• Function: provide movement and mechanical support (stability)
• proper function necessitates: freedom of opposed surfaces, correct distribution of load, maintenance of stability
• proper function depends on: geometry (congruent/incongruent); mechanical properties of extracellular matrices bone, cartilage, and connective tissue; integrity of ligaments, muscles and tendons
• proper physiological function: balance of matrix production and breakdown, reparative capabilities of cartilage.
• Hyaline cartilage: connective tissue that covers the surface of the articular surface of the joint. No nerve or blood supply (receives nutrients via diffusion from synovium)
• function: serves as a shock absorber and wear resistant surface
• composition: type II collagen, water, proteoglycans, chondrocytes
• collagen fibers: arranged in arches so that near the surface they are horizontal in orientation – allows the cartilage to resist tensile stresses and transmit vertical loads
• water, proteoglycans – give hyaline cartilage turgor and elasticity – limits friction
• chondrocytes – synthesize matrix and enzymatically digest it – secrete degradative enzymes (inactive form) and enzyme inhibitors Þ diseases destroy articular cartilage by activating the catabolic enzymes and decreasing production of inhibitors (accelerated matrix breakdown)

Osteoarthritis – Degenerative Joint Disease

• Definition: functional disorder of joints characterized by progressive erosion of articular cartilage
• Etiology: End-stage disease with multiple etiologies. NOT an invariable disease of wear and tear (more likely acute and chronic trauma). Breakdown of normal function is a result of:
• loss of capacity of articulating surfaces to move over one another easily
• loss of joint stability and pain
• pain Þ results from maldistribution of load, synovitis, and muscle spasm
• Gross Changes
• Early Changes:
• Ý hydration and ß proteoglycan-matrix (Chondromalacia or softening ) Þ results in mosaic pattern of color changes
• Erosion of/ulceration of cartilage (chondrocyte enzymes destroy surface layer – exposure of collagen fibers)
• Fibrillation – loss of normal smooth shiny surface
• Tidewater mark fragmentation
• Intermediate changes: Disruption of matrix
• Chronic Synovitis – collagenases, proteases, PGE₂)
• Ventricular cracks and breaks in cartilage – fraying and splitting of the perpendicularly oriented collagen fibers
• Late Changes:
• Further matrix degeneration, loss of proteoglycan, fissuring, erosion, and vascular invasion
• Eburnation (marble-like): dense and polished bone beneath the eroded cartilage
• Osteophyte (exostosis or lipping; spurs): compensatory overgrowth of bone and cartilage in areas of joint that do not bear weight (usually around the margins)
• Subchondral sclerosis – Mosaic Lines – increased turnover of bone Þ compaction (like Paget’s)
• Joint Narrowing – seen radiographically
• Cellular changes
• Focal cell necrosis: areas of cartilage with no cells or ghosts of cells
• Focal cell proliferation: clusters or packets of chondrocytes with increased staining around them (due to proteoglycan synthesis)
• Microfractures, microcallus formation, focal osteonecrosis
• Subarticular Cyst formation: cysts in the Marrow Space formed from either liquification degeneration, or necrosis of collagen; or via insertion of synovial fluid into the marrow space.
• "Joint Mice" (loose rice bodies): separated fragments of bone and cartilage resulting in free or loose bodies in joint space.
• Synovial changes
• synovial hypertrophy and hyperplasia
• cartilage and bone matrix degradation Þ inflammatory response Þ Pannus may form (overgrowth of inflamed tissue over articular cartilage) Þ chronic inflammation and scarring
• synovial changes result in disturbance of synovial nutrient functions and Ý enzymatic activity

• Definition: Immunologic systemic inflammatory disorder that principally attacks the synovium
• Mediators of tissue (joint) injury: Polymorphonuclear Leukocytes (PMN’s), synovial lining cells, lymphocytes, macrophages
• Incidence: 1% of population suffers from RA; male/female = 1:3; peak prevalence: 3^rd and 4^th decade; increased incidence among first degree relatives
• Mediators of Tissue (joint) injury in RA: polymorphonuclear leukocytes, synovial lining cells, lymphocytes, macrophages
• Clinical Manifestations: small joints of hands and feet are first affected (typically symmetrically). Especially proximal interphalangeal (PIP) and metacarpophalangeal (MP) joints
• Histology:
• Joints
• non-specific inflammatory synovitis
• thickening of synovium with formation of villous projections
• synovial hyperplasia and hypertrophy
• intense chronic inflammation with formation of lymphoid follicles
• fibrin deposition and necrosis within the synovium
• Pannus formation : inflammatory synovium covering articular cartilage – can invade articular cartilage and obliterate it
• Fibrous and bone ankylosis (ossification) with deformities – no movement of the joint
• Skin
• Rheumatoid Nodules – seen in 25% of patients Þ appear in subcutaneous tissue typically at pressure points (elbows, back of forearms, back of skull) can be present in lungs, spleen, and heart; firm non-tender nodules
• Central focus of fibrinoid necrosis surrounded by palisades (cells perpendicular to the outer contour of the necrotic zone) of epithelioid histiocytes (macrophages that look epithelial). External to that are lymphocytes, mf , plasma cells
• Nodules discovered in the synovium are considered DIAGNOSTIC of rheumatoid (all other findings are pathogenic but NOT pathognomic of RA)

Gouty Arthritis – monosodium urate

• Pathogenesis: precipitation of monosodium urate crystals in the joints during states of hyperuricemia (this is because synovial fluid is a poorer solvent for urate than plasma). Inorganic crystals incite inflammatory synovitis which destroys the articular structures in the joint
• Etiology: Enzyme defects (primarily unknown defects, some are HGPRT deficient – recall urate is the end product of purine metabolism)
• Histology:
• Acute arthritis:
• Dominant PMN
• Macrophage infiltration of synovium
• Chronic Arthritis:
• Syovial proliferation and pannus formation
• Destruction of underlying articular cartialge Þ eventually subchondral bone destruction Þ fibrous or bony ankylosis
• Tophi: chalky tophi are large deposits/masses of urate crystals surrounded by an intense inflammatory reaction (histiocytes, lymphocytes, fibroblasts, foreign body giant cells )
• Can be seen in synovium, bursae, periarticular ligamets, connective tissue
• Diagnoses: Alcohol, NOT formalin fixative should be used to preserve the crystal for microscopic evaluation.

Pseudogout – Calcium pyrophosphate dihydrate deposition disease – CPPD

• Pathogenesis: altered activity of matrix enzymes Þ Ý pyrophosphate Þ crystallization with calcium
• Etiology: hereditary (autosomal dominant); Sporadic, Secondary (metabolic dysfunction – hyperparathyroidism, hemochromatosis, Wilson’s disease)
• Histology: deposists of short, rhomboid crystals deposited in the joint capsule and other intra-articular joints