Glucocorticoids indirectly inhibit lipoxygenase and cycloxygenase.

-They inhibit the number of circulating lymphocytes by redistributing them into lymphoid tissue. -They increase the number of circulating neutrophils. -Use glucocorticoids if NSAIDs arent working. DMARD -Hydroxychloroquine or sulfasalazine for mild RA. -Methotrexate for moderate to severe RA. -Give TNF-a and methotrexate if still no response. -Methotrexate has poor response for large amounts of coffee intake. -Methotrexate can cause liver cirrhosis. -Methotrexate cannot be given in pregnancy or with liver, lung or kidney disease, or with alcohol use. -Leflunomide inhibits the synthesis of pyrimidines, preventing lymphocytes from going from G1 to S phase. -Leflunomide is teratogenic. -Hydrochloroquine is safe, can be used in pregnancy, and occasionally causes retinopathy. -Sulfasalazine is converted to sulfapyridine (active metabolite) and 5-aminosalicylic acid (anti-inflammatory). -TNF-alpha inhibitors cause serious infections and cannot be given to patients with TB. Gout -Colchicine inhibits the production of crystal-induced chemotactic factor. It also binds to tubulin, preventing leukocytes from migrating and phagocytosing. -Uricosuric drugs are used in the treatment of tophaceous gout. They can only be used in low uric acid excreters. They remove uric acid by competing with it in glomerulus reuptake. -Uricosuric drugs also increase the retention of other drugs, like penicillin. -Uricosuric drugs can cause kidney stones and can precipitate acute gouty attacks when initially started on treatment. -Allopurinol is used in tophaceous gout. It competes with xanthine oxidase. Use allopurinol when uric acid excretion is over 600 mg/day and with renal problems.

Liposarcomas tend to occur in the retroperitoneum. Lipomas tend to occur in subcutaneous tissue. Osteoid osteomas are painful at night and respond to aspirin. Osteoblastomas do not respond to aspirin. Osteosarcomas are cut and resected. Drugs for Rheumatoid Arthritis -

Aspirin has anti-pyretic, anti-inflammatory, and analgesic effect. Acetaminophen only has antiinflammatory and anti-pyretic effect. Aspirin 1. Gastric irritation Not for ulcer patients 2. Inhibits platelet aggregation Not preferred for hemophiliacs Not used prior to surgery * Used in prevention of coronary diseases 3. Displaces drugs from albumin Anticoagulants and anticonvulsants 4. Hypersensitivity reaction (especially in asthmatics) 5. Uricosuric effects Not given to gout patients 6. Children -- Reye's syndrome 7. Analgesic and antipyretic activities *8. Good anti-inflammatory activity Rheumatic Arthritis Ankylosing Sponylitis Reactive Arthritis -GU and GI are precipitating causes -Cant see, cant pee, cant climb a tree Psoriatic Arthritis -Sausage digits -DIP Osteoarthritis -Onchronosis of the joints and the spine -Arthritis in unusual places, asymmetrical Limited systemic scleroderma Diffuse systemic scleroderma Systemic sclerosis sine scleroderma Morphoea Linear scleroderma Introduction to Musculoskeletal System Musculoskeletal disorders cause: -Physical and social impact -Direct financial impact on treatment Anti-inflammatory *No gastric complications *Choice analgesic for ulcer patients *No effect on platelet aggregation *It is preferred. *Can be used Not useful *No displacement of drugs from albumin *No hypersensitivity reaction *No uricosuric effects *No association with Reye's syndrome Equal in potency No anti-inflammatory activity

-Indirect financial impact on loss of work and productivity Back pain accounts for half of all musculoskeletal impairments. Musculoskeletal impairments cause a disproportionate amount of healthcare usage, including much hospitalization (2nd to cardiac). The most common reason for a physician visit is musculoskeletal-related. Osteoporosis is related to age and affects women far more commonly than men. Hip fractures and vertebral fractures are direct consequences of osteoporosis. -Hip fractures have a 25% mortality rate and 3 times as many women as men have hip fractures. Human Limb Development The trilaminar disc of the embryo has an ectoderm layer, mesoderm, and endoderm. Muscle is developed exclusively from the mesoderm. The mesoderm develops into three layers: the somites, intermediate mesoderm (kidneys), and lateral plate mesoderm (serous membranes). -One somite is formed for every pair of spinal nerves. Each somite has a sclerotome (forms vertebrae) and a dermomyotome (forms dermis and muscles of trunk and limbs). Dermomyotomes are initially pluripotent. They receive differentiation signals and form muscles of three regions: deep back, trunk, limbs+superficial back. Myoblasts also come from dermomyotomes. -There are 8 dermatomyotomes for the upper limbs and 10 for the lower limbs. -The 5 somites next to the upper limb bud (C5-T1) will contribute to the adult upper limb. The same occurs with the six segments at L2-S2. Initially, palms and soles of feet face each other. In this orientation, there is a medial and a lateral compartment through the limb. Dermatomyotomes migrate into these compartments. Lateral compartment dermomyotomes become extension muscles while medial compartment dermomyotomes become flexion muscles. -Ventral primary rami (C5-T1 or L2-S3) grow into developing limb buds before dividing into anterior or posterior divisions. These correspond to embryonic anterior and posterior divisions of nerves. -Ventral primary rami innervate trunk muscles. -Multinucleated muscle fibers are formed from mononucleated myoblasts. Undifferentiated myoblasts can also form a synctial cell called a myotube. These myotubes eventually become myofibrils. -The hand paddle undergoes apoptosis between the fingers and the absence of this step leads to webbed fingers as an adult. Upper limbs rotate laterally while lower limbs rotate medially. As such, upper limbs have anterior compartments in the front while lower limbs have anterior compartments in the back. -The extension of C6-C8 somites of the upper limb bud explains the pattern seen in the adult.

Meromelia refers to part of a limb missing while amelia represents an entire limb missing. Phocomelia shows a flipper-like appendage instead of a true limb. Duplication of digits (polydactyly) or limbs (supernumerary limb) are also possible. Digits can fuse. -24 to 36 days of development is critical for limb development. Thalidomide is a famous teratogen. -Rotation occurs at about 6 to 7 weeks of development. Skeletal Muscle Growth and Function The individual unit of a muscle is the myofiber. Each muscle cell is surrounded by basal lamina. Endomysium surrounds each myofiber, perimysium separates muscle fascicles, and epimysium forms dense irregular connective tissue at the muscle periphery. -Nuclei are located at the periphery of myofibers in order to receive signals more efficiently. -Myofiber length is constant but cell diameter fluctuates with use. -Each myofiber contains dozens of myofibrils. Each myofibril is surrounded by sarcoplasmic reticulum and transverse tubules. Each myofibril is composed of hundreds of sarcomeres. Mitochondria are located between myofibrils while other organelles are at the periphery. Myoblasts require fibroblast growth factor to differentiate. -Red muscle fibers contain much myoglobin and mitochondria, making them fatigue resistant and slow twitch. These are postural muscles. -White muscle fibers are for fast twitch but fatigue quickly. These are for rapid eye movements and hand muscles. -There is much intermingling between fast twitch and slow twitch muscle fibers. Alpha-motor neurons are located in the ventral horn of the spinal cord. A motor unit consists of the alpha motor unit and the muscle fibers it innervates. -Acetylcholine released by the motor neuron depolarizes sarcolemma and T-tubules. This causes a release of calcium and T-tubules invaginate deeply into muscles, allowing calcium to be released and triggering a shortening of the sarcomere. -A triad consists of a T-tubule and 2 terminal cisternae of the sarcoplasmic reticulum. Each sarcomere has two triads. Muscle spindles and Golgi tendon organs provide feedback to the nervous system, allowing for proprioception. Muscle spindles are composed of intrafusal fibers (extrafusal fibers are normal muscle cells), which is a specialized type of muscle fiber composed of sensory and muscle cells. -Nuclear bag fibers can be static or dynamic while nuclear chain fibers can only be static. Nuclear bag fibers are sensed by II nerve fibers while nuclear chain fibers are sensed by Ia fibers. -A stretched muscle activates the nerve sensory fibers with the rate of change of muscle stretch being detected by Ia fibers. -Spindle sensory nerves synapse on alpha motor neurons, causing contractions of extrafusal fibers. -Muscle spindles allow for reflex contraction. -Golgi tendon organs prevent excessively heavy loads.

Gamma motor neurons modulate tension on intrafusal fibers in order to adjust the sensitivity of the muscle spindle. Stimulation of dynamic gamma motor neurons increases tension, thereby increasing sensitivity of dynamic bag fibers. The stimulation of static gamma motor neurons decreases the sensitivity of nuclear bag fibers. Golgi tendon organs monitor the force of muscle contraction. They use Ib sensory nerve endings and are located where muscle connects to bone. This provides negative feedback to alpha motor neurons. This causes excessively heavy loads to be dropped, preventing the muscle from injury. Bone Development and Growth Bone is calcified extracellular matrix. Organic components consist of type I collagen, fibronectin, GAGs, proteoglycans, and several specialized proteins (the mixture is collectively called osteoid). Calcification occurs from the deposition of hydroxyapatite crystals. The extracellular matrix is maintained by osteoblasts, osteocytes, and osteoclasts. -Bone undergoes appositional growth while cartilage undergoes both appositional and interstitial growth. -Mesenchymal cells lead to osteoblasts, which cause bone formation. -Osteoclasts break down bone and are responsible for resorption. Cartilage forms isogenous groups. It is surrounded by perichondrium, which is involved in cartilage repair. Chondrocytes become hypertrophied before dying and becoming calcified. Cartilage has type II collagen and hyaluronic acid. Bone has type I collagen. Bone formation -Intramembranous bone formation occurs when bone is formed directly in mesenchymal tissue. This applies to flat bones like the calveria, scapula, and sternum. Because of the mesenchymal cells, these tissues are highly vascularized. Mesenchymal cells differentiate to form a primary ossification center. -Osteoblasts secrete osteoid. Osteoblasts then become surrounded and differentiate into osteocytes after becoming surrounded by bone matrix. They then form lacunae. -Endochondral bone formation is the process by which cartilage is replaced by bone. This occurs in most bones including the long and short bones, vertebrae, pelvis, and base of the skull. -This process involves osteogenic cells, which differentiate into osteoblasts. These osteoblasts then form a bone collar around the diaphysis. The chondrocytes in the center of the diaphysis undergo apoptosis, forming a cavity known as the primary ossification center. -Osteoblasts deposit osteoid, progressively replacing the original calcified cartilage. Mineralization then forms a trabecular network and the formation of the marrow cavity. The ends of the bones remain cartilaginous. -Secondary ossification centers form at the epiphyses after birth. -Proliferation and hypertrophy of chondrocytes at the epiphyses allows for growth at the end of bones. Deposition on the outer surface allows for the increase in diameter.

-The epiphyseal plate is responsible for growth and remains present at the end of long bones in children. In adults, it is replaced by an epiphyseal line. The layers are the zone of resting, zone of cell proliferation, zone of cell maturation and hypertrophy, zone of calcification, and zone of ossification (bone deposited here). Fracture hematomas occur when blood vessels are transected or torn in the periosteum, osteon, or medullary cavity. Fractures cause cell death and inflammation with migration of neutrophils. Bone fragments are gradually resorbed over time. Eventually, the broken periosteum resolves into granulation tissue. A hyaline cartilage callus eventually forms where the fracture occurred. The bone formed is immature woven bone that eventually becomes remodeled into secondary bone. The synovial cavity is lined by synovial membrane, which is a layer of squamous-to-cuboidal epithelial cells. Synovial cavities contain type A phagocytic cells and type B fibroblast-like cells. The bones are lined with hyaline cartilage, termed articular cartilage. Spicules eventually form trabecular bone. Secondary ossification occurs at the epihphysis. Gross Structure and Function of Skeletal Muscle Muscles produce movement but are also important in moving lymph and venous blood. When the muscle isnt contracting, the fascia serves as connective tissue to hold the muscle in place. Skeletal muscle has the following subunits: -Myofilaments of actin and myosin -Myofibrils, consisting of bundled myofilaments -Muscle fibers, consisting of myofibrils; all myofilaments within the muscle fiber contract simultaneously because of the motor end plate The number of muscle fibers in a muscle is fixed during embryonic development due to the fusion of embryonic muscle cells. The length of a muscle can increase as actin-myosin segments are added to the ends of myofilaments. The increase in diameter occurs through the addition of myofilaments after birth. -Muscles are electrically silent at rest. -The amount of time a muscle remains contracted depends on the individual muscle. -Muscles contract by asynchronous recruitment until the number of motor units needed to generate the required force are recruited. Motor nerves typically enter muscle bundled with an artery and a vein. Each motor nerve carries somatomotor, somatosensory, and symp/post components. A motor unit is a single neuron in the motor nerve. Muscles with multiple orientations may only show contraction of the part of the muscle most suited for the particular movement.

