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Muscle physiology
BASIC SCIENCE
Muscle physiology
the binding of ATP to the myosin that allows it to detach from the actin filament. In the absence of ATP the cross-bridges remain attached in what is known as a rigour complex, as in rigor mortis. The energy liberated by the subsequent hydrolysis of the ATP causes the neck region of the myosin to extend so it is ready again to attach to the actin filament and repeat the cycle. The total force that is exerted is the sum of all the forces generated by the individual attached myosin molecules (or cross-bridges) minus any resistive force caused by cross-bridges that have failed to detach soon enough. This molecular mechanism means that the force generated depends on the velocity of movement and, characteristically force falls off rapidly as the velocity of shortening increases so there is a maximum speed of shortening at which no external force is generated. The maximum force that can be generated occurs when the muscle is not moving (isometric), as when supporting a weight or maintaining posture, but for many purposes muscles are required to move a load through a distance (work) and the speed with which this can be achieved defines the power of the muscle. Although force declines as speed of shortening increases, the power that can be generated, which is the product of force and velocity, reaches a maximum at around one-third of maximum shortening velocity. Thus there is an optimum velocity of movement at which maximum power is generated and at which the muscle is most efficient. It is for this reason that bicycle gearing is arranged to allow the leg muscles to work at, or close to their optimum speed (about 100 rpm in the case of cycling), independently of the load. The speed at which a muscle shortens, and to a large extent the power it can develop, depends on the speed of cross-bridge cycling, both the affinity of the binding step and the speed with which the cross-bridge can detach at the end of the working stroke and these differ between myosin isoforms that have relatively small differences in their amino acid sequences. Crossbridge activity is also influenced by the presence of different types of light-chain, small proteins associated with the neck region of the myosin molecule, and some of the proteins (troponins) associated with the actin filaments.
Carolyn A Greig David A Jones
Abstract Muscle has important metabolic functions, but this article will focus on its mechanical properties. We describe the mechanism by which a muscle generates force, examine the contractile properties of muscle, and discuss the measurement of whole body muscle force (and power) in health and disease.
Keywords Muscle contraction; muscle fatigue; muscle weakness
Mechanism of muscle force generation ‘‘All man can do is to move things, and his muscular contraction is his sole means thereto.’’ C.S. Sherrington, The Gifford Lectures, Edinburgh 1937e8 The molecular basis of force, movement and power The essence of muscle is that it can generate force and move, although muscles can only shorten; it requires an antagonist muscle to lengthen them again. The molecular basis for these actions is the interaction of the two proteins, actin and myosin, which are found in almost every cell type but are particularly abundant in skeletal muscle where they constitute about 80% of the total protein. The actin and myosin molecules form long interdigitating filaments. The thicker myosin filaments are arranged with the globular heads of the individual myosin molecules projecting outwards where they can bind to the actin filament. These actin and myosin filaments are highly organized in skeletal muscle and are apparent under the microscope as striations running across the muscle fibre and forming sarcomeres, the contractile unit of the muscle. The myosin head has a very strong affinity for actin and when it binds, the flexible neck region rotates pulling the actin filament towards the centre of the sarcomere. The amount of movement that can be generated by flexing one portion of a single molecule is very small and consequently to obtain a continuous movement it is important that the myosin head detaches from the actin filament at the end of its useful working stroke and then repeats the cycle bound to a site further along the actin filament. The energy for muscle contraction is provided by adenosine triphosphate (ATP) and it is
Control of contraction A single action potential gives a short, small, contraction, known as a twitch, generally lasting about 200 ms and generating about a tenth of the maximum force. If the muscle is stimulated repetitively at increasing frequencies the individual twitches begin to summate, the next twitch coming before the previous one has fully relaxed. At frequencies around 50e100 Hz the interior of the muscle fibre is flooded with calcium and the contraction is known as a fully fused tetanus. The precise shape of the relationship between the frequency of stimulation and force generated depends on the amount of calcium released per twitch (and this can be affected by drugs such as caffeine and dantrolene) and the speed with which the muscle relaxes. Fast fibres not only contract rapidly, they also relax rapidly so their twitch is of a shorter duration than that of slow fibres. Consequently they do not ‘fuse’ until higher frequencies.
