E. Simko WCVM

Reading material: E. Simko WCVM 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 NB - Put special emphasis on the topics covered during the lectures.

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 Objectives for Muscle dz: E. Simko WCVM Describe mechanisms of: Muscular regeneration Muscular repair

Objectives for Muscle dz: E. Simko WCVM 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

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

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

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

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

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

Response to injury - Atrophy Atrophy Hypertrophy Degeneration / Necrosis Inflammation

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

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

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

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

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

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

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

E. Simko WCVM Regeneration Regeneration and repair - Regeneration

E. Simko WCVM Regeneration and repair - Regeneration Regeneration

E. Simko WCVM Regeneration and repair - Regeneration Regeneration

Regeneration and repair - Repair E. Simko WCVM

Regeneration and repair - Repair

E. Simko WCVM Regeneration and repair - Repair

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

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

E. Simko WCVM Response to injury - Necrosis Necrosis 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 Vit E and/or Se deficiency Pathogenesis

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

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

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

E. Simko WCVM 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 O 2 * Death is due to toxemia and septicemia.

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

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

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

E. Simko WCVM Rhabdomyosarcoma Primary Secondary Rhabdomyoma