In terms of posture, very few bones or joints are specialized for stability. In the upper limbs, ligaments and connective tissue are primarily responsible for maintaining posture. -The presence of ligaments and connective tissue allows for muscles to be completely silent at rest. Contraction of a muscle involves actin and myosin filaments sliding past each other with the amount of force generated correlating with the amount of overlap. As such, a stretched muscle generates very little force. -Shortening contraction -Isometric contraction occurs when a muscle remains the same length during contraction. Isotonic contraction occurs when the amount of force remains the same but muscle length changes. -Lengthening contraction occurs when a muscle lengthens but is also actively contracting -The maximum amount of force is determined by the cross-section of the muscle because this correlates to how many myofilaments are available. The amount of movement a muscle can make is proportional to the length of a muscle. -Paralleled muscle fibers are adapted to movement -Pennate muscle fibers are adapted for force and are angled in order to have a much larger cross-sectional area. Some muscles connect to bone directly through their fascia (endomysium, perimysium, epimysium). Others connect through tendons. Tendons decrease overall movement of parallel fibered muscles. However, tendons decrease the overall amount of force generated by pennate muscles because tendons displace myofilaments. -Tendons take up a small amount of space, are 100-200 times stronger than muscle, and have a low metabolic cost. Muscles can be a prime mover, an antagonist, a fixator (stabilizes joint position), or a synergist (prevents unwanted movement). -Synergists are used when making a fist in order to keep the wrist straight and prevent the wrist from flexing. Musculoskeletal Tumors of Mesenchymal Origin Vimentin is an intermediate filament common to mesenchymal tissue. Desmin and actin are common to skeletal and smooth muscle. S-100 protein is found in sarcomas. Benign mesenchymal tumors are more common than malignant. Children usually get sarcomas but adults usually get carcinomas. -Sarcomas are more common in males. Fatty tumors -Lipomas are the benign tumors of adipocytes. -Liposarcomas present in the fifties and sixties. Tumor-like lesions -Nodular fasciitis is a reactive lesion to trauma but is not actually a sarcoma.

-Myositis ossificans is a reactive ossifying condition with granulation tissue. -Desmoid tumors Fibrous tumors -Fibrosarcoma -Fibrohistiocytoma Physiology of Skeletal Muscle Skeletons used for posture or movement have tendonous attachments at both ends of the muscle. Individual muscle cells are separated by sarcolemma, which is plasma membrane. Red fibers are Type I fibers. They have much mitochondria and much heme-containing proteins such as hemoglobin, myoglobin, and cytochromes. White fibers are type II fibers. Myosin is attached to the M-line. The myosin head requires ATP for binding. Myosin type I (found in type I fibers) hydrolyzes ATP slowly while myosin type II hydrolyzes ATP quickly. These types of myosin heads correspond with being found in type I or type II fibers. Thick filaments are made up of bundles of myosin tails. Thin filaments are made of actin, tropomyosin, and troponin. Troponin is composed of troponin C, troponin I, and troponin T. Troponin C binds to calcium. Actin forms a filamentous structure between two F-actin polymers. Tropomyosin covers the grooves in the actin polymers and covers seven actin monomers. -Troponin C binds to calcium. Troponin complex undergoes a conformational change, causing the movement of tropomyosin. Tropomyosin no longer covers actin, allowing myosin to bind. Myosin and actin slide past each other and bind, allowing for the generation of force. Myosin hydrolyzes ATP when it is bound to actin and calcium facilitates the binding of myosin to actin. The release of ADP and Pi is the rate-limiting step of muscle contraction. -Calcium binds to troponin C. Troponin C then undergoes a conformational change, which stops it from binding actin. The motor end plate contains a high concentration of nicotinic acetylcholine receptors. The binding of acetylcholine causes a depolarization along the sarcolemma, which causes the influx of calcium and eventually muscle contraction. -Calcium is located intracellularly in the sarcoplasmic reticulum. -The action potential is conducted along transverse tubules. -Ca-ATPase pumps calcium back into the sarcoplasmic reticulum. -A mutation in the ryanodine receptor causes calcium to leak out of the sarcoplasmic reticulum. This causes a large utilization of ATP as the cell tries to pump calcium back in and causes malignant hyperthermia since some of the energy from ATP hydrolysis is converted to heat.

Duchennes muscular dystrophy shows an absence of dystrophin while Beckers muscular dystrophy shows a mutated form of dystrophin. Both diseases show an abnormal excitationcontraction coupling in skeletal muscle. Tension is the force exerted by a contracting muscle while the load is the force exerted on the muscle by the object. Tension must be greater than the load for the muscle to shorten. In response to electrical stimulation, calcium is only released in an all-or-nothing response. Skeletal Muscle Plasticity and Adaptations to Exercise Muscles have different properties in terms of red or white, fast or slow twitch, Type I or Type II, metabolic characteristics, and myosin ATPase. Type I fibers are slow twitch while Type II fibers are fast twitch. Type IIa fibers show a fast contraction but are adapted to quickly utilizing either aerobic or anaerobic energy sources. They are known as fast oxidative-glycolytic fibers. Type IIb fibers have the greatest anaerobic potential and are known as fast glycolytic fibers. -Half of fibers are type I, a quarter are type IIa, and a quarter are type IIb -Endurance athletes and weightlifters show a switch from type IIb to type IIa fibers with a proportional increase in mitochondria and a greater capacity to use the citric acid cycle and oxidative metabolism. The number of type I and type II fibers are fixed but the proportion of myofilaments can be changed if one type of fiber is stimulated more than the other. -Aging shows a decrease in the amount of type II fibers, which accompanies a lack of strength. -Strength training shows gains in function through neuromuscular adaptation at first. Afterwards, muscle hypertrophy occurs and accounts for increases in strength gains. -Neuromuscular adaptation shows increased motor unit recruitment, increased firing frequency of motor units, increased motor unit synchronization, increased activation of synergist muscles, and increased inhibition of antagonist muscles. -Myonuclei are important for providing proteins to a cell and are responsible for controlling a certain area of the myofiber. As such, larger muscles gain more myonuclei so that the amount of myonuclei to cell area remains constant. Myonuclei are added through satellite cells. -Strength training causes an increase of strength by increasing the cross-sectional area of the muscle. Whether or not the proportion of type I to type II fibers changes is unknown. -The amount of myofilaments increases but total mitochondrial volume remains the same. Thus, the ratio of mitochondria to muscle filaments actually decreases. This increases the fibers anaerobic strength but reduces the fibers aerobic capabilities. -Capillary volume also remains the same. -Endurance training improves cardiovascular health by increasing the number of mitochondria and capillary volume. Delayed muscle onset soreness results from a combination of microscopic tears, fluid retention in the surrounding tissue, muscle spasms, tearing of the muscles connective tissue harness, acute inflammation, and cytotoxic damage from calcium influx. Eccentric muscle contraction (active lengthening, such as running downhill) leads to greater muscle damage. -Progressive resistance training must be used by increasing resistance used to train.

-Androgens are effective in increasing muscle mass by increasing protein synthesis and decreasing degradation. -Myostatin regulates muscle cell proliferation and is elevated in patients with muscle wasting diseases. Rheumatoid Arthritis and the Spondyloarthropathies Rheumatoid arthritis is a chronic, inflammatory systemic disease that largely targets synovial joints. The disease typically presents symmetrically and affects the small joints of the hands and feet (wrists and MCPs and PIPs but not DIPs), the wrists, knees, ankles, shoulders, hips, and other synovial joints as well (cervical spine is commonly affected). -Joint pain typically presents as morning stiffness and fatigue. The duration of morning stiffness is indicative of the progression of rheumatoid arthritis. -Rheumatoid arthritis preferentially affects women. It affects joints but there are also many extraarticular manifestations of the disease. -There is a peak in prevalence in the 20s and 30s and another peak in the 50s. -HLA-DR4 (prevalent in whites) and HLA-DRB1 are genes associated with rheumatoid arthritis. -Rheumatology is the study of joints. Rheumatism is fibromyalgia. The pathogenesis of rheumatoid arthritis shows synovial inflammation and proliferation with humoral and cellular immune responses that result in tissue damage. Specifically, activated Bcells and T-cells can be found in the synovium and this leads to the loss of hyaline cartilage as well as bone erosion. The triggering antigen is unknown. -Rheumatoid Factor is an antibody that targets the Fc region of IgG antibodies. It is positive in most people with rheumatic arthritis and other autoimmune diseases such as Sjogrens Syndrome, MCTD, and cryoglobulinemia. -False positives for rheumatoid factor occur in arthralgias (viral infection, liver disease, endocarditis) and has a low positive predictive value in these cases. -Detection of anti-citrullinated cyclic protein is specific to rheumatoid arthritis and is found in the synovium. -IL-1beta and tumor necrosis factor alpha are important cytokines. -Osteoclast differentiating factor causes macrophage differentiation into osteoclasts, which leads to bone erosion. -During pathology, synovial fluid increases in volume and in cell number with lymphocytes predominating early on. These lymphocytes form immune complexes with IgG and IgM antibodies as well as complement activation (C5a attracts more leukocytes). -Deposition into articular cartilage makes it difficult to clear immune complexes. Articular cartilage is composed of collagen and matrix proteoglycans. Cartilage is degraded by synovial and neutrophil collagenases and proteoglycans are degraded by proteases. Joint capsules and tendons become degraded in a similar fashion. Rheumatoid arthritis causes joint swelling from synovial thickening and increased synovial fluid volume, increases temperature and erythema over inflamed joints, causes pain and stiffness (particularly in the morning), and decreases the range of motion. The joint also contracts from fibrosis.

-The stereotypical presentation of rheumatic arthritis is joint pain in the wrists and fingers, specifically in the joint capsule. Eventually, the disease can cause deformities in the fingers. Early rheumatoid arthritis is characterized by vague symptoms with variable aching and inflammation and with little or no synovial swelling. Tissue damage causes joint deformities, tendon ruptures, reduction in cartilage thickness, bone erosion, and secondary osteoarthritis. Sometimes, joint fusion can occur. -Osteopenia and osteoporosis are also symptoms of rheumatoid arthritis -Anemia of chronic disease results from rheumatoid arthritis. -Muscle atrophy occurs from disuse as well as to rheumatoid myopathy. -Rheumatoid nodules can form and signify a more severe disease. -Circulating immune complexes can also be seen in the blood with some amount of immune complex deposition occurring in organs. This can result in vasculitis and infarction. -Peripheral nerve compression can result in neurologic involvement. -Sjogrens syndrome can also result. -Type I rheumatoid arthritis is self-limited with one flare-up and no remission, type II is intermediate, and type III is severe Juvenile idiopathic arthritis occurs before the age of 18. There can be iridocyclitis (inflammation of anterior chamber) but granulomas typically do not form. -The stereotypical presentation can be polyarticular, oligoarticular, or monoarticular. It can also be systemic or acute febrile. -Laboratory tests for erythrocyte sedimentation rate (anemic, low iron in red cells?). Synovial fluid analysis for rheumatoid factor works in adults but not as often in children. Anti-CCP is positive in adults as well. Radiographs allow for evaluation of damage from rheumatoid arthritis. -Eventually, joint contractures can occur along with muscle weakess, muscle loss, and osteoporosis. Medications can be NSAIDs and disease-modifying anti-rheumatic drugs, which reduce inflammation and pain and prevent remission. -Drugs that target signaling for inflammation and tissue damage are also effective. -Rehabilitation and orthopedic surgery can also be considered. -Immunosuppressive drugs are also effective. HLA-B27 arthritides differ from rheumatoid arthritis in that they show much spinal involvement, are usually asymmetrical, affect men more often, and usually lack rheumatoid factor. Seronegative arthritides are ankylosing spondylitis, reactive arthritis, psoriatic arthritis, enteropathic spondylitis, and juvenile spondyloarthropathy. -Clinical manifestations show spinal features and peripheral arthritis (hips, shoulders) instead of in the fingers, enthesopathy (tendon involvement), and extraarticular features. -There are genetic factors involved.