Carolyn A Greig PhD is a Senior Research Fellow in the Dept. of Clinical and Surgical Sciences (Geriatric Medicine) at The University of Edinburgh Royal Infirmary, Edinburgh, UK. Conflicts of interest: none declared. David A Jones PhD is a Professor of Muscle Physiology at the Institute for Biomedical Research into Human Movement and Health (IRM), Manchester Metropolitan University, Manchester, UK. Conflicts of interest: none declared.
SURGERY 28:2
Muscle fibre types A number of different myosin isoforms exist in mammalian skeletal muscle with maximum velocities of shortening that differ
55
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
cause is some other system so, for instance, weakness or fatigue may be secondary to endocrine disturbances, carcinoma, malnutrition and immobilization. Motor neuropathies are a major cause of muscle weakness since once a motor neuron or its axon is damaged the fibres it innervates are no longer stimulated and will atrophy. Reinnervation by nearby healthy axons can take place leading to fibre type grouping but there may be limits to how many fibres a single neuron can sustain and in aggressive motor neuron disease the reinnervation may not keep up with the loss. Normal muscle function depends on the correct working of the chain of command that extends from motivation to the interaction of actin and myosin within the muscle fibre and there
three- to four fold. The myosin isoforms can be identified by a variety of histochemical and immunological staining methods and fall into two main categories, Type 1 and Type 2, with the latter being subdivided into Types 2A, 2X and 2B. This classification also relates to the contractile characteristics of the fibres, with the Type 1 fibres being slowest and the Type 2 being faster in the order 2A < 2X < 2B. Human muscle appears not to contain the fastest 2B fibres that are found in rodent muscle. All the muscle fibres of a motor unit (all the fibres innervated by one motoneuron) have the same contractile, histological and biochemical properties. Type I fibres are less powerful than Type 2 fibres but they are more fatigue resistant and are recruited preferentially for maintaining and adjusting posture and in everyday low-intensity longer duration physical activity, whereas the fast Type 2 fibres are recruited for occasional bursts of high-intensity, shortduration muscular activity such as sprinting or jumping. Rapid contractions and high power entail high ATP turnover and this can only be met by glycolysis and the breakdown of phosphocreatine. Consequently levels of phosphocreatine, and the activity of glycolytic enzymes are higher in Type 2 fibres. In contrast, the Type 1 fibres have lower energy requirements which can be met by the oxidative metabolism of carbohydrate and fats and these fibres are characterized by their high content of lipid droplets and mitochondria, they also have more capillaries, and thus a better supply of oxygenated blood and more myoglobin. Most human muscles contain an equal mixture of slow and fast fibres, but there is considerable variation between people. This is most noticeable when comparing elite athletes such as marathon runners and sprinters who have a disproportionately high proportion of Type 1 and Type 2 fibres respectively. These two types of athletes differ not only in the ‘quality’ of their muscles, in terms of speed and fatigue resistance, but also with respect to muscle mass. Endurance athletes have relatively small muscles while power athletes are heavily muscled and there is considerable interest and controversy as to whether the athletes owe their muscle characteristics to genetic endowment or training. Definitive evidence is hard to gather as training generally starts at a young age and continues for many years which entails considerable ethical and practical difficulties. However, evidence from short-term training studies and comparisons of identical twins, suggest that genetics sets an upper limit to performance. Muscle bulk depends on the number of fibres in a muscle, which is set at or near birth, and the extent of hypertrophy (of the individual fibres) as the result of training. Likewise it seems that the proportions of Type 1 and 2 fibres are set very early in development, but the number of capillaries and mitochondria can be modified by suitable training. Endurance training also causes a shift in the expression away from the fastest Type 2X to the somewhat slower and more oxidative 2A fibres. Interestingly, strength training also causes the same shift in myosin expression which means that gains in speed as a result of strength training are more likely due to increases in muscle size, increased stiffness of tendons and improvements in muscle recruitment and coordination.
