muscle Flashcards
myofiber components
- Myofibrils:
- Actin and myosin filaments
- Arranged into sarcomeres (striated appearance)
- Sarcoplasmic reticulum:
- Sequesters calcium necessary to initiate actin and myosin interaction and contraction
Normal muscle function requires normal PNS
function
- Lower motor neurons
- Peripheral nerves
- Neuromuscular junctions
- Action potential arrives via motor neuron
- Terminal axons release acetylcholine
- Acetylcholine binds to acetylcholine receptors on post-
synaptic myofiber membrane - Sodium channels open in myofiber membrane, action
potential, muscle contracts
muscle dysfunction
Myopathy: primary pathology of the muscle
cell
* Neuromuscular disease: includes pathology
of LMN, peripheral nerves, neuromuscular
junction, muscle
clinical signs associated with neuromuscllar disease
Muscle atrophy – a decrease in muscle size
Muscle hypertrophy – an increase in muscle size
Muscle swelling – due edema, hemorrhage, inflammation
Weakness and exercise intolerance – direct or indirect decrease in muscle function
Muscle spasm – sudden, intense
Myotonia – a tonic spasm; delayed relaxation of a muscle after an initial contraction
Abnormal movement – lameness
Dysphagia
origin of injury
-exogenous: penetrating wound including IM injection
-hematogenous: microorganisms, toxins, immune complexes
-endogenous: excessive contraction, genetic defecfs, nutritional deficiencies
color changes of muscle
White / Pallor:
anemia
necrosis ± mineralization
denervation (atrophy)
fibrosis
Red:
congestion
hemorrhage
Black
hemorrhage
melanosis
melanoma
Green eosinophilic inflammation
Responses to Injury (identified grossly)
1.Necrosis and regeneration
2.Alteration in myofiber size
* Atrophy
* Hypertrophy
* Hypoplasia
3.Chronic myopathic change:
fibrosis/steatosis
necrosis in response to injury
- Necrosis and regeneration
* necrosis is common**
* wide range of etiologies
* often segmental
* regeneration is possible**
* satellite cells
* requires intact basal lamina
alteration in myofiber size response to injruy: atrophy causes and types
a. Atrophy
* entire muscle or individual myofibers
* potentially reversible
i. Physiologic atrophy: disuse atrophy, aging, cachexia
ii. Denervation atrophy: loss of innervation
iii. Endocrine associated: generalized muscle atrophy, hypothyroidism, hyperadrenocorticism, PPID
* Muscle has lots of hormone receptors
Responses to Injury
2. Alteration in myofiber size
b. Hypertrophy
* entire muscle or individual
myofibers
* response to increased workload
* addition of myofibrils
i. Physiologic hypertrophy
ii.Compensatory hypertrophy
c. Hypoplasia
* Piglets get Splay leg
* premature animals
* MDx. Myofibrillar
hypoplasia
Responses to injury
3. Chronic myopathic change
Chronic myopathic change
* fibrosis
* steatosis
- Accompanies variety of myopathic and
neuropathic conditions e.g. chronic
inflammation, denervation, degenerative
myopathy
causes of muscle ischemia
-occlusion of major BV ex saddlethrombus in cat
-external pressure: recumbancy disease in large animal
-compartment syndrome: edema reperfusion injury
-widespread vascular injury: trauma
recumbency necrosis (downer cow)
- Recumbency ->vascular occlusion
->myonecrosis - Myofiber necrosis due to recumbency can occur due to:
1. Decreased blood flow (artery compression)
2. Reperfusion injury if she gets up causing massive Ca influx into muscle cells
3. Increased intramuscular pressure causing compartment syndrome
4. Combination
compartment syndrome
-compression of tissues within a compartment
(nerves, blood vessels, muscle)
* compartment created by
* bone
* thick fascia
* increase in volume / pressure within muscle results in
compression, ischemia, necrosis
nutritional myopathy
Selenium/Vitamin E deficiency
➔ decreased antioxidant activity
➔oxidative injury to myofibers
➔Muscle necrosis and mineralization
Risk factors: sample high work load muscles
* neonates (selenium)
* farm animals (soils & plants)
* late winter (vitamin E)
nutritional myopathies of muscle
B. Nutritional Myopathies
* Muscle requires & receives a large amount of oxygen
* Therefore, muscle is susceptible to oxidative injury
(cell and tissue damage)
* Selenium (Se) & vitamin E are critical components of
antioxidants in muscle
* Se & vitamin E are derived from the diet
Toxic Myopathies
-Ionophore antibiotics
* feed additives (for coccidiosis)
* monensin
* Rumensin (Elanco)
-mixing errors, toxic to horses
toxic myopathies path (ionophore toxicity)
Ingest excess ionophore
