5 musculoskeletal high yield

Musculoskeletal and Connective Tissue Stephen Bagley, M.D Resident Physician, University of Pennsylvania MUSC1_1MS01- Musculoskeletal System: Dermatology Anatomy, physiology, and disease of: – – – – – Skin Muscles and ligaments Peripheral nerves Bones Connective tissue MUSC1_1MS01- Musculoskeletal and Connective Tissue Lecture - Dermatology MUSC1_1MS01- Skin layers from surface to base Epidermal layers: Basement membrane C – Stratum corneum L – Stratum lucidum G – Stratum granulosum S - Stratum spinosum Stratum basalis B – Stratum basalis Mnemonic: Californians Like Girls in String Bikinis Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane C – Stratum corneum • Top layer • Continuously sloughed off Stratum basalis • Composed of keratin filled anucleate cells • Calluses: stratum corneum hypertrophy Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane L – Stratum lucidum • This layer is only found in thick skin (e.g palms and soles) Stratum basalis Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane G – Stratum granulosum Stratum basalis Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane S - Stratum spinosum Stratum basalis Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane B – Stratum basalis • Home to stem cells Stratum basalis Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Basement membrane: • Separates the epidermis from the dermis en:wp, commons.wikimedia.org Used with permission FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- 10 Myositis Disorders • Characteristics: • Ongoing inflammation of the muscles • Labs: • ↑ Creatinine kinase levels FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450 MUSC6_4- Polymyositis • Characteristics: • Inflammation of multiple muscle groups • Progressive and symmetric • Proximal muscle groups affected the most (e.g hips and shoulders) • Etiology: • • CD8+ T-cell injury to myofibers Histology: • • Endomysial inflammation, within muscle fibers Labs: • ↑ Creatinine kinase levels Muscle biopsy on H&E showing endomysial inflammation Polymyositis HE.jpg, commons.wikimedia.org Used with permission FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450 MUSC6_4- Dermatomyositis • Characteristics: • Inflammation of multiple muscle groups • Proximal muscle groups affected the most (e.g hips and shoulders) • Histology: • • Perivascular (perimysial) inflammation, within muscle fibers Labs: • ↑ Creatinine kinase levels • ↑ Aldolase levels Perimysial inflammation Dermatomyositis – high mag.jpg, commons.wikimedia.org Used with permission FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450 MUSC6_4- Dermatomyositis: Signs and symptoms Signs/symptoms: • Heliotrope rash (periorbital) • “Shawl and face” rash • Gottron’s papules develop on the dorsal fingers, over joints • “Mechanic’s hands” (i.e callused hands) Other characteristics: • ↑ Risk of malignancy (e.g colon and ovarian cancer) • Antibodies: • ANA (sensitive yet non-specific) • Anti-Jo-1 (very specific) • Copyright Richard Usatine, M.D Used with permission • Copyright Richard Usatine, M.D Used with permission • Treatment: • Steroids to reduce inflammation Heliotrope rash FA 2013: 394.2 • FA 2012: 422.2 • FA 2011: 386.3 ME 3e: 450 • ME 4e: 450 MUSC6_4- Neuromuscular junction diseases Kaplan Pathology 2010 Figure 29.2 Neuromuscular Junction Physiology FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450 MUSC6_5- Myasthenia gravis • Etiology: • Antibodies against the post-synaptic acetylcholine receptors of the NMJ Bind to and inactivates the receptor • • Signs/symptoms: • • Muscle weakness that worsens with prolonged use Typically affects the facial muscles • Ptosis • Extraocular muscles • Double vision • • Respiratory muscle involvement Diagnostic tests: • Electromyography: repetitive nerve stimulation testing • • • Progressive decrease in action potential size of affected muscle groups Edrophonium (an achetylcholinesterase