Summary of the main disorders and diseases affecting skeletal muscle, arranged according to their main presenting symptom Weakness Secondary atrophic myopathies Hypothyroidism Malnutrition Cachexia Cushing’s syndrome Prolonged steroid therapy Alcohol injury to muscle, joint or tendon Immobilization Peripheral vascular disease Neuropathies Motor neuron disease Spinal muscular atrophy Multiple sclerosis Alcoholic neuropathy Diabetic neuropathy Muscular dystrophies Duchenne Becker Limb girdle Inflammatory myopathies Polymyositis and dermatomyositis Abnormal function Malignant hyperthermia Hypokalaemic periodic paralysis Hyperkalaemic periodic paralysis Myotonia Excessive fatiguability Glycolytic enzyme deficiencies Myophosphorylase (McArdle’s) Phosphofructokinase (Tarui’s) Mitochondrial enzyme Pyruvate dehydrogenase deficiencies Cytochromes Carnitine palmitoyl transferase Myasthenia gravis Peripheral vascular disease Chronic fatigue syndrome Post-viral states Overtraining Hypothyroidism Depression Most serious diseases; trauma and/or surgery
Muscle weakness Muscle weakness and fatigue are very common complaints and in many cases may be the first signs of disease where the primary
SURGERY 28:2
Table 1
56
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
are diseases and conditions that can disrupt the chain at almost any point and lead to a loss of function. The chain of command is often simplified into central and peripheral elements that can be separated on the basis of electrical stimulation of the motor nerve or its branches. If the problem is central in origin, voluntary force can be improved by superimposing electrical stimulation while this has no effect on peripheral causes of weakness. Central limitation is rarely a major factor in muscle weakness, the exception being where there is damage or inflammation of a joint, tendon or ligament that can provide a powerful inhibitory input to the alpha motoneuron. With the exception of conditions such as myasthenia (see previous article) where failure at the neuromuscular junction prevents muscle contraction, nearly all cases of muscle weakness are the result of loss of contractile material. Often this is evident as muscle atrophy but it may be masked by subcutaneous fat or by the replacement of muscle by fat and connective tissue as in the case of the pseudohypertrophic dystrophies. The broad categories leading to muscle wasting and weakness are listed in Table 1. With the atrophic myopathies the wasting and weakness are generally reversible once the underlying condition is treated. However with the destructive myopathies the outcomes are less promising even where the conditions can be stabilized as in the inflammatory diseases. Healthy ageing is accompanied by a decline in muscle strength, albeit slow, but progressive at a rate of approximately 1e2% per year from about the fourth to fifth decade. One theory for the loss of muscle with increasing age (termed ‘sarcopaenia’) is that it is secondary to loss of motor neurons that is only partially compensated for by reinnervation.1 Other ideas suggest that low-grade inflammation is a cause of muscle loss. The rate of
decline of muscle mass/strength is accelerated in the presence of disease or following acute illness or surgery. For example, the hip fracture survivor is 40% weaker and 70% less powerful than their healthy age-matched counterpart.2
Assessment of muscle performance in health and disease Importance of measuring muscle function Weakness and fatigue are two of the most common complaints of patients with a wide range of diseases and they are also common concerns of athletes who are training or recovering from injury. Muscle function testing is often an important aid to diagnosis and can also play a valuable role in assessing the severity of a problem and, in many cases, the progress of recovery and return to full function. Measures such as strength, size and mechanical quality allow the characterization of phenotypes, stratification of patients for surgery, and the evaluation of outcome following intervention. Assessing muscle loss, weakness and fatiguability Table 2 summarizes the range of tests that might be used to investigate people complaining of weakness or fatigue. These tests fall between two poles. At one end are detailed investigations of the contractile properties of an individual muscle while at the other are assessments of functional ability such as jumping or of endurance whilst exercising at some known proportion of maximum aerobic capacity. In an ideal situation a full investigation of, for example, a patient having difficulty climbing stairs might start with a careful documentation of this functional deficit, determining how fast he or she can climb a standard set of steps, followed by checks on balance and
Possible investigations of muscle function in relation to symptoms of weakness and fatigue Amount of contractile material
Isometric strength (with or without electrical stimulation) Anthropometry; CT, MRI or ultrasound imaging
Speed of the muscle
Relaxation from an isometric contraction The degree of fusion of a submaximal tetanus Shape of the force/velocity relationship; estimates of maximum velocity of shortening
Power and impulse (speed and strength)
Standing and vertical jump Stair running Wingate test Nottingham leg extensor power rig Isokinetic dynamometry Isokinetic cycling
Length of a muscle Fatiguability
Angle/force or torque relationship (range of movement) Repeated contractions (stimulated or voluntary; isometric or dynamic; with or without an intact circulation) Prolonged exercise at fixed percentage of VO2max 6- or 12-min walk tests Rating of Perceived Exertion (Borg 10- or 20-point scale)
Other investigations
Clinical history Biochemistry (creatine kinase, inflammatory markers, genetic investigation) Electromyography
Table 2
SURGERY 28:2
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Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
muscle loss. Muscle mass can be measured indirectly (as lean soft tissue) using dual energy X-ray absorptiometry (DEXA) however additional information is gained using ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) (Figure 1), which are able to distinguish tissue types, for example muscle and subcutaneous fat, due to the observable contrast differences and subsequently permit quantification of either cross-sectional area and/or volume.
