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 461 - 498

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

FractureRecumbency

E. Simko WCVM

Work hypertrophy

Compensatory hypertrophy

Response to injury - Hypertrophy

Response to injury

Myocyte necrosis Cell membrane disintegrationLeakage of cytosol substances (creatine kinase (CK), myoglobin)

Indicators of muscle damage.

Regeneration Repair

Both function & structure are re-established COMPLETELY

Function & structureare re-established

ONLY PARTIALLY(due to fibrosis)

Tissue injuryloss of functionand 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

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 recumbencyToo-tight plaster casts

E. Simko WCVM

Response to injury - Necrosis

(White muscle dz)

• Vit E and/or Se deficiency

• Economically important muscle dzin 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 diseaseTying-up (Transient exertional rhabdomyolysis)

Capture myopathy (wildlife)

Lesions: necrosis of the major muscles

Diagnosis: HistoryMyoglobinuriaMuscle necrosis

E. Simko WCVM

Response to injury - Inflammation

Lesions: Dry, red-black, porous necrotic musclesSerohemorrhagic exudation

DiagnosisDemonstration of Clostridial agentsPresence of the characteristic lesions

E. Simko WCVM

Response to injury - Inflammation

Gas gangrene and malignant edema

Bo, Eq, Ov, Cap, PoPenetrating 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.

Response to injury - Inflammation

E. Simko WCVM

• Systemic or local infectionsBacterialViralParasitic

Dz associated with clostridial toxins:TetanusBotulism

E. Simko WCVM

Response to injury - Inflammation

Masticatory Muscle MyositisEosinophilic myositis - acute formAtrophic myositis - chronic form

• Lesions: Acute - extremely swollen, hard, painful, musclesChronic - marked atrophy

• Autoantibodies against type IIM fibers

• Diagnosis:Muscle biopsySerology 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 receptorsAdult dogs with megaesophagus, aspiration pneumonia

Inherited autosomal recessive deficiency in AchRs

• Acquired

• Congenital

• DiagnosisCholinesterase inhibitors, Demonstration of Ab,

E. Simko WCVM

Rhabdomyosarcoma

Primary

Secondary

Rhabdomyoma