-There is an association with HLA-B27, particularly ankylosing spondylitis (90%) and reactive arthritis (80%). -The stereotypical presentation is inflammatory back pain and peripheral arthritis. -Diagnosis is made through laboratory data on HLA-B27 and CRP, MRI or radiography, and physical examination. Ankylosing spondylitis is a chronic inflammatory systemic disease that targets the sacroiliac joints and the cartilaginous and synovial joints of the spine. -Patients are predominantly HLA-B27 positive. -Ankylosing spondylitis typically occurs in young men (9:1). -Presentation shows low back pain and stiffness lasting over 3 months. -Inflammation starts at the sacroiliac joints and move upwards. Eventually, ankylosis (fusion) occurs at the paraspinal ligaments along with ossification. This leads to stiff posture and stiff gait. -There is reduced chest expansion from intercostal involvement. -Preipheral arthritis occurs in most patients over time. -Fusion of the sacroiliac joints is also a common complaint. Reactive arthritis shows asymmetric arthritis. It usually affects large joints like the hips and knees. It is precipitated by genitourinary or gastrointestinal infections. It can result in repeated attacks over many years. -Cant see, cant pee, cant climb a tree Psoriatic arthritis commonly occurs with psoriasis. It can affect the DIP joints and can result in nail pitting. It results in sausage digits and nail pitting. Treatment of spondyloarthropathies involves treatment of symptoms, NSAIDs, DMARDS, and TNF-alpha blockers. Reconstructive surgery for rheumatoid arthritis is indicated when there is a loss of function or unrelenting pain. JIA with eye complications usually presents as pauciarticular. Oligoarticular JIA is associated with antinuclear antibody but systemic JIA is associated with HLA-B27. Osteoarthritis for the Medical Student Osteoarthritis is the most common articular disease worldwide. Primary osteoarthritis affects the small joints in the hands, the cervical and lumbar spine, hips and knees, and joints in the feet. Secondary osteoarthritis can affect any joint and can be caused from sports injuries. This can be due to trauma, structural abnormalities, meniscectomy, congenital abnormalities, and infection. Secondary osteoarthritis affects unusual joint locations and in younger patients. -The cost of not treating rheumatoid arthritis is 30 times that of treating it. -Sepsis in the knee can lead to joint damage and so can plant thorns. -Hypermobility syndromes get osteoarthritis and heart murmurs. -Charcot joints result from degenerative neurological conditions. -Metabolic disorders like acromegaly, alkaptonuria, gout, and can cause osteoarthritis

-Onchronosis causes a buildup in dark pigment in joints and the spine. -Obesity causes osteoarthritis due to increased pressure on the knees. -Secondary osteoarthritis can result from repeated hemorrhage from hemophilia, Marfans syndrome, and bleeding disorders. -Osteoarthritis and osteoporosis have an inverse relationship. -Osteoarthritis shows cartilage loss, subchondral thickening, and marginal osteophytes. -Osteoarthritis is managed with acetaminophen and NSAIDs. Musculoskeletal Pharmacology Drugs for rheumatoid arthritis target the following areas: -Anti-inflammatory drugs that treat symptoms and have a quick therapeutic response but do not change or modify the disease process. -Disease-modifying drugs that change the disease process. NSAIDs block cyclo-oxygenase, which inhibits inflammation. Glucocorticoids have anti-inflammatory and immunosuppressive actions. They have transcriptional regulation in the nucleus and increase the expression of lipocortins, which blocks phospholipase A2. -Unlike NSAIDs, glucocrticoids do not directly inhibit cyclooxygenase. Instead, glucocorticoids affect transcriptional regulation. -Cortisol, cortisone, and prednisone are glucocorticoids. -These are used for pain relief and are used when NSAIDs are contraindicated (asthma). -Since glucocorticoids suppress the immune system, they cause increased susceptibility to infection. -Fluid retention is caused sodium retention. Triamcinolone, dexamethasone, and betamethasone do not have this property. DMARDs commonly used are hydroxychloroquine, sulfasalazine -Methotrexate acts as an anti-inflammatory and immunosuppressant. Methotrexate blocks the production of adenosine. -Leflunomide has a high half-life and becomes an active M1 metabolite. It inhibits dyhydroorotate dehydrogenase, which blocks pyrimidine synthesis. Leflunomide is category X teratogenic. -Hydroxychloroquine inhibits DNA and RNA synthesis. -Sulfasalazine is metabolized by bacteria and blocks TNF-alpha. It cannot be used by patients with sulfa allergies. However, it also causes folate deficiency and can lead to neural tube defects. -TNF-alpha inhibitors bind TNF-alpha and stop disease progression. It can be given with methotrexate. -Methotrexate and leflunomide have synergistic actions because they block purine and pyrimidine synthesis, respectively. Pathogenesis of Systemic Lupus Erythematosus Systemic lupus erythematous occurs when T-cells lose self-tolerance and display altered immune homeostasis.

-This can result if autoreactive T-cells escape destruction in the thymus (failure of clonal deletion), if clonal anergy fails so that only one signal is required to activate the cell, if there is decreased apoptosis, and if T-regs have impaired function in blocking T-cell proliferation or blocking antigen-presenting cells. -Systemic lupus also results from the spontaneous activation of B-cells, particularly if they express nuclearauto-antigens. The disease does not show abnormal cell-mediated immunity. -Interferon-alpha stimulates antigen-presenting cells. Mutations in Foxp3 lead to the disease, IPEX, and Foxp3 is necessary for T-regs to function appropriately. Genetic factors involve HLA-D2 and low TNF-alpha and mutations in the FcR region. Genetic factors typically cause T-cell defects such as hyper-responsiveness and resistance to tolerance induction or B-cell abnormalities such as hyper-responsiveness and producing nuclear autoantigens. Environmental triggers can be infectious agents, sunlight (UV radiation), and drugs that activate self-reactive T-cells by inhibiting DNA methylation. Therapies include histone epitopes in order to desensitize antigen-presenting cells and generating T-regs. Systemic Lupus Erythematosus Systemic lupus erythematous is a rheumatoid disorder that affects primarily young women of child-bearing age. The butterfly rash is pathognomonic. Pathology includes inflammatory changes, blood vessel abnormalities, and immune complex deposition in organs. Patients also become photosensitive. -The most common presenting feature is joint and musculoskeletal involvement. The pattern of joint involvement is very similar to that of rheumatoid arthritis and also results from inflammation of the synovial membrane. However, the inflammation is far less intense such that joint deformity rarely occurs. -SLE is less common in white people. African Americans, Hispanics, and Asians have increased rates. -Anemia can result from auto-antibodies targeted against red blood cells. -Leukopenia also results from the presence of auto-antibodies. -Thrombocytopenia also results from the presence of auto-antibodies. -The presence of lupus anticoagulant is associated with hypercoagulability. This leads to the condition known as antiphospholipid antibody syndrome. -There can also be respiratory and cardiac involvement such that radiography shows an increased heart shadow due to pericardial effusion. -Libman Sacks endocarditis occurs from vegetation on heart valves. -Neuropsychiatric lupus shows involvement in both the peripheral nervous system and central nervous system.

-Renal disease is the major cause of morbidity and mortality from systemic lupus erythematous. This results from the deposition of immunoglobulins and complement factors in the glomeruli. -Antinuclear antibodies are positive but this test is not definitive for systemic lupus erythematosus. Discoid lupus erythematosus is localized and usually shows skin lesions at the ears, face, and scalp. There is typically no other organ involvement. Antinuclear antibodies are the most characteristic serologic finding of systemic lupus erythematous. -Antinuclear antibodies are not cytotoxic and fetuses of mothers of the disease do not have health problems. -Antinuclear antibodies deposit in the glomeruli. Circulating DNA becomes an antigen and forms immune complexes at the glomerulus. This can occur if defects in apoptosis are present such that antigen-presenting cells pick up DNA and present them as antigens, causing lymphocytes to produce anti-dsDNA antibodies. -Immune complexes that deposit in the glomeruli also activate the complement system and cytotoxic factors then cause cell injury. -Failing to clear immune complexes in the glomeruli only compounds the problem. Neonatal lupus syndrome results when infants born to systemic lupus erythematous mothers present with lupus symptoms (photosensitive skin rash, congenital heart block) a few weeks after birth. However, the condition is benign and self-limited with the exception of heart block, which will persist. -Heart block occurs because of maternal antibodies that cross the placenta and attack fetal conduction tissues. Scleroderma Scleroderma is thickened hardened skin. -Limited systemic sclerosis shows CREST: calcinosis, Raynauds, esophageal dysfunction (muscle paralysis, no peristalsis), sclerodactyly, telangtasia. There tends to be distal limbs affected more than the hands and chest and pulmonary hypertension is typical. -These are all cutaneous findings (plus esophagus). -Diffuse systemic sclerosis shows early extra-cutaneous manifestations. The mouth shows contracture. The skin shows edema, induration, then atrophy. Swelling occurs in the entire finger rather than just a part of the finger as in rheumatic arthritis. -These are extra-cutaneous findings. -Systemic sclerosis sine scleroderma shows no skin findings. Instead, there are musculoskeletal, gastrointestinal (esophagus becomes impaired and prone to GERD, stomach delays gastric emptying, small intestine shows atony, large intestine shows infarction and pseudo-diverticula), pulmonary, cardiovascular, and renal symptoms. Arthritis in joints is common along with tendon rubs and muscular atrophy. -Watermelon stomach and pseudo-diverticula are common. -GI symptoms result because smooth muscle becomes replaced with collagen.

-Pulmonary system shows interstitial fibrosis. -Renal insufficiency leads to scleroderma renal crises. The vasculature of the kidney undergoes fibrinoid necrosis, which is a vascular problem. -These changes show the replacement of smooth muscle with collagen. Localized scleroderma -Morphoea shows plaque-like scleroderma and is most common. -Linear scleroderma is the most common type in children and shows longitudinal lesions on limbs. It can cause joint contractures and muscle atrophy. Scleroderma is caused by immunologic activity and vascular changes. There are an increased number of activated fibrogenic fibroblasts. Pharmacology of Muscle Relaxants Spasticity shows flexor muscle spasms, an elevated tonic stretch reflex, muscle weakness, and can result from cerebral palsy or stroke or multiple sclerosis. Spasticity results from upper motor neuron lesions and shows hyperexcitability. GABA and glycine agonists -Diazepam and other benzodiazepines are GABA-A agonists. They are muscle relaxants that also cause sedation. -Baclofen is a GABA-B agonist that acts presynaptically by opening potassium channels and closing chloride channels. -Progabide is a GABA-A and GABA-B agonist. -Gabapentin is an analogue of GABA that has no activity on GABA receptors although it blocks calcium channels. -Pregabalin is similar. -Glycine is not a GABA agonist but it blocks spasticity in the dorsal root ganglion. Other drugs -Tizantidine is related to clonidine and it increases presynaptic and postsynaptic inhibition. However, it also causes drowsiness, hypotension, and dry mouth. -Riluzole is a glutamate release blocker that only treats ALS. -Dantrolene blocks the release of calcium from the sarcoplasmic reticulum in skeletal muscle but it spares cardiac muscle and smooth muscle. However, it also induces muscle weakness and sedation. It is useful for treating malignant hyperthermia. -Only peripherally acting one. -Botulinum toxin blocks the release of acetylcholine. -Cyclobenzaprine produces a serotonergic block on the dorsal horn but also blocks 5HT2 receptors, leading to hallucination and sedation. Inflammatory Myopathies Polymyositis has an insidious onset with systemic symptoms. There is typically involvement of the shoulder, pelvic girdle, and neck muscles. Occasionally, the pharyngeal muscles become involved. Pulmonary involvement shows interstitial fibrosis but cardiac involvement is rare.