Measurement of muscle strength and power output Muscle strength provides a useful and convenient measure of function. Hand grip dynamometry has been shown to be predictive of future disability, morbidity and mortality but lacks precision and is difficult to standardize. Most major muscle groups can be measured but the quadriceps remains the most useful since it is a large proximal muscle that is affected in most muscle disorders, it is functionally important in everyday life and is very convenient for other investigations such as muscle biopsy and electromyography (EMG). The simplest way of measuring quadriceps strength is manual muscle testing with or without a hand-held myometer but these techniques are inaccurate. Knee extensor/elbow flexor strength can be measured using an isometric testing chair such as described by Edwards et al3 (Figure 2) or commercial ergometers that can be used in either isometric or isokinetic modes. For the purposes of assessing the size and strength of a muscle in order to document the extent of a disease or the progress of treatment or training, isometric testing is quite sufficient and in many ways preferable to isokinetic testing that introduces several complications such as consideration of the speed, length and range of movement of a muscle. Isokinetic testing is of particular value in assessing injuries affecting joints where the range of movement can be impaired or inhibition might occur at a certain position. Normal values are difficult to define since strength varies widely with age, sex, body shape and size and with habitual activity.
Figure 1 Magnetic resonance cross-sectional images at mid-thigh level in healthy women aged 23 y a and 80 y b and a woman with upper gastrointestinal cancer aged 75 y c.
eyesight, before proceeding to measurements of strength, range of movement and the fatiguability of individual muscle groups, the expectation being that an abnormality of muscle function might explain the overall functional deficit. A similar sequence could be envisaged for an athlete who was injured or was complaining of loss of form. Measurement of muscle mass The majority of common muscle complaints involve wasting and it is particularly useful in a clinical situation to know the extent of
Adjustable testing chair suitable for measuring isometric strength of the quadriceps, developed from the chair described by Edwards et al.3 Figure 2
SURGERY 28:2
58
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
Edwards et al3 suggest a useful rule of thumb is that the quadriceps strength is about 75% of the force of gravity on the body mass so that for a 70 kg subject, strength would be about 530 N. However a wide range of quadriceps strength is compatible with a normal active lifestyle; normative data for the isometric strength of several muscles and for a body sizes and ages have been published.4 Power is the product of the strength and speed of a muscle and is a critical component of performance in many sporting activities. However conventional tests of whole body power output are often inappropriate for frail patients. The Nottingham Power Rig5 was developed to measure the explosive power of the lower limb extensors safely (in a seated position) and has been shown to be suitable for use with very frail patients, even those recovering from hip fracture.6 Muscle power output measured using this technique is associated with selected measures of functional ability in both healthy older men and women and selected patient groups, although it is not clear whether this provides any more information than simply measuring isometric strength. A
SURGERY 28:2
REFERENCES 1 Young A. Muscle function in old age. In: Thomas PK, ed. Peripheral nerve changes in the elderly, New issues in neurosciences, vol. I, 1998: 141–56. 2 Phillips SK, Woledge RC, Bruce SA, et al. A study of force and crosssectional area of adductor pollicis muscle in female hip fracture patients. J Am Geriatr Soc 1998 Aug; 46: 999e1002. 3 Edwards RHT, Young A, Hosking GP, Jones DA. Human skeletal muscle function: description of tests and normal values. Clin Sci Mol Med 1977; 52: 283e90. 4 Muscular weakness assessment: use of normal isometric strength data. The National Isometric Muscle Strength (NIMS) Database Consortium. Arch Phys Med Rehabil 1996; 77: 1251e5. 5 Bassey EJ, Short AH. A new method for measuring power output in a single leg extension: feasibility, reliability and validity. Eur J Appl Physiol Occup Physiol 1990; 60: 385e90. 6 Mitchell SL, Stott DJ, Martin BJ, Grant SJ. Randomized controlled trial of quadriceps training after proximal femoral fracture. Clin Rehabil 2001 Jun; 15: 282e90.
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Ó 2009 Elsevier Ltd. All rights reserved.
