Lecture 18: Skeletal Muscle Pathology I Flashcards
Which of the following is heart vs skeletal muscle
Left: heart- single centrally located nucleus
Right: skeletal muscle- multiple nuclei on periphery
identify 1-6
- Mitochondria
- Glycogen
- Z line
- I band
- M line
- A band
what are myofibers
long and multinucleated cells, little to no regenerative capacity
what are satellite cells
run along length of myofibers and have full capacity of division, fusion, and can restore mature myofibers
what are the physiologic and morphological characteristics of type 1 muscle fibers
Phys: slow twitch, oxidative fatigue resistant, “red muscle” aerobic
Morph: high mitochondria and fat, low glycogen
what are the physiologic and morphological characteristics of type 2A muscle fibers
Phys: fast twitch, oxidative and glycolytic fatigue resistant
Morph: intermediate mitochondria, fat and glycogen
what are the physiologic and morphological characteristics of type 2B muscle fibers
fast twitch, fatigue sensitive, glycolytic “white muscle” anaerobic
Morph: low mitochondria and fat, high glycogen
which muscle fibers are used for long distance
type 1
which muscle fibers are used for short distance, high intensity
2B
how does the percentage of type 1 and type 2 muscle fibers differ in the fore and hindlimbs
more type 1 muscle fibers (postural) in forelimbs
More type 2 muscle fibers (locomotive) in hind limbs
what are the functions of muscle
- Posture and movement including respiration
- Homeostasis- glucose metabolism and body temp
the function of muscles is intimately related to the function of __
PNS
what is a neuropathic change in myofibers
effect of absence of nerve supply
what is a myopathic change in myofibers
primary changers are within muscle cells/fibers
neuromuscular diseases involve __
lower motor neurons, peripheral nerves, NMJ, and muscle
what is the epimysium
surrounds whole muscle
what is perimysium
surrounds fascicle
what is endomysium
around each muscle fiber
what are some clinpath findings that indicate skeletal muscle injury
- Elevated CK (muscle specific)
- Elevated LDH and AST
- Deficient carbonic anhydrase III
carbonic anhydrase III is critical for ___
acetylcholine receptor homeostasis in NMJ
carbonic anhydrase deficiency induces __ leading to __
accelerated degradation of AChR leading to myasthenia gravis
what is wrong in pallor muscle
necrosis, denervation, anemia, young animals
what is wrong in pale streaking muscle
necrosis and mineralization
what is wrong in dark red mottling muscle
congestion, hemorrhagic necrosis, inflammation, myoglobin staining and hypostatic congestion
what is wrong with green muscle
eosinophilic inflammation or putrefaction
what is wrong with lipofuscin (tan-brown) muscle
old animals
what is wrong with black muscle
melanoma
What wrong and what cause
Eosinophilic myositis- green discoloration due to abundant eosinophils in inflammation
Histo: tons of eosinophils
inflammation secondary to sarcocystis
from dog: what wrong and what could have caused this
pale streaks- necrosis and mineralization
Cause: Canine X-linked muscular dystrophy (Duchenne;s type)- dystrophin gene defect
what is dystrophin
structural link between muscle cytoskeleton and ECM to maintain muscle integrity
from horse- what wrong and what could have caused
Yellow streaks- denervation atrophy
Cause: equine motor neuron disease
type 1 postural muscle samples are best for what equine disorder
equine motor neuron disease
type 2 locomotive muscle samples are best for what equine disorder
equine polysaccharide storage myopathy
what muscles are best to submit for masticatory myositis in dogs
temporal and masseter
describe how to prepare muscle sample
- Collect muscle strip not larger than 1cm with myofibers running length wise
- Place on rigid surface (tongue depressor) to avoid contraction band artifacts after placing in fixative
how does the skin, subcutis and fascia act as defense mechanism of skeletal muscle
form structural barrier to protect from external injury
how does vasculature act as defense mechanism for skeletal muscle
collateral circulation protects against ischemia
Recruitment of monocytes, macrophages, neutrophils
Capillary endothelium resistant to tumor metastasis
what can cause disturbances of circulation and lead to a degenerative myopathy
- Occlusion of major blood vessel
- External pressure on muscle
- Compartment syndrome- swelling impedes blood- ischemia
- Vasculitis/vasculopathies
nutritional deficiency is a result in loss of __mechanism
Antioxidant defense
what are common nutritional deficiencies and is the result
vitamin E or selenium deficiency—> necrosis and pale—> oxidative injury—> white muscle disease
selenium is vital in __ system which protects against ___
glutathione perioxidase, oxidative injury
how do ionophore cause toxic myopathies
