How Muscle Works, and the Implications of Exercising

Source: Cocchiarella MD, Antonio; Kessel, MD Tamar. Musculoskeletal Network

Familiarity with the histophysiology and biochemistry is needed

ABSTRACT: Performing exercises can help patients maintain or improvethe range of motion of various joints, improve balance, support function, prevent bone tissue demineralization, lower blood pressure and cholesterol levels, and improve mood. Some familiarity with the histophysiology of the muscular system and the biochemistry of muscle work is needed to understand the implications of exercising and appropriately advise patients who have musculoskeletal disorders. Exercises may be divided into 2 groups: static and dynamic. Specific exercises may be classified as isometric, isotonic, or isokinetic. Exercises also may be classified clinically as active, active assistive, or passive. Muscle strength may be graded with the use of a system based on the muscle’s ability to move against gravity or a specific resistance. ( J Musculoskel Med. 2012;29:48-52)

Exercises to promote strengthening, conditioning, and pain control are prescribed regularly as part of the “medical armamentarium.” The literature is full of information indicating that exercise promotes well-being, although it also shows that vigorous exercise may be harmful, as in patients with myopathies.

Exercises can be thought of as body activity that requires physical exertion to develop, maintain, or increase fitness and skill. The performance of exercises can help maintain or improve the range of motion of various joints, improve balance, support function, prevent bone tissue demineralization, lower blood pressure and cholesterol levels, and improve mood. However, some familiarity with the histophysiology of the muscular system and the biochemistry of muscle work is needed to understand the implications of exercising and appropriately advise patients who have musculoskeletal disorders.

In this article, we provide a review of the histophysiology and biochemistry of muscle work. We also describe exercise goals and types.


Human skeletal muscles are composed of 2 types of fibers. They are type 1, or red, and type 2, or white, fibers.

Type 1 Fibers

These are called red fibers because of the high content of myoglobin and capillaries (hence, blood). They also are referred to as slow-twitching fibers because they demonstrate a rather slow speed to contraction and relaxation time compared with type 2 fibers. They produce their energy anaerobically and tire when their fuel supplies are gone. They have a large number of mitochondria to accommodate the oxidative phosphorylation processes needed for aerobic metabolism.

The aerobic pathway, which is very efficient, is needed in activities that require endurance. Therefore, the generated force is not explosive but rather submaximal and continuous, as when a person performs high-repetition, low-load activities.

Mitochondria are rod-shaped organelles in the cell cytoplasm. Through enzymatic activity, they convert oxygen, fatty acid, and glucose into adenosine triphosphate (ATP), the chemical energy necessary for the cell’s metabolism.

Type 2 Fibers

These are called white fibers because they lack a large number of capillaries and myoglobin and are fast-twitching. They are subdivided into type 2a and type 2b; type 2a fibers contain a larger concentration of oxidative enzymes than type 2b fibers.

Type 2b fibers generally are the fibers of anaerobic energy (ability to work), strength (physical energy), and power (ability to produce an effect). They contract quickly, yielding short bursts of energy, so that they are recruited mostly for brief and intense exercise (eg, sprinting and swimming). Because these fibers depend on anaerobic energy, they become vulnerable to the by-products of their own metabolism as increasing levels of work are performed: using glycolysis to produce ATP elevates metabolic lactic acid levels in the cell, generating muscle fatigue down to exhaustion.

The lactic acid hypothesis remains controversial in scientific review. It has been partially verified by the finding that patients with McArdle disease, who are unable to metabolize glycogen and thus produce lactate, do not exhibit a decrease in sarcolemma conduction velocity during exercise until there is an additional change in force output.1 However, the hypothesis also has been refuted by findings indicating that median power frequency changes and restitution postexercise are unrelated to blood lactate levels.2

Another type of fiber, 2m, is characterized by very fast contractions via the glycolytic pathway. These fibers are responsible for very fast movements, such as those of the eye muscles and vocal cords.

In the human body, the proportions of fast- and slow-twitching fibers in all muscle groups are determined genetically. Each muscle group has both types, in varying proportions.

Training can play an important role in the metabolic performance of these fibers. For example, a trained muscle with a high percentage of fast-twitching fibers may perform more efficiently to provide endurance than a deconditioned one with slow-twitching fibers. To a certain extent, therefore, these 2 types of fibers may interchange in their performance. However, the effects of training on a muscle are reversible: once muscle fibers no longer experience resistance or endurance demands, they atrophy rapidly.

Strength is the ability to generate maximal force at some particular moment; muscle endurance is the ability to sustain a submaximal force for an extended period. Physiologically, muscle work can be described as strength or endurance; skill may be a combination of the two.