Muscle physiology
the binding of ATP to the myosin that allows it to detach from the actin filament. In the absence of ATP the cross-bridges remain attached in what is known as a rigour complex, as in rigor mortis. The energy liberated by the subsequent hydrolysis of the ATP causes the neck region of the myosin to extend so it is ready again to attach to the actin filament and repeat the cycle. The total force that is exerted is the sum of all the forces generated by the individual attached myosin molecules (or cross-bridges) minus any resistive force caused by cross-bridges that have failed to detach soon enough. This molecular mechanism means that the force generated depends on the velocity of movement and, characteristically force falls off rapidly as the velocity of shortening increases so there is a maximum speed of shortening at which no external force is generated. The maximum force that can be generated occurs when the muscle is not moving (isometric), as when supporting a weight or maintaining posture, but for many purposes muscles are required to move a load through a distance (work) and the speed with which this can be achieved defines the power of the muscle. Although force declines as speed of shortening increases, the power that can be generated, which is the product of force and velocity, reaches a maximum at around one-third of maximum shortening velocity. Thus there is an optimum velocity of movement at which maximum power is generated and at which the muscle is most efficient. It is for this reason that bicycle gearing is arranged to allow the leg muscles to work at, or close to their optimum speed (about 100 rpm in the case of cycling), independently of the load. The speed at which a muscle shortens, and to a large extent the power it can develop, depends on the speed of cross-bridge cycling, both the affinity of the binding step and the speed with which the cross-bridge can detach at the end of the working stroke and these differ between myosin isoforms that have relatively small differences in their amino acid sequences. Crossbridge activity is also influenced by the presence of different types of light-chain, small proteins associated with the neck region of the myosin molecule, and some of the proteins (troponins) associated with the actin filaments.
Carolyn A Greig David A Jones
Abstract Muscle has important metabolic functions, but this article will focus on its mechanical properties. We describe the mechanism by which a muscle generates force, examine the contractile properties of muscle, and discuss the measurement of whole body muscle force (and power) in health and disease.
Keywords Muscle contraction; muscle fatigue; muscle weakness
Mechanism of muscle force generation ‘‘All man can do is to move things, and his muscular contraction is his sole means thereto.’’ C.S. Sherrington, The Gifford Lectures, Edinburgh 1937e8 The molecular basis of force, movement and power The essence of muscle is that it can generate force and move, although muscles can only shorten; it requires an antagonist muscle to lengthen them again. The molecular basis for these actions is the interaction of the two proteins, actin and myosin, which are found in almost every cell type but are particularly abundant in skeletal muscle where they constitute about 80% of the total protein. The actin and myosin molecules form long interdigitating filaments. The thicker myosin filaments are arranged with the globular heads of the individual myosin molecules projecting outwards where they can bind to the actin filament. These actin and myosin filaments are highly organized in skeletal muscle and are apparent under the microscope as striations running across the muscle fibre and forming sarcomeres, the contractile unit of the muscle. The myosin head has a very strong affinity for actin and when it binds, the flexible neck region rotates pulling the actin filament towards the centre of the sarcomere. The amount of movement that can be generated by flexing one portion of a single molecule is very small and consequently to obtain a continuous movement it is important that the myosin head detaches from the actin filament at the end of its useful working stroke and then repeats the cycle bound to a site further along the actin filament. The energy for muscle contraction is provided by adenosine triphosphate (ATP) and it is
Control of contraction A single action potential gives a short, small, contraction, known as a twitch, generally lasting about 200 ms and generating about a tenth of the maximum force. If the muscle is stimulated repetitively at increasing frequencies the individual twitches begin to summate, the next twitch coming before the previous one has fully relaxed. At frequencies around 50e100 Hz the interior of the muscle fibre is flooded with calcium and the contraction is known as a fully fused tetanus. The precise shape of the relationship between the frequency of stimulation and force generated depends on the amount of calcium released per twitch (and this can be affected by drugs such as caffeine and dantrolene) and the speed with which the muscle relaxes. Fast fibres not only contract rapidly, they also relax rapidly so their twitch is of a shorter duration than that of slow fibres. Consequently they do not ‘fuse’ until higher frequencies.
Carolyn A Greig PhD is a Senior Research Fellow in the Dept. of Clinical and Surgical Sciences (Geriatric Medicine) at The University of Edinburgh Royal Infirmary, Edinburgh, UK. Conflicts of interest: none declared. David A Jones PhD is a Professor of Muscle Physiology at the Institute for Biomedical Research into Human Movement and Health (IRM), Manchester Metropolitan University, Manchester, UK. Conflicts of interest: none declared.
