Muscle weakness is a lack of
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of mus ...
strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including
muscular dystrophy
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily af ...
and
inflammatory myopathy. It occurs in
neuromuscular junction disorders, such as
myasthenia gravis. Muscle weakness can also be caused by low levels of
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin '' kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmos ...
and other
electrolyte
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon ...
s within muscle cells. It can be temporary or long-lasting (from seconds or minutes to months or years). The term myasthenia is from my- from Greek μυο meaning "muscle" + -asthenia ἀσθένεια meaning "
weakness
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
".
Types
Neuromuscular fatigue can be classified as either "central" or "peripheral" depending on its cause. Central muscle fatigue manifests as an overall sense of energy deprivation, while peripheral muscle fatigue manifests as a local, muscle-specific inability to do work.
Neuromuscular fatigue
Nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the ...
s control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences
synaptic fatigue
Synaptic fatigue, or short-term synaptic depression, is an activity-dependent form of short term synaptic plasticity that results in the temporary inability of neurons to fire and therefore transmit an input signal. It is thought to be a form of ...
it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring
pathology
Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
, neuromuscular fatigue is seldom an issue.
For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice
strength trainers, the muscle's ability to generate force is most strongly limited by nerve’s ability to sustain a
high-frequency signal. After an extended period of maximum contraction, the nerve’s signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply ‘stop listening’ and gradually cease to move, often
lengthening. As there is insufficient stress on the muscles and tendons, there will often be no
delayed onset muscle soreness following the workout. Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force. It is this "neural training" that causes several weeks worth of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit. Past this point, training effects increase muscular strength through myofibrillar or sarcoplasmic
hypertrophy and metabolic fatigue becomes the factor limiting contractile force.
Central fatigue
Central fatigue
Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system (CNS; including the brain and spinal cord) which affec ...
is a reduction in the
neural
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
drive or nerve-based motor command to working muscles that results in a decline in the force output. It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity. There has been a great deal of interest in the role of
serotonergic pathways for several years because its concentration in the brain increases with motor activity. During motor activity, serotonin released in synapses that contact
motoneurons promotes muscle contraction. During high level of motor activity, the amount of
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the
axon initial segment of
motoneurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited.
Peripheral muscle fatigue
Peripheral muscle fatigue' during physical work is 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 manifests 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
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
and other
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
ic anaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue, though recent studies have indicated otherwise, actually finding that lactic acid is a source of energy.
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 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 Ca
2+ to stimulate
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
and
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
to contract.
Lactic acid hypothesis
It was once believed that
lactic acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
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
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
, lactic acid can increase intracellular acidity of muscles. This can lower the sensitivity of contractile apparatus to
calcium ions
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...
(Ca
2+) but also has the effect of increasing
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
ic Ca
2+ concentration through an inhibition of the
chemical pump that
actively transports calcium out of the cell. This counters inhibiting effects of
potassium ions (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 K
+ 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 Ca
2+.
Pathophysiology
Muscle cells work by detecting a
flow
Flow may refer to:
Science and technology
* Fluid flow, the motion of a gas or liquid
* Flow (geomorphology), a type of mass wasting or slope movement in geomorphology
* Flow (mathematics), a group action of the real numbers on a set
* Flow (psyc ...
of electrical impulses from the
brain
A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...
which signals them to
contract
A contract is a legally enforceable agreement between two or more parties that creates, defines, and governs mutual rights and obligations between them. A contract typically involves the transfer of goods, services, money, or a promise to tr ...
through the release of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
by the
sarcoplasmic reticulum. Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This causes there to be less calcium available for the muscle cell. In addition an enzyme is proposed to be activated by this released calcium which eats away at muscle fibers.
Substrates within the muscle generally serve to power muscular contractions. They include molecules such as
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...
(ATP),
glycogen
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.
Glycogen functions as one of ...
and
creatine phosphate
Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine trip ...
. ATP binds to the
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
head and causes the ‘ratchetting’ that results in contraction according to the
sliding filament model
Sliding may refer to:
* Sliding (dance), also floating or gliding, a group of footwork-oriented dance techniques
* Slide (baseball), an attempt by a baseball runner to avoid getting tagged out
*Sliding (motion)
Sliding is a type of frictional mo ...
. 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
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
, used to generate energy quickly once intramuscular creatine stores are exhausted, producing
lactic acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
as a metabolic byproduct. Contrary to common belief, lactic acid accumulation doesn't 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:
[Page 59 in: ][Neurologic Examination]
at First Year Medical Curriculum at University of Florida College of Medicine. By Richard Rathe. Created: January 15, 1996. Modified: December 19, 2000
* 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
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position ...
" or "
distal
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...
" based on the location of the muscles that it affects. Proximal muscle weakness affects muscles closest to the body's midline, while distal muscle weakness affects muscles further out on the
limbs. Proximal muscle weakness can be seen in
Cushing's syndrome and
hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...
.
True and perceived
Muscle weakness can be classified as either "true" or "perceived" based on its cause.
* True muscle weakness (or neuromuscular weakness) describes a condition where the force exerted by the muscles is less than would be expected, for example
muscular dystrophy
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily af ...
.
* Perceived muscle weakness (or non-neuromuscular weakness) describes a condition where a person feels more effort than normal is required to exert a given amount of force but actual muscle strength is normal, for example
chronic fatigue syndrome
Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The causes and mechanisms of the disease are not fully understood. Distinguishing core symptoms are ...
.
In some conditions, such as
myasthenia gravis, muscle strength is normal when resting, but ''true'' weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of
chronic fatigue syndrome
Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The causes and mechanisms of the disease are not fully understood. Distinguishing core symptoms are ...
, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions.
References
Further reading
*
External links
{{Myopathy
Symptoms and signs: Nervous and musculoskeletal systems
Neurological disorders
Muscular disorders