USMLE® Step 1 style questions USMLE
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A 15-year-old boy comes to his general practitioner because of generalized right knee pain that has gradually worsened over the past five months. He does not recall any trauma or any inciting event. He says that the pain is accompanied by catching and clicking of the joint and is worsened by physical activity. He works on a farm and enjoys playing soccer with his siblings but has been unable to do so for the past month due to his symptoms. His knee appears swollen and is tender on palpation medial to the patella. Range of motion is limited and the knee clicks as it extends. The McMurray test is negative. Imaging cannot be obtained because the patient is unable to travel to an imaging center. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
It was once thought that the “itis” part of osteoarthritis was a misnomer, and that inflammation didn’t play a role in its development, and that it was mostly a degenerative disease resulting from simple “wear and tear”.
Nowadays, it’s thought that inflammation does indeed play an important role in the development of osteoarthritis.
Alright, so a healthy joint consists of two bones, each with its own layer of articular cartilage, which is a type of connective tissue that allows the two bones to glide against each other essentially without friction.
With Osteoarthritis, we’re really talking about one particular kind of joint which is a synovial joint.
Along with articular cartilage, another important component of synovial joints, and where they get their name from, is the synovium, which along with the surface of the articular cartilage, forms the inner lining of the joint space.
The synovium’s composed of loose connective tissue, blood vessels, lymphatic vessels, and on the surface—”Type A” cells that clear cellular debris and “Type B” cells that produce components of synovial fluid, which helps lubricate the two articular surfaces.
One of the main issues in osteoarthritis is the progressive loss of this articular cartilage, which means there’s not much separating the two bones anymore, which adds a significant amount of friction between them, which then generates inflammation, and triggers pain through the nerve endings in this joint space.
Maintaining healthy articular cartilage is the chondrocyte’s job, a specialized cell responsible for maintaining everything cartilage-related.
The chondrocytes produce and are embedded within a strong gel or extracellular matrix which contains type II collagen, a protein that provides structural support, as well as proteoglycans, which are aggregates of protein and sugar molecules like as hyaluronic acid, chondroitin sulfate, and keratin sulfate.
All of these extracellular components give the cartilage elasticity and high tensile strength, which help weight-bearing joints distribute weight such that the underlying bone absorbs the shock and weight, and these are joints like the knees, hips, and the lower lumbar spine.
Okay, so chondrocytes are important for the articular cartilage, got it. That makes sense.
In healthy people, chondrocytes maintain a delicate balance between breaking down old cartilage—called catabolic activity, and producing new cartilage—called anabolic activity, through the use of both degradative enzymes and synthetic enzymes.
When something causes an increased expression of degradative enzymes, then the balance tips toward a net loss of cartilage, via loss of proteoglycans and collagen.
What sort of something though can cause an increased expression of degradative enzymes?
That’s the million dollar question, right? And the answer isn’t super straight forward.
The biggest risk factor for osteoarthritis seems to be age, and often the cartilage degrades over longer periods of time, which makes it really hard to pinpoint one single culprit.
As I mentioned earlier, inflammation also seems to be involved, and there are a number of proinflammatory cytokines like IL-1, IL-6, and TNF, among others, that seem to play a role.
Some of these are more involved in breaking down cartilage through proteolysis, meaning increased catabolism, whereas others are more involved in blocking the formation of new cartilage (meaning decreased anabolism).
Also, joint injury, which brings with it a lot of inflammation, seems to be a major risk factor for osteoarthritis, as well as mechanical stress and obesity.