overdose—> disruption of ionic equilibrium—> calcium overload—> skeletal and cardiac muscle necrosis
what are some clinical signs of ionophore toxicity
anorexia, diarrhea, weakness
__ and __ are extremely high with ionophore toxicity
CK and AST
what is the most common degenerative myopathy in cows and what is cause
Plant toxicity due to senna occidentalis
horse that lived with cows suddenly became very weak, off feed, colic signs, arrhythmias. This histo was taken- what wrong and what likely cause
Necrosis and fragmented muscle fibers
Cause: ionophore toxicity
what is exercise induced myonecrosis known as and what are some causes
capture myopathy
Causes: extreme stress, struggle or exertion
what are some signs of equine exertional rhabdomyolsis
sudden onset stiff gait, reluctance to move, swelling over muscles, especially gluteals
what blood work sign is consistent with equine exertional rhabdomyolysis
high CK and AST
what causes equine exertional rhabdomyolysis
high grain feeding and lack of regular exercise
what wrong here and identify 1
myositis ossificans
1. Osseous metaplasia
what is myositis ossificans
focal lesion of fibrosis with osseous metaplasia caused by muscle trauma
what is muscle dystrophy
inherited progressive, degenerative primary disease of myofibers characterized by ongoing necrosis and regeneration
what is myotonia/ channelopathies
inability of myofibers to relax, resulting in spasmodic contractions. Abnormal ion channel function
what wrong
congenital muscle steatosis- pale muscles, replace of muscles by adipocytes
Denervation atrophy
what wrong and cause
congenital muscular hyperplasia caused by genetic defect causing inactivation myostatin gene which regulates number and size of myofibers
what is malignant hyperthermia and cause
Cause: defect in ryanodine receptor triggered by anesthesia (halothene) or stress
Causes unregulated release of Ca2+ from SR leading to increased contraction that generates heat, severely increased body temp
in pigs what is malignant hyperthermia also called
Porcine stress syndrome or pork/pale soft exudative
what are metabolic myopatheis characterized by
reduced muscle cell energy production
what is type IV glycogen storage disease
glycogen branching enzyme deficiency
what does glycogen branching enzyme typically produce
alpha 1-6 branches in glucose
glycogen branching enzyme is necessary to build __
glycogen
what happens with deficient GBE
Glycogen lacks normal branched structure—> can’t effectively utilize glycogen as energy source—> tissues become weak and unable to function properly
in GBE deficiency what abnormal form of glycogen accumulates in cells
amylopectin
Foal born, very weak, no energy, can’t stand. Perform histopath and this is result what wrong and what stain was used
purple clumps are amylopectin which increase in glycogen storage disease type IV: GBE deficiency
Stain: PAS
from patient with GBE deficiency, what is arrow pointing at
hyaline inclusion
what is the cause of acquired myasthenia gravis
immune mediated disordered caused by circulating autoantibodies that target skeletal muscle acetylcholine receptor
autoantibodies in myasthenia gravis damage receptor due to __ or __
- direct effect on NMJ
- Formation of cross-linked antibodies that lead to receptor internalization
Why type of tumor has been associated with myasthenia gravis and what does it cause
thymoma- secondary loss of self tolerance to acetylcholine receptors (myoid cells involved)
how do you dx myasthenia gravis
detection of autoantibodies to acetylcholine receptor in blood
botulinum toxicity is characterized by profound __
flaccid paralysis
How does botulinum cause flaccid paralysis
toxin causes cleavage of SNARE proteins that are responsible for release of acetylcholine from pre synaptic vesicles
What botulism toxin type are dogs, ruminants and horses sensitive to
dogs: type C
Ruminants: type C and D
Horses: type C and B
what is the cause of tick paralysis
toxins produced by dermacentor or ixodes ticks that block acetylcholine release at axon terminal
Rhabdomyoma and rhabdomyosarcomas arise from ___
intramuscular pluripotent cells
what is a rhabdomyoma, where do they occur and in who
benign, smooth, pink, nodular, unencapsulated. Occur commonly inn larynx of adult dogs
what is a rhabdomyosarcoma, where do they occur and in who
malignant tumor, occur at young age most commonly in the neck, oral cavity, tongue
what is the most common primary neoplasm of skeletal muscle
hemangiosarcoma
5yr old dog presents with SQ mass, histo shows the following. Which is abnormal mass vs control. IHC was done- what does that tell you
left: rhabdomyosarcoma- Desmin +
Right: normal control
what are infiltrative lipomas
variant of lipoma that recurs if not completely excised, but does not metastasize, make muscle pale and weak
what causes vaccine associated sarcomas
IM vaccine sites or extended into underlying muscle from SQ injections
