BL.2.5: Osteoarthritis, Rheumatoid Arthritis Flashcards
Describe the symptoms and signs, synovial fluid analysis, and x-ray features of osteoarthritis.
The clinical features of osteoarthritis include joint pain, decreased joint mobility, hypertrophic bony spurs (osteophytes), infrequent joint inflammation, and lack of systemic involvement.Symptoms: pain with use, stiffness, relative preservation of function, rarely before 40, not systemicSigns: localized joint tenderness, bony enlargement, crepitance, restricted movement, variable swelling/instabilityJoint fluid non-inflammatory, no evidence of crystals, normal viscosity and glucoseX ray:Loss of joint space = cartilage gone, Bony sclerosis = increased bone as reaction to extra stress, Bony cysts = cracks in bone with synovial fluid within the cracks, Osteophytes = outgrowths of bone due to stress, altered shape of bone, joint effusion (non-inflammatory)
Discuss the risk factors for getting OA.
Obesity, trauma, advanced age, genetics,weight baring joints most affected after age 40, inflammatory joint disease
Explain the various therories on the pathogenesis of OA.
Primary (idiopathic) or secondary (injury)Basically, the cartilage is injured, and doesn’t grow back correctly.Injury of chondrocyteChondrocytes + synovium can release cytokines and inflammatory mediators that damage cartilageIncreases proteases and collagenasesReparative mechanisms of collagen and proteoglycan production failCartilage loses hydrophilicity (love of water), collagen is disruptedChondrocytes number increases then die outThere are hereditary forms-some with well characterized abnormal collagens.
Discuss the treatment of OA as it relates to the pathophysiology.
Presently basically only symptomatic treatments: Topicals, Analgesics, Anti-inflammatory drugs (NSAIDs), Physical Therapy, SurgeryUltimately need disease-modifying drugs– Prevent endogenous breakdown by inhibition proteases and collagenases– Increase the ability of the chondrocyte to synthesize matrix
What is rheumatoid arthritis?
Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, symmetric, inflammatory synovitis often leading to cartilage and bone destruction and joint deformities. Extra-articular manifestations also occur but are usually less extensive and severe than in the other diffuse connective tissue diseases”.”
Describe the general clinical, laboratory, and x-ray features of rheumatoid arthritis (RA), including joint distribution, synovial fluid analysis, serologies, and extra-articular manifestations.
Clinical: Symmetrical synovial joints (small joints, c-spine) affected, morning stiffness, swelling, pain, deformities, loss of functionSigns: joints warm, swollen, tender, limited ROM, deformitiesSerum: RF, ↑ESR or CRP, Anemia, Anti-CCP Ab,Synovial fluid: >2000 neutrophils (inf), low complement and glucoseExtra-articular manifestations: fatigue, malaise, anorexia, weight loss, low grade fever, rheumatoid nodules, end organ involvement (eyes, lungs, nerves)
Discuss the genetic factors that may determine the severity of RA.
Smoking, XX, increase in age, monozygotic twins, HLA-DR4 in 50% of patientsPTPN22 gene (encodes a protein tyrosine phosphatase);STAT4 gene (encodes a transcription factor that transmits signals induced by several key cytokines including IL-12, IL-23, and type 1 interferons); and theTRAF1-C5 gene locus (encodes TNF receptor-associated factor 1 and complement component 5, respectively).
Explain the pathogenesis of RA in the synovial tissue and synovial fluid, including cell types, cytokines, and proteolytic enzymes.
This disease process begins with inflammation in the synovium, with later destruction of the articular cartilage, bone, and peri-articular structures.Early findings1. Mild inflammation with microvascular injury, subsynovial edema, fibrin exudation and minimal synovial lining cell proliferation.2. Synovial fluid at this stage contains predominantly mononuclear cells.Later findings1. Increase in the synovial lining cells: macrophages (type A cells) derived from blood monocytes, and fibroblasts (type B cells) from local proliferation.2. Normally acellular sublining region of synovium shows fibroblast proliferation, growth of new blood vessels, and focal aggregates of CD4+ T lymphocytes, B cells and plasma cells.3. Evidence of microvascular injury continues.4. Pannus, an organized mass of granulation tissue consisting of macrophages, T cells, B cells, and fibroblasts, is common in established RA. It arises from inflamed synovium under the influence of numerous cytokines, and covers and invades the articular cartilage and juxta-articular bone, leading to the radiographic findings of loss of joint space and periarticular erosions.5. Synovial fluid contains primarily polymorphonuclear neutrophils at this stage.Fix this one
Discuss the treatment of RA as it relates to pathophysiology.
Anti-inflammatory/analgesic drugs are used to relieve patient symptoms, but these do not prevent tissue destruction.Disease-modifying anti-rheumatic drugs (DMARDs) are instituted early after diagnosis in an effort to prevent tissue destruction. These drugs have many mechanisms of action but they primarily inhibit various macrophage and lymphocyte functions. Newer therapeutic agents include biologic agents that inhibit the effects of cytokines, T cell co-stimulator molecules, or deplete B cellsPhysical therapy with exercise and physical modalities.Surgery for selected patients, including total joint replacements.
