Muscle Pathology/Metabolic Myopathies Flashcards
Hallmarks of subacute necrotizing myopathy
Causes
Nuclei are gone, hyper-eosinophilia, myophagocytosis by macrophages
Very low potassium
Ischemia/infarction, toxic agents (statins), HMGcoA reductase inhibitors, and more
Hallmarks of inflammatory myopathy
**autoimmune
Lymphocytes/T cells sensitized to muscle antigens, infiltrate fibers, germinal centers
Hallmark of regenerative muscle fibers
Nuclei are peripheral and small, migrate towards the center and enlarge to resemble cardiac muscle but multiple nuclei instead of single.
*trying to recover
Presentation of atrophied muscle fibers
Causes
No necrosis or inflammation* but variability in size of fibers- some very small, some very large
Nuclear clumps seen= severe atrophy of cell
Atrophy is nonspecific* many causes
Type 1 fibers
Slow twitch, many mitochondria and fat, red, oxidative phosphorylation
Type II fibers
White, fast twitch, glycogen, no fat (burn it quickly), goes into oxygen debt (lactic acid builds up)
Trichrome histochemical stain: stains what? Which fiber has more?
Mitochondria- blue dots inside the cell
More blue dots in type 1 fibers
Nuclei on periphery are bright purple
PAS stains what? Which fiber has more?
Stains glycogen- can add amylase to digest it and see where it was
Type II fibers
Dark pink= glycogen
Add substrate that cytochrome oxidase will oxidize and stain
Precipitates a dark chromatin color (deep purple)
Type 1’s will be dark because this enzyme is in mitochondria (complex IV)
Stains for ATPase- staining conditions stain which fibers
Different stains work well at different pH
This enzyme is important for myosin/actin sliding and contracting
Type 1- works well at low ph
Type 2- works well at higher ph
Ex) at ph 10, the darker stain ATPase will be type II.
Dark red
Only one of the fiber types atrophy*- what is the pattern/cause?
Only type II- diffuse atrophy, large fibers are normal size and small fibers are distorted
Type II atrophy is nonspecific: disuse, steroids, toxins, medications, any primary myopathy, subacute necrotizing changes, etc
Atrophy of Type I fibers is only caused by:
Pattern?
Motor neuron deficit/motor nerve problem
Innervation of muscle fibers by lower motor neuron (anterior horn)- some innervate type 1 and some are type 2–> alternate checker board pattern
Affects type 1 and 2’s**
Neurogenic atrophy- the muscle cells won’t die, but will shrink and get smaller, like in type II atrophy
Neurogenic atrophy- adaptation
Signs of this
Other motor neurons will reinnervate these fibers that lost theirs, will appear like normal cells but will be of a different type fiber now: big area where they are all the same fiber staining type (result of end stage neurodegenerative disease)
Can get ‘group atrophy’ of an entire fascicle
Distal weakness- muscles are not dying* (patients with muscle disease will have more proximal issues and higher CK levels)
Muscular Dystrophy histology and stains
Fibrosis, endomysium between cells get fibrotic and scarred, cells no longer function, extra connective tissue, collagen between muscle cells, fat replaced some muscle
Atrophy of muscle cells
Stain for sarcogylcan- normally will be around the entire membrane (dark orange border): severely diminished in MD
McArdle’s Disease is a deficiency in what enzyme
what staining pattern?
Symptoms
Glycogen phosphorylase b- results in crescent shaped accumulation of glycogen on type II fibers with PAS stain
Usually cramps with short, strenuous exercise (affects type II)
Second wind phenomenon
(Myoglobinuria is more frequent in lipid storage defect CPT)
Don’t see the normal increase in lactic acid levels because not going through glycolysis (CPT def will have normal LA increase)
Pompe’s Disease enzyme defect and staining
Alpha 1,4- glucosidase in lysosomes (acid Maltase in adults)
Glycogen accumulation in lysosomes, so it looks different from crescent shape in McArdle’s
Systemic carnitine deficiency
Infancy/childhood, impaired hepatic synthesis of carnitine , with reduced plasma and tissue carnitine levels, presents as progressive weakness, hepatic/CNS/cardiac problems, precipitated by fasting*
Myopathic carnitine deficiency
Childhood/early adult, impaired transport of carnitine from plasma into muscle cells, with reduced muscle carnitine but may have normal levels in plasma/liver, presents with proximal muscle weakness, myalgia with exertion, myoglobinuria
Defects in Carnitine Palmitoyltransferase Deficiency (CPT 1 and 2)
Define each
Symptoms
Histology
CPT 1 is outer mitochondrial membrane- FAcoA–> acyl carnitine to be transferred into mito by CAT
CPT 2 is inner mitochondrial membrane- removes the carnitine, releasing FA-Coa for BOX. Disease is more common here (auto rec)
Symptoms- recurring episodes of rhabomyolysis and myoglobinuria, triggered by prolonged exercise, precipitated by fasting or cold weather
*usually no warming signs, unlike glycogenoses which have cramping
Increased CK, coke-colored urine, maybe renal failure. Plasma carnitine and EMG may be normal
Usually don’t have glycogen storage or lipid storage, FA could accumulate in cytoplasm
Fiber with too much staining of cytochrome oxidase or trichrome stain
Pathology:
Cytochrome oxidase mutation- cells are hypoxia, so they make more mitochondria to try and compensate= accumulation of mitochondria seen that are all still dysfunctional
*Ragged red fiber- mitochondrial myopathy- abnormal cristae in whorls and ‘parking lot’ paracrystalline structures
(CPT defect will have normal mitochondria and increase in fat)
Diseases affecting the gylcolic pathway symptoms
Short duration high intensity activity leads to extreme muscle pain and weakness, but do well with low intensity long-duration exercises under fasting states
Mitochondrial Myopathies present
Tolerate short duration high intensity exercise, but low intensity long-duration exercises, particularly with fasting lead to extreme pain and weakness
Usually lactate levels are increased
Pompeii’s disease muscle weakness pattern
Non-specific*, inconsistent patterns, delayed or long lasting pain, not correlated with muscles muscles most active, or constant muscle pain
Polymyalgia rheumatica lab findings
Fibromyalgia lab findings
Will have normal EMG, CK, serum lactate and pyruvate, but elevated sedimentation rate
All lab findings are normal
