Weakness
Weakness may be true or perceived, with diverse causes.
Weakness is a symptom that can arise from numerous medical conditions, involving either true or perceived loss of muscle strength. It is notable as a primary feature of skeletal muscle diseases, neuromuscular junction disorders, and various systemic illnesses.
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- Neurology
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Pathophysiology
Muscle contraction depends on electrical impulses from the brain triggering calcium release from the sarcoplasmic reticulum. Fatigue, a reduced ability to generate force, can originate from nerve dysfunction or within muscle cells. Research from Columbia University indicates that muscle fatigue involves calcium leaking out of the muscle cell, reducing available calcium, and an enzyme activated by this leakage that degrades muscle fibers. Substrates such as ATP, glycogen, and creatine phosphate power contractions. ATP binds to the myosin head, enabling ratcheting in the sliding filament model. Creatine phosphate allows rapid ATP regeneration from ADP and inorganic phosphate, supporting powerful contractions lasting 5–7 seconds. Glycogen provides quick energy after creatine stores deplete, producing lactic acid as a byproduct. Lactic acid accumulation does not cause the burning sensation during oxygen exhaustion; instead, lactic acid recycles to pyruvate in the liver via the Cori cycle. Depletion of these substrates during exercise leads to metabolic fatigue, halting contractions due to insufficient intracellular energy.
Differential diagnosis
True weakness, or neuromuscular weakness, involves less force exerted than expected, as in muscular dystrophy. Perceived weakness, or non-neuromuscular weakness, describes a sensation of increased effort for a given force despite normal muscle strength. In myasthenia gravis, strength is normal at rest but true weakness appears after exercise. Some cases of Myalgic encephalomyelitis/chronic fatigue syndrome show objective post-exertion muscle weakness with delayed recovery, included in published definitions. Asthenia, meaning lack of strength, is a poorly defined condition encompassing true or perceived muscle weakness. For perceived weakness, asthenia involves feeling weak or tired muscles without actual strength loss, where normal force generation requires perceived extra effort. General asthenia occurs in chronic wasting diseases like tuberculosis and cancer, sleep disorders, chronic heart, lung, or kidney disorders, and is most marked in adrenal gland diseases. Asthenia can also be a symptom of mast cell activation syndrome and a side effect of medications such as Ritonavir. Differentiating psychogenic asthenia from true asthenia and myasthenia is often difficult, and apparent psychogenic asthenia in chronic disorders may progress to primary weakness.
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