AAOS Comprehensive Orthopaedic Review
Section 1 - Basic Science
Chapter 9. Skeletal Muscle
I. General Information
A. Skeletal muscles receive innervation from the peripheral nervous system.
B. They affect volitional control of the axial and appendicular skeleton.
II. Muscle Structure and Function
A. Muscle structure
1. Skeletal muscle fibers are highly specialized multinucleated cells characterized by a collection of contractile filaments called myofilaments (
Figure 1). Filaments are organized in a defined hierarchy, with the basic functional unit of muscle contraction being the sarcomere.
2. The largest functional unit is the myofibril, which is a string of sarcomeres arranged in series. Adjacent myofibrils are connected by a set of specialized proteins called intermediate filaments. These allow for mechanical coupling between myofibrils.
3. Endomysium is the connective tissue surrounding individual fibers.
4. Perimysium is the connective tissue surrounding collections of muscle fibers, or fascicles.
5. Epimysium is the connective tissue covering of the entire muscle.
B. Cell membrane systems
1. A specially designed membrane system exists within the cell that assists in activating the contractile properties of the muscle cell. The system consists of two main components: the transverse tubular system and the sarcoplasmic reticulum (
a. The transverse tubular system begins as invaginations of the cell membrane and extends into the cell, perpendicular to its long axis. It functions to relay the activation signal from the motor neuron to the myofibrils.
b. The sarcoplasmic reticulum is a system of membrane-bound sacs that function to collect, release, and re-uptake calcium stores to regulate the muscle contractile process.
i. Calcium channels and pumps are contained within the sarcoplasmic reticulum and are regulated by a complex enzymatic system.
ii. The portion of the sarcoplasmic reticulum that abuts the transverse tubules is called the junctional sarcoplasmic reticulum.
[Figure 1. Structural hierarchy of skeletal muscle. Whole skeletal muscles are composed of numerous fascicles of muscle fibers. Muscle fibers are composed of myofibrils arranged in parallel. Myofibrils are composed of sarcomeres arranged in series. Sarcomeres are composed of interdigitating actin and myosin filaments.]
[Figure 2. Schematic representation of the muscle cell. The muscle cell, which is specialized for the production of force and movement, contains an array of filamentous proteins as well as other subcellular organelles such as mitochondria, nuclei, satellite cells, sarcoplasmic reticulum, and the transverse tubular system. Note the formation of "triads," which represent the T-tubules flanked by the terminal cisternae of the sarcoplasmic reticulum. Also note that when the myofilaments are sectioned longitudinally, the stereotypic striated appearance is seen. When myofilaments are sectioned transversely at the level of the A- or I-bands, the hexagonal array of the appropriate filaments is seen.]
iii. The transverse tubule and the two adjacent sacs of the junctional reticulum together is called a triad.
C. Sarcomere composition
1. Sarcomeres are composed of two major types of contractile filaments:
a. Myosin (thick filaments)
b. Actin (thin filaments)
2. The two sets of filaments interdigitate, and it is the active interdigitation of these filaments that produces muscle contraction via a shortening translation of the filaments.
3. The arrangement of these filaments also creates the characteristic pattern of alternating bands of light and dark seen with microscopy.
a. Tropomyosin, another protein, is situated between two actin strands in its double-helix configuration. In the resting state, tropomyosin blocks the myosin binding sites on actin (
b. Troponin is a complex of three separate proteins that is intimately associated with tropomyosin.
i. When troponin binds calcium, a conformational change in the troponin complex ensues.
ii. This in turn results in a conformational change of tropomyosin, exposing the myosin-binding sites on actin.
iii. A resultant contractile protein interaction occurs, and muscle contraction is initiated.
D. Sarcomere organization
1. The structure of the sarcomere is shown in
a. The A-band is composed of both actin and myosin.
b. The M-line is a central set of interconnecting filaments for myosin.
c. The H-band contains only myosin.
[Figure 3. Features of regulation of muscle contraction. Structure of actin is represented by two chains of beads in a double helix. The troponin complex consists of calcium-binding protein (TN-C, black); inhibitory protein (TN-I, red); and protein binding to tropomyosin (TN-T, yellow). The tropomyosin (dark line) lies in each groove of the actin filament.]
d. The I-band is composed of actin filaments only, which are joined together at the interconnecting Z-line.
2. During muscle contraction, the sarcomere length decreases but the length of individual thick and thin filaments remains the same. During contraction, the thick and thin filaments bypass one another, resulting in increased overlap.
E. Nerve-muscle interaction
1. A motor unit consists of a single motor neuron and all of the muscle fibers it contacts.
a. Every muscle fiber is contacted by a single nerve terminal at a site called the motor end plate (
b. The number of muscle fibers within a motor unit varies widely.
