Muscles Degenerative - Pathology

()Map MUSCULOSKELETAL SYSTEM (Map) MUSCLES

Degeneration

Degenerate muscle fibres (Image sourced from Bristol Biomed Image Archive with permission)

• Different types of degeneration
• May, or may not, be reversible
• Cloudy swelling, hydropic, vacuolar, granular and fatty change
• Occur following many different types of insult and are usually segmental
• If regeneration does not occur after formation of small vacuoles, necrosis follows
  • Vacuolation -> floccular degeneration -> granular degeneration -> hyaline and Zenker’s degeneration
• Vacuolar degeneration:
  • Due to swelling of organelles or due to glycogen or fat accumulation
  • May be caused by hypokalaemia, hyperkalaemia or necrosis
• Histologically:
  • Swollen
  • Hypereosinophilic
  • Lost cross striations

Calcification

• Due to:
  • Old age - myofibres
  • Following necrosis - dystrophic calcification
    • May be visible grossly as white foci

Ossification

• Metaplasia of muscle to bone
• Localised
  • Only in single muscle or a single group of muscles
  • May be associated with trauma
  • Seen in horses and dogs
  • Histologically:
    • Central zone - proliferating undifferentiated cells and fibroblasts
    • Middle zone - osteoblasts depositing osteoid and bone
    • Outer zone - trabecular bone remodelled by osteoclasts
• Progressive (fibrodysplasia ossificans progressiva)
  • In connective tissue associated with skeletal muscle
  • Secondary involvement of muscle tissue
  • In pigs and cats
  • Histologically:
    • Bundles of dense fibrous connective tissue
    • May contain accumulations of cartilage, bone or calcium
  • Hyperplastic connective tissue -> compression of adjacent skeletal muscle -> atrophy

Pigmentation

• Lipofuscin
  • Wear and tear pigment accumulating in secondary lisosomes -> converted into compact residual bodies
  • Due to old age, past or recent cachexia or starvation
  • Mostly stored in skeletal muscle of old high producing dairy cattle
  • Masseters and diaphragm mainly involved
  • No clinical importance
  • Histologically:
    • Rounded yellow to brown granules at both poles of nucleus of the skeletal myofiber
• Melanin
  • As part of congenital melanosis of calves in fascial sheaths and epimysium
  • Grossly - black foci
• Myoglobin
  • After extensive muscle necrosis - rhabdomyolysis
  • Leaks to adjacent tissue after sudden injury
• May also be present after some types of intramuscular injections e.g. iron dextran or tetracycline

Necrosis

• Necrosis of an entire myofibre is uncommon
• Segmental necrosis is more typical
• Muscle cell contents may leak into the blood if the cell membrane is damaged
• Creatine kinase (CK) is an enzyme which leaks following injury
  • Used to measure the extent of muscle damage
• Often is followed by regeneration
• Histologically:
  • Hyaline hypercontracted fiber rounded at cross-section and increased diameter and eosin staining
    • May also be an artifact due to hypercontraction of normal fibres at fixation
  • Fragmenting portions of fibre -> floccular or granular
  • Normal portion of fibre may detach from necrotic part -> retraction caps
  • Infarction may cause discoid degeneration - necrotic fibres detach at Z lines
  • May mineralise
• Zenker's degeneration - secondary to systemic disease
  • Scattered small segments of necrosis and fast regeneration
  • Sacrolemmal tubes are intact

Atrophy

Atrophic muscle fibres (Image sourced from Bristol Biomed Image Archive with permission)

• Decreased myofibre or whole muscle diameter
• Myofibrils removed by disintegration -> sacrolemma too large -> forms folds
• Caused by:
  • Disuse (e.g. fracture, failure to use limb, recumbency)
    • Slower than denervation atrophy
    • Reversible unless too prolonger or severe to cause loss of myofibres
  • Denervation
    • Any interference or damage to its nerve supply results in muscle atrophy
      • Can be rapid - over 50% of muscle mass may be lost in a few weeks e.g. roarer horses with laryngeal hemiplegia
    • May be reversible if innervation re-established
    • Histologically:
      • Fibres become rounded in cross section unless compressed by normal fibres
      • Increased concentration of nuclei as they take much longer to disintegrate
      • Fibrous stroma of epimysium and endomysium condenses -> more prominent
      • End result in muscle consisting of almost only fibrous tissue
    • Sometimes replaced by fat tissue -> increased size of muscle = pseudohypertrophy
    • Muscle may have a mixture of atrophied and hypertrophied (due to increased work load) fibres if some motor units are not damaged
  • Metabolisation of muscle protein for nutrients during:
    • Malnutrition, cachexia, senility
    • Gradual onset except for some febrile diseases causing cachexia
    • Postural muscles are not affected, sometimes even hypertrophy
    • Histologically:
      • Some nuclei disappear as myofibre volume is decreased
    • Grossly:
      • Smaller, darker, thinner muscles

