• Unique connective tissue serving as a shock absorber
• Has no direct blood supply, innervation, or lymphatic drainage
• Type II collagen: Resists stress, transmits vertical loads
• Water and proteoglycans: give turgor, elasticity, limit friction
• Chondrocytes: Control matrix turnover 

• Articular cartilage can be destroyed by activation of catabolic enxymes and acceleration of matrix breakdown
• Cytokines produced by chondrocytes, synoviocytes, fibroblasts, and inflammatory cells contribute to joint destruction
• Destruction of articular cartialge by indigenous cells is the mechanism for many joint diseases  

• Most common joint disease
• Second only to CV disease in causing disability in elderly
• Characterized by progressive erosion of articular cartilage in weight bearing joints (hips, knees, vertebrae)
• Related to age, wear, tear, and decreased capacity of chondrocytes to maintain cartilage matrix.  Alterations in progeoglycans and collagen decreases cartilage resilience
• 80%of men and women > 70 yrs will have some evidence of osteoarthritis
• Primary
• Oligoarticular
• Secondary: Younger individuals with traumatically injured joints or developmental deformity of joints
• Insidious: Deep and aching pain made worse with use, morning stiffness, crepitus, and limitation of movement
• Bakers cyst
• No local heat, tenderness, no progression to bony ankylosis (fixed immobility)
• Osteophytes (bone spurs), and joint narrowing on X-ray
• Heberden nodes occur in women and are osteophytes at distal interphalangeal joints (DIPs)
• No known treatment to prevent or halt process
• Morphology:
• Early: Granularity and softening of joint cartilage surface
• Fissuring, pitting, flaking of cartilage
• Friction polishes underlying exposed bone- Eburnation (appearance of ivory)
• Small fractures lead to joint mice and subchondral cysts
• Joint mice- pieces of cartilage floating in synovial fluid
• Ostephytes form at margins of articular surface, synovium only minimally altered

• Systemic autoimmune process causing severe chronic synovitis leading to destruction and ankylosis of affected joints 
• Predominately affects women in the twenties to thirties
• Familial predisposition: positive for HLA-DRB1 and PTPN22
• Altered area acts as binding site for arthritogens
• An initial infection causes malaise, fatigue, and pain in muscles and small joints in hands and feet first
• Joints are red, painful, warm, and over time less mobile
• Synovium shows a proliferation synovitis with thickening and hyperplasia, intense inflammation (CD4+ cells), increased osteoclastic activity of underlying bone (erosive) subchondral cysts, osteoprosis
• Activation of CD4 T cells by an arthritogen causes cytokines to recruit lymphocytes, macrophages and leukocytes to the joint leading to injury and formation of a destructive pannus, erosion of underlying bone
• Rheumatoid Factor: IgM antibody against Fc portion of patients own IgG
• Circulating complexes of IgM/IgG contribute to the process but is not the sole factor in causation
• Anti-cyclic citrullinated peptide (anti-CCP)
• Present in many people with RA but not in people without RA
• Combination of positive rheumatoid factor and anti-CCP antibodies improces the specificity of of a diagnosis of RA
• Finding of a + anti-CCP antibody test with a negative RF, may identify very early RA or persons at risk to develop RA
• Pannus formation
• Mass of synovium and stroma with marked inflammation
• After destroying cartilage, bridge of fibrous tissue forms between bones, leading to immobility of joint (ankylosis)
• Inflammation may extend to tendons, ligaments, and skeletal muscle
• Radial Deviation of wrists
• Ulnar deviation of fingers
• Articular erosions
• Subchondral cysts
• Osteoporosis and fibrous ankylosis are results of inflammation
• Rheumatoid nodules: Usually cutaneous, can form in viscera. Central fibrinoid necrosis surrounded by palisating histiocytes and chronic inflammatory cells
• Usually arise in skin of ulnar area, elbows, occiput, and lumbosacral area.
• Soft tissue locations: lungs, spleen, pericardium, myocardium, heart valves, aorta

Four of the following

Morning stiffness

Arthritis in three or more joint areas

Arthritis of hand joints

Symmetric arthritis

Rheumatoid nodules

Serum rheumatoid factor

Typical radiographic changes

• Juvenile Onset
• Occurs before age 16
• Frequently systemic
• Larger Joints
• Absent rheumatoid nodules
• Absent rheumatoid factor
• ANA (+)
• Felty Syndrome
• RA, splenomegaly, neutropenia
• RA associated with ulcerative colitis and Sjogren syndrome  

• Nonerosive arthritis 
• Different from RA which is erosive on radiographs
• Involved 2 or more peripheral joints
• Tenderness, swelling, or effusion
• In acute phase neutrophils and fibrin enter the synovium with perivascular mononuclear cell infiltrate in subsynovial tissue
• Proliferative synovitis  

• Arthritis that is negative for RF
• HLA-B27 positive
• Ankylosing
• M>F
• Vertebrae and sacroiliac joints
• Follows an infection of adolescence
• Reiter Syndrom: arthritis, nondonococcal urethritis, or cervicitis and conjunctivitis
• Enteritis associated: follows GI infection
• Psoriatic: usually small joints of hands, feets, may extend to larger joints.

• May be blood borne or by direct extension to a joint, rapidly destructive
• Bacterial:
• MC: Staph aureus
• Gonococcus
• Strep
• H. influenza
• Gm (-) coliforms
• TB: spread from nearby bone, spinal involvement known as Potts disease
• Lyme: Follows skin infection, remitting and migratory, primarily large joints
• Viral: may be due to direct infection of joint or triggered autoimmune process (HIV) 

• Hyperuricemia with monosodium urate crystals in the joints triggering acute arthritis
•  M>F
• MC 20 yrs
• Primary: idiopathic, alcohol and obesity enhance a genetic predisposition
• Secondary: associated with increased nuleic acid turnover
• Hematologic diseases
• Drugs-loop and thiazide diuretics
• Renal Failure
• Uric acid is end product of purine metabolism
• Phagocytosis of crystals by neutrophils cause lysis of neutrophils which releases lysosomal enzymes
• Phagocytosis of crystals by monocytes which releases IL-1, TNF-alpha, IL-6, IL-4 and release of proteases
• Needle shaped crystals that are negatively bifurgenent (yellow when parallel to the light, blue when perpendicular to the light)

• Shares many clinical features of gout
• Hereditary, sporadic if assocaited with trauma or surgery
• Seen in osteoarthritis
• Crystals are rhomboid shaped and are positively bifurgent (BLUE when parallel to light and yellow when perpendicular to light)
• Knee most commonly involved joint  

• Ganglion
• Small multicystic lesion of joint capusles or tendon sheaths. 
• Arising from myxoid degeneration of connective tissue
• Palpable, subsutaneous nodule of the wrist
• Surgically treated
• No involvement of joint
• May erode bone
• Baker Cyst:
• Synovial cyst (herniation) of knee
• Associated with excess fluid

• A neoplastic process with tumor expression of colony-stimulated factor I, a chemoattractant for macrophages
• May be nodular- Giant Cell tumor of tendon 
• Diffuse- Pigmented villonodular synovitis, leading to destruction of underlying bone
• Pigmented macrophages (hemosiderin) give synovium a characteristic red-brown to orange-yellow color.
• Finger like projections cover synovial surface