Advanced Pathophysiology

Osteoarthritis

Osteo means bone and Arth refers to arthron, which means joint and Itis means inflammation. So, osteoarthritis is a disease involving inflammation of the bone and joint cartilage. 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. All right, 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 articular cartilage, forms the inner lining of the joint space. The synovium is 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 the 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 2 collagen, a protein that provides structural support as well as proteoglycans, which are aggregates of protein and sugar molecules like hyaluronic acid, chondroitin sulfate and keratan 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 in the weight. These are joints like the knees, the hips and the lower lumbar spine. Okay. 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 in collagen.

What sort of something though can cause an increased expression of degradative enzymes? Well, that's the million dollar question, right? The answer isn't super straightforward. The biggest risk factor for osteoarthritis seems to be age and often the cartilage degrades over long 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 interleukin-1, interleukin-6 and tumor necrosis factor, 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. Other risk factors include neurologic disorders, genetic factors, and even certain medications, suggesting that there are other mechanisms at play as well. Whatever the initial cause of articular cartilage damages, it gets the chondrocyte to start trying to repair the cartilage.

They initially start making less of the proteoglycans and more Type 2 collagen, but soon switch over to making a different college type, Type 1 collagen. Unfortunately, Type 1 collagen doesn't interact with the proteoglycans in the same way and there's this overall decrease in elasticity in the cartilage matrix, allowing it to break down. Eventually though, over the course of years, chondrocytes aren't able to keep up and they become exhausted and they can undergo apoptosis or program cell death. The cartilage gets softer, weaker, and continues to lose elasticity.

It starts to flake off into the synovial space called joint mice. As Type A cells in the synovium attempt to remove the debris, immune cells like lymphocytes and macrophages are recruited into the synovial membrane, which produces proinflammatory cytokines that ultimately cause inflammation of the synovium as well, called synovitis. Also, fibrillations form, essentially these cracks or clefts on what used to be smooth articular surface. The cartilage continues to erode away until the bone is exposed, allowing it to rub with the other bone, which causes bone eburnnation, making it look like polished ivory. Finally, on the edges, bone grows outward called osteophytes, which makes the joints look wider. Something that's most obvious when it seen in the distal and proximal interphalangeal joints or the finger joints. Called Hebrides nodes in the distal joints in Bouchard nodes in the proximal joints.

Osteoarthritis is really common and nearly everyone knows someone that suffers from it. People with osteoarthritis often feel stiffness in the morning, which usually lasts less than an hour, but comes back at the end of the day. This is an important difference between rheumatoid arthritis, an inflammatory disease that also affects the joints. With rheumatoid arthritis, morning stiffness usually lasts longer than an hour. The pain in osteoarthritis is usually a sharp ache or burning sensation, which also gets worse with prolonged activity, but usually the joints don't swell. Whereas, rheumatoid arthritis typically involves painful swelling.

Finally, management or treatment of osteoarthritis can involve non-pharmacological approaches like losing weight or a moderate exercise, as well as physical therapy. This can be especially important for large weight-bearing joints like the hips and the knees. Pharmacological treatments focus on reducing pain and inflammation. If neither of these approaches are successful though, sometimes patients might benefit from injections of hyaluronic acid into the joint, or they might need surgery to replace the effected joint. Thanks for watching. You can help support us by donating on Patreon or subscribing to our channel or telling your friends about us on social media.