Toxic myopathy

• Plants
  • E.g. Cassia occidentalis (coffee senna), Karwinskia humboldtiana (coyotillo), Eupatorium rugosum (white snakeroot), cotton seed
  • Lesion an skeletal and cardiac muscle
  • Grossly:
    • Pale areas with ill-defined borders
    • May involve very extensive necrosis
  • Histologically:
    • Segmental necrosis, no calcification
    • Regeneration may occur in surviving animals
• Drugs
  • E.g. corticosteroids, cholinesterase inhibitors, vincristine, dimethyl sulfoxide (DMSO)
  • Monensin is a coccidiostat toxic to horses, donkeys, zebras, cattle, sheep, dogs and birds
    • Causes muscle necrosis in heart and skeletal muscle
    • Grossly:
      • Pale streaks, mostly in hind limbs
    • Histologically:
      • Segmental necrosis
      • Possibly regeneration in surviving animals
    • Can cause rapid onset recumbency and potentially death
    • Usually due to mixing errors in feed
  • Also from intramuscular injections, e.g. oxytetracycline, lidocaine, chloramphenicol, produce local necrosis
    • As satellite cells are destroyes, repair is via fibrosis with some budding
• Chemicals
  • Iron injections can cause local myonecrosis
• Mycotoxins
  • Metabolites cause persistent tremors
  • Lesions in skeletal muscle only, possibly secondary to sustained contractions (similar to exertional myopathy)
  • Histologically:
    • Tiny foci of segmental necrosis

Endocrine myopathy

• Hyperadrenocorticism
  • Muscle weakness is a clinical sign
  • -> muscle atrophy
    • Type II myofibre atrophy is non-specific
    • Type IIB myofibre atrophy is preferential in hyperadrenocorticism
• Hypothyroidism can cause muscle atrophy

Nutritional myopathy

White muscle disease (Image sourced from Bristol Biomed Image Archive with permission)

White muscle disease (Image sourced from Bristol Biomed Image Archive with permission)

White muscle disease

• Very important economic disease of sheep, cattle and pig
• Caused by:
  • Deficiency of selenium, vitamin E or both
  • Exacerbated by rapid growth, unaccustomed exercise or other dietary factor
• Pathogenesis:
  • Oxygen free radicals (OFR) can damage cell membranes
  • Vitamin E usually mops up OFRs
  • Selenium as part of glutathione peroxidase neutralises effects of OFRs
  • If Vit E or Se are deficient -> the balance shifts to membrane damage, calcium entry and mitochondrial damage -> cell swells and dies -> segmental muscle necrosis
• Grossly:
  • Lesions are bilaterally symmetrical in hard working muscles (vary with species)
  • Early lesions are pale areas and streaks
    • Difficult to see especially in pale muscles
  • Later becoming calcified necrotic areas
    • More obvious
  • Pigs also have lesions in their heart and liver
• Histologically:
  • Segmental necrosis +/- calcification and regeneration
  • Multifocal and multiphasic lesions

Exertional myopathies

• Caused by intensive and exhaustive activity of major muscle masses
• Glycogen used up -> local heat and lactic acid -> muscle degeneration
• Other forms include capture myopathy, racing greyhounds, sheep chased by dogs