-Biopsy shows muscle fibers in states of necrosis and regeneration. There are many CD8+ cells and fibrous tissue will replace muscle fibers over time. -Dermatomyositis does not show muscle fibers replaced with collagen. There are also CD4+ cells. -Inclusion body myositis shows necrosis similar to poliomyositis. There are inclusion bodies. -Polymyositis shows CD8+ cells while dermatomyositis shows CD4+ cells. Diagnosis requires proximal muscle weakness, elevated muscle enzymes, myopathic EMG changes, and muscle biopsy showing inflammation. Dermatomyositis will also show skin rash. Inflammatory muscle diseases classically show increased insertional activity, fibrillations, and sharp positive waves; spontaneous, bizarre high-frequency discharges; and polyphasic short duration, low amplitude motor unit potentials. -MRI imaging is better than CT and ultrasound. Dermatomyositis shows polymyositis findings as well as cutaneous changes. Amyopathic dermatomyositis is dermatomyositis without muscle findings. -Histology shows mononuclear cell infiltrates and fiber atrophy. Juvenile dermatomyositis shows dermatomyositis findings but also includes vasculitis, calcification, and lipodystrophy. Most cases resolve by adulthood with early treatment showing better outcomes. Antisynthetase syndromes show anti-Jo1 antibodies and inflammatory myositis with interstitial lung disease, Raynauds, fever, and mechanics hands. Inclusion body myositis occurs in people over 50 and shows asymmetric involvement with either proximal or distal muscles. Fibromyalgia Fibromyalgia causes fatigue (sleep disturbance, no stage 4 sleep disturbance) and diffuse, chronic muscle pain. There is severe sleep disturbance, stiffness, headaches, irritable bowel and bladder syndrome, and depression. -Diagnosis involves widespread pain for over 3 months and 11/18 points of pain. -Sleep disturbance involves non-restorative sleep that leads to fatigue, cognitive difficulties, and other stress-related symptoms. -Sensory stimuli is often misinterpreted as pain. This may be due to increased levels of excitatory neurotransmitters such as glutamate and substance P. Additionally, tactile allodynia may result from central sensitization beyond an area of injury. -Fibromyalgia can occur as a result of other disorders such as post-Lyme disease infection. In this case, treating fibromyalgia is actually more important than giving the patient more antibiotics. Ehlers-Danlos syndrome and Lupus syndrome also result in fibromyalgia. -In older patients, polymyalgia rheumatica results in aching in proximal muscles but not specific muscle weakness.

-Medications can cause fibromyalgia. -Being on call causes symptoms similar to fibromyalgia. Fibromyalgia can be managed with regular exercise. Antidepressants are also effective because they cause deeper sleep. Crystal-Induced Arthropathies Crystal-induced arthropathies occur from the deposition of crystalline substances in articular and periarticular tissues. These crystals are typically monosodium urate, calcium pyrophosphate, and apatite crystals. -Crystal inflammation stimulates the release of inflammatory mediators such as arachadonic acid, IL-1, IL-6, IL-8, and TNF. -Gout results from an altered metabolism of uric acid and shows deposition of monosodium urate from supersaturated extracellular fluids. -Diagnosis of crystals involves a microscope to determine a characteristic birefringence. -Monosodium urate crystals are yellow when parallel and have negative birefringence. -Calcium pyrophosphate crystals are yellow when perpendicular and have positive birefringence. -Crystals can cause the release of inflammatory mediators from phagocytes and synoviocytes through non-specific signal transduction pathways. -Gout shows an overproduction of purines (and uric acid as waste product) and faulty renal excretion. -Hyperuricemia may be present for many years before gout occurs. -Acute arthritis presents in clinical gout and presents with a sudden onset of severe pain that lasts for days or weeks. The pain is precipitated by sodium urate crystals. -The first MTP joint is typically affected first. This is thought to occur because of cooler peripheral areas and because of walking. -Gout can also present with systemic symptoms such as fever and chills. -Tophaceous gout results from 10 or more years of gout and there are no longer any painfree periods. Eventually, tophi may become deposited in unusual places such as brain and spinal cord. -Gout is typically asymmetric and oligoarticular. Gout is diagnosed by seeing crystals. Hyperuricemia may be present in patients without gout and as such, it is not reliable as a diagnostic criterion. Additionally, elevated uric acid is typically present in gout patients but not always. -Synovial joint fluid in gout shows high WBCs and shows moderate inflammation. -Eventually, gout causes bone erosions from the joint surfaces and causes hypertrophic areas as well. Additionally, dense soft tissue is present at the joints. Treatment of acute attacks involves colchicines, NSAIDs, and corticosteroids. Chronic cases of gout use uricosuric drugs and allopurinol and xanthrin oxidase inhibitors. -Xanthrin oxidase inhibitors are used in urate overproducers, when tophi are already present, nephorlithiasis (kidney stones), or if excessive turnover is present.

Pseudogout manifests with crystals of calcium pyrophosphate deposits. This condition can mimic gout, septic arthritis, or rheumatoid arthritis. -There are typically acute attacks and the first attack is typically in the knee joint. However, all joints can become affected. -A low grade fever is typical with acute attacks. -Chronic attacks can present with osteoarthritis of the knees as well as rheumatic symptoms in multiple joints. -This disease is also associated with many diseases, including hyperparathyroidism and hemochromatosis. -Chondrocalcinosis shows an accumulation of deposits on the hyaline cartilaginous surfaces in the joints. -Treatment of associated conditions does not remove crystals and there is currently no way to remove crystals. -Basic calcium phosphates cause Milwaukee shoulder and rotator cuff disease. Calcinosis can occur in periarticular areas in patients with scleroderma. -Diagnosis involves x-rays of soft tissue that reveals calcification because crystals cannot be confirmed with a microscope (too small). Pharmacology of Gout Gout is caused by recurrent hyperuricemia and arthritis accompanied by severe pain. The pathogenesis involved crystal-induced chemotactic factor LTB4. Drugs that relieve inflammation can either treat acute attacks of gout (colchicines, NSAIDs) or long-term therapy management of gout (uricosuric agents, decrease production of uric acid). -Colchicine inhibits the production of crystal-induced chemotactic factor. It binds to tubulin in order to prevent polymerization. -NSAIDs block leukotrienes (important in gout) and cyclooxygenases (important in RA). Thus, the mechanisms of action by NSAIDs are different in RA and gout despite being the same class of drugs. -Indomethacin -Uricosuric agents are used in tophaceous gout (chronic form). They compete with the organic acid transport carrier, preventing the active reabsorption of uric acid. -Allopurinol is used to treat tophaceous gout. It is a xanthine oxidase inhibitor Overview of Musculoskeletal Radiology Always get two views of the same site. X-rays are good in diagnosing fractures, bony lesions, dislocations, erosions, soft tissue edema, and effusion. However, x-rays are not good at showing soft tissue. Additionally, x-rays cause ionizing radiation so it is necessary to protect the patient and to avoid repeated examinations. CTs shoot a thin fan beam of x-rays along a single plane of the patient. This gives significant multiple plane visualization and minute details within slices (imaging hamate) that allows for 3D reconstruction. -Advantages include matrix mineralization. -Disadvantages are adverse reactions to IV contrast agent and the dose of x-rays used, especially in children.

-CT scans are useful for arthrograms and image guided injections. MRI is excellent for soft-tissue imaging. -MRI is useful for imaging cartilage, ligaments, and soft tissue masses. -T1 and anatomy. -T2 and pathology. -PD is cartilage. -MRI cannot detect subtle calcifications but can detect avulsions and subtle calcific tendonitis. Ultrasound is useful for diagnosing tumoral calcinosis. This shows calcium sedimentation but this diagnosis can also be made through x-ray. Chronic osteomyelitis can be seen through imaging. So can chondrocalcinosis. X-rays are the first modality used and is good for the differential diagnosis of osseous lesions. It can image joint space narrowing and erosions but is not good with soft tissue. CT can image matrix mineralization Non-Narcotic Analgesics Non-narcotics act locally to block pain, reduce mild to moderate pain, and have no potential for addiction or tolerance. Aspirin, profens, and acetaminophen are examples of non-narcotic analgesics. In contrast, narcotic analgesics act in the CNS, control moderate to severe pain, and show addiction and tolerance. Opioids are examples of narcotic analgesics. -Aspirin has direct effects and is not a prodrug. Its pKa is 3.4, plasma pH is 7.4, and urine pH is 5.4. This means theres actually a gradient for the unionized form to get absorbed back into the plasma. Aspirin works against chronic postoperative pain or pain arising from inflammation because it inhibits the production of prostaglandins. Aspirin irreversibly blocks cyclooxygenase, unlike NSAIDs that reversibly block cyclooxygenase. Aspirin also elevates body temperature because it inhibits the production of IL-1. -Aspirin can uncouple oxidative phosphorylation, which means oxygen is consumed more rapidly to compensate. This leads to hyperventilation, which can produce respiratory alkalosis and also causes the generation of lactic acid which can lead to metabolic acidosis. -These can both be treated by urine alkalization in order to prevent the unionized form from returning to plasma. -Aspirin is correlated with Reyes syndrome -Acetaminophen is the active metabolite of acetanilid and phenacetin. Acetaminophen is rapidly absorbed. However, it has no anti-inflammatory activity because it only acts in the CNS. Artificial Joint Replacements

Surgical treatment for arthritis is considered when pain is unrelieved by medication, when arthritis interrupts sleep, when arthritis hinders the ability to perform daily activities, and when it reduces quality of life. -Surgery can mean osteotomy, debridement, arthrodesis, and arthroplasty -Osteotomy is used for joint malalignment and is joint sparing. It may prevent the need for joint replacement, though not indefinitely. Osteotomy is usually indicated for young and active patients. However, it requires some articular cartilage and should be limited to one compartment of the knee. -Osteotomy of the hip can be used in acetabular dysplasia and for congenital deformity of the proximal femur. -Osteotomy of the knee requires a stable knee. -Osteotomy cuts and realigns bone, corrects joint realignment, and is joint sparing. -Debridement removes inflamed synovium and irregular articular surfaces. -Debridement is better if it addresses specific lesions. -Arthrodesis is the fusion of joints and prevents pain by preventing motion. It is commonly done on the hand, wrist, spine, foot, and ankle. However, it puts increased stress on adjacent joints and requires the mobility of nearby joints to compensate. -Hip arthrodesis fuses in a slight flexion and is compensated by mobility of the spine, knee, and opposite hip. -Knee arthrodesis is done for severe and uncontrollable septic arthritis. The knee is fixed in a slight flexion and a slight valgus. It is rarely done. -Arthrodesis eliminates motion at the joint. -Arthroplasty replaces the joint surface with something else. Total joint arthroplasty can be done for pain relief, function, and motion but there is potential for wear, loosening, and infection. -Total joint replacement cannot be done with active infection. -It also cannot be done with morbid obesity, with progressive neurological disease (like Parkinsons), and in people under 45 years of age. Soft-tissue structures and unsatisfactory bone structures may not require orthopedic surgery. Additionally, morbid obesity, neuropathic joints, progressive neurological diseases, IV drug use, non-compliance, non-ambulator, and young age are all contraindications. Hip surface replacement uses a big head to reduce the risk of dislocation and uses metal/metal articulation. It is also bone sparing on the femoral side. However, there is risk of femoral neck fracture in older women and avascular necrosis. -Hip surface replacement has a lower risk of dislocation than total hip replacement because it uses a larger head. Complications of joint replacement involves infection and DVT. Rehabilitation is more difficult with knee replacement than total hip replacement.

