MSK Learning Objectives Lecture 1 Skeletal Muscle Growth and Function Dr. Ruth Wood, May 1, 2012 1.

. Review the cell structure of skeletal muscle.

2. Discuss muscle development

Mesoderm: migrate from myotomes Myoblasts: mitotically active Mytobut: fusion of myoblasts, differentiations Muscle fiber (immature): growth Muscle fiber (mature): future growth

3. Diagram a muscle spindle and describe how it senses muscle length. Muscle spindles are in the belly of the muscles and consist of specialized intrafusal fibers, together with sensory and motor nerve endings. Sensory nerve fibers in the spindle fire in response to changes in muscle stretch. Gamma motor neurons maintain tension on the intrafusal fibers. The muscle spindle reflex provides sensory feedback to regulate muscular contraction.
-Nuclear chain fibers, static bag fiber: respond to stretch -Dynamic nuclear bag fiber: respond to changes in the rate of stretch

4. Describe the location and function of the Golgi tendon organ. Golgi tension organs are free nerve endings at the junction with tendons and provide sensory input on muscle strain. Golgi tendon reflex protects the muscle from excessible heavy loads by causing the muscle to relax and drop the load. Lecture 2 Connective Tissue III: Bone Development Dr. Ying, May 1, 2012 1. Be able to distinguish the difference between intramembranous and endochondral bone formation and describe the steps involved in each. Intramembranous Bone Formation Endochondral Bone Formation Within a layer of condensed mesenchymal cells Within cartilage model, Cartilage replaced by bone Occur in flat bones (like skull, scapulae, sternum) Occur in long bones
1. Aggregation of mesenchymal cells 2. Differentiation into osteogenic cells, then osteoblasts which produce osteoid 3. Bony spicules are initially produced and fused to form trabaculae 4. Other mesenchymal aggregates form bone marrow 5. Primary Bone is replaced by lamellar bone 1. Periosteal bone collar is formed first: Chodrocyte prolif, hypertrophy, calcification, bv sprouting 2. Periosteal bud forms the 1 center of ossification (cavity): Periosteal collar extends along diaphysis 3. 2 ossification centers and epiphyseal growth place form 4. Epiphyseal plate replaced by an epiphyseal line, except articular surface: bvs from diaphysis and epiphysis intercommunicate

2. Be able to explain how bones grow in length and width.

Proliferation and hypertrophy of chondrocytes within the epiphyseal place, followed by calcification of the cartilage matrix, leads to an increase in bone length Bone deposition on the outer surface of the bone collar and resorption of bone on the inner surface results in progressive increase in diameter of the diaphysis.

3. Be able to outline the sequence of events in repair of bone fractures.

1. Formation of fracture hematoma: broken blood vessels clot, inflammation occurs, bone fragments begin the gradual resorption by osteoclasts 2. Cartilaginous callus formation: fibroblasts survive and replicate, fracture hematoma is changed into granulation tissue, a hyaline cartilage callus is formed around the ends of the bone 3. Bony callus formation: periosteal cells distal to the fracture gap develop into osteoblasts which form woven and bony trabeculae 4. Bone remodeling: primary replaced by secondary bone

4. Be able to describe the basic structure of synovial membranes.

The synovial membrane is a layer of squamous-to-cuboidal epithelial cells. There are 2 types of cells: Type A (phagocytic) and Type B (fibroblast-like). The synovial membrane secretes a colorless, viscous fluid rich in hyaluronic acid and proteins.

Lecture 3 Musculoskeletal Tumors Tumors of Mesenchymal Origins Dr. Pinsky, May 3, 2012 1. Define and use in context these words and roots:
actin: structural intracellular molecule that works in muscle contraction, common to skeletal and smooth m angio- : related to blood vessels chondro- : related to cartilage desmin: cytoskeletal element common to skeletal and smooth m fibro- : related to fibroblasts histio-: related to immune cells leio- : related to smooth muscle lipo- : adipose-related mesenchyme: undifferentiated tissue derived from embryologic mesoderm myoglobin: O2 carrying protein present only in skeletal muscle osteo-: related to bone osteoid: secreted by osteoblasts to create bone pluripotential: capable of differentiation into more than one tissue type rhabdo: related to skeletal muscle sarcoma: malignant tumor of mesenchymal origin tumor grade: Grade 1 (low, benign) III (high, malignant, more mitoses), grade by histological type, cellularity, nuclear pleomorphism and mitotic activity vimentin: an intermediate filament common to mesenchymal tissues

2. Delineate the typical age range, site, prognosis and gross and microscopic appearances (where given) and recognize clinically and histologically each of the following *starred* mesenchymal tumors/tumor-like lesions: See separate page for chart Lecture 4 Physiology of Skeletal Muscle Dr. Robert Farley, May 3, 2012 1. Describe the cellular structure of a skeletal muscle fiber. See Right 2. Know the difference between Type I and Type II skeletal muscle fibers Type 1: Red fibers rich in mitochrondria, Hb, Mb, and cytochromes, give a slowtwitch response to stimulation, more resistant to fatigue, most efficient for generating sustained forces Type 1I: White fibers relatively depleted in mitochondria, energy from glycolysis, fast twitch response, fatigue easily, most efficient for quick, intermittent movements.
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3. Name the major protein components of the thick and the thin filaments Thick filaments: myosin (two isozymes Type 1 myosin hydrolyzes ATP more slowly than Type II) Thin filaments: actin, tropomyosin, tropnonin 4. Explain the sliding filament model of muscle contraction, including the relationship between crossbridge formation, force generation, and ATP hydrolysis. Describe the role of calcium contraction.
Thin and thin filaments interdigitate and overlap part of their lengths and increase this overlap during contraction. This occurs through breaking and reformation of crossbridges between myosin heads on thick filaments and actin molecules on this filaments. Myosin cross bridges attach to actin at 90 and swivel to about 45. The energy for this process comes from hydrolysis of ATP by the myosin ATPase. Myosin is 1-200x more effiecient in ATPase action while bound to actin, so Ca2+ facilitates this interaction as Calcium binds troponin C, releasing actin for myosin binding.

5. Distinguish between isotonic and isometric contractions Isotonic: change in muscle length Isometric: no change in muscle length 7. Describe the force-velocity relationship for an isotonic contraction The rate and extent of muscle shortening and duration of contraction decrease as the size of load increases. Power is maximal when the load is 1/3max. 8. Explain the length-tension curve for an isometric contraction No work is done in an isometric contraction As the muscle is strength, resistive force increases After the muscles maximum, it can no longer stretch safely, and tension decreases

9. Describe the mechanism whereby force of contraction can be increased by increasing the frequency of motor nerve firing The action potential is short (~5msec) compared to the duration of the twitch (10-100msec), and it is possible to generate a second AP before the muscle has relaxed, which would release more calcium and generate even more force. Lecture 5 Skeletal Muscle Plasticity and Adaptions to Exercise Dr. Schroeder, May 3, 2012 1. Describe muscle fiber type characteristics and adaptations to exercise and aging.
Type I: slow twitch, endurance Type IIa: fast shortening speed, moderately well-developed capacity for energy transfer from both aerobic and anaerobic sources, represent fast-oxidative-glycolytic (FOG) fibers Type IIb: possesses greatest anaerobic potential and most rapid shortening and most rapid shortening velocity, represents true fast-glycolytic (FG) fibers.

2. Explain the neuromuscular and hypertrophic adaptations that are responsible for enhancing skeletal muscle force production.
Hypertrophic factors: hypertrophy, proportion of Type II/Type I fibers, myofilament packing Neuromuscular factors: #motor units recruited, firing rate (freq) of MU, MU synchronicity, activation of synergist muscles, inhibition of the antagonist muscles (first 4-6 wks of training)

3. Describe the process of exercise induced muscle damage and the importance to muscular adaptation.
Once a muscle fiber is injured large amounts of calcium may enter the cell, which is cytotoxic. Changes in pH, intramuscular high E phosphates, ionic balance, or T with unaccustomed exercise produce major alterations in the sarcoplasmic reticulum structure/function. This depresses the rates of Ca2+uptake and release and free Ca2+concentration. Ca2+ may then move into the cytosol of the damages fiber, contributing to the autolytic process that degrades both contractile and noncontractile structures, leading to reduced force capacity and muscle soreness. The muscle damage acts as a stimulus for initiation of the repair process and adaption. The greater the magnitude of muscle fiber damage the greater the compensatory adaption

4. Discuss several of the important factors that contribute to improving muscle mass and strength.
Genetics myostatin, androgens Nervous system activation Physical activity progressive resistance training Nutritional activity Endocrine influences Environmental factors

Lecture 6 and 7 Rheumatoid Arthritis and Spondyloarthropathies Dr. Shuntary Shinada, May 7, 2012 A. Introduction to Rheumatology
1. Recognize that there is a great variety of rheumatic diseases. 2. Recognize that rheumatic diseases affect all age groups. 3. Appreciate the financial impact of rheumatic diseases on society. MSK - $215 billion, Arthritis 82.5 billion 4. Appreciate the impact on the patient and family: emotional, financial, quality and quantity of life, disability.

B. Rheumatoid arthritis 1. Be familiar with the definition and clinical picture of Adult and Juvenile Idiopathic Arthritis.
RA: chronic, inflammatpry dieases, which the major target o synovial joints. Joint involvement in symmetrical. Joint inflammation cause swelling and pain. Morning stiffness and fatigue are prominent sx. JIA: form of arthritis with onset under 18yo. IT differs from adult RA in modes of onset and can cause growth

abnormalities. Nodules are less frequent and Rhematoid factor is only positive in 8-15% of cases. 2. Identify the role of genetics in rheumatoid arthritis.
Gender difference: Female-male: 3-1 Family studes show high prevalence in persons with 1 relatives. Associations vary by races and ethnicity: HLA-DR4 Ag in 50-70% of white American and N. European, 36-56% of Afro-Americans with RA HLA-DRB1 is the responsible gene with many alleles associated in difference races.

3. Appreciate pathogenetic mechanisms of rheumatoid arthritis.

In RA the synovium contains activated T-cells, B-lymphocytes, plasma cells, and monocytes/M, which produce cytokines (IL-1, TNF, Igs, etc) which propagates the inflammation. Synovial Ms and fibroblasts produce matrix metalloproteinases. Synovial fluid increases in volume and # of inflammatory cells.

