Rhabdomyolysis

Excerpt

Rhabdomyolysis means dissolution of skeletal muscle, and it is characterized by leakage of muscle cell contents, myoglobin, sarcoplasmic proteins (creatine kinase, lactate dehydrogenase, aldolase, alanine, and aspartate aminotransferase), and electrolytes into the extracellular fluid and the circulation. The word rhabdomyolysis is derived from the Greek words rhabdos (rod-like/striated), mus (muscle), and Lucis (breakdown). The common symptoms and signs are muscle weakness, pain/myalgia, and local swelling, and may be associated with dark red color urine/myoglobinuria. It can range from mild elevation in creatinine phosphokinase to medical emergencies like compartment syndrome, intravascular fluid depletion, Disseminated intravascular coagulation, pigment-induced acute kidney injury(AKI), and cardiac arrhythmias. Laboratory diagnosis of rhabdomyolysis shows elevations in serum creatine phosphokinase (CPK), and there is no specific established serum level cut-off. Many physicians use three to five times the upper limit of normal Values of 100 to 400 IU/L(approximately 1000 IU/liter) for diagnosis. Rhabdomyolysis is one of the major causes of acute renal failure. If identified early, the prognosis of acute kidney injury with rhabdomyolysis is relatively benign. The etiology of rhabdomyolysis can be classified as traumatic and nontraumatic. Important causes of traumatic rhabdomyolysis are crush syndrome from accidents, earthquakes, and other natural and manufactured disasters. Not every muscle trauma leads to rhabdomyolysis and renal failure. Alternative causes for acute renal failure, like dehydration, sepsis, and drugs, should always be evaluated. Seizures, alcohol use, drugs, and prolonged bedridden state are common causes of nontraumatic rhabdomyolysis.

Myolysis after the consumption of Coturnix coturnix, the common quail, has been well-known in Mediterranean countries for ages. Rhabdomyolysis history can be traced back to the time of the Old Testament when Israelites suffered from similar symptoms like rhabdomyolysis after consumption of quail during their departure from Egypt. This myolysis results from the consumption of hemlock herb-intoxicated quails (coturnism) during spring migration. A similar clinical presentation has also been reported from Italy after consuming robins, Chaffinches, and Skylarks. These birds are not susceptible to the active alkaloids from hemlock herbs. The first description of rhabdomyolysis in the modern era dates back to 1812, during the Berlin occupation by the Napeloean army by Baron Dominique Jean Larrey, a French surgeon. The first reported traumatic rhabdomyolysis and AKI cases in the 20th century were seen by German surgeon Ludwig Frankenthal around 1916 during World War I. The official German military medical records showed as many as 126 cases of rhabdomyolysis. Not aware of this deadly syndrome, the Allies entered World War II only to rediscover rhabdomyolysis in London by Eric Bywaters in 1940. Bywaters and Stead identified myoglobin as the offending agent for brown urine acute tubular necrosis in 1943 in animal experiments. Myoglobin is a 19 kilodalton oxygen-carrying protein loosely bound to plasma globulins. When in excess, it reaches the tubules, where it may cause obstruction and renal dysfunction. They formulated vigorous rehydration at the site of the accident and urine alkalinization to decrease myoglobin precipitation in renal tubules. Other rare causes of rhabdomyolysis include Haff disease (first described in 1924 in Russia; Haff means shallow lagoon in German, and it is commonly associated with crayfish ingestion; the exact nature of the toxin in the aquatic food chain is not very clear), mushroom poisonings, and most recently, genetic disorders in the late 20th century.

The common causes of rhabdomyolysis are trauma, exertion, muscle hypoxia, infections, metabolic and electrolyte disorders, drugs, toxins, and genetic defects. Recurrent episodes of rhabdomyolysis should prompt workup to identify underlying defects in muscle metabolism. The muscle damage can be from direct injury/trauma or metabolic inequalities resulting in direct sarcolemmic injury or ATP depletion within the muscle fiber. Depletion of ATP impairs intracellular calcium regulation (usually, muscle cells maintain low levels of calcium at rest and increased calcium necessary for actin–myosin-binding during contraction), resulting in a persistent increase in sarcoplasmic calcium, causing persistent contraction, energy depletion, and activation of calcium-dependent proteases, phospholipases and eventual destruction of myofibrillar, cytoskeletal, and membrane proteins, followed by lysosomal digestion of fiber contents.

Rhabdomyolysis clinically is a triad of myalgia, myoglobinuria (tea-colored urine), and weakness. Even though less than 10% of patients present with classic symptoms, most patients have mild abnormal laboratory findings and are asymptomatic. Elevated CPK is the most sensitive laboratory test for the evaluation of muscle injury. Unfortunately, the elevation of CPK level has no good correlation with the severity of muscle damage and renal failure. In general, CPK levels of more than 5000 international units/L will have some amount of significant muscle injury. Treatment of rhabdomyolysis mainly constitutes supportive care with adequate hydration, and the goal is to prevent acute renal failure.