Foot Physiology and Mechanics Ankle sprains are the most common injury to the ankle region which occurs with a simultaneous plantar flexion and intorsion. -Physical exam reveals edema, tenderness, ecchymosis on lateral ligaments, medial tenderness, and tenderness above ankle. -Differential diagnosis includes fractures of talus, ankle, 5th metatarsal, calcaneus, or peroneal subluxation. -Radiographs are required to rule out fractures. -Treatment of ankle sprain involves rest, ice, compression, and elevation. Ankle fractures occur with external rotation of the supinated foot. Problems occur to both lateral and medial sides of the ankles. -Physical examination would reveal tenderness to the fracture site, deformity, swelling pain, and neurovascular (?) -X-rays are required to rule out fracture of the medial or lateral fibular malleolus. -Treatment involves closed reduction and a cast or splint. -Follow-up at 1 and two weeks is required to ensure the ankle does not shift after swelling subsides. Hallux valgus is deviation of the big toe away from the midline. This can result from a bunion as a prominent medial eminence. -Women get bunions far more often because they are associated with high-heeled, narrow-toed shoes. -A typical history of bunions will present with pain in close toed shoes but not in bare feet or normal shoes. Physical exam will show a prominent medial eminence that is tender to palpation. -There is also a splayed forefoot. -Treatment for bunions involves wide shoes with low heels with a leather stretch over bunions. -Surgery is considered based on the degree of deformity. All surgery for bunions involve osteotomy. Diabetes causes ulcers, neuropathy, and vasculopathy. Ulcers can occur secondary to excess pressure. Significant peripheral neuropathy can result in numbness and tingling. Quantitative testing is done with monofilament testing. -Osteomyelitis (bone destruction) is common. -Treatment involves debridement of the callus and nonviable tissue. After the ulcer heals, custom orthotics are required for a lifetime with potential surgical revascularization. Heel pain and plantar fasciitis occur and lead to disabling foot pain. -Physical exam reveals point tenderness over the calcaneal tubercle and a tight calf muscle. Non-steriodal Anti-inflammatory Drugs

NSAIDs block the action of cyclooxygenase, which inhibits the production of prostaglandins, prostacyclins, and thromboxanes. At higher concentrations, NSAIDs can also block lipoxygenases and thereby inhibit leukotrienes. -At high doses, NSAIDs also act on leukocyte membranes and prevent inflammatory mediators. Aspirin acts locally to block pain and reduces mild to moerate pain but does not cause addiction or tolerance. This is in contrast to opioid analgesics which act in the brain, control moderate to severe pain, and lead to addiction and tolerance. -The inhibition of COX-1 is responsible for antithrombotic effects because of the lack of thromboxane. -The inhibition of COX-2 is prothrombotic because it blocks prostacyclin (vasodilator) in the endothelium. -Aspirin is non-ionized in the stomach. Once it gets absorbed to the gastric mucosa, it becomes ionized and gets trapped in the gastric mucosa. This causes local irritation and induces tissue damage. Enteric-coated tablets are used in order to allow aspirin to reach the intestines before dissolving. -Additionally, the inhibition of cyclooxygenases decreases the synthesis of prostaglandins, which inhibits the secretion of mucus and bicarbonate. -Lastly, cyclooxygenase prolongs GI bleeding. -These effects are specific to COX-1 inhibitors and do not occur in COX-2 inhibitors. -Hypersensitivity occurs with COX-1 inhibition and in patients with asthma. -In patients with congestive heart failure only, COX-2 inhibition leads to renal toxicity by decreasing the glomerular filtration rate. This also promotes the retention of salt and water, leading to severe edema. -COX-2 inhibition delay follicular rupture, causing reversible infertility in eomrn. -Rare side effects include hepatic toxicity, blood dyscracias, aplastic anemia, and agranulocytosis. Celecoxib and rofecoxib are selective cyclooxygenase 2 inhibitors. Because they do not affect COX-1, they are just as effective as analgesics but they do not decrease gastric acid secretion. NSAIDs cannot be given to children, to pregnant women (prevents closing of ductus arteriosus), to those with hemophilia or hepatic damage, or to patients with peptic ulcers. Non-Neoplastic Diseases of the Bone Bone formation can occur through intramembranous ossification (flat bones) in which fibrous tissue is replaced by bone or through endochondral ossification (long bones). -Osteoblasts are rich in alkaline phosphatase, which is also a marker of new bone formation. -Osteoclasts are involved in bone resorption. -Osteocytes are osteoblasts that have become surrounded by bone matrix. -Extracellular substance is called osteoid and is primarily type I collagen. The major mineral is calcium hydroxyapatite. Bone disease results in pain, deformity, mass, fracture, and radiologic abnormality.

-Congenital Diseases -Osteogenesis imperfecta is a group of hereditary disorders that shows abnormal type I collagen production. Type I shows survival into adulthood but type II is lethal. Fractures occur early in life because of ill-formed bone but blue sclera, lax ligaments, teeth, and deafness are also present. -Achondroplasia is relatively common and is a mutation in fibroblast growth factor 3. A defect in cartilage synthesis causes the failure of proliferation at the epiphysial plates, leading to short stature. However, membranous bones are unaffected. -Osteopetrosis (or Marble Bone) shows a defect in osteoclastic reabsorption that leads to dense bone. Bones become brittle and marrow space is limited, leading to pancytopenia (anemia, thrombocytopenia, susceptibility to infection) and nerve compression. -Marfan syndrome is a mutation in the fibrillin gene that leads to tall stature and long fingers. Ectopia lentis and cardiovascular lesions are also common complications. -Infections of Bone -Acute pyogenic osteomyelitis occurs from trauma and shows fever and pain. It is usually caused by S. aureus and results when organisms enter bone through the bloodstream and spread through inoculation by trauma (or surgery). -Sequestrum is bone necrosis as a result of acute inflammation. A reactive sleeve of new bone (involucrum) may develop beneath the periosteum as a result. -Radiology shows lytic and sclerotic features resulting from a combination of necrosis and new bone formation. -This responds to antibiotic therapy but not treating the disease leads to chronic suppurative osteomyelitis. The chronic condition shows sinus drainage to skin and secondary amyloidosis. -Tuberculosis of bone can occur with insidious onset and result in extensive bone destruction that is difficult to control. -Acid fast test (AFB test) is positive. -Immunocompromised patients are particularly at risk. -The spine (Pott disease) and long bones are commonly affected. -Radiographs show bone destruction. -Pathology shows subacute inflammation with granulomas and necrosis. -Metabolic Diseases of Bone -Osteoporosis results from a decrease in total bone mass. However, the ratio of mineralized to unmineralized bone is normal. This causes a patient to become susceptible to fracture. -Primary causes are due to aging and are idiopathic. -Secondary causes arise from immobilization, endocrine disorders, malnutrition, etc. -Osteomalacia (or Ricketts) is a structural abnormality caused by defective mineralization of osteoid. However, osteoid is present in normal amounts. -The lack of vitamin D leads to bone deformities.

-Hyperparathyroidism results in increased osteoclastic activity that leads to fracture and hemorrhage. -Bone Diseases of Unknown Cause -Paget disease leads to bone thickening that leads to deformities such as increasing skull size or bowing of long bones in legs. Radiologic findings show enlarged affected bones. -There is a marked increase of alkaline phosphatase due to osteoblastic activity. -Paget disease goes through an enlargement phase, a lucency phase (destructive phase), and then a mixed irregular sclerotic phase (patchy). -Thickened bone is Paget disease is actually very soft, which explains why there is a propensity towards fracture and bowing. -Because of bone growth, there is a risk of osteosarcoma. -Fibrous dysplasia shows a progressive replacement of bone with a proliferation of benign fibrous tissue. -Monostotic fibrous dysplasia affects one bone while polyostotic fibrous dysplasia affects multiple bones. -On imaging, fibrous dysplasia shows well-demarcated lesions. -Joint Diseases -Pyogenic arthritis is most commonly caused by Staph aureus and Neisseria. Infections typically travel through the bloodstream. -Tuberculous arthritis -Lyme Disease -Inflammatory arthritides -Rheumatoid arthritis shows a chronic, relapsing inflammatory disease that affects multiple organ systems. -Gout. -Degenerative arthritis results from aging or from a congenitally abnormal joint. Biomechanics of Fractures Bone is living tissue that provides skeletal integrity and keeps muscles under tension while at rest. Bone also provides for calcium storage and is metabolically active, subject to turnover. The ultimate strength of bone depends on bone density. Fractures occur when an applied force exceeds ultimate strength. Metabolism, structure, and the way the force is applied all determine the strength of bone. -Metabolic factors like renal osteodystrophy (disruption in calcium or parathyroid hormone), decreases in calcium, and the amount of matrix determine ultimate strength. -Osteoporosis occurs when the ratio of calcium to matrix is disrupted, when the amount of matrix is below normal, when the amount of bone is decreased, and in post-menopausal women. -Physical properties like cross sectional diameter affect strength in that a small cross sectional diameter with thick walls is stronger. -Age also affects bone in that bone quality decreases as bones lose wall thickness. Additionally, homeostasis is altered with age in that the cortex becomes thinner. Diameter will increase to compensate.

-The strength of bone can be determined through three point bending, torsional bending, and stress-strain curves. -Bones have less ultimate strength in tension than in compression. -An open fracture is more of an emergency than a closed fracture because the soft tissue surrounding the bone becomes compromised. Ligament failure and fractures can occur from the same force. A rapidly applied force will cause a fracture while a slowly applied force will cause a ligament rupture. Deformities require surgery because of the tension of muscles that will pull bone fragments out of place. -Olecranon fractures are fractures of the elbow joint. The triceps pull up on the elbow joint and cause a fragment of bone at the elbow. -Galeazzi fractures are fractures of the distal radius. Fractures occur because of the tension of the brachioradialis and the pronator quadratus. -Femoral fractures occur as subtrochanteric fractures. Deformities are caused by the iliopsoas, quadriceps, hamstring muscles, and abductors. Avascular necrosis can also result from fractures. This is particularly important when blood supply occurs in a retrograde fashion. This results in collapse of the bone, which manifests as fracture. -Femoral neck fractures interrupt blood supply from the retinacular arteries and cause a loss of blood supply to the femoral head. -Talus fractures cause the talar body to lose blood supply (blood flows from head to body). Wolfs Law states that bone constantly remodels itself to resist forces. Stress fractures occur when bone fails under fatigue. -Primary bone healing shows a fracture that stabilizes very rigidly such that all motion at the fracture site is eliminated. -Callous formation requires motion and axial motion is best. -A non-union is an arrest in the healing process such that healing does not occur over time. This leads to persistent fracture lines and sclerosis at the ends of bones. -Hypertrophic non-union occurs when bones show growth but do not undergo union. There is a buildup of callus at both ends. -Atrophic non-union occurs due to avascularity. -Fatigue failures of the bone can occur with a rapid change in activity, such as suddenly going from a sedentary lifestyle to running a marathon. These are called stress fractures. Factors affecting bone healing are metabolic factors such as nutrition, smoking, and NSAIDs. Blood supply from surrounding soft tissues also affects bone healing. -Primary bone healing stabilizes fractures in a way that eliminates all motion at the fracture site. Remodeling heals the bone across the fracture and does not involve inflammation. -Callus formation forms new bone over the old bone and requires motion to work. It is a form of fracture healing that will result in remodeling.

Adult Respiratory Distress Syndrome shows an inability of lung to oxygenate blood and pulmonary failure is treated by a ventilator. It is associated with trauma resulting in multiple fractures. Fat emboli occur because of bone marrow. Pulmonary emboli results from DVT. Compartment syndrome occurs when fluid gets trapped in a muscle compartment (fascia provides an impermeable barrier). This results in the five Ps: pain, pressure, paralysis, pulselessness, pallor. Fractures can also cause nerve injury. Vascular injuries can also occur because of fractures. -Tibial fractures injure the femoral nerve. -Shoulder injury can injure the axillary nerve. -Humerus can injure the radial nerve. -The distal femur can damage the superficial femoral artery. -Knee dislocations can injure the popliteal artery. SPP: Low Back Pain Excessive sitting and poor sitting posture contribute greatly to the prevalence of low back pain and pain radiating to the leg (sciatica). -Many problems occur from walking upright all the time. -All other mammals do not have a lumbral curve like humans do. Which contributes to back pain? All of these: -Cigarette smoking -Heavy lifting -Obesity -Sedentary Lifestyle -Sitting and slouching Back muscles, connective tissue and ligaments, intervertebral discs, facet joints, and vertebrae can cause back pain. Which spinal area is subject to chronic forces and stress? -L5-S1 Muscles tend to get smaller in obese patients, which predisposes them to back pain. What causes the most pressure on the nucleosus pulposis? -Lying -Sitting -Sitting erect -Sitting slumped -Stooping forward in lifting This one Mr. Jones has a disc herniation at L4-L5 that is compressing L5.

