Rhabdomyolysis is caused by extensive muscle damage, which multiple causes may trigger. Traumatic causes of rhabdomyolysis include a crush injury (e.g., individuals involved in a building collapse); prolonged immobilization due to surgical positioning or hospitalized individuals; high-voltage electrical injuries (e.g., from lightning or power supplies); and severe third-degree burns. Another important cause of rhabdomyolysis is compartment syndrome when increased pressure inside an enclosed anatomical space reduces blood supply and subsequent tissue necrosis.
Rhabdomyolysis may also occur after strenuous physical activity, especially in untrained individuals and in hot, humid environments that predispose to heat stroke. Impaired heat dissipation from wearing heavy sports equipment increases the risk of rhabdomyolysis. In addition, numerous metabolic or genetic disorders (e.g., inflammatory and metabolic myopathies, glycogen storage disorders, mitochondrial diseases, etc.) also increase the risk of rhabdomyolysis. Other conditions that may lead to rhabdomyolysis include hyperkinetic states, such as seizures, psychomotor agitation; delirium tremens; hyperthermia; viral or bacterial infections; electrolyte disorders, like hypokalemia and hypophosphatemia; use of amphetamines, cocaine, or alcohol; and several medications, including statins, colchicine, and propofol. Certain toxins, such as snake venom, insect venom from wasp and bee stings, and mushroom poisoning, are other known causes of rhabdomyolysis.
Regardless of the mechanism, muscle injury results in a cascade of events that leads to the influx of extracellular sodium and calcium into muscle cells. Excessive intracellular sodium causes an influx of water, distorting the integrity of the intracellular space. Excessive intracellular calcium causes a sustained myofibril contraction, resulting in ATP depletion within these cells. Normal cellular processes may be affected. Additionally, the elevation of calcium inside the cell activates intracellular proteases and lipases, promoting damage to the
cellular membrane and disrupting ion channels. An inflammatory process typically results, which can cause necrosis of
muscle fibers and release of
muscle breakdown products- like potassium and myoglobin, creatine kinase (CK), phosphate, uric acid, and various organic acids- into the bloodstream.