SURGERY 28:2
Muscle fibre types A number of different myosin isoforms exist in mammalian skeletal muscle with maximum velocities of shortening that differ
55
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
cause is some other system so, for instance, weakness or fatigue may be secondary to endocrine disturbances, carcinoma, malnutrition and immobilization. Motor neuropathies are a major cause of muscle weakness since once a motor neuron or its axon is damaged the fibres it innervates are no longer stimulated and will atrophy. Reinnervation by nearby healthy axons can take place leading to fibre type grouping but there may be limits to how many fibres a single neuron can sustain and in aggressive motor neuron disease the reinnervation may not keep up with the loss. Normal muscle function depends on the correct working of the chain of command that extends from motivation to the interaction of actin and myosin within the muscle fibre and there
three- to four fold. The myosin isoforms can be identified by a variety of histochemical and immunological staining methods and fall into two main categories, Type 1 and Type 2, with the latter being subdivided into Types 2A, 2X and 2B. This classification also relates to the contractile characteristics of the fibres, with the Type 1 fibres being slowest and the Type 2 being faster in the order 2A < 2X < 2B. Human muscle appears not to contain the fastest 2B fibres that are found in rodent muscle. All the muscle fibres of a motor unit (all the fibres innervated by one motoneuron) have the same contractile, histological and biochemical properties. Type I fibres are less powerful than Type 2 fibres but they are more fatigue resistant and are recruited preferentially for maintaining and adjusting posture and in everyday low-intensity longer duration physical activity, whereas the fast Type 2 fibres are recruited for occasional bursts of high-intensity, shortduration muscular activity such as sprinting or jumping. Rapid contractions and high power entail high ATP turnover and this can only be met by glycolysis and the breakdown of phosphocreatine. Consequently levels of phosphocreatine, and the activity of glycolytic enzymes are higher in Type 2 fibres. In contrast, the Type 1 fibres have lower energy requirements which can be met by the oxidative metabolism of carbohydrate and fats and these fibres are characterized by their high content of lipid droplets and mitochondria, they also have more capillaries, and thus a better supply of oxygenated blood and more myoglobin. Most human muscles contain an equal mixture of slow and fast fibres, but there is considerable variation between people. This is most noticeable when comparing elite athletes such as marathon runners and sprinters who have a disproportionately high proportion of Type 1 and Type 2 fibres respectively. These two types of athletes differ not only in the ‘quality’ of their muscles, in terms of speed and fatigue resistance, but also with respect to muscle mass. Endurance athletes have relatively small muscles while power athletes are heavily muscled and there is considerable interest and controversy as to whether the athletes owe their muscle characteristics to genetic endowment or training. Definitive evidence is hard to gather as training generally starts at a young age and continues for many years which entails considerable ethical and practical difficulties. However, evidence from short-term training studies and comparisons of identical twins, suggest that genetics sets an upper limit to performance. Muscle bulk depends on the number of fibres in a muscle, which is set at or near birth, and the extent of hypertrophy (of the individual fibres) as the result of training. Likewise it seems that the proportions of Type 1 and 2 fibres are set very early in development, but the number of capillaries and mitochondria can be modified by suitable training. Endurance training also causes a shift in the expression away from the fastest Type 2X to the somewhat slower and more oxidative 2A fibres. Interestingly, strength training also causes the same shift in myosin expression which means that gains in speed as a result of strength training are more likely due to increases in muscle size, increased stiffness of tendons and improvements in muscle recruitment and coordination.
