A specific kind of muscle damage often seen in survivors of earthquakes and car crashes can have immediate concerns for exercise professionals, especially those working with entry-level exercisers.

The condition is a syndrome called rhabdomyolysis (RM), which literally means the breakdown of striated muscle (Landau et al. 2012). While broadly defined, RM typically describes a weakening of the muscle cell membrane (or sarcolemma), resulting in muscle proteins leaking into the bloodstream. Elevated levels of muscle proteins (notably myoglobin) in the blood can trigger potentially life-threatening complications such as acute renal failure, blood clotting and hyperkalemia, an elevation of potassium in the blood that may lead to an abnormal heart rhythm.

While RM often results from crushing injuries like automotive accidents and building collapses and can be caused by blood restriction to tissues and by some drugs, exercise-induced RM or exertional RM (ERM) is the most frequent cause of RM-related hospitalization (Alpers & Jones 2010). Given the seriousness of this syndrome and the fact that exercise is a potential trigger, ERM should be on the minds of fitness professionals when they are working with any client. This review will help personal trainers understand the pathophysiology (functional changes that accompany a particular syndrome) of ERM; learn how to recognize ERM; and identify situations in which risk of ERM is increased.

Pathophysiology of ERM

Reports of RM date back thousands of years (Vanholder et al. 2000). In more recent history, RM cases were documented after the Sicilian earthquake in 1908 and in the German military literature after the First World War (Giannoglou, Chatzizisis & Misirli 2007). British physicians Eric Bywaters and Desmond Beall reported cases of RM in London bombing victims in 1940.Now, present-day researchers have observed an upswing in the exertion-induced variety of RM, triggered by intense exercise.

All RM causes have one thing in common: the loss of intracellular ionized calcium (Ca2+) homeostasis, or internal equilibrium (see Figure 1). Ca2+ resides in a special reservoir of tissue in muscle, known as the sarcoplasmic reticulum. It serves as a trigger for muscle contraction.

After intense muscle contraction, increases in sarcoplasmic calcium concentrations initiate a cascade of events that damage muscle cells and spill proteins into the blood. Abnormally high Ca2+ concentrations activate the release of protein-degrading enzymes called calpains and of sarcolemma-degrading enzymes called phospholipase A2 enzymes, which weaken the sarcolemmas and increase their permeability (Allen, Whitehead & Yeung 2005). When sarcolemmas become more permeable, potentially harmful proteins can leak into the blood.

Exertional Exercise and Rhabdomyolysis

The increase in Ca2+ release in the cell fluid, or sarcoplasm, after exertional exercise appears to be (at least in part) due to stretch-activated ion channels, or SACs (Allen, Whitehead & Yeung 2005). SACs are located on the sarcoplasmic reticulum and become activated by mechanical stretch with load; for example, with repetitive bouts of eccentric exercise, intense exercise or high-repetition exercise.

Activated SACs allow the flow of several cations (positively charged minerals), including Ca2+, into the cell fluid (Allen, Whitehead & Yeung 2005). Landau et al. (2012) report that consistent exercise risk factors for developing ERM appear to be low baseline fitness levels and early introduction of highly repetitive exercises like squats, push-ups and sit-ups. A common factor in ERM seems to be exertion beyond the point when fatigue would compel an individual to stop naturally, say the authors.

Landau and colleagues (2012) report examples of extreme exertion leading to ERM when exercisers attempted to do hundreds of push-ups in an afternoon or suffered from “squat jump syndrome” after being told to squat as low as possible and then jump as explosively as possible repeatedly until exhaustion. The authors observe that although extreme exercise loading is most associated with ERM, it can be brought on by seemingly “safe” exercise too, because some people are just more physiologically vulnerable. Exercising in hot environments predisposes exercisers to ERM, so trainers should always monitor clients carefully when heat becomes a factor.

Eccentric Exercise and Rhabdomyolysis

Stretch-activated ion channels are particularly prone to activation by eccentric contractions, which happen when a muscle is being stretched while it is trying to contract. SACs activated by eccentric contractions that lead to a dramatic increase in sarcoplasmic Ca2+ may explain why exercise-induced muscle damage is most associated with eccentric exercise (Landau et al. 2012).

Skeletal muscle is exceedingly responsive to demands imposed on it. The impressive plasticity of skeletal muscle is exemplified in the phenomenon known as the repeated bout effect. As explained in a previous IDEA Fitness Journal article (Bubbico & Kravitz 2010), this effect indicates that skeletal muscle rapidly adapts to eccentric exercise stress when the eccentric exercise is introduced at much lighter intensities up to a week before a person performs higher-intensity eccentric training. The targeted muscles prepare protective mechanisms that reduce cellular Ca2+ spillage and degrade protein leakage, reducing the chance of ERM.

Signs and Symptoms: The ERM Triad

Only a doctor can diagnose an individual with RM. However, early detection is important, which is why fitness professionals should be alert to signs of the syndrome so they can refer the client to a medical professional for prompt diagnosis.

