Muscle Pathology/Metabolic Myopathies

Question 1

Hallmarks of subacute necrotizing myopathy

Causes

Answer 1

Nuclei are gone, hyper-eosinophilia, myophagocytosis by macrophages
Very low potassium
Ischemia/infarction, toxic agents (statins), HMGcoA reductase inhibitors, and more

Question 2

Hallmarks of inflammatory myopathy

Answer 2

**autoimmune

Lymphocytes/T cells sensitized to muscle antigens, infiltrate fibers, germinal centers

Question 3

Hallmark of regenerative muscle fibers

Answer 3

Nuclei are peripheral and small, migrate towards the center and enlarge to resemble cardiac muscle but multiple nuclei instead of single.
*trying to recover

Question 4

Presentation of atrophied muscle fibers

Causes

Answer 4

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

Question 5

Type 1 fibers

Answer 5

Slow twitch, many mitochondria and fat, red, oxidative phosphorylation

Question 6

Type II fibers

Answer 6

White, fast twitch, glycogen, no fat (burn it quickly), goes into oxygen debt (lactic acid builds up)

Question 7

Trichrome histochemical stain: stains what? Which fiber has more?

Answer 7

Mitochondria- blue dots inside the cell
More blue dots in type 1 fibers

Nuclei on periphery are bright purple

Question 8

PAS stains what? Which fiber has more?

Answer 8

Stains glycogen- can add amylase to digest it and see where it was
Type II fibers

Dark pink= glycogen

Question 9

Add substrate that cytochrome oxidase will oxidize and stain

Answer 9

Precipitates a dark chromatin color (deep purple)

Type 1’s will be dark because this enzyme is in mitochondria (complex IV)

Question 10

Stains for ATPase- staining conditions stain which fibers

Answer 10

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

Question 11

Only one of the fiber types atrophy*- what is the pattern/cause?

Answer 11

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

Question 12

Atrophy of Type I fibers is only caused by:

Pattern?

Answer 12

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

Question 13

Neurogenic atrophy- adaptation

Signs of this

Answer 13

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)

Question 14

Muscular Dystrophy histology and stains

Answer 14

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

Question 15

McArdle’s Disease is a deficiency in what enzyme
what staining pattern?

Symptoms

Answer 15

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)

Question 16

Pompe’s Disease enzyme defect and staining

Answer 16

Alpha 1,4- glucosidase in lysosomes (acid Maltase in adults)

Glycogen accumulation in lysosomes, so it looks different from crescent shape in McArdle’s

Question 17

Systemic carnitine deficiency

Answer 17

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*

Question 18

Myopathic carnitine deficiency

Answer 18

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

Question 19

Defects in Carnitine Palmitoyltransferase Deficiency (CPT 1 and 2)
Define each
Symptoms
Histology

Answer 19

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

Question 20

Fiber with too much staining of cytochrome oxidase or trichrome stain
Pathology:

Answer 20

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)

Question 21

Diseases affecting the gylcolic pathway symptoms

Answer 21

Short duration high intensity activity leads to extreme muscle pain and weakness, but do well with low intensity long-duration exercises under fasting states

Question 22

Mitochondrial Myopathies present

Answer 22

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

Question 23

Pompeii’s disease muscle weakness pattern

Answer 23

Non-specific*, inconsistent patterns, delayed or long lasting pain, not correlated with muscles muscles most active, or constant muscle pain

Question 24

Polymyalgia rheumatica lab findings

Fibromyalgia lab findings

Answer 24

Will have normal EMG, CK, serum lactate and pyruvate, but elevated sedimentation rate

All lab findings are normal