The fast-twitching fibers are recruited to start a work as inertia is overcome or to produce a change in velocity or direction. If the work requires a low to moderate intensity of work at a constant velocity, then the slow-twitching fibers are used. In reality, if the fast-twitching fibers are mobilized to start a work, they fatigue rapidly, leaving the slow-twitching fibers to sustain the work.

When a muscle is injured, disuse from the injury itself may create atrophy, which results in the fast-twitching fibers rapidly losing size as well as strength; the slow-twitching fibers may retain both size and strength. Therefore, the ratio of strength to endurance ultimately may change, leading to muscle fatigue, which may then favor the development of substitution patterns and poor body mechanics.

The Henneman size principle states that motor units are recruited in an orderly manner from the smaller (lower threshold) to the larger (higher threshold) units and that the recruitment is dependent on the effort of the activity.3 Greater recruitment produces higher muscular force. However, the pervasive faulty assumption that maximal force (very heavy resistance) is required for recruitment of the higher threshold motor units and optimal strength is not supported by the size principle, motor unit activation studies, or resistance training studies. This flawed premise has resulted in the unsubstantiated heavier-is-better recommendation for resistance training.


Muscle motion is fueled by the breakdown of ATP, which generally occurs in a constant fashion. A rapid use of ATP could result in a quick muscle contraction, followed by a period of exhaustion.

This is another controversial topic. Insufficient intramuscular ATP often is thought to be the cause of fatigue, although considerable evidence suggests that this might not be the case. Numerous studies have demonstrated that ATP falls no more than about 70% of pre-exercise levels during high-intensity exercise. However, there is speculation that 70% to 80% of the sarcoplasmic ATP is restricted to the mitochondria and is unavailable to the cross-bridges. In other words, ATP is “compartmentalized” and, although sufficient ATP is inside the cell, it is not in the location where needed. However, a compelling argument against this hypothesis is that tension would develop in resting muscle from rigor cross-bridges because of a lack of ATP. Yet, this does not occur.

Muscle movement is the result of an incessant instantaneous breakdown and reconstitution of ATP. As fast as ATP fractures to free energy, it must be rebuilt. The methods that the muscles use to build up energy are aerobic (using oxygen) and anaerobic (not using oxygen).

The aerobic process takes place inside the mitochondria: the fuel for the aerobic process comes from glucose and fatty acids. Aerobic metabolism is by far the more efficient way to make ATP (39 moles of ATP from 1 mole of glucose), although it is not the faster.

Because the aerobic pathway produces more energy than needed for the formation of ATP, the excess, released as heat, contributes to keeping the body temperature at its most efficient level (37°C [98.6°F]). The aerobic pathway prefers fatty acids to glucose as fuel (called “glucose sparing”) because the CNS can use only glucose for its fuel needs.

Physical activity is the expression of both energy intensity and energy expenditure. The latter relates to the metabolic rate (resting metabolic rate), which then can be expressed in the metabolic equivalents of task (MET). MET indicates the rate of energy used in some activities compared with the amount of energy used during physical rest (1 MET is the amount of energy used during a determinate activity and relates to the person’s body mass; it is the equivalent of a metabolic rate consuming 3.5 mL of oxygen per kilogram of body weight per minute or a metabolic rate consuming 1 kcal per kilogram of body weight per hour) (Table 1).

Aerobic Cycle

Carbohydrates, lipids, and proteins to be used to perform muscular work need to be oxidized (loss of electrons from atoms) after chemical breakdown via the metabolic pathway of glycogenolysis and the citric acid cycle. These electrons, in the form of hydrogen ions (H+), are transported by the nicotinamide adenine dinucleotide system into the mitochondria, ultimately providing 39 moles of ATP per mole of glucose; the remaining energy is lost as production of heat, water, and carbon dioxide.

ATP then is used to perform muscle work through an aerobic process. The process can work efficiently only if adequate amounts of oxygen are delivered to the working muscle cell (a function of the cardiorespiratory and vascular systems) and used in the cell by the mitochondria (a function of cellular respiration) to accept the H+ electrons liberated during the breakdown of the organic fuels.

This pattern is seen only in work of low to moderate intensity, when oxygen demand and supply are in balance. As the intensity of work increases, this balance is broken. Therefore, energy must be obtained anaerobically, via glycogenolysis and glycolysis, an inefficient way that provides only 3 moles of ATP per mole of glucose and ultimately converts the pyruvates formed during the glycolysis into lactic acid.

Most of this metabolite is then transported out of the cell into the bloodstream, where it can accumulate up to a certain point. Beyond that point, the muscle fiber reaches the anaerobic threshold and further accumulation inhibits glycolysis and ATP production, ultimately leading to termination of the muscle work. However, when lactate is produced in this fashion, it is transported to the liver to be reconverted into glycogen.

