What is rhabdomyolysis?

Rhabdomyolysis is a serious medical condition characterized by the breakdown of skeletal muscle tissue, resulting in the release of muscle cell contents into the bloodstream. This release includes substances such as myoglobin, creatine kinase (CK), electrolytes (such as potassium and phosphate), and other intracellular proteins. When these substances are released into the bloodstream in excessive amounts, they can cause various complications, including kidney damage, electrolyte imbalances, and potentially life-threatening complications.


The breakdown of muscle tissue in rhabdomyolysis can occur due to various causes, including:


  • Trauma or Crush Injuries: Traumatic injuries, such as car accidents, falls, or crush injuries, can directly damage skeletal muscle tissue and lead to rhabdomyolysis.


  • Prolonged Immobilization: Prolonged immobilization or pressure on muscles, such as in cases of prolonged lying or sitting in one position (e.g., during prolonged surgeries or coma), can lead to muscle breakdown.


  • Extreme Physical Exertion: Intense physical activity or exertion, especially in untrained individuals or during extreme conditions such as heatstroke or marathon running, can lead to muscle breakdown and rhabdomyolysis.


  • Drug or Medication Use: Certain drugs and medications, including statins (used to lower cholesterol), certain antipsychotic medications, and recreational drugs such as cocaine and amphetamines, can cause rhabdomyolysis as a side effect.


  • Infections: Severe infections, such as influenza, sepsis, or viral myositis, can trigger an inflammatory response that leads to muscle breakdown and rhabdomyolysis.


What is the relationship between rhabdomyolysis and oxidative stress?

The relationship between rhabdomyolysis and oxidative stress is multifaceted, as the process of muscle breakdown in rhabdomyolysis can lead to the generation of reactive oxygen species (ROS) and oxidative stress. Several mechanisms contribute to oxidative stress in rhabdomyolysis:


  • Ischemia-Reperfusion Injury: During rhabdomyolysis, the breakdown of muscle tissue can lead to local ischemia (lack of oxygen) in the affected muscles. When blood flow is restored (reperfusion), it can result in the generation of ROS and oxidative stress, contributing to tissue damage and inflammation.


  • Inflammatory Response: Rhabdomyolysis triggers an inflammatory response in the affected muscles, characterized by the release of pro-inflammatory cytokines and recruitment of immune cells. Inflammatory processes can generate ROS and promote oxidative stress, which further exacerbates tissue damage and dysfunction.


  • Myoglobin Toxicity: Myoglobin, a protein found in muscle tissue, is released into the bloodstream during rhabdomyolysis. Myoglobin can be toxic to the kidneys and other tissues, and its breakdown can lead to the production of ROS and oxidative stress. The heme group of myoglobin can undergo redox cycling, leading to the generation of ROS such as hydrogen peroxide and superoxide radicals.


  • Electrolyte Imbalance: Rhabdomyolysis can result in electrolyte imbalances, particularly hyperkalemia (elevated potassium levels) and hypocalcemia (low calcium levels). These electrolyte disturbances can promote oxidative stress and contribute to tissue injury and dysfunction.


  • Mitochondrial Dysfunction: Rhabdomyolysis can lead to mitochondrial dysfunction in muscle cells, impairing cellular metabolism and increasing ROS production. Dysfunctional mitochondria may produce excessive ROS, leading to oxidative damage to cellular components and further exacerbating tissue injury.


  • Reactive Nitrogen Species (RNS): In addition to ROS, rhabdomyolysis can lead to the generation of reactive nitrogen species (RNS), such as nitric oxide and peroxynitrite, which can contribute to oxidative stress and tissue damage.


Overall, oxidative stress plays a significant role in the pathogenesis and progression of rhabdomyolysis, contributing to tissue injury, inflammation, and organ dysfunction.