Causes of rhabdomyolysis

Causes of rhabdomyolysis
Author
Marc L Miller, MD
Section Editors
Ira N Targoff, MD
Jeremy M Shefner, MD, PhD
Deputy Editor
Paul L Romain, MD
Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Oct 2012. | This topic last updated: Jun 12, 2012.
INTRODUCTION Rhabdomyolysis is a syndrome characterized by muscle necrosis and the
release of intracellular muscle constituents into the circulation. Creatine kinase (CK) levels are
typically markedly elevated, and muscle pain and myoglobinuria may be present. The severity of
illness ranges from asymptomatic elevations in serum muscle enzymes to life-threatening disease
associated with extreme enzyme elevations, electrolyte imbalances, and acute kidney injury.
The causes of rhabdomyolysis will be reviewed here. The clinical manifestations and diagnosis
of rhabdomyolysis; the clinical features and diagnosis of acute kidney injury due to
rhabdomyolysis; the management of patients with rhabdomyolysis, including methods to prevent
acute kidney injury and related metabolic complications; and the prevention and management of
acute compartment syndrome are discussed in detail separately. (See "Clinical manifestations
and diagnosis of rhabdomyolysis" and "Clinical features and diagnosis of heme pigment-induced
acute kidney injury (acute renal failure)" and "Prevention and treatment of heme pigmentinduced acute kidney injury (acute renal failure)" and "Crush-related acute kidney injury (acute
renal failure)" and "Acute compartment syndrome of the extremities".)
PATHOPHYSIOLOGY The clinical manifestations and complications of rhabdomyolysis
result from muscle cell death, which may be triggered by any of a variety of initiating events.
The final common pathway for injury is an increase in intracellular free ionized cytoplasmic and
mitochondrial calcium. This may be caused by depletion of ATP, the cellular source of energy,
and/or by direct injury and rupture of the plasma membrane [1,2]. The latter pathway of injury
also results in ATP depletion.
The increased intracellular calcium leads to activation of proteases, increased skeletal muscle
cell contractility, mitochondrial dysfunction, and the production of reactive oxygen species,
resulting in skeletal muscle cell death [1]. ATP depletion causes dysfunction of the Na/KATPase and Ca2+ATPase pumps that are essential to maintaining integrity of the myocyte. ATP
depletion leads to myocyte injury and the release of intracellular muscle constituents, including
creatine kinase and other muscle enzymes, myoglobin, and various electrolytes.