4. Identify the mechanisms of tissue damage.

Joint structures are damaged by substances produced by the inflamed hypertrophic synovium, pannus and leukocytes. Collagen degraded by synovial & neutrophil collagenases, and proteoglycans degraded by neutral protease and elastase. Granulomas (rheumatoid nodules) are seen in pressure points and produce IFN- and IL-4. As the disease progresses, granulation tissue forms as the edges of the synovial lining, known as pannus, with extensive angiogenesis (formation of new vessels) and production of enzymes that cause tissue damages. Osteoclast differentiating factor, IL1, and TNF cause M differentiation into osteoclasts which leads to bone erosion. Also, immune complexes are deposited in articular cartilage, where there is no mechanism for paid clearance.

5. Recognize the multisystemic nature of the disease.

Anemia present in ~80% patients, chronic disease anemia Muscle atrophy, rheumatoid myopathy, Rheumatoid nodules (granulomas) in pressure areas Vasculitis in 10% of patients leg ulcers, digital gangrene, neuropathy Pleuropulmonary manifestations, Carditis in 10% of pts, Premature CV disease Neuro- peripheral nerve compression Cancer increase risk of lymphoma Ocular inflammations episcleritis, sceromalacia, keraomalacia,

6. Identify therapeutic modalities for RA and comprehend their mechanisms of action.

Laboratory: Rheumatoid Factor (RF), Anti-CCP NSAIDs, COS inhibitors: short termrelief of inflammation and pain Disease Modifying Anti-Rheumatic Drugs (DMARDs) or Remittive Drugs may require 1-6 months for effectiveness, but may induce remission of disease activity with cesaiotn of inflammation an dpain, and normal sed rate. Combos used early to control Biologic drugs attack mediators of inflammation and tissue damage etanercept, adalimumab, golimumab, certolizumab, infliximab, rituximab, tocilzumab, abatecept 4

Corticosteroids are suce for control of rheumatoid synovitis in two forms: inctraarticular injections of long-acting esters for relief of local synovitis, and on occasionally orally in the smallest possible dose Physical medicine and Rehab: rest, exercise, splinting of joints, head and cold applications Reconstructive ortho surgery for severely damaged joints

C. Seronegative Spondyloarthropathies 1. Define and recognize the clinical picture of the Spondyloarthropathies:
HLA-B27 associated arthritides, which differ from RA are:
1. 2. 3. 4. 5. High incidence of spinal joint (axial skeleton) involvement Usually, assymetrical lower extremity joint involvement Mend involved much more frequently than women High frequency of HLA-B27, esp with spinal arthritis RF usually absent

Ankylosing Spondylitis: chronic, inflammatory, systemic disease with major target of sacroiliac joints, and cartilaginous and synovial joints of the spine; Symmetrical joint involvement; occurs mainly in young men. Characteristic outcome is ankylosis (fusion) of joints and ossification of paraspinal ligaments Clinical features: spinal features, peripheral arthritis, enthesopathy, extra-articular features Reactive Arthritis: chronic, recurring, inflammatory disease, consisting of urethritis or infectious diarrhea, conjunctivitis, arthritis, and mucocutaneous lesions. Exposure to certain infectious agents in a person positive for HLAB27 is considered to be part of the development of disease. Clinical features: arthritis, mainly lower extremities (asymmetrical), self-limited (2-6mo), recurs in 50% of pts, sausage toes/digits or dactylitis, uncommon permanent joint damage, X-rays may show periostitis near and involved joint. Enteropathy-associated (Crohns Disease, Ulcerative Colitis) arthritis: Psoriatic arthritis: chronic skin disease of unkown etiology with accompanying arthritis in 6% of pts. Involve peripheral joints, or sacroiliac (30%) and spinal joints (12%). Psoriatic spondylitis is assoc in 30-50% of pts. Clinical features: DIP joints commonly involved, nail pitting, sausage fingers/toes, skin lesions and arthritis exacerbate and remit together, remissions more frequent, radiology pencil-in-cup, whittling, periostitis, nonmarginal spinal syndesmophytes

2. Identify the genetic susceptibility to ankylosing spondylitis.

M:F 9:1. Familial aggregation studies estimate that genetic risk factors contribute to 80-90% of susceptibility to AS. Stronger concordant rates between dizygotic vs monozygotic twins.

3. Recognize the multisystemic nature of these diseases. 4. Identify therapeutic modalities and their mechanisms of action.
Patient and family education Pharm: NSAIDS, methotrexate and sulfasalazine, Anti-TNF PT is crucial: postural exercises, breathing exercises, swimming Reconstructive surgery of hips, spine may be needed Reactive Arthritis add antibiotics for infection, topical corticosteroid for eye or skin involvement Psoriatic Arthritis skin manifestations need attention, corticosteroid, tar creams, UV light

Lec 8 Osteoarthritis Dr. Daniel Arkfeld, May 7, 2012 1. Define osteoarthritis and distinguish its primary and secondary forms. Recognize the pattern of joint involvement.
Primary OA: no identifiable cause, involves: small joints in hand, C/L spine, hips and knees, 1st MTPs Secondary OA: had identifiable cause and involve any joint

2. Identify factors predisposing to osteoarthritis.

Trauma from overuse (athletes), Hypermobility Syndrome, Repeated hemorrhage (hemophilia, Marfans, bleeding do) Structural abnormalities: meniscectomy, congenital abn, avascular necrosis(AVN), and infection Charcot Jnts (Neuropathic Origin): Tabes dorsalis (knee), Diabetes (foot/ankle), syringomyelia (shoulder), peripheral nerve injury Metabolic d/os: Acromegaly, alkaptonuria, gout, hemochromatosis, chondrocalcinosis, Ocronosis (dark urine, dark pigment in eye, buildup of homogenitis acid in jnts/tissues) Consider 2 OA if arthritis is present in unusual locations or below age of 50 RFs: Aging, obesity, quadriceps muscle weakness, jnt overuse/injury, genetic susceptibility, dev abn 5

3. Differentiate between the clinical presentations of osteoarthritis and inflammatory arthritis. Osteoarthritis has osteophytes in joint while RA has smooth but compressed joint spaces 4. Identify the objectives of current treatment programs for osteoarthritis and the therapeutic modalities currently available to achieve these objectives. Non-pharm: patient education, weight loss, exercise (tai chi, yoga, pilates, water exercise), PT Pharm: control of pain Lec 9 Drugs of Rheumatoid Arthritis Dr. R. Gopalakrishna, May 7, 2012
1. Describe the anti-inflammatory action of glucocorticoids and their side effects associated with long-term use in RA pts. 2. Discuss the mechanism and efficacy of various disease-modifying second-line drugs for RA (methotrexate, leflunomide, hydroxychloroquine, salfasalazine, and TNF- inhibitors). Drug Mechanism Effect/Efficacy Side Effects Indirectly PLA2 activ. Overlaping anti-inflam/ Sodium retention Glucocorticoids
Prednisone Prenisolone Triamcinolon Dexamethasone Betamethasone

transcr. of lipocortins, esp lipomodulin Supress COX2 exp.

immunosupression # circ lymphocytes # circ PMNs Prod of IL-1

Hypothalamic-pituitary-adrenal suppression Growth retardation, Peptic ulceration, inf Osteoporosis, Myopathy, Cataracts, Hypoglyc Large dose: fluid and electrolyte imbalance Generally well tolerated GI disturbances, mild alopecia, myelosuppression (reduced by folate) Pneumonitis (6%), Liver cirrhosis more rare Contraindicatioed: pregnancy, liver, lung, or kidney dz, mod-high EtOH use No opportunistic infection If OD: give cholestyramine resin Diarrhea in 1/3 pts Elevate liver enzymes (ALT, AST) Teratogenic Relatively safe in pregnancy Less ocular damage, but risk of retinopathy

Disease Modifying Antirheumatic Drugs (DMARDs) -/ de novo purine synthesis For mod-severe RA Methotraxate
Use at low dose in RA: 2.5-5mg/wk

Leflunomide

Hydroxychloroquine (HCQ) Malaria medicine

Salfasalazine

-/ AICAR conv. to FAICAR AICAR accum inhib AMP deaminase intra and extracell. adenosine, AMP Adenosine cAMP inflam cytokines (TNF, etc) -/ de novo pyrimdine synthesis -/dihydroorotate DH cell cycle arrest and inhib of lymphocyte clonal expansion Unclear, interfere with func of lysosomes and prevent hydrolytic enz release Inhibit DNA/RNA synthesis Trap free radicals Unclear mech Metabolites: sulfapyridine (antibac), 5-aminoslaicylic acid (anti-inflam : -/COX,5-LOX) Adenosine, inhib IL-1, TNF Prevent TNF binding to cellsurface R and block inflam. cascade and prevent tissue destruction Unclear -/ migration and phagocytic actions of PMNs and M -/ lysosomal proteolytic action Metabolite: 6-mercaptopurine Lymphocyte celld eath transcr of IL-2 and other cytokines T-cell proliferation

Can be combined Caffeine (adenosine antag) poor response Other uses: psoriasis, psoriatic arthritis, SLE, sarcoidosis No in opportunistic infections Long half life of M1 metabolite

For mild RA, longer onset of action Other use: SLE, Sjorgens syndrome

TNF Inhibitors
Etanercept Infliximab

For mild RA More eff than HCQ, As eff as IM gold, penicillamine Other use: AS, Juvinile chronic arthritis, ulcerative colitis, Crohns dz Uses: psoriasis (+arth), JIA., giant cell arteritis, sarcoidosis, Wegeners granulomatosis, and ulcerative colitis (inflixamab only)

Nausea, vomiting, headache, diarrhea Sulfa allergic reactions Non teratogenic safe in early pregnancy (folate abs) Kernicterus no near-term pregnancy Serious inf. (sepsis, TB, demyelinating d/os) Containd: active inf, TB Drug-induced lupus (monitor for ANA)

(Gold salts)
Autothioglucose Gold thiomalate Auranofin

(Azathioprine) (Cyclosporine)

-/ organ transplant rejection Limited use in RA and Wegeners granulomatosis Allogenic organ transplantation Autoimmune dz: RA, uveitis, insulin-dep diabetes, SLE, psoriatic arthropathies