2. Chemical transmission of the electrical impulse passing down the cell membrane of the axon occurs at the motor end plate or neuromuscular junction (NMJ). The primary and secondary synaptic folds or invaginations of the cell membrane increase the surface area for communication.
3. Acetylcholine (ACh) is the neurotransmitter released into the synaptic cleft.
a. The electrical impulse reaches the terminal axon, and calcium ions are allowed to flow into the neural cell.
b. This increase in intracellular calcium causes the neurotransmitter vesicles to fuse with the axon membrane, and the ACh is released into the synaptic cleft.
[Figure 4. A, Electron micrograph of skeletal muscle illustrating the striated, banded appearance. A = A-band; M = M-line; I = I-band; Z = Z-line. B, The basic functional unit of skeletal muscle, the sarcomere.]
[Figure 5. Schematic representation of the motor end plate.]
c. ACh then binds to receptors on the muscle membrane, triggering depolarization of the cell, which in turn triggers an action potential.
d. This action potential is passed along through the sarcoplasmatic reticulum network.
e. The ACh is enzymatically deactivated by acetylcholinesterase located within the extracellular space.
4. Pharmacologic and physiologic alteration of neuromuscular transmission
a. Myasthenia gravis is a disorder resulting in a shortage of ACh receptors; it is characterized by severe muscle weakness.
b. Nondepolarizing drugs (eg, pancuronium, vecuronium, and curare)
i. Competitively bind to ACh receptor, blocking transmission.
ii. Site of action is the NMJ.
c. Polarizing drugs (eg, succinylcholine)
i. Bind to ACh receptor, causing temporary depolarization followed by failure of the impulse transmission.
ii. Site of action is the NMJ.
d. Reversible acetylcholinesterase inhibitors (eg, neostigmine, edrophonium)
i. Prevent breakdown of ACh.
ii. Allow for prolonged interaction with ACh receptor.
e. Irreversible acetylcholinesterase inhibitors (eg, nerve gases and certain insecticides)
i. Similarly prevent breakdown of ACh.
ii. Result in sustained muscle contraction.
III. Muscle Function
A. Nerve activation of muscle contraction
1. A muscle twitch (
Figure 6, A) is the muscle tension response to a single nerve stimulus.
a. If a second nerve stimulus arrives after the muscle tension has returned to baseline resting tension, there is no increase in muscle tension development.
b. Absolute refractory period—The time period during which no stimulus will produce a muscle contraction.
c. Relative refractory period—The time period during which the stimulus required for muscle activation is greater than the typical threshold stimulus level.
2. Paired twitch (Figure 6, B)—If a successive nerve stimulus arrives before the resting tension reaches baseline, the tension rises above the level of a single twitch.
a. This phenomenon is called summation (wave summation or temporal summation).
b. As the frequency of gross muscle stimulation increases, higher peak tensions develop (Figure 6, C).
c. A plateau of maximal tension eventually is reached (Figure 6, D) where there is no relaxation of muscle tension between successive stimuli (tetany).
B. Skeletal muscle can develop varying levels of muscle force, even though each individual motor unit contracts in an all-or-none fashion. This graded response is controlled by different mechanisms.
1. Spatial summation—Different motor units have different thresholds of stimulation, and therefore more motor units are activated with increased stimulus intensity.
2. Temporal summation—Increasing stimulus frequency results in increased tension development by each individual motor unit (eg, tetany).
3. Maximal force production is proportional to muscle physiologic cross-sectional area (PCSA); however, force production is not directly related to anatomic cross-sectional area.
a. Other factors that contribute to PCSA are surface pennation angle (fiber angle relative to the force-generating axis of the muscle), muscle density, and fiber length.
b. Longer fiber lengths allow for long excursions with less force production.
C. Types of muscle contraction
1. Isotonic—Muscle shortens against a constant load. Muscle tension remains constant.
2. Isokinetic—Muscle contracts at a constant velocity.
3. Isometric—Muscle length remains static as tension is generated.
4. Concentric—Muscular contraction that results in decrease in muscle length. This occurs when the resisting load is less than the muscle force generated.
5. Eccentric—Muscular contraction that accommodates an increase in muscle length. This occurs when the resisting load is greater than the muscle force generated.
[Figure 6. Twitch (A and B) and tetanus (C and D). As the frequency of stimulation is increased, muscle force rises to an eventual plateau level known as fused tetanus.]
6. Isotonic and isokinetic contractions can demonstrate either concentric action or eccentric action. However, isometric contractions do not fit the definition of either concentric or eccentric action.
