Peripheral regulation  therefore depends on the localized 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 through interference with the ability of Ca2+ to stimulate actin and myosin to contract. Lactic acid hypothesis
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.
ATP binds to the myosin head and causes the ‘ratchetting’ that results in contraction according to the sliding filament model. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of glucose, used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid as a metabolic byproduct. Contrary to common belief, lactic acid accumulation doesnt actually cause the burning sensation we feel when we exhaust our oxygen and oxidative metabolism, but in actuality, lactic acid in presence of oxygen recycles to produce pyruvate in the liver which is known as the Cori cycle.Substrates produce metabolic fatigue by being depleted during exercise, resulting in a lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so. Diagnosis
Grading
The severity of muscle weakness can be classified into different "grades" based on the following criteria:
Grade 0: No contraction or muscle movement. Grade 1: Trace of contraction, but no movement at the joint. Grade 2: Movement at the joint with gravity eliminated. Grade 3: Movement against gravity, but not against added resistance. Grade 4: Movement against external resistance with less strength than usual. Grade 5: Normal strength. Classification
Proximal and distal
Muscle weakness can also be classified as either "proximal" or "distal" based on the location of the muscles that it affects.