Dermatitis, lesions of mucous membr (mouth) Kidney toxicity, proetinuria Blood dyscrasias: tcp, leucopenia, aplastic an. Contraind:Hx of heavy metal tox, pregnancy, penicillamine (chelates gold) BM suppression (leucopenia) Susceptibility to infections Susceptibility to infections (opportunistic)

3. Select the appropriate drug(s) to treat RA patient, considering the patients clinical status. Choosing a DMARD:
1. 2. 3. 4. 5. For mild RA: hydroxychloroquine or sulfasalazine For moderate to severe RA: Initially methotrexate (MTX) alone. If the response is inadequate: Hydroxychloroquine, sulfasalazine, or leflunomide is added to MTX. Not responding to this combination: TNF- inhibitor is added to methotrexate. Choosing a combination therapy:
a. MTX + hydroxychloroquine or sulfasalazine: no additive toxicity. b. MTX + leflunomide: synergistic interaction; MTX -/de novo purine synth, leflu. -/ de novo pyrimidine synth c. MTX + TNF- Inhibitors: MTX production of autoABs to TNF - inhibitors prolongs actions

Lecture 10 Pathogenesis of Systemic Lupus Erythematosus Dr. David Horwitz, May 9, 2012 1. Define Lupus
Systemic disorder of generalized autimmunity with a wide variety of clinical symptoms, characterized by the production of antibodies to the cell nucleus which predominantly effects young women. SLE is a T and B cell disorder of immune regulation caused by a loss of tolerance to self-antigens with the consequence of altered homeostasis often triggered by infections, and followed by decreased clearance of apoptotic cells and impaired regulators.

2. Describe the Pathogenesis of SLE

1. Multiple etiologies: genetic, gender, environment 2. T cells lose self-tolerance altered immune homeostasis
a. Clonal deletion: auto-aggressive T-cells escape destruction in thymus b. Clonal anergy: signal 1 stimulates immunity w/o signal 2 c. Apoptosis: autoreactive T/B cell apoptosis and clearance of dead cells (leads to ANA) d. T-regs: impaired fuction and decreased # inability to block T-cell prolif, inability to control immunogenic APCs (Bcells + DCs), loss of tolerogenic APCs, decreased production of anti-inflammatory cytokines like IL-10 and TGF

3. B cell abnormalities:
a. spontaneous activation b. Become APCs for neuclear uto-antigens producing numerous autoantibodies IFN stimulates APCs to activate autoreactive T cells c. Hyper-responsive d. Failure of ABs binding FcR to inhibit Ig production and further production of autoABs

3. Explain susceptibility and environmental triggers

Genetics: 25% identical twin concordance, complement deficiency (C1q, C2, C4), immune R dysfunction (HLA-D2, low TNF, FcR 2/3a/b, IL10, TLR, IRF-5, PTPN22, MBL) Environmental Triggors: Infections agents (co-stim for activating autoreactive T-cells), Sunlight (cellular injury from UV radiation alters self-Ags), Drugs (procainamide, hydralazine inhibits DNA-methylation)

Lecture 11 Systemic Lupus Erythematosus Dr. Francisco Quasimorio, May 9, 2012 1. Present a clinical overview of systemic lupus erythematosus (SLE), a prototype of human autoimmune dz
The clinical course of this disease is a chronic irregular course with periods of active disease in between periods of inactivity, but patients may go into disease remission. Patients who die early often die of opportunistic infection, while patients that die later die of accelerated atherosclerosis or other complications. Derm: Malar Skin Rash: butterfly distribution (nasolabial fold spared), photosensitivity, alopecia, cutaneous vasculitis (around nail beds), mucosal ulcers, chronic discoid LE, Inflamatory dermatitis MSK: polyarthritis, myalgia, synovitis, myositis Visceral: serositis, pneumonitis, FUO Renal: proteinuria, nephritic syndrome, hpt, edema, glomerulonephritis, major cause of M&M Neuropsych: strokes, seizures, psychosis Hematologic/Vascular: anemia, leucopenia, tcp, purpura, vasculitis, thrombosis (gangrene), accel. atherosclerosis Resp: Pleurisy w or w/o effusion, interstitial lung fibrosis, acut lupus pneumonitis, alveolar hemorrhage, functional abnormalities, pulmoray hpt, diaphragmatic dysfunction, airways obstructed Cardiac: pericarditis +/- effusion, pericardial tamponade, constrictive pericarditis, myocarditis, Libman Sacks endocarditits, 7

Pathology: Inflammatory changes, blood vessel abnormality, immune complex deposits Dx: multisystem involvement, immunologic abnormality, and exclusion of other medical conditions. AND 4+ of:
1.Malar rash 2.Discoid rash 3.Photosensitivity 4.Oral Ulcers 5.Arthritis, non-erosive 6.Serositis 7.Renal disorder 8.Hematologic disorder 9.Neurological disorder 10.Immunologic disorder 11.Positive ANA

2. To discuss the role of antinuclear antibodies and other types of autoantibodies in the pathogenesis of tissue injury in SLE
ANA are autoantibodies to nuclear Ags, and there are several types with varying antigenic specificity (IgG, M, A isotypes). ANA are seen in SLE and other diseases. There are 2 specific types characteristic of SLE: Anti-dsDNA, and Anti-Smith (spliceosome). ANA alone does not cause lupus does not affect fetuses that are ANA + (mother has SLE), nor does it affect human volunteers injected with ANA containing plasma or have any cytotoxicity in culture. ANA may be secondary as a DNA Ag may bind to the renal glomeruli and the circulating ANA reacts to the planted DNA to form immune complexes in situ. These immune complexes activate the complement system causing inflammation and further damage. The source of DNA Ags may be from defects in apoptosis. DNA Ags are taken up by dendritic cells and presented to T/B cells and ANA are formed.

Lecture 12 Systemic Sclerosis Dr. Elizabeth Ortiz, May 9, 2012 1. Present the clinical features of systemic sclerosis (SSc). Discuss the various categories of SSc.
1. Limited SSc: CREST a. Calcinosis: joint deposition, not really treatable b. Raynauds Phenomenon: over exaggeration of normal vascular response to hot/cold (2-4th digits, white, blue or red
in fingers), + tingling, numbing from lack of blood flow to digits

c. Esophageal dysfunction: collagen deposition of smooth muscle of lower 2/3 of esophagus d. Sclerodactyly: fibrosis and thickening of skin around digits and joints, joints themselves spared, contractures and
ulcerations, hypopigmentation of skin, can get ischemia and autoamputation

e. Telangiectasia: dilated blood vessels in face, palate (non-specific) blanch when touched 2. Diffuse: skin is thick, waxy and tight; stages of skin involvement edema, induration then atrophy a. CREST b. MSK: arthritis (symmetric, polyarticular, small/large joints), tendon rubs (squeaky, leathery rubs w/ movement, worse
prognosis), muscle atrophy, myositis

c. GI: Esophagus (dilation, impairs mobility, lower esophageal sphincter dysfunction, GERD with mucosal ulcerations),
Stomach (delayed gastric emptying, gastic antral vascular exctasia watermelon stomach), Small Intestine (atony with obstruction, stasis with malabs, pneumotosis cystoides), Large Intestine (Pseudo-diverticula, infarction); overall, atrophy of smooth m and replacement with collagen, atrophy and fibrosis of submucosa/mucosa, degenerative and inflammatory changes in bvs d. Pulmonary: pulmonary fibrosis, hyperplasia and scelrosis of pulmonary a and branches (pulm hpt), superimposed infection, micro-aspirations +/- aspiration pneumonia, lung cancer e. CV: myocardial fibrosis, conduction deficits, pericarditis, pulmonary hpt heart failure f. Renal: malignant HPT + renal insufficiency = scleroderma renal crisis

3. Localized Scleroderma: only affects the skin, no internal organ problems a. Morphoea: plaque-like, most common, lesions usually oval, on 1 area of the body, >1cm, not painful b. Linear Scleroderma: most common in children, longitudinal band-like lesions, usually on limbs, can lead to joint
contractures and muscle atrophy

2. Discuss the pathogenesis, theories and the possible role of lymphocytes, cytokines and other factors Incompletely understood, but key elements include immune activation, vascular damage, excessive synthesis of extracellular matrix (deposition of increased amnts of structurally normal collagen) Theory: immunologic activity + vascular changes = # activated fibrogenic fibroblasts Immune abnormalities: 95% of pts have auto-ABs, pathogenic capabilities still unclear Theory: Initiating event vascular bed change (immune cells, fibroblasts, endothelial cells) GF and cytokine production fibroblast activation fibrosis

Lecture 13 Pharmacology of Muscle Relaxants Dr. Joe Miller, May 9, 2012 1. Diagram the reflex arc. Indicate major sites of action of spasmolytic drugs. Fusiform efferents, dorsal horn of spinal cord, dorsal root, ventral roots, motor end plate, muscle itself 2. Contrast the mechanisms of action of centrally and peripherally acting spasmolytics Centrally action spamolytics act on the CNS and nerves that innervate spastics muscles. Peripheraly acting drugs work on the muscle itself. 3. Specify the clinical use of cyclobenzaprine and related centrally acting muscle relaxants
Drug Diazepam Mechanism/Effect GABA-A agonist Cl- channel opening Orally active , GABA-B ag. Presyn: open K+, close Ca2+ ch Specific --/ Substance P fibers GABA A/B agonist Work on Gly neurons Ca channel block No GABA A/B activity GABA agonist 2 blocker? Increase pre/post-syn inhib Glu-release blocker Block release of Ca from sarcoplasmic reticulum Peripherally active ACh vesicular release block 5HT2 Block? Clincal Use Anxiolytics, Sedation, Amnesia, Anticonvulsant, Muscle Relaxant, EtOH withdrawal Intrathecal: sev spasticity, m pain Anti-craving in alcoholics Anti-migraine action Not in US market Spasmolytic (dorsal horn involved?) Anti-epileptic MS spasticity Muscle spasm, fibromyalgia Spamolytic (similar to baclofen) Analgesic ALS Malignant hyperthermia Muscle contraction Local spastic d/o Cerebral plasy Local muscle spasm from tissue trauma or muscle strain Adverse Effects Dependence, withdrawal, daytime drowsiness and confusion, ataxia and cognitive impairment at dose

