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Skeletal muscle

Skeletal muscle

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Skeletal muscle

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  1. Skeletal muscle E. Simko WCVM

  2. Reading material: 1. Review the normal structure and function of skeletal muscle (in your notes or general textbooks) 2. McGavin M.D. 1995, Muscle, Chapter 9 in Thomson's Special Veterinary Pathology, Carlton W.W. et al, pp 461 - 498 NB - Put special emphasis on the topics covered during the lectures. E. Simko WCVM

  3. Objectives for Muscle dz: • Describe mechanisms of: • Muscular regeneration • Muscular repair • Define following conditions and give examples: • Denervation atrophy • Disuse atrophy • Malnutrition atrophy • Muscular hypertrophy • Ischemic myopathy • - Occlusion of the vascular system • - External pressure on a muscle • Swelling of a muscle in a non-expandable • compartment E. Simko WCVM

  4. Objectives for Muscle dz: You should be able to define, describe pathogenesis, list lesions and know how to diagnose the following conditions/diseases: • Nutritional myopathy (White muscle disease) • Toxic myopathy (Monensin toxicity) • Exertional myopathy • Gas gangrene and malignant edema • Blackleg • Botulism • Tetanus • Myasthenia gravis • Masticatory muscle myositis E. Simko WCVM

  5. Skeletal muscle Unique features • Complex biochemistry and physiology • Simple pathology • Very long multinucleated cells • Segmental necrosis • Unique regeneration E. Simko WCVM

  6. Muscle (epimysium) Muscle bundle (perimysium) Myocyte (endomysium) E. Simko WCVM

  7. Myocyte Endomysium Basal lamina Satellite cell Plasmalemma Nucleus Mitochondria Myofibril Myosin Actin E. Simko WCVM

  8. Type I fibers (red) • Postural • Oxidative • Slow contracting • Slow fatiguing • Type II fibers (white) • Fast movement • Glycolytic • Fast contracting • Fast fatiguing E. Simko WCVM

  9. Review Contractile mechanism (Histology & physiology notes) Rigor mortis (Thomson's Special Veterinary Pathology p. 396) E. Simko WCVM

  10. Response to injury - Atrophy Response to injury • Atrophy • Hypertrophy • Degeneration / Necrosis • Inflammation

  11. Response to injury - Atrophy Atrophy • Denervation Suprascapular nerve paralysis (sweeney) Radial nerve paralysis in dogs • Disuse Fracture Recumbency • Malnutrition E. Simko WCVM

  12. Response to injury - Hypertrophy Hypertrophy Work hypertrophy Compensatory hypertrophy E. Simko WCVM

  13. Response to injury Necrosis Myocyte necrosis Cell membrane disintegration Leakage of cytosol substances (creatine kinase (CK), myoglobin) Indicators of muscle damage.

  14. Tissue injury loss of function and structure Regeneration and repair Regeneration Repair Both function & structure are re-established COMPLETELY Function & structure are re-established ONLY PARTIALLY (due to fibrosis) E. Simko WCVM

  15. Regeneration and repair Prerequisites for regeneration: • Debridement • Tissue scaffold • Germinal cells • Blood supply Repair (scarring) If any of these is missing E. Simko WCVM

  16. Regeneration and repair Basal lamina SCAFFOLD Satellite cell GERMINAL CELLS BLOOD SUPPLY DEBRIDEMENT E. Simko WCVM

  17. Regeneration and repair - regeneration Regeneration See regeneration described in Thomson’s Spec. Path on page 467 and 468, Figure 9-5.

