Alt Musculoskeletal Fcn I Class Notes PDF

Review of Synovial Joint Anatomy [Synovial Joint Structures and Tissues] Joint Capsule (articular capsule) -- dense irregular collagenous connective tissue Synovial Membrane -- loose connective inner membrane to the joint capsule. Produces synovial fluid Synovial fluid -- contains hyaluronic aci...

Review of Synovial Joint Anatomy [Synovial Joint Structures and Tissues] Joint Capsule (articular capsule) -- dense irregular collagenous connective tissue Synovial Membrane -- loose connective inner membrane to the joint capsule. Produces synovial fluid Synovial fluid -- contains hyaluronic acid. Lubricates joint space Articular cartilage -- hyaline cartilage tissue that covers the end of each bone. Subchondral bone -- thin layer of compact bone beneath the articular cartilage. Bone layer to which cartilage is attached. Meniscus -- articular disc in knee, made of fibrous cartilage. Attached to joint cartilage [Histology of the Articular Cartilage] *Avascular, flexible, high tensile strength* **Cells** Chondrocytes -- cells in the cartilage. Secrete proteoglycans and collagen **Intracellular Matrix** Proteoglycans (aggrecan) -- helps form a stiff gel Collagen fibers (type II) -- provides tensile strength Arthritis [Types] Osteoarthritis -- chronic, degenerative, inflammatory disease Inflammatory arthritis -- e.g., rheumatoid arthritis, Sjogren syndrome, Lyme disease, juvenile rheumatoid arthritis, gout Infectious arthritis -- infection destroys articular cartilage Post-traumatic arthritis -- direct injury to articular cartilage Osteoarthritis *Osteoarthritis (OA) is a chronic, degenerative, and inflammatory disease affecting synovial joints.* **Characterized by:** Joint space collapse Sclerosis -- thickening of the bone Osteoarthritic cysts Osteophytes [\ ] [Risk Factors/Etiologies] **Age** Usually affects persons \> 40 years old *Note:* Age-related changes in cartilage contribute to the development of OA **Sex** More common in females **Genetics** Multiple gene mutations confer genetic susceptibility to developing OA **Obesity** Excessive weight damages joint cartilage **Occupations and activities** Repetitive motions Sports and strenuous exercise **Trauma** Sprains, strains, dislocation, fractures [\ ] [Pathophysiology] **Enzymatic degradation of articular cartilage** Increased levels of IL-1 lead to increased synthesis of matrix degrading enzymes -- matrix metalloproteinases (MMPS) Cause denaturing/destruction of proteoglycans and collagen Growth factors (e.g., TGFβ) attempt to replace the lost matrix through cartilage synthesis IL-1 also appears to suppress the cartilage repair process **Wear & tear, mechanical stresses** **Effects on the cartilage matrix and other joint tissues** Inflammation at the site Hyaline cartilage softens, turns yellow-gray and loses its glisten, then flakes and thins Fissures appear (fibrillations) In some areas cartilage becomes absent, leaving subchondral bone exposed **\ ** **Effects on the Bone** Irregular thickening at sites bearing high stresses Development of osteoarthritic cysts or osseous necrosis Development of osteophytes **Effects on the Joint Capsule** Thickening and adhesion to the underlying deformed bone Synovitis may develop [Clinical Consequences] **Joint Pain and Stiffness** Deep, aching joint pain exacerbated by overuse Joint stiffness during rest (gelling) Peripheral joints commonly affected: hands and feet (DIP/PIP/MP joints), knees Central joints commonly affected: lower cervical spine, lumbosacral spine, shoulders, and hips *\ * *Possible Mechanisms of Joint Pain* Subchondral bone changes Weight-bearing stress Stretching of the joint capsule from effusions and stretching of the periosteum from bone growth/osteophytes Synovitis or inflammation of surrounding bursae Osteophyte fragments in synovial fluid Periarticular muscle spams **Swelling, Enlargement, and Deformity of Joints** *Often observed in the hands and feet* Bouchard nodes -- palpable enlargements in PIP joints Heberden nodes -- palpable enlargements in DIP joints *Causes of Swelling, Enlargement, and Deformity* Thickening of subchondral bone Osteophytes Joint effusions due to synovitis Rheumatoid Arthritis *Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease* **Characterized by:** Synovitis Joint destruction [Risk Factors/Etiologies] *Cause unknown, but several risk factors have been identified* **Genetics** Individuals with 1^st^ degree family member with RA at 4x risk Genetics may account for between 