Baclofen

Progabine Glycine Gapapentin Pregabalin Tixantidine Rluzole Dantrolene

Memory loss Drowsiness, hypotension, dry mouth Muscle weakness, sedation

Botulinum Toxin Cyclobenzaprine

Sedation, Hallucination

Lecture 14 Inflammatory Myopathies Dr. Thomas Beardmore, May 11, 2012 1. Evaluate a patient with complaints of muscular weakness and pain.
Inflammatory Myopathy: Proximal Muscle Weakness, Elevated muscle enzymes (CK, Aldolase, ALT, AST, LDH), Myopathic EMG changes, Muscle biopsy with inflammation, Skin rash for DM, Routine blood tests normal

2. Differentiate the clinical features of dermatomyositis and polymyositis.

Polymyositis Insidious onset over several months, usually with systemic sx Weakness of shoulder and pelvic girdle, neck muscles, 50% with pain and tenderness, occ. involvement of pharyngeal m Pulmonary: interstitial fibrosis Cardiac: rare, usually subclinical Muscle fibers in various stages of necrosis and regeneration Predominanatly endomesial, particularly CD8+ Muscle fibers displaced w/ fibrous CT and fat over time EMG: Triad
1. insertional activity, fibrillations, sharp + waves 2. spontaneous, bizarre high-freq discharges 3. polyphasic short dur., low amplitude motor unit potentials

Dermatomyositis PM findings + Grottons papules, heliotripic discoloration of eyelids with/without periorbital edema, Shawl sign, V sign, cuticle changes Fiber invasion rare, perivascular B lymphocytes and CD4+ cells eMononuc. infiltrates, Prifasscicular infiltrates, fiber atrophy

3. Recognize the histologic features of muscle in inflammatory myopathies.

Inflammatory invasion of muscle tissue, esp in perimysium, In DM see mononuclear cell infiltrates, fiber atrophy

4. Recognize the serologic muscle enzyme changes seen in myopathies.

CPK: up to 10-12x normal Aldolase, AST, ALT, LDH Myoglobinuria usually absent Acute phase reactants frequently normal Routine blood tests are normal

5. Know how proximal and distal muscular weakness is manifest and that proximal weakness predominates in dermatomyositis and polymyositis. Lecture 15 Fibromyalgia Dr. Daniel Arkfeld, May 11, 2012 1. Clinical Features
Hallmark: diffuse, chornic muscle pain, profound fatigue (stiff/sore in am), 40% males have sleep apnea Criteria: Widespread pain for more than 3 mo, tenderness to palpation 11 of 17 pts Fatigue, pain, sleep disturbance, stiffness, headaches, irritable bowel, headaches, irritable bowel and bladder syndrome, depression and axiety, depression/anxiety, Represents a continuum of pain and fatigue

2. Approaching a patient with diffuse MSK complains

Is this systemic rheumatic syndrome? Is this endocrinopathy? Is this a toxic/drug rxn? IS this a generalized softtissue pain syndrome?

3. Associated Diseases
Lyme Disease: After treatment, fibromyalgia may occur Ehlers-Danlos Syndrome: CT disease, hypermobility of joints Lupus: common sx Polymyalgia rheumatica: more likely DX when pt >60yo, proximal muscle myalgias and stiffness w/o specific muscle weakness, high ESR, anemia Temporal Arteritis & PMR: prox. muscle tenderness w/o objective weakness, tender right temporal scalp region

4. Characteristics of Inflammatory Dz
Hx: Asso with sig morning stiffness, pain better with movement, insidious onset of pain PE: Objective findings of inflammation (swelling, erythema, warmth, detectable joint fluid), musle weakness, focal neurological abn Lab: ESR and CRP for generalized inflammation, autoABs helpful in selected dos, organ specific tests can suggest internal organ involvement (liver, renal, muscle)

5. Therapy
Goals: keep patient functional in spite of pain Techniques: listen and reassure, educate regarding non-destructive nature of dz, treat depression, emphasize sleep hygiene, regular conditioning exercise program, encourage social interaction and employment For central/neuropathic pain: gabapentin, pregabalin, topiramate, tramadol, substance P blockade, narcotics

Lecture 16 Crystal-Induced Arthropathies Dr. Glenn, Ehresmann, May 11, 2012 1. Identify characteristic crystals associated with arthritis.
Crystal Monosodium Urate Calcium Pyrophosphate (CPP) Hydroxyapatite Calcium Oxalate Crytalline Lipids Crystalized Proteins Crystine Crystals Clinical DO Gout Pseudogout Calcified periarthritis Primary/Secondary Oxalate Gout Cholesterol Emboli Syndrome Cryoglobulinemia Cystinosis

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2. Understand the pathogenesis of hyperuricemia and gout based on the purine biosynthetic pathway and renal handling of urate.
In gout, there is altered metabolism of uric acid which results in tissue deposition of monosodium urate from supersaturated ECFs. Clinical features: arthritis, tophi, kidney stones, nephropathy. Stimulate release of inflammatory mediators arachidonic acid metabolities, IL 1, 6, 8, and TNF Systemic Sx (fever, chills). Major problem lies in purine metabolism: De novo synthesis: substrates, amidotransferease, IMP Purine Degradation: Common pathway via xanthine oxidase (XO) to uric acid excretory product Renal handling: normally there is large renal excretion/smaller gut excretion, solubility is important. In gout, there is overproduction via the de novo pathway (large excretion) or underexcretion with normal purine metabolism can be exacerbated by diuretics and low dose ASA.

3. Understand the pathogenesis and treatment of Ca2+ pyrophosphate deposition dz (CPPD) or pseudogout.
Pathogenesis: normal plasma and urinary excretion of inorganic phosphate, but synovial fluid pyrophosphate elevated. Chondrocytes liberate PP; crystals form in joint fluid and cytokine production increased Can be present in cartilage, unlike gout. First attack tends to be in the knee (patella-femoral joint), self-limited but responds to treatment. Asymptomatic between attacks, low grade fever common with acute attack. CPPD deposition is associated with aging and degenerative arthritides and suspected to be associated with various endocrinopathies, most notably hyperparathyroidism and hemochromatosis. Ca containing crystals appear to activate PMNs in the same manner as MSU crystals. Treatment: does not remove crystals, aspiration of affected joints and corticosteroids helpful, but cannot treat the long-term course of disease.

SPP #3 Crystal Induced Arthropathy 1. Recognize that naturally occurring crystals can cause arthritis. 2. Recognize the relationship between hyperuricemia and gout. All patients with gout are hyperuricemic but not all hyperuricemics have gout. - Understand the relationship between the purine biosynthetic pathway, overproduction of uric acid & gout. Gout patients way have high uric acid production, which leads to deposits. This overproduction stems from the de novo purine synthesis pathway, where there is an over production of IMP, the precursor of uric acid or an over expression of xanthine oxidase, the enzyme that converts IMP to uric acid. - Understand the relationship of increased/decreased excretion of uric acid with the development of gout. If a patient has normal production of uric acid, but decreased secretion, there can be a build up of uric acid which can lead to gout. This is much more common (90% of patients), and thus can be a target of drugs (uricosuric agents) 3. Recognize the difference between treatment of acute inflammation in gout and treatment of the hyperuricemic state. Crystals are taken up by leukocytes which then secrete inflammatory factors, and cause many of the symptoms of acute attack and thus is a good target for therapeutic intervention. For over-producers, it makes sense to treat the production problem through inhibition of the purine synthesis pathway. 4. Identify crystals through their characteristic findings on microscopy. Gout: Parallel yellow, perpendicular blue CPPD: Parallel blue, Perpendicular yellow

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Lecture 17 Pharmacology of Gout Dr. GPK, May 11, 2012 1. Rationale for treating acute gout with colchicine and NSAIDs Relief of inflammation that occurs in response to synoviocyte release of crystal-induced chemotactic factor (CCF), LTB4, prostaglandins and IL-1 after phagoctosing urate crystals. Colchicine: used for acute gout, toxic at high dose, diarrhea, safe at low dose for prophylactic therapy Indomethacin/NSAIDs: less toxic for acute gout, indomethacin not safe for prophylaxis, NSAIDs useful 2. Mechanism of action of uricosuric drugs and allopurinol in chronic gout therapy
Drug Colchicine Mechanism
Inhibits production of CCF Binds tubulin, prevent polym. -/ leukocyte migration Result: release of lactic acid, superoxide, and lysosomal enzymes, production of leukotrience and prostaglandins Inhibit COX and lipoxygenase (anti-lipo most important)

Adverse Effects
Affects rapidly-prolif epithelial cells of GI Diarrhea, nausea, vomiting Transient leucopenia or alopecia Toxic doses: BM depression Toxic in long-term use Aspirin contraindicated inhibits uric acid secretion Contraindicated: gastric ulcer, kidney complications, CHF, hypersensitivity rxn Renal stone formation give with sodium bicarbonate Acute gouty attacks Conraindicated: uric acid overproducers, stones in kidney, lowered GFR, aspirin

NSAIDs
Indomethacin, Naproxen, Ipuprofen, Sulindac

(Glucocorticoids)
Corticotrophin (ACTH)

When NSAIDs ineffective or contraindicated Impair active reabsorption of uric acid from glomerular filtrate which increases its excretion Interferes with other drugs utilizing rnal organ organic acid transport (indomethacin, methotrexate, ampicillin, penicillin) Maintains high blood plasma levels of pencillin G (used in gonorrhea) Sulf has anti-platelet effect, otherwise, Probenecid prefered Analog of hypoxanthine Impairs oxidation of hypoxanthine and xanthine Reduce synthesis of uric acid Use when uricosuric drugs are contraindicated

Uricosuric Agents
Probenecid Sulfinpyrazone

Allopurinol

Long term use: skin rashes Decrease P540 activity

3. Select drugs to treat hyperuricemia based on the patients clinical status

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Lecture 18 X-Rays and Other Imaging to See Kids Bones Dr. White, May 15, 2012 1. Know advantages and disadvantages of radiographs, CT and MRIs
Advantages Radiographs
First modality obtained Differential dx of osseus lesions (bony lesions, dislocations, subluxations, erosions, ST edema, calcifications, effusion) Many benefits including joint space narrowing/erosions Multiple plane visualization Minute details within slices, subtle fractures 3D reconstruction Matrix mineralization Good for image guided injection, arthrogram, bone/doft tissue biopsiesguided RF ablation Excellent for soft tissues ligaments, cartilage, solid or cystic soft tissue masses RF: detected by overlying coil T1: anatomy T2/STIR: pathology PD: cartilage Routine study depending on indication MR arthrogram, MRI w/o and w IV contrast