A patient present with bilateral leg pain, lower extremity weakness, saddle anesthesia, and difficulty holding urine. Which of these is correct? -Spinal stenosis -Causa equina syndrome This one -Spondylolysthesis -Compression fracture Case #1: Musculoskeletal strain Case #2: Depression Case #3: Metastatic cancer, Clinical Applications of the Spine C5-biceps C6-brachoradialis C7-triceps L4-patellar S1-achilles Spinal cord injury occurs most commonly from vehicle accidents. Immobilization should include a rigid cervical collar and a firm spine board. Patients should be log rolled. Central Cord Syndrome -Upper extremities show LMN signs -Lower extremities show UMN signs Brown-Sequard Syndrome -Caused by penetrating injury -Loss of contralateral pain and temperature with sparing of ipsilateral motor and light touch and proprioception Anterior Cord Syndrome -Loss of motor and loss of pain/temperature -Preservation of touch and proprioception Posterior Cord Syndrome -Loss of proprioception and light touch -Sparing of motor, pain, and temperature -Foot Slapping Gait Cauda Equina Syndrome -Results from loss of central spinal canal space, possibly from a space occupying lesion

-Loss of L1-S5 -Saddle anesthesia, lower extremity pain, loss of bowel and bladder control. -This is a surgical emergency Cervical myelopathy is disease of the spinal cord that is caused by compression of the spinal cord. It is characterized by clumsiness in the hand and gait imbalance. It is diagnosed with a constellation of symptoms rather than on radiography and can be caused by a variety of factors. -There are positive Hoffmans signs, a positive Babinski test, and ankle clonus. -Surgical intervention is required if progress stops but non-intervention is preferred. In the case of surgery, the central canal would be widened. Cervical radiculopathy is compression of the spinal nerve root. -Symptoms follow specific dermatomes -C5-shoulder, biceps reflex -C6-thumb, triceps reflex -C7-middle finger, brachoradialis reflex -C8-little finger, decrease in finger flexion -Cervical spondylolysis and disc herniation can cause cervical radiculopathy -Spurlings test will reproduce the symptoms of pain because of compression -Non-operative treatment is preferable but operations are indicated if symptoms do not respond to other treatments or if weakness occurs. Lumbrical radiculopathy shows dermatomal pain that radiates below the knee. -There is often motor weakness, sensory changes, and loss of reflex -Straight leg-raising test (L5, S1) and femoral stretch test (L2, L3, or L4) will elicit pain, useful in diagnosis -L4 is required for patellar reflex -S1 is required for achilles reflex Lumbar spine stenosis results from a narrowing of the spinal canal. -This can result from spondylolisthesis, facet osteophytes, disc herniations, synovial cysts, or hypertrophy of ligamentum flavum. -There is a burning or tightness in the buttocks that occurs when walking. -Old people who like to lean on carts do it in order to find relief. -Wide decompression and segmental fusion are potential operative therapies. SPP: Shoulder Injury and Elbow Injury The axis of orientation of the glenoid fossa is pointed forwards in primates and cats. Humans are pointed laterally. This causes shoulders to be susceptible to injury. What is most commonly broken from a fall on a bicycle? -AC separation -Fracture of clavicle This one -Fracture of humerus -Rotator cuff tear -Shoulder dislocation

Ten-foot fall backward onto arm and shoulder. What is the most likely injury? -AC separation -Fracture of clavicle -Fracture of humerus This one -Rotator cuff injury -Shoulder dislocation Fall while skiing and there is severe pain and cannot move shoulder. What is most likely injury? -AC separation -Fracture of clavicle -Fracture of humerus -Rotator cuff injury -Shoulder dislocation This one Falls onto steps on the front of shoulder. What is the most likely injury? -AC separation This one, it heals on its own -Fracture of clavicle -Fracture of humerus -Rotator cuff tear -Shoulder dislocation Impingement Syndrome can be caused by shoulder instability (under 30 years old), chronic rotator cuff and supraspinatus tendon (over 40), or tears of the supraspinatus tendon (over 60 years old). What sign is most suggestive of shoulder impingement syndrome? -Tenderness to forceful palpation just inferior to acromion The impingement test tests the supraspinatus, patient has arm laterally and is actively abducting. Tennis elbow can result from lateral epicondylitis (tennis), medial epicondylitis (golf), other ligamentous injury, trauma, arthritis, or neuropathy. -In tennis elbow, the muscle most frequently involved is the extensor carpi radialis brevis Orthopedic Soft Tissue Sports Medicine Injuries Soft tissue injuries are typically sports-specific because of the nature of repetitive, stereotyped motions involved in different sports. Arthroscopy is a minimally invasive procedure with a low morbidity that has low cost and quick recovery. Rehabilitation focuses on recovery from injury, attaining full range of motion, and strengthening (in that order).

Disorders of the meniscus give mechanical problems. The meniscus has poor healing ability due to a lack of blood supply. A damaged meniscus can be sewn back together. A torn meniscus is very painful. -McMurrays test is used to diagnose a meniscal tear. -The absence of an intact meniscus leads to long term arthritis. -Menisci can be transplanted. There are sensory neurons in ligaments that allow for sensory feedback. -The ACL is the most commonly torn ligament. They tear from slower movements than they do at faster movements. It is common to tear the ligaments in the absence of a contact injury. -Damage to the ligament commonly causes a tear in the meniscus and articular cartilage as well. -Lachmanns test tests the movement of the knee in order to assess the integrity of the ligaments. -Grafts of the ligament involve filling a bone with collagen and allowing the bone to heal and form a new ligament. The achilles tendon of cadavers is commonly used. -Bone-tendon-bone is used commonly. -Rejection of grafts does not occur because collagen does not incite an inflammatory response. The inferior glenohumeral ligament holds the shoulder in place. Dislocation typically must occur a number of times before surgery is considered. Rotator cuff problems occur because of tendons, not ligaments. -The vast majority of rotator cuff problems involve the supraspinatus. -Adhesive capsulitis (frozen shoulder) results gradually over time and leads to loss of movement. SPP: Knee Ligaments are responsible for protecting menisci. The meniscus distributes the load of weight across the joint and removing the meniscus causes arthritis in 5-10 years. The articular cartilage beneath the meniscus has no ability to repair itself. -Valgus stress causes MCL injury -Varus stress causes LCL injury -Direct blow to anterior knee causes a PCL injury. This usually is caused by a dashboard injury in a car accident. -An injury to a ligament like an ACL or MCL injury will prevent a person from walking. However, returning to the sport indicates a meniscus injury. -The majority of ACL injuries are non-contact. -A pivot shift and a Lachman test (anterior drawer test) are diagnostic of a torn ACL. -In the absence of an ACL ligament, the meniscus will become a shock absorber. As such, repairing an ACL also protects the meniscus. -A person with significant knee swelling will flex their knee because it provides the least amount of pain.

-MRI has the best resolution of soft tissue and is preferred when looking for meniscal tears. -An MCL tear will usually heal on its own. Case: 35-year-old male was playing soccer when he injured his left knee. -No contact -Could not return to the field Bone and Joint Infections I Septic arthritis can involve the joint space, which shows a high mortality and morbidity (disability). The knee and hip are most commonly involved but any joint can become infected. Organisms typically invade from the bloodstream, spread from a contiguous site (abscess, osteomyelitis), or inoculation. -Infection typically involves a single joint. Organisms that enter the joint space then adhere to articular cartilage (very little fluid movement, hard to flush bacteria out). Neutrophils follow suit. Cartilage becomes damaged through increased intraarticular pressure, bacterial toxins, and the inflammatory process itself. Cartilage destruction then leads to joint space narrowing. -Staph aureus is the most common organism followed by Strep. -Treatment involves debridement and antimicrobial treatment. -Mycobacterium and Borrelia Burgdorferi are less common bacteria involved in infection of the joint (not on the east coast, Borrela Burgdorferi causes a chronic form of articular infection). -Coccidioides immitus is a common fungal infection of the joint because of trophism but Sporothrix schenckii is also common (gardening). -Parvovirus, rubella, HIV, and HTLV can infect the joint as viral causes. Treatment can involve debridement, arthroscopic surgery, or serial debridement. Antibiotic treatment would involve a systemic antibiotic (cephalosporin+vanco) for 2-4 weeks. Local antibiotics are Osteomyelitis is infection of the bone. However, the pathophysiology and management are different based on the specific joint infected. -Hematogenous spread is the most common form of spread while direct inoculation is common in adults. Adjacent spread is also possible. -Vertebral osteomyelitis can result from the spread from the GU tract or from IV drug use. In antimicrobial therapy, longer treatment is better because there is no known optimum time. However, textbooks recommend 4-6 weeks. -Osteomyelitis is never cured because the risk of recurrence is always present. As such, osteomyelitis can only be controlled due to factors involving the particular organism, surgical skill at debridement, and specific risk factors involving the patient. The exception is amputation, which actually has zero chance of remission but is typically not done.

Vertebral osteomyelitis involves vertebral bodies with subsequent destruction of the bone. It is the most common of hematogenous spread of osteomyelitis in adults and typically spreads from the GU tract. -Symptoms are non-specific back pain with low grade fevers and prolonged illness. -Diagnosis is made based on radiographs showing erosion of vertebral bodies and a narrowing of disk space. -Confirmation is done by biopsy, which also allows for identification of the organism and allows for the choice of therapy. -The most common is Staph aureus but E. coli is also common. IV drug users get MRSA, P. aureginosa, and Serratia. -Mycobacterium tuberculosis is called Potts Disease and it is the most common skeletal target of M. tuberculosis. Therapy is required for 12 months. -Unlike in long bone osteomyelitis, vertebral osteomyelitis does not require debridement (spine has good vascular supply, makes debridement unnecessary) but spine stabilization is required to prevent vertebral compression. The sacroiliac joint is usually infected only in IV drug users, patients with indwelling catheters, and patients with endocarditis. -Infection of the joint is typically caused by spread of osteomyelitis from adjacent bones. -Patients present with fever and severe sacral and pelvic pain. -Diagnosis is made from MRI. Blood cultures are positive, which is not true of osteomyelitis of other joints. Brodies abscess is a chronic, localized abscess of the bone often seen in the distal tibia. Most patients are under 25 years old. -Brodies abscess can be confused with a neoplasm. Sickle cell disease causes osteomyelitis, also with Staph aureus. They are also at particular risk for Salmonella because its encapsulated. This is because of acute infarct of the bone. Bone and Joint Infections II Diagnosis of septic arthritis shows clinical symptoms that include fever and chills, painful joints, swelling, erythema, limited motion, and joint effusion. Early septic arthritis shows soft tissue swelling but late septic arthritis shows joint narrowing (because of cartilage destruction) -MRI is useful for determining bone involvement and soft tissue abscesses. -Ultrasound is good for determining joint effusion. -Laboratory diagnosis shows elevated C-reactive protein, elevated erythrocyte sedimentation rate, elevated white blood cell count, and positive blood cultures. -Synovial fluid analysis looks for increased WBCs and cultures are necessary to select appropriate antibiotic therapy. -Staph aureus is most common organism Septic arthritis leads to cartilage destruction, pain and loss of function, degenerative arthritis, avascular necrosis of the femoral head, subluxation and dislocation of the joint, and recurrent infections.