40-65% of seropositive cases **Sex** Females 2.5-3x more likely to develop RA than males **Age** Typically presents between age 30 and 60 **Environmental** Cigarette smoke Pollution Occupational exposures **Infections** **Hormones** Strong link between female hormonal changes and RA symptoms Increase risk as estrogen and progesterone levels decrease with age [Pathophysiology] **Overview** Environmental trigger initiates autoimmunity in genetically susceptible individual Citrullinated proteins are formed, recognized as foreign antigen, and presented to immune system CD4 positive T cells are activated B cells stimulated to produce auto-antibodies (anti-CCP, RF) **T cell response** CD4 positive T cells migrate to joint Secrete cytokines (IFN-γ, IL-17) T cells stimulate synovial macrophages, which produce inflammatory cytokines (TNF-𝛼, IL-1, IL-6) Synovial cells proliferate, resulting in the formation of a pannus T cells express receptor activator nuclear factor κβ ligand (RANKL) **B cell response** B cells activated by CD4 positive T cells, resulting in production of autoantibodies (RF, anti-CCP) Autoantibodies enter joint space Immune complexes form Complement system activated **Effects on cartilage** Matrix metalloproteinases (MMP) induce cartilage destruction **Effects on bone** RANKL induces osteoclast maturation bone resorption **Effects on synovial membrane** Swelling due to leukocyte infiltration Synovial cells increase in number and size synovial hyperplastic thickening Chronic synovial inflammation [Clinical Consequences] **Articular Manifestations** Joint swelling and tenderness Morning stiffness Decreased joint mobility Joint deformities Cysts in the articular cartilage or subchondral bone **Extraarticular Manifestations** Osteopenia Systemic Periarticular Focal Muscle weakness Skin disease Eye involvement Lung disease Cardiac disease Vascular disease Kidney disease Sjogren's syndrome Nervous system Hematological abnormalities Gout *Inflammatory syndrome caused by an excess of uric acid in the blood and synovial fluid.* Age of onset for males 40 -- 50, females \> 50 [Physiology Review] **What is uric acid?** Byproduct of protein metabolism, specifically purine Removed from the body by the kidneys At low levels acts as an antioxidant At high levels acts a pro-oxidant, increasing free radicals and inducing inflammatory changes **What is Urate?** A salt precipitate of uric acid The urate responsible for gout is called monosodium urate (MSU) MSU precipitates when the plasma concentration of uric acid is \> 6.8 mg/dl [Pathophysiology] **MSU crystal deposition** *Effects are often manifested in the joints but can affect other soft tissues, including the kidneys* Synovial fluid Subcutaneous tissue Kidneys **Inflammatory Response** Initiated by injury from MSU Crystals Inflammatory cytokines and mediators are released Neutrophil synovitis: Neutrophil phagocytosis of the crystals induces the release of more inflammatory mediators (amplification) Eventually leads to significant tissue damage [Etiologies - Physiological] **Overproduction of uric acid/urate** An accelerated rate of purine synthesis or breakdown, leading to an overproduction of uric acid **Overconsumption of purine** Purine-rich diet -- alcohol, red meat, fish **Underexcretion of purine** Decreased kidney filtration of urate at the glomerulus, or increased reabsorption in the proximal tubules **Genetic predisposition** Enzyme deficiency, leading to an increased production of uric acid [\ ] [Etiologies - Environmental] **Alcohol Abuse** Due to high purine content **Obesity** Insulin resistance raises uric acid levels **Medications - thiazide diuretics** Cause hyperuricemia [Clinical Consequences] **Asymptomatic Hyperuricemia** *Could persist for life* Serum levels are elevated but symptoms are not present **Acute Gouty Arthritis** *Abrupt "attacks" lasting hours to weeks* Occurs with acute changes in uric acid levels Joint becomes hot, red, tender, and swollen After recovery symptoms resolve completely Common sites: Fingers, toes, heel, tibial surface, ulnar surface, Achilles tendon, olecranon bursa **\ ** **Tophaceous Gout** *Chronic state of disease* Visible tophi form within various soft tissues Tophi are painless, but cause joint stiffness and reduced ROM **Renal Calculi** *Caused by MSU crystal deposits in the kidney tubules* Leads to tubule obstruction and dilation **Renal Disease** *Caused by MSU crystal deposits in the interstitial tissue* Causes chronic renal disease and progressive renal failure