Disadvantages
Not good and showing soft tissues Ionizing radiation: avoid repeat, protect pt

CT

Adverse rxn to IV contrast agent Dose of radiation more than radiographs (esp in children)

MRI

Subtle calcifications may not be apparent avulsion, subtle calcific tendonitis Correlate with radiographs

Lecture 19 Non-narcotic Analgesics Dr. GPK, May 15, 2012 1. Describe the mechanism of analgesic/antipyretic action of aspirin and acetaminophen 2. Discuss the metabolic basis for acute toxicity induced by these drugs. 3. Select rationalistic therapeutic approach to treat acute toxicity 4. Discuss the relative merits of aspirin and acetaminophen for clinical use.
Dosing and Pharmacokinetics Aspirin Analgesic/antipyretic dose: 0.6g/d Anti-inflammatory dose: 4-6g/d Rapid abs in stomach, b/c pH Hydrolyzed to salicylate by esterase (plasma, liver, RBC) T1/2 aspirin = 15min, salicylate = 2-3h (15h) Renal excretion: not und salicylate, unionized Aspirin irrev. inactivate cyclooxygenase (COX) inhibit synthesis of prostaglandins Sacicylate rev. inhibits COX Mild:10-20g; Severe: 20-30g.d Uncoupling of oxidative phosphorylation (heat production and metabolic rate) in O2 consumption CO2 Metabolic acidosis:lactic acid generation Hyperglycemia in adults G6P activity Acetaminophen Rapid and complete absorption (<1hr) Therapeutic plasma level: 9ug/mL (5-25) 20-50% protein bound in plasma Half life: 2hr at therapeutic doses Liver biotransformation (90%), CytP450 (5%) Renal excretion Weak inhibitory activity against COX in CNS Unknown therapeutic action Analgesic and antipyretic, no anti-inflam. 10-15g cetrilobular hepatic necrosis generation of toxic quinoeimine metabolite by P450 pathwaycellular glutathione accum of intracellular Ca2+ and cell death
Stage 1: initial sx, 2-24h, anorexia, nausea, vomiting, malaise Stage 2: improvement, 2-3d, SGOT, SGPT, bili, PT Stage 3: life-threatening, 3-5d, hepatic necrosis w/ peak abn in hepatic fxn Stage 4: recovery, 7-8d, normal hep fxn

Mechanism of action Metabolic basis for acute toxicity

Therapeutic approach to treat toxicity

Urine alkalization to secretion (NaHCO3) Bicarbonate to correct metabolic acidosis Potassium for hpyokalemia Do not give to childrenwith VZV or influensa

Glutathione synthesis Given 8-10h after ingestion, ineffective after 16h N-acetylcysteine convert to cysteine, precursor of GSH Methionine: same as N-ac., hepatic encephalopathy if given after 16h Cysteamine: GI/CNS tox

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Clinical use, merits

Other Agents

In post-op pain, superior to opiates 1. Gastric irritation, not for ulcer pts 2. Inhibits platelet aggregation, no hemophiliacs, no presurgery, prevent coronary artery dz 3. Displace drug from albumin 4. Hypersensitivity rxn, esp in asthmatics 5. Uricosuric effects 6. Children Reyes syndrome 7. Analgesic and antipyretic activities 8. Good inflammatory activity Diflunisal: 3-4x more potent as analgesic and antiinflammatory agent, no pyretic, osteoarthritis and MSK strains/sprains Methylsalicylate (Ben-Gay): abs through intact skin, topical for muscle/joint pain

1. No gastric complications, Choice analgesic for ulcer pts 2. No effect on platelet aggregation, preferred for hemophil., can be used prior to surgery, not useful for CAD 3. No displacement of drugs from albumin 4. No hypersensitivity rxn 5. No uricosuric effects 6. No association with Reyes syndrome 7. Equal in potency 8. No anti-inflammatory activity

Lecture 20 Artificial Joint Replacements Dr. Donald Longjohn, May 15, 2012 1. Know when surgery is indicated for joint problems Indications for surgery: Pain unrelieved by nonoperative means (Meds, injections, therapy), Reduces quality of life, appropriate surgery available, acceptable risk for surgery Indications for joint surgery: presense of joint dz, level of pain, interference with sleep, impact on function (walking distance, ambulatory aids, ability to perform ADLs) 2. Know the surgical options current available for joint problems. Identify the best surgical option for a patient profile Surgical options for Arthritis: Osteotomy: correct joint malalignment (abn force distribution) by cutting bone and realigning, force on involved surface by redistribution, joint spared but shortens bone Indications: young, active, OA due to malalignment/trauma, cartilage remaining Debridement: remove inflamed synovium and smooth irregular articular surfaces, better if there is a specific lesions that are addressed (degen meniscal tears, loose bodies in knees), not used much now Arthrodesis (fusion of joint): eliminates motion at joint, increases stress on adjacent joints, rarely done Arthroplasty (replacement): resection or total, total is best for pain relief, function and motion, potential for wear, loosening and infection; incidence of THA increasing, most dont require revision Hip surface replacement: big head so less risk of dislocation, metal/metal articulation, Risk of femoral neck fracture (esp older, women) Total Knee (TKA): increasing incidence, more difficult rehab than THA, functioning extensor mechanism is required for good function, not true only lasts 10t (90% chance of 10y, 80% of 20y) 3. Know the contraindications for joint replacement *Active infection, morbid obesity, progressive neurological dz, young age (<45yo) Also: IV drug use, non-ambulatory, non-compliance, neuropathic joints 4. Have a basic understanding of arthroplasty including longevity, limitations and complications. Complications of THA: Infection, Nerve damage, DVT (40-70%), PE, average mortality Complications of TKA: Infection, DVT, PE Great chance of lasting 10-20ys (~85%) Lecture 21 Foot Pathophysiology and Mechanics Dr. David Thordarson, May 15, 2012 1. Gain familiarity with the mechanism of injury, clinical findings, and basic treatment of ankle sprains Mechanism of Injury: inversion which in plantarflexion Physical Exam: Edema, tenderness, ecchymosis, possible tenderness medially or above ankle Treatment: RICE Relative Rest (ace wraps, elastic wrap, air casts, brace), Ice, Compression, Elevation
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2. Become familiar with pathoanatomy, physical examination, and treatment principles of bunions Hallux Valgus: deviation of big toe away from midline, bunion-prominent medial eminence, not exostosis Pathogenesis: Female:Male 8:1 with variable genetics, associated with high heeled, narrow toes shoes PE: prominent medial eminence, tenderness to palpation, radiographs-splaying to first 2 MTs& hallux Treatment: wide shoes, low heels, stretch leather over bunion Surgical: only indicated for pain, osteotomy (braking bone), prolonged disability 3. Understand pathogenesis and basic treatment principles of diabetic foot ulcers Pathogenesis: secondary to excess pressule, neuropathy and vasculopathy PE: skin integrity, erythema/drainage, pulses, sensation, peripheral neuropathy Treatment: debridement of callus and non-viable tissue, antibiotics as needed for infection with total contact casting to decrease pressure and shear across ulcer site; after ulcer heals, custom orthorics, surgical revascularization as indicated 4. Understand pathoanatomy, clinical findings, and treatment of plantar fasciitis Pathogenesis: inflammation/microscopic tearing of plantar fascia, 50% have spur PE: pain worst in morning, gradually improve, pain upon starting walking after sitting, point tender of medial calcaneal tubercle, 80% overweight/obese, tight calf muscle, inability to dorsiflex Treatment: Adress overuse (lose weight, crosstrain, job modification), calf stretching, NSAID, heal orthotic (heel cup, pad), warm soak with/without Epsom salt or contrast bath, PT, night splint Lecture 22 NSAIDS Dr. GPK, May 16, 2012 1. Describe the mechanism of anti-inflammatory actions of NSAIDs. Inhibit COX (prostaglandin H synthase) that converts arachidonic acid to endoperoxides, inhibiting production of prostaglandins, prostacyclins, and thromboxanes. Some non-aspirin NSAIDs also inhibit lipoxegenase, inhibiting leukotriene production. At inflammatory doses (high), they effect the leukocyte membrane and prevent activation. 2. Discuss various side effects induced by prolonged treatment with NSAIDs.
1. Inhibition of platelet function (due to COX-1 inhibition): inhibit platelet agg, BT by thromboxane synthesis 2. Gastric Ulceration and bleeding
Direct Acid effect: NSAIDs are organic acids with low pKa, upon absorption, the drugs ionize at intracellular pH, leading to accumulation of ionized drug in stomach mucosa local irritation (Prevent: buffered aspirin to reduce abs in stomach, enteric coated tablets Inhibition of gastric cytoprotection: PGE2 & PGI2 synthesis (promote mucus, HCO3- secretion) (Prevention: misoprostol (PGE1 analog), Omeprazole (proton-pump inhibitor), COX-2 inhibitors (do not decrease cytoprotection)) Prolongation in GI bleeding: inhibit platelet aggregation and prolong BT

3. Hypersensitivity Reactions (due to COX1 inhibition): 10-15% of pts with asthma 4. Alteration in Renal Function (due to COX2 inhibition)
Renal toxicity: renal blood flow and glomerular filtration rate in pts with CHF or hep atic cirrhosis with ascites, enhance nephrotoxicity of aminoglycosides, cisplatin, cyclosporine Edema: retention of salt and water, PG-induced inhibition of reabs of Cl- and action of ADH

5. Effect on reproductive tissue (due to COX2 inhibition): ovulation, fertility, prolongation of gestation 6. CNS disturbances: tinnitus, decreased hearing, vertigo reversible

Non-aspirin NSAIDs: Hepatic toxicity, blood dyscrasias, aplastic anemia, agranulocytosis 3. Describe some properties of non-aspirin NSAIDs including COX2 inhibitors. Selective COX-2 inhibitors (celecoxb, rofecoxib) are as effective as NSAIDs as anti-inflammatory agents but cause lower GI irritation and disturbance of platelet function. Clinical uses: OA, RA, acute pain, dysmenorrheal, familial adenomatous polyposis. Side effects include prothrombotic activity due to decreased synthesis of prostacycling (vasodilator)

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4. Select the appropriate NSAID to treat rheumatoid arthritis patient.

