Rhabdomyolysis

Abstract

The term rhabdomyolysis refers to disintegration of striated muscle, which results in the release of muscular cell constituents into the extracellular fluid and the circulation. One of the key compounds released is myoglobin, an 18,800-Dalton oxygen carrier. It resembles hemoglobin, but contains only one heme moiety. Normally, myoglobin is loosely bound to plasma globulins and only small amounts reach the urine. When massive amounts of myoglobin are released, the binding capacity of the plasma protein is exceeded. Myoglobin is then filtered by the glomeruli and reaches the tubules, where it may cause obstruction and renal dysfunction (1). The degree of rhabdomyolysis that can manifest ranges from a subclinical rise of creatine kinase (CK) to a medical emergency comprising interstitial and muscle cell edema, contraction of intravascular volume, and pigment-induced acute renal failure (ARF). Today, rhabdomyolysis is one of the leading causes of ARF (1,2). The prognosis of rhabdomyolysis-associated ARF is relatively benign (3). One major cause of rhabdomyolysis is the crush syndrome, i.e., myolysis is linked to traumatic compression of muscle followed by reperfusion, as is frequently seen in accidents or disasters. Muscular trauma, however, does not always lead to rhabdomyolysis, not all rhabdomyolysis leads to ARF, and not all ARF related to crush is attributable to rhabdomyolysis. Alternative causes of ARF in rhabdomyolysis may include dehydration, sepsis, and drug nephrotoxicity. Most cases of rhabdomyolysis in peacetime are nontraumatic; they are most frequently the consequence of seizures, alcohol abuse, or compression as a result of coma (see below) (4). Historical Notes Rhabdomyolysis was observed in ancient times (5). The Old Testament refers to a plague suffered by the Israelites during their exodus from Egypt after abundant consumption of quail (Book of Numbers 11:31-35). Myolysis after the consumption of quail is well known in the Mediterranean region. It is the result of intoxication by hemlock herbs, which are consumed by quails during their spring migration (6). Remarkably, indirect evidence substantiates that this biblical episode occurred in springtime (5). In modern times, the first cases of crush syndrome and ARF were reported during the Sicilian earthquake in Messina in 1908 and in the German military medical literature during World War I (7). The latter concerned cases of rhabdomyolysis observed after soldiers had been buried in trenches. In modern English medical literature, the authors of the first detailed report of ARF related to the crush syndrome were Bywaters and Beall. They observed the condition in four victims of the bombing of London during the Battle of Britain in 1940 (7). The authors pointed to the link between rhabdomyolysis and renal failure. The role of myoglobin was later classified in greater detail in an experimental publication (8). It was only decades later, in the early 1970s, that nontraumatic causes of rhabdomyolysis were recognized and identified as a potential cause of ARF (9, 10). Etiology It is beyond the scope of this review to discuss the many conditions in which rhabdomyolysis may occur, but we shall summarize the most frequent ones (Table 1).Table 1: Etiology of rhabdomyolysisTrauma and Compression Traumatic rhabdomyolysis is mainly the result of traffic or occupational accidents. Compression of the muscles may also be induced by torture, abuse, or long-term confinement in the same position (orthopedic problems; surgical interventions necessitating specific positions for a long time; psychiatric conditions; coma). Occlusion of the Muscular Vessels Thrombosis, embolism, or clamping of vessels during surgery may all result in muscle cell necrosis if oxygen deprivation is maintained for prolonged periods (11). ARF occurs only if a critical mass of muscle has become necrotic, e.g., after total vascular occlusion involving at least one limb, after multiple diffuse emboli, or during generalized shock. Strainful Exercise of Muscles Strenuous muscular exercise may cause myolysis, especially in untrained subjects or in individuals exercising under extremely hot or humid conditions (12, 13). Muscle necrosis more frequently occurs after downhill walking than after uphill climbing. The combination of muscular exertion, hypoxemia, and corticosteroid-induced myopathy may cause myolysis in patients with status asthmaticus (14). Because K+ is essential for vasodilation of the microvasculature of the muscles, exercise will cause more rapid muscle ischemia in hypokalemic subjects (15). Electrical Current High-voltage electrical injury and lightning strikes cause rhabdomyolysis in at least 10% of the subjects surviving the primary accident, even if the wounds of the site of entry are small (16). Myolysis is attributable to thermal injury, or to electrical disruption of sarcolemmal membranes. The latter results in pore formation, loss of barrier function, and massive calcium in