-Treatment involves antibiotic therapy, arthroscopic surgery, or needle aspiration (not the hip). Total joint replacements have complications with foreign body and biofilms that can adhere to biomaterial surfaces. Biofilms make antibiotic therapy and antibody production ineffective and allows the organism to exist in a subclinical state with the possibility of recurrent infection. -Treatment of infected replacement joints involves debridement and synovectomy if caught early enough, removal of implants and reimplantation if later. Antibiotic therapy is required for at least 6 weeks. Hematogenous spread to joints is the most common method of entry into joints by children and IV drug users. Direct inoculation occurs from open fractures and during surgery. Spread from an adjacent infection is also possible. -Type I is medullary, hematogenous osteomyelitis -Type II is superficial, ulcer with exposed bone -Type III is localized, cortex and medullary canal involvement -Type IV diffuse, cortical involvement that spreads to the medullary canal Type A host is normal. Type B host can be compromised if there is systemic compromise (malignancy, diabetes, etc.) or local compromise (irradiated area, reduced vascularity). Type C host is so sick from other disease that the host receives no treatment. Pediatric osteomyelitis occurs most often as hematogenous spread and is often Type I medullary. -Hematogenous osteomyelitis occurs from bacterial seeding that localizes in the venous sinusoids of the metaphysis. -The metaphysis is targeted because of arteries in the epiphysis and because of reduced phagocytosis. This leads to infarct and bone necrosis. -The periosteum is stripped from the bone because of purulent exudates traveling through the Haversian and Volkmanns canals, isolating cortical bone from blood supply and producing more dead bone. -Diagnostic workup for pediatric osteomyelitis involves WBCs, erythrocyte sedimentation rate, C-reactive protein, blood cultures, bone aspiration and biopsy, and imaging. -Treatment involves antibiotics and surgery -Treatment of post-trauma or post-surgical osteomyelitis involves infection control, fracture stabilization, soft tissue coverage, and bone grafts. -Infection control involves debridement and antibiotic therapy (local and systemic). -Soft tissue coverage is done to improve vascularity to the site. -Bone grafting provides a scaffolding for new bone formation. -Bone grafts usually come from the iliac crest. The fibula is used if the hip is inaccessible. Pediatric Orthopedics Fracture Types -I, physis

-II, physis and metaphysis -III, epiphysis and physis -IV, metaphysis, epiphysis and physis -V, crush injury to physis Children can get fractures that adults cannot: plastic deformation, torus (buckle) fractures, and greenstick (incomplete) fractures. However, fractures can remodel and this depends on years of remaining growth, location of the fracture, and growth activity of the physis. Remodeling potential is particularly high near the shoulder, wrist, and knee. -Children are most commonly injured through blunt trauma from child abuse, falls from heights, and motor vehicle accidents. -Upper extremity injuries are more common than lower extremity injuries. -Pediatric bones are unique because they have a physis, thick periosteum, and porous cortical bone. Thick periosteum allows for increased elasticity, which can hide maximal displacement of the fracture. Buckle fractures result from a failure in compression. Fractures can remodel in unique ways. Asymmetrical growth of the physeal plates can allow for bent bones to align themselves. -The most common fracture in children is of the supracondylar humerus. This brings risk of injury. A slipped capital femoral epiphysis (SCFE) is a common hip problem in adolescents. The physis widens and causes the femoral head (the epiphysis part) to slip posteroinferiorly. -A stable SCFE is weight-bearing but an unstable SCFE is not. An unstable SCFE is at higher risk of avascular necrosis. -The disease can be acute, chronic, or acute-on-chronic -Obligate external rotation is a classic finding. -The biggest risk factors are obesity and African Americans. -Knee pain is a common symptom. Legg-calve-perthes disease is idiopathic avascular necrosis of the femoral head. It can be bilateral and occurs more often in boys. -Group Herring A refers to lateral pillar intact -Group Herring B refers to lateral pillar >50% intact -Group Herring C refers to lateral pillar <50% intact -Diagnosis is made based on clinical history but confirmed by plain radiographs (or MRI or bone scan). Radiography will show a flattened femoral head due to insufficient blood supply. -50% of patients will need hip replacements by age 50. Scoliosis is an abnormal curvature of the spine. -Congenital form results from one or more vertebra not completely forming or the vertebrae not separating. -Neuromuscular scoliosis results from a medical condition that affects the nerves and muscles (cerebral palsy, muscular dystrophy, spina bifida). -Adolescent idiopathic scoliosis is the most common type.

-Bracing and surgery are used to correct scoliosis. Bracing only works in skeletally immature patients. -Early signs show uneven shoulders, prominent shoulder blades, uneven wasitlines, lumbar prominence, and leaning to one side. Lower extremity alignment issues can be normal and may not require treatment. Children naturally develop bow legged (varus deformity) then become knock kneed (valgus deformity) before correcting. Rotational alignment also occurs such that in-toeing occurs naturally before becoming corrected by 10 years of age. In-toeing can be caused by metatarsus adductus, internal tibial torsion, and femoral anteversion. -Metatarsus adductus is present in the first year of life and resolves itself spontaneously. -Internal tibial torsion is common in the first three years of life and resolves itself spontaneously. -Femoral anteversion is present at birth and occurs until 5 years of age. -Surgery is only required in 0.1% of cases. SPP Diagnostic tests required to be ordered would be: -Electromyogram and nerve conduction studies. Carpal tunnel syndrome will show early denervation of the thenar muscles. Splints are put in a neutral wrist position because it minimizes the amount of pressure. Overview of Hand Surgery Upper limbs develop between 4th and 8th weeks of gestational age. Internal organs also develop at this age. -Synyldactyly is fusion of the fingers. Simple synyldactyly shows no bone in the fusion but complex does. More complete --Trauma can result in hand fractures that deform the articular congruity, angulation, and rotation. Extra-articular deformities must not have rotational deformities. Intra-articular deformities need anatomic reduction. -Bennetts fracture shows an intra-articular fracture at the base of the first metacarpal. -Damage to flexor tendons are difficult to treat. Trauma to zone 2 (between MCP joint and middle phalanx where flexor digitorum superficialis connects) is especially difficult to treat. Infections can occur to any area of the body and infections can have devastating consequences. Infections of the hand are particularly difficult to treat. -Flexor tenosynovitis can lead to scarring from infection. Tendon sheath infection shows diffuse swelling of the finger, tenderness along the flexor sheath, finger held in a slightly flexed position, and excruciating pain with passive extension of the finger. -Necrotizing fasciitis is often caused by Strep and surgical debridement is the main modality of treatment.

Nerve injury can be repaired but it requires one month for the initial healing before regrowth occurs. -Nerve injury also results from compression neuropathy in the Carpal tunnel. This compresses the median nerve of the wrist. -Tinels occurs when tapping on the nerve recreates the sensation. -Phalens occurs when flexing the wrist produces numbness. -Durkins Compression occurs when pressure over the carpal tunnel reproduces the symptoms. Vasculature has much collateral circulation such that injury to the radial or ulnar artery is often not threatening to the limb or digit. Allens test assesses collateral circulation to avoid a disastrous result. Reconstruction of the hand is considered in both traumatic and non-traumatic cases. Rheumatoid arthritis causes microvascular injury with edema of sub-synovial tissue and synovial cell proliferation. Progression of the disease shows hypertrophy and hyperplasia of the synovial cells. Joint swelling causes joints to become lax and deformed with subluxation of the tendons and joints.

Anatomy Introduction to Limbs Types of Joints -Fibrous joints are connected by dense connective tissue, allowing for very little movement between bones. Examples include sutures in the skull and interosseous membranes between the radius and the ulna and between the tibia and the fibula. There is no joint cavity and no movement. -Cartilaginous joints are articulating surfaces joined by fibrocartilage and no intervening space. Examples include intervertebral disks, the pubic symphysis, and the ends of growing long bones in kids. They are all in the midline of the body. There is no joint space and very limited movement. -Synovial joints allow for the greatest amount of activity. They all have a joint cavity, hyaline (on ends of bones, weight-bearing surfaces), a joint capsule (somatosensory and proprioceptive fibers), synovial lining membrane (no weight-bearing capability), and synovial fluid (lubrication, provides nutrients for hyaline cartilage). Most synovial joints have ligaments. Intracapsular ligaments are thickenings of the joint capsule while extracapsular ligaments are separate from the capsule. The glenohumoral joint (shoulder) is a synovial joint between the head of the humerus and the glenoid cavity of the scapula. -Supraspinatus and deltoid muscles allow for abduction of the glenohumoral joint. -Infraspinatus, teres minor, and posterior part of deltoid allow for lateral rotation. -Pectoralis major, latissumus dorsi, teres major, and subscapularis allow for medial rotation. -Coracobrachialis, anterior deltoid, short head of bicep and upper part of pectoralis major allow for flexion. -Teres major, latissimus dorsi, long head of triceps, and posterior deltoid allow for extension. Parts: Humerus:Greater tubercle of humerus, lesser tubercle of humerus, intertubercular groove, head of humerus Scapula: Coracoid process of scapula, glenoid cavity, acromion process The hip joint is a synovial joint between the acetabulum of the pelvis and the head of the femur. -Gluteus medius, gluteus minimus, and tensor fasciae latae allow for abduction. -Piriformis, obturator internus, obturator externus, and quadrates femoris allow for lateral rotation. -Iliopsoas, Sartorius, rectus femoris, and several other muscles allow for flexion at the hip. Muscles of the upper extremity are innervated by C5-T1. Lower limb muscles are innervated by L3-S3. Cutaneous nerves contain somatosensory and symp/post components. Named motor nerves contain somatosensory, symp/post, and somatomotor components. -The upper plexus is the brachial plexus -The lower plexus is the lumbosacral plexus

-The thumb is C6, middle and index fingers and C7, and ring and pinky fingers are C8 (ring finger has some variability). -The knee cap and medial side of the big toe are L4, the dorsum and middle toes are L5, and the little toe and lateral side of the foot are S1. There is much anastomoses around joints with large degrees of movement. -Subclavian artery becomes axillary artery past first rib. Axillary artery becomes brachial artery. Innervation Patterns of the Limbs The brachial plexus is a complex of nerves innervating C5-T1. The plexus is formed specifically by ventral rami (as are all somatic plexuses). There are 5 roots, 3 trunks, 6 divisions, 3 cords, and 5 terminal branches. These nerves can either be somatosensory or somatomotor nerves. Because of how the nerves are organized, no terminal branch has innervation from only a single spinal cord segment. As such, damage to one spinal cord segment weakens several muscles instead of eliminating innervation to just one muscle. Damage to one terminal branch completely paralyzes several muscles. As such, peripheral lesions are more damaging. -The ulnar nerve only has innervation from C8 and T1. This is predicted by the brachial plexus. -The axillary nerve only has innervation from C5 and C6 even though it looks like it should have innervation from C5-T1. -The musculocutaneous, median, and ulnar nerves are derived from anterior divisions of the plexus. As such, they innervate the anterior compartments of the limb. -The axillary and radial nerves are derived from the posterior divisions of the plexus and innervate the posterior compartments of the limb. -Musculuocutaneous, median, and ulnar nerves get anterior compartments and are responsible for flexion. -Axillary and radial nerves get posterior compartments and are responsible for extension. This is exclusive. The musculocutaneous, ulnar, and median nerves do not get any. An upper brachial lesion causes stretching of the C5 and C6 roots. It can occur when a babys shoulder gets caught on the mothers pubic bone or when someone falls and stretches the plexus. This presents with the affected limb rotated and held tightly against the chest wall and a medially flexed wrist. -This damages the suprascapular nerve (all), axillary nerve (all), musculuocutaneous nerve (most), and radial nerve (some). A lower brachial plexus lesion involves tearing of C8 and T1. This occurs from pulling on the arm during childbirth or falling and trying to catch something, causing body weight to stretch the lower brachial plexus. Many of the small muscles in the hand become unusable. -The damaged nerves are the ulnar nerve The skin of the upper limb is innervated by somatosensory nerves from the brachial plexus. Their cell bodies are in C5-T1. Innervation of somatosensory sensation is slightly different from somatomotor innervation. The five nerves are radial, musculocutaneous, median, ulnar, and axillary.

