Rhabdomyolysis

Essentials of Diagnosis

Muscular pain, tenderness, or weakness.
Elevated creatine kinase MM.

General Considerations

Rhabdomyolysis is a disorder resulting from an injury or a metabolic defect in the skeletal muscle cell (myocyte) resulting in lysis of the cell membrane (sarcolemma) and leakage of its contents (myoglobin, enzymes, phosphorus, potassium) into the blood. Myoglobin is readily filtered by the glomerulus and when it appears in the urine it defines the term myoglobinuria. Although some patients experience few symptoms, most demonstrate muscular pain, tenderness, stiffness, and weakness. Serum creatine kinase (CK) of the MM isoform is nearly always elevated. A rare exception is diabetic myonecrosis, in which painful infarction of skeletal muscle, usually in the thigh, often occurs in the absence of a significant elevation in CK.

Table 11–1 shows a general classification for the causes of rhabdomyolysis.

Table 11–1. Causes of Rhabdomyolysis.

Exertion and physical trauma

Direct trauma

Crush syndrome

Prolonged pressure with coma

Electrical shock

Thermal burns

Freezing

Excessive exercise

Athletic injury

Convulsive seizures

Punitive exercise

Hereditary myopathies

Myophosphorylase deficiency (McArdle’s disease)

Carnitine palmitoyltransferase deficiency

Acquired metabolic disorders

Hyperthyroidism

Diabetic ketoacidosis

Potassium deficiency

Phosphorus deficiency with acute hypophosphatemia

Alcoholism

Acute hyponatremia

Hypoxia and ischemia

Carbon monoxide poisoning

Vascular occlusion

Atheromatous embolism

Compartment syndrome

Drugs

Cocaine

Ephedra compounds

Amphetamine derivatives

3-Hydroxy-3-methylglutaryl coreductase inhibitors (statins)

Lipid-lowering drugs

Infectious disorders

Bacterial

Clostridial infection

Legionella

Streptococcal infection

Staphylococcal infection

Pneumococcal pneumonia

Viral

Influenza

Coxsackie

HIV

Toxins

Snake venom

Poisonous mushrooms

Quail fed on sweet parsley seeds

Fish poisoning (Haff disease)

Miscellaneous

Malignant hyperthermia

Neuroleptic malignant syndrome

Pathogenesis

Normal subjects can develop modest rhabdomyolysis after intense exertion. Violent, repetitive activities or a grand mal seizure are good examples. Presumably, exhaustive exercise not only may directly injure structural components of muscle cells, but may also deplete energy stores, which lowers the normal threshold for injury. Other factors that lower the threshold for injury include poor physical condition or preexistent injury, typified by alcoholic myopathy. For any given unit of work, women unexplainably show much less rhabdomyolysis than men. Volume depletion and exercise in the heat, perhaps by causing overheating of muscle and reduced blood flow, are potentiating factors. Eccentric muscle contractions (running downhill) are more likely to cause rhabdomyolysis than concentric contractions (running uphill). Fasting lowers the threshold presumably by limiting substrates for muscle contraction. Severe trauma and crush injury commonly cause rhabdomyolysis and the related acute renal failure often contributes to the mortality of these conditions. Direct muscle injury during surgery may cause modest elevations of muscle enzymes.

Inherited Metabolic Myopathies

A number of specific enzyme derangements are responsible for exertional rhabdomyolysis by impairing energy metabolism. Classic examples are myophosphorylase deficiency (McArdle’s syndrome) and carnitine palmityltransferase deficiency.