Download Response to injury

E. Simko WCVM
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
Objectives for Muscle dz:
Describe mechanisms of:
• Muscular regeneration
• Muscular repair
Define following conditions and give examples:
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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
Objectives for Muscle dz:
You should be able to define, describe pathogenesis,
list lesions and know how to diagnose the following
conditions/diseases:
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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
Unique features
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Complex biochemistry and physiology
Simple pathology
Very long multinucleated cells
Segmental necrosis
Unique regeneration
E. Simko WCVM
Muscle (epimysium)
Muscle bundle (perimysium)
Myocyte (endomysium)
E. Simko WCVM
Endomysium
Basal lamina
Satellite cell
Plasmalemma
Nucleus
Mitochondria
Myofibril
Myosin
Actin
E. Simko WCVM
Type I fibers (red)
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Postural
Oxidative
Slow contracting
Slow fatiguing
Type II fibers (white)
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Fast movement
Glycolytic
Fast contracting
Fast 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
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Atrophy
Hypertrophy
Degeneration / Necrosis
Inflammation
Response to injury - Atrophy
• Denervation
Suprascapular nerve paralysis (sweeney)
Radial nerve paralysis in dogs
• Disuse
Fracture
Recumbency
• Malnutrition
E. Simko WCVM
Response to injury - Hypertrophy
Work hypertrophy
Compensatory hypertrophy
E. Simko WCVM
Response to injury
Myocyte necrosis
Cell membrane disintegration
Leakage of cytosol substances
(creatine kinase (CK), myoglobin)
Indicators of muscle damage.
Tissue injury
loss of function
and structure
Regeneration
Repair
Both function & structure
are re-established
COMPLETELY
Function & structure
are re-established
ONLY PARTIALLY
(due to fibrosis)
E. Simko WCVM
Regeneration and repair
Prerequisites
for regeneration:
• Debridement
• Tissue scaffold
• Germinal cells
• Blood supply
If any of
these is
missing
Repair
(scarring)
E. Simko WCVM
Regeneration and repair
Basal lamina
SCAFFOLD
Satellite cell
GERMINAL CELLS
BLOOD SUPPLY
DEBRIDEMENT
E. Simko WCVM
Regeneration and repair - regeneration
See regeneration described in
Thomson’s Spec. Path on page 467 and
468, Figure 9-5.
Regeneration and repair - Regeneration
Regeneration
E. Simko WCVM
Regeneration and repair - Regeneration
Regeneration
E. Simko WCVM
Regeneration and repair - Regeneration
Regeneration
E. Simko WCVM
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
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
Response to injury - Necrosis
(White muscle dz)
• Vit E and/or Se deficiency
• Economically important muscle dz
in 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
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
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 O2
* Death is due to toxemia and septicemia.
E. Simko WCVM
Response to injury - Inflammation
• 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
• 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
Congenital & hereditary disorders
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
Primary
Rhabdomyosarcoma
Rhabdomyoma
Secondary
E. Simko WCVM