JOINT PATHOLOGY Bone & Soft Tissue Pathology MKU Pathology — Dr. Lilian Bosire --- I. JOINT STRUCTURE — OVERVIEW Classification of Joints Solid (Non-synovial) J
JOINT PATHOLOGY Bone & Soft Tissue Pathology MKU Pathology — Dr. Lilian Bosire --- I. JOINT STRUCTURE — OVERVIEW Classification of Joints Solid (Non-synovial) Joints — Synarthroses - Lack a joint space; allow minimal movement; provide structural integrity - Fibrous synarthroses: Cranial sutures, tooth-jawbone bonds - Cartilaginous synarthroses (synchondroses): Symphyses — manubriosternal, pubic symphysis Synovial Joints - Have a joint space → wide range of motion - Formed at ends of bones via endochondral ossification - Strengthened by dense fibrous capsule, ligaments, and muscles - Boundary = synovial membrane — anchored to the capsule; does NOT cover the articular surface; forms villous folds near osseous insertion Synovial Membrane Two cell types in 1–4 cell deep layers: - Type A synoviocytes — specialized macrophages; phagocytic activity - Type B synoviocytes — fibroblast-like; synthesize hyaluronic acid and proteins - Lacks a basement membrane → allows efficient exchange of nutrients, gases, and waste between blood and synovial fluid Synovial Fluid - Hyaluronic acid-rich plasma filtrate - Acts as a viscous lubricant - Provides nutrition to avascular articular cartilage Hyaline Cartilage Composition: Water (70%), Type II collagen (10%), Proteoglycans (8%), Chondrocytes - Type II collagen → resists tensile stress, transmits vertical loads - Water + proteoglycans → limit compression and friction - Avascular, alymphatic, aneural - Chondrocytes synthesize and digest matrix; half-life of proteoglycans = weeks; type II collagen = years - Chondrocytes secrete degradative enzymes in inactive forms + enrich matrix with enzyme inhibitors - Disease destroys cartilage by activating degradative enzymes and reducing inhibitor production - Key cytokines driving destruction: IL-1, TNF — released by chondrocytes, synoviocytes, fibroblasts, and inflammatory cells --- II. ARTHRITIS Arthritis = inflammation of joints. Major types: Feature Osteoarthritis Rheumatoid Arthritis --- --- --- Primary abnormality Mechanical cartilage injury Autoimmunity Role of inflammation Secondary; exacerbates damage Primary driver Joints involved Weight-bearing (knees, hips) Small joints first; progresses Pathology Cartilage degeneration, osteophytes, subchondral cysts Pannus, ankylosis Serum antibodies None ACPA, rheumatoid factor Other organs No Yes (lungs, heart, vessels) --- III. OSTEOARTHRITIS (OA) Also called degenerative joint disease . Most common joint disease. Definition & Epidemiology - Primarily a degenerative disease of cartilage, not primarily inflammatory (despite the name) - Primary OA: Idiopathic, aging-related; usually oligoarticular; onset 50 years; ~40% of people 70 years affected - Secondary OA: Younger individuals with predisposing factors — joint deformity, prior injury, diabetes, ochronosis, hemochromatosis, marked obesity - Knees and hands more common in women; hips more common in men Pathogenesis - Principal mechanism: biomechanical stress on articular cartilage - Genetic polymorphisms in matrix components and signaling molecules predispose to chondrocyte injury - Chondrocytes proliferate and synthesize proteoglycans, but degradation exceeds synthesis - Chondrocytes secrete MMPs → degrade type II collagen network - Cytokines involved: TGF-β (induces MMPs), TNF, prostaglandins, nitric oxide - Chronic low-level inflammation contributes to disease progression - Advanced disease: chondrocyte loss + severe matrix degradation Morphology — Sequential Changes Early: - Chondrocytes proliferate and form clusters - Matrix water content increases; proteoglycan concentration decreases - Horizontal collagen fibers in superficial zone are cleaved → surface becomes granular and soft (fibrillation) Progressive: - Fissures and clefts form - Full-thickness cartilage sloughs → loose bodies (joint mice) in joint space - Exposed subchondral bone becomes new articular surface - Friction burnishes exposed bone → bone eburnation (ivory-like appearance) Late: - Subchondral bone undergoes sclerosis and microfractures - Synovial fluid forced into subchondral regions → subchondral cysts - Osteophytes — mushroom-shaped bony outgrowths at joint margins, capped by fibrocartilage/hyaline cartilage that gradually ossifies - Synovium: mildly congested and fibrotic, minimal inflammation Clinical Features - Asymptomatic until 50s in primary OA - Deep, achy pain worsening with use - Morning stiffness (brief, unlike RA) - Crepitus , limited range of motion - Osteophytes on spinal foramina → nerve root compression → radicular pain, muscle spasm, neurological deficits - Heberden nodes — prominent osteophytes at distal interphalangeal joints; common in women - Wrists, elbows, shoulders usually spared - Deformities develop but joint fusion does NOT occur (contrast with RA) - Radiographic severity does not correlate well with pain/disability Treatment - No disease-modifying agents available - Pain management, NSAIDs, intraarticular corticosteroids, activity modification - Severe cases → arthroplasty --- IV. RHEUMATOID ARTHRITIS (RA) Definition & Epidemiology - Chronic autoimmune disorder → nonsuppurative proliferative and inflammatory synovitis - Progresses to articular cartilage destruction and joint fusion (ankylosis) - Extraarticular: skin, heart, blood vessels, lungs - Prevalence ~1%; peaks in 2nd–4th decades; 3× more common in women Pathogenesis Initiating event: CD4+ helper T cells reactive to self antigens (particularly citrullinated proteins) Genetic factors: - 50% of risk is genetic - HLA-DR4 associated with ACPA-positive RA - An epitope on citrullinated vinculin mimics microbial epitopes → presented by HLA-DR4 → breaks tolerance Environmental triggers: - Infection (including periodontitis) and smoking promote citrullination of self-proteins → new epitopes → autoantibody production Key cytokines and mediators: - IFN-γ from Th1 cells → activates macrophages and resident synovial cells - IL-17 from Th17 cells → recruits neutrophils and monocytes - RANKL from activated T cells → stimulates bone resorption - TNF and IL-1 from macrophages → stimulate synovial cells to secrete proteases → cartilage destruction - TNF is the most important mediator → basis for anti-TNF biologic therapy Autoantibodies: - Anti-citrullinated peptide antibodies (ACPAs) — specific for citrullinated fibrinogen, type II collagen, α-enolase, vimentin; present in up to 70% of RA patients ; diagnostic marker - Rheumatoid factor (RF) — IgM and IgA autoantibodies that bind IgG Fc regions; present in 80% of individuals; may be deposited in joints as immune complexes; not specific (can occur without RA) - Together, ACPAs + T cells reactive to citrullinated proteins → drive disease persistence Morphology Synovial changes (pannus formation): - Synovium becomes edematous, thickened, hyperplastic with bulbous villi - Histologic features: 1. Synovial cell hyperplasia and proliferation 2. Dense lymphoid infiltrates — CD4+ T cells, B cells, plasma cells, dendritic cells, macrophages; often form germinal centers 3. Increased vascularity (angiogenesis) 4. Fibrinopurulent exudate on synovial and joint surfaces 5. Osteoclastic erosion of subchondral bone → periarticular erosions and subchondral cysts - Pannus = mass of edematous synovium + inflammatory cells + granulation tissue + fibroblasts; grows over and erodes articular cartilage - Pannus bridges apposing bones → fibrous ankylosis → eventually ossifies → bony ankylosis (joint fusion) Rheumatoid nodules: - Firm, nontender, round-oval subcutaneous masses - Sites: forearm, elbows, occiput, lumbosacral area - Histology: central fibrinoid necrosis surrounded by palisaded activated macrophages + lymphocytes + plasma cells (resembles necrotizing granuloma) Extraarticular manifestations: - Leukocytoclastic vasculitis — acute necrotizing vasculitis of small/large arteries → purpura, cutaneous ulcers, nail bed infarction; may affect pleura, pericardium, lungs → chronic fibrosing process - Ocular: