Muscle fatigue refers to the decline in muscle force generated over sustained periods of activity or due to pathological issues. Muscle fatigue has a number of possible causes including impaired blood flow, ion imbalance within the muscle, nervous fatigue, loss of desire to continue, and most importantly, the accumulation of lactic acid in the muscle.
Lactic Acid Accumulation
Long-term muscle use requires the delivery of oxygen and glucose to the muscle fiber to allow aerobic respiration to occur, producing the ATP required for muscle contraction. If the respiratory or circulatory system cannot keep up with demand, then energy will be generated by the much less efficient anaerobic respiration.
In aerobic respiration, pyruvate produced by glycolysis is converted into additional ATP molecules in the mitochondria via the Krebs Cycle. With insufficient oxygen, pyruvate cannot enter the Krebs cycle and instead accumulates in the muscle fiber. Pyruvate is continually processed into lactic acid. With pyruvate accumulation, lactic acid production is also increased. This lactic acid accumulation in the muscle tissue reduces the pH, making it more acidic and producing the stinging feeling in muscles when exercising. This further inhibits anaerobic respiration, inducing fatigue.
Lactic acid can be converted back to pyruvate in well-oxygenated muscle cells; however, during exercise the focus in on maintaining muscle activity. Lactic acid is transported to the liver where it can be stored prior to conversion to glucose in the presence of oxygen via the Cori Cycle. The amount of oxygen required to restore the lactic acid balance is often referred to as the oxygen debt.
Ion Imbalance
Contraction of a muscle requires Ca+ ions to interact with troponin, exposing the actin binding site to the myosin head. With extensive exercise, the osmotically active molecules outside of the muscle are lost through sweating. This loss changes the osmotic gradient, making it more difficult for the required Ca+ ions to be delivered to the muscle fiber. In extreme cases, this can lead to painful, extended maintenance of muscle contraction or cramp.
Nervous Fatigue and Loss of Desire
Nerves are responsible for controlling the contraction of muscles, determining the number, sequence, and force of muscular contractions. Most movements require a force far below what a muscle could potentially generate, and barring disease nervous fatigue is seldom an issue. However, loss of desire to exercise in the face of increasing muscle soreness, respiration, and heart rate can have a powerful negative impact on muscle activity.
Metabolic Fatigue
Depletion of required substrates such as ATP or glycogen within a muscle result in fatigue as the muscle is not able to generate energy to power contractions. Accumulation of metabolites from these reactions other than lactic acid, such as Mg2+ ions or reactive oxygen species, can also induce fatigue by interfering with the release of Ca+ ions from the sarcoplasmic reticulum or through reduction in the sensitivity of troponin to Ca+.
Exercise and Aging
With sufficient training, the metabolic capacity of a muscle can change, delaying the onset of muscle fatigue. Muscle specified for high-intensity anaerobic exercise will synthesise more glycolytic enzymes, whereas muscle for long endurance aerobic exercise will develop more capillaries and mitochondria. Additionally, with exercise, improvements to the circulatory and respiratory systems can facilitate better delivery of oxygen and glucose to the muscle.
With aging, levels of ATP, CTP, and myoglobin begin to decline, reducing the muscle's ability to function. Muscle fibers shrink or are lost and surrounding connective tissue hardens, making muscle contraction slower and more difficult. Exercise throughout life can help reduce the impact of aging by maintaining a healthy oxygen supply to the muscle.