Peripheral

Peripheral muscle fatigue during physical work is considered an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigue--affecting a national average of 72% of adults in the work force in 2002. This causes contractile dysfunction that is manifested in the eventual reduction or lack of ability of a single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-optimal aerobic metabolism, generally results in the accumulation of lactic acid and other acidic anaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue.

The fundamental difference between the peripheral and central theories of muscle fatigue is that the peripheral model of muscle fatigue assumes failure at one or more sites in the chain that initiates muscle contraction. Peripheral regulation is therefore dependent on the localised metabolic chemical conditions of the local muscle affected, whereas the central model of muscle fatigue is an integrated mechanism that works to preserve the integrity of the system by initiating muscle fatigue through muscle derecruitment, based on collective feedback from the periphery, before cellular or organ failure occurs. Therefore the feedback that is read by this central regulator could include chemical and mechanical as well as cognitive cues. The significance of each of these factors will depend on the nature of the fatigue-inducing work that is being performed.

Though not universally used, ‘metabolic fatigue’ is a common alternative term for peripheral muscle weakness, because of the reduction in contractile force due to the direct or indirect effects of the reduction of substrates or accumulation of metabolites within the muscle fiber. This can occur through a simple lack of energy to fuel contraction, or interference with the ability of Ca2+ to stimulate actin and myosin to contract.

Metabolites

Metabolites are the substances (generally waste products) produced as a result of muscular contraction. They include ADP, Mg2+, reactive oxygen species and inorganic phosphate. Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules actin and myosin to calcium.

Chloride

Intracellular chloride inhibits the contraction of muscles, preventing them from contracting due to "false alarms", small stimuli which may cause them to contract (akin to myoclonus). This natural brake helps muscles respond solely to the conscious control or spinal reflexes but also has the effect of reducing the force of conscious contractions.

Potassium

High concentrations of potassium also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the t-tubule system and around the muscle fiber in general. This has the effect of depolarizing the muscle fiber, preventing the sodium-potassium pump from moving Na+ out of the cell. This reduces the amplitude of action potentials, or stops them entirely, resulting in neurological fatigue.

Lactic acid

It was once believed that lactic acid build-up was the cause of muscle fatigue.The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract. The impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.

Produced as a by-product of fermentation, lactic acid can increase intracellular acidity of muscles. This can lower the sensitivity of contractile apparatus to Ca2+ but also has the effect of increasing cytoplasmic Ca2+ concentration through an inhibition of the chemical pump that actively transports calcium out of the cell. This counters inhibiting effects of K+ on muscular action potentials. Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions. Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca2+.

Associated conditions

Muscle weakness may be due to problems with the nerve supply, neuromuscular disease such as myasthenia gravis or problems with muscle itself. The latter category includes polymyositis and other muscle disorders

• Amyotrophic lateral sclerosis
• Botulism
• Centronuclear myopathy
• Myotubular myopathy
• Dysautonomia
• Charcot-Marie-Tooth
• Hypokalemia
• Motor neurone disease
• Muscular dystrophy
• Myasthenia Gravis
• Progressive muscular atrophy
• Spinal muscular atrophy
• Cerebral Palsy
• Infectious mononucleosis
• Herpes Zoster
• Vitamin D deficiency
• Fibromyalgia
• Celiac Disease

• Asthenia
• Paresis
• Debility
• Malaise
• Cataplexy
• Hypotonia
• Muscle atrophy
• Mononucleosis
• Dystrophy
• Fatigue (medical)