Neural transmission failure is a key factor in central fatigue during endurance activities due to its impact on the efficiency of signal transmission from the brain to the muscles. Prolonged physical activity can lead to the depletion of neurotransmitters in the central nervous system, which are crucial for maintaining neural communication. When these neurotransmitters are depleted, the transmission of nerve impulses becomes less efficient, leading to a decrease in motor neuron excitability. This results in a reduced ability of the brain to effectively communicate with muscles, causing a decline in muscle activation and coordination. This impairment in neural function can significantly impact an athlete's performance, especially in activities requiring sustained concentration and muscular endurance.

Different types of muscle fibres exhibit varied responses to fatigue in high-intensity and endurance activities. Type II (fast-twitch) fibres, which are predominant in high-intensity, short-duration activities like sprinting, fatigue quickly due to their reliance on anaerobic metabolism, leading to rapid depletion of energy stores and accumulation of metabolic by-products like lactic acid. On the other hand, Type I (slow-twitch) fibres, utilised in endurance activities like long-distance running, are more resistant to fatigue. They rely on aerobic metabolism, enabling them to sustain activity for longer periods due to efficient energy use and lower rates of lactic acid production. However, these fibres are susceptible to fatigue from factors like glycogen depletion and electrolyte imbalances over extended periods.

Psychological factors can independently cause fatigue, and they often play a significant role in an athlete's overall experience of fatigue. Mental fatigue can arise from prolonged cognitive activities, stress, lack of motivation, or inadequate mental recovery. This type of fatigue impacts an athlete's concentration, decision-making, and perceived exertion, which can influence physical performance even in the absence of physiological fatigue. However, psychological and physiological factors often interact, as physical exhaustion can lead to mental fatigue and vice versa. For instance, the perception of effort can be heightened by physical fatigue, making a task seem more challenging mentally. Understanding and managing these psychological aspects are crucial for optimal performance in sports.

The body's thermoregulatory response during exercise is a critical factor contributing to fatigue. During physical activity, the body generates heat, and its core temperature rises. The body responds by increasing blood flow to the skin and sweating to dissipate heat. However, this thermoregulatory process can lead to dehydration and electrolyte imbalances, exacerbating fatigue. Additionally, the diversion of blood to the skin reduces the amount of blood available to muscles, decreasing the delivery of oxygen and nutrients essential for sustained exercise. Furthermore, high body temperatures can directly impair muscle function and CNS efficiency, contributing to both physical and mental fatigue. Therefore, managing heat stress through hydration, appropriate clothing, and acclimatisation is essential in preventing thermoregulatory-induced fatigue during exercise.

The accumulation of lactic acid in muscles during high-intensity activities plays a significant role in muscle fatigue. When exercising intensely, the body relies on anaerobic respiration, leading to the production of lactic acid as a by-product. This acidification within muscle cells interferes with various biochemical pathways that produce energy. It disrupts the pH balance, hindering enzyme function crucial for energy production and muscle contraction. Additionally, the increase in hydrogen ions, a component of lactic acid, can inhibit the release of calcium ions from the sarcoplasmic reticulum, further impairing muscle contraction. Therefore, lactic acid accumulation can significantly reduce muscle efficiency and force generation, contributing to the sensation of fatigue.