  18. Regeneration and repair - Regeneration Regeneration E. Simko WCVM

  19. Regeneration and repair - Regeneration Regeneration E. Simko WCVM

  20. Regeneration and repair - Regeneration Regeneration E. Simko WCVM

  21. Regeneration and repair - Repair Repair E. Simko WCVM

  22. Regeneration and repair - Repair Repair E. Simko WCVM

  23. Regeneration and repair - Repair Repair E. Simko WCVM

  24. Response to injury - Necrosis Ischemia Vascular occlusion Saddle thromboembolus (Fe, Eq) Equine Purpura Hemorrhagica External pressure on muscle Prolonged recumbency Too-tight plaster casts Muscle swelling in non-expandable compartment Pressure in muscle exceeds perfusion pressure in capillaries E. Simko WCVM

  25. Response to injury - Necrosis (White muscle dz) Nutritional Myopathy • Vit E and/or Se deficiency • Economically important muscle dzin Bo, Ov, Cap, Po and Eq • Lesions: opaque, white muscle (mineralization) Ruminants: skeletal muscles and heart Pigs: liver (hepatosis diatetica) heart (mulberry heart disease) E. Simko WCVM

  26. Response to injury - Necrosis Pathogenesis Vit E and/or Se deficiency Loss of protection against free radicals Peroxidation of membrane lipids Disturbance of membrane permeability Influx of calcium into cytosol Accumulation of calcium in mitochondria Damaged mitochondria Energy exhaustion Necrosis E. Simko WCVM

  27. Response to injury - Necrosis Diagnosis Histology Se and Vit E levels in the liver, feed E. Simko WCVM

  28. Response to injury - Necrosis Monensin toxicity • Feed additive overdose • Lesions: necrosis (ill-defined, pale streaks) in myocardium and skeletal muscles • Pathogenesis: Interferes with ion transmembrane transport Calcium influx and mitochondiral damage Energy exhaustion Necrosis E. Simko WCVM

  29. Response to injury - Necrosis Diagnosis Histology Monensin levels in feed and stomach content E. Simko WCVM

  30. Response to injury - Necrosis Exertional myopathy Excessive muscle activity Sudden production of heat and lactic acid & ??? Coagulation of contractile proteins Muscle swelling and decrease blood perfusion Ischemia and necrosis * Often with myoglobinuria E. Simko WCVM

  31. Response to injury - Necrosis Equine Rhabdomyolysis (muscle necrosis) Azoturia (Monday morning disease Tying-up (Transient exertional rhabdomyolysis) Capture myopathy (wildlife) Lesions: necrosis of the major muscles Diagnosis: History Myoglobinuria Muscle necrosis E. Simko WCVM

  32. Response to injury - Inflammation Clostridial myositis Lesions: Dry, red-black, porous necrotic muscles Serohemorrhagic exudation Diagnosis Demonstration ofClostridial agents Presence of the characteristic lesions E. Simko WCVM

  33. Response to injury - Inflammation Gas gangrene and malignant edema Bo, Eq, Ov, Cap, Po Penetrating wounds infected by C. septicum, C. perfringens, C. novyi, and C. chauvoei Blackleg (Bo, Cap, Ov) Activation of spores of C. chauvoei disseminated from the GI tract to muscles * Clostridial requirements for low O2 * Death is due to toxemia and septicemia. E. Simko WCVM

  34. Response to injury - Inflammation Other infections • Systemic or local infections • Bacterial • Viral • Parasitic • Dz associated with clostridial toxins: • Tetanus • Botulism E. Simko WCVM

  35. Response to injury - Inflammation Immune-mediated myositides Masticatory Muscle Myositis Eosinophilic myositis - acute form Atrophic myositis - chronic form • Autoantibodies against type IIM fibers • Lesions: • Acute - extremely swollen, hard, painful, muscles • Chronic - marked atrophy • Diagnosis: • Muscle biopsy • Serology for autoantibodies Polymyositis E. Simko WCVM

  36. Congenital & hereditary disorders Myasthenia Gravis Muscle weakness and fatigue exacerbated by exercise and resolves with rest (in dogs and occ. in cats and goats • Acquired Autoimmune dz - Ab against acetylcholine receptors Adult dogs with megaesophagus, aspiration pneumonia • Congenital Inherited autosomal recessive deficiency in AchRs • Diagnosis Cholinesterase inhibitors, Demonstration of Ab, E. Simko WCVM

  37. Neoplasia Primary Rhabdomyosarcoma Rhabdomyoma Secondary E. Simko WCVM