

  Describe the pathological features of acute and chronic pyogenic osteomyelitis
• Lecture Outline


  1. Osteoarthritis vs. rheumatoid arthritis

  2. Gout

  3. Acute and chronic pyogenic osteomyelitis

  
• Normal Joint


  In addition to having a mobile articular surface, synovial joints also provide shock absorption and facilitate weight distribution
• Articular Cartilage


  • Aggrecan
  • Type II Collagen
• Proteoglycans such as aggrecan

  Provide a hydrated gel structure
• Aggrecan and type II collagen


  Prevent wear and tear of cartilage
• Synovial membrane lines non-articulating surfaces, secreting synovial fluid
• Joint capsule and ligaments provide stability
• Osteoarthritis (OA)


  Aetiology: Wear and tear, mechanical stress, genetic factors, low-level chronic inflammation?

  Pathogenesis: Wear and tear combined with underlying weakening of articular cartilage

  
• Altered chondrocyte homeostasis


  • Decrease in proteoglycans
  • Cleavage of type II collagen fibres
• Cartilage Fibrillation in OA

  1. Early: Chondrocytes proliferate (hyperplasia); Hyperstimulation? Feedback loop? Genetic predisposition?

  2. Late: Chondrocytes die; Exhaustion? Failure? Apoptosis?

  
• • Outcome of OA: Cartilage is dehydrated
  • Exposed surface becomes frayed or fibrillated
  • Pieces of cartilage in joint space (joint mice)
• Although OA is predominantly caused by wear-and-tear, genetic factors and weakened cartilage may be important predisposing factors
• Narrow Joint Space in OA

  The gradual loss of articular cartilage results in the narrowing of the joint space, which may deform the alignment of the joint and restrict movement

  
• Narrow Joint Space in OA

  • Increased joint space laterally and decreased medially, causing medial tilting of the knee joint (varus deformity)

  
• Eburnation


  Refers to the polishing of the bone at the articular surface to an ivory-like finish, caused by wear and tear from repeated use of the joint
• Osteophyte


  • A bony outgrowth around a joint, such as in osteoarthritis
  • Heberden nodes if at distal interphalangeal joints
  • Bouchard nodes if at proximal interphalangeal joints

  
• Osteosclerosis


  Refers to the thickening of trabecular bone, presenting as subchondral osteosclerosis in osteoarthritis

  
• Subchondral Cysts in OA

  A cavity beneath the articular cartilage lined with a fibrous capsule, and filled with synovial fluid
• Gross Presentation of OA

  • Pitted articular cartilage due to surface degeneration
  • Erosion of articular cartilage at weight-bearing surfaces, exposing underlying bone
• Manifestations of OA
• Rheumatoid Arthritis (RA)


  Aetiology: Multifactorial risk factors; genetics (HLA), smoking, citrullinated proteins, microbial? Epstein Barr Virus (EBV)?

  Pathogenesis: Systemic autoimmune disease characterised by chronic inflammatory polyarthritis
• Autoimmunity


  An immune response against self-antigens is an autoimmune response

  Autoimmune disease is thought to arise from a failure of self-tolerance, predisposed by genetic susceptibility, and triggered by environmental factors and other stimuli
• Many defined autoimmune diseases are chronic systemic diseases involving chronic inflammation, but short-lived autoimmune reactions can also occur in association with other pathologies (e.g. post-viral infection)
• Environmental factors may also contribute to some autoimmune diseases (e.g. infections, smoking)
• Autoimmunity in RA


  • ~80% of patients have autoantibodies
  • Anti-nuclear antibodies (ANAs) – An anti-nucleus or nucleolar protein antibody, non-specific for RA
  • Rheumatoid factor (RF) – An anti-IgG antibody, non-specific for RA
  • Anti-citrullinated peptide antibodies (ACPAs) – Antibodies against citrullinated self-proteins, more specific to RA compared to other autoimmune diseases
• Although rheumatoid arthritis is well defined as an autoimmune disease, the aetiology of its autoimmunity is less well understood
• ACPAs in RA


  Anti-citrullinated peptide antibodies (ACPAs) may form immune complexes and induce chronic inflammation in the joints of patients with RA
• Pathogenesis of RA


  1. Inflammatory synovitis involving TH1 and TH17 cells (Trigger = ???)

  2. Proinflammatory cytokines activate macrophages and B cells

  3. Activated plasma cells produce autoantibodies, which may form immune complexes in synovial tissue, and may directly activate osteoclasts

  4. Activated macrophages produce more proinflammatory cytokines such as TNF, which activate osteoclasts, and induces proliferation of synoviocytes, fibroblasts, etc.

  5. Inflamed synovial tissue (pannus) forms containing these proliferating cells and other inflammatory cells, which release more proinflammatory cytokines

  6. Release of proteolytic enzymes from activated cells (e.g. osteoclasts) results in the enzymatic degradation of cartilage and bone
• Pannus


  The inflamed fibrotic synovial tissue, it is thickened and opaque compared to the normal thin transparent synovium

  
• Pannus in RA


  • Single layer of synoviocytes
  • Hyperplasia of synoviocytes
  • Underlying synovial tissue infiltrated with inflammatory cells (e.g. lymphocytes, macrophages, fibroblasts, etc)
• 1. ray Presentation of RA

  • Enzymatic degradation of the bone and cartilage occurs beneath the pannus
  • Erosion not localised around weight-bearing points such as with osteoarthritis
  • Loss of articular cartilage will result in narrowing joint space

  
• Gross Presentation of RA

  • Inflamed synovium (pannus) around the joint and infiltrating over the joint
  • Erosion of articular cartilage and bone by enzymatic degradation

  
• Manifestations of RA
• Rheumatoid nodules


  Firm subcutaneous nodules containing inflammatory cells (palisaded macrophages), fibrous tissue, and central fibrinoid necrosis
• Gout


  • Aetiology: Primary – Diet? Genetics?
  • Secondary – Increased uric acid production secondary to another pathology (e.g. leukaemia, renal failure)

  Pathogenesis: Hyperuricaemia with excess uric acid in plasma and tissues, resulting in urate crystals forming in synovial joints
• Acute Gout


  Monosodium urate (MSU) crystals form at low temperatures in synovial fluid, as synovial fluid is a poor solvent; hence gout often affects the joints in the toes

  The formation of MSU crystals within the joints triggers acute inflammation, involving an infiltration of neutrophils