➔increased movement of cations across cell membrane
➔disruption of ionic equilibrium
➔calcium overload of skeletal (and cardiac) muscle
➔muscle necrosis (pale areas in muscle)
Equine exertional rhabdomyolysis (exertional myopathy)
-equine polysaccharide storage myopathy**, high grain diet, lack of regular exercise
➔altered carbohydrate metabolism in muscle
➔insufficient energy production by muscle cells
➔muscle necrosis and oxidative injury**
➔ edema within nonexpendable fascia
➔ ischemia
➔compartment syndrome
➔myoglobin release (red tinge to muscle)
➔releases from muscle to kidney–>myoglobinuric nephrosis**
- Capture myopathy in wildlife
-exertional myopathy
-capture and / or restraint of wild animals
➢ ‘stress’, catecholamines, acidosis,
hyperthermia
➢ muscle necrosis
➢ myoglobin release
➢ myoglobinuric nephrosis
Malignant hyperthermia
- Genetic defect of calcium-release channel (ryanodine receptor-ryr1)**
of skeletal muscle sarcoplasmic reticulum
➢Halothane anesthesia or stress
➢Uncontrolled Ca release
➢Excess muscle contraction
➢Hyperthermia
➢Death - Autosomal recessive disorder in pigs (autosomal dominant in dogs and humans)
-porcine stress syndrome: white, pale, wet muscle. myonecrosis
Myositis ossificans (traumatic myopathies)
- Rare
- Metaplastic bone formation
- Previous trauma, fibrosis
- Injection
- Exercise
- DDx extraskeletal osteosarcoma
Congenital and Inherited Myopathies
1. Arthrogryposis
- persistent congenital flexure
- often a neuromuscular
disease
path:
In utero infection or toxin ingestion or genetic defect
➢Nervous system lesion
➢Failure of innervation/denervation of skeletal muscle
➢Atrophy, persistent flexure, myopathic change/steatosis
Muscular dystrophies
-congenital and inherited myopathy
* group of heterogeneous diseases
* inherited
* progressive
* muscle weakness and wasting
* degenerative
* necrosis
* regeneration
* fibrosis and steatosis
X-Linked Muscular Dystrophy (Duchenne’s Type)
X-linked recessive mutation in dystrophin gene
➢Decreased dystrophin, cytoskeletal protein in muscle
➢Repeated necrosis and regeneration of skeletal muscle
➢Also, necrosis of cardiomyocytes and fibrosis
➢Progressive weakness, muscle atrophy, splaying of distal limbs
Pathogenesis of Acquired (Immune-mediated)
Myasthenia Gravis
Thymoma, loss of self-tolerance
➢Autoantibody against acetylcholine receptors on muscle
➢Damage of receptors and blockage of acetylcholine binding
➢Prevents muscle contraction
➢Episodic weakness and collapse
➢Megaesophagus
Botulism
-Clostridium botulinum spores in soil or GI tract of animal
➢Spores germinate under anaerobic/alkaline conditions
➢Within GI tract
➢Soil/rodent carcass in spoiled feed
➢C. botulinum produces neurotoxin**
➢Toxin absorbed by animal through alimentary system
➢Toxin irreversibly blocks acetylcholine release at myoneural junctions
➢Flaccid paralysis
➢Respiratory paralysis = death
* horses sensitive
tick paralysis
-Dermacentor or Ixodes tick attach to animal
➢Tick produces toxin that blocks acetylcholine release from axon terminals
➢Flaccid paralysis
➢Tick removal = recovery
clostridial myositis (inflammatory bacterial infection) path
Ingestion of Clostridial spores during grazing
➔spores pass through intestinal mucosal barrier and enter circulation
➔dissemination to tissues (especially striated muscle and liver)
➔ spores multiply in low oxygen environments (i.e. trauma, horses:
penetrating trauma)
➔ toxin production
➔ vascular damage
➔ hemorrhage, edema, necrosis of adjacent myofibers
➔ systemic dissemination of the toxin (toxemia)
➔death
Clostridial myositis causes
- Farm animals – black leg= Clostridium chauvoei
- Horses – malignant edema= Clostridium septicum,
masticatory myositis of dogs
-immune mediated myositis
Antibodies to unique type 2M myosin of masticatory muscle
➢Acute inflammation (edema, pain) of temporalis and masseter
➢Chronic atrophy
always bilateral
if other muscles in body involved: polymyositis
neoplasia
- Primary neoplasia of striated muscle
- Rhabdomyoma
- Rhabdomyosarcoma
- Arise from intramuscular pluripotential
stem cells - Primary neoplasia of supporting
connective, adipose, vascular, or
neural tissue - Hemangiosarcoma
parasitc
- Protozoal myopathy
- Neospora caninum (dogs, cattle)
- Sarcocystis spp. (farm animals, horses)
- Nematodes
- Trichinella spiralis (pigs, bear
neospora canium dogs
➢In utero transmission to fetus
➢Peripheral nervous system and skeletal muscle are
invaded by protozoa, including ventral spinal roots
➢ Denervation atrophy