Anaerobic Cycle

The second process of supplying energy to muscles is anaerobic gycolysis, the breakdown of sugar. This method allows muscles to borrow from their stores of glucose to make ATP. In a rapid way, through various steps, enzymes transform glucose into pyruvic acid and, in the process, make ATP. If a muscle fiber has enough oxygen (a function of cellular respiration), pyruvic acid slips into the mitochondria for further processing into the aerobic pathway. This is possible only if enough oxygen is available; therefore, pyruvic acid remains outside the mitochondria, where enzymatic activity will transform it into lactic acid.

Accumulation of lactic acid within the muscle cell makes the cell’s internal environment more acidic; this interferes with the work of the enzymes that break down glucose. Therefore, anaerobic glycolysis cannot proceed.

However, not all is lost: once the aerobic pathway is in full operation, it can use some of the energy it has created to transform lactic acid back to pyruvic acid, which the mitochondria will use directly to generate more energy. The liver also can manufacture glyco-gen from lactic acid and in so doing control the accumulation of this acid.

When the body uses creatine phosphate (anaerobic glycolysis), it borrows against its own resources. The labored breathing at the end of a peak muscular work is the body’s way of repaying the “oxygen debt,” or “recovery oxygen uptake.” This labored breathing allows the body to produce enough energy aerobically to rebuild stores of creatine phosphate.

Excess postexercise oxygen consumption (EPOC), informally called “afterburn,” is a measurably increased rate of oxygen intake after strenuous activity intended to erase the body’s oxygen debt.4,5 In the past, the term “oxygen debt” was popularized to explain or perhaps attempt to quantify anaerobic energy expenditure, particularly in regard to lactic acid and lactate metabolism; the term is still widely used. However, direct and indirect calorimeter experiments have definitively disproved any association of lactate metabolism with causality of elevated oxygen uptake.

Excess postexercise oxygen consumption (EPOC) (the “afterburn effect”), an increased rate of oxygen intake after strenuous activity, is designed to erase the body’s oxygen debt.4,5 The term “oxygen debt” has been used to try to explain or quantify anaerobic energy expenditure in terms of lactic acid and lactate metabolism, but associations of lactate metabolism with causality of elevated oxygen uptake have been disproved with calorimeter experiments. In recovery, EPOC is used in the processes that restore the body to a resting state and adapt it to the exercise that was performed (eg, hormone balancing and replenishment of fuel stores).

In a resting muscle, only the aerobic pathway is in force; exercising stimulates the anaerobic pathway. The mechanism initially depends on creatine phosphate that releases energy-producing molecules of ATP, regardless of whether oxygen is present.

In a burst of intense activity, creatine phosphate is both the first source of energy and the first one to be depleted. This process allows muscles to react instantly without waiting for the heart, lungs, and blood to supply extra oxygen. After creatine phosphate is used, it must be rebuilt, and this is done at the expense of ATP. In fact, some ATP molecules power muscle fibers; others rebuild creatine phosphate.



Patients’ exercise goals are to strengthen muscles, increase endurance, improve biomechanical function of joints, and increase overall function. Exercises designed to increase aerobic capacity traditionally included continuous training techniques, such as exerting for an extended period, usually 30 to 60 minutes at the intensity of about 60% of the maximal volume at which oxygen can be consumed. Although this technique is effective, it can be strenuous, especially for untrained, sedentary patients, and very boring. In addition, the stored ATP is depleted in a very short time while lactate accumulates, and it is not replenished until termination of the work time.

A different training approach, the intermittent technique, may offer patients bigger dividends. They exercise at intensities even greater than in the continuous technique, thereby increasing the stimulus on the cardiovascular system and prolonging the time to fatigue. The technique consists of a series of repeated submaximal exercise bouts, immediately followed by recovery periods, at a fixed rate (eg, 10 seconds work/10 seconds rest). In this fashion, a patient may exercise at an energy level even 2.5 times that of the continuous method before fatiguing.

At the beginning of the exercise time, the fast-twitching muscle fibers are recruited heavily because oxygen is inadequate. As exercising continues, the slow-twitching fibers become recruited in larger numbers. As long as the work intensity remains constant and submaximal, the picture does not change: the fibers produce energy aerobically. As the intensity of work increases significantly and the cardiovascular system cannot transport enough oxygen to meet the demands, the slow-twitching fibers are forced to supply a greater proportion of the energy anaerobically. If this is continued long enough, it leads to accumulation of lactate, causing muscle fatigue.

Although patients may find the intermittent technique less boring, using it has been found to produce opioid analgesic–like substances in increasing quantities as the muscle work continues. In fact, endorphins and enkephalins are thought to affect mood as well as modulate central pain perception.


Exercises may be divided into 2 groups: static (the work is done without changing muscle length) and dynamic (muscle length varies). Specific exercises may be classified as isometric, isotonic, or isokinetic.

