Pathophysiology of Osteoarthritis and Gout PDF

Pathophysiology of Osteoarthritis and Gout PHMD1010 Sept 20, 2024 Dr. Lucy Marzban, DMLS PhD Associate Professor, College of Pharmacy University of Manitoba [email protected]  Learning objectives Describe the e...

Pathophysiology of Osteoarthritis and Gout PHMD1010 Sept 20, 2024 Dr. Lucy Marzban, DMLS PhD Associate Professor, College of Pharmacy University of Manitoba [email protected]  Learning objectives Describe the etiology and pathogenesis of OA and gout Identify the signs and symptoms of OA and gout Describe the diagnostic criteria for OA and gout Explain the tests used for diagnosis of OA and gout Describe the treatment goals for OA and gout Compare and contrast clinical manifestations of OA, RA, and gout  Definition of osteoarthritis “Osteo” “bone” “Arthritis” “inflammation of joint” Definition Osteoarthritis (OA) is a chronic joint disease that leads to destruction and immobility of joints It occurs when the protective cartilage that cushions the ends of bones wears down over time Other names: “osteoarthrosis” and “degenerative joint disease”  Different types of osteoarthritis There are two types of OA: Primary (idiopathic) - most common form of disease - no predisposing factor is apparent Secondary - pathologically is not distinguishable from primary - has a known underlying cause  Epidemiology of OA OA is the most common type of joint disease Joint distribution of OA in males and females 55 years: - hip OA is more common in males - OA of hands, thumb base, and knee are more common in females The prevalence and pattern of involved joints vary in different races (genetic? life-style?)  Risk factors for OA age Age is the most important risk female sex factor for OA race genetic factors joint injuries (sport, accident) repeated stress (job, sport) obesity - ↑stress to weight-bearing joints (hips, knees) - fat produces proteins that cause inflammation congenital developmental defects prior inflammatory joint disease metabolic & endocrine disorders (diabetes, hemochromatosis)  Risk factors for OA, cont’d Typically a combination of loading and susceptibility (local, systemic) risk factors is required to cause disease or its progression. local joint factors (e.g. previous injuries, muscle weakness, malalignment) systemic factors use (loading) factors affecting joint (e.g. age, acting on joint (e.g. sex, genetic factors) obesity, physical activities) susceptibility osteoarthritis or to OA its progression  Joints most often affected by OA Neck (cervical OA usually affects the segment of spine) joints in a non-symmetric manner Low back (lumbar segment of spine) Hips OA most often affects Base of thumb hands, knees, hips, and Ends of fingers spine (proximal and distal interphalangeal) Knees Base of big toe https://en.wikipedia.org/wiki/Osteoarthritis  Healthy joint and OA Healthy joint Osteoarthritis The ends of bones are encased in The cartilage becomes worn away, smooth cartilage that are protected spurs grow out from the edge of by joint capsule lined with synovial bone, synovial fluid increases, and membrane and fluid joint becomes stiff and sore https://en.wikipedia.org/wiki/Osteoarthritis  OA at specific joints Osteoarthritis of knees OA of hips - more common in females - affects both males and than males females - may affect one or both - may affect one or both hips knees A) Increased subchondral bone density B) Joint space is narrowed, subchondral osteophytes (narrowing of joint space) sclerosis with scattered oval radiolucent cysts, peripheral osteophyte lipping (arrows) https://en.wikipedia.org/wiki/Osteoarthritis Pathologic Basis of Disease; Robbins & Cotran  OA at specific joints, cont’d Severe osteoarthritis and osteopenia of carpal joint and 1st carpometacarpal joint OA of the hands https://en.wikipedia.org/wiki/Osteoarthritis - mainly affects females - most often affects the base of thumb and joints at the end of fingers Bouchard’s nodes (formation of hard knobs at middle finger joints) Heberden’s nodes (formation of hard knobs https://en.wikipedia.org/wiki/Osteoarthritis at farthest finger joints)  OA at specific joints, cont’d OA of the neck and back (spondylosis) - most common type of arthritis in spine - can occur anywhere in spine but is more common in lower back and neck - may cause no problem - pain and stiffness are most common symptoms OA of the foot - generally affects the joint at the base of big toe Comparison of morphologic features of RA and OA Pathologic Basis of Disease; Robbins & Cotran  Pathogenesis of OA Pathologic changes of joint in OA include: 1. surface of joint is damaged 2. surrounding bone grows thicker 3. leading to joint damage and immobility The main pathologic feature of OA is progressive loss of articular cartilage but it also involves other tissues: - subcondral bone - synovium - ligaments - neuromuscular tissues  Pathogenesis of OA, cont’d The important articular changes in OA: Early stage: - cartilage is thicker than normal Progression of disease: - joint surface is breached, vertical clefts (fibrillation) - cartilage is metabolically active - chondrocytes replicate and form clusters Late Stage: - cartilage becomes hypocellular Bone remodeling and hypertrophy: - appositional bone growth occurs in subchondrial region leading to bony “sclerosis”  Pathogenesis of OA, cont’d Extracellular matrix of a normal cartilage is composed of: Proteoglycans (PGs) which are responsible for the compressive stiffness of the tissue and its ability to withstand load Collagen which provides tensile strength and resistance to shear Matrix metalloproteinases (MMPs) which can degrade all extracellular matrix components.  Pathogenesis of OA, cont’d The primary changes in OA begin in the cartilage MMPs appear to have an important role in the loss of cartilage matrix in OA Synthesis and secretion of MMPs might be stimulated by IL-1β or by other factors (e.g. mechanical stimuli)  Signs and symptoms of OA Pain - deep pain localized to the involved joint - usually aggravated by joint use and relieved by rest - nocturnal pain interferes with sleep and is observed particularly in advanced OA of hip Stiffness of involved join - mainly after a period of inactivity - usually lasts 6.8 mg/dl) is necessary, but not sufficient, for development of gout. Major risk factors: - age and sex - duration of hyperuricemia (gout: after 20-30 yrs) - family history of gout - heavy alcohol consumption - obesity - drugs that reduce urate excretion (thiazides, salicylates) - diet (high levels of animal proteins) - diabetes, hypertension, atherosclerosis  Diagnostic tests for gout Laboratory tests serum uric acid (confirm diagnosis) 24 h urine uric acid (to assess risk of kidney stones) synovial fluid test (even if clinical appearance strongly suggests gout, diagnosis should be confirmed by needle aspiration of inflamed joints (UA crystals) Radiography X-Ray findings are not specific does not help to differentiate between RA, OA, and gout cystic changes https://en.wikipedia.org/wiki/Gout  Treatment goals for gout Treatment goal is to control inflammation and pain Two approaches are used: 1. control of inflammation: - NSAIDS - Glucocorticoids 2. decrease deposition of urate in joints: - hyperuricemic therapy (↓ production, ↑ excretion, ↑breakdown of uric acid) Summary – Differences between RA and OA Age of onset RA: 3rd to 5th decade of life OA: >45 years of age Signs and symptoms RA: morning stiffness, pain, joint swelling, systemic features, pain worsened at night OA: Deep ache in involved joints, pain worsened by use, crepitus, non-symmetrical pattern Summary – Differences between RA and OA Joint distribution RA: Fingers (middle joints), wrists, knee, hands, ankles OA: First and middle finger joints, hips, knees, cervical and lumbar spine Radiographic findings RA: Juxta-articular osteopenia, erosions, narrowing of joint space OA: Osteophytes, sclerosis, narrowing of joint space Laboratory findings RA: elevated ESR, RF(+) OA: normal ESR, RF (-)  Summary, Gout Gout is a chronic disease caused by overproduction or underexcretion of uric acid. Presents mono- or oligoarticular joint inflammation. It starts with acute attacks which are very painful followed by chronic attacks in some patients. Diagnosis is confirmed by the presence of uric acid crystals in the joint in the presence of clinical findings.