Summary of the main disorders and diseases affecting skeletal muscle, arranged according to their main presenting symptom Weakness Secondary atrophic myopathies Hypothyroidism Malnutrition Cachexia Cushing’s syndrome Prolonged steroid therapy Alcohol injury to muscle, joint or tendon Immobilization Peripheral vascular disease Neuropathies Motor neuron disease Spinal muscular atrophy Multiple sclerosis Alcoholic neuropathy Diabetic neuropathy Muscular dystrophies Duchenne Becker Limb girdle Inflammatory myopathies Polymyositis and dermatomyositis Abnormal function Malignant hyperthermia Hypokalaemic periodic paralysis Hyperkalaemic periodic paralysis Myotonia Excessive fatiguability Glycolytic enzyme deficiencies Myophosphorylase (McArdle’s) Phosphofructokinase (Tarui’s) Mitochondrial enzyme Pyruvate dehydrogenase deficiencies Cytochromes Carnitine palmitoyl transferase Myasthenia gravis Peripheral vascular disease Chronic fatigue syndrome Post-viral states Overtraining Hypothyroidism Depression Most serious diseases; trauma and/or surgery
Muscle weakness Muscle weakness and fatigue are very common complaints and in many cases may be the first signs of disease where the primary
SURGERY 28:2
Table 1
56
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
are diseases and conditions that can disrupt the chain at almost any point and lead to a loss of function. The chain of command is often simplified into central and peripheral elements that can be separated on the basis of electrical stimulation of the motor nerve or its branches. If the problem is central in origin, voluntary force can be improved by superimposing electrical stimulation while this has no effect on peripheral causes of weakness. Central limitation is rarely a major factor in muscle weakness, the exception being where there is damage or inflammation of a joint, tendon or ligament that can provide a powerful inhibitory input to the alpha motoneuron. With the exception of conditions such as myasthenia (see previous article) where failure at the neuromuscular junction prevents muscle contraction, nearly all cases of muscle weakness are the result of loss of contractile material. Often this is evident as muscle atrophy but it may be masked by subcutaneous fat or by the replacement of muscle by fat and connective tissue as in the case of the pseudohypertrophic dystrophies. The broad categories leading to muscle wasting and weakness are listed in Table 1. With the atrophic myopathies the wasting and weakness are generally reversible once the underlying condition is treated. However with the destructive myopathies the outcomes are less promising even where the conditions can be stabilized as in the inflammatory diseases. Healthy ageing is accompanied by a decline in muscle strength, albeit slow, but progressive at a rate of approximately 1e2% per year from about the fourth to fifth decade. One theory for the loss of muscle with increasing age (termed ‘sarcopaenia’) is that it is secondary to loss of motor neurons that is only partially compensated for by reinnervation.1 Other ideas suggest that low-grade inflammation is a cause of muscle loss. The rate of
decline of muscle mass/strength is accelerated in the presence of disease or following acute illness or surgery. For example, the hip fracture survivor is 40% weaker and 70% less powerful than their healthy age-matched counterpart.2
Assessment of muscle performance in health and disease Importance of measuring muscle function Weakness and fatigue are two of the most common complaints of patients with a wide range of diseases and they are also common concerns of athletes who are training or recovering from injury. Muscle function testing is often an important aid to diagnosis and can also play a valuable role in assessing the severity of a problem and, in many cases, the progress of recovery and return to full function. Measures such as strength, size and mechanical quality allow the characterization of phenotypes, stratification of patients for surgery, and the evaluation of outcome following intervention. Assessing muscle loss, weakness and fatiguability Table 2 summarizes the range of tests that might be used to investigate people complaining of weakness or fatigue. These tests fall between two poles. At one end are detailed investigations of the contractile properties of an individual muscle while at the other are assessments of functional ability such as jumping or of endurance whilst exercising at some known proportion of maximum aerobic capacity. In an ideal situation a full investigation of, for example, a patient having difficulty climbing stairs might start with a careful documentation of this functional deficit, determining how fast he or she can climb a standard set of steps, followed by checks on balance and
Possible investigations of muscle function in relation to symptoms of weakness and fatigue Amount of contractile material
Isometric strength (with or without electrical stimulation) Anthropometry; CT, MRI or ultrasound imaging
Speed of the muscle
Relaxation from an isometric contraction The degree of fusion of a submaximal tetanus Shape of the force/velocity relationship; estimates of maximum velocity of shortening
Power and impulse (speed and strength)
Standing and vertical jump Stair running Wingate test Nottingham leg extensor power rig Isokinetic dynamometry Isokinetic cycling
Length of a muscle Fatiguability
Angle/force or torque relationship (range of movement) Repeated contractions (stimulated or voluntary; isometric or dynamic; with or without an intact circulation) Prolonged exercise at fixed percentage of VO2max 6- or 12-min walk tests Rating of Perceived Exertion (Borg 10- or 20-point scale)
Other investigations
Clinical history Biochemistry (creatine kinase, inflammatory markers, genetic investigation) Electromyography
Table 2
SURGERY 28:2
57
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
muscle loss. Muscle mass can be measured indirectly (as lean soft tissue) using dual energy X-ray absorptiometry (DEXA) however additional information is gained using ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) (Figure 1), which are able to distinguish tissue types, for example muscle and subcutaneous fat, due to the observable contrast differences and subsequently permit quantification of either cross-sectional area and/or volume.
