muscle

Question 1

myofiber components

Answer 1

• Myofibrils:
• Actin and myosin filaments
• Arranged into sarcomeres (striated appearance)
• Sarcoplasmic reticulum:
• Sequesters calcium necessary to initiate actin and myosin interaction and contraction

Question 2

Normal muscle function requires normal PNS
function

Answer 2

• 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

Question 3

muscle dysfunction

Answer 3

Myopathy: primary pathology of the muscle
cell
* Neuromuscular disease: includes pathology
of LMN, peripheral nerves, neuromuscular
junction, muscle

Question 4

clinical signs associated with neuromuscllar disease

Answer 4

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

Question 5

origin of injury

Answer 5

-exogenous: penetrating wound including IM injection
-hematogenous: microorganisms, toxins, immune complexes
-endogenous: excessive contraction, genetic defecfs, nutritional deficiencies

Question 6

color changes of muscle

Answer 6

White / Pallor:
anemia
necrosis ± mineralization
denervation (atrophy)
fibrosis

Red:
congestion
hemorrhage

Black
hemorrhage
melanosis
melanoma

Green eosinophilic inflammation

Question 7

Responses to Injury (identified grossly)

Answer 7

1.Necrosis and regeneration
2.Alteration in myofiber size
* Atrophy
* Hypertrophy
* Hypoplasia
3.Chronic myopathic change:
fibrosis/steatosis

Question 8

necrosis in response to injury

Answer 8

1. Necrosis and regeneration
   * necrosis is common**
   * wide range of etiologies
   * often segmental
   * regeneration is possible**
   * satellite cells
   * requires intact basal lamina

Question 9

alteration in myofiber size response to injruy: atrophy causes and types

Answer 9

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

Question 10

Responses to Injury
2. Alteration in myofiber size

Answer 10

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

Question 11

Responses to injury
3. Chronic myopathic change

Answer 11

Chronic myopathic change
* fibrosis
* steatosis

• Accompanies variety of myopathic and
  neuropathic conditions e.g. chronic
  inflammation, denervation, degenerative
  myopathy

Question 12

causes of muscle ischemia

Answer 12

-occlusion of major BV ex saddlethrombus in cat
-external pressure: recumbancy disease in large animal
-compartment syndrome: edema reperfusion injury
-widespread vascular injury: trauma

Question 13

recumbency necrosis (downer cow)

Answer 13

• 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

Question 14

compartment syndrome

Answer 14

-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

Question 15

nutritional myopathy

Answer 15

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)

Question 16

nutritional myopathies of muscle

Answer 16

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

Question 17

Toxic Myopathies

Answer 17

-Ionophore antibiotics
* feed additives (for coccidiosis)
* monensin
* Rumensin (Elanco)

-mixing errors, toxic to horses

Question 18

toxic myopathies path (ionophore toxicity)

Answer 18

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)

Question 19

Equine exertional rhabdomyolysis (exertional myopathy)

Answer 19

-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**

Question 20

2. Capture myopathy in wildlife

Answer 20

-exertional myopathy
-capture and / or restraint of wild animals
➢ ‘stress’, catecholamines, acidosis,
hyperthermia
➢ muscle necrosis
➢ myoglobin release
➢ myoglobinuric nephrosis

Question 21

Malignant hyperthermia

Answer 21

• 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

Question 22

Myositis ossificans (traumatic myopathies)

Answer 22

• Rare
• Metaplastic bone formation
• Previous trauma, fibrosis
• Injection
• Exercise
• DDx extraskeletal osteosarcoma

Question 23

Congenital and Inherited Myopathies
1. Arthrogryposis

Answer 23

• 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

Question 24

Muscular dystrophies

Answer 24

-congenital and inherited myopathy
* group of heterogeneous diseases
* inherited
* progressive
* muscle weakness and wasting
* degenerative
* necrosis
* regeneration
* fibrosis and steatosis

Question 25

X-Linked Muscular Dystrophy (Duchenne’s Type)

Answer 25

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

Question 26

Pathogenesis of Acquired (Immune-mediated) Myasthenia Gravis

Answer 26

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

Question 27

Botulism

Answer 27

-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**

Question 28

tick paralysis

Answer 28

-Dermacentor or Ixodes tick attach to animal ➢Tick produces toxin that blocks acetylcholine release from axon terminals ➢Flaccid paralysis ➢Tick removal = recovery

Question 29

clostridial myositis (inflammatory bacterial infection) path

Answer 29

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

Question 30

Clostridial myositis causes

Answer 30

* Farm animals – black leg= Clostridium chauvoei * Horses – malignant edema= Clostridium septicum,

Question 31

masticatory myositis of dogs

Answer 31

-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

Question 32

neoplasia

Answer 32

* Primary neoplasia of striated muscle * Rhabdomyoma * Rhabdomyosarcoma * Arise from intramuscular pluripotential stem cells * Primary neoplasia of supporting connective, adipose, vascular, or neural tissue * Hemangiosarcoma

Question 33

parasitc

Answer 33

* Protozoal myopathy * Neospora caninum (dogs, cattle) * Sarcocystis spp. (farm animals, horses) * Nematodes * Trichinella spiralis (pigs, bear

Question 34

neospora canium dogs

Answer 34

➢In utero transmission to fetus ➢Peripheral nervous system and skeletal muscle are invaded by protozoa, including ventral spinal roots ➢ Denervation atrophy