inhibitor) improves symptoms Other characteristics: • Associated with thymoma FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450 Kaplan Immunology-Microbiology 2010 Figure I-13-5 MUSC6_5- Lambert-Eaton syndrome • Etiology: • Antibodies against the presynaptic calcium channels of the neuromuscular junction Antibody mediated attack • • Decreased acetylcholine release with neuronal transmission Signs/symptoms: • • Proximal muscle weakness that improves with repeated use Other characteristics: • Associated with malignancy, occurring as a paraneoplastic syndrome (e.g small cell lung cancer) FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450 Kaplan Pathology 2010 Figure 29.2 MUSC6_5- Lambert-Eaton syndrome • Diagnostic tests: • Electromyography: repetitive nerve stimulation testing • Progressive increase in action potential size of affected muscle groups Antibody mediated attack • Edrophonium does not improve symptoms Kaplan Pathology 2010 Figure 29.2 FA 2013: 394.3 • FA 2012: 422.3 • FA 2011: 386.4 ME 3e: 450 • ME 4e: 450 MUSC6_5- Scleroderma (progressive systemic sclerosis – PSS) • Two types • Diffuse scleroderma • Excessive fibrosis and collagen deposition throughout the body • Rapidly progressive • Sites of involvement: • Skin involvement (thick and leathery) • Visceral organ involvement • Lungs involvement (interstitial lung fibrosis) is usually the cause of death • Etiology: • Anti Scl-70 antibodies against topoisomerase FA 2013: 395.1 • FA 2012: 423.1 • FA 2011: 387.1 ME 3e: 107, 264 • ME 4e: 107, 264 Perioral Scleroderma Involvement Copyright Richard Usatine, M.D Used with permission MUSC6_6- Scleroderma (progressive systemic sclerosis – PSS) • Two types Diffuse scleroderma: CREST syndrome: • Sites of involvement: • • • • • Calcinosis Raynaud’s phenomenon Esophageal dysmotility (associated with GERD) Sclerodactyly Telangiectasia • Limited skin involvement • More benign course • Etiology: • Telangiectasias fingers scleroderma Copyright Richard Usatine, M.D Used with permission Anti centromere antibodies FA 2013: 395.1 • FA 2012: 423.1 • FA 2011: 387.1 ME 3e: 107, 264 • ME 4e: 107, 264 MUSC6_6- Tumor Necrosis Factor Alpha (TNF-α) Inhibitor: • General characteristics: • A class of drugs that inhibit the affects of TNF-α • TNF-α is an important inflammatory mediator FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448 MUSC6_7- Etanercept • Mechanism: • Recombinant form of the human TNF receptor that binds TNF • Decreases the net effect of TNF-α • Clinical Use: • Rheumatoid arthritis • Psoriasis • Ankylosing spondylitis FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448 MUSC6_7- Infliximab • Mechanism: • Anti-TNF antibody • Decreases the net effect of TNF-α • Clinical use: • Crohn’s disease • Rheumatoid arthritis • Ankylosing spondylitis • Adverse effects: • Predisposition to infections • Particularly latent tuberculosis reactivation • It’s important to assess for signs of TB prior to initiating Infliximab FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448 MUSC6_7- Adalimumab • Mechanism: • Anti-TNF antibody • Decreases the net effect of TNF-α • Clinical use: • Rheumatoid arthritis • Psoriasis • Ankylosing spondylitis FA 2013: 406.2 • FA 2012: 432.1 • FA 2011: 393.1 ME 3e: 448 • ME 4e: 448 MUSC6_7- Musculoskeletal and Connective Tissue: Summary • Anatomy, physiology, and disease of: • Skin • Muscles and ligaments • Peripheral nerves • Bones • Connective tissue MUSC6_8- ... patients Copyright Richard Usatine, M.D Used with permission FA 2013: 3 95. 2 • FA 2012: 423.2 • FA 2011: 387.2 ME 3e: 157 • ME 4e: 157 MUSC1_2- Pustule Name Description Pustule Blister containing pus... Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane C – Stratum... Kaplan Pathology 2010: Figure 11-1 FA 2013: 378.1 • FA 2012: 404.1 • FA 2011: 370.1 ME 3e: 451 • ME 4e: 451 MUSC1_1- Skin layers from surface to base Epidermal layers: Basement membrane L – Stratum