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SPUC 11/28/2011 Skeletal Muscle Pathology

SPUC 11/28/2011 Skeletal Muscle Pathology. Overview Slides: 2 - 12 Case 1-9 EM Images Follow. Histochemical Fiber Typing. Type I Type II Twitch sIow fast Turkey Meat Dark – drumstick White – Breast analogy (weight bearing) (rapid / skilled movement)

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SPUC 11/28/2011 Skeletal Muscle Pathology

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  1. SPUC11/28/2011Skeletal Muscle Pathology Overview Slides: 2 - 12 Case 1-9 EM Images Follow

  2. Histochemical Fiber Typing Type IType II • Twitch sIow fast • Turkey Meat Dark – drumstick White – Breast analogy (weight bearing) (rapid / skilled movement) • Metabolism Oxidative Glycolytic • NADH (oxidative) Dark (more mitochondria) Light • Fat More Less • Glycogen Less More • ATPase • 4.3 / 4.6 Dark Light • 9.4 Light Dark Jogging Sprinting “One Slow Fat Red Ox”

  3. Type I Fibre Hypotrophy vs. Neurogenic Change Fiber Type Determination

  4. I. Myopathic: Damage to muscle fibers A. Active Degeneration: “Rhabdomyolysis” (“immaculate necrosis”) Macrophage infiltrate Lymphocytic “invasion” Regeneration: Basophilia Atrophic, rounded fibers, Inflammation Macrophages Lymphocytes B. Chronic – Classic, Non-Specific - Hypertrophy - Atrophy, rounded - Type I hypotrophy - Centralized nuclei (>3 – 5% of fibers) - Split fibers - Connective tissue deposition Material: Fibrosis, fat Location: Endomysial, Perimysial C.Other Vacuolation Lipid increased Glycogen increased Mitochondria # increased (ragged red fibers) / altered biochemistry / inclusions Myosin loss (critical illness myopathy) Histopathologic Inventory II. Neurogenic: Loss of innervation of myofibers A. Active • Atrophic, angulated fibers with enhanced esterase +/- NADH activity B. Subacute to Chronic - Grouped atrophy - Target and targetoid change C. Subacute to Chronic - Fiber type grouping - Marked excess of type I or type II myofibers - Diffuse - Within occasional fascials - Nuclear cluster fibers (chronically denervated) III. Type II Myofiber Atrophy A. Active • Selective atrophy of Type II (fast twitch) fibers

  5. Histochemical Fiber Typing Type IType II • Twitch sIow fast • Turkey Meat Dark – drumstick White – Breast analogy (weight bearing) (rapid / skilled movement) • Metabolism Oxidative Glycolytic • NADH (oxidative) Dark (more mitochondria) Light • Fat More Less • Glycogen Less More • ATPase • 4.3 / 4.6 Dark Light • 9.4 Light Dark Jogging Sprinting “One Slow Fat Red Ox”

  6. Etiologic Approach to Differential Diagnosis Symptoms / Signs / Imaging / Biopsy / Resection / Autopsy Abnormal Normal Reactive / Hyperplastic Non-Neoplastic Neoplastic Primary “Metastatic” Other Developmental Hematopoietic Traumatic Degenerative Infectious • Bacterial • Fungal • Viral • Parasitic Toxic - Metabolic Vascular Inflammatory • Infarct (hypoxia- ischemia) • - Focal vs. Global • - Pale • - Hemorrhagic • conversion • Hemorrhage • Autoimmune (connective tissue disease) • Paraneoplastic • Sarcoid (neoplastic divide)

  7. Etiologic Categories: Myopathic • Developmental / Degenerative • Dystrophy • “Congenital” • Childhood-onset • Adult-onset • Congenital myopathy • Congenital fiber type disproportion • Centronuclear / Myotubular • Central core / Minicore(multi-mini core) • Nemaline rod • Protein Aggregate myopathy (myosin, actin, desmin) • Tubular aggregate • Cylindrical spiral • Ullrich / Bethlem • Vascular • Ischemia / Infarct – not related to vasculitis • Thrombosis • Diabetic infarct • Compartment syndrome • Traumatic • Exercise-related • Physical trauma • Crush and compartment syndrome  swelling  vascular compromise  ischemia • Neoplastic • Inflammatory • Inflammatory Myopathy – primary myofiber involvement • Polymyositis • Dermatomyositis • Connective Tissue Disease, NOS • Inclusion Body Myositis • Other – muscle involvement in a systemic disease • Sarcoid • Vasculitis • Infectious • Parasitic • Trichinosis • Viral myositis • Influenza • Enterovirus • Bacterial myositis • Toxic - Metabolic - Endocrine • Metabolic • Mitochondrial • Lipid storage / transport diseases • Glycogen storage disease • Toxic • Cholesterol lowering drugs • Steroid / Cushing myopathy • Endocrine • Thyroid hormone: hyper- or hypo-thyroidism

  8. Inflammatory Myopathies: Histology (COX = cytochrome oxidase histochemistry) (After Kissel, Seminar Neurol, 2002)

  9. Mitochondrial Cytopathy: Muscle Note: Findings vary considerably among mitochondrial cytopathy syndromes

  10. Dalkilic I, Kunkel LM. Current Opinion Genetics and Development. 13:231, 2003.

  11. Dystrophy-Associated Proteins (Dalkilic I. Current Opinion Genetics and development. 13:231, 2003.)

  12. SPUC11/28/2011Skeletal Muscle Pathology Case 1

  13. Thick Section Toluidine Blue

  14. EM – Medium Mag.

  15. EM – High Mag.

  16. EM – Medium Mag.

  17. SPUC11/28/2011Skeletal Muscle Pathology Case 2

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  19. SPUC11/28/2011Skeletal Muscle Pathology Case 3

  20. SPUC11/28/2011Skeletal Muscle Pathology Case 4

  21. SPUC11/28/2011Skeletal Muscle Pathology Case 5

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  23. SPUC11/28/2011Skeletal Muscle Pathology Case 6

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  25. SPUC11/28/2011Skeletal Muscle Pathology Case 7

  26. SPUC11/28/2011Skeletal Muscle Pathology Case 8

  27. 2.50 µm

  28. 2.50 µm

  29. SPUC11/28/2011Skeletal Muscle Pathology Case 9

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