Equine rhabdomyolysis

• Azoturia (Monday morning disease)
  • Acute
  • Due to exercise following a prolonged period of rest
  • Clincal signs:
    • Unable to move
    • Sweating
    • Tremors
    • Swollen and hard lumbar, gluteal and femoral muscles
  • Myoglobin leaks from muscle cells -> leaks into urine -> urine is dark red/brown (myoglobinuria) -> damages renal tubules
  • Grossly:
    • Salmon pink muscles -> dark, moist, swollen +/- pale streaks
  • Histologically:
    • Segmental myofibre necrosis
      • Multifocal and monophasic, but may be multiphasic if repeated bouts
    • Both, type IIA and IIB fibres affected; type IIB preferentially affected in acute disease
    • Minor inflammatory reaction and calcification

• Tying-up
  • Similar to azoturia but much milder
  • Grossly - normal muscle
  • Histologically - same as azoturia

Porcine stress syndrome

• Malignant hyperthermia
• Pigs, dogs, humans
• Possibly a cellular defect resulting in high intacellular calcium ion concentration
  • -> Activates myofibrillar ATPase -> rapid intracellular glycolysis -> increase in body heat -> denature protein -> cell death -> leakage of cellular content -> oedema
• Grossly:
  • Muscles are pale, soft and exudative
• Histologically:
  • Segmental hypercontraction
  • Monophasic, multifocal segmental necrosis
• Inherited
• Triggered by halothane anaesthesia, stress of handling, transportation or slaughter

Neuromuscular junction diseases

Aquired myasthenia gravis

• See congenital MG

Botulism

• Caused by:
  • Ingestion of Clostridium botulinum toxin which inhibits acetyl choline release
• Diagnosis by demonstration of toxin in faeces, ingested material or serum

Circulatory disturbances

Congestion

• Localised or generalised stasis -> dark red muscle
• E.g. in ruminal tympany (bloat) - congestion of muscles cranial to thoracic inlet
• May resemble haemorhage grossly

Ischaemia

• Firstly segmental necrosis
• -> death of satellite cells
  • Causes regeneration but myoblast precursors have to be recruited from viable fibres
• -> death of all cells
• Mostly healed by fibrosis and scar formation
• May attempt regeneration by budding

Main causes:

• Vascular occlusion
  • Infarction from embolism is rare due to collateral circulation
  • Extension of infarcts depends on size of vessels occluded
    • Small capillaries -> segmental necrosis
    • Large arteries -> whole muscle areas, including sattelite cells, are killed
  • Healed by fibrosis
  • May be due to:
    • Blockage of iliac arteries by aortic-iliac thrombosis in horses
    • Blockage of aortic bifurcation in cats
    • Dirofilaria immitis arteritis in dogs
    • Vasculitis due to bluetongue virus in sheep
    • Equine purpura haemorrhagica
      • Non-contagious, sporadic
      • Grossly:
        • Subcutaneous oedema
        • Scattered haemorrhagic foci throughout skin and muscles
        • Vasculitis -> infarcts of muscles
      • May cause myoglobinuria if extensive
      • Possibly immune mediated
      • In horses post streptococal infection, especially strangles
• External pressure
  • During prolonged recumbency, e.g. anaesthesia, inability to rise, or due to too tightly fitting bandages or casts
  • Post anaesthesia myopathy especially in horses
    • Dorsal recumbancy -> gluteals and longissimus ischaemia
    • Lateral recumbancy -> triceps brachii, pectoralis, deltoideus and brachiocephalicus ischaemia
  • Caused by pressure on muscle > perfusion pressure of capillaries
  • Downer cows - vetral recumbency -> ischaemia of pectoral muscles and muscles of limbs tucked under the animal
  • Pregnant ewes with twins or triplets -> internal abdominal oblique muscle ischaemic necrosis -> potential rupture
• Muscle swelling where it cannot expand
  • E.g. supracoracoid muscle infarction in some breeds of turkeys after flapping their wings
    • Surrounded by inelastic fascial sheath and bone

Trauma

• Due to:
  • Direct transection of myofibres
  • Compression of myofibres
  • Secondary from haemorrhage (bruising)
    • May increase muscle pressure -> ischaemia -> necrosis
  • Partial rupture - e.g. of diaphragm in road traffic accident
  • Complete rupture - e.g. quadriceps of racing greyhounds
  • Myorrhexis (tearing) - e.g. slippery floor causing 'splits' in cattle -> adductor muscle tear
• Healing is by regeneration
• Fibrosis (scarring) will compromise function
• During fractures, fragments may cause further trauma if moved