Hypothesis 3: Arthritis Bonnie’s primary clinical signs are a partial weight bearing left hind limb lameness, stifle joint effusion, distension of the stifle joint capsule, and pain in the stifle joint. These signs would all fit a hypothesis of arthritis localized to the left stifle joint. There are several different kinds of arthritis, which are defined below. Some of these kinds are more or less likely, depending on the history of the case. The positive cranial drawer sign seen under sedation is not something we would expect to see with arthritis, however, possibly the cranial cruciate ligament was damaged as a result of the arthritic changes in the joint. This would result in joint laxity and allow for the positive cranial drawer sign. Osteoarthritis: Defined as a disease characterized by joint pain, tenderness, decreased range of motion, crepitus, occasional effusion, and varying degrees of inflammation without systemic effects. Nearly all osteoarthritis is secondary to some type of trauma. Abnormal forces exerted on normal cartilage result to damage of the cartilage matrix and chondrocytes. Normal forces acting an abnormal cartilage, such as that found with osteochondrosis, can also result in osteoarthritis. This initiates a complex series of events that leads to deterioration of the joint. Damages to the chondrocytes leads to increased catabolic and anabolic activity. This leads to the release of inflammatory mediators such as cytokines and PGs that result in the breakdown of proteoglycan and collagen. Synovial macrophages move into remove the debris, the joint capsule begins to thicken, there is increased activity of synoviocytes. Ultimately, the catabolic activity of the chondrocytes exceeds the rate of anabolism, which leads to degenerative changes. Subchondral bone is subjected to increased stress, and responds by thickening (sclerosis). Eventually, the bone remodels and osteophytes are produced. Clinical signs include altered gait, joint swelling, crepitus (due to friction of thickened synovium and joint capsule as it moves over abnormal cartilage and osteophytes), decreased range of motion(capsule fibrosis or pain associated with the motion of the joint), muscle atrophy, and pain (most predominant sign). Nociceptors for the pain reception are located primarily in the fibrous joint capsule, but also in the subchondral none, ligaments, muscles, and tendons. Degenerative Joint Disease is a noninflammatory non-infectious degeneration of articular cartilage accompanied by bone formation at the synovial margins with fibrosis. Primary DJD is of unknown etiology. Secondary DJD occurs in response to abnormalities that cause joint instability ie. Cranial cruciate ligament rupture, abnormal loading of articular cartilage, or in response to other joint disease ie. infection or immune mediated. For osteoarthritis or DJD to have developed in Bonnie’s stifle, there needs to have been some predisposing factor, such as abnormal cartilage (osteochondrosis) or abnormal forces (trauma). We are well past the age at which OCD is usually diagnosed, although Labs are one of the predisposed breeds, we will rule that out as a cause. However, trauma is a possibility. Bonnie is a very active dog and yet remains overweight. The activity and the excess weight could have placed undue stress on the joint, leading to the development of arthritis. Or, Bonnie could have injured it somehow during exercise. There was a rather acute onset of lameness in this case, not the more chronic and progressive onset expected with osteoarthritis and DJD. More likely, we will see a diagnosis of trauma which can lead to and predispose to arthritic changes in the joint. Infectious arthritis: Infection is due through the inoculation of the synovial membrane of bacteria. These bacteria cause an inflammatory reaction. The colonization of bacteria elicit a biochemical insult causing a massive influx of neutrophils. These neutrophils produce cytokines and free radicals that destroy the surround synovial membrane. Bacterial contamination of the synovium causes inflammation, and promotes formation of fibrin, clotting factors, PMNs, and proteinaceous serous effusion into the joint. The fibrin deposition inhibits synovial fluid penetration. The bacteria lysozomal enzymes break down the cartilage matrix. This cascade of events results in the loss of proteoglycan and collagen from the articular cartilage. This event, coupled with mechanical trauma, leads to rapid cartilage destruction. In this case, possible etiologies for an infectious arthritis could be an extension of osteomyelitis, trauma, or hematogenous spread of bacteria via the peridontitis. Radiographic change is similar to any nonerrosive joint disease. Early signs include synovial effusion, increase synovial mass, soft tissue swelling which is indicated by a distended joint capsule. Animals with septic arthritis usually exhibit a marked unilateral lameness. Onset of clinical signs may be acute or gradual. With chronic septic arthritis, clinical signs include single or multiple limb lameness, with subacute endocarditis, weight bearing lameness, reduced range of motion, crepitus, and joint swelling. Bonnie has an acute, unilateral limb lameness, which is compatible with acute septic arthritis. We do not see any systemic signs such as fever, but this does not have to be present with septic arthritis. Since the lameness is unilateral, hematogenous spread is less likely. As mentioned before, Bonnie is an active dog, and could have received a small penetrating wound that inoculated the stifle joint with bacteria. No wound was noticed, and it is doubtful that one would have gone unnoticed by this particular owner, but it remains a possibility Rheumatoid arthritis: Occurs in small/toy breed dogs 8 months to 8 years of age. It is accompanied by fever, malaise, anorexia and lymphadenopathy in earlier stages. It is an erosive noninfectious inflammatory joint disease. It is characterized by chronic, bilaterally symmetrical erosive destruction of the joints. Etiology is unknown, but considered immune-mediated. There is an altered native IgG or tissue debris that stimulates production of IgM. These resultant immune complexes are deposited in the synovium and initiate an inflammatory response because PMNs engulf the complexes, die in the synovium or joint, and release enzymes. This is followed by synovial cell proliferation, cartilage and subchondral bone destruction, joint swelling, and rupture of the collateral ligaments. This results in a non-functional joint. Most affected dogs have a history of stiffness after rest and limping. Radiographic changes include 6 of the following 9 diagnostic criteria: synovial effusion, joint capsule distension, perichondral decreased bone opacity, subchondral bone destruction, cyst formation. Perichondral osteolysis and erosion, narrowing of the joint space, decrease opacity of the epiphyses next to the infected joints, mushrooming of the ends of the metatarsals, and varying degrees of luxation/subluxation. Diagnosis is also made by joint tap, with the presence of slight turbidity, yellow or pink color, decreased viscosity, 10,000-40,000 Nucleated cells/mm (20-80% being PMNs). Immune tests can also be performed to check for rheumatoid factor. They are positive in 25% of cases, with 1:8 or higher indicative of rheumatoid arthritis. This is the least likely form of arthritis to be present, due to the signalment and rarity.