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CHAPTER TEST 
LEARNING
OBJECTIVESRhabdomyolysis (literally dissolution
of striated muscle) is myonecrosis
on a massive scale with leakage
of myofiber contents, including
myoglobin, CK, and other proteins
into the circulation. Myonecrosis
is caused by two basic mechanisms,
mechanical physical injury
and energy depletion. Failure
of ATP-powered pumps allows influx
of calcium into the myofiber.
Calcium activates proteases and
phospolipases, leading to disintegration
of plasma membrane, contractile
filaments, and other myofiber
contents.
The causes of rhabdomyolysis are
listed in the table below.
| Trauma, crush |
| Excessive exertion, including status epilepticus, and alcohol withdrawal |
| Muscle ischemia, including compartment syndromes |
Inherited metabolic disorders
affecting energy metabolism.
These include:
|
| Muscle viral and bacterial infections, especially influenza and enteroviruses |
| Hyperthermia |
| Electrolyte imbalance and other severe metabolic derangements |
| Toxins (alcohol, heroin, cocaine) |
| Drugs, especially lipid-lowering agents |
Clinically, rhabdomyolysis is
characterized by weakness, myalgia,
and muscle swelling, and biochemically
by elevation of CK, which is proportionate
to the extent of myonecrosis.
Muscle regenerates rapidly following
myonecrosis. The most important
complication of severe rhabdomyolysis
is renal failure. When plasma
myoglobin exceeds 0.5-1.5 mg/dl,
it leaks into the urine and when
its urine concentration rises
above 100 mg/dl, it gives urine
a red-brown color (myoglobinuria)
and precipitates in distal tubules
in the form of casts. Myoglobinuria
is used synonymously with rhabdomyolysis.
A large proportion of acute renal
failure cases and associated deaths
are caused by rhabdomyolysis.
Myoglobin causes intrarenal vasoconstriction,
tubular injury, and tubular obstruction
by casts.
The lipid lowering agents statins, which are the most frequently prescribed drugs today, cause a range of neuromuscular adverse efects, which include myalgia, elevated CK, rhabdomyolysis, immune-mediated myopathy, mitochondrial myopathy, and peripheral neuropathy. Furthermore, stains can unmask or precipitate symptoms of other myopathies. The muscle biopsy in statin-related neuromuscular disorders may show myonecrosis, inflammatory myopathy, mitochondrial abnormalities, or denervation atrophy.
While statins are the most
frequent cause of drug-induced
neuromuscular adverse effects,
numerous other agents, partially
listed in the table below, can
cause muscle disease by a variety
of mechanisms.
DRUG INDUCED MUSCLE DISEASES
| DRUGS, AGENTS | MUSCLE DISEASE, PATHOLOGY |
| Alcohol, drugs of abuse, statins, emetine, hypokalemia, ε-aminocaproic acid | Myonecrosis |
d-penicillamine, phenytoin,
α-interferon, |
Inflammatory myopathy |
| AZT, cyclosporin, statins | Mitochondrial myopathy |
| IV corticosteroids and neuromuscular blockade agents | Myosin loss, critical illness myopathy |
| Corticosteroids | Type 2 fiber atrophy |
Antimalarials, amiodarone, perhexilene, Cochicine, vinristine |
Vacuolar myopathy (lysosomal) Vacuolar myopathy (sarcoplasmic reticulum) |
Further reading
Bosch X, Poch E, Grau JM. Rhabdomyolysis
and Acute Kidney Injury. N Engl J Med 2009;361:62-72 PubMed
Mastaglia, F. Iatrogenic myopathies. Curr Opin Neurol 2010, 23:445–9. PubMed
Updated: July, 2011
