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QUICK REVIEW Organization of Skeletal Muscle

Neuromuscular diseases include a wide-ranging variety of pathologies that can produce significant disability for the patient. The history and physical examination are very important in narrowing the differential, and the muscle biopsy provides an additional layer of granularity to assist in making the diagnosis. To understand muscle pathology, one must understand the organization of the skeletal muscle and the histochemical stains that provide the means necessary to distinguish between potential differentials (Figures 19-1 and 19-2).


  • Perimysium: Connective tissue surrounding the fascicles

  • Endomysium: Connective tissue surrounding the muscle fibers inside the fascicles

  • Epimysium: Connective tissue covers the outer surface of the muscle

Muscle Fibers

  • Myofibrils: An elongated structure containing cytoskeletal elements allowing the muscle to contract

  • Sarcomere: Thick (myosin) and thin filaments (actin, troponin, tropomyosin)

  • The striated muscle appearance is created by pattern of alternating dark and light bands

Sarcolemma (Plasma Membrane)

  • Sarcoplasma: Specialized cytoplasm of a muscle cell

  • Nuclei and mitochondria are located just beneath the sarcolemma

  • Sarcoplasmic reticulum extends between the myofibrils


Organization of skeletal muscle. (A) An entire skeletal muscle is enclosed within a dense connective tissue layer called the epimysium continuous with the tendon binding it to bone. (B) Each fascicle of muscle fibers is wrapped in another connective tissue layer called the perimysium. (C) Individual muscle fibers (elongated multinuclear cells) are surrounded by a very delicate layer called the endomysium, which includes an external lamina produced by the muscle fiber (and enclosing the satellite cells) and ECM produced by fibroblasts. (From Mescher AI, Junqueira's Basic Histology, 12th ed. McGraw Hill Lange New York 2010, Chapter 10, Figure 10-3, page 170.)

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Structure of a myofibril: a series of sarcomeres. (A) Diagram indicates that each muscle fiber contains several parallel bundles called myofibrils. (B) Each myofibril consists of a long series of sarcomeres that contain thick and thin filaments and are separated from one another by Z discs. (C) Thin filaments are actin filaments with one end bound to α-actinin, the major protein of the Z disc. Thick filaments are bundles of myosin, which span the entire A band and are bound to proteins of the M line and to the Z disc across the I bands by a very large protein called titin, which has spring-like domains. (D) The molecular organization of the sarcomeres has bands of greater and lesser protein density, resulting in staining differences that produce the dark and light-staining bands seen by light microscopy and TEM. (From Mescher AI, Junqueira's Basic Histology, 12th ed. McGraw Hill Lange New York 2010, Chapter 10 Figure 10-8, page 173.)

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WHAT TO DO Evaluation of Myopathies

To appropriately work up a myopathy, the following elements should be included:


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