-A decrease in sensation of cutaneous nerves indicates damage to terminal nerves. -Dermatomes show damage to spinal cord while cutaneous nerve maps are for damage to terminal nerves. The lumbosacral plexus is formed from the ventral rami of L1-S3. The sciatic nerve is composed of the tibial nerve (L4-S3) and the fibular nerve (L4-S2). Somatosensory innervations are: -L4 tests the kneecap and inner surface of the big toe -L5 tests toes 2-4. -S1 tests little toe and back of limb The femoral nerve passes under the inguinal ligament in order to reach the anterior compartment of the thigh (posterior, embryologically). The lithotomy position can compress this nerve against the inguinal ligament. The obdurator nerve passes through the obdurator canal. It can be damaged from pelvic fractures near the superior pelvic ramus, causing anesthesia to the medial compartment of the thigh. The common fibular nerve (peroneal nerve) is exposed on the lateral side of the leg. It is susceptible to overuse (shin splints). -The deep fibular nerve can be tested on the webbing next to the big toe. -The superficial nerve can be tested on the anterior shin and dorsum of middle toes. Gross Structure and Function of Skeletal Muscle Flexor carpi radialis The deltoid is a multifunction muscle that is unique because it produces all of the anatomical movements associated with a typical joint. -The anterior part causes flexion and medial rotation because it is in front of the humeral head. It can also produce adduction. -The lateral fibers are responsible for abduction. -The posterior part is responsible for extension, lateral rotation, and adduction. -Major anatomical action is abduction. The biceps brachii muscle attaches to the coracoid process, the supraglenoid process, and the radial tuberosity. It weakly flexes the arm at the shoulder joint and strongly flexes the forearm. It also causes supination. -Its primary action is flexion at the elbow. Pronation uses the pronator quadratus and the pronator teres. -Supination uses the biceps brachii as a prime mover in speedy or powerful movements but not in slow movements. -The supinator muscle is a prime mover during supination. -The triceps brachii is a synergist that is used during any movements of the biceps brachii. -The shoulder muscles are synergists when the biceps brachii is involved in supination.

Abduction of the arms -Sternoclavicular joint transmits forces on the upper limb to the trunk. The articular disk connects the clavicular head to the sternum. This joint has much mobility. -Acromioclavicular joint is given strength by the coracoclavicular ligament. -Glenohumoral joint -Scapulothoracic joint -Deltoid muscle -Trapezius muscle -Supraspinatus muscle -Serratus anterior muscle protracts scapula, lower fibers rotate glenoid fossa upwards Human Gait Human involves cycles of coordinated lower limb actions that repeat themselves. Nearly all lower limb muscles are involved in walking. Walking involves a stance phase and a swing phase. Walking always has one limb in contact with the surface while running does not. While walking, the body is displaced vertically and laterally. -During the swing phase, the swinging limb and hip should sag due to gravity. This is prevented by the actions of the gluteus medius and minimus (innervated by the superior gluteal nerve). -Additionally, the swinging limb has a tendency to rotate medially. Lateral rotators prevent this from occurring. The lateral rotators are the piriformis, obturator internus, obturator externus, and quadratus femoris. The center of gravity is posterior to the hip joints but anterior to the ankles and knees. The soleus muscles and erector spinae prevent the body from swaying forward. Heel Strike -Gluteus maximus and hamstrings contract trunk to prevent the trunk from flying forward from the momentum of walking. -Ankle dorsiflexors contract eccentrically. -Gluteus medius and gluteus minimus contract to prevent pelvis from sagging. Flat Foot -Gluteus medius and gluteus minimus contract to prevent pelvic tilting. -Quadriceps contract eccentrically to control the amount of knee flexion. Mid-Stance -Gluteus medius and gluteus minimus contract isometrically to prevent pelvis from tilting. -The plantar flexors contract eccentrically to prevent dorsiflexion at the ankle. Heel Off -The plantor flexors contract concentrically to allow back leg to push off. -Gluteus medius and gluteus minimus contract isometrically to prevent pelvic tilting.

Preswing/Toe Off -The plantar flexors contract concentrically to push the back leg forward. -The hip is flexed by the iliopsoas to bring the thigh forward. -The rectus femoris muscle prevents excessive flexion at the knee. Early Swing -The ankle dorsiflexors (TA, EDL, EHL) contract concentrically to dorsiflex the ankle, allowing the foot to clear the ground. -The iliopsoas contracts concentrically to flex the hip and move it forward. -The rectus femoris contracts isometrically to prevent excessive flexion at the knee. Late Swing -The ankle dorsiflexors (TA, EDL, EHL) contract isometrically to hold the ankle in position for a heel strike. -The hamstrings contract eccentrically to prevent the moving leg from crashing. The positioning of the cruciate ligaments and joint capsule pass anterior to the knee and keep the knee taut. The contraction of the soleus muscle initiates the onset of walking forward. Gait abnormalities: -A lesion to the superior gluteal nerve will paralyze the gluteus medius and gluteus minimus. This results in Trendelenburg gait. This was more common when polio was prevalent. -A loss of motor function to the iliopsoas muscle would make it impossible to bring the leg forward. -Paralysis of the hamstrings (tibial nerve in the thigh) causes the patient to lean back at the moment of heel-strike. -A lesion to the femoral nerve paralyzes the quadriceps. This prevents the knee from extension and patients compensate. -A lesion of the tibial nerve in the popliteal fossa causes paralysis of the calf. This results in a shuffling gait and an inability to plantarflex. -A lesion of the dorsiflexors (deep fibular nerve) causes patients to have a high-stepping gait so that toes dont hit the ground and to place the entire foot on the ground at once instead of heel-toe. -Paralysis of the adductor muscles (obdurator nerve) causes a slightly abducted gait when walking. Functional Anatomy of the Hand The skeleton of the hand contains carpal bones of the wrist, metacarpal bones of the hand, and phalanges of the digits. The heads of the metacarpals form the knuckles of the hand. -The anatomical snuff box is formed between the abductor pollicis longus and the extensor pollicis brevis. Because the radial artery crosses in this area, it is prone to damage from laceration. Thenar muscles of the hand are innervated by the median nerve. -Abductor pollicis brevis (abducts)

-Flexor pollicis brevis (flexes) -Opponens pollicis (rotates) Hypothenar muscles of the little finger are innervated by the ulnar nerve. -Abductor digit minimi -Flexor digit minimi -Opponens digiti minimi Interossei muscles are innervated by the ulnar nerve. The dorsal parts do abduction of the fingers (and adduction of the 3rd digit). The palmar parts do adduction of the digits (except the 3rd digit). Both parts extend the IP joint and flex the MP joint. Lumbricals are innervated by median nerve (1,2) and ulnar nerve (3,4). They originate from a tendon and are found on the palmar side of the hand. They flex the MP joint and extend the IP joint (as do the interossei muscles). -The lumbricals attach to the extensor hood on the finger. Abductor policis Damage to the ulnar nerve (such as fracture of the elbow) causes a claw hand. The patient cannot adduct or abduct the fingers (loss of interossei) and cannot squeeze paper placed between fingers. Damage to the median nerve (cutting wrist) causes ape hand. Patients cannot oppose thumb and little finger due to loss of thenar muscles. Patient cannot pick up a briefcase handle. Damage to the radial nerve prevents a patient from extending the wrist or metacarpophalangeal joint. However, the patient can still extend digits. Also, cutaneous innervation to the posterior hand is still preserved. The Knee Joint The knee joint must be weight-bearing and stable with a good range of flexion and extension. The knee is made up of the femur, tibia, and patella. To allow for the femur to balance on top of the tibia, the weight-bearing surfaces are large. The articulation surfaces are the medial and lateral tibiofemoral joints (first two articulations) and the patella that articulates with the femur. -These three articulations share the same synovial space. -Stabilization is created by large bearing surfaces, articular discs (menisci), strong collateral and cruciate ligaments, strong fibrous capsule, and tendons and ligaments from other muscles. The femoral and tibial condyles are covered in hyaline cartilage. The meniscus is a semilunar cartilage on the tibial condyles. The menisci are fibrocartilage positioned on top of the tibial condyles in order to create a concave surface to receive the femoral condyles. The medial and lateral menisci are thicker at the lateral borders to facilitate their concave shape. The menisci is

attached to the tibia through a number of ligaments, including fibrous joint capsules at the periphery. -The menisci allow for stabilization, shock absorption, lubrication, and spacing. -The menisci cover 2/3 of the articular surface. -The medial meniscus is C-shaped. The medial meniscus is also attached to the medial collateral ligament. -The lateral meniscus is O-shaped. -The tendon of the popliteus passes between the lateral collateral ligament and the lateral lemniscus. Injuries to the menisci cause detachment of a horn from bone or in a tear or longitudinal split. This causes pain, swelling, clicking, and locking of the knee. Joint congruency and motion or compromised. -McMurrays test looks for meniscal tears. A positive test elicits a pain or click. Collateral ligaments -The medial collateral ligament and lateral collateral ligament limit side-to-side movement. -The MCL attaches to the medial epicondyle of the femur and medial condyle of the tibia. It is attached to the medial meniscus. -The LCL attaches to the lateral epicondyle of the femur and the head of the fibula. It is not attached to the lateral meniscus. -The valgus stress test assesses the MCL (pushes in). -The varus stress test assesses the LCL (pushes out). -The collateral ligaments are taut during extension in order to prevent hyperextension. -The cruciate ligaments are strong cords that span between the intercondylar eminence of the tibia and the intercondylar surface of the femur. The cruciate ligaments provide knee stability by holding the femur and tibia together. -The anterior cruciate ligament arises from the anterior aspect of the tibia. It attaches to the lateral femoral condyle. The ACL prevents anterior displacement of the tibia. -The posterior cruciate ligament arises from the posterior aspect of the tibia. It attaches to the medial femoral condyle. The PCL prevents posterior movement of the tibia. -Injuries tend to occur when the knees are semi-flexed because they are almost always taut. -The anterior drawer test and posterior drawer test test the integrity of the ACL and PCL, respectively. All synovial joints have a fibrous capsule lined by synovial membrane. In the case of the knee, the fibrous capsule is reinforced by multiple tendons and ligaments. -The synovial membrane of the knee also attaches to margins of articulate surfaces as well as to peripheral edges of menisci.

-The synovial membrane excludes the ACL and PCL from the joint cavity but not from the fibrous capsule. Bursa -Subcutaneous prepatellar bursa -Subcutaneous and subtendinous infrapatellar bursae -Suprapatellar bursa (the only bursa in the synovial cavity) The patellofemoral joint shows articulation of the patella with the femoral condyles. The patella is a sesamoid bone, which means it formed from the tendon of the quadriceps muscle. It acts as a pulley during extension of the quadriceps muscle. Rotation of the lower leg correlates to damage of the menisci (pain on medial rotation shows medial meniscus tear, lateral pain shows lateral meniscus tear). The unhappy triad is the MCL, ACL, and lateral lemniscus (these injuries often occur concurrently)

Glenohumeral Joint Abduction Supraspinatus Deltoid

Adduction

Flexion Corachobrachialis Deltoid Bicep (short head) Pectoralis Major Medial Pectoralis Major Latissimus Dorsi Teres Major Subscapularis Anterior Posterior

Extension Teres Major Latissimus Dorsi Triceps Deltoid Lateral Infraspinatus Teres Minor Deltoid

Innervation

Hip Joint Abduction Gluteus Medius, Minimus Tensor Fasciae Latae Flexion Iliopsoas Sartorius Rectus Femoris

Adduction

Extension

Medial

Lateral Piriformis Obdurator Internus Obdurator Externus Quadratus Femoris

Anterior

Posterior

Innervation

Median Nerve -First two lumbricals -Thenar muscles of the thumb

Ulnar Nerve -Second two lumbricals -Hypothenar muscles -All interossei -Adductor pollicis -Lumbricals 3 and 4 -Abductor digiti minimi -Flexor digiti minimi -Opponens digiti minimi Obdurator Nerve Superior Gluteal Nerve -Gluteus minimus -Gluteus medius Inferior Gluteal Nerve -Gluteus maximus