Drug Indomethacin Dose (mg/d) 100 t1/2 (hrs) 2-11 Comments/Uses
Most potent inhibitor of COX (100x aspirin), more severe CNS side effects Limited uses in RA; used in acute gout and osteoarthritis Used to treat patent ductus arteriosis in neonates Used as tocolytic agents, halt progression of labor Prodrug (sulfoxide) in administered form, sulfoxide poor COX inhibitor, cause less GI irritation/bleeding; In liver, reduced to active sulfide Sulfide form is strong inhibitor of COX (500x) Sulindac is secreted into bile and reabs, enterohepatic recirculation Sulfide metabolite is not secreted into biled longer t1/2 Inactive sulfone excreted by kidney, useful in pts with kidney problems Minimal effect on platelet aggregation No displacement from albumin, used w/ warfarin, hypoglycemic agents Shorter t1/2, incidence of anaphylaxis than other NSAIDs SEs, Displace aspirin from albumin, less action along with aspirin Better than aspirin for dysmenorrheal No interaction w/ warfarin or hypoglycemia agents Lesser GI complication Equipotent to aspirin in inhibiting COX 20x more potent than aspirin in inhibiting COX Potent inhibitor of leukocyte migration Equipotent to aspirin in inhibiting COX One dose/day (favor compliance) Potentially dangerous in elderly accumulation risk Higher incidence of GI ulcers, some with major bleeding As potent as indomethacin in inhibiting COX, treated for few days at a time No inhibitory effect on platelet aggregation Diarrhea is a common SE

Sulindac

400

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Tolmetin Profens: Ibuprofen Naproxen Fenoprofen Piroxicam Meclofenamate

1600

2400 750 2400 20 400

2 13 2 50 2

Lecture 23 Non-neoplastic Diseases of Bones, Joints, and Connective Tissues Dr. Cosgrove, May 16, 2012 1. Define and use in context the following terms: arthritis: swelling of the synovium arthralgia: joint pain effusion: escape of fluid involucrum: new bone resorption monostotic: one bone involved osteoblasts: mononuclear, secrete procollagen, alkaline phosphate rich osteoclast: multinucleate, resorb bone osteocyte: mononuclear cells in lacunae osteoid: type 1 collagen layed down by osteoblasts osteopenia: low bone mineral density osteophyte: new bone osteoporosis: Decrease in total bone mass w/ microarchitectural deterioration pannus: marked hyperplasia causing flap pathologic fracture: fracture due to erosion or other pathology polyostotic: multiple bone involvemnet rheumatoid nodule: central necrosis, palisading histiocyte, chr. inflam sequestrum: bone necrosis synovitis: swelling of the synovium tophus (pl. tophi): soft tissue depositing that occurs in gout

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2. Identify the (most common) etiology, and discuss the significant clinical and pathologic features for each of the following disease states:
Etiology Congenital Diseases Deffective synthesis/ Osteogenesis secretion of pro-collagens Imperfecta
4 forms: AD most common, AR more rare/lethal

Clinical Features
Fratures early in life Improper healing Short statures Abn collagen affects sclearae (blue), ligaments, teeth Short, curled bones Dwarfism, normal dev of ribs/skull, but long bones fail to elongate Nerve compression, marrow impingement with anemia, tcp, susceptibility to inf. Tall stature, arachnodactyly, lax ligaments, ectopia lentos, mitral valve prolapse, cystic medial necrosis of aorta Fever, pain, limp

Pathologic features Abn osteoid matrix

Achondroplasia AD, dwarfism

Pt mutation in FGFR3 Suppressed cartilage production at epiphysis Rare Decreased osteoclastic reabs Bones enlarged but brittle AD, risk w paternal age Mut in fibrillin gene FBNI, affects tissue with high elastic content Children, young adults, previously healthy Related to trauma Bac: S. aureus, Some fungal, salmonella in sickle cell pt Enter via blood, contiguous spread or trauma Complication of acute osteomyelitis

Osteopetrosis

Enlarged, dense vertebra on Xray Aorta, CT degenerating

Marfan Syndrome

Infections of Bone

Acute Pyogenic Osteomyelitis

Acute inflammation: Abscesses Bone necrosis: Sequestrum Reactive new bone: Involucru m Acute and chronic inflammation Involucrum and Sequestrum Draining sinuses to skin 2 amyloidosis, Squamous Cell CA Necrotizing granulomata, chronic inflam AFB stain oft (+) Thinned cortical and trabecular bone, normal structures, changes often subtle Bone trabeculae with thick seams of periph. osteoid

Chronic osteomyelitis

Ulceration and necrosis

TB of bone

Immunosuppressed pts, developing nations

Gradual onset, fever, weight loss Spine commonly effects (Pott dz) X-Ray: Bone destruction, soft tissue masses 1: aging, females, whites, idiopathic 2: Immobilization, endocrine d/o, drugs, malnutrition, malabsorption All bones affected, sx in weight-bearing bones Fractures, height, deformity, pain Softe, weak bones, fracture easily Soft weak bones, fracture easily Deformities due to epiphyseal disruption

Metabolic Bone Disease in total bone mass w/ Osteoporosis

microarchitectural deterioration Bone loss that produces sx

Osteomalacia Rickets

Structural abn of bone due tp defective osteoid min. due to Vit D deficiency Osteomalacia in children

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Etiology Bone Diseases of Unknown Cause Anglos, 3-10% of US pop, Pagets over 40yo Disease
Monostotic or Polyostotic

Clinical Features
Pain, deformities, fractures Serum alkaline phosphatase Enlargement, deformity of aff. bones Stages: 1.Lytic: Irreg. bone resorption 2.Mixed: Irreg bone form active osteoblasts/clasts very vascular bone 3.Sclerotic: bone enlarge., osteoblastic act. Monostotis: 70%, single bone aff, incidental X-ray finding, pain, deformity, fractures Polystotis: 30%, mult bones, with craniofacial involvement, pain, disfigurement, deformity, fractures, 510% with assoc abn (ex.Albright synd)

Pathologic Features Irregular, thick trabeculae, prominent cement lines

Fibrous Displasia

Replacement of localized bone areas by abn prolif of fibrous tissue and irreg arranged woven bone

Radiologic: well-demarcated, lucent, ground glass lesion Gross: expansion of medullary space by grey-tan tissue, cortex intact Histo: mature fibrous tissue w/ admixeds woven trabec.

Joint Disease Pyogenic arthritis

TB Arthritis

Developing countries

Single, large joint Pain, warmth, erythema Fever, chills, high WBC Synovial fluid: PMNs, gram stain +, culture s. aureas usual cause Single, large joint, swelling, pain, minimal warms/erythema Synovial fluid: PMNs, lymphs, +AFB

Hyperplasia, acute inflammation of synovium

Rheumatoid Arthritis

Auto-immune disease

Hyperplasia, acute chornic inflammation, granulomata, necrosis, +AFB Synovium: Marked hyperplasia (pannus), lymphs, plasma cells, M0, lymphoid follicles, fibrin
Rheumatoid nodules: central necrosis, palisading histiocyte, chr. inflam

Crystalinduced arthritis Osteoarthritis

Gout, old mine, increased serum Uric Acid

Acute: MSU crystal deposit in synovium, sudden, severe attacks of pain, Fluid has PMNs, needle-shaped crystals Chr: large masses of MSU, tophi in soft tiss.

Primary: aging Secondaty: trauma, congetnial anomalies

Aff. weight bearing joints, fingers (Herberden nodes) Synovium: Mild hyperplasia, chr inflammation Early: fissures, clefts, uneven loss and prolif of chondroc. Late: cartilage loss, osteophyte formation, deformities

3. List the major microbiologic agent(s) responsible for acute pyogenic osteomyelitis, infectious arthritis, Lyme disease and Pott disease. APO: S. aureus, fungus in immunosuppresed Inf arthritis: S. aureus, neisseria, strep, H. influenza, other gram (-) Lyme: Borrelia burgdorferi Pott dz: Tuberculosis 4. Presented with an image and appropriate background information, identify the gross and/or microscopic appearance of the following conditions: See above chart acute pyogenic osteomyelitis osteoarthritis (DJD) Pott disease fibrous dysplasia Paget disease rheumatoid arthritis Lecture 24 Biomechanics of Fractures Dr. Lee, May 17, 2012 1. Understand the factors that contribute to fractures. Strength of bone metabolic, structural, modality of force applied, age effects 2. Understand the factors that contribute to fracture healing Metabolic (nutrition, smoking, NSAIDs) and local biology (blood supply from surrounding soft tissues)
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3. Understand principles of fracture treatment. Restore axial alignment, anatomy, and pre-injury state as quickly as possible 4. Understand complications of fractures. Non-union: arrest in the healing process, sclerosis at bone ends Hypertrophic: bones and ends viable, build up fo callous Atrophic; vascularity compromised, bone degenerates at break Other complications: Adult Respiratory Distress Syndrome (ARDS), Fat emboli, PE, compartment syndrome, nerve injury, vascular injury, injury to soft itssue SPP #4: Low Back Pain Dr. Abbott, May 17, 2012 1. Describe at least 3 differences between todays humans and our ancestors, and between humans and other primates that help explain why humans are predisposed to back pain. Our ancestors were hunters and gatherers and evolved for this lifestyle. We are sedentary today. We have a lordotic curve of the spine while other primates are arched. We walk bipedally 2. Describe at least lifestyle 5 factors that lead to back pain in Americans today. Excessive sitting, poor sitting posture, static posture, way people lift/carry, way people walk/run 3. List and describe the 6 most common etiologies of low back pain. Muscle of ligamentous strain (usually from acute injury) Disk degeneration or rupture Osteoarthritis Vertebral fracture or collapse (freq in older persons with osteoporosis) Psychosocial factors (hysteria, malingering, etc) Spinal stenosis 4. In addition to #2 above, list 4 serious causes of low back pain that must be ruled out in any case of low back pain, and describe 2 or 3 signs or symptoms (red flags) for each cause. Neoplasm, Infection, Metabolic problems, Extrinsic diseases (ie aortic aneurism) Red Flags: AGE > 50 y.o. or < 20 y.o., History of cancer, Constitutional symptoms, IV drug abuse, Immune suppression, Recent infection, Pain worse at night, Trauma, Progressive neurologic symptoms 5. List the specific symptoms and signs of compression/compromise of specific L-S nerve roots.
Screening Exam Strength Sensory Reflexes Pain L4 Squat and Rise Weak extension of leg at knee Numbness at knee Loss of knee-jerk reflex Along front of leg L5 Heel Walking Weak dorsiflexion of foot Numbness at web of big toe, lateral calf No reflexes lost Along side of leg L6 Walk on toes Weak plantar flexion of foot Numbness along back of calf, lateral foot Loss of ankle jerk Along back of leg