A typical triad of symptoms includes reddish-brown (cola-colored) urine, muscular pain and weakness. Reddish-brown urine may indicate myoglobinuria (presence of myoglobin in the urine) and can be a powerful diagnostic tool of RM (Giannoglou, Chatzizsis & Misirli 2007). Reddish-brown urine, however, is present in only about half of RM cases. Therefore, its absence does not rule out RM (Giannoglou, Chatzizsis & Misirli 2007). Unfortunately, muscular pain and weakness are nonspecific, subjective and commonly experienced after intense and/or unaccustomed exercise without adverse effects. Muscle stiffness and swelling may also be symptoms of RM (Giannoglou, Chatzizsis & Misirli 2007).

Taken together, these symptoms should lead fitness professionals to suspect the possibility of ERM if clients report ongoing muscle soreness and weakness following exercise. Clients who report reddish-brown urine should be immediately referred to a medical professional.

How Fitness Level and Too Much Unaccustomed Exercise Affect ERM Risk

A client’s fitness level is particularly important to consider when designing a workout or exercise program (Landau et al. 2012). In other words, what type of exercise training (if any) has the client done in the past to prepare for the ensuing workout? How long and how much has he trained? ERM may occur when an individual is unaccustomed and unprepared for the mode or intensity of the exercise ahead. So an entry-level client attempting an extreme conditioning program could put herself at risk for ERM.

Practical Application: Avoiding ERM

Fitness professionals understand the importance and effectiveness of high-intensity training. However, when designing an exercise program, it is important for exercise professionals to carefully apply the principles of initial fitness level and progressive overload so that the exercise stress challenges the client appropriately. This is particularly imperative when a client is new to exercise, returning to exercise after a hiatus or embarking on a new training phase or novel training stimulus. Trainers should also take extra care when introducing eccentric exercise, when clients are exercising in a hot environment or when a client has any genetic risk factors for rhabdomyolysis (see the sidebar “Genetic Risk Factors for Rhabdomyolysis”).

Figure 1. Pathophysiology of Rhabdomyolysis

Source: Adapted from Landau et al. 2012.
Rhabdomyolysis at a Glance

Definition. Muscle breakdown that leaks harmful proteins into the bloodstream.

Causes. Crushing injuries; repetitive bouts of eccentric exercise, intense exercise or high-repetition exercise; blood restriction to tissues; some drugs.

Threats. Renal failure, blood clotting, irregular heart rate.

Who is vulnerable. Beginning exercisers; those starting new, high-intensity regimens; people with genetic predisposition.

Symptoms. Reddish-brown tint in urine; ongoing muscle soreness and weakness after exercise.

Genetic Risk Factors for Rhabdomyolysis

Some genetic variations may predispose people to experience RM. Many of these variations result in a deficiency of enzymes important in ATP production or calcium handling. According to Landau et al. (2012), the most common inherited genetic alterations known to increase risk of RM are the following:

  • McArdle’s disease. McArdle’s patients may have an increased risk of developing RM because of a reduced ability to utilize glycogen to make ATP.
  • Carnitine palmitoyltransferase II deficiency. Carnitine palmitoyltransferase II is an enzyme required for long-chain fatty acids to enter the mitochondria (ATP synthesis factory), where they may be broken down for energy. People with genetic deficiencies in this enzyme appear to have an increased risk of RM because of reduced ability to produce ATP from fat.
  • Myoadenylate deaminase deficiency. Myoadenylate deaminase is an enzyme that is important for re-formation of ATP. Individuals with a genetic deficiency in this enzyme may have an increased risk of RM because of a reduced ability to re-form ATP during intense exercise.


Allen, D.G, Whitehead, N.P, & Yeung, E.W. 2005. Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: Role of ionic changes. The Journal of Physiology, 567 (Pt. 3), 723–35.
Alpers, J.P., & Jones, L.K. 2010. Natural history of exertional rhabdomyolysis, a population-based analysis. Muscle & Nerve, 42, 487–91.
Bubbico, A., & Kravitz, L. 2010. Eccentric exercise. IDEA Fitness Journal, 7 (9), 50–59.
Giannoglou, G.D., Chatzizisis, Y.S., & Misirli, G. 2007. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. European Journal of Internal Medicine, 18, 90–100.
Landau, M.E, et al. 2012. Exertional rhabdomyolysis: A clinical review with a focus on genetic influences. Journal of Clinical Neuromuscular Disease, 13 (3), 122–36.
Vanholder, R., et al. 2000. Rhabdomyolysis. Journal of the American Society of Nephrology, 11 (8), 1553–61.

Mike Deyhle

Mike Deyhle, CSCS, is a masterÔÇÖs-degree student in exercise science at the University of New Mexico, Albuquerque. His research interests include exercise-induced muscle damage and signal transduction in exercise physiology. He is a former gymnast who enjoys rock climbing, cycling and playing classical guitar.

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