Bonnie is a spayed female 6 year old Labrador Retriever that would be considered overweight.  She is an active dog that takes part in 3-mile runs and hiking trips along with periodically playing fetch and chasing other animals.  While not with the owner, she is primarily an indoor dog and the owner reports no history of distinct trauma.  On orthopedic exam under sedation a 4-5 mm cranial drawer was elicited in her left stifle compared to a 2 mm one on her right stifle.  Considering all these factors, degenerative joint disease with potential secondary cranial cruciate ligament rupture should be considered a possible etiology.  
	Based on Bonnie's age, in general her body has begun to go through changes associated with aging.  Such degenerative changes also occur in joints, such as the stifle. These may result in a progressive instability of the stifle that subsequently places abnormal stresses on intra-articular supportive structures, such as the cranial cruciate ligament. The cranial cruciate ligament runs in a proximal to distal spiral of about 90 degrees.  When the stifle is flexed it loosens and twists on itself limiting internal rotation and cranial displacement of the tibia.  In extension, it becomes taut and keeps the stifle from hyperextending.  If this ligament is overloaded chronically as the joint goes through its normal range of motion, logically it will begin to weaken.  Alterations in microstructure occur including a loss of fiber-bundle organization and hyalinization of collagen fibrils.  Overall, there is a loss of tensile strength and stiffness, predisposing the ligament to damage from even minimal trauma.  Although degenerative changes due to aging most certainly play a role, aging is a physiologically normal process that all animals go through.  Therefore, the contributions of other factors, applicable to Bonnie's case, should also be considered.  
	Poor conditioning most certainly plays a role in that joints need to be adequately supported by surrounding musculature.  Without strong musculature, again, intra-articular structures are exposed to increased loading.  Although, Bonnie does seem to be very active, a more thorough history would help reveal how regular her activity really is. Stifle joints that are exposed to sporadic bouts of high intensity activity are more prone to degeneration and CrCL rupture.  This is a direct result of sudden overloading of structures that may not have sufficient strength or support.  Additional inquiry may help to pinpoint a specific pattern to Bonnie's lameness.  Lameness that is episodic and recurring after bouts of exercise suggests a chronic problem.
	Bonnie's obesity either applies excessive strain on the stifle primarily or exacerbates any pre-existing abnormal forces from other causes secondarily.
	Structurally incorrect conformation may also be contributing to Bonnie's lameness.  Some large breed dogs inherently stand with their femurs at a greater angle in respect to their tibias.  This decreases the space within the intracondylar notch that the cruciate ligaments can pass through.  Ultimately, these breeds are predisposed to partial or complete tears of the craniomedial band of the CrCL as it runs past the roof of the notch.  A second anatomical problem that may be a possibility involves abnormal tibial conformation.  Secondary to this, within the dog's normal gait, small degrees of excessive internal tibial rotation or hyperextension may be occurring.  Eventually, these repeated minor stresses would wear down the ligament and decrease its functional effectiveness through aforementioned degenerative processes.  Valgus or varus deformities may incur the same results.  Malformation that results in degenerative joint disease is generally referred to as postural arthrosis.
	Immune mediated breakdown of the CrCL may also have occurred over a long duration of time. Bonnie's body may have considered its endogenous collagen as foreign and thus incited an immune response against its own ligaments.  Anticollagen antibodies and macrophages would be recruited to the area to rid the body of the "invading tissue".  The antibodies would form immune complexes with collagen fibrils or cells and the macrophages would release chemical mediators.  These chemical mediators would cause chondrocytes to increase collagenase production, an enzyme that degrades ligaments and tendons.  
	Primary degenerative joint disease is characterized by disorganization and loss of articular surfaces and tissue proliferation within and adjacent to these surfaces. Its etiology may be multifactorial but generally speaking, abnormal stress placed chronically on a joint plays a significant role.   Cartilage damage begins to occur early in degenerative joint disease.  As chondrocytes are damaged, increased amounts of the lysozyme cathespin are released.  This enzyme is responsible for degrading proteoglycans, the hydrophilic structural units of cartilage that provide it with compressive stability.  As a result, cartilage resiliency decreases and clefts in the tissue begin to form through a process called fibrillation.  These initially small tears can over time deepen and eventually expose underlying bone.  
Increased loads placed on the exposed subchondral bone cause hemorrhage and bone necrosis.  Subsequently, osteochondral repair takes place at these sites and the bone becomes sclerotic.  Cysts may develop beneath these areas due to loss of trabeculae and fibromyoid degeneration of the marrow.   
Bony proliferations, or osteophytes, may occur at the interfaces between articular cartilage and synovial membrane. The trochlear ridge, the caudal surface of the tibial plateau, and the inferior pole of the patella are all potential sites of osteophyte formation. Their presence, even in the absence of cartilage damage, indicates an abnormally functioning joint. Osteophyte development begins with deposition of mineral outside existing bony cortex. The mature osteophyte is formed through an ongoing process of bone deposition, resorption, and remodeling that is dictated by pressures placed on the stifle. At this end stage, they are capped with fibrocartilage and freely communicate with the marrow.  Radiographically, these changes can be detected at the previously mentioned sites approximately 2-5 weeks after onset of development.   Enlargements along the medial surface of the knee can usually be felt at this point on exam.  
In addition, degradation products that are released into the joint space secondary to cartilage damage cause inflammation and changes in the joint capsule. The joint capsule is composed of two major layers: a fibrotic outer layer, and a cellular inner synovium.  The synovial layer is composed of a synoviocytes that lay adjacent to the joint surface and a subsynovial layer composed primarily of collagen, elastin, fibrocytes, and vessels.  Advanced stages of DJD are characterized by hypertrophy and hyperplasia of the synoviocytes as well as increased numbers of fibroblasts in the subsynovial layer.  Prominent vasculature and collagen fibers can also be noted.  As a result, the subsynovium folds onto itself forming villi that may protrude into the joint space.  This increased fibrosis of the synovial tissue and villi formation contribute to joint stiffness and pain.  The inflammation present, also defined by the cellular hypertrophy and hyperplasia, lymphocytic infiltration, and increased vascularity all contribute to joint capsule fibrosis and joint perfusion.