Chapter: Essentials of Anatomy and Physiology: Muscular System


Fatigue is a temporary state of reduced work capacity. Without fatigue, muscle fibers would be worked to the point of structural dam-age to them and their supportive tissues.


Fatigue is a temporary state of reduced work capacity. Without fatigue, muscle fibers would be worked to the point of structural dam-age to them and their supportive tissues. Historically it was thought that buildup of lactic acid and the corresponding drop in pH (acidosis) was the major cause of fatigue. However, it is now established that there are multiple mechanisms underlying muscular fatigue.

These mechanisms include:


1.         Acidosis and ATP depletion due to either an increased ATP consumption or a decreased ATP production


2.         Oxidative stress, which is characterized by the buildup of excess reactive oxygen species (ROS; free radicals)


3.         Local inflammatory reactions


Acidosis and ATP Depletion

Anaerobic respiration results in breakdown of glucose to lactate and protons, accounting for lowered pH. Lowered pH has several cellular effects, including decreased effectiveness of Ca2+ on actinand overall less Ca2+ release from the sarcoplasmic reticulum. Lactic acidosis can also result when liver dysfunction results in reduced clearance of lactate (such as using it to produce glucose, for example). Usually, increased lactate levels are due to increased anaerobic respiration production of ATP when aerobic respiration production of ATP is reduced. Increases in lactate are also seen in patients with mitochondrial disorders and chronic obstructive pul-monary disease (COPD).


 However, to what extent ATP reductions are responsible for muscular fatigue is still not clear. Recent studies have demonstrated that cytoplasmic ATP levels stay relatively constant even in the face of decreasing muscle force production. But decreased ATP does cause fatigue. More specifically, it is the localized decreases in ATP levels or those associated with specific transport systems that are correlated with muscle fatigue.

Oxidative Stress

During intense exercise, increases in ROS production cause the breakdown of proteins, lipids, or nucleic acids. In addition, ROS trigger an immune system chemical called interleukin (IL)-6. IL-6 is a mediator of inflammation, which is the most likely cause of muscle soreness.


In addition to the stimulation of IL-6 by ROS, which causes inflammation, the immune system is directly activated by exercise. T lymphocytes, a type of white blood cell, migrate into heavily worked muscles. The presence of immune system intermediates increases the perception of pain, which most likely serves as a signal to protect those tissues from further damage.

 An example of muscle fatigue occurs when a runner col-lapses on the track and must be helped off. The runner’s muscle can no longer function regardless of how determined the run-ner is. Under conditions of extreme muscular fatigue, muscle may become incapable of either contracting or relaxing. This condition, called physiological contracture, occurs when there is too little ATP to bind to myosin myofilaments. Because bind-ing of ATP to the myosin heads is necessary for cross-bridge release between the actin and myosin, the cross-bridges between the actin and myosin myofilaments cannot be broken, and the muscle cannot relax.

 The most common type of fatigue, psychological fatigue, involves the central nervous system rather than the muscles them-selves. The muscles are still capable of contracting, but the individ-ual “perceives” that continued muscle contraction is impossible. A determined burst of activity in a tired runner in response to pressure from a competitor is an example of how psychological fatigue can be overcome.

 Although fatigue reduces power output, the overall benefit is that it prevents complete exhaustion of ATP reserves, which could lead to severe damage of the muscle fibers.

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