6. Describe at least 4 psychosocial issues that may be associated with back pain. Depression, Anxiety, Hypochondriasis/Hysteria, Acute remunerative back pain Lecture 25 Clinical Applications of the Spine Dr. Smith, May 17, 2012 1. Learn the basics of a neurological examination for acute spinal cord injury (SCI) Motor exam: diaphragmatic breathing indicates intact C4 5 Upper and 5 lower extremities groups; Strength tested 0-5
C5- Shoulder abduction/elbow flexion, bicep reflex C6- Elbow flexion/wrist extension. bracioradialis reflex C7- Elbow extension/ wrist flexion. triceps reflex C8- Finger flexion T1- Hand intrinsics L2 L3 L4 L5 S1 S2 Hip flexion Knee extension Ankle dorsiflexion, patellar reflex Great toe extension Ankle PF/ eversion/hip extension, Achilles reflex Knee flexion

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2. Understand complete vs. incomplete SCI and the syndromes associated with incomplete injuries Complete: loss of motor/sensory function below the injury level Incomplete: preserved motor and sensory function below the injury level
Central cord syndrome: central gray matter destroyed, white preserved, extension injury in arthritic C-spine o Present with quadriplegia with preserve perianal sensation o UE>LE involvement UE flaccid and worse deficit o Good prognosis Brown-Sequard Syndrome: hemisection, penetrating injury (GSW or stab wound) o loss contralateral pain/T o loss of ipsilateral ipsi motor and light touch propioception o most recover ambulation, bowel, bladder Anterior Cord Syndrome: pressure on anterior cord or infarc o loss of motor and pain/T sensation o preserved light touch and proprioception (dorsal column) o poor prognosis if no sacral sensation to pinprick after 24h Posterior Cord Syndrome: very rare o loss of light touch, propioception o motor, pain, T intact o foot slapping gait from loss of propioception Cauda Equina Syndrome: space occupying lesion within L/S canal o disc herniated, tumor, epidural hemotoma, epidural abscess o Sx: saddle anesthesia, lower ext. pain, sensorimotor loss, bowel-bladder dysfunction o Surgical emergency decompress ASAP

3. Be able to distinguish the clinical and radiographic differences between the basic spinal compressive pathologies
Cervical Myelopathy: disease of spinal cord, symptoms of hand clumsiness or gait instability Characterized: clumsiness of hand and gait imbalance Etiology: degen spondylosis, congenital stenosis, ossification of posterior longitudinal ligament, tumor, epidural abscess, trauma, kyphosis Pathophysiology: disc dehydration, annular tears, herniated disk, disc narrowing, posterior spurs Clinical: neck pain, coordination/dexterity loss, balance/gait abn, sensory changes (diffuse numbness, tingling), bladder/bowel dysfunction Neuro Exam: tandem gait testing, reflex testing (UE variable, LE hyperreflexic), disinhibition of reflex arc, Hoffmans sign, Babinski+, Ankle clonus Not dx by radiograph, MRI contraindicated, myelomalacia is bright on T2, signal change on T1 is bad prognosis Cervical Radiculopathy: spinal nerve compression which follows a dermatome and may be associated with weakness numbness and hyporeflexia Etiology: cervical spondylosis, disc herniation Clinical: occipital headache, pain in neck, shoulder, arms, parasthesisa, weakness or clumsiness Neuro exam: Spurling test, hyporeflexia May have referred pain or other MSK pathology Lumbar Radiculopathy: dermatomal pain usually radiating below the knee and may be associated with weakness numbness and hyporeflexia Etiology: disc herniations and synovial facet cysts Clinical: axial back pain, radicular pain, neurogenic claudication Neuro Exam: straight-leg raising test (esp L5, S1), Femoral stretch test (L2-4), motor weakness, absent reflexes L4-5 Hern disc: shooting pain with numbness in the great toe, worse sitting/driving Lumbar Spinal Stenosis: narrowing of spinal canal Etiology: spondylolithesis (slippage of vertebrae), fact osteophytes, disc herniations, synovial cysts, hypertrophy of ligamentum flavum Clinical: 50+yo, back and leg pain, +/- radicular distribution, burning/tightness in buttocks (walking) Neuro: induced with exercise, loss of DTR, muscle weakness, SLR rarely+ Consider coexisting Dx

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SPP #5: Shoulder Injury and Elbow Injury Dr. Abbott, May 17, 2012 1. Describe the location and function of the rotator cuff muscles of the shoulder. See Right 2. Describe the 2 most common etiologies, and the basic pathophysiology of impingement syndrome. List signs and symptoms. Most common site of pathology: suprapinatus tendon Rubbing/compression of the tendon under surface of the arch (coracoids-coracoacromial ligament-ant. acromion). Onset is indidious or sudden. Pain in the lateral upper arm, may radiate distally, worse at night disrupting sleep, worse with reaching overhead. Increasing weakness or stiffness. On exam, tenderness to forceful palpation just inferior to the acromion. Pain is at subacromial front (vague) of the shoulder with radiation to the deltoid insertion. Epidemiology: <30yo: shoulder instability >40yo: chronic rotator cuff/supraspinatus tendonitis >60yo: partial and full-thickness tears of the supraspinatus tendon and OA common 3. Describe anatomical site and pathophysiology of lateral epicondylitis. Extensor carpi radialis brevis 4. List signs and symptoms and differential of elbow lateral epicondylitis Signs and Sx: sharp pain brought on by gripping, carrying brief case, tenderness over lateral epicondyle (no warmth/swelling), normal range of motion, DDx: Lateral epicondylitis (tennis elbow), Medial epicondylitis (golfers elbow), Other ligamentous injury, Trauma,
Arthritic/inflammatory process, Neuropathy

Lecture 26 Orthopaedic Soft Tissue Injury and Sports Medicine Injuries Dr. Vangsness, May 17, 2012 1. Understand the structure & function of collagen in soft tissues Collagen maintains structural integrity of soft tissues 2. Be familiar with three common soft musculoskeletal tissue injuries 3. Appreciate the healing/surgical treatment of these tissues as it pertains to the athlete/high demand pt 4. Know the Treatment Plans for These Common Injuries
Function Injury/Healing Meniscus Load-bearing, shock absorption, joint stability and lubrication Very painful Poor healing (periph vascularity) Arthritis dev w/o intact men. Transplant with cadaver men. Suture if peripheral Ligament tensile and viscoeleastic properties, effects of age Failure from load deformation and stress/strain, L ~10% Common injury of ACL ACL: Non-op (brace, rehab) Op if high demand/young pt Shoulder: non-op unless 20-40yo Tendon Tight collagen bundles and tensile strength, Pathology from age-related changes, function to move muscles/bones, pain Rotator cuff (<50yo) Non-op: PT to motion/strength If PT fails, surgical correction

Surgical & Trtmnt Plan for demand pt

SPP #7: Knee Pain Dr. Hatch, May 17, 2012 1. Obtain an appropriately focused history in a patient with a knee injury. Mechanism of injury and type of pain important 2. Describe the functional anatomy of the knee joint. Ligaments exist to protect menisci and menisci exist to protect articular cartialge
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3. Describe the typical symptoms of meniscal and ligamentous injury.

Meniscal Injury: twisting or quick stop, sever pain, locking, clicking, catching sensation; knee locks in flexed position, giving way/buckling, immediate swelling and difficulty walking immediately following Ligamentous: inappropriate movement of tibia, snap or pop at injury, giving way/buckling, continued participation in activity after injury

4. Describe the physical examination of the knee joint.

Lachman test: knee at 20-30 deg, stabilize left femer and pull tibia (ACL) Ant/Post drawer: knee at 90deg and try to displace tibia ant or post (ACL/PCL) Pivot Shift/Valgus Laxi: recreate climnical sx of instability (ACL) McMurray: audible or palpable click or clunk by simultaneously flexing/extending knee while internally/externally rotating (meniscus tear, patellofemoral problem) Joint Effusion: degenerative or post-traumatic arthritis, inflammatory dz, subluxing patella, overexertion Patellofemoral crepitation: asymptomatic, PF subluxation, chondromalacia patella, degen joint dz

5. Describe the physical findings associated with the meniscal and ligamentous injuries of the knee.
Patellofemoral o Inspection o Palpation o Can give feelings of instability ACL Stability Tests o Lachman o Anterior Drawer o Pivot Shift PCL Stability Tests o Posterior Drawer o Posterior Sag Collateral ligament evaluation o MCL- Valgus stress test o LCL Varus Stress test Meniscus Evaluation o Joint Line Palpation o McMurrays o Bounce Test

6. Describe other knee conditions that may mimic meniscal or ligamentous injuries to the knee.
Chondromalacia Patella, Subluxation, Dislocation can present with medial joint pain and giving way of the knee. An increased Q-angle, + Apprehension test, PF stress with pain and crepitation and X-rays lead to this diagnosis. Loose Bodies in the knee joint can cause "clunks and clicks" and "buckling" of the knee. P.E. and X-rays, and, if necessary, arthroscopy will aid in the diagnosis. Bursitis - both pes anserinus and medial collateral ligament bursitis present with medial joint pain. But the pain is very localized to these structures and a diagnostic injection of local anesthetic will confirm the diagnosis by complete, temporary, relief of pain. Tendonitis - Patella and Popliteal tendonitis and Iliotibial "Band" Friction Syndrome are seen in runners and are differentiated by their locality and relation to specific sports activity.

