Hypothesis 2 Inflammation has led to the pain and restricted range of motion of the hip joint, both of which contribute to the lameness. Chronic inflammation: Chronic inflammation could have developed out of a low-grade infection in the joint, which clinical signs may have taken days to weeks to develop. As this infection grew and the inflammation worsened, it put pressure on the joint until pain developed. The chronic presence of inflammatory mediators led to damage of the articular cartilage, which also led to pain, especially during exercise and weight bearing on the hip joints. It should be noted that it would be expected that the source of infections, if systemic, would have affected more than just the hip joints. If the source was direct implantation of infectious agents, then trauma would have been noted, though it would have been unlikely to occur bilaterally. Ostoarthritis: Although osteoarthritis is not considered to be an inflammatory disease, it involves inflammatory mediators and is included under this hypothesis. An inherited abnormality of the components that make up cartilage (hypothesis 1) or a traumatic incident (hypothesis 3) causing abnormal forces on normal cartilage or normal forces on abnormal cartilage results in damage to the cartilage matrix and chondrocytes. This damage results in an inflammatory response involving cytokines that decrease the ability of chondrocyte to produce normal proteoglycans and cartilage. Reparative efforts are made, but catabolic activity within the joint exceeds anabolic activity. The catabolic function of the normal joint is to produce degradative enzymes, while the anabolic function is to produce collagen, a fibrous structural protein, and proteoglycans, which provide compressive stiffness. The collagen framework limits the ability to proteoglycans to swell, thus keeping cartilage turgid and allowing it to resist compressive forces. With osteoarthritis, the collagen framework is broken down and proteoglycans are lost. The cartilage swells and loses its tensile and compressive strength, leading to more loss of cartilage matrix, more stress to subchondral bone, fissures and clefts in subchondral bone. The subchondral bone becomes sclerotic, absorbs less force, and experiences more stress and damage. Fibroplasia and increased vascularity of the joint capsule aids in joint stability, but reduces range of motion. Inactivity can lead to muscle weakness. Pain is elicited via mechanical stimulation (such as exercise). These changes cause the altered gait, joint swelling, fibrosis, effusion, crepitus, decreased range of motion, muscle atrophy, and pain. Tests would include thorough physical exam, complete history, and radiographs to visualize the fissures, swelling, etc. Canine Rheumatoid Arthritis: Chronic, progressive, erosive polyarthritis results from an immune reaction to an unknown antigen. Antigen antibody complexes form and are bound by complement that creates chemotactic attraction for neutrophils which engulf the complexes and die in the joint, releasing enzymes. This process is more common in small and toy breed dogs from 9 months to 8 years of age. It results in shifting lameness affecting the smaller, more distal joints, usually localizing to a few joints. The process results in instability, deformity, and laxity in the joint. Anorexia, muscle atrophy, cyclic fever, and generalized lymphadneopathy are also seen. Diagnosis is based on radiographs showing joint erosion and degeneration, joint tap, negative culture, Rheumatoid factor positive serum or synovia, negative LE prep, negative CoombsÕ test, negative ANA, serum protein electrophoresis showing low albumin, low A/G ratio, and high B1 and B2 globulin, and synovial biopsy. Other forms of non-septic arthritis, including canine SLE associated arthritis, idiopathic non- deforming arthritis, and chronic infectious disease, affect all result in polyarthritis, especially in smaller joints, and have other physical findings including anorexia and lymphadenopathy which do not apply here.