Isometric. These are static-type exercises because the muscle contracture does not generate movement. The muscle is working against a fixed resistance (as with trying to lift an object that is anchored to the floor). Because there is no joint movement, technically no work is being done because work itself is the product of a force and the amount of displacement in the line of that force. Only tension is obtained.

Isotonic. These are dynamic-type exercises because the contracture changes muscle length (shortening, or concentric; lengthening, or eccentric), causing joint motion. Because the lever of the arm and the gravitational forces change continuously, these exercises do not deliver constant resistance to the contracting muscle. They usually involve performing a specified number of weight-lifting repetitions.

Isokinetic. These are dynamic-type exercises that are designed to provide a constant and equal resistance to the muscle at all points during the range of motion. The speed of the muscular contracture becomes a controlled variable. The angular velocity of motion is specified, and the resistance is automatically accommodated to the exerted force so that specific velocity is maintained. The joint moves through the range against a mechanical device, which generates a torque, ie, the muscle is forced to work while producing torsion and rotation about a definite axis. These exercises usually are performed using specific machinery.

Exercises may be classified clinically as active, active assistive, or passive (Table 2). From a performance point of view, isometric exercises are indicated to increase strength and static duration (how long a particular muscle can sustain a specific force). Isotonic exercises are indicated to increase strength and dynamic endurance (repetitive isotonic exercises stress the cardiovascular system); these exercises generally improve function.

Muscle strength may be graded with the use of a system based on the muscle’s ability to move against gravity or a specific resistance (0 to 5; higher grades indicate greater strength) (Table 3). There are intermediate values; eg, a 3+ grade means that the muscle is stronger than a 3 but not as strong as a 4.

Note that the system is totally subjective and influenced by the experience level of the examiner. The main value of muscle strength grading is in monitoring patients’ progress at follow-up appointments and monitoring their progress in therapy.


1. Linssen WH, Stegeman DF, Merks MJ, et al. Electromyographic evidence of delayed fatigue-induced sarcolemmal excitability impairment in McArdle’s disease. J Electromyogr Kinesiol. 1996;6:147-157.

2. Jansen R, Ament W, Verkerke GJ, Hof AL. Median power frequency of the surface electromyogram and blood lactate concentration in incremental cycle ergometry. Eur J Appl Physiol Occup Physiol. 1997;75:

3. Carpinelli RN. The size principle and a critical analysis of the unsubstantiated heavier-is-better recommendation for resistance training. J Exerc Sci Fit. 2008;6:

4. Bahr R. Excess postexercise oxygen consumption—magnitude, mechanisms and practical implications. Acta Physiol Scand Suppl. 1992;605:1-70.

5. Bielinski R, Schutz Y, Jéquier E. Energy metabolism during the postexercise recovery in man. Am J Clin Nutr. 1985;42:69-82.

Recommended readings

The authors recommend the following sources for readers who are seeking more information:

• DeLateur B. Therapeutic exercise to develop strength and endurance. In: Kottke FJ, Lehmann JF, eds. Krusen’s Handbook of Physical Medicine and Rehabilitation. 4th ed. Philadelphia: WB Saunders; 1990:21-72. This book helps physicians learn how to skillfully assess their patients’ needs and implement therapeutic strategies and effectively rehabilitate patients to maximum performance levels.

• deVries HA. Healthy elderly patients. In: Franklin BA, Gordon SG, Timmis GC, eds. Exercise in Modern Medicine. Baltimore: Williams & Wilkins; 1989:215-236. This text reviews the basic fundamentals of exercise physiology and describes the healthy adult with respect to exercise testing and the conditioning process.

• McArdle WD, Katch FI, Katch VL. Human energy expenditure during rest and physical activity. Exercise Physiology: Energy, Nutrition and Human Performance. 6th ed. Baltimore: Lippincott, Williams & Wilkins; 2006:187-200. This textbook integrates basic concepts and relevant scientific information to provide a foundation for understanding nutrition, energy transfer, and exercise training.

• Powers SK, Howley ET. Exercise metabolism. Exercise Physiology: Theory and Application to Fitness and Performance. 7th ed. New York: McGraw-Hill Com-panies, Inc; 2008. Chapters in this book contain guidelines for exercise testing and prescription.

• Shephard RJ. Energy balance in humans. Physiology and Biochemistry of Exercise. New York: Praeger Publishers; 1982:1-19. Written especially for exercise science and physical education students, this text provides a solid foundation in theory.

• Wilmore JH, Costill DL, Kenney WL. Structure and function of exercising muscle. Physiology of Sport and Exercise. 4th ed. Champaign, IL: Human Kinetics; 2007:
24-46. This, the leading textbook for undergraduate exercise physiology courses, presents the complex relationship between human physiology and exercise.