7. Describe the MRI findings of meniscal and ligamentous tears of the knee joint.
Shows tear (white) in damaged structure

8. Outline the treatment for meniscal and ligamentous tears of the knee joint.
Conservative treatment with PT and a brace, arthroscopic meniscal repair/excision followed by PT or arthroscopic meniscal repair/excision plus ACL recontrustion followed by PT and a brace.

9. Describe rehabilitation after a knee injury.

Depends on patients desires for his life. Can be very intense or moderate

Lecture 27 Bone and Joint Infections I Dr. Holtom, May 18, 2012 1. Understand the pathophysiology of infectious arthritis.
Enter the joint from the bloodstream, from a contiguous site, or from direct inoculation (trauma, surg) The course of infection: Organisms enter joint space, adhere to cartilage Neutrophils enter joint space and synovial membrane Damage to cartilage within 48h - pressure, bacterial toxins, leukocyte proteases and inflammatory cytokines, invasion of cartilage by bac/inflam cells Cartilage destruction leads to joint space narrowing, further erosive damage to cartilage, possible extension to bone and soft tissue

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2. Know the common microbiologic causes of infectious arthritis.

Common Bacteria: 50% S. aureus, 20% Strep (mainly pyogenes), 5% H. influenza, 4% E.coli, 3% Neisseria gonorrhea (rare in practice) Less common: TB (common worldwide), B. brugdorferi (lyme dz), treponema pallidum, brucella Fungal: Coccidioides immitis, sporothrix schenckii (rose thorns), candida, Cryptococcus Viral: Parvo B19, rubella, HIV, HTLV-1

3. Know the appropriate antibiotic therapy for infectious arthritis.

Debridement followed by systemic 3rd gen cephalosporins +vanco for 2-4wks

4. List the common microbiologic causes of osteomyelitis.

Its always Staph aureus, really depends on etiology (Salmonella in sickle cell pts)

5. Understand the principles of antibiotic therapy for osteomyelitis.

Depends on clinical situation and cultures, generally give antibiotics for 4-6wks

6. Be familiar with the clinical findings, microbiologic causes, and therapies of special types of OM.
Vertebral OM Clinical findings Non-specific back pain Low grade fevers Prolonged illness (sev months) Adjacent vertebral bodies affected Fever +acute, sev. sacral pelvic pain OM of adjacent bones + Blood cultures Distal tibia w/ single lesion, <25yo Acute, subacute fever, pain) or chronic (afebrile, chr. dull pain) Microbiological Cause S. aureus (50% Enterics (E.coli) 25% IVDA: MRSA, P. aeruginosa, Serratia spp Mycobac TB Potts Dz S. aureus Gram (-) bacilli in IVDA S. aureus Therapies Antimicrobials for 4-6wks No debridement unless epidural abscess found Spine stabilization as needed IV Antibiotics for 4-6wks Surgery usually not necessary

Sacroiliac joint infection Brodies Abscess

Lecture 28 Bone and Joint Infections II Dr. Zalavras, May 18, 2012 1. Understand the diagnostic features and treatment of septic arthritis
History of predisposing factors, fever and chills, painful, swollen, red joint with limited motion, and joint effusion. Imaging studies show early soft tissue swelling and later joitn narrowing which signifies carialge destruction. Laboratory Exams include CRP (most reliable), sed rate, WBCs (50%), (+) blood cultures (50%). Synovial fluid analysis shows thick and cloudy fluid with PMNs and (+) cultures. 2. Know the complications that occur from septic arthritis. Cartilage destruction, pain and loss of function, degenerative arthritis, avascular necrosis of femoral head, subluxation and dislocation, and recurrent infections.

3. Explain the adverse role that biofilm plays in infections.

Biofilm protects the organism from antibiotics and host defense mechanisms including AB formation and phagocytosis. It allows the infection to exist in a subclinical state and to recur.

4. Describe the anatomic and physiologic classifications of osteomyelitis

Anatomical: Type I - medullary Type II - superficial Type III - localized Type IV diffuse (bone unstable) Physiological: A Host normal B Host Immunocompromised (systemic or local) C Host Treatment not indicated

5. Understand the diagnostic features and treatment of osteomyelitis.

Acute exudative inflammation, increased vascularity, pain of the bone, edema, PMNs. Lab values: WBC, ESR and CRP, + blood cutlreus, bone aspiriration/biopsy, X-rays show periosteal elevation after 7-10d, and late cortical and marrow destruction.

6. Describe the principles of debridement, local antibiotic therapy, soft tissue coverage, and bone grafting.
Surgical debridement to remove all necrotic bone and soft tissue Culture specimens of pus, soft tissue and bone + Sytsemic and/or local antibiotic therapy Fracture stabilization if necessary Soft tissue coverage, as vascularity improves healing Bone grafting to provide scaffold for new bone

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Lecture 29 Pediatric Orthopaedics Dr. Choi, May 21, 2012 Prequiz (Or, important points!) 1. Name three differences between adult and pediatric bones Children have a physis (growth plate), a thick periosteom and a more porous cortex. 2. Name three fracture patterns unique to children Bending pattern Buckle pattern (torus) Greenstick fracture (incomplete) Complete (typical in adults) Children have GREAT ability to remodel 3. What is the most common operative fracture in kids Supracondylar humerus fractures from falling with outstretched hand Lecture Objectives: 1. Understand the basics of fracture disease in children.
Plastic deformation (or bowing/bending), torus (or buckle) fractures, and greenstick (or incomplete) fractures are fracture patterns unique to growing child/adolescent.

2a. Now the natural history of knee alignment from birth to age 7y? During normal development, children are bow legged, and then become knock kneed. Special shoes or wedges make no difference b. Most common causes of in-toeing (pidgeon toes)?
Natural history: Out-toed and birth, then in-toed until 10y Causes: 1. Metatarsus adductus: foot deformity in 1st year of life, spontaneous resolutions by 2-4yo, curved foot 2. Internal tibial torsion: common 1-3y, expect spontaneous recovery by 4yo 3. Femoral anteversion: femur twisted internally (knees internally rotated), present at birth, sit in W position, resoved to normal adult values by 8-10y

c. Know that rotational problems require surgery in only 0.1% of cases 3. Identify 2+ causes of limping in the growing child/adolescent slipped capital femoral epiphysis (SCFE) and Legg-Calve-Perthes (LCP) Disease. Understand the disease, epidemiology, natural history, and basic treatment principles for SCFE, LCP, and scoliosis.
SCFE
Disease Clinical Presentation Causes
Physis widens, leads to slippage of the femoral head posteriorly Present w hip, thigh or knee pain PE: obligate ext rotation Xray: slipped off like ice cream Unclear exact cause Obesity, Af.Am., delayed bone age, certain endocrinopathies, renal osteodystrophy Most common adolescent hip pr Adolescent boys, 10-16yo 10-15% bilateral Early arthritis

LCP
Idiopathic avascular necrosis involving the femoral head Limp, w groin hip, thigh or knee pain usually activity related XRay: flattened femora head w partial disloc Unknown. Temp disruption of blood supply

Scoliosis
Abn lateral curvature of the spine Uneven shoulders, Prominent shoulder blades, Uneven waistline, Lumbar prominence, Leaning to one side Unclear, genetics?

Epidemiology Natural History Basic treatment principles

Boys (4:1), 4-8yo (1:2000 kids) 10% bilateral Good long term prognosis, younger = better Spontaneous improvement <6-8y Concern for early arthritis 50% need hip replacement by 50y Conservative, non-op activity mod, antiinflammatories, PT Rarely: surgical repair

2-4% adolescent, ages 10-16

Large curves may affect growth Measurable diff of pulm at 20 >80-100 may affect heart/lungs <25:Observation 25-40: Bracing, growing child <50: Surgery

Prevent further slippage Surgery: pinning/screwing

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SPP#5:Carpal Tunnel Syndrome Dr. Cantwell, May 17, 2012 1. Obtain a focused history on a patient complaining of numbness of the fingers. PQRTSA of the pain/numbness. Look at nervous and vascular systems. Also could be affected higher up (brachial plexus, pressure on subclavian artery) 2. Describe the causes of CTS. Injury to carpal bones, thickening of tendons or bursa 3. Describe the risk factors leading to CTS. 1. Space occupying lesions- recent or old wrist fracture, infection, local edema, ganglion or lipoma, aberrant muscle belly, foreign body, flexor tenosynovitis (such as seen with rheumatoid arthritis). 2. Systemic conditions - pregnancy (fluid retention), obesity, diabetes, thyroid dysfunction, arthritis, amyloidosis. 3. Overuse Syndromes - postural habits of the wrist joint which produce forced flexion or extension positions, constricting bands or bandages around the wrist. 4. Describe the symptoms and signs of CTS. Glove of numbness/tingling, worse when wrist flexed Pain of median nerve due to hypersensitivity Thenar muscle atrophy Decreased sensation to light touch/pin prick over median nerve 5. Perform the pathognomonic tests to diagnose CTS (Phalen's sign, Tinel's sign). Tinels: place pressure on median nerve under Palmaris longus tendon if pain, + Phalens: fully flex wrist (against other wrist), if positive, numbness/tingling 6. Be familiar with the differential diagnoses in CTS.
Carpal Tunnel Syndrome Cervical radiculitis/radiculopathy Peripheral neuropathy Brachial plexopathy Thoracic Outlet Syndrome Occlusive Vascular Disease

7. Describe the electromyographic and nerve conduction findings found in CTS. Can show just how bad the CTS is. Shows increase in the distal median sensory latency time and distal median motor conduction time at the level of the wrist and early denervation of the thenar muscles. 8. Outline the non-operational and surgical treatment of CTS. Non-op: splinting to remove pressure, NSAID, steroid injection into carpal canal Surgical: remove pressure in carpal canal Lecture 30 Overview of Hand Surgery Dr. Stevanovic, May 21, 2012 1. Obtain a general overview of hand surgical problems and an approach to the field of hand surgery. Dont touch nerves. Make sure there is a collateral circulation. Zones of tendons at right. Infection: 4 signs on Kanavel: * Slight flexion of finger * Fusiform swelling * Tenderness along flexor sheath * Pain with passive extension 2. Have a basic knowledge of hand anatomy. Study gross anatomy 3. Understand a basic concept of hand evaluation Determine what structure is maintained in order to determine what can be done.

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