D. Force-velocity relationship (
Figure 7)—Under experimental conditions, a load is applied to a contracting muscle until no change in length is seen (isometric length). As higher external load is applied, the muscle begins to lengthen and tension increases rapidly (eccentric contraction). If load is decreased from the isometrically contracting muscle, the muscle force will rapidly decrease and the muscle will shorten in length (concentric contraction). Progressively decreased loads result in increased contraction.
1. Concentric contractions—The force generated by the muscle is always less than the muscle's maximum force. As seen from the force-velocity curve, the force drops off rapidly as velocity increases. For example, when the muscle velocity increases to only 17% of maximum, the muscle force has decreased to 50% of maximum.
2. Eccentric contractions—The absolute tension quickly becomes very high relative to the maximum isometric tension. Eccentric generates the highest tension and greatest risk for musculotendinous injury. The absolute tension is relatively independent of the velocity.
E. Fiber types
1. The muscle fibers of each motor unit share the same contractile and metabolic properties.
2. These muscle fibers may be one of three primary types (types I, IIA, or IIB), characterized according to their structural, biochemical, and physiologic characteristics (
a. Type I fibers (slow-contracting, oxidative)
i. High aerobic capacity
[Figure 7. The muscle force-velocity curve for skeletal muscle obtain using sequential isotonic contractions. Note that force increases dramatically upon forced muscle lengthening and drops precipitously upon muscle shortening.]
ii. Resistant to fatigue
iii. Contain more mitochondria and more capillaries per fiber than other types
iv. Slower contraction and relaxation times than other fiber types
b. Type IIA (fast-contracting and oxidative and glycolytic)—Intermediate fiber type between the slow oxidative type I fiber and the fast glycolytic type IIB fiber.
c. Type IIB (fast-contracting, glycolytic)
i. Primarily anaerobic
ii. Least resistant to fatigue
iii. Most rapid contraction time
iv. Largest motor unit size
d. Strength training may result in an increased percentage of type IIB fibers, whereas endurance training may increase the percentage of type IIA fibers.
A. Three main energy systems provide fuel for muscular contractions.
1. The phosphagen system (
The adenosine triphosphate (ATP) molecule is hydrolyzed and converted directly to adenosine diphosphate (ADP), inorganic phosphate, and energy. ADP may also be further hydrolyzed to create adenosine monophosphate (AMP), again releasing inorganic phosphate and energy.
[Table 1. Characteristics of Human Skeletal Muscle Fiber Types]
[Figure 8. Energy sources for anaerobic activity.]
Creatine phosphate is another source of high-energy phosphate bonds. However, its high-energy phosphate bond is used by creatine kinase to synthesize ATP from ADP.
Myokinase is used to combine two ADP molecules to create one ATP molecule and one AMP molecule.
Total energy from the entire phosphagen system is enough to fuel the body to run approximately 200 yards.
No lactate is produced via this pathway; also, no oxygen is used.
2. Anaerobic metabolism (glycolytic or lactic acid metabolism) (
a. Glucose is transformed into two molecules of lactic acid, creating enough energy to convert two molecules of ADP to ATP.
b. This system provides metabolic energy for approximately 20 to 120 seconds of intense activity.
c. Oxygen is not used in this pathway.
3. Aerobic metabolism (
a. Glucose is broken into two molecules of pyruvic acid, which then enter the Krebs cycle, resulting in a net gain of 34 ATP per glucose molecule.
b. Glucose exists in the cell in a limited quantity of glucose-6-phosphate. Additional sources of energy include stored muscle glycogen.
c. Fats and proteins also can be converted to energy via aerobic metabolism.
d. Oxygen is used in this pathway.
B. Training effects on muscle
1. Strength training usually consists of high-load, low-repetition exercise and results in increased muscle cross-sectional area. This is more likely due to muscle hypertrophy (increased size of muscle fibers) rather than hyperplasia (increased number of muscle fibers).
[Figure 9. Diagram summarizing ATP yield in the anaerobic and aerobic breakdown of carbohydrates. Glycolysis and anaerobic metabolism occur in the cytoplasm; oxidative phosphorylation occurs in the mitochondria.]
a. Increased motor unit recruitment or improved synchronization of muscle activation is another way weight training contributes to strength gains.
b. Strength training results in adaptation of all fiber types.
c. Little evidence exists at a microscopic, cellular level that muscle cell injury is required to generate muscle strengthening or hypertrophy.
2. Endurance training
a. Aerobic training results in changes in both central and peripheral circulation as well as muscle metabolism. Energy efficiency is the primary adaptation seen in contractile muscle.
