You may or may not have heard of it before, but rhabdomyolysis affects more than just lifters, although it tends to be weight lifters that worry over it (or have a lack of worry) the most. In this article, we will discuss what rhabdomyolysis is, what situations it occurs, and as well as understand the cellular and tissue pathophysiology of the condition.

What is Rhabdomyolysis?

Rhabdomyolysis is a condition in which the kidneys begin to, or completely, die due to a mass exposure to muscle cell contents due to extreme trauma.

Why does it occur?

 Mass trauma induced by a series of stressors, such as extreme workout bouts, crush injury, surgery, genetic muscle diseases, viral infections, and/or a host of other contributors [1][2]. Essentially, irrecuperable muscle damage leading to muscle cell death increases a ton of products in serum (myoglobin, creatine kinase, calcium, and much more) that the kidneys have to clear from the blood [1][2].

Understanding the 


Take any of these stressors mentioned above – insane levels of weight lifting (as in, hours in the gym, lifting to failure over and over again then coming back for more – of course, this can vary depending on the person), and the myocytes (muscle cells) must adapt to the extreme nature of the trauma. Unfortunately, while the muscle cells are used to the stimulus of lifting creating microtrauma within the cell and on the cell membrane – eventually enough is enough. As a result, an inability to recover from deep perturbations of the cell membrane leads to an uncontrolled efflux of calcium into the cytosol, and especially into the mitochondria [2]. This sudden, uncontrolled release of calcium from the sarcoplasmic reticulum, primarily, leads to an oversaturation of calcium in the mitochondrion, which is in close proximity with the sarcoplasmic reticulum [3]. Once the mitochondrion is saturated with calcium through calcium uniporters, primarily, the membrane potential destabilizes (increasing from its normal -180 mV), and apoptotic (aka, cell death) proteins become active [3][4].

Mitochondrial Calcium Uniporter (MCU) allows calcium into the mitochondria. Notice the proximity of the Sarcoplasmic Reticulum.

Two mechanisms lead to the beginning of this apoptotic mechanism: either calcium swells the mitochondrion, and/or apoptotic inducing proteins are released (from the within the mitochondrion) once the mitochondrial membrane is permeabilized (the way it ends up permeabilized is unclear, possibly through the beginning of mitophagy via the lysosome or through the opening of a permeability transition pore allowing ions through) [3]. The fragmentation of mitochondria in the cell leads to an even more compromised cellular energy state (lowered ATP), leading to a highly unlikely recovery by the cell via the sarcoplasmic-endoplasmic reticular calcium ATPase pumps sequestering calcium back into the sarcoplasmic reticulum, or the efflux of calcium back out of the cell via plasma membrane Ca2+ ATPase [2][3][5].

A. Apoptosis of a cell (not muscle).

B. Necrosis of a cell (not muscle). [8]

Without going into every detail on each organelle - bottom line, the cell kills itself from external damage. Necrosis occurs.

Once the cell’s membrane has permeabilized, many of the substances housed in the cell are released and end up in the blood; like phosphates, enzymes (lactate dehydrogenase, creatine kinase, etc.), ions (potassium, calcium, etc.), and most importantly for this scenario – myoglobin [2][6].

Due to sarcolemmal damage, the remaining, non-necrotic muscle cells pull in water, leaving less in the blood stream. This reduction in blood volume leads to the pituitary gland releasing antidiuretic hormone (aka, vasopressin) which acts on the kidneys to release renin [2][5].  Simultaneously, aldosterone may also be released from the adrenal cortex [6]. These hormones lead to vasoconstriction of the blood vessels and the retention of water by the renal system [5]. However, since many muscle cells have undergone necrosis and released their contents, myoglobin is much higher in serum.

Nephron of a kidney. Myoglobin can

also obstruct deeper areas of the nephron, decreasing filtration rate. 

The increase in myoglobin is especially detrimental, because it contains ferrous oxide/iron that reacts with oxygen to form free radicals via ferric oxide [5]. Intracellularly, the cell can control this production of reactive oxygen species (free radicals) by neutralizing them, but as the cell housing the myoglobin no longer exists, these free radicals are formed, uninhibited [2][5]. This, in the nephrons (“plumbing” system that accepts blood and clears it) of the kidneys leads to damage of the endothelial cells lining the glomerular capillaries that accept blood and clear it of unwanted metabolites. So, not only is less blood perfusing the kidneys, leading to less exchange of general metabolites, but the myoglobin is sitting in the glomerular capillaries in higher concentration (more myoglobin per ml of blood/water). This increased myoglobin produced reactive oxygen species leads to further localized vasoconstriction and damage to the nephron tubules, and glomerular capsules [5].


Rhabdomyolysis affects you through damage of kidneys. The kidneys are bombarded with myoglobin released from dying muscle cells. Rhabdomyolysis occurs due to overdoing it in training, crush injury, diseases, and other stressors.

Writer: Nicolas Verhoeven
[1] Rhabdomyolysis: MedlinePlus Medical Encyclopedia. (2018). Retrieved from https://medlineplus.gov/ency/article/000473.htm

[2] Zimmerman, J. L. (2013). Rhabdomyolysis. Chest, 144(3), 1058-1065. Retrieved from https://doi.org/10.1378/chest.12-2016

[3] Giorgi, C. (2012). Mitochondrial Ca2+ and apoptosis. Cell Calcium, 52(1), 36-43. doi:10.1016/j.ceca.2012.02.008

[4] Contreras, L., Drago, I., Zampese, E., & Pozzan, T. (2010). Mitochondria: The calcium connection. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1797(6-7), 607-618. doi:10.1016/j.bbabio.2010.05.005

[5] Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicology Pathology, 35(4), 495-516. doi:10.1080/01926230701320337

[6] Bosch, X. (2009). Rhabdomyolysis and Acute Kidney Injury. New England Journal of Medicine, 361(14), 361-372. doi:10.1056/NEJMra0801327

[7] Martinez, J. J. (2009). Rhabdomyolysis due to primary hyperaldosteronism. Endocrinology Nutrition, 56(8), 431-4. doi:10.1016/S1575-0922(09)72715-9

[8] https://www.researchgate.net/figure/Characteristic-apoptotic-necrotic-and-oncotic-cells-in-transmission-electron-microscope_fig1_274088124

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