Measurement of muscle strength and power output Muscle strength provides a useful and convenient measure of function. Hand grip dynamometry has been shown to be predictive of future disability, morbidity and mortality but lacks precision and is difficult to standardize. Most major muscle groups can be measured but the quadriceps remains the most useful since it is a large proximal muscle that is affected in most muscle disorders, it is functionally important in everyday life and is very convenient for other investigations such as muscle biopsy and electromyography (EMG). The simplest way of measuring quadriceps strength is manual muscle testing with or without a hand-held myometer but these techniques are inaccurate. Knee extensor/elbow flexor strength can be measured using an isometric testing chair such as described by Edwards et al3 (Figure 2) or commercial ergometers that can be used in either isometric or isokinetic modes. For the purposes of assessing the size and strength of a muscle in order to document the extent of a disease or the progress of treatment or training, isometric testing is quite sufficient and in many ways preferable to isokinetic testing that introduces several complications such as consideration of the speed, length and range of movement of a muscle. Isokinetic testing is of particular value in assessing injuries affecting joints where the range of movement can be impaired or inhibition might occur at a certain position. Normal values are difficult to define since strength varies widely with age, sex, body shape and size and with habitual activity.
Figure 1 Magnetic resonance cross-sectional images at mid-thigh level in healthy women aged 23 y a and 80 y b and a woman with upper gastrointestinal cancer aged 75 y c.
eyesight, before proceeding to measurements of strength, range of movement and the fatiguability of individual muscle groups, the expectation being that an abnormality of muscle function might explain the overall functional deficit. A similar sequence could be envisaged for an athlete who was injured or was complaining of loss of form. Measurement of muscle mass The majority of common muscle complaints involve wasting and it is particularly useful in a clinical situation to know the extent of
Adjustable testing chair suitable for measuring isometric strength of the quadriceps, developed from the chair described by Edwards et al.3 Figure 2
SURGERY 28:2
58
Ó 2009 Elsevier Ltd. All rights reserved.
BASIC SCIENCE
Edwards et al3 suggest a useful rule of thumb is that the quadriceps strength is about 75% of the force of gravity on the body mass so that for a 70 kg subject, strength would be about 530 N. However a wide range of quadriceps strength is compatible with a normal active lifestyle; normative data for the isometric strength of several muscles and for a body sizes and ages have been published.4 Power is the product of the strength and speed of a muscle and is a critical component of performance in many sporting activities. However conventional tests of whole body power output are often inappropriate for frail patients. The Nottingham Power Rig5 was developed to measure the explosive power of the lower limb extensors safely (in a seated position) and has been shown to be suitable for use with very frail patients, even those recovering from hip fracture.6 Muscle power output measured using this technique is associated with selected measures of functional ability in both healthy older men and women and selected patient groups, although it is not clear whether this provides any more information than simply measuring isometric strength. A
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REFERENCES 1 Young A. Muscle function in old age. In: Thomas PK, ed. Peripheral nerve changes in the elderly, New issues in neurosciences, vol. I, 1998: 141–56. 2 Phillips SK, Woledge RC, Bruce SA, et al. A study of force and crosssectional area of adductor pollicis muscle in female hip fracture patients. J Am Geriatr Soc 1998 Aug; 46: 999e1002. 3 Edwards RHT, Young A, Hosking GP, Jones DA. Human skeletal muscle function: description of tests and normal values. Clin Sci Mol Med 1977; 52: 283e90. 4 Muscular weakness assessment: use of normal isometric strength data. The National Isometric Muscle Strength (NIMS) Database Consortium. Arch Phys Med Rehabil 1996; 77: 1251e5. 5 Bassey EJ, Short AH. A new method for measuring power output in a single leg extension: feasibility, reliability and validity. Eur J Appl Physiol Occup Physiol 1990; 60: 385e90. 6 Mitchell SL, Stott DJ, Martin BJ, Grant SJ. Randomized controlled trial of quadriceps training after proximal femoral fracture. Clin Rehabil 2001 Jun; 15: 282e90.
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Ó 2009 Elsevier Ltd. All rights reserved.