[Figure 10. Foodstuffs (fats, carbohydrates, proteins) containing carbon and hydrogen for glycolysis, fatty acid oxidation, and the Krebs cycle in a muscle cell.]
b. Mitochondrial size, number, and density increase. Enzyme systems of the Krebs cycle, respiratory chain, and those involved with the supply and processing of fatty acids by mitochondria all increase markedly.
c. Metabolic adaptations occur that result in an increased use of fatty acids rather than glycogen.
d. The oxidative capacity of all three fiber types increases. In addition, the percentage of the more highly oxygenated type IIA fibers increases.
V. Muscle Injury and Repair
A. Cytokines and growth factors regulate the repair processes after muscle injury. Sources of cytokines include infiltrating neutrophils, monocytes, and macrophages; activated fibroblasts; and stimulated endothelial cells.
1. Necrotic muscle fibers are removed by macrophages. New muscle cells are thought to arise from satellite cells, which are undifferentiated cells that exist in a quiescent state until needed for a reparative response.
2. The simultaneous formation of fibrotic connective tissue or scar may interfere with a full recovery of muscle tissue after injury.
B. Delayed-onset muscle soreness (DOMS) is muscle ache and pain that typically occurs 24 to 72 hours after intense exercise.
1. DOMS is primarily associated with eccentric loading-type exercise.
2. Several theories have been proposed to explain DOMS, the most popular being that structural muscle injury occurs and leads to progressive edema formation and resultant increased intramuscular pressure.
3. These changes seem to occur primarily in type IIB fibers.
C. Muscle contusion is a nonpenetrating blunt injury to muscle resulting in hematoma and inflammation. Characteristics include:
1. Later development of scar formation and variable amount of muscle regeneration.
2. New synthesis of extracellular connective tissue within 2 days of the injury, with peak at 5 to 21 days.
3. Myositis ossificans (bone formation within muscle) secondary to blunt trauma. This sometimes mimics osteogenic sarcoma on radiographs and biopsy. Myositis ossificans becomes apparent approximately 2 to 4 weeks post-injury.
4. Muscle strain
a. Both complete and incomplete muscle tears usually occur by passive stretch of an activated muscle.
b. Muscles at greatest risk are those that cross two joints, eg, the rectus femoris and gastrocnemius.
c. Incomplete muscle tears also typically occur at the myotendinous junction, with hemorrhage and fiber disruption. A cellular inflammatory response occurs for the first few days, with the muscle demonstrating decreased ability to generate active tension. In an animal model, force production normalized after 7 days.
d. Complete muscle tears typically occur near the myotendinous junction. They are characterized by muscle contour abnormality.
5. Muscle laceration
a. After complete laceration of muscle, fragments heal by dense connective scar tissue. Regeneration of muscle tissue across the laceration or reinnervation is not predictable, and only partial recovery is likely.
b. Muscle activation does not cross the scar.
c. Unstimulated muscle segment shows histologic characteristics of denervated muscle.
D. Immobilization and disuse
1. Immobilization and disuse results in muscle atrophy with associated loss of strength and increased fatigability.
2. A nonlinear rate of atrophy occurs, with changes occurring primarily during initial days. Atrophy is seen at a cellular level, with loss of myofibrils within the muscle fibers.
3. Atrophic changes are related to the length at which muscle is immobilized. Atrophy and strength loss are more prominent when muscle is immobilized under no tension; eg, when the knee is immobilized in extension, quadriceps atrophy is greater than hamstring atrophy.
4. Muscle fiber held under stretch creates new contractile proteins with sarcomeres added onto existing fibrils. This slightly offsets the atrophy of cross-sectional muscle mass.
Top Testing Facts
1. Muscle fiber is a collection of myofibrils.
2. Fascicles are collections of muscle fibers.
3. Actin's binding sites for myosin are blocked by tropomyosin.
4. Know all bands and lines of sarcomere organization—A, I, H, M, and Z. (See section II.D and Figure 4.)
5. Site of action of both depolarizing and nondepolarizing drugs is the NMJ.
6. Maximal force production is proportional to muscle physiologic cross-sectional area (PCSA).
7. Phosphagen energy system has enough ATP for approximately 20 seconds of activity.
8. DOMS peaks at 24 to 72 hours post-exercise, is most common in type IIB fibers, and is associated primarily with eccentric exercise.
9. Eccentric contraction generates the highest tension and greatest risk for musculotendinous injury.
10. Muscle strain is most likely in muscles that cross two joints.
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Garrett WE Jr, Best TM: Anatomy, physiology, and mechanics of skeletal muscle, in Buckwalter JA, Einhorn TA, Simon SR (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 683-716.
Lieber RL: Form and function of skeletal muscle, in Einhorn TA, O'Keefe RJ, Buckwalter JA (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2007, pp 223-242.